Neuro Flashcards Preview

• unconscious collapse and decreased GCS at presentation without cardio/resp arrest 
• preceding hx helps 
• Quadriparesis with upgoing plantars 
• check the eyes - loss of VOR - the vestibulo-ocular reflex
• pupillary changes, ptosis 
• CT angiogram if NCCT excludes brainstem and large hemispheric ICH 

- ant spinal aa supplies most of the spine 

- the pos spine supplied by various arteries - so if infarct then ant spine 

• suitable drugs have narrow therapeutic index
• close relation of plasma levels to therapeutic/toxic effects
• wide inter-individual variation in metabolism
• must monitor phenytoin (zero order kinetics)
• useful to monitor carbamazepine +- phenobar, ? lamotrigine
• valproate levels only useful for monitoring compliance
• trough levels important if half life is short – carbamazepine, not phenobarb

• responsible for pain and temperature 
• input from small sensory fibres in the peripheral nerves 
• cross in spinal cord just above site of entry 

typically seen during complex partial seizures

stereotyped automatisms

• lip smacking/chewing (operculum)
• limb postures – as above

reactive automatisms

• semi-purposeful interaction with environment – planned actions do not occur 

 Diabetes

 Alcohol

 Uraemia

 Toxic / drugs

 Paraneoplastic (some)

 Nutritional

- on 2 drugs 

still not achieved remissed --> refer for surgery if appropriate candidates 

Phenytoin (PHT) - Saturable – zero order kinetics

Causes purple glove syndrome and phosphenytoin

Carbamazepine (CBZ)

Stevens-johnson syndrome in East Asians – 8% carry HLA B*1502

Hyponatramia common – but more so with valproate

Valproate

Teratogenicity especially at doses above 800mg day

IV form available

Lamotrigine

Danger of SJS – must start slowly – (12.5-25mg daily)

Half life halved by CBZ, PHT, doubled by VPA) 

• ​damage to half of the spinal cord 
• results in paralysis and loss of proprioception on the same (ipsilateral side of the injury) 
• loss of pain and temperature on the opposite (contra-lateral) side as the lesion
• affects dorsal-column-medial lemniscus tract, corticospinal tract, contralateral- - affects spinothalamic. 

​Pure Brown-Séquard syndrome is associated with the following:

Interruption of the lateral corticospinal tracts:

- Ipsilateral spastic paralysis below the level of the lesion

- Babinski sign ipsilateral to lesion

- Abnormal reflexes and Babinski sign may not be present in acute injury.

Interruption of posterior white column:

- Ipsilateral loss of tactile discrimination, vibratory, and position sensation below the level of the lesion

Interruption of lateral spinothalamic tracts:

- Contralateral loss of pain and temperature sensation. This usually occurs 2-3 segments below the level of the lesion.

NCS‐ Segmental Demyelination

 Motor slowing,

 Conduction block, dispersion

 Long distal/F‐wave latencies

 Absent/low ampl. SNAPs (UL>LL)

 CSF protein elevated;

 MRI

-  Nerve root hypertrophy , enhancement

 Nerve biopsy‐

-  inflammation + atrophy

-  segmental demyelination /remyelination

Symptomatic stenosis 70‐99% ‐ strong evidence of benefit

(NASCET, ECST) NB not if already severely disabled

• Symptomatic stenosis 50‐70% ‐ benefit if low surgical

morbidity and good life expectancy

• Carotid occlusion/trickle flow – low risk of recurrent stroke,

generally not suitable for surgery

• Asymptomatic carotid stenosis – surgery rarely indicated

– risk of stroke on optimal medical therapy (antiplatelet,

statin, antihypertensives) estimated ~0.5%pa

• Carotid stenting currently has a higher risk of stroke than

endarterectomy (possible role in patients aged

 Amyotrophic lateral sclerosis

• Most common form

• Mixed UMN & LMN

• Limbs & Bulbar involvement



enzyme inducing AEDs promote oestrogen and progestin metabolism (CBZ, PHT, PHB, PRM) 

high dose depot is effective

implanon not effective

progestin IUD has acceptable failure rate 

• reduced/absent sensory potentials lower>>upper limbs 
• low amplitude distal motor responses, mildly delayed F-waves 
• conduction velocities: mildly reduced consistent with loss of large myelinated nerve fibres 
  • EMG - neurogenic distal >> proximal muscles 
  • motor units: high amplitude, long duration, polyphasic, rapid firing 
  • fibrillations, positive sharp waves

History & Exam

 Fatigue, variability, pure motor.

