24 December 2020
14:09
Degenerative cervical myelopathy
Degenerative cervical myelopathy (DCM) has a number of risk factors, which include smoking due to its effects on the intervertebral discs, genetics and occupation - those exposing patients to high axial loading [1].
The presentation of DCM is very variable. Early symptoms are often subtle and can vary in severity day to day, making the disease difficult to detect initially. However as a progressive condition, worsening, deteriorating or new symptoms should be a warning sign.
DCM symptoms can include any combination of [1]:
· Pain (affecting the neck, upper or lower limbs)
· Loss of motor function (loss of digital dexterity, preventing simple tasks such as holding a fork or doing up their shirt buttons, arm or leg weakness/stiffness leading to impaired gait and imbalance
· Loss of sensory function causing numbness
· Loss of autonomic function (urinary or faecal incontinence and/or impotence) - these can occur and do not necessarily suggest cauda equina syndrome in the absence of other hallmarks of that condition
· Hoffman's sign: is a reflex test to assess for cervical myelopathy. It is performed by gently flicking one finger on a patient's hand. A positive test results in reflex twitching of the other fingers on the same hand in response to the flick.
The most common symptoms at presentation of DCM are unknown, but in one series 50% of patients were initially incorrectly diagnosed and sometimes treated for carpal tunnel syndrome [2].
An MRI of the cervical spine is the gold standard test where cervical myelopathy is suspected. It may reveal disc degeneration and ligament hypertrophy, with accompanying cord signal change.
All patients with degenerative cervical myelopathy should be urgently referred for assessment by specialist spinal services (neurosurgery or orthopaedic spinal surgery). This is due to the importance of early treatment. The timing of surgery is important, as any existing spinal cord damage can be permanent. Early treatment (within 6 months of diagnosis) offers the best chance of a full recovery but at present, most patients are presenting too late. In one study, patients averaged over 5 appointments before diagnosis, representing >2 years.
Currently, decompressive surgery is the only effective treatment. It has been shown to prevent disease progression. Close observation is an option for mild stable disease, but anything progressive or more severe requires surgery to prevent further deterioration. Physiotherapy should only be initiated by specialist services, as manipulation can cause more spinal cord damage.
References
1. Baron EM, Young WF. Cervical spondylotic myelopathy: a brief review of its pathophysiology, clinical course, and diagnosis. Neurosurgery. 2007 Jan;60(1 Supp1 1):S35-41.
2. Behrbalk E, Salame K, Regev GJ, Keynan O, Boszczyk B, Lidar Z. Delayed diagnosis of cervical spondylotic myelopathy by primary care physicians. Neurosurg Focus. 2013 Jul;35(1):E1.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Cluster headache
Cluster headaches are known to be one of the most painful conditions that patients can have the misfortune to suffer. The name relates to the pattern of the headaches - they typically occur in clusters lasting several weeks, with the clusters themselves typically once a year.
Cluster headaches are more common in men (3:1) and smokers. Alcohol may trigger an attack and there also appears to be a relation to nocturnal sleep.
Features
· pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours
· clusters typically last 4-12 weeks
· intense sharp, stabbing pain around one eye (recurrent attacks 'always' affect same side)
· patient is restless and agitated during an attack
· accompanied by redness, lacrimation, lid swelling
· nasal stuffiness
· miosis and ptosis in a minority
Management
· acute: 100% oxygen (80% response rate within 15 minutes), subcutaneous triptan (75% response rate within 15 minutes)
· prophylaxis: verapamil is the drug of choice. There is also some evidence to support a tapering dose of prednisolone
· NICE recommend seeking specialist advice from a neurologist if a patient develops cluster headaches with respect to neuroimaging
Some neurologists use the term trigeminal autonomic cephalgia to group a number of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended such patients are referred for specialist assessment as specific treatment may be required, for example it is known paroxysmal hemicrania responds very well to indomethacin
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Status epilepticus
This is a medical emergency. The priority is termination of seizure activity, which if prolonged will lead to irreversible brain damage.
Management
· ABC
o airway adjunct
o oxygen
o check blood glucose
· First-line drugs are benzodiazepines such as diazepam or lorazepam
o in the prehospital setting diazepam may be given rectally
o in hospital IV lorazepam is generally used. This may be repeated once after 10-20 minutes
· If ongoing (or 'established') status it is appropriate to start a second-line agent such as phenytoin or phenobarbital infusion
· If no response ('refractory status') within 45 minutes from onset, then the best way to achieve rapid control of seizure activity is induction of general anaesthesia.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Parkinson's disease: management
Parkinsons disease should only be diagnosed, and management initiated, by a specialist with expertise in movement disorders. However, it is important for all doctors to be aware of the medications used in Parkinson's given the prevalence of this condition. NICE published guidelines in 2017 regarding the management of Parkinson's disease.
For first-line treatment:
· if the motor symptoms are affecting the patient's quality of life: levodopa
· if the motor symptoms are not affecting the patient's quality of life: dopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAO‑B) inhibitor
Whilst all drugs used to treat Parkinson's can cause a wide variety of side-effects NICE produced tables to help with decision making:
| Levodopa | Dopamine agonists | MAO‑B inhibitors | |
| Motor symptoms | More improvement in motor symptoms | Less improvement in motor symptoms | Less improvement in motor symptoms |
| Activities of daily living | More improvement in activities of daily living | Less improvement in activities of daily living | Less improvement in activities of daily living |
| Motor complications | More motor complications | Fewer motor complications | Fewer motor complications |
| Adverse events | Fewer specified adverse events* | More specified adverse events* | Fewer specified adverse events* |
* excessive sleepiness, hallucinations and impulse control disorders
If a patient continues to have symptoms despite optimal levodopa treatment or has developed dyskinesia then NICE recommend the addition of a dopamine agonist, MAO‑B inhibitor or catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct. Again, NICE summarise the main points in terms of decision making:
| Dopamine agonists | MAO‑B inhibitors | COMT inhibitors | Amantadine | |
| Motor symptoms | Improvement in motor symptoms | Improvement in motor symptoms | Improvement in motor symptoms | No evidence of improvement in motor symptoms |
| Activities of daily living | Improvement in activities of daily living | Improvement in activities of daily living | Improvement in activities of daily living | No evidence of improvement in activities of daily living |
| Off time | More off‑time reduction | Off‑time reduction | Off‑time reduction | No studies reporting this outcome |
| Adverse events | Intermediate risk of adverse events | Fewer adverse events | More adverse events | No studies reporting this outcome |
| Hallucinations | More risk of hallucinations | Lower risk of hallucinations | Lower risk of hallucinations | No studies reporting this outcome |
Specific points regarding Parkinson's medication
NICE reminds us of the risk of acute akinesia or neuroleptic malignant syndrome if medication is not taken/absorbed (for example due to gastroenteritis) and advise against giving patients a 'drug holiday' for the same reason.
Impulse control disorders have become a significant issue in recent years. These can occur with any dopaminergic therapy but are more common with:
· dopamine agonist therapy
· a history of previous impulsive behaviours
· a history of alcohol consumption and/or smoking
If excessive daytime sleepiness develops then patients should not drive. Medication should be adjusted to control symptoms. Modafinil can be considered if alternative strategies fail.
If orthostatic hypotension develops then a medication review looking at potential causes should be done. If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance) can be considered.
Consider glycopyrronium bromide to manage drooling of saliva in people with Parkinson's disease.
Further information regarding specific anti-Parkinson's medication
Levodopa
· usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine
· reduced effectiveness with time (usually by 2 years)
· unwanted effects: dyskinesia (involuntary writhing movements), 'on-off' effect, dry mouth, anorexia, palpitations, postural hypotension, psychosis, drowsiness
· no use in neuroleptic induced parkinsonism
· it is important not to acutely stop levodopa, for example if a patient is admitted to hospital. If a patient with Parkinson's disease cannot take levodopa orally, they can be given a dopamine agonist patch as rescue medication to prevent acute dystonia
Dopamine receptor agonists
· e.g. bromocriptine, ropinirole, cabergoline, apomorphine
· ergot-derived dopamine receptor agonists (bromocriptine, cabergoline) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored
· patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence
· more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patients
MAO-B (Monoamine Oxidase-B) inhibitors
· e.g. selegiline
· inhibits the breakdown of dopamine secreted by the dopaminergic neurons
Amantadine
· mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses
· side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis
COMT (Catechol-O-Methyl Transferase) inhibitors
· e.g. entacapone, tolcapone
· COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy
· used in conjunction with levodopa in patients with established PD
Antimuscarinics
· block cholinergic receptors
· now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson's disease
· help tremor and rigidity
· e.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)
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| Image sourced from Wikipedia | |
Diagram showing the mechanism of action of Parkinson's drugs
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Stroke: types
The Bamford/Oxford Stroke Classification (also known as the Bamford Classification) classifies strokes based on the initial symptoms. A summary is as follows:
The following criteria should be assessed:
· 1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
· 2. homonymous hemianopia
· 3. higher cognitive dysfunction e.g. dysphasia
Total anterior circulation infarcts (TACI, c. 15%)
· involves middle and anterior cerebral arteries
· all 3 of the above criteria are present
Partial anterior circulation infarcts (PACI, c. 25%)
· involves smaller arteries of anterior circulation e.g. upper or lower division of middle cerebral artery
· 2 of the above criteria are present
Lacunar infarcts (LACI, c. 25%)
· involves perforating arteries around the internal capsule, thalamus and basal ganglia
· presents with 1 of the following:
· 1. unilateral weakness (and/or sensory deficit) of face and arm, arm and leg or all three.
· 2. pure sensory stroke.
· 3. ataxic hemiparesis
Posterior circulation infarcts (POCI, c. 25%)
· involves vertebrobasilar arteries
· presents with 1 of the following:
· 1. cerebellar or brainstem syndromes
· 2. loss of consciousness
· 3. isolated homonymous hemianopia
Other recognised patterns of stroke:
Lateral medullary syndrome (posterior inferior cerebellar artery)
· aka Wallenberg's syndrome
· ipsilateral: ataxia, nystagmus, dysphagia, facial numbness, cranial nerve palsy e.g. Horner's
· contralateral: limb sensory loss
Weber's syndrome
· ipsilateral III palsy
· contralateral weakness
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Migraine: management
It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines.
Acute treatment
· first-line: offer combination therapy with an oral triptan and an NSAID, or an oral triptan and paracetamol
· for young people aged 12-17 years consider a nasal triptan in preference to an oral triptan
· if the above measures are not effective or not tolerated offer a non-oral preparation of metoclopramide* or prochlorperazine and consider adding a non-oral NSAID or triptan
Prophylaxis
· prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients.
· NICE advise either topiramate or propranolol 'according to the person's preference, comorbidities and risk of adverse events'. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives
· if these measures fail NICE recommend 'a course of up to 10 sessions of acupuncture over 5-8 weeks'
· NICE recommend: 'Advise people with migraine that riboflavin (400 mg once a day) may be effective in reducing migraine frequency and intensity for some people'
· for women with predictable menstrual migraine treatment NICE recommend either frovatriptan (2.5 mg twice a day) or zolmitriptan (2.5 mg twice or three times a day) as a type of 'mini-prophylaxis'
· pizotifen is no longer recommend. Adverse effects such as weight gain & drowsiness are common
*caution should be exercised with young patients as acute dystonic reactions may develop
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Motor neuron disease: features
Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, progressive muscular atrophy and bulbar palsy.
There are a number of clues which point towards a diagnosis of motor neuron disease:
· fasciculations
· the absence of sensory signs/symptoms*
· the mixture of lower motor neuron and upper motor neuron signs
· wasting of the small hand muscles/tibialis anterior is common
Other features
· doesn't affect external ocular muscles
· no cerebellar signs
· abdominal reflexes are usually preserved and sphincter dysfunction if present is a late feature
The diagnosis of motor neuron disease is clinical, but nerve conduction studies will show normal motor conduction and can help exclude a neuropathy. Electromyography shows a reduced number of action potentials with increased amplitude. MRI is usually performed to exclude the differential diagnosis of cervical cord compression and myelopathy
*vague sensory symptoms may occur early in the disease (e.g. limb pain) but 'never' sensory signs
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Myasthenia gravis
Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases*. Myasthenia is more common in women (2:1)
The key feature is muscle fatigability - muscles become progressively weaker during periods of activity and slowly improve after periods of rest:
· extraocular muscle weakness: diplopia
· proximal muscle weakness: face, neck, limb girdle
· ptosis
· dysphagia
Associations
· thymomas in 15%
· autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE
· thymic hyperplasia in 50-70%
Investigations
· single fibre electromyography: high sensitivity (92-100%)
· CT thorax to exclude thymoma
· CK normal
· autoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine kinase antibodies
· Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used anymore due to the risk of cardiac arrhythmia
Management
· long-acting acetylcholinesterase inhibitors
o pyridostigmine is first-line
· immunosuppression may be used if
o prednisolone initially
o azathioprine, cyclosporine, mycophenolate mofetil may also be used
· thymectomy
Management of myasthenic crisis
· plasmapheresis
· intravenous immunoglobulins
*antibodies are less commonly seen in disease limited to the ocular muscles
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a rare but dangerous condition seen in patients taking antipsychotic medication. It carries a mortality of up to 10% and can also occur with atypical antipsychotics. It may also occur with dopaminergic drugs (such as levodopa) for Parkinson's disease, usually when the drug is suddenly stopped or the dose reduced.
The pathophysiology is unknown but one theory is that the dopamine blockade induced by antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle damage.
It occurs within hours to days of starting an antipsychotic (antipsychotics are also known as neuroleptics, hence the name) and the typical features are:
· pyrexia
· muscle rigidity
· autonomic lability: typical features include hypertension, tachycardia and tachypnoea
· agitated delirium with confusion
A raised creatine kinase is present in most cases. Acute kidney injury (secondary to rhabdomyolysis) may develop in severe cases. A leukocytosis may also be seen
Management
· stop antipsychotic
· patients should be transferred to a medical ward if they are on a psychiatric ward and often they are nursed in intensive care units
· IV fluids to prevent renal failure
· dantrolene may be useful in selected cases
o thought to work by decreasing excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing the release of calcium from the sarcoplasmic reticulum
· bromocriptine, dopamine agonist, may also be used
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| |
Venn diagram showing contrasting serotonin syndrome with neuroleptic malignant syndrome. Note that both conditions can cause a raised creatine kinase (CK) but it tends to be more associated with NMS.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Parkinson's disease: features
Parkinson's disease is a progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra. This results in a classic triad of features: bradykinesia, tremor and rigidity. The symptoms of Parkinson's disease are characteristically asymmetrical.
Epidemiology
· around twice as common in men
· mean age of diagnosis is 65 years
Bradykinesia
· poverty of movement also seen, sometimes referred to as hypokinesia
· short, shuffling steps with reduced arm swinging
· difficulty in initiating movement
Tremor
· most marked at rest, 3-5 Hz
· worse when stressed or tired, improves with voluntary movement
· typically 'pill-rolling', i.e. in the thumb and index finger
Rigidity
· lead pipe
· cogwheel: due to superimposed tremor
Other characteristic features
· mask-like facies
· flexed posture
· micrographia
· drooling of saliva
· psychiatric features: depression is the most common feature (affects about 40%); dementia, psychosis and sleep disturbances may also occur
· impaired olfaction
· REM sleep behaviour disorder
· fatigue
· autonomic dysfunction:
o postural hypotension
Drug-induced parkinsonism has slightly different features to Parkinson's disease:
· motor symptoms are generally rapid onset and bilateral
· rigidity and rest tremor are uncommon
Diagnosis is usually clinical. However, if there is difficulty differentiating between essential tremor and Parkinson's disease NICE recommend considering 123I‑FP‑CIT single photon emission computed tomography (SPECT).
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| Image sourced from Wikipedia | |
A Lewy body (stained brown) in a brain cell of the substantia nigra in Parkinson's disease. The brown colour is positive immunohistochemistry staining for alpha-synuclein.
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| Image sourced from Wikipedia | |
Discoloration of the substantia nigra due to loss of pigmented nerve cells.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:17
Tuberous sclerosis
Tuberous sclerosis (TS) is a genetic condition of autosomal dominant inheritance. Like neurofibromatosis, the majority of features seen in TS are neurocutaneous.
Cutaneous features
· depigmented 'ash-leaf' spots which fluoresce under UV light
· roughened patches of skin over lumbar spine (Shagreen patches)
· adenoma sebaceum (angiofibromas): butterfly distribution over nose
· fibromata beneath nails (subungual fibromata)
· café-au-lait spots* may be seen
Neurological features
· developmental delay
· epilepsy (infantile spasms or partial)
· intellectual impairment
Also
· retinal hamartomas: dense white areas on retina (phakomata)
· rhabdomyomas of the heart
· gliomatous changes can occur in the brain lesions
· polycystic kidneys, renal angiomyolipomata
· lymphangioleiomyomatosis: multiple lung cysts
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Comparison of neurofibromatosis and tuberous sclerosis. Note that whilst they are both autosomal dominant neurocutaneous disorders there is little overlap otherwise
*these of course are more commonly associated with neurofibromatosis. However a 1998 study of 106 children with TS found café-au-lait spots in 28% of patients
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Brachial plexus
| Origin | Anterior rami of C5 to T1 |
| Sections of the plexus | · Roots, trunks, divisions, cords, branches · Mnemonic:Real Teenagers Drink Cold Beer |
| Roots | · Located in the posterior triangle · Pass between scalenus anterior and medius |
| Trunks | · Located posterior to middle third of clavicle · Upper and middle trunks related superiorly to the subclavian artery · Lower trunk passes over 1st rib posterior to the subclavian artery |
| Divisions | Apex of axilla |
| Cords | Related to axillary artery |
Diagram illustrating the branches of the brachial plexus
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| Image sourced from Wikipedia | |
Cutaneous sensation of the upper limb
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| Image sourced from Wikipedia | |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Multiple system atrophy
There are 2 predominant types of multiple system atrophy
· 1) MSA-P - Predominant Parkinsonian features
· 2) MSA-C - Predominant Cerebellar features
Shy-Drager syndrome is a type of multiple system atrophy.
Features
· parkinsonism
· autonomic disturbance
o erectile dysfunction: often an early feature
o postural hypotension
o atonic bladder
· cerebellar signs
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Psychogenic non-epileptic seizures
Psychogenic nonepileptic seizures are sometimes referred to as pseudoseizures.
Factors favouring pseudoseizures
· pelvic thrusting
· family member with epilepsy
· much more common in females
· crying after seizure
· don't occur when alone
· gradual onset
Factors favouring true epileptic seizures
· tongue biting
· raised serum prolactin*
Video telemetry is useful for differentiating
*why prolactin is raised following seizures is not fully understood. It is hypothesised that there is spread of electrical activity to the ventromedial hypothalamus, leading to release of a specific prolactin regulator into the hypophyseal portal system
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Subdural haemorrhage
A subdural haematoma is a collection of blood deep to the dural layer of the meninges. The blood is not within the substance of the brain and is therefore called an ‘extra-axial’ or ‘extrinsic’ lesion. They can be unilateral or bilateral.
Subdural haematomas can be classified in terms of their age:
· Acute
· Subacute
· Chronic
Although the collection of blood is within the same anatomical compartment, acute and chronic subdurals have important differences in terms of their mechanisms, associated clinical features and management:
Acute subdural haematoma
An acute subdural haematoma is a collection of fresh blood within the subdural space and is most commonly caused by high-impact trauma. Since it is associated with high-impact injuries, there is often other brain underlying brain injuries.
There is a spectrum of severity of symptoms and presentation depending on the size of the compressive acute subdural haematoma and the associated injuries. Presentation ranges from an incidental finding in trauma to severe coma and coning due to herniation.
CT imaging is the first-line investigation and will show a crescentic collection, not limited by suture lines. They will appear hyperdense (bright) in comparison to the brain. Large acute subdural haematomas will push on the brain (‘mass effect’) and cause midline shift or herniation.
Small or incidental acute subdurals can be observed conservatively. Surgical options include monitoring of intracranial pressure and decompressive craniectomy.
Chronic subdural haematoma
A chronic subdural haematoma is a collection of blood within the subdural space that has been present for weeks to months.
Rupture of the small bridging veins within the subdural space rupture and cause slow bleeding. Elderly and alcoholic patients are particularly at risk of subdural haematomas since they have brain atrophy and therefore fragile or taut bridging veins.
Presentation is typically a several week to month progressive history of either confusion, reduced consciousness or neurological deficit.
Infants also have fragile bridging veins and can rupture in shaken baby syndrome.
On CT imaging they similarly are crescentic in shape, not restricted by suture lines and compress the brain (‘mass effect’). In contrast to acute subdurals, chronic subdurals are hypodense (dark) compared to the substance of the brain.
