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Flashcards in Neuro Deck (118):
1

myasthenia clinical features 

Variable weakness

-  not mental fatigue

-  Worse with exertion, later in day

-  ?ppt by infection, antibiotics

 Pattern

-  Ocular/ Facial‐ most!

-  Bulbar

-  Truncal

-  Limbs

2

Would you discontinue AEDs if someone has not had a seizure in 2yrs - and if so - who would you not consider an ideal candidate for this? 

- yes - if in remission for at least 2 yrs - 60% still in remission after 2 yrs 

- unfavourable factors - previous unsuccessful withdrawal, abnormal EEG, syndrome (JME) seizure types -juvenile myoclonic epilepsy - cannot withdraw

3

What is Fampridine PR?

- drug used to improve walking speed in MS - medication for symptomatic management in MS and does not alter the disability progression - has been thought to cause seizures in some patients esp with incorrect dosing.

4

What is the evidence for warfarin in AF with stroke

Evidence for warfarin in primary/secondary prevention of

ischemic stroke in patients with AF:

• Warfarin is much better than placebo:

• SPAF, EAFT…

• Warfarin is much better than aspirin + clopidogrel:

• ACTIVE‐W

• Aspirin + clopidogrel is no better than aspirin:

• ACTIVE‐A

• Age alone does not alter the overall benefit of warfarin but

aspirin gets riskier for no benefit:

• BAFTA Lancet 2007 370:493‐503

5

What is PML?

- rare progressive demyelinating and potentially fatal infection of the brain - caused by opportunistic reactivation of JC-virus ( a polyoma virus) induced oligondendrolgliopathy - association of PML with 3 humanised monoclonal antibodies - Natalizumab, rituximab and other immunosupp MMF, MTX, aza

6

What is transverse myelitis? 

  • ​condition in which the spinal cord is inflamed 
  • inflam damages nerve fibres and causes them to lose their myelin coating leading to decreased electrical conductivity in CNS 
  • MOST common is idiopathic 
  • bimodal peak 10-19, 30-39 M=F 
  • presentation with cord syndromes - sensorimotor/autonomic evolving over hours/days - bilateral signs, limb weakness, stiffness, muscle spasm. 
  • urinary retention, constipation, autonomic dysreflexia 
  • preceding non specific viral illness is ocmmon - fever, nausea, myalgia 
  • clearly defined sensory level, progression to nadir of clinical deficits between 4hrs and 21days after symptom onset 

7

what is juvenile myoclonic epilepsy of janz? 

idiopathic primary generalized epilepsy

  • age of onset – usually 12-17 yrs
  • myoclonic seizures on waking (100%)
  • +/- generalized tonic-clonic seizures (90%)
  • plus ? absence seizuresi n 10-15%
  • 90% will never remit – ie lifelong treatment

EEG:

  • Generalised polyspike-wave-discharges 3-6Hz – 30-40% show photosensitivity

High heritability – two single gene causes identified – minority of cases – EFHC1 – unknown function and CLCN2 – voltage gated chloride channel

Treatment = Valproate, Lamotrigine

Carbamazepine worsens control 

8

When is epilepsy surgery beneficial 

 

  • 1% of pts may be suitable – principally mesial temporal sclerosis and other focal temporal lobe lesions
  • 75-85% pts are seizure free post surgery – with 10% having late relapse
  • extratemporal and non-lesional resections do worse
  • typical pathologies
    • mesial temporal sclerosis
    • cavernous haemangiomas – cavernomas

9

What is the oral treatment for MS?

Fingolimod - the FIRST tablet to be available on the PBS - it selectively retains circulating lymphocytes in lymphoid organs - acts on four of five sphingosine 1 phosphate receptors - on admin - rare cases of heart block in the first 6 hrs - do not administer with Beta blockers within first 2-4weeks. Can cause macular oedema in 1st 3 months. Superior to IFN B1a in relapse rate but not disability.