 Serology‐AChRAb, MuSK Ab

 Electrophysiology

 Repetitive stimulation

 Single fibre EMG - most sensitive 

 Pharmacology‐AChEsterase

Inhibitors

 Tensilon test

 Trial of neo/pyridostigmine

antibiodies sensitive but not specific

most trial pts were pre-treated with alteplase 

indications in 2015 -

• CPTII deficiency 
• carnitine palmitoyl transferase assay 
• muscle bx - moth eaten fibres, Type IIb fibre atrophy and moderate lipid stasis

20-30x higher in young epileptics

total death rate

- increases by 3 or more in young epileptics – depends on syndrome

? caused by cardiac arrhythmias or apnoea

related to frequency and types of seizures

1 = 2/year, absences --> no increase

needs to be raised when discussing treatment and compliance 

Provoked seizures – avoid the provoking stimulus – DUH

Generalised seizures – valproate à lamotrigine/topiramate/levetiractam

Absence seizures à valproate/lamotrigine/ethosuximide/levetiracetam (avoid carbamazepine/tiagabine)

Partial seizures à carbamazepine à levetiracetam, topiramate, gabapentin, oxcarbazepine, valproate, tiagabine

Phenytoin still used as IV form – but levetiracetam and valproate also IV forms 

• protein accumulation in nerve cells
• usually involves uml and lmn 
• progressive degeneratio of motor neurons - 
  • ​Amyotrophic muscle atrophy, weakness, fasiculation (LMN)
  • lateral sclerosis: gliosis post degeneration of corticospinal tracts (UMN) 

Total Anterior Cerebral Infarct (TACI)

– Large infarct, poor prognosis

– Hemiparesis, hemianopia, cortical signs

Partial Anterior Cerebral Infarct (PACI)

– Smaller, better prognosis, risk of recurrence

– 2 of 3 TACI symptoms

• Hemiparesis, cortical signs, hemianopia

Lacunar Infarct (LACI)

– No cortical signs, relatively good prognosis

– Pure motor hemiparesis, pure sensory stroke, sensorimotor stroke, ataxic

hemiparesis, dysarthria‐clumsy hand

Posterior Cerebral Infarct (POCI)

– Stroke with brainstem and/or cerebellar features

– Variable prognosis

– Ataxia, ophthalmoplegia, quadriparesis, crossed signs

on 2 meds and still have not acheived remission --> refer for surgery if suitable 

It was about BP lowering in ICH 

- aggressive BP lowering vs standard care 

- showed no increase in serious adverse events 

multiple secondary outcomes improved 

treat BP aggressively to

Treat BP aggressively long term -

 Progressive bulbar palsy

• Presenting sx in ~20% of all px

• Most commonly seen 􁈺and worst prognosis in􁈻 in menopausal women

• Lower cervical‐thoracic area 

rarely confined to bulbar region only 

• disorder of synapse antibody blockade, defect of synapse 
• antibody production against NMJ - AChr or MUSK - ? LRP4, Agrin 
• thymic hyperplasia
• Ab and immune complexes at NMJ 
• ? associated wiht auto-immune disease - organ specific +- FH
  • graves, hashimoto's thyroiditis, pernicious anaemia, vitilligo, diabetes, pemphigus, chronic active hepatitis 
• thymoma 15% - invasive rare
• chronic myopathy - long standing/untreated

 AEDs are bad, in a dose‐ dependent manner

•  Valproate is worst

•  Polytherapy is bad

•  Folate supplementation is good

 • No AED exposure ~3%

 • Monotherapy ~6%

 • High‐dose valproate ~10%

 • Conflicting data on polytherapy

 • Levetiracetam low risk

 • No proof for folate supplementation

The classic epidemiological definition…

– Stroke is the rapid onset of focal (or global,

as in subarachnoid haemorrhage) cerebral

deficit, lasting >24 hrs or leading to death,

with no apparent cause other than a

vascular one

– TIAs are the same phenomenon

- HOWEVER - modern definition -TIAs that last than 1hr usually only a few mins, pt with symptoms have stroke. 

