Neurology Flashcards
1
Q
What is the clinical pattern of a left MCA stroke?
A
Right hemiparesis (face/arm > leg),
Aphasia
Right sensory/visual inattention
Right hemianopia
2
Q
What is the clinical pattern of a right MCA stroke?
A
Left hemiparesis (face/arm > leg)
Dysarthria
Left sensory/visual inattention
Left hemianopia
3
Q
What are clinical features of a lacunar stroke?
A
Isolated face/arm/leg weakness OR numbness
Dysarthria
4
Q
What are clinical features of basilar artery/brainstem stroke?
A
Diplopia
Vertigo
Dysarthria
Dysphagia
Ataxia
Hemi/tetraparesis
Ipsilateral face/contralateral body numbness or weakness
5
Q
What are common causes of ischaemic stroke?
A
- Atherosclerotic carotid artery disease
- cardioembolic (Afib)
6
Q
What is the risk of stroke in untreated TIA in the first week post event?
A
10%
7
Q
What work up is indicated for TIA?
A
- CT Head
- ECG
- Carotid imaging
- DAPT (or DOAC if AFib)
- Anti-hypertensive
- high dose statin
8
Q
What investigations are indicated for ischaemic stroke mechanism?
A
- Arterial pathology:
- CT-A (aortic arch to cerebral vertex) or carotid doppler USS - Cardiac source of embolism:
- ECG or holter
- ECHO: akinetic segment, endocarditis, bubble study if age < 60 and no other cause - Rare cause
- thrombophilia
- vasculitis
- Fabry’s disease
9
Q
What investigations can be used to investigate mechanism for ICH?
A
- CT-A to exclude vascular malformation
- CT-V in patients with suspicion of venous sinus thrombosis
- Catheter angiography if high suspicion of AVM
- delayed MRI (8 weeks post stroke) to exclude underlying lesion or microangiopathy
10
Q
What patients with ischaemic stroke are eligible for thrombolysis?
A
- last known well <4.5h
OR 4.5-9h from midpoint of sleep with favourable perfusion imaging - potentially disabling deficit
11
Q
What are contraindications to thrombolysis for stroke?
A
-Haemorrhage on CT brain
-Extensive hypodensity on CT brain
- active systemic bleeding
- Recent GI/GU bleeding, surgery or trauma (relative)
- BP >185/105 or BSL < 2.7
- infective endocarditis
- Aortic dissection
- malignant brain tumour
- INR > 1.7
- PLT < 100
- DOAC < 48 hours ago unless Dabi reversed for low Xa level
12
Q
What are risk factors for symptomatic ICH post tPA for ischaemic stroke seen on CT head?
A
CT hypodensity
Severe leukoaraiosis (diffuse white matter abnormality)
Large core
Severe hypoperfusion
Delayed reperfusion
13
Q
What is orolingual angiodema post tPA for stroke and how is it managed?
A
Swelling of lips and tongue, occurs in 2% of patients (up to 5% in those on ACEi)
Usually unilateral (contralateral to stroke side)
Occurs 15-105 minutes post stroke
Managed with hydrocortisone
14
Q
Which sites of vessel occlusion are indications for consideration of thrombectomy in ischaemic stroke?
A
- ICA + M1
- tandem disease (cervical + intracranial)
- large proximal M2
- Basilar
15
Q
Who should endovascular thrombectomy for ischaemic stroke be considered for?
A
- major vessel occlusion
- ICA or M1 in 0-24 hour window
- basilar in 0-24 hour window
- good premorbid function
16
Q
What management strategies are used for ICH?
A
- Target SBP 140
- Reverse anticoagulants
- stroke unit
17
Q
What is the indication for carotid endarterectomy?
A
Within 2 weeks of TIA or stroke in relevant territory with carotid stenosis 70-99%
18
Q
When is warfarin indicated for stroke prophylaxis in Afib?
A
- mechanical heart valves
- Valvular AFib (moderate -severe MS or rheumatic MS)
- CrCl < 30 mL/min
19
Q
What preventative care is indicated in patients with Afib with absolute contraindications to anticoagulation?
A
LAA closure
20
Q
In what patients with TIA and stroke is DAPT indicated and for how long?
A
High risk TIA = ABCD2 >4
Minor stroke with NIHSS 0-3
Given for 21 days
21
Q
What is the ABCD2 score for TIA?
A
Estimate of risk of stroke post TIA
Age: >60 = 1 pt
BP >140/90 = 1 pt
Clinical features of TIA:
- Unilateral weakness = 2pt
- Speech disturbance without weakness = 1 pt
- all others = 0 pt
Duration of symptoms
- <10 minutes =0
- 10-59 minutes = 1 pt
- >60 = 2 pt
Diabetes = 1 pt
22
Q
What medications are indicated post ischaemic stroke and TIA?