10

Treatment of MG

- control symptoms - Anti-cholinesterase inhibitors - Mestinon 

- induce remission 

- avoid relapse 

- minimise side effects , avoid extreme temps, tirednesss 

- prednisolone 

- other immuno-supp - aza, cyclo, myco, cyclophos ?thymectomy 

ivig plasma exchange

11

What causes a thunderclap headache when SAH and ICH excluded -

Consider reversible cerebral vasconstriction syndrome - esp in marijuana smokers 

12

What is Alemtuzumab - lemtrada for MS?

anti CD52 antibody CD52 is a B and T cell antigen - but therapy depletes B cells more than T cells Monoclonal ab to CD52 - ablates circulating lymphocytes B cells recover fastest SE: increase in early infections esp HzV, VZV and pneumonia. a few cases of PML

13

What are the MS subtypes

1) RRMS - relapsing - remitting (most common, F/M 3:1 - most aggressive, relapses decrease after 1st 5 yrs 2) SPMS - secondary progressive MS - 1/3 have relapses 3)PPMS - 20% of males, behaves exactly like secondary progressive disease 4) progressive relapsing MS -

14

IV TPA contraindications expanded

Too mild, rapidly improving, too severe?

• Symptoms suggestive of SAH despite normal CT

• Seizure at onset

• BSL

• BP >185/110

• Head trauma or prior stroke within 3 months

• Non‐compressible arterial puncture within 7 days

• Any history of previous intra‐cranial hemorrhage

• Evidence of active bleeding or acute trauma (fracture) on

examination

• If on anticoagulation: warfarin+INR>1.7/heparin w/ abnormal APTT

• Platelets

RELATIVE Contra‐indications

• Myocardial infarction within 3 months

• Gastrointestinal or genitourinary hemorrhage within 21 days

• Major surgery within 14 days

• CT >1/3 MCA hypodensity ---> beyond our help

 

 

15

What about AEDs in the elderly 

need to consider hepatic and renal function 

drug interactions 

- CBZ least tolerated - 31% ceased 

- LTG best tolerated - 12% ceased 

efficacy similar 

16

For dx of MS what criteria are used

Mcdonald criteria - dissemination in space and time - so need minimum 2 lesions in 2+ regions in CNS - periventricular, juxtacortical, infratentorial and spinal cord

17

what is the clinical course of MG 

• Untreated‐ spontaneous remission in 12‐ 21%

• Mildmoderate/severe over months

– Spread from eyes>face>bulbar>trunk, limbs

• Pure ocular MG

– ~50% generalised MG in

• GeneralisedMG

– Maximal worsening occurs in 1st 2‐3yrs

– Most of relapses, variability occurs in first 7 yrs

– Improvement less likely in more severe cases

18

What is the treatment for CIDP

 Prednisolone‐ daily

 IVIG‐ ~4 weekly

 Plasma Exchange

 IV Methyl Prednisolone – pulse

 +/‐ Azathioprine

 +/‐ Cyclosporin A, Mycophenolate, Rituximab

 ? (Cyclophosphamide +/‐IVMP +/‐ Plasma Exchange)

19

Tx for PML and MS

1. stop immunosuppressant immediately 2. consider immune reconstitution - plasma exchange to remove antibodies 3. risk of severe immune reconstitution inflame syndrome (IRIS) with cerebral oedema and clinical deterioration can use mirtazepine (possible reduction of virus entry into cells) can use Mefloquine - some anti JCV activitis - trial ongoing IV methylpred - given at fire sign of IRIS - 7 day course

20

Ischaemic stroke classification 1 

 • Large artery thromboembolism

• Cortical infarction, >50% relevant large artery stenosis,

absence of cardiac source

 • Cardiogenic embolism

• Cortical infarction, sometimes >1 vascular territory,

identifiable cardiac source (most often Afib), absence of

large artery disease

 • Lacunar Infarction

• Subcortical infarction, absence of large artery or cardiac

source, clinical syndromes

21

Nerve conduciton studies in demyelinating neuropathy 

 Nerve conduction studies

 Conduction velocity: Very slow (Upper extremity

 Conduction block: Failure of impulse conduction along an anatomically intact axon

 Dispersion of motor response

 Prolonged distal latencies & F‐waves

 EMG

 Reduced motor unit recruitment (fast firing motor units) in clinically weak muscles

22

what are the first line drugs for genreralised epilepsy 

  • first line - valproate, ethosuximide 
  • new AEDs - lamotrigine, topiramate, levetiracetam
  • second line - clonazepam/clobazam 

23

what is the inflam response in MS

Bias towards Th1 and Th17 lymphocytes environment with T reg cell dysfunction secreted cytokines disrupt BBB and up-regulation of endothelium - hence T cells enter CNS

24

Define epilepsy

 

tendency to recurrent unprovoked seizures of primary cerebral origin (requires at least two unprovoked seizures

typically a clinical diagnosis, history is paramount

seizure – transient occurrence of signs and or/symptoms due to abnormal excessive activity in the brain.