TIAs have very high short term risk of stroke - upto 20% within 3 months, HIGHEST risk in first 48hrs!!! 

Endocrine abnormalities (effect of AEDs)

– Increased SHBG levels

– Hyperandrogenism

– Polycystic ovaries

– Menstrual irregularities

– Anovulatory cycles

– Obesity

– Insulin resistance

Axonopathy! - most common aeitology is diabetes, alcohol, uraemia, toxic/drugs, nutritonal and occs paraneoplastic

they account for 75% of peripheral nerve pathology. 

• First line ---> carbamazepine, phenytoin or valproate 
• New AEDs - any 
• third line - clonazepam/clobazam 

CBZ vs LTG, TPM, GBP, OXC: LTG best tolerated;

CBZ and LTG most efficacious

VPA vs TPM, LTG: VPA better tolerated than TPM

and more efficacious than LTG

Tx with interferons (avonex) with Glatiramer acetate AND Terifluonomide - delays onset of clinically defined MS and reduces MRI activity markedly. not pubs approved

Cervical spine: vertebrae C1-C7, roots C1-C8.

Cervical roots emerge above

• i.e. C6 emerges at C5/6

Thoracic & lumbar roots emerge below

• i.e. L5 emerges at L5/S1

 Distal symmetric polyneuropathy

 Lumbosacral polyradiculopathy (caudaequina syndrome; CMV)

 Inflammatory demyelinating polyradiculoneuropathy

 Sensory neuronopathy

 HIV treatment neuropathies eg. ddI, ddC,d4T, lamivudine etc

Oligodendrocytes! - responsible for myelination, one cell can myelinated many fibres in CNS. Patho: 1) inflammation - focal + global infiltration with T cells - CD3, CD4, CD8 and macrophages 2) Demyelination - loss of oligodendrocytes 3) axonal loss - apoptosis and neuronal die-back

lesion with selective, disassociative sensory loss - think central cord lesion 

with syrinx can have lower moter neuro  signs a well as it spreads out 

Def: A syrinx is a rare, fluid-filled neuroglial cavity within the spinal cord 

Study of Osteoporotic Fractures

– Accelerated bone loss in patients on AEDs (phenytoin)

– Increased risk of hip fracture OR ~2

– Not due to seizures

Epilepsy and/or AED use fracture risk OR ~2

– Risk increases with cumulative AED exposure, regardless of

type

potential mechanisms - balance, bone density, vit D metabolism, calcium absorption, bone modelling

need to take measures for bone health - ie smoking cessation, calcium, vit D levels, DEXA

A joke! Benign MS is not benign high chance of further disease activity if not treated. truly benign MS can only be diagnosed after 20yrs and in retrospect

Progressive muscular atrophy

• Only develop LMN signs 􁈺without UMN signs􁈻;

• Older males 􁈺more commonly􁈻

• Improved survival 􁈺median 48 months cf 36months􁈻

This is for MS - so you need 2+ relapses at least 1 month apart - i.e. new lesion on follow-up MRI brain or simultaneous non enhancing and contrast enhancing lesions

disorders that are like MS but need to be differentiated from them - need to have +ve anti-aquaporin4 (AQP4) igG and 1 core clinical feature - like optic neuritis, acute myelitis. usually bilaterally.

1. focal - 60% 

then eneralised tonic clonic 35% 

Characteristics

Epileptic seizures rarely exceed 2 minutes

Eyes open, slowing of bilaterally synchronous clonic movements

Lateral tongue biting is fairly specific 

 Flail‐arm syndrome

• Symmetric proximal and distal bi‐brachial wasting 􀵅 positive babinski sign

􁈺Hu et al 1998􁈻

• ~ 10% of patients; M:F  9:1 􁈺flail arm group􁈻

• Trend toward improved survival in flail‐arm group 􁈺57 months cf 39months􁈻

ABCD2 – a prognostic score

• Age ≥60 years = 1

• BP (systolic >140 and/or diastolic ≥90) = 1

• Clinical features

• unilat weakness =2; speech =1; other =0

• Duration

• >60 mins =2; 10-59 =1;

• Diabetes

2 day ABCD2 risk:

1% if = 0-3

4.1% if = 4-5

8.1% if = 6-7

Although ignores carotid stenosis and AF 

MEDICAL EMERGENCY

• Death rate 10% - depends on underlying cause – encephalitis or tumour
• > 1 seizure with incomplete recover between or continuous or recurrent seizures for > 30mins (> 5mins medically observed) is a good predictor of CSE development – so TREAT it
• ABC – remove danger
• Stop seizures – benzo/IV/PR/oral/GEL
• Keep seizures stopped – IV phenytoin/levetiracetam/valproate
• Transfer to ICU 

MRI is gold standard as noted But can do CSF - oligoclonal bands but not in serum - indicates clonal B cells behind BBB Beware if any polymorphs Can do VERs/VEP - visual pattern evoked afferent volleys to occipital cortex - shows optic nerve demyelination

 Peroneal @ knee vs sciatic @ hip vs L5

usually sciatic nerve - may lose ankle jerk-tibial nerve 

• General increase in most types of birth defect

• Specific associations

– Neural tube defects and hypospadias (VPA, CBZ)

– Congenital heart defects (PHT, VPA, PB)

– Craniofacial abnormalities (PHT, VPA, PB, PRM)

– Genitourinary defects (PHT,

Not safe - although no proper clinical studies - but in rats - demonstrated teratogenicity

active metabolite of leflunomide - approved to treat RA - selective reversible dihydroorotate -interferes with lymphocyte proliferation by inhibiting pyrimidine synthesis in lymphocytes -reducing tyrosine kinase activity - may prevent interaction of lymphocytes and antigen-presenting cells

• Axonopathy - is the commonest 
• usually chronic - weeks to months 
• predilection for large diameter, long nerve fibres 
• distal symmetric pattern 
• sensory>motor areflexia 
• routine nerve conduciton studies only test for large nerve fibres

• Consider all

• Rapidly improving deficit may indicate good collaterals rather

than reperfusion – high chance of later worsening

• Non‐contrast CT brain + CT angiogram +/‐ CT perfusion

• Key eligibility:

• ischaemic stroke,

• Are there exclusion criteria for thrombolysis?

• Key exclusions: uncontrolled BP >185/110 at presentation,

recent ischaemic stroke, ICH, current anticoagulation,

excess bleeding risk

Progressive inflammatory vs degenerative myopathy

Most common inflamm disease in older popn 

– Onset >60 yrs, ?1/100,000

– Disabling but not fatal

– Wheelchair dep’t in 5‐10yrs

– Auto‐immune disease in 15%

• Proximal & distal weakness

– Selective pattern ? Asymmetrical

– espQuads, Iliopsoas, FDP

– also triceps, biceps, Tibialis ant.

– Depressed reflexes

– Dysphagia in up to 40%

•  Most common cause of flaccid paralysis in the developed world
• occurs at all ages, peaks in young adulthood and late life
• slight male predominance
• increase of 20% with every 10 year rise in age after the first decade 
• Clinical​

  • ascending, bilateral symmetric weakness progressing over 12hrs to 28days before plateau is reached

  • variable degree of sensory involvement 

  • generalized hyporeflexia or areflexia – 10% have normal or brisk reflexes

  • cranial n involvement, bulbar involvement 

The most common precipitating illness leading to Guillain-Barre syndrome? – CAMPYLOBACTER JEJUNI GASTROENTERITIS 

•  3 days to 6 weeks before onset
• 30% of infections attributed to C.jejuni and incidence of GBS is estimated to be 0.25-0.65 per 1000 cases of c.jejuni.
• associated with acute motor axonal neurppathy
• may be secondary to presence of molecular mimicry between gangliosides and antecedent infectious agents – lipooligosaccharide on bacteria mimic gangliosides.
• Flu like respiratory illness – in EBV, CMV, VzV, mycoplasma pneumonia 

• progression upto 1-3 weeks after symptom onset
• recovery over weeks to months
• resp insufficiency in 25% patients
• mortality 1-2.5% 2* to pulmonary Cx
• 85% full functional recovery
• 15% permanent deficit 

• more common in eastern asia
• clinically – opthalmoplegia, ataxia, areflexia
• often distal paresthesia
• strong link to GQ!b IgG autoantibodies
• disease peaks 1 week – improvement in 2 weeks
• excellent prognosis – full recovery by 6 months
• likely to make recovery without treatment  - IVIG but not plasmapharesis -_> slight hastening of recovery from opthalmoplegia or ataxia à but time to complete recovery same.
• immune trigger

• autoantigens bind to myelin – activation of complement and MAC – macrophages remove myelin debris

  GM1 and GD1a antigens for axonal neuropathy – nodes of ranvier – abs – then directed against these antigens – disappearance of sodium channels – nerve conduction failure and degeneration. 

