Neurology Flashcards
Stroke
acute neurological condition resulting from a disruption in cerebral perfusion either due to ischaemia (ischaemic stroke) or haemorrhage (haemorrhage stroke)
characterised by acute onset focal neurological deficits the pattern being dictated by the affected vessel and last >24h
4th most common single cause of death in UK
Transient ischaemic attack (TIA)
acute onset focal neurological deficits which resolve within 24h
Middle cerebral artery (MCA) stroke symptoms
Most commonly affected vessel
-contralateral weakness/hemiparesis and sensory loss
(more marked in upper limbs & lower half of face than in lower limbs)
-contralateral homonymous hemianopia
-gaze deviation (if superior MCA division)
-Aphasia
Broca’s/expressive (if superior MCA branch)
Wernicke’s/receptive (if inferior MCA branch)
conductive aphasia (if inferior MCA branch)
-Hemineglect, usually contralateral (if non dominant hemisphere)
Anterior cerebral artery (ACA) stroke symptoms
-contralateral hemiparesis/weakness & sensory loss (more pronounced in lower limbs than upper limbs)
-dysarthria
-limb apraxia (inability to perform precise, voluntary movements)
-frontal release sign
urinary incontinence
Posterior cerebral artery (PCA) stroke symptoms
- contralateral homonymous hemianopia with macular sparing
- contralateral sensory loss especially light touch/pinprick/proprioception
- memory deficits
- if dominant (left hemisphere): visual agnosia, expressive aphasia
- if non dominant (right hemisphere): prosopagnosia (inability to recognise faces)
Posterior inferior cerebellar artery (PICA) stroke symptoms
lateral medullary syndrome (Wallenberg syndorme)
ipsilateral nystagmus, vertigo, limb ataxia, Horner syndrome, ↓pain & temp sensation to face, bulbar palsy (dysphagia/dysphonia)
Anterior inferior cerebellar artery (AICA) stroke symptoms
lateral pontine syndrome
contralateral loss of pain & temp sensation
ipsilateral limb & gait ataxia, loss of facial pain & temp sensation, facial muscle weakness, ↓lacrimation, vertigo, nystagmus, hearing loss, Horner syndrome
Basilar artery stroke
locked in syndrome
Weber’s syndrome
stroke in branches of PCA supplying midbrain
Ipsilateral CNIII palsy
contralateral weakness of upper & lower extremities
Lenticulostriate arteries (Deep MCA branches) stroke symptoms
No cortical signs (e.g. neglect/visual loss/aphasia)
presents as isolated hemiparesis, hemisensory loss, limb ataxia
Oxford stroke classification (Bamford classification)
asses the following features:
- unilateral hemiparesis and/or hemisensory loss of face, arm, leg
- homonymous hemianopia
- higher cognitive dysfunction e.g. aphasia
Total anterior circulation infarct (Bamford classification)
~15% of strokes
involves MCA & ACA
Presents with
- unilateral hemiparesis and/or hemisensory loss of face, arm, leg
- homonymous hemianopia
- higher cognitive dysfunction e.g. aphasia
Partial anterior circulation infarct (Bamford classification)
~25% of strokes
involves smaller arteries of anterior circulation
presents with 2 of
- unilateral hemiparesis and/or hemisensory loss of face, arm, leg
- homonymous hemianopia
- higher cognitive dysfunction e.g. aphasia
Lacunar infarcts (Bamford classification)
~25% of strokes
involves perforating arteries around basal ganglia/thalamus/internal capsule
Presents with 1 of
- unilateral weakness and/or sensory deficit of face/arms/legs
- pure sensory stroke
- ataxic hemiparesis
Posterior circulation infarcts (Bamford classification)
~25%
involves vertebrobasilar arteries
Presents with 1 of
- cerebellar/brainstem syndromes
- LOC
- isolated homonymous hemianopia
Assessment & investigations of stroke
FAST assessment
ROSIER score
non-contrast CT head (GOLD standard)*
serum glucose* (to exclude hypoglycaemia)
FBCs/U&Es/LFTs/Coag
ECG (check for AF)
Consider MRI & carotid artery doppler
Differential diagnosis for stroke
Hypoglycaemia (must be excluded) Seizure disorders complicated migraines subdural haematoma hypertensive encephalopathy brain tumour
Ischaemic stroke
A stroke due to vascular occlusion/stenosis causing ischaemia, leading to cerebral infarction due to insufficient cerebral blood flow
~85% of all strokes
Subtypes of ischaemic strokes
Thrombotic e..g thrombus in large vessel such as the carotids
Embolic e.g. embolus from heart in AF
global cerebral ischaemia e.g. in cardiac arrest
Risk factors for ischaemic stroke
AF ↑ age FH of stroke previous ischaemic stroke HTN smoking hyperlipidaemia previous TIA peripheral arterial disease carotid artery stenosis diabetes