A
- Antiplatelet or anticoagulant
- Antihypertensive aiming SBP < 130
- Statin or fibrate aiming LDL < 1.8
23
Q
In which patients should PFO closure be considered?
A
Age < 60 years with embolic stroke without other cause for stroke seen with PFO seen on bubble study
24
Q
What lifestyle modifications are recommended post stroke or TIA?
A
Smoking cessation
Alcohol reduction
Weight management
Diet adjustment
Physical activity
25
What is the diagnostic criteria of Parkinsons disease?
Slowness and/or stiffness (cog wheel) and/or resting tremor
26
What feature distinguishes Parkinson's from multiple systems atrophy?
ANS involvement
27
What is Levodopa and how does it treat symptoms of Parkinson's disease?
Dopamine precursor with enzyme inhibitor
Effective for slowness and stiffness, less effective for tremor
28
What are examples of dopamine agonists used for Parkinsons disease? What are there side effects?
Pramipexole
Ropinirole
Sleepiness
Impulse control disorder: gambling, shopping, hypersexuality
29
What is the role of Selegiline, rasagiline and safinamide in Parkinson's disease?
MAOI-B
Enzyme inhibition increases dopamine present in synapse
30
What are examples and the role of catechol-o-methyl transferase inhibitors in Parkinson's disease?
Entecapone and opicapone
Prevent the methylation of levodopa to 3-O-methyldopa, thus increasing the bioavailability of levodopa in the GIT
Reduce the amount of "off" time
31
What is the mechanism of action and role of amantadine in Parkinson's disease?
Weak antagonist of NMDA receptor to increase dopamine release and block dopamine re uptake
Reduces dyskinesia
32
What are the benefits of apo-morphine and deep brain stimulation over oral dopamine agents in Parkinson's?
Overcome GI issues that impact absorption of oral meds
33
What is apomorphine and how is it given in Parkinson's?
D1 and D2 receptor agonist
Metabolised by liver so given via continuous subcutaneous infusion
34
What are non-motor symptoms are Parkinson's disease?
- constipation
- bladder dysfunction (alpha blockers)
- postural hypotension (fludrocortisone, pyridostigmine
- excess in inadequate saliva
- dysphagia
- speech
- Neuropsychiatric: impulse control, depression, anxiety,
- sleep disorder (clonazepam)
- cognitive impairment (rivastigmine)
- Psychosis (quetiapine, clozapine)
34
What are characteristics of frontal onset seizures?
Focal clonic motor
Hypermotor behaviour
35
What are characteristics of Temporal onset seizures?
Mesial: autonomic, dysmnesic, deja vu, jamais vu, gustatory, olfactory
Lateral/posterior neocortical: auditory, complex visual, dysphasia
36
What are characteristics of parietal onset seizures?
Somatosensory (positive symptoms help distinguish from neuropathy)
37
What are characteristics of occipital onset seizures?
Simple visual
38
What are the different types of generalised seizures?
- Absence: behavioural arrest, automatisms (childhood only)
- Myoclonic: limb jerks/twitching without loss of consciousness
- Tonic: co-contraction of agonist + antagonist muscles <15 secs +/- vocalisation
- Atonic: loss of muscle tone
- Clonic: repetitive jerking movements
- Generalised tonic-clonic: tonic posturing followed by clonic limb movements
39
What is the role and goal of AEDs in seizures?
Only indicated for seizure prophylaxis in epilepsy with risk of recurrent seizure > 60%
Treatment goal: no seizure, no side effects, no lifestyle limitations
40
What AEDs are contraindicated in HLA-B*1502 allele (Chinese descent)?
Carbamazepine
Lamotrigine
Phenytoin
41
What AEDs interfere with OCP?
- topiramate reduces estradiol
- carbamazepine reduces estradiol and progestin
- lamotrigine reduces progestin
- Phenytoin reduces estradiol and progestin
42
What AEDs are affected by OCP?
- Lamotrigine reduced by OCP
- valproate reduced by OCP
43
What AEDs have no effect on OCP?
- levetriacetam
- lacosamide
44
What AEDs should be used for the treatment of partial epilepsy?
Sodium channel antagonists:
- carbamazepine
- phenytoin
- lamotrigine
- oxcarbazepine
- lacosamide
- zonisamide
- parampanel
45
What AEDs should be used for the treatment of Generalised Genetic epilepsy?