If the chronic subdural is an incidental finding or if it is small in size with no associated neurological deficit then it can be managed conservatively with the hope that it will dissolve with time. If the patient is confused, has an associated neurological deficit or has severe imaging findings then surgical decompression with burr holes is required.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Third nerve palsy
Features
· eye is deviated 'down and out'
· ptosis
· pupil may be dilated (sometimes called a 'surgical' third nerve palsy)
Causes
· diabetes mellitus
· vasculitis e.g. temporal arteritis, SLE
· false localizing sign* due to uncal herniation through tentorium if raised ICP
· posterior communicating artery aneurysm
o pupil dilated
o often associated pain
· cavernous sinus thrombosis
· Weber's syndrome: ipsilateral third nerve palsy with contralateral hemiplegia -caused by midbrain strokes
· other possible causes: amyloid, multiple sclerosis
*this term is usually associated with sixth nerve palsies but it may be used for a variety of neurological presentations
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Trigeminal neuralgia
Trigeminal neuralgia is a pain syndrome characterised by severe unilateral pain. The vast majority of cases are idiopathic but compression of the trigeminal roots by tumours or vascular problems may occur.
The International Headache Society defines trigeminal neuralgia as:
· a unilateral disorder characterised by brief electric shock-like pains, abrupt in onset and termination, limited to one or more divisions of the trigeminal nerve
· the pain is commonly evoked by light touch, including washing, shaving, smoking, talking, and brushing the teeth (trigger factors), and frequently occurs spontaneously
· small areas in the nasolabial fold or chin may be particularly susceptible to the precipitation of pain (trigger areas)
· the pains usually remit for variable periods
NICE Clinical Knowledge Summaries list the following as red flag symptoms and signs suggesting a serious underlying cause:
· Sensory changes
· Deafness or other ear problems
· History of skin or oral lesions that could spread perineurally
· Pain only in the ophthalmic division of the trigeminal nerve (eye socket, forehead, and nose), or bilaterally
· Optic neuritis
· A family history of multiple sclerosis
· Age of onset before 40 years
Management
· carbamazepine is first-line
· failure to respond to treatment or atypical features (e.g. < 50 years old) should prompt referral to neurology
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Epilepsy: localising features of focal seizures
| Location | Typical seizure type |
| Temporal lobe (HEAD) | Hallucinations (auditory/gustatory/olfactory), Epigastric rising/Emotional, Automatisms (lip smacking/grabbing/plucking), Deja vu/Dysphasia post-ictal) |
| Frontal lobe (motor) | Head/leg movements, posturing, post-ictal weakness, Jacksonian march |
| Parietal lobe (sensory) | Paraesthesia |
| Occipital lobe (visual) | Floaters/flashes |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Facial nerve palsy
The facial nerve is the main nerve supplying the structures of the second embryonic branchial arch. It is predominantly an efferent nerve to the muscles of facial expression, digastric muscle and also to many glandular structures. It contains a few afferent fibres which originate in the cells of its genicular ganglion and are concerned with taste.
Supply - 'face, ear, taste, tear'
· face: muscles of facial expression
· ear: nerve to stapedius
· taste: supplies anterior two-thirds of tongue
· tear: parasympathetic fibres to lacrimal glands, also salivary glands
Causes of bilateral facial nerve palsy
· sarcoidosis
· Guillain-Barre syndrome
· Lyme disease
· bilateral acoustic neuromas (as in neurofibromatosis type 2)
· as Bell's palsy is relatively common it accounts for up to 25% of cases f bilateral palsy, but this represents only 1% of total Bell's palsy cases
Causes of unilateral facial nerve palsy - as above plus
| Lower motor neuron · Bell's palsy · Ramsay-Hunt syndrome (due to herpes zoster) · acoustic neuroma · parotid tumours · HIV · multiple sclerosis* · diabetes mellitus | Upper motor neuron · stroke |
LMN vs. UMN
· upper motor neuron lesion 'spares' upper face i.e. forehead
· lower motor neuron lesion affects all facial muscles
*may also cause an UMN palsy
Path
Subarachnoid path
· Origin: motor- pons, sensory- nervus intermedius
· Pass through the petrous temporal bone into the internal auditory meatus with the vestibulocochlear nerve. Here they combine to become the facial nerve.
Facial canal path
· The canal passes superior to the vestibule of the inner ear
· At the medial aspect of the middle ear, it becomes wider and contains the geniculate ganglion.
- 3 branches:
· 1. greater petrosal nerve
· 2. nerve to stapedius
· 3. chorda tympani
Stylomastoid foramen
· Passes through the stylomastoid foramen (tympanic cavity anterior and mastoid antrum posteriorly)
· Posterior auricular nerve and branch to posterior belly of digastric and stylohyoid muscle
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Neuropathic pain
Neuropathic pain may be defined as pain which arises following damage or disruption of the nervous system. It is often difficult to treat and responds poorly to standard analgesia.
Examples include:
· diabetic neuropathy
· post-herpetic neuralgia
· trigeminal neuralgia
· prolapsed intervertebral disc
NICE updated their guidance on the management of neuropathic pain in 2013:
· first-line treatment*: amitriptyline, duloxetine, gabapentin or pregabalin
o if the first-line drug treatment does not work try one of the other 3 drugs
o in contrast to standard analgesics, drugs for neuropathic pain are typically used as monotherapy, i.e. if not working then drugs should be switched, not added
· tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain
· topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
· pain management clinics may be useful in patients with resistant problems
*please note that for some specific conditions the guidance may vary. For example carbamazepine is used first-line for trigeminal neuralgia
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Peripheral neuropathy
Peripheral neuropathy may be divided into conditions which predominately cause a motor or sensory loss
Predominately motor loss
· Guillain-Barre syndrome
· porphyria
· lead poisoning
· hereditary sensorimotor neuropathies (HSMN) - Charcot-Marie-Tooth
· chronic inflammatory demyelinating polyneuropathy (CIDP)
· diphtheria
Predominately sensory loss
· diabetes
· uraemia
· leprosy
· alcoholism
· vitamin B12 deficiency
· amyloidosis
Alcoholic neuropathy
· secondary to both direct toxic effects and reduced absorption of B vitamins
· sensory symptoms typically present prior to motor symptoms
Vitamin B12 deficiency
· subacute combined degeneration of spinal cord
· dorsal column usually affected first (joint position, vibration) prior to distal paraesthesia
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Phenytoin
Phenytoin is used in the management of seizures.
Mechanism of action
· binds to sodium channels increasing their refractory period
Adverse effects
Phenytoin is associated with a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic. Phenytoin is also an inducer of the P450 system.
Acute
· initially: dizziness, diplopia, nystagmus, slurred speech, ataxia
· later: confusion, seizures
Chronic
· common: gingival hyperplasia (secondary to increased expression of platelet derived growth factor, PDGF), hirsutism, coarsening of facial features, drowsiness
· megaloblastic anaemia (secondary to altered folate metabolism)
· peripheral neuropathy
· enhanced vitamin D metabolism causing osteomalacia
· lymphadenopathy
· dyskinesia
Idiosyncratic
· fever
· rashes, including severe reactions such as toxic epidermal necrolysis
· hepatitis
· Dupuytren's contracture*
· aplastic anaemia
· drug-induced lupus
Teratogenic
· associated with cleft palate and congenital heart disease
Monitoring
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose should be checked if:
· adjustment of phenytoin dose
· suspected toxicity
· detection of non-adherence to the prescribed medication
*although not listed in the BNF
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Stroke by anatomy
| Site of the lesion | Associated effects |
| Anterior cerebral artery | Contralateral hemiparesis and sensory loss, lower extremity > upper |
| Middle cerebral artery | Contralateral hemiparesis and sensory loss, upper extremity > lower Contralateral homonymous hemianopia Aphasia |
| Posterior cerebral artery | Contralateral homonymous hemianopia with macular sparing Visual agnosia |
| Weber's syndrome (branches of the posterior cerebral artery that supply the midbrain) | Ipsilateral CN III palsy Contralateral weakness of upper and lower extremity |
| Posterior inferior cerebellar artery (lateral medullary syndrome, Wallenberg syndrome) | Ipsilateral: facial pain and temperature loss Contralateral: limb/torso pain and temperature loss Ataxia, nystagmus |
| Anterior inferior cerebellar artery (lateral pontine syndrome) | Symptoms are similar to Wallenberg's (see above), but: Ipsilateral: facial paralysis and deafness |
| Retinal/ophthalmic artery | Amaurosis fugax |
| Basilar artery | 'Locked-in' syndrome |
Lacunar strokes
· present with either isolated hemiparesis, hemisensory loss or hemiparesis with limb ataxia
· strong association with hypertension
· common sites include the basal ganglia, thalamus and internal capsule
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Syringomyelia
Syringomyelia (‘syrinx’ for short) describes a collection of cerebrospinal fluid within the spinal cord.
Syringobulbia is a similar phenomenon in which there is a fluid-filled cavity within the medulla of the brainstem. This is often an extension of the syringomyelia but in rare cases can be an isolated finding.
Causes include:
· a Chiari malformation: strong association
· trauma
· tumours
· idiopathic
The classical presentation of a syrinx is a patient who has a ‘cape-like’ (neck and arms) loss of sensation to temperature but preservation of light touch, proprioception and vibration. Classic examples are of patients who accidentally burn their hands without realising. This is due to the crossing spinothalamic tracts in the anterior commissure of the spinal cord being the first tracts to be affected. Other symptoms and signs include spastic weakness (predominantly of the upper limbs), paraesthesia, neuropathic pain, upgoing plantars and bowel and bladder dysfunction. Scoliosis will occur over a matter of years if the syrinx is not treated. It may cause a Horner’s syndrome due to compression of the sympathetic chain, but this is rare.
Investigation requires a full spine MRI with contrast to exclude a tumour or tethered cord. A brain MRI is also needed to exclude a Chiari malformation.
Treatment will be directed at treating the cause of the syrinx. In patients with a persistent or symptomatic syrinx, a shunt into the syrinx can be placed.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Wernicke's encephalopathy
Wernicke's encephalopathy is a neuropsychiatric disorder caused by thiamine deficiency which is most commonly seen in alcoholics. Rarer causes include: persistent vomiting, stomach cancer, dietary deficiency. A classic triad of ophthalmoplegia/nystagmus, ataxia and confusion may occur. In Wernicke's encephalopathy petechial haemorrhages occur in a variety of structures in the brain including the mamillary bodies and ventricle walls.
Features
· nystagmus (the most common ocular sign)
· ophthalmoplegia
· ataxia
· confusion, altered GCS
· peripheral sensory neuropathy
Investigations
· decreased red cell transketolase
· MRI
Treatment is with urgent replacement of thiamine
Relationship with Korsakoff syndrome
If not treated Korsakoff's syndrome may develop as well. This is termed Wernicke-Korsakoff syndrome and is characterised by the addition of antero- and retrograde amnesia and confabulation in addition to the above symptoms.
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From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
5-HT3 antagonists
5-HT3 antagonists are antiemetics used mainly in the management of chemotherapy-related nausea. They mainly act in the chemoreceptor trigger zone area of the medulla oblongata.
Examples
· ondansetron
· granisetron
Adverse effects
· constipation is common
· prolonged QT interval
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Brain tumours
The majority of adult tumours are supratentorial, where as the majority of childhood tumours are infratentorial.
| Type of tumour | Features |
| Metastases | Metastatic brain cancer is the most common form of brain tumours. They are often multiple and not treatable with surgical intervention. Tumours that most commonly spread to the brain include: · lung (most common) · breast · bowel · skin (namely melanoma) · kidney |
| Gliolastoma multiforme | • Glioblastoma is the most common primary tumour in adults and is associated with a poor prognosis (~ 1yr). • On imaging they are solid tumours with central necrosis and a rim that enhances with contrast. Disruption of the blood-brain barrier and therefore are associated with vasogenic oedema. • Histology: Pleomorphic tumour cells border necrotic areas • Treatment is surgical with postoperative chemotherapy and/or radiotherapy. Dexamethasone is used to treat the oedema. |
| Meningioma | • The second most common primary brain tumour in adults • Meningiomas are typically benign, extrinsic tumours of the central nervous system. They arise from the dura mater of the meninges and cause symptoms by compression rather than invasion. • They typically are located at the falx cerebri, superior sagittal sinus, convexity or skull base. • Histology: Spindle cells in concentric whorls and calcified psammoma bodies • Investigation is with CT (will show contrast enhancement) and MRI, and treatment will involve either observation, radiotherapy or surgical resection. |
| Vestibular schwannoma | • A vestibular schwannoma (previously termed acoustic neuroma) is a benign tumour arising from the eighth cranial nerve (vestibulocochlear nerve). Often seen in the cerebellopontine angle. It presents with hearing loss, facial nerve palsy (due to compression of the nearby facial nerve) and tinnitus. • Neurofibromatosis type 2 is associated with bilateral vestibular schwannomas. • Histology: Antoni A or B patterns are seen. Verocay bodies (acellular areas surrounded by nuclear palisades) • Treatment may involve observation, radiotherapy or surgery. |
| Pilocytic astrocytoma | • The most common primary brain tumour in children • Histology: Rosenthal fibres (corkscrew eosinophilic bundle) |
| Medulloblastoma | • A medulloblastoma is an aggressive paediatric brain tumour that arises within the infratentorial compartment. It spreads through the CSF system. Treatment is surgical resection and chemotherapy. • Histology: Small, blue cells. Rosette pattern of cells with many mitotic figures |
| Ependymoma | • Commonly seen in the 4th ventricle • May cause hydrocephalus • Histology: perivascular pseudorosettes |
| Oligodendroma | • Benign, slow-growing tumour common in the frontal lobes • Histology: Calcifications with 'fried-egg' appearance |
| Haemangioblastoma | • Vascular tumour of the cerebellum • Associated with von Hippel-Lindau syndrome • Histology: foam cells and high vascularity |
| Pituitary adenoma | • Pituitary adenomas are benign tumours of the pituitary gland. They are either secretory (producing a hormone in excess) or non-secretory. They may be divided into microadenomas (smaller than 1cm) or macroadenoma (larger than 1cm). • Patients will present with the consequences of hormone excess (e.g. Cushing’s due to ACTH, or acromegaly due to GH) or depletion. Compression of the optic chiasm will cause a bitemporal hemianopia due to the crossing nasal fibers. • Investigation requires a pituitary blood profile and MRI. Treatment can either be hormonal or surgical (e.g. transphenoidal resection). |
| Craniopharyngioma | • Most common paediatric supratentorial tumour • A craniopharyngioma is a solid/cystic tumour of the sellar region that is derived from the remnants of Rathke’s pouch. It is common in children, but can present in adults also. It may present with hormonal disturbance, symptoms of hydrocephalus or bitemporal hemianopia. • Histology: Derived from remnants of Rathke pouch • Investigation requires pituitary blood profile and MRI. Treatment is typically surgical with or without postoperative radiotherapy. |
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| © Image used on license from Radiopaedia | |
Meningioma - MRI showing the typical well-circumscribed appearance. A dural tail can be where the tumour 'connects' to the dura. It is seen in around 65% of meningiomas.
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| © Image used on license from Radiopaedia | |
Glioblastoma multiforme - CT showing a peripherally enhancing lesion within the left frontal lobe. Note the contrast to the more homogenous meningioma above.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Carbamazepine
Carbamazepine is chemically similar to the tricyclic antidepressant drugs. It is most commonly used in the treatment of epilepsy, particularly partial seizures, where carbamazepine remains a first-line medication. Other uses include
· trigeminal neuralgia
· bipolar disorder
Mechanism of action
· binds to sodium channels increases their refractory period
Adverse effects
· P450 enzyme inducer
· dizziness and ataxia
· drowsiness
· headache
· visual disturbances (especially diplopia)
· Steven-Johnson syndrome
· leucopenia and agranulocytosis
· hyponatraemia secondary to syndrome of inappropriate ADH secretion
Carbamazepine is known to exhibit autoinduction, hence when patients start carbamazepine they may see a return of seizures after 3-4 weeks of treatment.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Common peroneal nerve lesion
The sciatic nerve divides into the tibial and common peroneal nerves. Injury often occurs at the neck of the fibula
The most characteristic feature of a common peroneal nerve lesion is foot drop.
Other features include:
· weakness of foot dorsiflexion
· weakness of foot eversion
· weakness of extensor hallucis longus
· sensory loss over the dorsum of the foot and the lower lateral part of the leg
· wasting of the anterior tibial and peroneal muscles
From <https://www.passmedicine.com/review/textbook.php?s=#>
Meningitis
Most common adult cause (mortality)
· meningococcus (10%)
· pneumococcus (25%)
Diagnosis
· if partially treated with antibiotics, negative CSF culture, but glucose, protein and white cells unchanged
Neurological sequalae
· sensorineural hearing loss (most common)
· other neurological: epilepsy, paralysis
· infective: sepsis, intracerebral abscess
· pressure: brain herniation, hydrocephalus
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:18
Meningitis
Most common adult cause (mortality)
· meningococcus (10%)
· pneumococcus (25%)
Diagnosis
· if partially treated with antibiotics, negative CSF culture, but glucose, protein and white cells unchanged
Neurological sequalae
· sensorineural hearing loss (most common)
· other neurological: epilepsy, paralysis
· infective: sepsis, intracerebral abscess
· pressure: brain herniation, hydrocephalus
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Migraine: diagnostic criteria
The International Headache Society has produced the following diagnostic criteria for migraine without aura:
| Point | Criteria |
| A | At least 5 attacks fulfilling criteria B-D |
| B | Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated) |
| C | Headache has at least two of the following characteristics: · 1. unilateral location* · 2. pulsating quality (i.e., varying with the heartbeat) · 3. moderate or severe pain intensity · 4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) |
| D | During headache at least one of the following: · 1. nausea and/or vomiting* · 2. photophobia and phonophobia |
| E | Not attributed to another disorder (history and examination do not suggest a secondary headache disorder or, if they do, it is ruled out by appropriate investigations or headache attacks do not occur for the first time in close temporal relation to the other disorder) |
*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and gastrointestinal disturbance is more prominent.
Migraine with aura (seen in around 25% of migraine patients) tends to be easier to diagnose with a typical aura being progressive in nature and may occur hours prior to the headache. Typical aura include a transient hemianopic disturbance or a spreading scintillating scotoma ('jagged crescent'). Sensory symptoms may also occur
If we compare these guidelines to the NICE criteria the following points are noted:
· NICE suggests migraines may be unilateral or bilateral
· NICE also give more detail about typical auras:
Auras may occur with or without headache and:
· are fully reversible
· develop over at least 5 minutes
· last 5-60 minutes
The following aura symptoms are atypical and may prompt further investigation/referral;
· motor weakness
· double vision
· visual symptoms affecting only one eye
· poor balance
· decreased level of consciousness.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Multiple sclerosis
Multiple sclerosis is chronic cell-mediated autoimmune disorder characterised by demyelination in the central nervous system.
Epidemiology
· 3 times more common in women
· most commonly diagnosed in people aged 20-40 years
· much more common at higher latitudes (5 times more common than in tropics)
Genetics
· monozygotic twin concordance = 30%
· dizygotic twin concordance = 2%
A variety of subtypes have been identified:
Relapsing-remitting disease
· most common form, accounts for around 85% of patients
· acute attacks (e.g. last 1-2 months) followed by periods of remission
Secondary progressive disease
· describes relapsing-remitting patients who have deteriorated and have developed neurological signs and symptoms between relapses
· around 65% of patients with relapsing-remitting disease go on to develop secondary progressive disease within 15 years of diagnosis
· gait and bladder disorders are generally seen
Primary progressive disease
· accounts for 10% of patients
· progressive deterioration from onset
· more common in older people
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Neurofibromatosis
There are two types of neurofibromatosis, NF1 and NF2. Both are inherited in an autosomal dominant fashion
NF1 is also known as von Recklinghausen's syndrome. It is caused by a gene mutation on chromosome 17 which encodes neurofibromin and affects around 1 in 4,000
NF2 is caused by gene mutation on chromosome 22 and affects around 1 in 100,000
Features
| NF1 | NF2 |
| Café-au-lait spots (>= 6, 15 mm in diameter) Axillary/groin freckles Peripheral neurofibromas Iris hamatomas (Lisch nodules) in > 90% Scoliosis Pheochromocytomas | Bilateral vestibular schwannomas Multiple intracranial schwannomas, mengiomas and ependymomas |
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Comparison of neurofibromatosis and tuberous sclerosis. Note that whilst they are both autosomal dominant neurocutaneous disorders there is little overlap otherwise
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Normal pressure hydrocephalus
Normal pressure hydrocephalus is a reversible cause of dementia seen in elderly patients. It is thought to be secondary to reduced CSF absorption at the arachnoid villi. These changes may be secondary to head injury, subarachnoid haemorrhage or meningitis.
A classical triad of features is seen
· urinary incontinence
· dementia and bradyphrenia
· gait abnormality (may be similar to Parkinson's disease)
It is thought around 60% of patients will have all 3 features at the time of diagnosis. Symptoms typically develop over a few months.
Imaging
· hydrocephalus with an enlarged fourth ventricle
· in addition to the ventriculomegaly there is typically an absence of substantial sulcal atrophy
Management
· ventriculoperitoneal shunting
· around 10% of patients who have shunts experience significant complications such as seizures, infection and intracerebral haemorrhages
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Radial nerve
Continuation of posterior cord of the brachial plexus (root values C5 to T1)
Path
· In the axilla: lies posterior to the axillary artery on subscapularis, latissimus dorsi and teres major.