Presentation of ischaemic stroke
sudden onset of focal neurological deficits depending on which vessel is involved
impaired consciousness (but LOC is uncommon in stroke)
nausea
vomiting
headache
Ischaemic stroke on CT
hyperdense occluded vessel
hypo attenuated brain parenchyma (dark)
Management of ischaemic stroke
Reperfusion therapy:
IV thromobolysis e.g. alteplase/tenecteplase
give within ≤4.5h of symptom onset
NB a hemorrhagic stroke must be excluded
–
Thrombectomy
offer in addition to IV thrombolysis if within 6h
offer within 24h if confirmed anterior circulation stroke
BP control
Aspirin 300mg
rehab PT/OT/SALT
Long term secondary prophylaxis in ischaemic stroke
1st line: 75mg clopidogrel
2nd line: 75mg aspirin + MR dipyridamole
Contraindications for thrombolysis
Previous intracranial haemorrhage Intracranial neoplasm Active bleeding Pregnancy Uncontrolled hypertension
Haemorrhagic stroke
A stroke due to the rupture of a blood vessel leading to intracerebral (intraparenchymal) / subarachnoid / intraventricular haemorrhage
~15% of all strokes
Risk factors for hemorrhagic stroke
↑age HTN arteriovenous malformation (AVM) anticoagulation therapy male gender heavy alcohol use family history of intracerebral haemorrhage haemophilia & other clotting disorders asian ethnicity
Presentation of hemorrhagic stroke
generally gradually progressive worsening of focal neurological deficits
later on:
↑ ICP (nausea & vomiting, LOC, confusion, fixed dilated pupils)
Hemorrhagic stroke on CT
hyperlattenuation (bright) new blood with surrounding hypo attenuated (dark) oedema
Management of haemorrhagic stroke
reverse anticoagulation / stop anticoagulants
Consider surgical intervention
rehab PT/OT/SALT
Transient ischaemic attack (TIA)
temporary focal ischaemia that results in reversible neurological deficits without acute infarction (Tissue based definition, not time based)
most pts have complete reversal if symptoms within 1h
↑ risk of stroke after TIA
Investigations for Transient ischaemic attack (TIA)
FBCs/U&Es/FLTs/blood glucose/coag
MRI(1st line imaging)
NB CT is no longer recommended 1st line
Management of Transient ischaemic attack (TIA)
If TIA in the last 7 days then TIA clinic within 24h
If TIA >7days ago then TIA clinic within 7 days
NB pt should not drive until seen by TIA clinic
300mg aspirin immediately
then 75 mg clopidogrel daily lifelong
if pt has a bleeding disorder/ taking anticoagulant = needs immediate admission for imaging to exclude a haemorrhage
Primary prevention of strokes
lifestyle advice (diet/smoking/exercise/alcohol)
statin therapy
treat HTN
treat AF (asses with CHADS-VASC score fro stroke risk & HAS-BLED score to asses risk of bleeding)
Secondary prevention of strokes
300mg aspirin daily for 2 weeks once haemorrhage excluded
then 75 mg clopidogrel daily lifelong (75mg aspirin + MR dipyridamole if clopidogrel not tolerated)
statins
carotid endarterectomy/carotid artery stenting if stenosis >70%
Epilepsy/seizure disorders
A seizure is defined as a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain
epilepsy is defined as a chronic neurological condition characterised by any of the following
- ≥2 unprovoked seizures (reflex seizures) occurring >24h apart
- 1 unprovoked seizure with an underlying predisposition to seizures
- diagnosis of an epilepsy syndrome
Focal seizures
originating within the networks linked to one hemisphere, often seen with underlying structural disease
Types of focal seizure
Focal aware (simple partial): awareness unimpaired, no post octal symptoms, with focal motor/sensory/autonomic/psychic symptoms
Focal impaired awareness (complex partial):
awareness impaired at seizure onset/following simple partial aura, some post octal symptoms
focal to bilateral (secondary generalised):
focal seizure that spreads widely triggering a usually convulsive general seizure
Generalised seizures
originating at some point within & rapidly engaging bilaterally distributed networks leading to simultaneous onset of widespread electrical discharge with no localising features referable to a single hemisphere
NB all include loss of awareness
Absence seizure
non motor seizures
common presentation of epilepsy in childhood
brief LOC, interrupted motion/activity, blank stares, unresponsiveness, usually lasting 5-30 sec
may have subtle automatisms
consciousness rapidly returns
may occur multiple times during day
Tonic-clonic seizure
prodrome may occur hours before seizure e.g. mood change, irritability, anxiety
sudden LOC without warning