- valproate
- levetiracetam
- topiramate
- lamotrigine
- ethyl succinamide
- Phenobarbitol
- zonisamide
- perampanel
46
What AEDs should be avoided in each of these situations:
- mycolonus
- hepatic disease
- renal disease
- Myoclonus: avoid sodium channel blockers and lamotrigine
- Hepatic disease: sodium valproate
- renal disease: levetiracetam
47
Which AEDs should be avoided in the following co-morbidities?
- behavioural disorders
- PCOS
- Insomnia
- Tremors
- cognitive issues
- nephrolithiasis
- pancytopenia
- behavioural disorders: levetriacetam
- PCOS: valproate
- Insomnia: lamotrigine
- Tremors: valproate
- cognitive issues: topiramate, phenobarbitol
- nephrolithiasis: topiramate, zonisamide
- pancytopenia: carbamazepine
48
Which AEDs should be considered in the following co-morbidities?
- behavioural disorders
- migraines
- Chorea
- Diabetes Mellitus
- behavioural disorders: valproate, lamotrigine
- migraines: topiramate, valproate
- Chorea: carbamazepine
- Diabetes Mellitus: topiramate, gabapentin
49
Which AEDs should not be combined?
-Typically those that share the same mechanism of action e.g levetiracetam with brivaracetam
- Phenytoin with carbamazepine (induce metabolism of each other)
- Phenobarbital with valproate (valproate increase phenobarbitol, phenobarbital reduces valproate)
- rufinamide with valproate
50
When should patients with epilepsy be referred to a neurologist?
- refractory epilepsy (on more than 2 agents)
- if surgical candidate
- if pregnant, co-morbid neurology
51
What is the diagnostic gold standard for PNES?
Video EEG + neuropsyciatric evaluation
52
What non-pharmacological strategies are useful in Alzheimer's disease?
- minimise anti-cholinergic drugs
- correct sensory impairment
- offer cognitive stimulation therapy (not cognitive training)
53
What pharmacological therapies are useful for the treatment of Alzheimer's dementia?
1.Acetyl choline esterase inhibitors:
MMSE at least 10
temporary improvement in cognition and memory
Side effects; bradycardia, weight loss, vivid dreams
- donepezil
- glantamine
- rivastigmine
2. NMDAR antagonist:
MMSE 10-14 and intolerat on AChEis
Improve cognitive function and behaviour
- memantine
Contraindicated in seizures
SEs: GI upset, headache
54
How should BPSD be managed?
Identify precipitant and exclude medical causes
Try to manage non-pharmacologically
No evidence to support anti-depressants except if pre-alzheimers depression
Agitation - citalopram (SSRI)
Antipsychotics for severe symptoms (risperidone has best evidence)
55
What clinical features are suggestive of an NMJ disorder?
Ptosis
Diplopia
Ophthalmoplegia
Dysarthria
Dyspnoea
Limb weakness
Fatigue
Paraesthesia (LEMS)
56
What clinical features are suggestive of myopathy?
Negative symptoms:
- weakness
- fatigue
- exercise intolerance
- muscle atrophy
Positive symptoms:
- cramps
- stiffness/myotonia
- contracture
- muscle hypertrophy
- myalgia
- myoglobulinuria
57
What muscle weaknesses are associated with which muscle and NMJ disorders?
1. Proximal symmetric muscle weakness = most myopathies
2. Distal symmetric muscle weakness = distal myopathies or neuropathy
3. Proximal arm + distal leg = muscular dystrophy (other rare)
4. Assymetrical proximal leg + distal arm = inclusion body myositis, myotonic dystrophy
5. Proximal (ptosis, ophthalmoplegia)
- asymmetric = myasthenia gravis
- symmetric = oculopharyngeal muscular dystrophy, myotonic dystrophy
6. Proximal symmetrical (neck extensor) = isolated neck extensor myopathy, myasthenia gravis
7. Proximal symmetric bulbar (tongue, pharyngeal, diaphragm) = myasthenia gravis, LEMS, oculopharyngeal muscular dystrophy, amyotrophic lateral sclerosis
8. Episodic proximal symmetric with trigger = McArdle disease, carnitine palmitoyltransferase deficiency
9. Episodic symmetric proximal weakness without trigger = primary periodic paralysis, channelopathies
10. Episodic stiffness = myotonic dystrophy, channelopathies
58
What are characteristics of inflammatory myopathies?
Symmetric and proximal muscle involvement, typical shoulder and hip
Can involve facial and neck muscles
May have myalgia or muscle tenderness
59
What are clinical features of dermatomyositis?
Subacute onset proximal muscle weakness preceded by rash (photosensitive areas, heliotrope = purple, gottron papules = scaly eruptions over bony prominences)
May have GIT, cardiac and resp involvement
Often associated with malignancy
CK levels often raised
60
What are the histopathological and radiological features of dermatomyositis?