· Enters the arm between the brachial artery and the long head of triceps (medial to humerus).
· Spirals around the posterior surface of the humerus in the groove for the radial nerve.
· At the distal third of the lateral border of the humerus it then pierces the intermuscular septum and descends in front of the lateral epicondyle.
· At the lateral epicondyle it lies deeply between brachialis and brachioradialis where it then divides into a superficial and deep terminal branch.
· Deep branch crosses the supinator to become the posterior interosseous nerve.
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| Image sourced from Wikipedia | |
In the image above the relationships of the radial nerve can be appreciated
Regions innervated
| Motor (main nerve) | · Triceps · Anconeus · Brachioradialis · Extensor carpi radialis |
| Motor (posterior interosseous branch) | · Supinator · Extensor carpi ulnaris · Extensor digitorum · Extensor indicis · Extensor digiti minimi · Extensor pollicis longus and brevis · Abductor pollicis longus |
| Sensory | The area of skin supplying the proximal phalanges on the dorsal aspect of the hand is supplied by the radial nerve (this does not apply to the little finger and part of the ring finger) |
Muscular innervation and effect of denervation
| Anatomical location | Muscle affected | Effect of paralysis |
| Shoulder | Long head of triceps | Minor effects on shoulder stability in abduction |
| Arm | Triceps | Loss of elbow extension |
| Forearm | Supinator Brachioradialis Extensor carpi radialis longus and brevis | Weakening of supination of prone hand and elbow flexion in mid prone position |
Patterns of damage
· wrist drop
· sensory loss to small area between the dorsal aspect of the 1st and 2nd metacarpals
Axillary damage
· as above
· paralysis of triceps
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| Image sourced from Wikipedia | |
The cutaneous sensation of the upper limb- illustrating the contribution of the radial nerve
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Thoracic outlet syndrome
Thoracic outlet syndrome (TOS) is a disorder involving compression of brachial plexus, subclavian artery or vein at the site of the thoracic outlet. TOS can be neurogenic or vascular; the former accounts for 90% of the cases.
Epidemiology
· given the lack of widely agreed diagnostic criteria, the epidemiology of TOS is not well documented
· patients are typically young thin women possessing long neck and drooping shoulders
· peak onset occurs in the 4th decade
Aetiology
· TOS develops when neck trauma occurs to individuals with anatomical predispositions
· neck trauma can either be a single acute incident or repeated stresses
· anatomical anomalies can either be in the form of soft tissue (70%) or osseous structures (30%)
· a well-known osseous anomaly is the presence of cervical rib
· examples of soft tissue causes are scalene muscle hypertrophy and anomalous bands
· there is usually a history of neck trauma preceding TOS
Clinical presentation of neurogenic TOS
· painless muscle wasting of hand muscles, with patients complaining of hand weakness e.g. grasping
· sensory symptoms such as numbness and tingling may be present
· if autonomic nerves are involved, the patient may experience cold hands, blanching or swelling
Clinical presentation of vascular TOS:
· subclavian vein compression leads to painful diffuse arm swelling with distended veins
· subclavian artery compression leads to painful arm claudication and in severe cases, ulceration and gangrene
Examinations:
· neurological examination and musculoskeletal examination are necessary
· stress manoeuvres such as Adson's manoeuvres may be attempted although they have limited utility
· careful examinations should aim to rule out other pathologies of the cervical spine, the shoulder or peripheral nerves. For instance, cervical radiculopathy, shoulder injuries and carpal tunnel syndrome
Investigations:
· chest and cervical spine plain radiographs to check for any obvious osseous abnormalities e.g. cervical ribs, exclude malignant tumours or other differentials e.g. cervical spine degenerative changes
· other imaging modalities may be helpful e.g. CT or MRI to rule out cervical root lesions
· venography or angiography may be helpful in vascular TOS
· an anterior scalene block may be used to confirm neurogenic TOS and check the likelihood of successful surgical treatment
Treatment:
· there is a limited evidence base
· conservative management with education, rehabilitation, physiotherapy, or taping is typically the first-line management for neurogenic TOS
· surgical decompression is warranted where conservative management has failed especially if there is a physical anomaly. Early intervention may prevent brachial plexus degeneration
· in vascular TOS, surgical treatment may be preferred
· other therapies being investigated include botox injection
Further reading
1. Huang JH, Zager EL; Thoracic outlet syndrome. Neurosurgery. 2004 Oct55(4):897-902
2. Al-Hashel JY, El Shorbgy AA, Ahmed SF, et al; Early versus Late Surgical Treatment for Neurogenic Thoracic Outlet Syndrome. ISRN Neurol. 2013 Sep 102013:673020. doi: 10.1155/2013/673020.
3. Kuhn, J. E., Lebus V, G. F., & Bible, J. (2015). Thoracic outlet syndrome. Journal of the American Academy of Orthopaedic Surgeons, 23(4), 222-232. https://doi.org/10.5435/JAAOS-D-13-00215
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Aphasia
The table below lists the major types of aphasia. Remember that dysarthria is different and refers to a motor speech disorder.
| Type of aphasia | Notes |
| Wernicke's (receptive) aphasia | Due to a lesion of the superior temporal gyrus. It is typically supplied by the inferior division of the left MCA This area 'forms' the speech before 'sending it' to Broca's area. Lesions result in sentences that make no sense, word substitution and neologisms but speech remains fluent Comprehension is impaired |
| Broca's (expressive) aphasia | Due to a lesion of the inferior frontal gyrus. It is typically supplied by the superior division of the left MCA Speech is non-fluent, laboured, and halting Comprehension is normal |
| Conduction aphasia | Classically due to a stroke affecting the arcuate fasiculus - the connection between Wernicke's and Broca's area Speech is fluent but repetition is poor. Aware of the errors they are making Comprehension is normal |
| Global aphasia | Large lesion affecting all 3 of the above areas resulting in severe expressive and receptive aphasia May still be able to communicate using gestures |
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Diagram showing the main types of aphasia
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Arnold-Chiari malformation
Arnold-Chiari malformation describes the downward displacement, or herniation, of the cerebellar tonsils through the foramen magnum. Malformations may be congenital or acquired through trauma.
Features
· non-communicating hydrocephalus may develop as a result of obstruction of cerebrospinal fluid (CSF) outflow
· headache
· syringomyelia
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Autonomic dysreflexia
This clinical syndrome occurs in patients who have had a spinal cord injury at, or above T6 spinal level. Briefly, afferent signals, most commonly triggered by faecal impaction or urinary retention (but many other triggers have been reported) cause a sympathetic spinal reflex via thoracolumbar outflow. The usual, centrally mediated, parasympathetic response however is prevented by the cord lesion. The result is an unbalanced physiological response, characterised by extreme hypertension, flushing and sweating above the level of the cord lesion, agitation, and in untreated cases severe consequences of extreme hypertension have been reported, e.g. haemorrhagic stroke.
Management of autonomic dysreflexia involves removal/control of the stimulus and treatment of any life-threatening hypertension and/or bradycardia.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Dermatomes
The table below lists the major dermatome landmarks:
| Nerve root | Landmark | Mnemonics |
| C2 | Posterior half of the skull (cap) | |
| C3 | High turtleneck shirt | |
| C4 | Low-collar shirt | |
| C5 | Ventral axial line of upper limb | |
| C6 | Thumb + index finger | Make a 6 with your left hand by touching the tip of the thumb & index finger together - C6 |
| C7 | Middle finger + palm of hand | |
| C8 | Ring + little finger | |
| T4 | Nipples | T4 at the Teat Pore |
| T5 | Inframammary fold | |
| T6 | Xiphoid process | |
| T10 | Umbilicus | BellybuT-TEN |
| L1 | Inguinal ligament | L for ligament, 1 for 1nguinal |
| L4 | Knee caps | Down on aLL fours - L4 |
| L5 | Big toe, dorsum of foot (except lateral aspect) | L5 = Largest of the 5 toes |
| S1 | Lateral foot, small toe | S1 = the smallest one |
| S2, S3 | Genitalia |
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From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Epilepsy: a very basic introduction
Epilepsy is a common neurological condition characterised by recurrent seizures. There are around 500,000 people in the UK with epilepsy, of whom around two-thirds achieve satisfactory seizure control with antiepileptic medication.
Epilepsy most commonly occurs in isolation although certain conditions have an association with epilepsy:
· cerebral palsy: around 30% have epilepsy
· tuberous sclerosis
· mitochondrial diseases
It should be remembered that epilepsy is not the only reason people have seizures. The table below shows some of the more common causes of recurrent seizures seen in clinical practice. Patients may of course develop one-off seizures following any insult to the brain, for example infection, trauma or metabolic disturbance.
| Disorder | Notes |
| Febrile convulsions | · typically occur in children between the ages of 6 months and 5 years · around 3% of children will have at least one febrile convulsion · usually occur early in a viral infection as the temperature rises rapidly · seizures are typically brief and generalised tonic/tonic-clonic in nature |
| Alcohol withdrawal seizures | · occur in patients with a history of alcohol excess who suddenly stop drinking, for example following admission to hospital · chronic alcohol consumption enhances GABA mediated inhibition in the CNS (similar to benzodiazepines) and inhibits NMDA-type glutamate receptors.Alcohol withdrawal is thought to be lead to the opposite (decreased inhibitory GABA and increased NMDA glutamate transmission) · the peak incidence of seizures is at around 36 hours following cessation of drinking · patients are often given benzodiazepines following cessation of drinking to reduce the risk |
| Psychogenic non-epileptic seizures | · previously termed pseudoseizures, this term describes patients who present with epileptic-like seizures but do not have characteristic electrical discharges · patients may have a history of mental health problems or a personality disorder |
Classification of seizures
The basic classification of epilepsy has changed in recent years. The new basic seizure classification is based on 3 key features:
· 1. Where seizures begin in the brain
· 2. Level of awareness during a seizure (important as can affect safety during seizure)
· 3. Other features of seizures
Focal seizures
· previously termed partial seizures
· these start in a specific area, on one side of the brain
· the level of awareness can vary in focal seizures. The terms focal aware (previously termed 'simple partial'), focal impaired awareness (previously termed 'complex partial') and awareness unknown are used to further describe focal seizures
· further to this, focal seizures can be classified as being motor (e.g. Jacksonian march), non-motor (e.g. déjà vu, jamais vu; ) or having other features such as aura
Generalised
· these engage or involve networks on both sides of the brain at the onset
· consciousness lost immediately. The level of awareness in the above classification is therefore not needed, as all patients lose consciousness
· generalised seizures can be further subdivided into motor (e.g. tonic-clonic) and non-motor (e.g. absence)
· specific types include:
· → tonic-clonic (grand mal)
· → tonic
· → clonic
· → typical absence (petit mal)
· → myoclonic: brief, rapid muscle jerks
· → atonic
Unknown onset
· this termed is reserved for when the origin of the seizure is unknown
Focal to bilateral seizure
· starts on one side of the brain in a specific area before spreading to both lobes
· previously termed secondary generalized seizures
In addition a number of special forms of epilepsy are recognised in children:
| Syndrome | Notes |
| Infantile spasms (West's syndrome) | Brief spasms beginning in first few months of life · 1. Flexion of head, trunk, limbs → extension of arms (Salaam attack); last 1-2 secs, repeat up to 50 times · 2. Progressive mental handicap · 3. EEG: hypsarrhythmia · usually 2nd to serious neurological abnormality (e.g. TS, encephalitis, birth asphyxia) or may be cryptogenic · poor prognosis |
| Lennox-Gastaut syndrome | May be extension of infantile spasms (50% have hx) · onset 1-5 yrs · atypical absences, falls, jerks · 90% moderate-severe mental handicap · EEG: slow spike · ketogenic diet may help |
| Benign rolandic epilepsy | · paraesthesia (e.g. unilateral face), usually on waking up |
| Juvenile myoclonic epilepsy (Janz syndrome) | Typical onset in the teens, more common in girls · 1. Infrequent generalized seizures, often in morning · 2. Daytime absences · 3. Sudden, shock like myoclonic seizure · usually good response to sodium valproate |
Symptoms and signs
As well as the seizure activity described above patients who have had generalised seizures may
· bite their tongue
· experience incontinence of urine
Asking about such features can be useful way of detecting epileptic seizures when taking a history from a patient who presents with a 'blackout' or 'collapse'.
Following a seizure patients typically have a postictal phase where they feel drowsy and tired for around 15 minutes.
Investigations
Following their first seizure patients generally have both an electroencephalogram (EEG) and neuroimaging (usually a MRI).
Management
Most neurologists now start antiepileptics following a second epileptic seizure.
As a general rule:
· sodium valproate is used first-line for patients with generalised seizures
· carbamazepine is used first-line for patients with partial seizures
Antiepileptics are one of the few drugs where it is recommended that we prescribe by brand, rather than generically, due to the risk of slightly different bioavailability resulting in a lowered seizure threshold.
It is useful when thinking about the management of epilepsy to consider certain groups of patients:
· patients who drive: generally patients cannot drive for 6 months following a seizure. For patients with established epilepsy they must be fit free for 12 months before being able to drive
· patients taking other medications: antiepileptics can induce/inhibit the P450 system resulting in varied metabolism of other medications, for example warfarin
· women wishing to get pregnant: antiepileptics are generally teratogenic, particularly sodium valproate. It is important that women take advice from a neurologist prior to becoming pregnant, to ensure they are on the most suitable antiepileptic medication. Breastfeeding is generally considered safe for mothers taking antiepileptics with the possible exception of the barbiturates
· women taking contraception: both the effect of the contraceptive on the effectiveness of the anti-epileptic medication and the effect of the anti-epileptic on the effectiveness of the contraceptive need to be considered
The table below looks at some of the more commonly used antiepileptics:
| Drug | Mechanism of action | Uses | Adverse effects |
| Sodium valproate | Increases GABA activity | First-line for generalised seizures | · increased appetite and weight gain · alopecia: regrowth may be curly · P450 enzyme inhibitor · ataxia · tremor · hepatitis · pancreatitis · thrombocytopaenia · teratogenic (neural tube defects) |
| Carbamazepine | Binds to sodium channels increasing their refractory period | First-line for partial seizures | · P450 enzyme inducer · dizziness and ataxia · drowsiness · leucopenia and agranulocytosis · syndrome of inappropriate ADH secretion · visual disturbances (especially diplopia) |
| Lamotrigine | Sodium channel blocker | Used second-line for a variety of generalised and partial seizures | · Stevens-Johnson syndrome |
| Phenytoin | Binds to sodium channels increasing their refractory period | No longer used first-line due to side-effect profile | · P450 enzyme inducer · dizziness and ataxia · drowsiness · gingival hyperplasia, hirsutism, coarsening of facial features · megaloblastic anaemia · peripheral neuropathy · enhanced vitamin D metabolism causing osteomalacia · lymphadenopathy |
Acute management of seizures
Most seizures terminate spontaneously. When seizures don't terminate after 5-10 minutes then it is often appropriate to administer medication to terminate the seizure. Patients are often prescribed these so family members may administer them in this eventuality, often termed 'rescue medication'. Benzodiazepines such as diazepam are typically used are may be administered rectally or intranasally/under the tongue.
If a patient continues to fit despite such measures then they are termed to have status epilepticus. This is a medical emergency requiring hospital treatment. Management options include further benzodiazepine medication, infusions of antiepileptics or even the use of general anaesthetic agents.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Fourth nerve palsy
Overview
· supplies superior oblique (depresses eye, moves inward)
Features
· vertical diplopia
o classically noticed when reading a book or going downstairs
· subjective tilting of objects (torsional diplopia)
· the patient may develop a head tilt, which they may or may not be aware of
· when looking straight ahead, the affected eye appears to deviate upwards and is rotated outwards
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:19
Headache
Headache accounts for a large proportion of medical consultations. The table below summarises the main characteristics of common or important causes:
| Condition | Notes |
| Migraine | Recurrent, severe headache which is usually unilateral and throbbing in nature May be be associated with aura, nausea and photosensitivity Aggravated by, or causes avoidance of, routine activities of daily living. Patients often describe 'going to bed'. In women may be associated with menstruation |
| Tension headache | Recurrent, non-disabling, bilateral headache, often described as a 'tight-band' Not aggravated by routine activities of daily living |
| Cluster headache* | Pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours with clusters typically lasting 4-12 weeks Intense pain around one eye (recurrent attacks 'always' affect same side) Patient is restless during an attack Accompanied by redness, lacrimation, lid swelling More common in men and smokers |
| Temporal arteritis | Typically patient > 60 years old Usually rapid onset (e.g. < 1 month) of unilateral headache Jaw claudication (65%) Tender, palpable temporal artery Raised ESR |
| Medication overuse headache | Present for 15 days or more per month Developed or worsened whilst taking regular symptomatic medication Patients using opioids and triptans are at most risk May be psychiatric co-morbidity |
Other causes of headache
Acute single episode
· meningitis
· encephalitis
· subarachnoid haemorrhage
· head injury
· sinusitis
· glaucoma (acute closed-angle)
· tropical illness e.g. Malaria
Chronic headache
· chronically raised ICP
· Paget's disease
· psychological
*some neurologists use the term trigeminal autonomic cephalgia to group a number of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended such patients are referred for specialist assessment as specific treatment may be required, for example it is known paroxysmal hemicrania responds very well to indomethacin
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
HSMN
Hereditary sensorimotor neuropathy (HSMN) is a relatively new term which encompasses Charcot-Marie-Tooth disease (also known as peroneal muscular atrophy). Over 7 types have been characterised - however only 2 are common to clinical practice
· HSMN type I: primarily due to demyelinating pathology
· HSMN type II: primarily due to axonal pathology
HSMN type I
· autosomal dominant
· due to defect in PMP-22 gene (which codes for myelin)
· features often start at puberty
· motor symptoms predominate
· distal muscle wasting, pes cavus, clawed toes
· foot drop, leg weakness often first features
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Lambert-Eaton syndrome
Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer and to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against presynaptic voltage-gated calcium channel in the peripheral nervous system.
Features
· repeated muscle contractions lead to increased muscle strength (in contrast to myasthenia gravis)
o in reality, this is seen in only 50% of patients and following prolonged muscle use muscle strength will eventually decrease
· limb-girdle weakness (affects lower limbs first)
· hyporeflexia
· autonomic symptoms: dry mouth, impotence, difficulty micturating
· ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)
EMG
· incremental response to repetitive electrical stimulation
Management
· treatment of underlying cancer
· immunosuppression, for example with prednisolone and/or azathioprine
· 3,4-diaminopyridine is currently being trialled
o works by blocking potassium channel efflux in the nerve terminal so that the action potential duration is increased. Calcium channels can then be open for a longer time and allow greater acetylcholine release to the stimulate muscle at the end plate
· intravenous immunoglobulin therapy and plasma exchange may be beneficial
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Median nerve
The median nerve is formed by the union of a lateral and medial root respectively from the lateral (C5,6,7) and medial (C8 and T1) cords of the brachial plexus; the medial root passes anterior to the third part of the axillary artery. The nerve descends lateral to the brachial artery, crosses to its medial side (usually passing anterior to the artery). It passes deep to the bicipital aponeurosis and the median cubital vein at the elbow.
It passes between the two heads of the pronator teres muscle, and runs on the deep surface of flexor digitorum superficialis (within its fascial sheath).
Near the wrist it becomes superficial between the tendons of flexor digitorum superficialis and flexor carpi radialis, deep to palmaris longus tendon. It passes deep to the flexor retinaculum to enter the palm, but lies anterior to the long flexor tendons within the carpal tunnel.
Branches
| Region | Branch |
| Upper arm | No branches, although the nerve commonly communicates with the musculocutaneous nerve |
| Forearm | Pronator teres Flexor carpi radialis Palmaris longus Flexor digitorum superficialis Flexor pollicis longus Flexor digitorum profundus (only the radial half) |
| Distal forearm | Palmar cutaneous branch |
| Hand (Motor) | Motor supply (LOAF) · Lateral 2 lumbricals · Opponens pollicis · Abductor pollicis brevis · Flexor pollicis brevis |
| Hand (Sensory) | · Over thumb and lateral 2 ½ fingers · On the palmar aspect this projects proximally, on the dorsal aspect only the distal regions are innervated with the radial nerve providing the more proximal cutaneous innervation. |
Patterns of damage
Damage at wrist
· e.g. carpal tunnel syndrome
· paralysis and wasting of thenar eminence muscles and opponens pollicis (ape hand deformity)
· sensory loss to palmar aspect of lateral (radial) 2 ½ fingers
Damage at elbow, as above plus:
· unable to pronate forearm
· weak wrist flexion
· ulnar deviation of wrist
Anterior interosseous nerve (branch of median nerve)
· leaves just below the elbow
· results in loss of pronation of forearm and weakness of long flexors of thumb and index finger
Topography of the median nerve
| | |
| Image sourced from Wikipedia | |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Migraine: pregnancy, contraception and other hormonal factors
SIGN produced guidelines in 2008 on the management of migraine, the following is selected highlights:
Migraine during pregnancy
· paracetamol 1g is first-line
· NSAIDs can be used second-line in the first and second trimester
· avoid aspirin and opioids such as codeine during pregnancy
Migraine and the combined oral contraceptive (COC) pill
· if patients have migraine with aura then the COC is absolutely contraindicated due to an increased risk of stroke (relative risk 8.72)
Migraine and menstruation
· many women find that the frequency and severity of migraines increase around the time of menstruation
· SIGN recommends that women are treated with mefanamic acid or a combination of aspirin, paracetamol and caffeine. Triptans are also recommended in the acute situation
Migraine and hormone replacement therapy (HRT)
· safe to prescribe HRT for patients with a history of migraine but it may make migraines worse
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Myasthenia gravis: exacerbating factors
The most common exacerbating factor is exertion resulting in fatigability, which is the hallmark feature of myasthenia gravis . Symptoms become more marked during the day
The following drugs may exacerbate myasthenia:
· penicillamine
· quinidine, procainamide
· beta-blockers
· lithium
· phenytoin
· antibiotics: gentamicin, macrolides, quinolones, tetracyclines
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Reflexes
The common reflexes are listed below:
| Reflex | Root |
| Ankle | S1-S2 |
| Knee | L3-L4 |
| Biceps | C5-C6 |
| Triceps | C7-C8 |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Sodium valproate
Sodium valproate is used in the management of epilepsy and is first-line therapy for generalised seizures. It works by increasing GABA activity.