often bladder/bowel incontinence
Motor symptoms:
-Tonic: generalised muscle contraction, including apnoea, tongue biting, cyanosis, octal cry
-Clonic: rhythmic muscle twitching/jerking
Postictal:
hyper salivation, confusion, amnesia, unresponsiveness
Myoclonic seizure
sudden jerk of limb/face/trunk, pt may be thrown to the ground suddenly/violently or have a disobedient limb
Atonic seizure
sudden loss of muscle tone leading to fall, no LOC
also known as drop attacks
usually lasts ~2sec
Aetiology of seizures
mostly idiopathic
seizures with focal onset are more likely to have underlying disease
causes include cerebrovascular disease, brain neoplasm, head injury, neurodegenerative disease, drugs (e.g. isoniazid), CNS infection`
Focal seizures with intact awareness
from focal cerebral regions confined to 1 hemisphere
may have a prodrome
consciousness is always retained
features can include motor (clonic involuntary repetitive movements of contralateral limb/facial muscles) or sensory or psychiatric symptoms (parasthesia, vertigo, unusual/intense smells, complex sounds, hallucinations)
focal seizures with impaired awareness
frequently originate in temporal lobes
may have sensory/psychic symptoms (hallucinations, disorientation)
sudden behavioural arrest
impaired consciousness
automatisms e.g. lip smacking, chewing, fumbling
Investigating seizures
Pt history &collateral (key)
EEG (indicated after any unprovoked seizure)
MRI head (CT head if MRI unavailable)
Bloods (FBC/U&Es/LFTs/glucose/prolactin/creatinine/Ca2+)
ECG
LP (if CNS infection suspected)
consider short term video-EEG or inpatient video-EEG) or polysomnogrpahy
EEG results for epilepsy
may show generalised epileptiform activity (bursts of abnormal discharges) or focal localising abnormality
but also frequently normal even after provocation e.g. hyperventilation, visual stimuli, sleep deprivation
if seizure caught = epileptiform discharges
Management of simple focal seizures
1st line: carbamazepine or lamotrigine
2nd line: levetiracetam/sodium valproate
Management of generalised tonic-clonic seizures
1st line: sodium valproate
2nd line: carbamazepine/lamotrigine
Management of absence seizures
1st line: ethosuximide/sodium valproate
2nd line: lamotrigine
NB carbamazepine may exacerbate absence seizures
Atonic seizures treatment
Sodium valproate
Driving and epilepsy
6 months no driving:
if first time seizure & no underlying structural abnormality and no epileptiform activity on EEG
12 months no driving:
if first time seizure but not meeting above criteria
Epileptics:
can drive if seizure free fro 12 months
no driving whilst withdrawing/till 6months after withdrawing epilepsy medication
Status epilepticus
single seizure lasting >5 min or ≥2 seizures within a 5 minute period or without pt returning to baseline between seizures
Management of status epilepticus
ABCDE assessment
IV lorazepam/rectal diazepam/buccal midazolam (repeat dose at 10 minutes)
If seizure continues then IV phenytoin or phenobarbital
if no response/refractory (>45min) then RSI (with propofol/midazolam)
Sudden unexpected death in epilepsy (SUDEP)
defined as sudden, unexpected, non-witnessed, non-traumatic , non-drowning death of a person with epilepsy with or without a seizures excluding documented status epileptics and in whom post-mortem examination does not reveal a structural/toxicological cause of death
usually occurs in those with chronic epilepsy
often occurring in sleep, usually in a young person/young adult with medically intractable epilepsy
Parkinson’s disease (PD)
idiopathic PD is a neurodegenerative disordering rthat involves progressive depletion of dopaminergic neutrons in the basal ganglia, particularly the substantial migration
generally idiopathic but some genetic predispositions exist (LRRK2, SNCA, PINK-1, Parkin)
2nd most common neurodegenerative disorder after alzheimers
Epidemiology of parkinson’s
onset usually age 60-65yrs
more common in men
NB juvenile parkinson is onset <21 yrs
NB young onset PD is onset age 21-40 yrs
Pathophysiology of Parkinson’s
selective loss nigrostriatal dopaminergic neutrons of the substantiated migration pars compacta
occurs with findings of intracytoplasmic eosinophilic inclusion (lewy bodies) & neuritis composed of misfolded, clumped alpha-synuclein
lead to ↓ activity of direct pathway & ↑activity of indirect pathway leading to ↑ inhibitory activity from globes pallidus/substatia migration zone reticulata to the thalamus leading to ↓ output to the cortex