25

What is Glatiramer acetate (cop axone) and when is it used?

- synthetic polypeptide containing myelin basic protein - promote proliferation of Th2 cytokines, alters macrophage function. Reduces interferon gamma. Induces Th1 --> Th2 Adverse - daily injection, rare reaction with palpitations, chest pain dyspnoea, pregnancy category B

26

What is Multiple sclerosis?

- autoimmune inflammatory disease - affects CNS - demyelination and axonal degeneration - 50% need walking stick at 15 yrs

27

drug induced neuropathy 

A image thumb
28

29

What is the pharmacokinetic explanation for vaproate-dose-effect? 

 • Beta‐oxidation of VPA saturates at

approximately 800 mg/day.*

– Percentage of VPA excreted as glucuronide

increases:

• from 12.8% at 400 mg/day to 49.4% at 2000 mg/day.

– Glucuronide more reactive than products of betaoxidation. - doses above 1000mg are toxic

30

Where do motor tracts cross? ipsilateral or contralateral symptoms? 

  • cross in the lower medulla 
  • originate from a long cortical strip - posterior frontal lobe 
  • compact in the internal capsule and in the spinal cord 
  • any lesion in the spinal cord will give ipsilateral problems
  • anything in the brainstem or above will give contralateral problems

31

what is impaired consciousness in epilepsy 

inability to encode new memories

inability to interact purposefully with environment – test by asking pt to obey commands 

32

What is Dimethyl Fumarate - Tecfidera

it is an oral drug - also used for psoriasis and MS - activates NRF-2 pathway vs oxidative stress and causes mild neutropenia SE: flushing, GIT - but may settle in 1-3/12.

33

What does the lumbar puncture show in transverse myelitis? 

demonstrates spinal cord inflammation - pleocytosis or elevated IgG index 

IgG index is a measure of intrathecal synthesis of immunoglobulin

34

Classification of ICH

 Deep

• Putamen, thalamus, brainstem, cerebellum

• Usually due to hypertension and rupture of deep penetrating arteries

  Lobar

• Superficial

• Often secondary to amyloid angiopathy, tumour, arteriovenous malformation, venous sinus thrombosis

melanoma met bleeding most common

35

What is Natalizumab (Tysabri) and when used?

Monoclonal ab to alpha4 integrin (VCAM1) inhibits tissue migration of lymphocytes and monocytes into CNS In other words - binds to alpha4 intern (VLA-4) on lymphocytes stopping them from binding to endothelial VCAM1 and crossing BBB. Used as mono therapy for RELAPSING-REMITTING MS - given monthly IV- relapse risk reduction 67% LFT abnormalities can occur - transaminitis

36

What are the risk factors to develop PML

1. duration of exposure > 2yrs 2. previous exposure to an immunosupp - methotrexate, aza, cycle 3. JCV serology positive

37

what is demyelinating neuropathy 

  • primary destruction of the myelin sheath leaving the axon intact 
  • secondary axonal degeneration common late in the disease course
  • weakness - proximal and distal wasting 
  • tendon reflexes reduced
  • many causes incl immune/inflammatory, drugs/toxins, metabolic, 

38

What are the major SE of interferons

1) Flu like symptoms at commencement 2) Injection site reactions - ice skin before injection 3) LFT abnormalities are mild - screen at 1 and 6 months after starting treatment

39

What are the clinical features of PMS

Subacute onset progressive cortical symptoms/signs behaviours and neuropsych alteration hemiparesis

40

Where do dorsal columns cross over? 

