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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 

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