Hitso: perifasicular muscle fibre atropy is specific
MRI:
- STIR sequence demonstrates hyperintensity or oedema in patchy distribution as well as oedema of subcutaneous tissue and fascia
61
What are characteristic clinical features of the following dermatomyositis antibodies:
- Anti-M2
- Anti-TIF-1gamma
- Anti-NXP-2
- Anti-MDA-5
- Anti-SAE
- Anti-M2: skin rash, moderate muscle involvement, good response to immunotherapy
- Anti-TIF-1gamma: strong association with cancer, severe skin rash, minimal muscle involvement
- Anti-NXP-2: increased risk of malignancy, classic skin rash, subcutaneous calcifications
- Anti-MDA-5: severe skin rash, no muscle involvement, rapidly progressive ILD
- Anti-SAE: classic rash, mild muscle involvement, dysphagia
62
What is anti-synthetase syndrome and it's clinical features?
- autoimmune condition associated with serum autoantibodies to aminoacyl transfer RNA synthetases
- inflammatory myopathy
- ILD
- arthritis
- raynauds
- fever
- dry cracked hands
63
What are the clinical features of the following anti-synthetase antibodies:
- anti-Jo1
- anti-PL-7
- anti-PL-12
- anti-glycyl- transfer RNA synthetase, anti-OJ, anti-KS
- anti-Zo, anti-Ha
- anti-Jo1: muscle involvement, progressive ILD, mild skin rash
- anti-PL-7: severe ILD, moderate muscle involvement
- anti-PL-12: severe ILD, mild or no muscle involvement
- anti-glycyl- transfer RNA synthetase, anti-OJ, anti-KS: high association with ILD
- anti-Zo, anti-Ha: possible ILD
64
What is the most common antisynthetase autoantibody?
Anti-Jo-1
65
What are clinical features of immune-mediated necrotising myopathies?
- Severe proximal muscle weakness, often no extramuscular involvement
- Markedly elevated serum CK
- anti-3-hydroxy-3-methyglutaryl coenzyme A reductase antibody associated with statin use
66
What are the clinical features of the following immune-mediated necrotising myopathy subtypes:
- anti-SRP
- anti-HMGCoA reductase
- antibody negative immune mediated necrotising myopathy
- anti-SRP: severe muscle involvement, rarely lung involvement, no skin involvement
- anti-HMGCoA reductase: severe muscle involvement, no skin or lung involvement
- antibody negative immune mediated necrotising myopathy: increased risk of malignancy
67
What is overlap myositis and what are the associated autoantibodies?
Autoimmune myopathy occuring with another autoimmune connective tissue disorder (SLE, Sjogrens, RA, systemic sclerosis)
-antiRo52: most common
- Anti-PMScl: associated with systemic sclerosis, lung and oesophageal involvement
- anti-Ku: associated with systemic sclerosis, joint involvement, raynaids, ILD
- anti-U1 RNP: associated with scleroderma, SLE and glomerulonephritis
68
What are the features of polymyositis?
Diagnosis of exclusion
Subacute proximal muscle weakness, elevated CK, myopathic EMG
Muscle biopsy shows endomysial inflammation with CD8+ T-cell infiltrates
69
What is the management of inflammatory myopathies?
1. Investigations:
- CK, myositis antibodies
- EMG
- MRI
- muscle biopsy
- CT chest + PFTs (ILD)
- consider cancer screening
2. Immunosuppression:
- high dose steroids
- steroid sparing immunotherapy: azathioprine, methotrexate, mycopheylate, cyclosporin, tacrolimus, IVIg, rituximab, cyclophosphamide
- IVIg esp for refractory dermatomyositis, immune-mediated necrotising myopathy
- rituximab for refractory dermatomyositis and polymyositis, antisynthetase syndrome, refracrotry anti-SRP antibody immune mediated necrotising myopathy
70
What are clinical features of sporadic inclusion body myositis?
Most common acquired muscle disease in >50y
Slow progressive muscle weakness involving quads, finger flexors and ankle dorsiflexors
Neck, facial and bulbar weakness can occur
Decreased knee jerk often early sign
Modest CK elevation
Can be associated with anti-NT5C1A - often more severe with bulbar symptoms + higher mortality
EMG: mixed myopathy/neuropathic process
MRI may show anterior thigh muscle selectively involved
71
How is sporadic inclusion body myositis managed?
- no treatment cures or slows disease
- symptom support e.g. mobility aids
72
How are toxic myopathies treated?
Identify and stop causative agent
Provide supportive care
73
What is rhabdomyolysis, how does it present and how is it diagnosed?