Adverse effects
· teratogenic
o maternal use of sodium valproate is associated with a significant risk of neurodevelopmental delay in children
o guidance is now clear that sodium valproate should not be used during pregnancy and in women of childbearing age unless clearly necessary. Women of childbearing age should not start treatment without specialist neurological or psychiatric advice.
· P450 inhibitor
· gastrointestinal: nausea
· increased appetite and weight gain
· alopecia: regrowth may be curly
· ataxia
· tremor
· hepatotoxicity
· pancreatitis
· thrombocytopaenia
· hyponatraemia
· hyperammonemic encephalopathy: L-carnitine may be used as treatment if this develops
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Spinal cord lesions
The diagram belows shows cross-section view of the spinal cord:
| | |
| Image sourced from Wikipedia | |
Motor lesions
Amyotrophic lateral sclerosis (motor neuron disease)
· affects both upper (corticospinal tracts) and lower motor neurons
· results in a combination of upper and lower motor neuron signs
Poliomyelitis
· affects anterior horns resulting in lower motor neuron signs
Combined motor and sensory lesions
| Disorder | Tracts affected | Clinical notes |
| Brown-Sequard syndrome (spinal cord hemisection) | 1. Lateral corticospinal tract 2. Dorsal columns 3. Lateral spinothalamic tract | 1. Ipsilateral spastic paresis below lesion 2. Ipsilateral loss of proprioception and vibration sensation 3. Contralateral loss of pain and temperature sensation |
| Subacute combined degeneration of the spinal cord (vitamin B12 & E deficiency) | 1. Lateral corticospinal tracts 2. Dorsal columns 3. Spinocerebellar tracts | 1. Bilateral spastic paresis 2. Bilateral loss of proprioception and vibration sensation 3. Bilateral limb ataxia |
| Friedrich's ataxia | Same as subacute combined degeneration of the spinal cord (see above) | Same as subacute combined degeneration of the spinal cord (see above) In addition cerebellar ataxia → other features e.g. intention tremor |
| Anterior spinal artery occlusion | 1. Lateral corticospinal tracts 2. Lateral spinothalamic tracts | 1. Bilateral spastic paresis 2. Bilateral loss of pain and temperature sensation |
| Syringomyelia | 1. Ventral horns 2. Lateral spinothalamic tract | 1. Flacid paresis (typically affecting the intrinsic hand muscles) 2. Loss of pain and temperature sensation |
| Multiple sclerosis | Asymmetrical, varying spinal tracts involved | Combination of motor, sensory and ataxia symptoms |
Sensory lesions
| Disorder | Tracts affected | Clinical notes |
| Neurosyphilis (tabes dorsalis) | 1. Dorsal columns | 1. Loss of proprioception and vibration sensation |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Stroke management: other issues
This background note focuses on other issues in acute stroke management, particularly management of fluids, glycaemic control, blood pressure management, feeding assessment/management and disability scales.
Fluid management
· As in all patients in hospital, regular assessment for fluid status must be undertaken to ensure patients remain normovolaemic
· The NICE guidelines recommend assessing the hydration of all patients with acute stroke on admission, with regular review during their stay
· Greater than 80% of patients who cannot swallow post stroke will recover within 2-4 weeks
· However, it is important to manage fluids in this immediate post-event period as hypovolaemia can worsen the ischaemic penumbra, as well as increase risk of other complications such as infection, deep vein thrombosis, constipation and delirium
· Conversely, over-hydration can also complicate matters by leading to cerebral oedema, cardiac failure and hyponatraemia, therefore it is important to regularly review fluid status in these patients
· Recommendations for management:
o Oral hydration is preferable in all patients who are able to safely swallow
o Intravenous hydration may be necessary otherwise, and although studies have remained contentious regarding choice of intravenous fluid, UptoDate currently recommend isotonic saline without dextrose as the agent of choice in most patients
o Other factors to take into consideration when choosing fluid agent include electrolyte disturbances and/or cardiovascular status
Glycaemic control
· It is important to closely monitor and control blood sugar, particularly if they are nil by mouth due to concerns regarding swallowing safety post stroke, and/or in diabetics
· Post stroke, patients with hyperglycaemia have increased mortality independent from their age and the severity of stroke
o This is likely due to increased tissue acidosis from anaerobic metabolism, free radical generation, and increased blood brain barrier permeability post injury
· The NICE guidelines recommend maintaining a blood sugar level between 4 and 11 mmol/L in people with acute stroke
· Diabetic patients
o It is important to provide intensive management for diabetics post acute stroke
o The NICE guidelines suggest optimising insulin treatment using intravenous insulin and glucose infusions
o Hypoglycaemia also needs to be managed appropriately, as alone it can cause neuronal injury as well as mimic stroke-related neurological deficits
Blood pressure management
· Use of anti-hypertensive medications should only be used for blood pressure control in patients post ischaemic stroke if there is a hypertensive emergency with one or more of the following serious concomitant medical issues (according to the NICE guidelines):
o Hypertensive encephalopathy
o Hypertensive nephropathy
o Hypertensive cardiac failure/myocardial infarction
o Aortic dissection
o Pre-eclampsia/eclampsia
· This is because lowering blood pressure too much can potentially compromise collateral blood flow to the affected region, and possibly hasten the time to complete and irreversible tissue infarction
· If if treatment is indicated, UptoDate recommend cautious lowering of blood pressure by approximately 15% in the first 24-hours after stroke onset
· UptoDate suggest using intravenous labetalol, nicardipine and clevidipine as first-line agents, due to the possibility for rapid and safe titration to control blood pressure
· However, in patients who are candidates for thrombolytic therapy for acute stroke, blood pressure should be reduced to 185/110mmHg or lower
o Elevated BP can affect thrombolytic eligibility and delay treatment
o Timely management of elevated BP is crucial when patients are otherwise eligible for intravenous thrombolysis
o After thrombolytic therapy, UptoDate recommend ensuring that the blood pressure is stabilised and maintained at or below 180/105mmHg for at least 24 hours after treatment
Feeding assessment and management
· All patients presenting with acute stroke must be screened for safe swallowing function prior to further oral intake, as dysphagia is common after stroke
o This is to reduce the risk of aspiration and subsequent complications
o This includes prior to any oral intake of food, fluids, and/or medications
· If there are any concerns regarding swallowing, the NICE guidelines recommend specialist assessment of swallowing
o This should preferably within 24 hours of admission and not greater than 72 hours after
o Prior to assessment is undertaken, a patient should remain nil by mouth to prevent complications
· Recommendations for patients deemed unsafe for oral intake:
o Patients should receive nasogastric tube feeding, ideally within 24 hours of admission, unless they have had thrombolytic therapy
o If nasogastric tube feeding is not tolerated, patients should be considered for a nasal bridle tube/gastrostomy instead
o Medications need to be assessed to determine if formulations are available for nasogastric feeding, or if conversion to subcutaneous or intravenous forms are required
· Nutritional support may be required for patients at risk of malnutrition post stroke, whether a result from dysphagia, poor oral health or reduced ability to self-feed due to weakness or paralysis
Disability scales
· Stroke can result in a number of complications and subsequent disability, therefore disability scales are often used as a measure of functional decline post event and subsequent improvement after medical intervention
· Disability, often measured in terms of functional status (notably, basic activities of daily living), is often the leading cause of morbidity after stroke
· After a patient is medically stabilised after a stroke, they may require transfer to a rehabilitation team for ongoing treatment depending on their level of disability
· Disability is most commonly measured using the Barthel index (BI), an outcome measure for stroke
o Describes 10 tasks, and is scored according to amount of time or assistance required by the patient for each given task
o Tasks: feeding, moving from wheelchair to bed, personal toileting, getting on/off toilet, bathing, walking on level surface, ascending/descending stairs, dressing, controlling bowels and controlling bladder
o The total score is from 0 to 100, with 0 being completely dependent, and 100 being completely independent
· This index should be used to assess the functional status of a patient post stroke, and to monitor their improvement with ongoing rehabilitation to regain independence after the event
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Ulnar nerve
Overview
· arises from medial cord of brachial plexus (C8, T1)
Motor to
· medial two lumbricals
· aDductor pollicis
· interossei
· hypothenar muscles: abductor digiti minimi, flexor digiti minimi
· flexor carpi ulnaris
Sensory to
· medial 1 1/2 fingers (palmar and dorsal aspects)
Path
· the ulnar nerve travels through the posteromedial aspect of the upper arm to the flexor compartment of the forearm
· it then enters the palm of the hand via the Guyon's canal, superficial to the flexor retinaculum and lateral to the pisiform bone
| | |
| Image sourced from Wikipedia | |
Branches
| Branch | Supplies |
| Muscular branch | Flexor carpi ulnaris Medial half of the flexor digitorum profundus |
| Palmar cutaneous branch (Arises near the middle of the forearm) | Skin on the medial part of the palm |
| Dorsal cutaneous branch | Dorsal surface of the medial part of the hand |
| Superficial branch | Cutaneous fibres to the anterior surfaces of the medial one and one-half digits |
| Deep branch | Hypothenar muscles All the interosseous muscles Third and fourth lumbricals Adductor pollicis Medial head of the flexor pollicis brevis |
Patterns of damage
Damage at wrist
· 'claw hand' - hyperextension of the metacarpophalangeal joints and flexion at the distal and proximal interphalangeal joints of the 4th and 5th digits
· wasting and paralysis of intrinsic hand muscles (except lateral two lumbricals)
· wasting and paralysis of hypothenar muscles
· sensory loss to the medial 1 1/2 fingers (palmar and dorsal aspects)
Damage at elbow
· as above (however, ulnar paradox - clawing is more severe in distal lesions)
· radial deviation of wrist
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Absence seizures
Absence seizures (petit mal) are a form of generalised epilepsy that is mostly seen in children. The typical age of onset of 3-10 years old and girls are affected twice as commonly as boys
Features
· absences last a few seconds and are associated with a quick recovery
· seizures may be provoked by hyperventilation or stress
· the child is usually unaware of the seizure
· they may occur many times a day
· EEG: bilateral, symmetrical 3Hz spike and wave pattern
Management
· sodium valproate and ethosuximide are first-line treatment
· good prognosis - 90-95% become seizure free in adolescence
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Brachial plexus injuries
Erb-Duchenne paralysis
· damage to C5,6 roots
· winged scapula
· may be caused by a breech presentation
Klumpke's paralysis
· damage to T1
· loss of intrinsic hand muscles
· due to traction
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Brown-Sequard syndrome
Overview
· caused by lateral hemisection of the spinal cord
Features
· ipsilateral weakness below lesion
· ipsilateral loss of proprioception and vibration sensation
· contralateral loss of pain and temperature sensation
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Cataplexy
Cataplexy describes the sudden and transient loss of muscular tone caused by strong emotion (e.g. laughter, being frightened). Around two-thirds of patients with narcolepsy have cataplexy.
Features range from buckling knees to collapse.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Cavernous sinus
The cavernous sinuses are paired and are situated on the body of the sphenoid bone. It runs from the superior orbital fissure to the petrous temporal bone.
Relations
| Medial | Lateral |
| Pituitary fossa Sphenoid sinus | Temporal lobe |
Contents
| Lateral wall components | (from top to bottom:) Oculomotor nerve Trochlear nerve Ophthalmic nerve Maxillary nerve |
| Contents of the sinus | (from medial to lateral:) Internal carotid artery (and sympathetic plexus) Abducens nerve |
Blood supply
Ophthalmic vein, superficial cortical veins, basilar plexus of veins posteriorly.
Drains into the internal jugular vein via: the superior and inferior petrosal sinuses
| | |
| Image sourced from Wikipedia | |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Cerebellar syndrome
Unilateral cerebellar lesions cause ipsilateral signs.
Useful and well-known mnemonic to remember symptoms of cerebellar disease is DANISH:
· D - Dysdiadochokinesia, Dysmetria (past-pointing), patients may appear 'Drunk'
· A - Ataxia (limb, truncal)
· N - Nystamus (horizontal = ipsilateral hemisphere)
· I - Intention tremour
· S - Slurred staccato speech, Scanning dysarthria
· H - Hypotonia
Causes
· Friedreich's ataxia, ataxic telangiectasia
· neoplastic: cerebellar haemangioma
· stroke
· alcohol
· multiple sclerosis
· hypothyroidism
· drugs: phenytoin, lead poisoning
· paraneoplastic e.g. secondary to lung cancer
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Cerebral perfusion pressure
The cerebral perfusion pressure (CPP) is defined as being the net pressure gradient causing blood flow to the brain. The CPP is tightly autoregulated to maximise cerebral perfusion. A sharp rise in CPP may result in a rising ICP, a fall in CPP may result in cerebral ischaemia. It may be calculated by the following equation:
CPP= Mean arterial pressure - Intra cranial pressure
Following trauma, the CPP has to be carefully controlled and the may require invasive monitoring of the ICP and MAP.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Cerebrospinal fluid
The CSF fills the space between the arachnoid mater and pia mater (covering surface of the brain). The total volume of CSF in the brain is approximately 150ml. Approximately 500 ml is produced by the ependymal cells in the choroid plexus (70%), or blood vessels (30%). It is reabsorbed via the arachnoid granulations which project into the venous sinuses.
Circulation
1. Lateral ventricles (via foramen of Munro)
2. 3rd ventricle
3. Cerebral aqueduct (aqueduct of Sylvius)
4. 4th ventricle (via foramina of Magendie and Luschka)
5. Subarachnoid space
6. Reabsorbed into the venous system via arachnoid granulations into superior sagittal sinus
Composition
· Glucose: 50-80mg/dl
· Protein: 15-40 mg/dl
· Red blood cells: Nil
· White blood cells: 0-3 cells/ mm3
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Charcot-Marie-Tooth disease
Charcot-Marie-Tooth Disease is the most common hereditary peripheral neuropathy. It results in a predominantly motor loss. There is no cure, and management is focused on physical and occupational therapy.
Features:
· There may be a history of frequently sprained ankles
· Foot drop
· High-arched feet (pes cavus)
· Hammer toes
· Distal muscle weakness
· Distal muscle atrophy
· Hyporeflexia
· Stork leg deformity
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
CNS tumours
- 60% = Glioma and metastatic disease
· 20% = Meningioma
· 10% = Pituitary lesions
In paediatric practice medulloblastomas (neuroectodermal tumours) were the commonest lesions, astrocytomas now account for the majority.
Tumours arising in right temporal and frontal lobe may reach considerable size before becoming symptomatic. Whereas tumours in the speech and visual areas will typically produce early symptoms.
Diagnosis
MRI Scanning provides the best resolution.
Treatment
Usually surgery, even if tumour cannot be completely resected conditions such as rising ICP can be addressed with tumour debulking and survival and quality of life prolonged.
Curative surgery can usually be undertaken with lesions such as meningiomas. Gliomas have a marked propensity to invade normal brain and resection of these lesions is nearly always incomplete.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Complex regional pain syndrome
Complex regional pain syndrome (CRPS) is the modern, umbrella term for a number of conditions such as reflex sympathetic dystrophy and causalgia. It describes a number of neurological and related symptoms which typically occur following surgery or a minor injury. CRPS is 3 times more common in women.
There are two types of CRPS:
· type I (most common): there is no demonstrable lesion to a major nerve
· type II: there is a lesion to a major nerve
Features
· progressive, disproportionate symptoms to the original injury/surgery
· allodynia
· temperature and skin colour changes
· oedema and sweating
· motor dysfunction
· the Budapest Diagnostic Criteria are commonly used in the UK
Management
· early physiotherapy is important
· neuropathic analgesia in-line with NICE guidelines
· specialist management (e.g. Pain team) is required
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Dystrophinopathies
Overview
· X-linked recessive
· due to mutation in the gene encoding dystrophin, dystrophin gene on Xp21
· dystrophin is part of a large membrane associated protein in muscle which connects the muscle membrane to actin, part of the muscle cytoskeleton
· in Duchenne muscular dystrophy there is a frameshift mutation resulting in one or both of the binding sites are lost leading to a severe form
· in Becker muscular dystrophy there is a non-frameshift insertion in the dystrophin gene resulting in both binding sites being preserved leading to a milder form
Duchenne muscular dystrophy
· progressive proximal muscle weakness from 5 years
· calf pseudohypertrophy
· Gower's sign: child uses arms to stand up from a squatted position
· 30% of patients have intellectual impairment
Becker muscular dystrophy
· develops after the age of 10 years
· intellectual impairment much less common
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Electromyography
Electromyography (EMG) is used to evaluate the physiological properties of muscles at rest and whilst contracting
General characteristics of an abnormal EMG are listed below
| Condition | Characteristic |
| Neuropathy | • Increased action potential duration • Increased action potential amplitude |
| Myopathy | • Decreased action potential duration • Decreased action potential amplitude |
Specific characteristics of abnormal EMGs are shown in the table below
| Condition | Characteristic |
| Myasthenia gravis | Diminished response to repetitive stimulation |
| Lambert-Eaton syndrome | Incremental response to repetitive stimulation |
| Myotonic syndromes | extended series of repetitive discharges lasting up to 30 seconds |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Encephalitis
Features
· fever, headache, psychiatric symptoms, seizures, vomiting
· focal features e.g. aphasia
· peripheral lesions (e.g. cold sores) have no relation to presence of HSV encephalitis
Pathophysiology
· HSV-1 responsible for 95% of cases in adults
· typically affects temporal and inferior frontal lobes
Investigation
· CSF: lymphocytosis, elevated protein
· PCR for HSV
· CT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal in one-third of patients
· MRI is better
· EEG pattern: lateralised periodic discharges at 2 Hz
Management
· intravenous aciclovir should be started in all cases of suspected encephalitis
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:20
Epilepsy in children: syndromes
Infantile spasms (West's syndrome)
· brief spasms beginning in first few (4-6) months of life; M>F
· 1. Flexion of head, trunk, limbs → extension of arms (Salaam attack); last 1-2 secs, repeat up to 50 times
· 2. Progressive mental handicap
· 3. EEG: hypsarrhythmia
· usually 2nd to serious neurological abnormality (e.g. TS, encephalitis, birth asphyxia) or may be cryptogenic
· poor prognosis
· vigabatrin/steroids
Typical (petit mal) absence seizures
· onset 4-8 yrs
· duration few-30 secs; no warning, quick recovery; often many per day
· EEG: 3Hz generalized, symmetrical
· sodium valproate, ethosuximide
· good prognosis: 90-95% become seizure free in adolescence
Lennox-Gastaut syndrome
· may be extension of infantile spasms (50% have hx)
· onset 1-5 yrs
· atypical absences, falls, jerks
· 90% moderate-severe mental handicap
· EEG: slow spike
· ketogenic diet may help
Benign rolandic epilepsy
· most common in childhood, M>F
· paraesthesia (e.g. unilateral face), usually on waking up
Juvenile myoclonic epilepsy (Janz syndrome)
· onset: teens; F:M = 2:1
· 1. Infrequent generalized seizures, often in morning
· 2. Daytime absences
· 3. Sudden, shock like myoclonic seizure (these may develop before seizures)
· usually good response to sodium valproate
Neonatal period - try vitamin B6
· 2nd: hypoglycaemia, meningitis, head trauma
· pyridoxine dependency (AR, IV B6)
· benign familial neonatal seizures (AD)
· benign neonatal convulsions (5th day)
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:21
Extradural haematoma
An extradural (or ‘epidural’) haematoma is a collection of blood that is between the skull and the dura. It is almost always caused by trauma and most typically by ‘low-impact’ trauma (e.g. a blow to the head or a fall). The collection is often in the temporal region since the thin skull at the pterion overlies the middle meningeal artery and is therefore vulnerable to injury.
The classical presentation is of a patient who initially loses, briefly regains and then loses again consciousness after a low-impact head injury. The brief regain in consciousness is termed the ‘lucid interval’ and is lost eventually due to the expanding haematoma and brain herniation. As the haematoma expands the uncus of the temporal lobe herniates around the tentorium cerebelli and the patient develops a fixed and dilated pupil due to the compression of the parasympathetic fibers of the third cranial nerve.