  • dorsal columns responsible for joint position and vibration 
  • input from large sensory fibres in peripheral nerves 
  • cross in medulla 
  • cross over in lower brainstem 

41

What is the primary tx for MS - first treatment available

Interferon B1 - avonex or 1FNB1b - betaferon It binds to receptors on immune cells - decreases antigen presentation and T cell proliferation, decreases cytokine and MMP expression Major reaction is flu like symptoms and injection site necrosis

42

what is primary lateral sclerosis 

 Primary lateral sclerosis

• 2‐3.7% of all patients with MND;

• pure UMN syndrome

• Slow rate of progression 􁈺Pringe et al 1992􁈻

43

What is the link between AED and PCOS

- menstrual irregularities and polycystic ovaries more common -regardless of which AED 

hyperandrogenism associated with VPA - avoid in child-bearing 

PCOS prevalence 12.5-26% compared to 6.6% (seems to be associated with VPA)

44

WHAT ABOUT EPILEPSY AND CONTRACEPTION 

Pregnancy and epilepsy

  • proconvulsant effect of oestrogen vs progesterone
  • background malformation rate – 2%
  • roughly doubles on one AED
  • valproate especially more than 1g a day and polypharmacy particularly teratogenic
  • no agent known to be safe

Contraception

  • combined OCPs – increased oestrogen metabolism with PHT, CBZ, PB, LTG levels lowered
  • progesterone – anticonvulsant effect 

45

what is the difference between simple partial and compex partial seizures 

Simple partial – consciousness preserved

Motor or sensory incl special sensory

Autonomic

Psychic

 

Complex partial – consciousness impaired –not lost

Simple partial onset – aura

Or consciousness impaired from onset 

46

Ix and diagnosis of PML

CTB - often normal - occasional areas of hypo density MRI brain - almost always abnormal - very often sub-cortical U fibers, large >3cm lesions, contrast enhancement in 41% with early PML (60-76% overall) Ix - serology 55% of normal adults have JCV antibodies DNA - JCV PCR of CSF - 74-93% sensitive, 92-100% specific. PCR of PBMC or urine not helpful, CNS biopsy still required frequently

47

What is chronic inflammatory demyelinating polyneuropathy (CIDP)

Symmetric motor & sensory deficits

-  Proximal & distal weakness>wasting

-  Absent or  reflexes

-  Distal LL>UL sensory loss ‐20% painful; autonomic/resp uncommon

 Gradual onset over months‐years; progressive > 2M

 10% acute onset

 Natural history variable

 Chronic progressive 60%

 Relapsing ‐remitting 30%

 Monophasic 10%

 Spontaneous remission not uncommon but difficult to predict

M>F, all ages (mean 50yrs)

48

What is subacute combined degeneration of spinal cord? 

  • also known as Lichteim's disease 
  • refers to degeneration of pos and lateral columns of spinal cord 
  • 2* to Vit B12 deficiency - most common
  • other causes - vitamin E deficiency, copper deficiency 
  • presents with patchy loss of myelin in dorsal and lateral columns - weakness of legs, arms, trunk, tingling, and numbness that progressively wrosens 
  • made worse with nitric oxide in those with B12 deficiency 
  • can precipitate copper def if taking zinc - displaces zinc 

49

What is the classic basilar occlusion? 

  • 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 

50

Which artery supplies most of the spinal cord - hence if it is a spinal cord infarct what aa is likely? 

- ant spinal aa supplies most of the spine 

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

51

what are the key important facts about monitoring phenytoin and other drug levels? would you measure valproate levels? 

 

  • 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

52

where does the spinothalamic tract cross? 

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

53

what are automatisms in seizures? 

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 

54

What are the most common causes of axonopathy? 

 Diabetes

 Alcohol

 Uraemia

 Toxic / drugs

 Paraneoplastic (some)

 Nutritional

55

What is pharmcoresistant epilepsy? 

- on 2 drugs 

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

56

important facts about old AEDs

 

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) 

 

57

What is brown-sequard syndrome? 

  • ​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.

 

58

what are the emg findings for CIDP

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

59

What are the indications for carotid endarterectomy and % of stenosis - ? use in total occlusion

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

60

what is ALS - amyotropic lateral sclerosis? umn or lmn? involvement? 