Rhabdo = breakdown and necrosis of muscle tissue resulting in release of intracellular contents into blood stream
Presents with asymptomatic AKI, metabolic and electrolyte abnormalities
Diagnosis = CK > 1000 or 5xULN
74
How is rhabdomyolysis treated?
- treat underlying cause of muscle insult
- aggressive fluid management
- treat electrolyte imbalances
75
What are dystrophinopathies and their clincial features?
Absence or decrease in function of dystrophin protein in skeletal muscle
X-linked inheritance
Progressive symmetrical skeletal muscle weakness, starting with lower limb
Duchenne = severe phenotype
Becker = mild phenotype, more severe cardiac involvement
76
How are dystrophinopathies diagnosed and managed?
Diagnosed with raised serum CK, genetic testing and absence/reduced dystrophin on muscle biopsy
Management:
- oral steroids
- MDT care
- carrier testing (women may have cardiomyopathy)
77
What is facioscapulohumeral muscular dystrophy?
Due to hypomethylation of subteleomeric region of chromosome 4q resulting aberrant expression transcription factor DUX4
95% AD inheritance
78
What are the clinical features of facioscapulohumeral muscular dystrophy?
Presents with asymmetric weakness of orbicularis oculi, orbicularis oris, rhomboids, serratus anterios, biceps, triceps, paraspinals, recuts abdominis and tibialis anterior
Associated with retinal vasculopathy and hearing loss
79
How is facioscapulohumeral muscular dystrophy diagnosed and managed?
Based on clinical phenotype and genetic testing
Managed with supportive and symptom based care
80
What are the clinical features of myotonic dystrophy?
AD inherited
Triad:
- progressive weakness
- myotonia (impaired muscle relaxation)
- early onset cataracts
Type 1 = most common
- CTG repeat in DMPK gene
- affects distal muscles + face
- prominent myotonia: percussion or action
Type 2:
- CCTG repeat in CNBP gene
- affects proximal muscles
- pain more prominent than myotonia
81
What is the diagnosis and management of myotonic dystrophy?
- CK, EMG demonstrating "dive bomber" waxing/waning myotonia, genetic testing
- screen for co-morbidities: Cardiac, respiratory dysfunction, cataracts, diabetes, hypothyroidism, IBS, SIBO
- supportive care: mexiletine, aerobic exercise
82
What are clinical features of myoclonic epilepsy with ragged red fibres (MERRF)?
Progressive epilepsy in childhood
Mycolonus independent of epilepsy
Myopathy
Ragged red fibres with modified Gomori trichome stain = disease mitochondrial accumulation in subsarcolemmal regions of muscle fibre
Mutation in mitochondrial DNA tRNA(lys) gene
83
What are clinical features of mitochondrial encephalomyopathy, lactic acidosis and stroke-like syndrome (MELAS)?
Onset in infancy to late adulthood
Present with stroke-like events in non-vascular territories, cognitive impairment, epilepsy, myopathy, elevated lacate
Mutation in mitochondrial DNA tRNA(leu) gene
84
What are clinical features of Chronic progressive external ophthalmoplegia (CPEO) and CPEO plus syndrome
Adult-onset progressive external ophthalmoplegia +/- skeletal myopathy
Caused by large single deletion in mitochondrial DNA
85
What are clinical features of Kearns-Sayre syndrome (KSS)?
Onset before age 20
Main = external ophthalmoplegia, retinitis pigmentosa, sensorineural hearing loss
May have myopathy, cardiomyopathy, cardiac conduction defects
Large deletion in mitochondrial DNA
86
What are clinical features of Pompe disease (glycogen storage disease type 2)?
AR inheritance
Mutation in GAA gene resulting in enzymatic acid maltase deficiency
Variable phenotype from severe to mild myopathy with elevated CK
Diagnosis confirmed with enzymatic or genetic testing
Managed with high protein diet, avoid intense exercise, enzyme replacement
Screen for cardiomyopathy and conduction deficits
87
What are the different types of primary periodic paralyses?
1. Hypokalaemic periodic paralyses: mutation in calcium channel CACNA1s, triggered by carb-rich meals or prologed rest
2. Hyperkalaemic periodic paralysis: mutation in sodium channel SCN4A, triggered by fasting or exercise, often painful myotonia in eyes and hands
3. Andersen-Tawil syndrome: mutation in potassium channel KCNJ2, assocaited with prolonged QT and hypokalaemia
88
What are the clinical features of primary periodic paralyses?
AD inherited
Onset in childhood, may present as adults
Complete paralysis of alll 4 limbs with absent reflexes
Investigated with CK, potassium, EMG, genetic testing
Managed by avoiding triggers, stabilising potassium
89
What are the clinical features of myasthenia gravis?