• preceding illness less common than in GBS
• evolution > 4 weeks, progression over at 2 months
• relapsing remitting – more common in young
• relatively symmetric upper and lower limbs
• usually distal and proximal weakness – if only distal – then think other etiologies
• usually sensorimotor – numbness or tingling – sometimes pain
• reduced absent reflexes
• postural or action tremor 

• immune mediated demyelination
• T cell activation is predominant factor
• Macrophages and humoral factors are also important

Nerve conduction studies

• most important investigation tool
• conduction block most common abnormality
• slow conduction velocities
• temporal dispersion
• increased distal motor latencies
• proximal stimulation increases Dx yield
• most have some “axonal change” 

IV immunoglobulins

• improvement in 60%
• better earlier response than methylpred – relapse higher
• variable maintenance treatment

plasma exchange

• improvement in 80%
• used for pts who are very weak or experience a relapse on another therapy
• can be considered as long term therapy

steroids

• often avoided
• traditionally 60-100mg oral pred taken daily or alt day then taper
• pulsed cortico similar results with less side effects 

• auto-antibodies block VGCC and decrease calcium influx during depolarization of pre synaptic membrane which required for release of acetylcholine from pre-synaptic motor nerve terminals
• rare condition
• M:F 5-1
• 50% have underlying malignancy
• may precede tumour by months-years
• usually small cell lung cancer
• other paraneoplastic syndromes may exist
• HLA- 88, -DR3 asssociated – same as MG 

• difficulty walking is initial symptoms in most
• bulbar and ocular muscles spared or mildly affected – e.g ptosis
• strength improves immediately after exercise
• autonomic dysfunction – dry mout, postural hypotension, erective dysfunction - - ie increasing ACH – increasing calcium release.
• Unlike MG – symptoms typically out of proportion to degree of weakness on examination
• Tendon refelexes absent or reduced – can be increased by brief activation of appropriate muscles or tapping the tendon 

VGCC auto antibodies - 85-90% positive 

• accumulation of alpha synuclein
• cytoplasmic lewy bodies
• diagnostic criteria  - UK brain bank
  • bradykinesia and one of – rigidity, 4-6Hz rest remor, postural instability not due to other cause.
  • Supportive criteria (3 criteria) required – unilateral onset, rest tremor, persistent asymmetry, progressive course more than 10yrs, L-dopa response  - should be excellent (70-100%), severe L-dopa induced chorea or if response lasts more than 5 yrs – all support parkinsons 

• REM sleep behavior disorder – act out their dreams – vivid nightmares, 50% at 10+ years  - can use clonazepam or small dose melatonin for tx
• Impaired olfaction
• Constipation - ? GIT disease pre
• Depression
• Parkinsons start in Dorsal motor nucleus in the vagus – or gut, olfactory bulb, to brainstem à limbic à cortex 

direct dopamine agonists

• ergot-derived – cabergoline  - problem with fibrosis – cardiac, pulmonary, retroperitoneal
• non ergot derived – sifrol – pramipexole  - behavior – OCD, gamble, shopaholics, sexual behaviours 

Diagnostic criteria

All of – onset age over 40, progressive course, bradykinesia, supranuclear gaze palsy

+ Any three of – dysarthria, dysphagia, minimal/absent tremor, neck/flex worse than extremities rigidity, frequent falls/gait disturbance early

And none of – early/prominent ataxia, unexplained neuropathy, prominent dysautonomia – isolated postural BP allowed 

autonomic failure – urinary incontinence, + erectile dysfunction in men

and poorly L-dopa responsive parkinsonism – bradykinesia + 1 other of rigidity, tremor or postural instability

OR cerebellar syndrome 

• probable CBS – greater one yr duration, greater than 50yrs of age,  insidious onset/gradual progression
• asymmetric presentation of 2 of :   
  • limb rigidity or akinesia
  • limb dystonia
  • limb myoclonus
• plus 2 of
  • orobuccal or limb apraxia
  • alient limb – not just limb elevation
  • cortical sensory deficit
• CBD may also present as non-fluent aphasia