Cardinal features of Parkinson’s
Bradykinesia (hypokinesia, difficulty initiating movements, short shuffling gait, ↓ arm swing)
rigidity (cogwheel)
tremor (resting tremor, 4-6Hz, typically pin rolling of thumb & index)
Presentation of Parkinson’s
gradually worsening symptoms
early stage:
constipation, anosmia, sleep disturbance
later:
Motor symptoms:
(Bradykinesia, rigidity, tremor) usually unilateral
postural instability, Prakinson’s gait (shuffling), micrographia, ↓ facial expression
Non motor symptoms:
urinary urgency, orthostatic hypotension, impaired sexual function, psychiatric problems (e.g. depression, anxiety, sleep disturbance), fatigue, sleep fragmentation
Diagnostic criteria for Parkinson’s
Bradykinesia plus ≥1 of:
- muscular rigidity
- 4-6Hz resting tremor
- postural instability not caused by primary visual/vestibular/proprioceptive dysfunction
Investigating Parkinson’s
Generally clinical diagnosis
investigations to exclude differentials: CT/MRI brain SPECT scan Flurodopa PET genetic testing 24h urine copper (for Wilson's disease) ceruloplasmin (for Wilson's disease)
Non-pharmacological management of Parkinson’s
specialist referral health & social care assessment physiotherapy physical activity nutritional support SALT
Surgical:
Deep brain stimulation (DBS) - for advanced PD not adequately controlled by medication
Pharmacological treatment of Parkinson’s
Motor symptoms with affected QoL: Levodopa (L-Dopa)
Motor symptoms no affecting QoL: dopamine agonists/Levodopa
NB decarboxylase inhibitors e.g. carbidopa or COMT inhibitors e.g. entecapone/tolcapone may be offered with L-dopa when it begins to show ↓ effectiveness
SSRIs for depression
L-Dopa (levodopa)
dopamine precursor
may be combined with decarboxylase inhibitors e.g. carbidopa/benserazide to prevent peripheral metabolisation
honeymoon period of 5-10yrs before adverse effects arise
NOT effective in neuroleptic induced parkinsonism
Dopamine agonists
e.g. bromocriptine, cabergoline, rotigotine, apomorphine, pramipexole
similar adverse effects to L-Dopa but more severe & common
MAO-B inhibitors
e.g. selegiline, rasegiline
↓ breakdown of dopamine secreted by dopaminergic neutrons
early monotherapy may delay need for L-Dopa
Amantadine
NMDA antagonists
drug of choice for akinetic crisis
cannot be used long term, loses effect
COMT inhibitors
e.g. entecapone, tolcapone
inhibit catechol-O-methyltransferase = ↓ peripheral L-Dopa breakdown & ↓ CNS dopaminergic breakdown
usually used in conjunction with L-Dopa in those with established PD
L-Dopa adverse effects
usually arise after 5-10yrs honeymoon period
On-Off effect
Motor fluctuations (hypokinesia, dyskinesia)
Akinetic crisis
visual hallucinations
orthostatic hypotension (↓ with carbidopa)
Nausea & vominting (↓ with carbidopa)
On-Off effect of L-Dopa
pt may switch from controlled symptoms/dyskinesia to no effect/immobility over a few minutes
due to ↓ action of L-Dopa / wearing off of medication
may be helped by COMT inhibitors, prolongs release L-Dopa preparations or dopamine agonists
Motor fluctuations of L-Dopa
Hypokinesia:
end of dose akinesia (wearing off effect), freezing
Dyskinesia (hyperkinesia):
usually at beginning/end of dose or at peak
cana ct long acting dopamine agonist/ COMT inhibitors
Akinetic crisis in Parkinson’s
condition caused by severe dopamine deficiency which may be cause by sudden L-Dopa suddenly discontinued
worsened motor symptoms + severe akinesia
treated with apomorphine, amantadine, L-Dopa
Other causes of Parkinson’s
Drug induced e.g. antipsychotics or metoclopramide (usually rapid bilateral onset of symptoms)
Toxins
Wilson’s disease
Alzheimers with Parkinsonism
Parkinson-plus syndromes (MSA, progressive supra nuclear palsy)
post-encephalitis
Hallmark of drug induced Parkinson’s
bilateral symptoms
rapid onset
Parkinson-plus syndrome
rare neurodegenerative conditions presenting with Parkinsonism and a variety of other features
have less favourable prognosis than Parkinson’s
generally do not respond to L-Dopa, have earlier involvement of autonomic nervous system and early onset of postural instability with frequent falls & dementia
Multiple system atrophy (MSA)
Parkinson plus syndrome
adult onset neurodegenerative disease characterised by neuronal degeneration in the substantia nigra
Presentation:
parkinsonism, cerebellar dysfunction (ataxia, tremor, dysarthria), urinary incontinence, erectile dysfunction, orthostatic hypotension
clinical diagnosis (hot cross bun sign on MRI)
only symptomatic treatment available