Ocular and generalised subtypes
Fluctuating and fatigable muscle weakness that worsens with exercise and improves with rest
- ptosis (asymmetric) + binocular diplopia = most common presenting symptom)
- bulbar weakness: flaccid dysrthria, dysphagia, jaw closure weakness
- facial weakness (weak smile)
- neck flexion weaker than extension
- proximal symmetric limb weakness
90
What are common triggers for myasthenia gravis?
- surgery
- pregnancy/post partum
- heat
- stress
- infection
- bone marrow transplant
- drugs: antibiotics, magnesium, b-blockers, CCBs, anaesthetics, checkpoint inhibitors
91
What is myasthenic crisis and how is it managed?
Respiratory failure secondary to severe weakness of diaphragm and accessory muscle
Needs venitaltion support in ICU, steroids and IVIg or plasma exchange
92
What investigations are used for myasthenia gravis?
- antibodies: diagnostic, not for monitoring, anti-AChR, anti-MUSK if ACHRneg, Anti-LRP4 if double negative
- Repetitive stimulation electrodiagnostic testing: CMAP >10%
- single-fibre electromyography = most sensitive for neuromuscular transmission problem
- ice pack test = highly sensitive and specific for myasthenic ptosis
- edrophonium test = AChi that should improve symptoms in 1-2 minutes
- CT chest to look for thymoma
- TFTs as often autoimmune thyroid disease concurrent
93
How is myasthenia gravis diagnosed?
Auto-antibody present + weakness consistent with diagnosis
If auto-antibody negative, then need other investigations
94
What is the significane of anti-MUSK in myasthenia gravis?
- often atypical presentation (neck extensor, shoulder + resp muscle, or sever oculobulbar + facial muscle weakness)
- better response to plasma exchange than IVIg
- less response to cholinesterase inhibitors
95
What are differential diagnoses of myasthenia gravis?
LEMS
Congenital myasthenic syndromes
Botulism
Lyme disease
Bulbar ALS
Brainstem ischaemia
GBS
Mitochondrial disorders
Oculopharyngeal muscular dystrophy
96
What is the treatment of myasthenia gravis?
Pyridostigmine:
- increase bioavailability of acetyl choline at synaptic cleft
+/- immunosuppression (steroids, azathioprine, mycophenylate, rituximab)
Thymectomy for thymoma OR in generalised MG with anti-ACHR antibodies
Acute exacerbation, pre-op or in refractory cases:
- IVIg
- plasma exchange
97
What defines refractory myasthenia gravis?
Unchanged or worsening symptoms after steroid treatment AND failed at least 2 other immunosuppressants
98
What are the clinical features of immune checkpoint inhibitor related myasthenia gravis and myositis?
ICI-related MG:
- prominent bulbar and respiratory manifestations
- associated myocarditis
- overlap with other immune related adverse events
ICI-related myositis:
- large spectrum ranging from myalgia to severe generalised weakness with respiratory muscle involvement
- 40% have myocarditis
99
What are the common investigation findings for LEMS?
Investigations:
- VGCC antibodies (85%, 100% in paraneoplastic)
- nerve conduction studies: low baseline motor amplitude, increased after brief exercise
- Repetitive stimulation: decrement with low frequency, increment with fast frequency
100
What is the management of LEMS?
- malignancy screening + treatment
- 3,4-diaminopyridine +/- pyrostigmine
- manage autonomic symptoms
- IVIG or plasma exchange
- chronic immunosuppression
101
How does botulism present and how is it diagnosed?
Acute descending flaccid weakness with respiratory and autonomic dysfunction
- blurred vision, diplopia/ophthalmoplegia, facial weakness, dysarthria, dysphagia
- fixed dilated pupils, dry mouth
Stool PCR to identify organism
Nerve conduction studies show low baseline motor amplitudes that increase after brief exercise
Repetitive stimulation shows decrement with low frequency, increment with fast frequency
102
What is the treatment of botulism?
-ICU admission for respiratory and autonomic dysfunction
- IV human botulism immunoglobulin or heptavalent anti-toxin
- notify public health
103
What is Guillain-Barre syndrome and how does it typically present?
Inflammatory immune mediated disease of peripheral nervous system (peripheral nerves and nerve roots)
Classic presentation is acute onset of weakness and sensory symptoms in lower limbs that ascend to upper limbs and cranial nerves
104
What is the most common cause of acute flaccid paralysis?
Guillain-Barre syndrome
105
What are common triggers fro Guillain-barre syndrome?