On imaging, an extradural haematoma appears as a biconvex (or lentiform), hyperdense collection around the surface of the brain. They are limited by the suture lines of the skull.
In patients who have no neurological deficit, cautious clinical and radiological observation is appropriate. The definitive treatment is craniotomy and evacuation of the haematoma.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:21
Foot drop
Foot drop is a result of weakness of the foot dorsiflexors.
Possible causes include:
· common peroneal nerve lesion - the most common cause
· L5 radiculopathy
· sciatic nerve lesion
· superficial or deep peroneal nerve lesion
· other possible includes central nerve lesions (e.g. stroke) but other features are usually present
A common peroneal nerve lesion is the most common cause . This is often secondary to compression at the neck of the fibula. This may be caused by certain positions such as leg crossing, squatting or kneeling. Prolonged confinement, recent weight loss, Baker's cysts and plaster casts to the lower leg are also known to be precipitating factors.
Examination
· if the patient has an isolated peroneal neuropathy there will be weakness of foot dorsiflexion and eversion. Reflexes will be normal
· weakness of hip abduction is suggestive of a L5 radiculopathy
Bilateral symptoms, fasiculations or other abnormal neurological findings (e.g. hyperreflexia) are indications for specialist referral.
If the examination suggests a peroneal neuropathy then conservative management is appropriate. Leg crossing, squatting and kneeling should be avoided. Symptoms typically improve over 2-3 months.*
*BMJ 2015;350:h1736 - Foot drop
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:21
Guillain-Barre syndrome
Guillain-Barre syndrome describes an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni)
Pathogenesis
· cross reaction of antibodies with gangliosides in the peripheral nervous system
· correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated
· anti-GM1 antibodies in 25% of patients
Miller Fisher syndrome
· variant of Guillain-Barre syndrome
· associated with ophthalmoplegia, areflexia and ataxia. The eye muscles are typically affected first
· usually presents as a descending paralysis rather than ascending as seen in other forms of Guillain-Barre syndrome
· anti-GQ1b antibodies are present in 90% of cases
From <https://www.passmedicine.com/review/textbook.php?s=#>
Guillian-Barré Syndrome
GBS is a rare condition, but is important to recognise as it can be life-threatening. GBS will be covered in more detail in another tutorial.
The take-home points for GBS are:
· Often triggered by a viral illness, commonly campylobacter gastroenteritis
· Driven by an auto-immune process causing demyelination of the nerves
· Motor function and muscle weakness is the most prominent feature
· Pattern starts distally and ascends inwards towards the body
· Progresses for up to 4 weeks
· The big threat is weakness to the breathing and swallowing muscles
· Treated with immune modifying therapies
· Recovery takes a LONG time ("GBS - Gets Better Slowly")
The Time Place Type description for this disease would be:
Acute symmetrical diffuse sensorimotor polyneuropathy.
From <https://mle.ncl.ac.uk/cases/page/17650/>
24 December 2020
17:21
Internuclear ophthalmoplegia
Overview
· a cause of horizontal disconjugate eye movement
· due to a lesion in the medial longitudinal fasciculus (MLF)
o controls horizontal eye movements by interconnecting the IIIrd, IVth and VIth cranial nuclei
o located in the paramedian area of the midbrain and pons
Features
· impaired adduction of the eye on the same side as the lesion
· horizontal nystagmus of the abducting eye on the contralateral side
Causes
· multiple sclerosis
· vascular disease
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:21
Intracranial venous thrombosis
Overview
· can cause cerebral infarction, much lesson common than arterial causes
· 50% of patients have isolated sagittal sinus thromboses - the remainder have coexistent lateral sinus thromboses and cavernous sinus thromboses
Features
· headache (may be sudden onset)
· nausea & vomiting
Sagittal sinus thrombosis
· may present with seizures and hemiplegia
· parasagittal biparietal or bifrontal haemorrhagic infarctions are sometimes seen
Cavernous sinus thrombosis
· other causes of cavernous sinus syndrome: local infection (e.g. sinusitis), neoplasia, trauma
· periorbital oedema
· ophthalmoplegia: 6th nerve damage typically occurs before 3rd & 4th
· trigeminal nerve involvement may lead to hyperaesthesia of upper face and eye pain
· central retinal vein thrombosis
Lateral sinus thrombosis
· 6th and 7th cranial nerve palsies
| | |
| © Image used on license from Radiopaedia | |
CT with contrast demonstrating a superior sagittal sinus thrombosis showing the typical empty delta sign. Look at the 'bottom' of the scan for the triangular shaped dural sinus. This should normally be white due to it being filled with contrast. The empty delta sign occurs when the thrombus fails to enhance within the dural sinus and is outlined by enhanced collateral channels in the falx. This sign is seen in only about 25%-30% of cases but is highly diagnostic for sagittal sinus thrombosis
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:21
Lamotrigine
Lamotrigine is an antiepileptic used second-line for a variety of generalised and partial seizures.
Mechanism of action
· sodium channel blocker
Adverse effects
· Stevens-Johnson syndrome
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Levodopa
Overview
· usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of L-dopa to dopamine
· reduced effectiveness with time (usually by 2 years)
· no use in neuroleptic induced parkinsonism
Adverse effects
· dyskinesia
· 'on-off' effect
· postural hypotension
· cardiac arrhythmias
· nausea & vomiting
· psychosis
· reddish discolouration of urine upon standing
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Migraine
Migraine is a common type of primary headache. It is characterised typically by:
· a severe, unilateral, throbbing headache
· associated with nausea, photophobia and phonophobia
· attacks may last up to 72 hours
· patients characteristically go to a darkened, quiet room during an attack
· 'classic' migraine attacks are precipitated by an aura. These occur in around one-third of migraine patients
· typical aura are visual, progressive, last 5-60 minutes and are characterised by transient hemianopic disturbance or a spreading scintillating scotoma
· formal diagnostic criteria are produced by the International Headache Society (see below)
Epidemiology
· 3 times more common in women
· prevalence in men is around 6%, in women 18%
Common triggers for a migraine attack
· tiredness, stress
· alcohol
· combined oral contraceptive pill
· lack of food or dehydration
· cheese, chocolate, red wines, citrus fruits
· menstruation
· bright lights
Migraine diagnostic criteria
| A | At least 5 attacks fulfilling criteria B-D |
| B | Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated) |
| C | Headache has at least two of the following characteristics: · 1. unilateral location* · 2. pulsating quality (i.e., varying with the heartbeat) · 3. moderate or severe pain intensity · 4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) |
| D | During headache at least one of the following: · 1. nausea and/or vomiting* · 2. photophobia and phonophobia |
| E | Not attributed to another disorder (history and examination do not suggest a secondary headache disorder or, if they do, it is ruled out by appropriate investigations or headache attacks do not occur for the first time in close temporal relation to the other disorder) |
*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and gastrointestinal disturbance is more prominent.
From <https://www.passmedicine.com/review/textbook.php?s=#>
The mnemonic CHOCOLATE is useful for remembering the common precipitants.
· Chocolate
· Hangovers
· Orgasms
· Cheese
· Caffeine
· The oral contraceptive pill
· Lie-ins
· Alcohol
· Travel
· Exercise
From <https://www.passmedicine.com/question/questions.php?q=0>
24 December 2020
17:22
Motor neuron disease: management
Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, progressive muscular atrophy and bulbar palsy
Riluzole
· prevents stimulation of glutamate receptors
· used mainly in amyotrophic lateral sclerosis
· prolongs life by about 3 months
Respiratory care
· non-invasive ventilation (usually BIPAP) is used at night
· studies have shown a survival benefit of around 7 months
Prognosis
· poor: 50% of patients die within 3 years
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Multiple sclerosis: investigation
Diagnosis requires demonstration of lesions disseminated in time and space
MRI with contrast should be used to view demyelinating lesions
MRI
· high signal T2 lesions
· periventricular plaques
· Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum
CSF
· oligoclonal bands (and not in serum)
· increased intrathecal synthesis of IgG
Visual evoked potentials
· delayed, but well preserved waveform
| | |
| © Image used on license from Radiopaedia | |
MRI showing multiple white matter plaques penpendicular to the corpus callosum giving the appearance of Dawson fingers
| | |
| © Image used on license from Radiopaedia | |
MRI from a young patient with multiple sclerosis. Widespread periventricular, juxtacortical, post fossa and upper cervical cord high T2 regions are noted. Note the difference in the lesions with varying degrees of contrast enhancement and restricted diffusion indicating active/recent demyelination. This satisfies the diagnostic criteria in terms of separation in terms of time space.
| | |
| © Image used on license from Radiopaedia | |
MRI FLAIR from the same patient as above. The numerous lesions are more easily identified than in the above T2 image.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Narcolepsy
Overview
· associated with HLA-DR2
· it is associated with low levels of orexin (hypocretin), a protein which is responsible for controlling appetite and sleep patterns
· early onset of REM sleep
Features
· typical onset in teenage years
· hypersomnolence
· cataplexy (sudden loss of muscle tone often triggered by emotion)
· sleep paralysis
· vivid hallucinations on going to sleep or waking up
Investigation
· multiple sleep latency EEG
Management
· daytime stimulants (e.g. modafinil) and nighttime sodium oxybate
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Nutrition - Refeeding syndrome
Refeeding syndrome describes the metabolic abnormalities which occur on feeding a person following a period of starvation. The metabolic consequences include:
· Hypophosphataemia
· Hypokalaemia
· Hypomagnesaemia
· Abnormal fluid balance
These abnormalities can lead to organ failure.
Re-feeding problems
If patient not eaten for > 5 days, aim to re-feed at < 50% energy and protein levels
High risk for re-feeding problems
If one or more of the following:
· BMI < 16 kg/m2
· Unintentional weight loss >15% over 3-6 months
· Little nutritional intake > 10 days
· Hypokalaemia, Hypophosphataemia or hypomagnesaemia prior to feeding (unless high)
If two or more of the following:
· BMI < 18.5 kg/m2
· Unintentional weight loss > 10% over 3-6 months
· Little nutritional intake > 5 days
· History of: alcohol abuse, drug therapy including insulin, chemotherapy, diuretics and antacids
Prescription
· Start at up to 10 kcal/kg/day increasing to full needs over 4-7 days
· Start immediately before and during feeding: oral thiamine 200-300mg/day, vitamin B co strong 1 tds and supplements
· Give K+ (2-4 mmol/kg/day), phosphate (0.3-0.6 mmol/kg/day), magnesium (0.2-0.4 mmol/kg/day)
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Paroxysmal hemicrania
Paroxysmal hemicrania (PH) is defined by attacks of severe, unilateral headache, usually in the orbital, supraorbital or temporal region. These attacks are often associated with autonomic features, usually last less than 30 minutes and can occur multiple times a day.
PH sits within the group of disorders called trigeminal autonomic cephalgias which also contains cluster headache, a condition which shares many features with PH.
Importantly, PH is completely responsive to treatment with indomethacin.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Post-lumbar puncture headache
Headache following lumbar puncture (LP) occurs in approximately one-third of patients. The pathophysiology of is unclear but may relate to a 'leak' of CSF following dural puncture. Post-LP headaches are more common in young females with a low body mass index
Typical features
· usually develops within 24-48 hours following LP but may occur up to one week later
· may last several days
· worsens with upright position
· improves with recumbent position
| Factors which may contribute to headache | Factors which do not contribute to headache |
| Increased needle size Direction of bevel Not replacing the stylet Increased number of LP attempts | Increased volume of CSF removed Bed rest following procedure Increased fluid intake post procedure Opening pressure of CSF Position of patient |
Management
· supportive initially (analgesia, rest)
· if pain continues for more than 72 hours then specific treatment is indicated, to prevent subdural haematoma
· treatment options include: blood patch, epidural saline and intravenous caffeine
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Progressive supranuclear palsy
Overview
· aka Steele-Richardson-Olszewski syndrome
· a 'Parkinson Plus' syndrome
Features
· postural instability and falls
o patients tend to have a stiff, broad-based gait
· impairment of vertical gaze (down gaze worse than up gaze - patients may complain of difficultly reading or descending stairs)
· parkinsonism
o bradykinesia is prominent
· cognitive impairment
o primarily frontal lobe dysfunction
Management
· poor response to L-dopa
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Raised intracranial pressure
As the brain and ventricles are enclosed by a rigid skull, they have a limited ability to accommodate additional volume. Additional volume (e.g. haematoma, tumour, excessive CSF) will therefore lead to a rise in intracranial pressure (ICP).
Pathophysiology
· the normal ICP is 7-15 mmHg in adults in the supine position
· cerebral perfusion pressure (CPP) is the net pressure gradient causing cerebral blood flow to the brain
· CPP = mean arterial pressure - ICP
Causes
· idiopathic intracranial hypertension
· traumatic head injuries
· infection
o meningitis
· tumours
· hydrocephalus
Features
· headache
· vomiting
· reduced levels of consciousness
· papilloedema
· Cushing's triad
o widening pulse pressure
o bradycardia
o irregular breathing
Investigations and monitoring
· neuroimaging (CT/MRI) is key to investigate the underlying cause
· invasive ICP monitoring
o catheter placed into the lateral ventricles of the brain to monitor the pressure
o may also be used to take collect CSF samples and also to drain small amounts of CSF to reduce the pressure
o a cut-off of > 20 mmHg is often used to determine if further treatment is needed to reduce the ICP
Management
· investigate and treat the underlying cause
· head elevation to 30º
· IV mannitol may be used as an osmotic diuretic
· controlled hyperventilation
o aim is to reduce pCO2 → vasoconstriction of the cerebral arteries → reduced ICP
o leads to rapid, temporary lowering of ICP. However, caution needed as may reduce blood flow to already ischaemic parts of the brain
· removal of CSF, different techniques include:
o drain from intraventricular monitor (see above)
o repeated lumbar puncture (e.g. idiopathic intracranial hypertension)
o ventriculoperitoneal shunt (for hydrocephalus)
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Restless legs syndrome
Restless legs syndrome (RLS) is a syndrome of spontaneous, continuous lower limb movements that may be associated with paraesthesia. It is extremely common, affecting between 2-10% of the general population. Males and females are equally affected and a family history may be present
Clinical features
· uncontrollable urge to move legs (akathisia). Symptoms initially occur at night but as condition progresses may occur during the day. Symptoms are worse at rest
· paraesthesias e.g. 'crawling' or 'throbbing' sensations
· movements during sleep may be noted by the partner - periodic limb movements of sleeps (PLMS)
Causes and associations
· there is a positive family history in 50% of patients with idiopathic RLS
· iron deficiency anaemia
· uraemia
· diabetes mellitus
· pregnancy
The diagnosis is clinical although bloods such as ferritin to exclude iron deficiency anaemia may be appropriate
Management
· simple measures: walking, stretching, massaging affected limbs
· treat any iron deficiency
· dopamine agonists are first-line treatment (e.g. Pramipexole, ropinirole)
· benzodiazepines
· gabapentin
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Seizures: acute management
Most seizures are self-limiting and stop spontaneously but prolonged seizures may be potentially life-threatening.
Basics
· check the airway and apply oxygen if appropriate
· place the patient in the recovery position
· if the seizure is prolonged give benzodiazepines
BNF recommend dose for rectal diazepam, repeated once after 10-15 minutes if necessary
| Neonate | 1.25 - 2.5 mg |
| Child 1 month - 1 year | 5 mg |
| Child 2 years - 11 years | 5 - 10 mg |
| Child 12 years - 17 years | 10 mg |
| Adult | 10 - 20 mg (max. 30 mg) |
| Elderly | 10 mg (max. 15 mg) |
Midazolam oromucosal solution may also be used:
| Neonate | 300 mcg/kg (unlicensced) |
| Child 1 - 2 months | 300 mcg/kg (max. 2.5mg, unlicensced) |
| Child 3 - 11 months | 2.5 mg |
| Child 1 - 4 years | 5 mg |
| Child 5 - 9 years | 7.5 mg |
| Child 10 - 17 years | 10 mg |
| Adult | 10 mg (unlicensced) |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Spontaneous intracranial hypotension
Spontaneous intracranial hypotension is a very rare cause of headaches that results from a CSF leak. The leak is typically from the thoracic nerve root sleeves.
Risk factors include connective tissue disorders such as Marfan's syndrome.
Key features
· strong postural relationship with the headache generally much worse when upright. Patients may, therefore, be bed-bound
Investigations
· MRI with gadolinium: typically shows pachymeningeal enhancement
Management
· usually conservative
· if this fails an epidural blood patch may be tried
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:22
Stroke: a very basic introduction
Strokes represent an important cause of morbidity and mortality. In the UK alone there are over 150,000 strokes per year, with over 1.2 million stroke survivors. Stroke is the fourth largest cause of death in the UK and kills twice as many women than breast cancer each year.
The prevention and treatment of strokes has undergone significant changes over the past decade. What was previously considered a devastating but untreatable condition is now viewed more as a 'brain attack', a condition which requires emergency assessment to see if patients may benefit from new treatments such as thrombolysis.
| | |
| © Image used on license from PathoPic | |
Pathological specimen showing the results of an ischaemic stroke to the occipito-parietal region of the cerebrum. Note there has been some secondary haemorrhage in the affected area.
What is a stroke?
A stroke (also known as cerebrovascular accident,CVA) represents a sudden interruption in the vascular supply of the brain. Remember that neural tissue is completely dependent on aerobic metabolism so any problem with oxygen supply can quickly lead to irreversible damage.
There are two main types of strokes:
· ischaemic: these can be further subdivided between into episodes which last greater than 24 hours (termed an ischaemic stroke) and episodes where symptoms and signs last less than 24 hours (transient ischaemic attacks, TIAs, sometimes termed 'mini-strokes' by patients)
· haemorrhagic
The table below shows the basic differences:
| Ischaemic | Haemorrhagic | |
| Essential problem | 'Blockage' in the blood vessel stops blood flow | Blood vessel 'bursts' leading to reduction in blood flow |
| Proportion of strokes | 85% | 15% |
| Subtypes | Thrombotic stroke · thrombosis from large vessels e.g. carotid Embolic stroke · usually a blood clot but fat, air or clumps of bacteria may act as an embolus · atrial fibrillation is an important cause of emboli forming in the heart | Intracerebral haemorrhage · bleeding within the brain Subarachnoid haemorrhage · bleeding on the surface of the brain |
| Risk factors | General risk factors for cardiovascular disease · age · hypertension · smoking · hyperlipidaemia · diabetes mellitus Risk factors for cardioembolism · atrial fibrillation | Risk factors · age · hypertension · arteriovenous malformation · anticoagulation therapy |
Symptoms and signs
Stroke is defined by the World Health Organization as a clinical syndrome consisting of 'rapidly developing clinical signs of focal (at times global) disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin'. In contrast, with a TIA the symptoms and signs resolve within 24 hours.
Features include:
· motor weakness
· speech problems (dysphasia)
· swallowing problems
· visual field defects (homonymous hemianopia)
· balance problems
Cerebral hemisphere infarcts may have the following symptoms:
· contralateral hemiplegia: initially flaccid then spastic
· contralateral sensory loss
· homonymous hemianopia
· dysphasia
Brainstem infarction
· may result in more severe symptoms including quadriplegia and lock-in-syndrome
Lacunar infarcts
· small infarcts around the basal ganglia, internal capsule, thalamus and pons
· this may result in pure motor, pure sensory, mixed motor and sensory signs or ataxia
| | |
| © Image used on license from PathoPic | |
An example of a lacunar infarct affecting the internal capsule.
One formal classification system that is sometimes used is the Oxford Stroke Classification (also known as the Bamford Classification), whichclassifies strokes based on the initial symptoms. A summary is as follows:
The following criteria should be assessed:
· 1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
· 2. homonymous hemianopia
· 3. higher cognitive dysfunction e.g. dysphasia
| Stroke type | Notes |
| Total anterior circulation infarcts (TACI, c. 15%) | · involves middle and anterior cerebral arteries · all 3 of the above criteria are present |
| Partial anterior circulation infarcts (PACI, c. 25%) | · involves smaller arteries of anterior circulation e.g. upper or lower division of middle cerebral artery · 2 of the above criteria are present |
| Lacunar infarcts (LACI, c. 25%) | · involves perforating arteries around the internal capsule, thalamus and basal ganglia · presents with 1 of the following: · 1. unilateral weakness (and/or sensory deficit) of face and arm, arm and leg or all three. · 2. pure sensory stroke. · 3. ataxic hemiparesis |
| Posterior circulation infarcts (POCI, c. 25%) | · involves vertebrobasilar arteries · presents with 1 of the following: · 1. cerebellar or brainstem syndromes · 2. loss of consciousness · 3. isolated homonymous hemianopia |
Whilst symptoms alone cannot be used to differentiate haemorrhagic from ischaemic strokes, patients who've suffered haemorrhages are more likely to have:
· decrease in the level of consciousness: seen in up to 50% of patients with a haemorrhagic stroke
· headache is also much more common in haemorrhagic stroke
· nausea and vomiting is also common
· seizures occur in up to 25% of patients
| | |
| © Image used on license from PathoPic | |
Pathological specimen showing the consequence of an intracerebral haemorrhage
Over recent years there has been a public health campaign to raise awareness of stroke symptoms. The FAST campaign uses the following mnemonic:
· Face - 'Has their face fallen on one side? Can they smile?'