Progressive supra nuclear palsy (PSP)
presents with vertical gaze palsy (especially downward gaze), postural instability & frequent falls, wide base stance, retropulsion, bradykinesia, dysarthria, apathy, disinhibition, frontal lobe dysfunction
MRI: midbrain atrophy (hummingbird sign)
Corticobasal degeneration
neurdegeneration of the cerebral cortex & basal ganglia
presents with asymmetric motor abnormalities, alien limb phenomenon (pt perceives affected limb as not belonging to them), apraxia, cortical sensory loss
Huntington’s disease (HD)
slow progressive neurodegenerative disorder characterised by chorea ( characterised by jerky involuntary movements), incoordination, cognitive decline , personality change & psychiatric symptoms
typically develops ages 35
Genetics of Huntington’s
autosomal dominant inherited disease caused by mutation in Huntingtin gene (chromosome 4(
leads to trinucleotide repeat disorder with expansion of a CAG trinucleotide
exhibits phenomenon of anticipation
Pathophysiology of Huntington’s
leads to degeneration of cholinergic & GABAergic neutrons in the striatum of the basal ganglia at start of indirect pathway leading to ↑ cortical activity
Presentation of Huntington’s
Early stages:
personality change, self neglect, apathy, clumsiness, fidgeting, fleeting facial grimacing
Initial stage:
chorea (involuntary, sudden, irregular, non-repetitive arrhythmic movements of limbs/neck/head/face)
athetosis (involuntary writhing movements particularly of head/fingers)
hyperreflexia, saccadic eye movement slowed (head turning to shift gaze)
Advanced stages:
hypokinetic motor symptoms (dystonia, bradkykinesia, rigidity), akinetic mutism, motor impersistence (inability to sustain simple voluntary acts), dysarthria, dysphagia, clonus, spasticity
cognitive decline, behavioural change, dementia, more depressive disorder, aggression, psychosis
Investigations of Huntington’s
generally clinical diagnosis
CAG genetic testing (≥40 CAG repeats = positive, ≤28 CAG repeats = normal, 28-40 CAG repeats = expanded sequence)
Management of Huntington’s
SSRIs for depression & behavioural disorders
psychotherapy
physiotherapy
early palliative care input
atypical antipsychotics for psychosis & chorea
prognosis of Huntington’s
currently relentless progressive disorder with steadily worsening symptoms
disease duration till death ~20yrs
death most commonly caused by intercurrent illness e.g. pneumonia
2nd most common cause of death = suicide
Multiple sclerosis (MS)
inflammatory immune mediated chronic degenerative disease characterise by repeated episodes of inflammation of the nervous tissue in the brain & spinal cord leading to demyelination
Epidemiology of Multiple sclerosis (MS)
3:1 female:male ratio
onset usually age 20-40 yrs
more common in white population
Family history = biggest risk factor
Subtypes of Multiple sclerosis (MS)
relapsing & remitting MS: (RR-MS)
most common form (~85-90%)
acute exacerbations lasting 1-2 months followed by periods of remission (≥ 30 days of clinical stability)
secondary progressive disease : (SP-MS)
pts who have deteriorated & developed neurological signs & symptoms between relapses
~65% of pts with RR-MS develop SP-MS within 15 yrs of diagnosis
primary progressive disease (PP-MS)
~10% of pts
progressive deterioration from onset
more common in older pts
Presentation of Multiple sclerosis (MS)
wide range of signs & symptoms, depend on location of lesions
often unspecific e.g. fatigue, headache, lethargy
Optic/visual symptoms: optic neuritis (common early presenting feature, acute impaired vision & colourblindness) generally unilateral relative afferent pupillary defect intranuclear ophthalmoplegia, optic atrophy, eye movement issues
Sensory:
pins&needles, parenthesia/numbensss, trigeminal neuralgia, Lhermitte sign (shooting electric sensation in limb on neck flexion)
Motor: spastic weakness (most commonly in legs)
Cerebellar:
ataxia, intention tremor, scanning, speech, nystagmus
others: neuropathic pain, cranial nerve palsies, sensory ataxia, bowel&bladder dysfunction, sexual dysfunction Uthoff phenomenon (reversible worsening neurological symptoms on ↑ body temp)
Lhermitte sign
shooting electric sensation in limbs on neck flexion
Uhthoff’s phenomenon
reversible worsening neurological symptoms on ↑ body temp
Investigating Multiple sclerosis (MS)
- MRI brain/spinal cord (multiple sclerotic plaques, commonly in periventricular white matter)
- contrast enhanced MRI (enhancement of active lesions)
- Lumbar puncture (CSF = oligo clinical bands & ↑ CSF IgG)