GI + resp infection:
- campylobacteri jejuni
- CMV
- EBV
- mycoplasma pneumoniae
- haemophilus influenzae
- hepatitis E
- Zika
- SARS-CoV-2
- influenza
Surgical trauma
Vaccination (influenza)
Pregnancy
Immunosupression
106
What are clinical features of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype of GBS?
- most common
- presents with pain/paraesthesia without sensory deficit
- motor polyradiculopathy with acute progressive symmetric weakness involving proximal + distal muscles
- reduced absent deep tendon reflexes
- 50% have cranial nerve involvement
- dysautnomia
- sphincter dysfunction
107
What are clinical features of acute motor axonal neuropathy (AMAN) subtype of GBS?
<10%, more common than AMSAN
More common in Asia and South America
Motor weakness in lower limb, less sensory and autonomic involvement
Reflexes may be preserved
108
What are clinical features of acute motor sensory axonal neuropathy (AMSAN) subtype of GBS?
Severe involvement of sensory and motor nerves
Poor prognosis
109
What are clinical features of Miller-Fisher syndrome subtype of GBS?
Triad:
- ophthalmoplegia
- Ataxia
- areflexia
Often presents with diplopia
110
What are clinical features of Bickerstaff brainstem encephalitis subtype of GBS?
Ophthalmoplegia
Ataxia
Altered consciousness
Hyperreflexia
111
How ist are characteristic CSF findings in GBS?
Normal cell count (WCC may be increased post IVIg)
Elevated protein level
112
What are characteristic NCS and EMG findings of GBS?
Early NCS:
- normal
- Prolonged F wave latencies
- ADIP: sural sparing pattern
Late NCS:
- ADIP: prolonged distal motor latencies, reduced motor nerve conduction velocities, prolonged F wave latencies, increased temporal dispersion, conduction blocks at non-compressible sites
- AMAN: decreased compound muscle action potential amplitudes
- ASMAN: decreased compound muscle and sensory nerve action potential amplitudes
113
What antibodies are associated with which GBS subtypes?
-ADIP: Antiglycan antibodies (LM1 and GM1) in 25-30%
-AMAN: GM1, GD1a, GalNAc-GD1a, GM1b
-Motor predominant: GalNAc-GD1a, GM1b in 10-15%
- Miller Fisher: GQ1b in 80%
114
What radiological findings support a diagnosis of GBS?
Enlarged cervical nerve roots on peripheral nerve ultrasound (early)
Nerve root enhancement on gadolinium-enhanced MRI
115
How is GBS managed?
- Admit to hospital with ICU
- DVT prophylaxis
- early PT and rehab
- monitor for complications
ICU admission if deteriorating resp function, autonomic instability, aspiration risk
1st line = IVIg, 2 weeks of symptom onset
2nd line = Plasma exchange, given within 4 weeks of symptom onset
116
What is the typical MRI brain finding in ALS/MND?
Typically normal, may see sclerosis of cortico-spinal tract
117
How is MND diagnosed?
Progressive motor impairment preceded by normal motor development
AND
Presence or upper and lower motor neuron dysfunction in at least 1 body region OR lower motor neuron dysfunction in at least 2 body regions
MRI to exclude spinal/brain pathology
Nerve conduction studies + EMG
118
What is the split hand presentation of MND?
Wasting of FDI and APB (thenar muscles) with preservation of ADM (hypothenar muscles)
119
What cognitive and behavioural symptoms can be seen in MND/ALS?
- 50% have cognitive impairment
- 80% have behavioural impairment
- 15% have ALSFTD diagnosis (ALS + FTD)
120
What treatments are available for MND/ALS?
- Riluzole (stimulates glutamate uptake), gives 9 month benefit
- MDT care
- NIV
- Inspiratory muscle training
- Symptomatic treatments
- baclofen or botox for spasticity
- amitriptyline for sialorrhea
- genetic testing
121
What are common features of persistent postural perceptual dizziness?
-Persistent sensation of rocking or swaying unsteadiness without vertigo, lasting 3 months or more
- aggravated by upright posture, head or body motion
- symptoms present most days
- type of FND, associated with anxiety, depression, worse with stress
122
What are features of bilateral vestibulopathy/vestibular hypofunction?
Ataxia + oscillopsia without vertigo
Can be caused by aminoglycoside therapy
123
Where are the neuronal bodies for sensory and motor nuerons?
Sensory = dorsal root ganglia
Motor = anterior horn of spinal cord
124
What are involved in assessment of a sensory large fibre neuropathy?
Vibration
Proprioception
Light touch
Rombergs
125
What are involved in assessment of a sensory small fibre neuropathy?
Pinprick
Temperature
Reflexes (preserved)
126
What is the pattern of sensory loss of gangliopathy?