· Arms - 'Can they raise both arms and keep them there?'
· Speech - 'Is their speech slurred?'
· Ttime - 'Time to call 999 if you see any single one of these signs.'
Investigations
Patients with suspected stroke need to have emergency neuroimaging. The main cause for urgency is to see whether a patient may be suitable for thrombolytic therapy to treat early ischaemic strokes. The two types of neuroimaging used in this setting are:
· CT
· MRI
| | |
| Image sourced from Wikipedia | |
CT scan of the brain showing a right-hemispheric ischemic stroke
Management
Ischaemic strokes
Urgent neuroimaging classifies the stroke as either ischaemic or haemorrhagic. If the stroke is ischaemic, and certain criteria are met, the patient should be offered thrombolysis. Example criteria include:
· patients present with 4.5 hours of onset of stroke symptoms
· the patient has not had a previous intracranial haemorrhage, uncontrolled hypertension, pregnant etc
Once haemorrhagic stroke has been excluded patients should be given aspirin 300mg as soon as possible and antiplatelet therapy should be continued.
Transient ischaemic attacks
Remember with TIAs the, by definition, symptoms last less than 24 hours although in the vast majority of cases the duration is much shorter, typically 1 hour or so. For this reason most patients symptoms will have resolved before they see a doctor.
The ABCD2 prognostic score has previously been used to risk stratify patients who present with a suspected TIA. However, data from studies have suggested it performs poorly and it is therefore no longer recommended by NICE Clinical Knowledge Summaries. Instead, NICE recommend:
Immediate antithrombotic therapy:
· give aspirin 300 mg immediately, unless contraindicated e.g. the patient has a bleeding disorder or is taking an anticoagulant (needs immediate admission for imaging to exclude a haemorrhage)
If the patient has had more than 1 TIA ('crescendo TIA') or has a suspected cardioembolic source or severe carotid stenosis:
· discuss the need for admission or observation urgently with a stroke specialist
If the patient has had a suspected TIA in the last 7 days:
· arrange urgent assessment (within 24 hours) by a specialist stroke physician
If the patient has had a suspected TIA which occurred more than a week previously:
· refer for specialist assessment as soon as possible within 7 days
Haemorrhagic strokes
If imaging confirms a haemorrhagic stroke neurosurgical consultation should be considered for advice on further management. The vast majority of patients however are not suitable for surgical intervention. Management is therefore supportive as per haemorrhagic stroke. Anticoagulants (e.g. warfarin) and antithrombotic medications (e.g. clopidogrel) should be stopped to minimise further bleeding. If a patient is anticoagulated this should be reversed as quickly as possible. Trials have shown improved outcomes in patients who have their blood pressure lowered acutely and this is now part of many protocols for haemorrhagic strokes.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
17:23
Multiple sclerosis: management
Treatment in multiple sclerosis is focused at reducing the frequency and duration of relapses. There is no cure.
Acute relapse
High dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse. It should be noted that steroids shorten the duration of a relapse and do not alter the degree of recovery (i.e. whether a patient returns to baseline function)
Disease modifying drugs
Beta-interferon has been shown to reduce the relapse rate by up to 30%. Certain criteria have to be met before it is used:
· relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided
· secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)
· reduces number of relapses and MRI changes, however doesn't reduce overall disability
Other drugs used in the management of multiple sclerosis include:
· glatiramer acetate: immunomodulating drug - acts as an 'immune decoy'
· natalizumab: a recombinant monoclonal antibody that antagonises Alpha-4 Beta-1-integrin found on the surface of leucocytes, thus inhibiting migration of leucocytes across the endothelium across the blood-brain barrier
· fingolimod: sphingosine 1-phosphate receptor modulator, prevents lymphocytes from leaving lymph nodes. An oral formulation is available
Some specific problems
Fatigue
· once other problems (e.g. anaemia, thyroid or depression) have been excluded NICE recommend a trial of amantadine
· other options include mindfulness training and CBT
Spasticity
· baclofen and gabapentin are first-line. Other options include diazepam, dantrolene and tizanidine
· physiotherapy is important
· cannabis and botox are undergoing evalulation
Bladder dysfunction
· may take the form of urgency, incontinence, overflow etc
· guidelines stress the importance of getting an ultrasound first to assess bladder emptying - anticholinergics may worsen symptoms in some patients
· if significant residual volume → intermittent self-catheterisation
· if no significant residual volume → anticholinergics may improve urinary frequency
Oscillopsia (visual fields apper to oscillate)
· gabapentin is first-line
From <https://www.passmedicine.com/review/textbook.php?s=#>
Tuesday, 22 December 2020
18:30
Subacute combined degeneration of spinal cord
Basics
· due to vitamin B12 deficiency
· dorsal + lateral columns affected
· joint position and vibration sense lost first then distal paraesthesia
· upper motor neuron signs typically develop in the legs, classically extensor plantars, brisk knee reflexes, absent ankle jerks
· if untreated stiffness and weakness persist
21 December 2020
21:52
Stroke: management
The Royal College of Physicians (RCP) published guidelines on the diagnosis and management of patients following a stroke in 2004. NICE updated their stroke guidelines in 2019.
Selected points relating to the management of acute stroke include:
· blood glucose, hydration, oxygen saturation and temperature should be maintained within normal limits
· blood pressure should not be lowered in the acute phase unless there are complications e.g. Hypertensive encephalopathy*
· aspirin 300mg orally or rectally should be given as soon as possible if a haemorrhagic stroke has been excluded
· with regards to atrial fibrillation, the RCP state: 'anticoagulants should not be started until brain imaging has excluded haemorrhage, and usually not until 14 days have passed from the onset of an ischaemic stroke'
· if the cholesterol is > 3.5 mmol/l patients should be commenced on a statin. Many physicians will delay treatment until after at least 48 hours due to the risk of haemorrhagic transformation
Thrombolysis for acute ischaemic stroke
Thrombolysis with alteplase should only be given if:
· it is administered within 4.5 hours of onset of stroke symptoms (unless as part of a clinical trial)
· haemorrhage has been definitively excluded (i.e. Imaging has been performed)
Contraindications to thrombolysis:
| Absolute | Relative |
| - Previous intracranial haemorrhage - Seizure at onset of stroke - Intracranial neoplasm - Suspected subarachnoid haemorrhage - Stroke or traumatic brain injury in preceding 3 months - Lumbar puncture in preceding 7 days - Gastrointestinal haemorrhage in preceding 3 weeks - Active bleeding - Pregnancy - Oesophageal varices - Uncontrolled hypertension >200/120mmHg | - Concurrent anticoagulation (INR >1.7) - Haemorrhagic diathesis - Active diabetic haemorrhagic retinopathy - Suspected intracardiac thrombus - Major surgery / trauma in the preceding 2 weeks |
Thrombectomy for acute ischaemic stroke
Mechanical thrombectomy is an exciting new treatment option for patients with an acute ischaemic stroke. NICE incorporated recommendations into their 2019 guidelines. It is important to remember the significant resources and senior personnel to provide such a service 24 hours a day. NICE recommend that all decisions about thrombectomy take into account a patient's overall clinical status:
· NICE recommend a pre-stroke functional status of less than 3 on the modified Rankin scale and a score of more than 5 on the National Institutes of Health Stroke Scale (NIHSS)
Offer thrombectomy as soon as possible and within 6 hours of symptom onset, together with intravenous thrombolysis (if within 4.5 hours), to people who have:
acute ischaemic stroke and
· confirmed occlusion of the proximal anterior circulation demonstrated by computed tomographic angiography (CTA) or magnetic resonance angiography (MRA)
Offer thrombectomy as soon as possible to people who were last known to be well between 6 hours and 24 hours previously (including wake-up strokes):
· confirmed occlusion of the proximal anterior circulation demonstrated by CTA or MRA and
· if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion or diffusion-weighted MRI sequences showing limited infarct core volume
Consider thrombectomy together with intravenous thrombolysis (if within 4.5 hours) as soon as possible for people last known to be well up to 24 hours previously (including wake-up strokes):
· who have acute ischaemic stroke and confirmed occlusion of the proximal posterior circulation (that is, basilar or posterior cerebral artery) demonstrated by CTA or MRA and
· if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion or diffusion-weighted MRI sequences showing limited infarct core volume
Secondary prevention
NICE also published a technology appraisal in 2010 on the use of clopidogrel and dipyridamole
Recommendations from NICE include:
· clopidogrel is now recommended by NICE ahead of combination use of aspirin plus modified-release (MR) dipyridamole in people who have had an ischaemic stroke
· aspirin plus MR dipyridamole is now recommended after an ischaemic stroke only if clopidogrel is contraindicated or not tolerated, but treatment is no longer limited to 2 years' duration
· MR dipyridamole alone is recommended after an ischaemic stroke only if aspirin or clopidogrel are contraindicated or not tolerated, again with no limit on duration of treatment
With regards to carotid artery endarterectomy:
· recommend if patient has suffered stroke or TIA in the carotid territory and are not severely disabled
· should only be considered if carotid stenosis > 70% according ECST** criteria or > 50% according to NASCET*** criteria
*the 2009 Controlling hypertension and hypotension immediately post-stroke (CHHIPS) trial may change thinking on this but guidelines have yet to change to reflect this
**European Carotid Surgery Trialists' Collaborative Group
***North American Symptomatic Carotid Endarterectomy Trial
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
21:52
Visual field defects
The main points for the exam are:
· left homonymous hemianopia means visual field defect to the left, i.e. Lesion of right optic tract
· homonymous quadrantanopias: PITS (Parietal-Inferior, Temporal-Superior)
· incongruous defects = optic tract lesion; congruous defects = optic radiation lesion or occipital cortex
A congruous defect simply means complete or symmetrical visual field loss and conversely an incongruous defect is incomplete or asymmetric. Please see the link for an excellent diagram.
Homonymous hemianopia
· incongruous defects: lesion of optic tract
· congruous defects: lesion of optic radiation or occipital cortex
· macula sparing: lesion of occipital cortex
Homonymous quadrantanopias*
· superior: lesion of the inferior optic radiations in the temporal lobe (Meyer's loop)
· inferior: lesion of the superior optic radiations in the parietal lobe
· mnemonic = PITS (Parietal-Inferior, Temporal-Superior)
Bitemporal hemianopia
· lesion of optic chiasm
· upper quadrant defect > lower quadrant defect = inferior chiasmal compression, commonly a pituitary tumour
· lower quadrant defect > upper quadrant defect = superior chiasmal compression, commonly a craniopharyngioma
*this is very much the 'exam answer'. Actual studies suggest that the majority of quadrantanopias are caused by occipital lobe lesions. Please see the link for more details.
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
23:04
Tremor
The table below lists the main characteristics of the most important causes of tremor
| Conditions | Notes |
| Parkinsonism | Resting, 'pill-rolling' tremor Bradykinesia Rigidity Flexed posture, short, shuffling steps Micrographia 'Mask-like' face Depression & dementia are common May be history of anti-psychotic use |
| Essential tremor | Postural tremor: worse if arms outstretched Improved by alcohol and rest Titubation Often strong family history |
| Anxiety | History of depression |
| Thyrotoxicosis | Usual thyroid signs e.g. Weight loss, tachycardia, feeling hot etc |
| Hepatic encephalopathy | History of chronic liver disease |
| Carbon dioxide retention | History of chronic obstructive pulmonary disease |
| Cerebellar disease | Intention tremor Cerebellar signs e.g. Past-pointing, nystagmus etc |
Other causes
· drug withdrawal: alcohol, opiates
From <https://www.passmedicine.com/question/questions.php?q=0>
22 December 2020
16:35
Parkinsonism
Causes of Parkinsonism
· Parkinson's disease
· drug-induced e.g. antipsychotics, metoclopramide*
· progressive supranuclear palsy
· multiple system atrophy
· Wilson's disease
· post-encephalitis
· dementia pugilistica (secondary to chronic head trauma e.g. boxing)
· toxins: carbon monoxide, MPTP
*Domperidone does not cross the blood-brain barrier and therefore does not cause extra-pyramidal side-effects.
From <https://www.passmedicine.com/question/questions.php?q=0>
22 December 2020
19:18
Triptans
Triptans are specific 5-HT1B and 5-HT1D agonists used in the acute treatment of migraine. They are generally used first-line in combination therapy with an NSAID or paracetamol.
Prescribing points
· should be taken as soon as possible after the onset of headache, rather than at onset of aura
· oral, orodispersible, nasal spray and subcutaneous injections are available
Adverse effects
· 'triptan sensations' - tingling, heat, tightness (e.g. throat and chest), heaviness, pressure
Contraindications
· patients with a history of, or significant risk factors for, ischaemic heart disease or cerebrovascular disease
From <https://www.passmedicine.com/question/questions.php?q=0>
22 December 2020
19:20
Transient ischaemic attack
The original definition of a transient ischaemic attack (TIA) was time-based: a sudden onset of a focal neurologic symptom and/or sign lasting less than 24 hours, brought on by a transient decrease in blood flow. However, this has now changed as it is recognised that even short periods of ischaemia can result in pathological changes to the brain. Therefore, a new 'tissue-based' definition is now used: a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischaemia, without acute infarction.
Patients often use the term 'mini-stroke' for TIAs.
Assessment and referral
The ABCD2 prognostic score has previously been used to risk stratify patients who present with a suspected TIA. However, data from studies have suggested it performs poorly and it is therefore no longer recommended by NICE Clinical Knowledge Summaries. Instead, NICE recommend:
Immediate antithrombotic therapy:
· give aspirin 300 mg immediately, unless
· 1. the patient has a bleeding disorder or is taking an anticoagulant (needs immediate admission for imaging to exclude a haemorrhage)
· 2. the patient is already taking low-dose aspirin regularly: continue the current dose of aspirin until reviewed by a specialist
· 3. Aspirin is contraindicated: discuss management urgently with the specialist team
If the patient has had more than 1 TIA ('crescendo TIA') or has a suspected cardioembolic source or severe carotid stenosis:
· discuss the need for admission or observation urgently with a stroke specialist
If the patient has had a suspected TIA in the last 7 days:
· arrange urgent assessment (within 24 hours) by a specialist stroke physician
If the patient has had a suspected TIA which occurred more than a week previously:
· refer for specialist assessment as soon as possible within 7 days
Advise the person not to drive until they have been seen by a specialist.
Further management
Antithrombotic therapy
· clopidogrel is recommended first-line (as for patients who've had a stroke)
· aspirin + dipyridamole should be given to patients who cannot tolerate clopidogrel
· these recommendations follow the 2012 Royal College of Physicians National clinical guideline for stroke. Please see the link for more details (section 5.5)
· these guidelines may change following the CHANCE study (NEJM 2013;369:11). This study looked at giving high-risk TIA patients aspirin + clopidogrel for the first 90 days compared to aspirin alone. 11.7% of aspirin only patients had a stroke over 90 days compared to 8.2% of dual antiplatelet patients
With regards to carotid artery endarterectomy:
· recommend if patient has suffered stroke or TIA in the carotid territory and are not severely disabled
· should only be considered if carotid stenosis > 70% according ECST* criteria or > 50% according to NASCET** criteria
*European Carotid Surgery Trialists' Collaborative Group
**North American Symptomatic Carotid Endarterectomy Trial
From <https://www.passmedicine.com/question/questions.php?q=0>
Wednesday, 23 December 2020
00:56
Brain abscess
Brain abscesses may result from a number of causes including, extension of sepsis from middle ear or sinuses, trauma or surgery to the scalp, penetrating head injuries and embolic events from endocarditis
The presenting symptoms will depend upon the site of the abscess (those in critical areas e.g. motor cortex) will present earlier. Abscesses have a considerable mass effect in the brain and raised intracranial pressure is common.
· headache
o often dull, persistent
· fever
o may be absent and usually not the swinging pyrexia seen with abscesses at other sites
· focal neurology
o e.g. oculomotor nerve palsy or abducens nerve palsy secondary to raised intracranial pressure
· other features consistent with raised intracranial pressure
o nausea
o papilloedema
o seizures
Investigations
· Assessment of the patient includes imaging with CT scanning
Management
· surgery
o a craniotomy is performed and the abscess cavity debrided
o the abscess may reform because the head is closed following abscess drainage.
· IV antibiotics: IV 3rd-generation cephalosporin + metronidazole
· intracranial pressure management: e.g. dexamethasone
22 December 2020
19:33
Brain lesions
The following neurological disorders/features may allow localisation of a brain lesion:
Gross anatomy
Parietal lobe lesions
· sensory inattention
· apraxias
· astereognosis (tactile agnosia)
· inferior homonymous quadrantanopia
· Gerstmann's syndrome (lesion of dominant parietal): alexia, acalculia, finger agnosia and right-left disorientation
Occipital lobe lesions
· homonymous hemianopia (with macula sparing)
· cortical blindness
· visual agnosia
Temporal lobe lesion
· Wernicke's aphasia: this area 'forms' the speech before 'sending it' to Brocas area. Lesions result in word substituion, neologisms but speech remains fluent
· superior homonymous quadrantanopia
· auditory agnosia
· prosopagnosia (difficulty recognising faces)
Frontal lobes lesions
· expressive (Broca's) aphasia: located on the posterior aspect of the frontal lobe, in the inferior frontal gyrus. Speech is non-fluent, laboured, and halting
· disinhibition
· perseveration
· anosmia
· inability to generate a list
Cerebellum lesions
· midline lesions: gait and truncal ataxia
· hemisphere lesions: intention tremor, past pointing, dysdiadokinesis, nystagmus
More specific areas
| Area | Associated conditions |
| Medial thalamus and mammillary bodies of the hypothalamus | Wernicke and Korsakoff syndrome |
| Subthalamic nucleus of the basal ganglia | Hemiballism |
| Striatum (caudate nucleus) of the basal ganglia | Huntington chorea |
| Substantia nigra of the basal ganglia | Parkinson's disease |
| Amygdala | Kluver-Bucy syndrome (hypersexuality, hyperorality, hyperphagia, visual agnosia |
From <https://www.passmedicine.com/question/questions.php?q=0#>
22 December 2020
19:40
Cranial nerves
The table below lists the major characteristics of the 12 cranial nerves:
From <https://www.passmedicine.com/question/questions.php?q=0#>
| I (Olfactory) | Smell | Cribriform plate | |
| II (Optic) | Sight | Optic canal | |
| III (Oculomotor) | Eye movement (MR, IO, SR, IR) Pupil constriction Accomodation Eyelid opening | Palsy results in · ptosis · 'down and out' eye · dilated, fixed pupil | Superior orbital fissure (SOF) |
| IV (Trochlear) | Eye movement (SO) | Palsy results in defective downward gaze → vertical diplopia | SOF |
| V (Trigeminal) | Facial sensation Mastication | Lesions may cause: · trigeminal neuralgia · loss of corneal reflex (afferent) · loss of facial sensation · paralysis of mastication muscles · deviation of jaw to weak side | V1: SOF, V2: Foramen rotundum, V3: Foramen ovale |
| VI (Abducens) | Eye movement (LR) | Palsy results in defective abduction → horizontal diplopia | SOF |
| VII (Facial) | Facial movement Taste (anterior 2/3rds of tongue) Lacrimation Salivation | Lesions may result in: · flaccid paralysis of upper + lower face · loss of corneal reflex (efferent) · loss of taste · hyperacusis | Internal auditory meatus |
| VIII (Vestibulocochlear) | Hearing, balance | Hearing loss Vertigo, nystagmus Acoustic neuromas are Schwann cell tumours of the cochlear nerve | Internal auditory meatus |
| IX (Glossopharyngeal) | Taste (posterior 1/3rd of tongue) Salivation Swallowing Mediates input from carotid body & sinus | Lesions may result in; · hypersensitive carotid sinus reflex · loss of gag reflex (afferent) | Jugular foramen |
| X (Vagus) | Phonation Swallowing Innervates viscera | Lesions may result in; · uvula deviates away from site of lesion · loss of gag reflex (efferent) | Jugular foramen |
| XI (Accessory) | Head and shoulder movement | Lesions may result in; · weakness turning head to contralateral side | Jugular foramen |
| XII (Hypoglossal) | Tongue movement | Tongue deviates towards side of lesion | Hypoglossal canal |
Some cranial nerves are motor, some sensory and some are both. The most useful mnemonic is given below.