McDonald criteria
used to diagnose Multiple sclerosis (MS)
based on dissemination in time & space of CNS lesions
disseminated in time = appearance of new lesions overtime / multiple relapses / active & old lesions on MRI
disseminated in space = presence of lesions in different regions of the CNS
Management of active multiple sclerosis (MS) relapses
1st line: high dose steroids e.g. oral/IV methylprednisolone (help shorten length of relapse)
2nd line: plasma exchange
Disease modifying drugs for Multiple sclerosis (MS)
Beta-interferon (↓ relapses rate by ~30%)
NB must have RR-MS/SP-MS + ≥2 relapses inlets 2 years + walk ≥100m unaided
Rituximab / ocrelizumab / alemtuzumab / fingolimod
Symptomatic treatments for Multiple sclerosis (MS)
Fatigue: trial of amantadine
Spasticity: baclofen / gabapentin + physiotherapy
bladder dysfunction: intermittent self catheterisation
Nystagmus (affecting visual acuity): gabapentin
Myasthenia gravis (MG)
chronic autoimmune disorder of the post synaptic membrane at the neuromuscular junction (NMJ) in skeletal muscle
the pathological process involves autoantibodies directed against the post synaptic acetylcholine receptors (AChR) leading to impaired neuromuscular transmission
Epidemiology of Myasthenia gravis (MG)
More common in women
women present earlier than men (usually during childbearing age)
males present later (age 40-70)
Aetiology of Myasthenia gravis (MG)
80-90% have autoantibodies against nicotinic AChR on post synaptic membrane of NMJ
5-10~ have autoantibodies against muscle specific tyrosine kinase (MuSK)
Associated conditions with Myasthenia gravis (MG)
Thymoma (in 10-15% of pts)
Thymic hyperplasia (65% of pts)
other autoimmune conditions: SLE, thyroiditis, RA
Presentation of Myasthenia gravis (MG)
Muscle fatiguability:
weakness worsens with activity & improves with rest
generally diurnal variation (worse in evening)
Eye muscle weakness:
patois, diplopia, blurred vision
Bulbar muscle weakness:
slurred speech, dysphagia, dysarthria, difficulty chewing
NO muscle wasting or fasciculations
Normal tone
unimpaired sensation
normal reflexes
Investigating Myasthenia gravis (MG)
AChR & MuSK antibody tests (+ve/↑ levels)
CT thorax (exclude thymoma)
single fibre EMG (↑ variability in motor latencies (jitter) or complete block in some neuromuscular transmission)
repetitive nerve stimulation (>10% ↓ in compound action potential amplitude between 1st & 4th potential of 10 = decremental response)
Edrophonium (tension) test: not commonly used, give short acting acetylcholinesterase inhibitor reversing symptoms
Management of Myasthenia gravis (MG)
1st line: Long acting acetylcholinesterase inhibitor
e.g. pyridostigmine (symptomatic treatment)
Immunosuppressant (usually in addition to pyridostigmine)
initially prednisolone then one of the below
e.g. azathioprine, cyclosporine, tacrloimus
emergent: rituximab, eculizumab, belimumab
thymomectomy (even if no thymoma)
Lambert-Eaton myasthenia syndrome (LEMS)
rare autoimmune disease of the NMJ that leads to impaired presynaptic release of acetylcholine (ACh) due to production of autoantibodies against presynaptic voltage gated Ca2+ channels required for presynaptic vesicle fusion to allow ACh release
rare condition
more common in males
Risk factors/Associated conditions for Lambert-Eaton myasthenia syndrome (LEMS)
associated with Small cell lung carcinoma
Risk factors:
cancer (found within 2 years of LEMS onset)
long term smoking history
Presentation of Lambert-Eaton myasthenia syndrome (LEMS)
generally insidious symptom onset
proximal muscle weakness (improves throughout day)
usually proximal muscles of lower limbs so gaits affected, then progresses to arms
limb-girdle weakness
hyporeflexia/arefelxia
autonomic symptoms (dry mouth, sexual dysfunction, constipation, postural hypotension)
ocular/oropharyngeal muscles rarely affected
repeated muscle contraction = ↑ strength initially before ↓ muscle strength (Lambert sign)
Presentation of Lambert-Eaton myasthenia syndrome (LEMS)
generally insidious symptom onset
proximal muscle weakness (improves throughout day)
usually proximal muscles of lower limbs so gaits affected, then progresses to arms
limb-grille weakness
hyporeflexia/arefelxia
autonomic symptoms (dry mouth, sexual dysfunction, constipation, postural hypotension)
ocular/oropharyngeal muscles rarely affected
repeated muscle contraction = ↑ strength initially before ↓ muscle strength (Lambert sign)
differences between myasthenia gravis & Lambert-Eaton syndrome