 Amyotrophic lateral sclerosis

• Most common form

• Mixed UMN & LMN

• Limbs & Bulbar involvement

61

What AEDs to use with contraception

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 

62

EMG and nerve conduction studies in axonopathy? 

  • 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

63

MG diagnosis

 

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

 

 

64

endovascular clot retrieval and indications 

most trial pts were pre-treated with alteplase 

indications in 2015 -

65

what is the commonest familial metabolic cause of rhabdo 

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

66

what is the risk of sudden death in epilepsy? 

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 

67

what are the treatment guidelines for epilepsy? 

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 

68

What is motor neuron disease? 

  • 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) 

69

Oxfordshire stroke classification 

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

70

What is pharmacoresistant epilepsy? 

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

71

What was the Interact2 trial? 

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 -

72

What is progressive bulbar palsy ?

 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 

73

what is myasthenia pathology? 

  • 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

74

AEDs and congential malformations - things to know 

 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

75

Define stroke and TIA 

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!!! 

76

what are the endocrine abnormalities of AEDs on fertility 

Endocrine abnormalities (effect of AEDs)

– Increased SHBG levels

– Hyperandrogenism

– Polycystic ovaries

– Menstrual irregularities

– Anovulatory cycles

– Obesity

– Insulin resistance

77

What is the commonest neuropathy type and the major causes? 

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

they account for 75% of peripheral nerve pathology. 

78

what are the first line drugs for focal seizures? 

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

79

The 2007 lancet study on first AED selection - what were the outcomes 

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

80

spinal cord

A image thumb
81

best treatment for CIS in MS?

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

82

What is the anatomy of cervical roots? 

 

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

83

What is HIV neuropathy 

 Distal symmetric polyneuropathy

 Lumbosacral polyradiculopathy (caudaequina syndrome; CMV)

 Inflammatory demyelinating polyradiculoneuropathy

 Sensory neuronopathy

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

84

What are the main cells involved in MS - pathogenesis?

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

85

What is syrinx syndrome? 

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 

86

What is the relationship between AEDs and fractures 

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

87

HOT topic - what is benign MS?

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

88

what is progressive muscular atrophy? 

Progressive muscular atrophy

• Only develop LMN signs 􁈺without UMN signs􁈻;

• Older males 􁈺more commonly􁈻

• Improved survival 􁈺median 48 months cf 36months􁈻

89

What is dissemination in time?

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

90

What are the neuromyelitis optical spectrum disorders?

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.

91

what are the most commonest type of seizures 

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 

92

what is flail-arm syndrome 

 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􁈻

93

What is the TIA to Stroke risk score? 

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 

94

what is the management of status epilepticus? 

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 

95

How to diagnose MS

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

96

what causes foot drop after THR under spinal? 

 Peroneal @ knee vs sciatic @ hip vs L5

usually sciatic nerve - may lose ankle jerk-tibial nerve 

97

What are the birth defects associated with AEDs? 

• 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,

98

How safe is Terifluonomide in pregnancy

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

99

What is Terifluonomide - how does it work

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

100

What is commonest neuropathy? 

  • 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

101

What is the approach to suspected acute stroke and contraindications for therapy? 

• 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

 

102

What is inclusion body myositis? 

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%

103

What is Guillian Barre syndrome? 

 

  •  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 

104

What is the antecedent event in GBS ?

  •  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 

105

what is the natural hx and prognosis of GBS

  • 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 

106

What is miller fischer syndrome? 

  • 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. 

 

107

What is CIDP 

  • 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 

108

What is the pathogenesis and nerve conduction studies pattern in CIDP

  • 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” 

109

What is the treatment of CIPD 

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 

110

What is lambert/eaton syndrome 

  • 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 

111

clincial features of lambert/eaton syndrome 

  • 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 

112

define parkinson's disease - diagnostic criteria 

  • 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 

113

What are the pre parkinson's disease symptoms 

  • 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 

114

What are the common problems with non l dopa based strategies for PD 

direct dopamine agonists

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

115

what are the dx criteria for PSP 

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 

116

what are the dx criteria for multisystem atrophy 

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 

117

what are the dx criteria for corticobasal 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 

118