CN I ----------------------------------------------------------------------→XII
Some Say Marry Money But My Brother Says Big Brains Matter Most
S = Sensory, M = Motor, B = Both
| | |
| Image sourced from Wikipedia | |
View from the inferior surface of the brain showing the emergence of the cranial nerves
| | |
| Image sourced from Wikipedia | |
Diagram showing the nuclei of the cranial nerves in the brainstem
Cranial nerve reflexes
| Reflex | Afferent limb | Efferent limb |
| Corneal | Ophthalmic nerve (V1) | Facial nerve (VII) |
| Jaw jerk | Mandibular nerve (V3) | Mandibular nerve (V3) |
| Gag | Glossopharyngeal nerve (IX) | Vagal nerve (X) |
| Carotid sinus | Glossopharyngeal nerve (IX) | Vagal nerve (X) |
| Pupillary light | Optic nerve (II) | Oculomotor nerve (III) |
| Lacrimation | Ophthalmic nerve (V1) | Facial nerve (VII) |
From <https://www.passmedicine.com/question/questions.php?q=0#>
22 December 2020
19:52
Glasgow Coma Scale: adults
| Modality | Options |
| Motor response | 6. Obeys commands 5. Localises to pain 4. Withdraws from pain 3. Abnormal flexion to pain (decorticate posture) 2. Extending to pain 1. None |
| Verbal response | 5. Orientated 4. Confused 3. Words 2. Sounds 1. None |
| Eye opening | 4. Spontaneous 3. To speech 2. To pain 1. None |
Glasgow coma scale (GCS) scores are generally expressed in the following format 'GCS = 13, M5 V4 E4 at 21:30'.
From <https://www.passmedicine.com/question/questions.php?q=0#>
22 December 2020
20:16
Bell's palsy
Bell's palsy may be defined as an acute, unilateral, idiopathic, facial nerve paralysis. The aetiology is unknown although the role of the herpes simplex virus has been investigated previously. The peak incidence is 20-40 years and the condition is more common in pregnant women.
Features
· lower motor neuron facial nerve palsy - forehead affected*
· patients may also notice post-auricular pain (may precede paralysis), altered taste, dry eyes, hyperacusis
Management
· in the past a variety of treatment options have been proposed including no treatment, prednisolone only and a combination of aciclovir and prednisolone
· following a National Institute for Health randomised controlled trial it is now recommended that prednisolone 1mg/kg for 10 days should be prescribed for patients within 72 hours of onset of Bell's palsy. Adding in aciclovir gives no additional benefit
· eye care is important - prescription of artificial tears and eye lubricants should be considered
Prognosis
· if untreated around 15% of patients have permanent moderate to severe weakness
*upper motor neuron lesion 'spares' upper face
From <https://www.passmedicine.com/question/questions.php?q=0#>
21 December 2020
21:51
Guillain-Barre syndrome: features
Guillain-Barre syndrome describes an immune-mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni).
Initial symptoms
· around 65% of patients experience back/leg pain in the initial stages of the illness
The characteristic features of Guillain-Barre syndrome is progressive, symmetrical weakness of all the limbs.
· the weakness is classically ascending i.e. the legs are affected first
· proximal muscles (e.g. hips/shoulders) are usually affected before than the distal ones (e.g. feet/hands)
· reflexes are reduced or absent
· sensory symptoms tend to be mild (e.g. distal paraesthesia) with very few sensory signs
Other features
· there may be a history of gastroenteritis
· respiratory muscle weakness
· cranial nerve involvement
o diplopia
o bilateral facial nerve palsy
o oropharyngeal weakness is common
· autonomic involvement
o urinary retention
o diarrhoea
Less common findings
· papilloedema: thought to be secondary to reduced CSF resorption
Investigations
· lumbar puncture
o rise in protein with a normal white blood cell count (albuminocytologic dissociation) - found in 66%
· nerve condution studies may be performed
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
21:51
DVLA: neurological disorders
The guidelines below relate to car/motorcycle use unless specifically stated. For obvious reasons, the rules relating to drivers of heavy goods vehicles tend to be much stricter
Epilepsy/seizures - all patient must not drive and must inform the DVLA
· first unprovoked/isolated seizure: 6 months off if there are no relevant structural abnormalities on brain imaging and no definite epileptiform activity on EEG. If these conditions are not met then this is increased to 12 months
· for patients with established epilepsy or those with multiple unprovoked seizures:
· → may qualify for a driving licence if they have been free from any seizure for 12 months
· → if there have been no seizures for 5 years (with medication if necessary) a ’til 70 licence is usually restored
· withdrawawl of epilepsy medication: should not drive whilst anti-epilepsy medication is being withdrawn and for 6 months after the last dose
Syncope
· simple faint: no restriction
· single episode, explained and treated: 4 weeks off
· single episode, unexplained: 6 months off
· two or more episodes: 12 months off
Other conditions
· stroke or TIA: 1 month off driving, may not need to inform DVLA if no residual neurological deficit
· multiple TIAs over short period of times: 3 months off driving and inform DVLA
· craniotomy e.g. For meningioma: 1 year off driving*
· pituitary tumour: craniotomy: 6 months; trans-sphenoidal surgery 'can drive when there is no debarring residual impairment likely to affect safe driving'
· narcolepsy/cataplexy: cease driving on diagnosis, can restart once 'satisfactory control of symptoms'
· chronic neurological disorders e.g. multiple sclerosis, motor neuron disease: DVLA should be informed, complete PK1 form (application for driving licence holders state of health)
*if the tumour is a benign meningioma and there is no seizure history, licence can be reconsidered 6 months after surgery if remains seizure free
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
21:51
Epilepsy: classification
The basic classification of epilepsy has changed in recent years. The new basic seizure classification is based on 3 key features:
· 1. Where seizures begin in the brain
· 2. Level of awareness during a seizure (important as can affect safety during seizure)
· 3. Other features of seizures
Focal seizures
· previously termed partial seizures
· these start in a specific area, on one side of the brain
· the level of awareness can vary in focal seizures. The terms focal aware (previously termed 'simple partial'), focal impaired awareness (previously termed 'complex partial') and awareness unknown are used to further describe focal seizures
· further to this, focal seizures can be classified as being motor (e.g. Jacksonian march), non-motor (e.g. déjà vu, jamais vu; ) or having other features such as aura
Generalised
· these engage or involve networks on both sides of the brain at the onset
· consciousness lost immediately. The level of awareness in the above classification is therefore not needed, as all patients lose consciousness
· generalised seizures can be further subdivided into motor (e.g. tonic-clonic) and non-motor (e.g. absence)
· specific types include:
· → tonic-clonic (grand mal)
· → tonic
· → clonic
· → typical absence (petit mal)
· → atonic
Unknown onset
· this termed is reserved for when the origin of the seizure is unknown
Focal to bilateral seizure
· starts on one side of the brain in a specific area before spreading to both lobes
· previously termed secondary generalized seizures
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
21:51
Epilepsy: treatment
Most neurologists now start antiepileptics following a second epileptic seizure. NICE guidelines suggest starting antiepileptics after the first seizure if any of the following are present:
· the patient has a neurological deficit
· brain imaging shows a structural abnormality
· the EEG shows unequivocal epileptic activity
· the patient or their family or carers consider the risk of having a further seizure unacceptable
It should be remembered that the following are only general guidelines. For example, maternal use of sodium valproate is associated with a significant risk of neurodevelopmental delay in children. Guidance is now clear that sodium valproate should not be used during pregnancy and in women of childbearing age unless clearly necessary.
Sodium valproate is considered the first line treatment for patients with generalised seizures with carbamazepine used for focal seizures.
Generalised tonic-clonic seizures
· sodium valproate
· second line: lamotrigine, carbamazepine
Absence seizures* (Petit mal)
· sodium valproate or ethosuximide
· sodium valproate particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsy
Myoclonic seizures**
· sodium valproate
· second line: clonazepam, lamotrigine
Focal seizures
· carbamazepine or lamotrigine
· second line: levetiracetam, oxcarbazepine or sodium valproate
*carbamazepine may exacerbate absence seizures
**carbamazepine may exacerbate myoclonic seizures
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
21:52
Headache: red flags
Headache is one of the most common presenting complaints seen in clinical practice. The vast majority of these will be caused by common, benign conditions. There are however certain features in a history which should prompt further action. In the 2012 guidelines NICE suggest the following:
· compromised immunity, caused, for example, by HIV or immunosuppressive drugs
· age under 20 years and a history of malignancy
· a history of malignancy known to metastasis to the brain
· vomiting without other obvious cause
· worsening headache with fever
· sudden-onset headache reaching maximum intensity within 5 minutes - 'thunderclap'
· new-onset neurological deficit
· new-onset cognitive dysfunction
· change in personality
· impaired level of consciousness
· recent (typically within the past 3 months) head trauma
· headache triggered by cough, valsalva (trying to breathe out with nose and mouth blocked), sneeze or exercise
· orthostatic headache (headache that changes with posture)
· symptoms suggestive of giant cell arteritis or acute narrow-angle glaucoma
· a substantial change in the characteristics of their headache
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
21:52
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension (also known as pseudotumour cerebri and formerly benign intracranial hypertension) is a condition classically seen in young, overweight females.
Risk factors
· obesity
· female sex
· pregnancy
· drugs*: oral contraceptive pill, steroids, tetracycline, vitamin A, lithium
Features
· headache
· blurred vision
· papilloedema (usually present)
· enlarged blind spot
· sixth nerve palsy may be present
Management
· weight loss
· diuretics e.g. acetazolamide
· topiramate is also used, and has the added benefit of causing weight loss in most patients
· repeated lumbar puncture
· surgery: optic nerve sheath decompression and fenestration may be needed to prevent damage to the optic nerve. A lumboperitoneal or ventriculoperitoneal shunt may also be performed to reduce intracranial pressure
*if intracranial hypertension is thought to occur secondary to a known causes (e.g. Medication) then it is of course not idiopathic
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
21:52
Motor neuron disease: types
Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. In some patients however, there is a combination of clinical patterns
Amyotrophic lateral sclerosis (50% of patients)
· typically LMN signs in arms and UMN signs in legs
· in familial cases the gene responsible lies on chromosome 21 and codes for superoxide dismutase
Primary lateral sclerosis
· UMN signs only
Progressive muscular atrophy
· LMN signs only
· affects distal muscles before proximal
· carries best prognosis
Progressive bulbar palsy
· palsy of the tongue, muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei
· carries worst prognosis
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
21:52
Multiple sclerosis: features
Patient's with multiple sclerosis (MS) may present with non-specific features, for example around 75% of patients have significant lethargy.
Diagnosis can be made on the basis of two or more relapses and either objective clinical evidence of two or more lesions or objective clinical evidence of one lesion together with reasonable historical evidence of a previous relapse.
Visual
· optic neuritis: common presenting feature
· optic atrophy
· Uhthoff's phenomenon: worsening of vision following rise in body temperature
· internuclear ophthalmoplegia
Sensory
· pins/needles
· numbness
· trigeminal neuralgia
· Lhermitte's syndrome: paraesthesiae in limbs on neck flexion
Motor
· spastic weakness: most commonly seen in the legs
Cerebellar
· ataxia: more often seen during an acute relapse than as a presenting symptom
· tremor
Others
· urinary incontinence
· sexual dysfunction
· intellectual deterioration
From <https://www.passmedicine.com/review/textbook.php?s=#>
22 December 2020
18:15
Ataxia
Cerebellar hemisphere lesions cause peripheral ('finger-nose ataxia')
wide-based gait with loss of heel to toe walking,
Cerebellar vermis lesions cause gait ataxia
Ataxic gaits are often caused by cerebellar lesions. The mnemonic 'PASTRIES' can be used to remember the causes of an ataxic gait.
P - paraneoplastic syndrome
A - abscess/atrophy
S - stroke/sclerosis (multiple sclerosis)
T - trauma
R - raised ICP
I - infection
E - ethanol and poisons
S - spinocerebellar ataxia (progressive degenerative genetic disease)
Ataxic gaits typically occur following cerebellar injury, the causes of which can be remembered by the mnemonic 'pastries'
P - Posterior fossa tumour
A - Alcohol
S - Multiple sclerosis
T - Trauma
R - Rare causes
I - Inherited (e.g. Friedreich's ataxia)
E - Epilepsy treatments
S - Stroke
22 December 2020
19:07
Stroke: assessment
Whilst the diagnosis of stroke may sometimes be obvious in many cases the presenting symptoms may be vague and accurate assessment difficult.
The FAST screening tool (Face/Arms/Speech/Time) is widely known by the general public following a publicity campaign. It has a positive predictive value of 78%.
A variant of FAST called the ROSIER score is useful for medical professionals. It is validated tool recommended by the Royal College of Physicians.
ROSIER score
Exclude hypoglycaemia first, then assess the following:
| Assessment | Scoring |
| Loss of consciousness or syncope | - 1 point |
| Seizure activity | - 1 point |
| New, acute onset of: | |
| • asymmetric facial weakness | + 1 point |
| • asymmetric arm weakness | + 1 point |
| • asymmetric leg weakness | + 1 point |
| • speech disturbance | + 1 point |
| • visual field defect | + 1 point |
A stroke is likely if > 0.
Investigations
A non-contrast CT head scan is the first line radiological investigation for suspected stroke
From <https://www.passmedicine.com/question/questions.php?q=0>
22 December 2020
16:23
Essential tremor
Essential tremor (previously called benign essential tremor) is an autosomal dominant condition which usually affects both upper limbs
Features
· postural tremor: worse if arms outstretched
· improved by alcohol and rest
· most common cause of titubation (head tremor)
Management
· propranolol is first-line
· primidone is sometimes used
From <https://www.passmedicine.com/question/questions.php?q=0>
Tuesday, 22 December 2020
22:45
Wernicke's encephalopathy
Wernicke's encephalopathy is a neuropsychiatric disorder caused by thiamine deficiency which is most commonly seen in alcoholics. Rarer causes include: persistent vomiting, stomach cancer, dietary deficiency. A classic triad of ophthalmoplegia/nystagmus, ataxia and confusion may occur. In Wernicke's encephalopathy petechial haemorrhages occur in a variety of structures in the brain including the mamillary bodies and ventricle walls.
Features
· nystagmus (the most common ocular sign)
· ophthalmoplegia
· ataxia
· confusion, altered GCS
· peripheral sensory neuropathy
Investigations
· decreased red cell transketolase
· MRI
Treatment is with urgent replacement of thiamine
Relationship with Korsakoff syndrome
If not treated Korsakoff's syndrome may develop as well. This is termed Wernicke-Korsakoff syndrome and is characterised by the addition of antero- and retrograde amnesia and confabulation in addition to the above symptoms.
| | |
| A useful mnemonic to remember the features of Wernicke's encephalopathy is CAN OPEN Confusion Ataxia Nystagmus Ophthamoplegia PEripheral Neuropathy Retrograde amnesia and confabulation are features of Korsakoff's psychosis | |
Wednesday, 23 December 2020
00:53
Cataplexy
Cataplexy describes the sudden and transient loss of muscular tone caused by strong emotion (e.g. laughter, being frightened). Around two-thirds of patients with narcolepsy have cataplexy.
Features range from buckling knees to collapse.
22 December 2020
20:39
Vestibular schwannoma (acoustic neuroma)
Vestibular schwannomas (sometimes referred to as acoustic neuromas) account for approximately 5% of intracranial tumours and 90% of cerebellopontine angle tumours.
The classical history of vestibular schwannoma includes a combination of vertigo, hearing loss, tinnitus and an absent corneal reflex. Features can be predicted by the affected cranial nerves:
· cranial nerve VIII: vertigo, unilateral sensorineural hearing loss, unilateral tinnitus
· cranial nerve V: absent corneal reflex
· cranial nerve VII: facial palsy
Bilateral vestibular schwannomas are seen in neurofibromatosis type 2.
Patients with a suspected vestibular schwannoma should be referred urgently to ENT. It should be noted though that the tumours are often slow growing, benign and often observed initially.
MRI of the cerebellopontine angle is the investigation of choice. Audiometry is also important as only 5% of patients will have a normal audiogram.
Management is with either surgery, radiotherapy or observation.
From <https://www.passmedicine.com/question/questions.php?q=0#>
22 December 2020
20:47
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension (also known as pseudotumour cerebri and formerly benign intracranial hypertension) is a condition classically seen in young, overweight females.
Risk factors
· obesity
· female sex
· pregnancy
· drugs*: oral contraceptive pill, steroids, tetracycline, vitamin A, lithium
Features
· headache
· blurred vision
· papilloedema (usually present)
· enlarged blind spot
· sixth nerve palsy may be present
Management
· weight loss
· diuretics e.g. acetazolamide
· topiramate is also used, and has the added benefit of causing weight loss in most patients
· repeated lumbar puncture
· surgery: optic nerve sheath decompression and fenestration may be needed to prevent damage to the optic nerve. A lumboperitoneal or ventriculoperitoneal shunt may also be performed to reduce intracranial pressure
*if intracranial hypertension is thought to occur secondary to a known causes (e.g. Medication) then it is of course not idiopathic
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From <https://www.passmedicine.com/question/questions.php?q=0#>
Comparing neurology diseases
01 January 2021
18:29
progressive polyneuropathy and hyporeflexia 3 weeks following a gastrointestinal infection - this is very suggestive of Guillain-Barre syndrome.
Myasthenia gravis typically presents with muscle fatigue particularly after exercise and ocular manifestations - droop of the upper eyelids is typical with weakness of external ocular muscles producing diplopia. In contrast to Guillain-Barre syndrome, tone is normal, sensation is unimpaired and tendon reflexes are normal in myasthenia gravis.
In polymyositis, diffuse weakness in the proximal muscles develops. Distal muscles are spared and weakness may vary from week to week or month to month. This is in contrast to Stephen's progressive distal limb weakness.
Acute transverse myelitis presents with an acute episode of weakness or paralysis of both legs, with sensory loss and loss of control of bowels and bladder. Commonly there is associated back or leg pain. This is a differential to consider here, however no bladder or bowel dysfunction is mentioned and there is also no mention of back pain in Stephen's history. Furthermore the history of gastrointestinal infection 3 weeks ago points more towards a diagnosis of Guillain-Barre syndrome.
Posterior circulation ischaemic stroke may present with motor or sensory deficits, however symptoms can often also include dizziness, diplopia, dysarthria, dysphagia, disequilibrium, ataxia, or visual field deficits - Stephen does not have any of these symptoms. Furthermore in a posterior circulation stroke, th
From <https://www.passmedicine.com/question/questions.php?q=0>
Hypotension with compensatory tachycardia 4D's
01 January 2021
19:03
Of all the other options, one would expect a compensatory tachycardia on standing. The '4Ds' can be useful in remembering causes of postural hypotension with compensatory tachycardia.
· Deconditioning.
· Dysfunctional heart: aortic stenosis.
· Dehydration: disease (acute illness, adrenal insufficiency), dialysis, drugs (diuretics, narcotics).
· Drugs: anti-anginals, anti-parkinsonian medications (levodopa), antidepressants, antipsychotics, anti–benign prostatic hyperplasia drugs (tamsulosin).
From <https://www.passmedicine.com/question/questions.php?q=0>
01 January 2021
20:51
Pontine haemorrhage
Is a life-threatening condition. It often occurs as a complication secondary to chronic hypertension. Patients often present with reduces Glasgow coma score, quadriplegia, miosis, and absent horizontal eye movements.
Hyperkinetic movement
05 January 2021
13:23
common types of hyperkinetic movements:
| Tremor | An oscillatory, usually rhythmic (to-and-fro) movement of one or more body parts, such as the neck, tongue, chin, or vocal cords or a limb. The rate, location, amplitude, and constancy vary depending on the specific type of tremor. |
| Dystonia | Both agonist and antagonist muscles of a body region contract simultaneously to produce a twisted posture of the limb, neck, or trunk. In contrast to chorea, dystonic movements repeatedly involve the same group of muscles. They do not necessarily flow or affect different muscle groups randomly. |
| Myoclonus | Sudden, brief, shock like jerks are caused by muscular contraction (positive myoclonus) or inhibition (negative myoclonus, such as asterixis). |
| Chorea | Involuntary, irregular, purposeless, nonrhythmic, often abrupt, rapid, and unsustained movements seem to flow randomly from one body part to another; they are unpredictable in timing, direction, and distribution. |
| Tics | Abnormal, stereotypic, repetitive movements (motor tics) or abnormal sounds (phonic tics) can be suppressed temporarily but may need to be “released” at some point. The release provides internal “relief” to the patient until the next “urge” is felt. |
From <https://mle.ncl.ac.uk/cases/page/17516/>
Action tremors can occur on different types of movement
· Postural - occurs when limbs/body specifically postured against gravity (see video at 0:40)
· Kinetic - occurs on goal-directed movement e.g. lifting a glass to lips
The most common action tremor is essential tremor, sometimes called benign essential tremor. This is a slowly progressive neurological disease that can significantly impact a patient's quality of life. It is often inherited in an autosomal dominant pattern. Patients will often report that their tremor improves with alcohol.
Treatment approach includes
Conservative: relaxation techniques, reduce caffeine
Medical: propanolol, primidone
Surgical: deep brain stimulation (only for very severe/refractory cases)
From <https://mle.ncl.ac.uk/cases/page/17513/>
Physiological tremor
It is normal to sometimes experience a physiological tremor, often an action/postural tremor. Physiological tremor can be exacerbated by stress, anxiety and fatigue. You have probably noticed this in yourself when nervous or after intense exercise. This can also be exacerbated by beta agonists e.g. salbutamol.
It is worth mentioning that tremors with a lower amplitude (amount of movement), tend to have a high frequency (movements per second). A normal physiological tremor demonstrates a high frequency (10Hz) but a low amplitude.