MG: commonly affects ocular/oropharyngeal muscles
LE: doesn’t commonly affected ocular/oropharyngeal muscles
MG: normoreflexic
LE: hyporeflexia/areflexia
MG: autonomic symptoms uncommon
LE: autonomic symptoms common
MG: decremental response to repetitive stimulation
LE: incremental response to repetitive stimulation
MG: AChR antibodies positive
LE: no AChR antibodies
MG: good effect with acetylcholinesterase inhibitors
LE: little effect with acetylcholinesterase inhibitors
Investigating Lambert-Eaton myasthenia syndrome (LEMS)
AChR antibodies (-ve)
CT/MRI chest (for potential chest malignancy)
anti-VGCC antibodies (+ve)
consider bronchoscopy
EMG (incremental response to repetitive stimulation )
screen for underlying cancer for 2yrs after diagnosis
Management of Lambert-Eaton myasthenia syndrome (LEMS)
extensive search & treatment of underlying cancer
1st line: 3,4-diaminopyridine (improves muscle strength)
Immunosuppression:
IVIG, azathioprine, methotrexate, prednisolone
Charcot-Marie-Tooth disease (CMT)
the most common hereditary peripheral neuropathy, heterogenous group of inherited neuropathies
both motor & sensory nerves are usually affected with symmetrical changes on nerve conduction studies
progressive nerve disorder due to impaired axonal or Schwann cell growth & function
Charcot-Marie-Tooth disease (CMT) genetics
commonly autosomal dominant inheritance
CMT1A most common (>50% of cases)
different subtypes have different onsets
Presentation of Charcot-Marie-Tooth disease (CMT)
slow insidious onset & slow progression
CMT1 onset by age 10
muscle weakness & wasting starting distally in intrinsic muscles of feet moving into lower leg & thigh (foot drop, atrophy of calf muscles - champagne bottle legs, per caves, hammer toe)
ascending flaccid paralysis beginning distally
sensory loss follow some pattern of motor loss (↓ vibration & light touch) ↓ proprioception (sensory ataxia, high stepping gait)
Investigating Charcot-Marie-Tooth disease (CMT)
nerve conduction studies (↓ conduction velocity, ↓ action potential amplitude, generally symmetrical deficits in all tested nerves, ↑ distal latencies)
genetic testing for CMT genes
Management of Charcot-Marie-Tooth disease (CMT)
rehabilitation (stretching, mild-moderate exercise, orthotic devices)
analgesia for neuropathic/non-neuropathic pain
Surgical:
orthopaedic surgery to counteract foot & ankle problems
Guillain-Barre syndrome (GBS)
describes an immune mediated demyelinating polyneuropathy frequently this is post-infectious, cross-reactive autoantibodies attack the hosts own axonal antigens leading to inflammatory & demyelinating polyneuropathy with axonal degeneration
epidemiology of Guillain-Barre syndrome (GBS)
slightly more common in males
peak age 15-35 yrs & 50-75 yrs
Aetiology of Guillain-Barre syndrome (GBS)
frequently preceding GI infection or URTI ~1-7 weeks prior to symptoms onset
campylobacter jejune classically implicated
Subtypes of Guillain-Barre syndrome (GBS)
Acute inflammatory demyelinating polyneuropathy (AIDP): acute form of GBS, 60-80% of cases, peak symptoms <4 weeks
Chronic inflammatory demyelinating polyneuropathy (CIDP): chronic for of GBS, usually anti-GM1 antibodies, presents similar to GBS but lasts >8 weeks
Miller-Fisher syndrome: limited form of GBS involving cranial nerves
Presentation of Guillain-Barre syndrome (GBS)
initially back & leg pain (neuropathic)
progressive ascending symmetrical weakness of all limbs (usually legs affected first, bilateral ascending flaccid paralysis, proximal before distal muscles, areflexia/hyperreflexia, hypotonia)
Paraesthesia (peripheral, symmetrically starting in hand & feet)
Investigating Guillain-Barre syndrome (GBS)
Nerve conduction studies (↓ conduction velocity)
lumbar puncture (↑ protein, normall WCC)
antibody studies (antiganglioside antibodies)
ECG
FBC/U&Es/LFTs
Management of Guillain-Barre syndrome (GBS)
Plasma exchange
IVIG, can be given longterm e.g. CIDP (need to give DVT prophylaxis)
pain relief for neuropathic pain
NB: Steroids not recommended for treatment
Polyneuropathy/peripheral neuropathies
a disorder involving damage to multiple peripheral nerve fibres i.e. a generalised disease of the peripheral nerves
frequently a manifestation of systemic illness
classical presentation is a symmetric distal burning sensation or paresthesia
Aetiology of Polyneuropathies
Demyelinating:
CIDP, CMT , GBS, toxic polyneuropathy
Axonal:
diabetic neuropathy, alcohol abuse, HIV, lead poisoning, hypothyroidism
General presentation of polyneuropathies