Severe truncal, facial or non-length dependent sensory loss
(e.g. paraneoplastic, sjogrens affecting DRG)
127
What causes of neuropathy present acutely (<1 motnh)?
Infection (listeria)
Vasculitic
GBS
Porphyria
Toxins
128
What causes of neuropathy present subacutely?
Toxic
Nurtritional
Malignancy/paraneoplastic
Metabolic
129
What causes of neuropathy are relapsing?
Demyelinating (CIDP, HNPP, porphyria)
repeated toxic exposure
Vasculitis
130
What are the most common causes of autonomic neuropathies?
Diabetes
Amyloidosis
GBS
131
What features suggest a demyelinating neuropathy?
Weakness without atrophy
Length independent
Asymmetric or patchy distribution
Early loss of proximal reflexes
Myokymia (eye twitching)
132
What conditions can cause facial diplegia?
GBS
CIDP
Amyloidosis (familial)
Lyme
Sarcoid
133
What disease cause facial sensory loss?
Coeliac neuropathy
Sjogren
134
What neuropathy and cancer are associated with anti-Hu antibodies?
Sensory neuropathy
Small cell lung cancer
135
What is the role of EMG/NCS in work up of neuropathy?
Only asses large fibres
Exclude muscular, radicular and MND
Differentiated axonal and demyelinating
136
Why is palmar sensation spared in carpal tunnel syndrome?
Palmar cutaneous branch leaves median nerve proximal to carpal tunnel
137
What are the patterns of diabetic neuropathy?
Symmetric:
- glove and stocking sensorimotor (most common)
- glove and stocking small fibre (pain)
- autonomic
Asymmetric:
- cranial neuropathy (pupil sparing CNIII)
- multifocal or entrapment
- radiculoplexus neuropathy (proximal motor)
138
What's the most common pattern of alcohol-related neuropathy?
Length-dependent sensory
Often painful
139
What Ig subtype of monoclonal gammopathy is most strongly associated with peripheral neuropathy?
IgM
140
What monoclonal antibody is associated with DADS phenotype of neuropathy?
Anti-MAG
(Distal Acquired Demyelinating Symmetric = sensory)
141
Which antibody is associated with sensory ataxic neuropathy and cryoglobulinaemia?
Anti-Gd1b
142
What are features of B12 deficient neuropathy?
Painless peripheral sensory loss
Absent ankle jerks
Sensory ataxia
Acute onset
Upper + lower limb
Symmetric hyperdense signal in dorsal column of spinal cord on MRI
143
What are common features of Guillain-Barre syndrome?
Acute flaccid paralysis
Symmetrical limb weakness
Hyporeflexia
(most common is sensory + motor)
144
How do you distinguish CIDP from length dependent neuropathy?
Proximal weakness
Generalised areflexia
145
What are the characteristic electrophysiological features of CIDP?
Partial conduction block
conduction velocity slowing
prolonged distal motor latencies
delay or disappearance of F waves
temporal dispersion and distance dependant reduction of motor amplitudes
146
What are the four locations typical for demyelination in MS?
Juxta-cortical
Periventricular
Callosal
Infratentorial
147
What is the most effective treatment for MS in clinical studies?
HSCT (recent study showing Ocrelizumab as effective)
148
What treatments for MS are safer in pregnancy?
Dimethyl fumarate
Glatiramer acetate
Natalizumab until 3rd trimester
149
What are first line treatments for spasticity in MS?
Baclofen
Gabapentin
(BOTOX for focal)
150
What is the difference between encephalitis and encephalopathy?
Encephalopathy = altered consciousness > 24 hours
Encephalitis = encephalopathy + evidence of CNS inflammation (2 of):
- fever
- seziure or focal neurology
- CSF pleocytosis
- EEG findings
- imaging suggestive
151
What features help distinguish ADEM from encephalitis?
Younger age
Recent vaccine or infection
Absence of fever
Multifocal neuro signs
Imaging displays demyelination
152
What neurological signs are suggestive of HSV encephalitis?
Aphasia
Personality change
Focal seizures
153
What viruses can cause an ecephalitis that presents with multifocal lower motor neurone signs and flaccid paralysis?
- poliomyelitis
- enterovirus
- West nile virus
154
What is the role of EEG in the work up of encephalitis?
To distinguish from generalised encephalopathy
(PLEDs are seen in HSV)
155
What is the best imaging for encephalitis?
MRI
156
What characteristic changes on MRI are seen with in encephalitis with each of the following?
- HSV
- JEV
- Nipah virus
- eastern equine encephalitis virus
- HSV: frontotemproal
- JEV: thalamic
- Nipah virus: diffuse punctate lesions
- eastern equine encephalitis virus: diffuse brainstem and basal ganglia