Functional tremor
Functional tremor is a tremor that is caused by the nervous system not working properly but not due to an underlying neurological disease ( https://www.neurosymptoms.org/functional-tremor/4594357998). Tremors that have a high amplitude AND frequency are more likely to be functional in nature. Features that point towards a functional tremor diagnosis are: abrupt onset, incongruous examination findings, variable, and changes or reduces frequency/amplitude on distraction. These tremors may have a variable frequency and can sometimes be 'entrained' (tremor frequency switches to match exactly the frequency of a voluntary rhythmical movement performed by the unaffected limb.) Functional tremors can be extremely disabling for patients.
Intention tremor
Intention tremors are tremors that are worsened during the endpoint of a directed movement towards a target. It has low frequency and a high amplitude. We see this when the cerebellar system is affected because the patient cannot precisely co-ordinate their movement to the target. Notice how the below tremor increases as the person tries to touch their nose.
From <https://mle.ncl.ac.uk/cases/page/17513/>
| Type of tremor | Description | Examples |
| Resting tremor | Occurs when the affected extremity is at complete rest and diminishes with movement | Parkinson’s disease |
| Postural tremor | Occurs when the affected limb is held in position against gravity. | Essential tremor Medication induced tremor Physiological tremor |
| Kinetic tremor | Occurs during voluntary movement. | Essential tremor |
| Intention tremor | Marked increase in tremor amplitude during the terminal portion of a targeted movement | Cerebellar tremor |
From <https://mle.ncl.ac.uk/cases/page/17513/>
Dystonias:
Dystonia is caused by sustained or intermittent muscle contractions / spasms that often lead the patient to hold abnormal postures or positions. This frequently causes discomfort and pain for the patient. Dystonia can have a genetic cause or be acquired from mechanisms such as trauma, stroke and drug toxicity. We will look at drug induced hyperkinesia later in this tutorial.
· Focal: one body part affected
· Segmental: adjacent body parts affected
· General: entire body affected
From <https://mle.ncl.ac.uk/cases/page/17517/>
Approach to management:
· Conservative: education, relaxation, massage
· Medical: A small % of patients respond to dopaminergic medication (e.g. levodopa). Benzodiazepines are also used.
· Surgical: BoTox injection, especially useful in focal dystonia. Deep brain stimulation may be used in severe cases.
Myoclonus:
You will have experienced myoclonus in the form of hypnic jerks when you have been falling asleep. These are the jolty / jerking limb movements that occur at the point of sleep onset. This is a normal nocturnal motor phenomenon but is a form of myoclonus. You can watch the video below to see an example of pathological myoclonus.
When myoclonus is pathological it is more often a feature of an underlying disease than a primary disorder. The characteristics of the myoclonus can help to localise the area of pathology but this is not something you need to know as a medical student.
Chorea:
Chorea is dervied from the Ancient Greek word for dance and describes an involuntary movement that is brief, irregular, nonrhythmic, non purposeful and flows from one body part to another in a random fashion. The movements typically last longer than myoclonus and are briefer than dystonia (although dystonia may be combined with chorea in some patients).
It is usually present at rest and may increase with distracting manoeuvres such as counting or performing mental arithmetic. The movements may be partially suppressible or incorporated into voluntary movements to make them less conspicuous. They usually disappear in sleep. Chorea can be unilateral or bilateral. It can affect all body parts: face, trunk, and limbs.
There are various causes of chorea that include drug-induced, stroke related and genetic causes. We will focus on Huntington's disease as a cause of chorea in the next chapter.
Tics:
You will likely be familiar with tics as a result of Tourette's syndrome (TS). A tic is an involuntary movement or vocalization that is usually of sudden onset, brief, repetitive, and stereotyped, but nonrhythmic. They are different to other hyperkinetic movements in that they are suppressible but irresistible.
A tic is usually associated with a premonitory “buildup” sensation or feeling of discomfort that is often localized to the affected area. Usually, the individual experiences a sensation of relief once the tic has occurred. Unlike most movement disorders, tics can persist during sleep.
They can be classified as motor, phonic or vocal and as simple or complex based on the manifestation. TS is thought to involve abnormalities in corticostriatothalamocortical circuitry. The video below shows some patient experiences with TS.
Huntington's disease
05 January 2021
13:38
Huntington's disease (HD) is the most frequent cause of a hereditary neurodegenerative choreic syndrome. It is caused by a faulty gene on chromosome 4, producing a mutant form of a protein called Huntingtin, which is thought to increase the rate of neuronal death in the brain. It is relatively rare disorder and affects about 8,000 people in the UK. HD is an autosomal disorder and therefore each child of an affected parent has a 50% chance of developing the disease (ref). We will take a deeper look into the genetics after we have learnt a bit more about the disease.
It is important that you recognise that HD is not only a movement disorder but also has marked cognitive and behavioural effects. In fact, the earliest signs of the disease in a patient are often subtle cognitive or mood related changes. Read the diagram below from https://hopes.stanford.edu/stages-of-huntingtons-disease/#46539 to appreciate the complex nature of the disease. Patients symptoms are highly variable and will present unique difficulties dependent on their particular lifestyle.
Motor symptoms include chorea, dystonia, and tics. Characteristically, the first motor symptom exhibited is a chorea (hence HD is also known as Hungtinton's chorea). The examination in the video below is very useful, in terms of being able to see specific signs but also in helping you to develop a general neurological impression of a patient with established HD.
We learned earlier that Hungtinton's disease has an autosomal dominant inheritance. The huntingtin gene (on the short arm of chromosome 4) codes for the huntingtin protein. The specific pathology of the disease is not completely characterised but mutated huntingtin protein aggregates are found in the basal ganglia, specifically the dorsal striatum (caudate and putamen), and these areas show increased neuronal death rates. There is thought to be a toxic gain-of-function in the mutant huntingtin protein.
A section of the genetic code for this protein has something called a trinucleotide repeat expansion. This is a repeating sequence of three nucleotides. In the case of huntingtin, this is a CAG repeat (which encodes glutamine and hence is known as a polyglutamine disease).
Patients with 40 or more repeats will develop the disease (100% penetrance) but patients with 36-39 repeats show a reduced penetrance. 27-35 repeats are classified as in the 'intermediate CAG range' and less than this is normal. For example, if a patient has a repeat number of 40, they are certain to develop the disease (assuming they survive until disease onset). A patient with 36 repeats may or may not develop HD and a patient with fewer repeats than this will not.
| Number of CAG repeats | Classification |
| <27 | Normal |
| 27-35 | Intermediate CAG range |
| 36-39 | Reduced penetrance |
| >39 | 100% penetrance |
The intermediate CAG range refers to people who, despite not having the disease, are at risk of passing on mutant alleles due to repeat expansion. This number of trinucleotide repeats causes the sequence to be unstable during DNA replication. There is a small risk that within one generation an error in replication can expand the repeat number into the disease range. This occurs much more in sperm than ova generation and thus repeat expansion mainly occurs in paternal alleles (ref). Further to this, expansion of repeats already in the disease range leads to an earlier onset and faster progression of symptoms. This phenomenon is known as anticipation. Each successive affected generation has a chance of inheriting a greater number of repeats, again most commonly from the father, and having an earlier disease onset.
Usually symptomatic onset is between the ages of 30 and 50, although onset can range from childhood/adolescence to individuals older than 70 years of age. There is a juvenile form, also known as the Westphal variant HD, due to a very large repeat count.
Other trinucleotide repeat disorders you may come across include Friedreich's ataxia, fragile X syndrome and types of myotonic dystrophy and spinocerebellar ataxia (of these, only spinocerebellar ataxia is a polyglutamine repeat).
From <https://mle.ncl.ac.uk/cases/page/17512/>
No disease modifying therapies are currently available for HD on the NHS. HCurrent treatments include:
Conservative: Symptomatic / supportive therapy to alleviate the symptoms
Medicine: Anti-choreic medication – atypical antipsychotics, tetrabenazine
Surgical: Deep brain stimulation for pharmacological resistant chorea with significant disability
Ultimately, there is no cure for HD at present and treatment revolves around supportive care (such as modifications in the patient's house by occupational therapists, physiotherapy, speech and language therapy and additional carers) and symptomatic relief. Tetrabenazine is approved for the treatment of chorea in HD. Antipsychotics can be used to treat psychiatric symptoms, as well as often also helping with chorea
Early symptoms
Motor:
Begin in extremities of body, people experience involuntary twitches in their fingers, toes and face. Onlookers generally don't notice these motions, or assume that they are just nerveous twitches.
People in the early years of HD also experience a subtle loss of coordination, and may have more trouble performing complicated motions
Cognitive symptoms:
Cognitive symptoms also become noticeable in the early stages of HD, as it become more difficult for people to think through complicated tasks
Behavioral:
Can be fairly serious even when motor and cognitive symptoms are quite minor. Depression, irritability, and inhibition are common in the early stages, some patients experience hypersexuality, which can cause problems in relationships
Mid-stage HD
Drug induced movement disorder
05 January 2021
13:54
Drug-induced movement disorders can be caused by a wide variety of drugs, including illicit substances (e.g. cocaine and amphetamines). We will focus on some important examples in this tutorial.
Tardive dyskinesia
The most common cause of drug-induced movement disorders are dopamine receptor blocking agents. Antipsychotics, metoclopramide and prochlorperazine are prevalent examples that you will undoubtedly prescribe during your career. These medications can cause various movement disorders including tremor, neuroleptic malignant syndrome (covered in the next section), dystonia and parkinsonism.
One of these disorders is called tardive dyskinesia. Classically, there are involuntary movements of the mouth, tongue and jaw (oro-buccal-lingual). There are various other 'tardive syndromes' that can affect the trunk and extremities, including causing choreiform movements. You can see a more classic example in the video below.
The exact pathophysiology of tardive dyskinesia in unclear. A common theory is that there is a dopamine hypersensitivity in the nigrostriatal pathway after chronic pharmacological blockage .
Tardive dyskinesia can be diagnosed if:
Patient had at least 3 months exposure to a dopamine receptor blocking agent (1 month if patient >60yrs old).
Symptoms present for at least 1 month after medication discontinued
Symptoms can emerge during or up to 4 weeks after stopping the medication - hence the name tardive (late/delayed appearance). You do not need to memorise these criteria but they are useful to appreciate the delayed onset of the disorder .
Treatment can be difficult and therefore prevention is crucial. Dopamine receptor blocking medications should be used in the lowest dose for the shortest time possible. Treatment involves withdrawing the offending agent and this may require an analysis of benefit vs. harm (e.g. if the antipsychotic is treating schizophrenia). There is usually a delay before improvement and changes can be irreversible. Tetrabenazine can be effective in some people who have not responded to treatment withdrawal.
neuroleptic malignant syndrome (NMS)
Dopamine receptor blocking drugs can cause a severe neurological emergency called neuroleptic malignant syndrome (NMS). This can also be induced by sudden cessation of dopaminergic medications e.g. levodopa.
NMS is a clinical diagnosis, supported by the diagnostic criteria below. NMS is characterised by high temperatures, rigidity, autonomic dysfunction and altered mental status (often agitated confusion). Patients may demonstrate hyporeflexia.
| Major (need all 3) | Minor (at least 2) |
| Exposure to dopamine antagonist or withdrawal of dopaminergic | Diaphoresis (sweating) |
| Rigidity | Dysphagia |
| Hyperthermia | Tremor |
| Incontinence | |
| Altered levels of consciousness | |
| Mutism | |
| Tachycardia | |
| Elevated or labile BP | |
| Leukocytosis | |
| Elevated CK |
Adapted from Diagnostic and Statistical Manual of Mental Disorders, 5th Edition
A common scenario for this to occur would be with a patient already on an antipsychotic e.g. haloperidol (highest risk) who is then given a dopamine blocking antiemetic such as metoclopramide. The high temperature and altered mental state would make you think about infection but is important to take note of the patient's medications. Rigidity, a new tremor and a raised CK should make you think about NMS.
The pathophysiology of NMS is thought to be due to the abrupt loss of dopaminergic activity in the nigrostriatal pathway and basal ganglia, with fever thought to be due to dopamine blockade in the hypothalamus (which plays a role in thermoregulation).
Treatment approach:
· Stop the dopamine blocking medication
· Supportive care: IV fluids, correct metabolic abnormalities
· Medications in severe cases: bromocriptine (a dopamine agonist, to increase dopaminergic activity) and dantrolene (muscle relaxant to reduce rigidity, acts by inhibiting inhibiting calcium release from the sarcoplasmic reticulum in muscle cells.)
(ref)
From <https://mle.ncl.ac.uk/cases/page/17522/>
Serotonin syndrome:
Serotonin syndrome is another drug-induced syndrome that causes hyperthermia and neurological changes. In patients with polypharmacy you may need to differentiate this from NMS.
Serotonin syndrome can be caused by prescription of multiple serotonergic drugs or medication overdose. This essentially leads to serotonin toxicity and hyperstimulation in the central nervous system. The video below is a good primer for the topic.
Serotonin syndrome can be caused by multiple classes of drugs that affect signaling in presynaptic and postsynaptic serotonergic neurons (in the raphe nuclei of the brainstem). The picture below demonstrates a serotonin synapse and how medications affect this.
· MAO inhibitors: reduced breakdown of serotonin
· Illicit drugs: promote serotonin release into the synaptic cleft or directly stimulate the postsynaptic cleft (amphetamines, ecstasy and cocaine)
· Tricyclic antidepressants: reduce serotonin re-uptake into the presynaptic neurone (amitriptyline)
· SSRIs and SNRIs: reduce serotonin re-uptake into the presynaptic neurone (fluoxetine, sertraline, duloxetine)
· Synthetic opioids: multiple effects on serotonergic neurons (tramadol, fentanyl)
(ref)
The table below shows the diagnostic criteria for serotonin syndrome. As is characterised by the acute onset of symptoms, commonly after a serotonergic medication change/overdose.
Approach to treatment:
· Withdraw serotonergic agents
· Supportive care: IV fluids, cooling
· Medications in severe cases: Benzodiazepines can be used to reduce agitation and myoclonus. Cyproheptadine (a serotonin antagonist) is sometimes used but the evidence base for this is not strongly established.
We can see that a lot of symptoms overlap with NMS. Differentiating between the two conditions clearly begins with checking the patient's medications and any recent changes. If a patient is pharmacologically at risk of both, their neurological symptoms are most helpful in distinguishing between the two.
| Serotonin Syndrome | Neuroleptic Malignant Syndrome | |
| Timing | More acute (<24hours) | More gradual (days-weeks) |
| Drugs | Serotonergic | Dopaminergic |
| Neurological reactivity | Increased: hyperreflexia, clonus, tremor | Decreased: rigidity, hyporeflexia |
| GI Features | Diarrhoea, increased bowel sounds | Usually normal |
From <https://mle.ncl.ac.uk/cases/page/17514/>
Future treatments
05 January 2021
14:02
Spinal Muscular Atrophy:
Recent advances in genetic medicine have allowed for the development of new treatments for single gene disorders. This is in the form of a new class of drugs called anti-sense oligonucleotides (ASOs). These compounds bind to specific mRNAs and ultimately affect protein expression in various desired ways, dependent on the disease we are treating.
For neurological disorders this has led to the development of treatments for Spinal Muscular Atrophy (SMA), and emerging treatments for Huntington's disease and MND (single gene variants).
The SMN protein is particularly important in promoting the survival of alpha motor neurons, which exit through the ventral roots of the spinal cord to directly innervate skeletal muscle and initiate contraction. In SMA the SMN1 gene is mutated or deleted homozygously in a way that ultimately results in insufficient levels of SMN protein.
The SMN2 gene is a pseudogene copy of SMN1, which means that it is a mutated copy which produces little or no functional protein. In this case very little functional protein is produced. This is because a single nucleotide mutation in exon 7 of SMN2 leads to it being removed in the majority of mRNAs. This resultant protein is non-functional / rapidly degraded.
Nusinersen is an ASO which binds to a complimentary sequence after exon 7 and causes mRNA processing to include this exon. Thus, functional SMN protein is produced. For many patients this leads to significant motor function and survival benefits.
From <https://mle.ncl.ac.uk/cases/page/17569/>
Huntington's disease
The pathology of Huntington's disease has been covered in the 'Hyperkinesia' tutorial. You will recall that this is an autosomal dominant condition in which a mutant copy of the huntingtin gene has an expansion of the CAG triplet repeats. This leads to the production of a toxic gain-of-function mutant huntingtin protein.
Lowering mutant huntingtin protein levels in the brain has been shown to improve symptoms of the disease. ASOs have therefore been developed to reduce the levels of this protein. In this case, rather than ASO binding resulting in increased levels of a protein, the ASO binding to mutant mRNA targets this mRNA for degradation
Motor neurone disease
The pathology and types of MND have been covered in the 'Motor Neurone Disease' lecture from this week's content. Amyotrophic lateral sclerosis (ALS) can be classified as either sporadic or familial / inherited (5-10%) . The familial forms of ALS (FALS) have a mutation in one of several genes known to cause ALS. These genes are therefore being researched as targets for ASOs.
So far, the most promising research has been undertaken with ASOs in patients with mutant SOD1 genes. Multiple point mutations in this gene have been found to be associated with FALS. However, the mechanism by which these mutations cause ALS is poorly characterised. Despite this results have been promising.
At the time of writing there are ongoing clinical trials for SOD1 ASOs. As with Huntington's, the purpose of the ASO is to target mutant mRNA for degradation.
The SOD1 gene is located on chromosome 21. If mutations in the SOD1 gene cause a gain-of-function,
if there is a gain of function from an allele, it is more likely that only one copy of the gene will be required to cause the disease. Conversely, if there is a loss-of-function in an allele, it is often the case that with wild type (normal) allele will produce enough protein to compensate for this. Thus there is a recessive pattern of inheritance. Again, this is not a hard and fast rule and dominant loss-of-function mutations can also occur.
From <https://mle.ncl.ac.uk/cases/page/17569/>
05 January 2021
15:08
Progressive Multifocal Leukoencephalopathy (PML)
This is a rare condition, you don't need to know everything about it.
Just be aware that PML is the big risk that neurologists think about when using DMTs, especially Natalizumab. The strongest DMTs carry the greatest risk.
PML is caused by reactivation of the JC virus in the CNS. Much of the general population has already been exposed to the JC virus and carries it in an inactive form. When the immune system is suppressed by DMTs, this virus can reactivate in the brain and cause significant neurological problems and even death. MS patients will have blood tests to assess the amount of JC virus antibody in their blood. This can guide treatment decisions.
From <https://mle.ncl.ac.uk/cases/page/17721/>
Differentials diffuse neuropathies
05 January 2021
15:34
· Motor neurone disease - A mix of UMN and LMN signs. Motor only with absence of sensory involvement. Fasiculation is more prominent in MND.
· Myasthenia gravis - Neuromuscular junction pathology. Muscle weakness that is fatiguable and varies over the day. Motor only with absence of sensory involvement. Weakness is more proximal. Reflexes are normal. MG may manifest with bulbar involvement, unlike peripheral neuropathy.
· Spinal cord syndrome - A spinal cord lesion will cause UMN signs. Weakness/sensory loss below the level of the lesion.
· Cauda Equina syndrome - Cauda Equina syndrome can look like a peripheral neuropathy. Bladder and bowel disturbance can also be present in autonomic neuropathy. Look for Cauda Equina red flag signs e.g. urinary retention, saddle anaesthesia, loss of anal tone etc. Back pain may be present. Have a low threshold for MRI spine if you suspect Cauda Equina syndrome.
· Myopathies - Motor only with no sensory involvement. Weakness is more proximal than distal (where larger muscle groups are.) Reflexes are normal. Fasiculation is unlikely.
From <https://mle.ncl.ac.uk/cases/page/17594/>
Acute multi-focal neuropathy
05 January 2021
15:36
Acute multi-focal neuropathy
An acute multi-focal neuropathy picture of random nerves being "picked off" suddenly is an alarming condition for a neurologist. A hyper-acute rapid onset suggests a vascular cause, fast action and urgent neurology referral is required to save the nerve from irreversible damage. A vasculitic neuropathy is rare, but worth being aware of due to the devastating consequences of delayed treatment.
From <https://mle.ncl.ac.uk/cases/page/17650/>
05 January 2021
15:37
Chronic inflammatory demyelinating polyneuropathy (CIDP):
A demyelinating process, causing predominantly painless motor symptoms. Can be seen on EMG studies. Treated with immune-modifying therapies e.g. steroids/IVIG/plasma exchange. May have future relapses and require further treatment.
From <https://mle.ncl.ac.uk/cases/page/17651/>
Sub-acute (weeks) are rare causes of a diffuse peripheral neuropathy and will be mostly invested/managed by a neurologist. Be aware of the basic principles.
05 January 2021
15:37
Paraneoplastic:
Cancer can cause a paraneoplastic immune-mediated peripheral neuropathy, especially small cell lung cancer and lymphoma. If suspected, investigations to look for an underlying cancer (e.g. CT chest/abdo/pelvis) may be indicated. Remember, some chemotherapy regimes may also cause a peripheral neuropathy.
Sub-acute (weeks) are rare causes of a diffuse peripheral neuropathy and will be mostly invested/managed by a neurologist. Be aware of the basic principles.