symmetric numbest, paraesthesia starting in the feet & distal lower extremities
if severe may be glove & stocking distribution
balance & gait may be impaired
hyporeflexia
distal muscle wasting
Investigating polyneuropathies
FBC, HbA1c, TFTs, LFTs, Vit B12, folic acid serum toxin screen hepatitis serology HIV test nerve conduction studies EMG
Diabetic neuropathy
progressive peripheral nerve injury due to chronic hyperglycaemia
presents with distal symmetric sensory loss, burning feet syndrome (symptoms worse at night), trophic skin changes, autonomic features (erectile dysfunction, gastric atony)
Alcoholic neuropathy
progressive peripheral nerve injury due to thiamine deficiency in chronic alcohol abuse + subacute combined degeneration of the spinal cord affecting dorsal columns
presents with symmetrical distal sensory loss (especially proprioception), burning feet syndrome
HIV neuropathy
progressive peripheral nerve injury due to HIV virus
presents with distal symmetrical neuropathy affecting sensory & motor nerves, may be exacerbated by retroviral therapy, autonomic features (erectile dysfunction, bladder dysfunction)
Motor neurone disease (MND)
a rare neurological condition of unknown cause which can affect upper motor neurone (UMN) & lower motor neurons (LMN)
subtypes include amyotrophic lateral sclerosis (ALS), progressive bulbar palsy, progressive muscular atrophy, primary lateral sclerosis
generally presents around age 40, more common in men
General features of motor neurone disease
fasciculations absence of sensory signs/symptoms mixture of UMN & LMN signs no cerebellar signs ocular muscles spared muscle atrophy
Amyotrophic lateral sclerosis (ALS)
~50% of MND pts
3 patterns: limb onset (most common), bulbar onset (20%), respiratory onset (rare)
Presentation:
often starts as weakness in hands & feet
fasciculations, cramps, muscle stiffness
bulbar symptoms (dysarthria, dysphagia, tongue atrophy)
in advanced disease: cognitive impairment, autonomic features, respiratory failure
Progressive bulbar palsy
~20% of MND pts
presents with palsy of tongue, muscles of mastication/swallowing, facial muscles
worst prognosis
Primary lateral sclerosis
UMN signs only
e.g. hypertonia, hyperreflexia, upping plantar reflex, spasticity in bulbar muscles, exagerated jaw jerk, weakness mainly in arm extensors & leg flexors
Progressive muscular atrophy
LMN signs only
distal muscles affected before proximal, weakness, atrophy, hyporeflexia, hypotonia
Myotonic dystrophy
an inherited myopathy effecting skeletal/cardiac/smooth muscle
most common form of adult onset muscular dystrophy
autosomal dominant trinucleotide repeat disorder, disease severity relates to number of repeats
DM-1 = chronic progressive, more severe
DM-2 = milder disease course
Presentation of myotonic dystrophy
myotonia (delayed muscle relaxation following normal muscle contraction) muscle weakness muscle atrophy myalgia bilateral ptosis dysarthria dysphagia cataracts arrhythmia testicular atrophy/features of ovarian insufficiency frontal balding cognitive impairment
Investigating myotonic dystrophy
EMG (to identify myotonia spontaneous discharges of waxing & waning amplitudes & frequencies) genetic testing muscle biopsy CK (↑) FHS (↑) testosterone (↓)
Duchenne muscular dystrophy (DMD)
most common muscular dystrophy
X-linked recessive mutation of dystrophin gene
presents by age 3
progressive muscle paresis & atrophy (starts in pelvic girdle then spreads), weak reflexes, waddling gait, calf pseudo pseudohypertrophy, delayed motor milestones, scoliosis
Becker’s muscular dystrophy (BMD)
X-linked recessive mutation of dystrophin gene (partially functioning)
milder clinical course than Duchenne & slower progression
Similar presentation to Duchenne but less severe
delayed walking, muscle cramps on exercise, children struggle with sport, muscle weakness (mainly in proximal limbs), pseudohypertrophy of calves
Facioscapulohumeral muscular dystrophy (FSHD)
common adult onset muscular dystrophy
autosomal dominant inheritance
presents with progressive muscular weakness (asymmetrical) affecting face, scapula, upper arm, muscle pain is common
Limb-girdle muscular dystrophy (LGMD)
rare group of muscular dystrophies
generally autosomal recessive
presents with paresis & subsequent atrophy of pelvic & shoulder girdle muscle
Investigating muscular dystrophies
Creatine kinase (↑↑↑, 50-100x)
LFTs (↑ transaminase)
EMG (myopathic reading)
Muscle biopsy (absent dystrophin gene in DMD, ↓ quantity of dystrophin in BMD)
