Epilepsy

1. Epilepsy Subspecialty seminar Oct 25, 2006

2. defn • Two or more unprovoked seizures. • seizure is an abnormal electrical activity of the brain due to hyper synchronous firing of aggregates of neurons.

3. CON • Normally there are highly differentiated electrical signals with in the brain that sustain the normal life • “Electrical rebellion” that results in to monotonous discharge firing in synchrony across the brain • ‘Sacire’ to take possession of • Most prevalent of the neurological disorders

4. Magnitude of the problem • World wide incidence 0.3-.0.5% prevalence 5-10/1000 • Ethiopia prevalence 5.2/1000 GTC 81% Partial complex 13.9 simple partial 5.7 The commonest of all neurological problems

5. Classification • Partial and Generalized • Partial when the seizure arises from discreet area of the cortex • Generalized when there is clinical or EEG Manifestation of simultaneous i/v of both hemispheres . • Partial sz are common ones in adults • Temporal lobe epilepsy commonest of the partials szs

7. Partial szs • Simple partial no loss of consciousness area involved →type of sz Motor → convulsive temporal →Auditory halln →behavioral abn limbic → Psychic Post ictal paralysis 13.5% Epilepsia partialis continua JACKSONIAN march

8. Complex partial sz • Ass with alteration in consciousness • Stereotypical aura • Automatism • Post ictal confusion • Amnesia • Protean range of manifestations • Consider as DDx in any pt with paroxysmal abnormal behavior esp if the pt seems not to be fully aware of it

9. con • Partial sz with sec generalizn Aura sterotyped clear Generalized szs -Absence sz Common in children difficult to dx easy to treat transient lapses of consciousness Subtle motor manifestations 70% remission rate classic EEG findings

10. ..con Tonic clonic the sterotype sz in the public mind • the commonest sz of metabolic abnormalities • 10% of the general popn at one time during their life • Cx by: Loss of consciousness tonic stiffning clonic phase Post ictal confusion Headache/muscle pain usually lasts for a minute

11. con Tonic /Clonic szs Atonic sudden loss of postural tone predisposes to trauma Consciousness briefly impaired Myoclonic brief reigonal or generalized contraction of the muscles due to metabolic disturbance Part of syndromes

12. Epilepsy syndromes Juvenile myoclonic epilepsy adolescents benign ass with other sz Lennox Gastaut syd. multiple sz Cognitive abn characterstic EEG MTLE hippocampal sclerosis partial complex sz most studied

13. Mechanism • Imbalance b/n excitation and inhibition of the neuron endogenous factor Epileptogenic PPting seizure

14. …contd • Epileptogenic HI,stroke,malignancies infections,drugs.. • Endogenous family Hx Genetic abnormalities • PP factors sleep deprivation photo menses Epileptogenesis refers to transformation of the normal neuronal network in to that of chronically hyperexcitable one

15. ..con Structural abnormalities selective loss of neurones (inhibitory or excitatory ) sprouting and reorganization chronic hyperexcitable network

16. Con Partial • Inhibitory neuronal loss exicitatory neurons that stimulate the inhibitory pathways are also lost • Abnormal integration of neurons with reorganization • New neuron differentiation with formation of new synapses • Alteration in the composition and expression of GABA receptors

17. MTLE

18. …con • Neuronal loss • Reorganization gradually lowers • Neurogenesis sz threshold

19. Mechanism Absence • Alteration in the circuitry b/n the thalamus and the cortex • Normally the rhythm of cortical stimulation is influenced by thalamus • The thalamocortical circuit underlies the physiological cortical excitation including sleep • Either fires in a burst form or in a tonic manner • In turn it is influenced by the RAS

20. Thalamo cortical circuit

21. Mechanism • Developmental influences • Cortical malformations proliferation migration cortical organization Being identified using high resoln neuroimaging • Change in the neuronal microenvironment key buffering function • Channelopathies

22. con • Focal Discreet lisions with disruption of the balance • Generalized Network abnormalities Intrinsic neuronal abnormalities

23. Evaluation • Is it a seizure? • DDx for Sz • Does it have any reversible cause? • Is medication worth initiating? • HX preictal, ictal post ,ictal ,frequency family hx drugs systemic illnesses

24. …Con • pptin factors • P/E look for atherosclerotic Markers signs of trauma skin abnormalities neurological abn LAB CBC,U/A, OFTs electrolytes LP EEG

25. …CON • Neuroimaging MRI/CT • functional studies

26. evaluation

27. Treatment • Treat the underlying cause • Treat the ppting factor • Prevent recurrence • Address psychosocial issues

28. General principles • The lower possible dose • Single drug • Appropraite for the type • Start low and go slow • depends on the frequency of the sz • Side effect profile • Drug interaction • Clinical monitoring

29. …con • Serum drug levels • Switch to another class of drug if not controlled by one • Use two drugs if single therapy of two different classes fail • Follow up acc the control of sz • Issue of discontinuation

30. Antiepileptic drugs • mode of action ion channels/N.transmitters • act on Na channels phenytoin,carbama lamotrigine,topiramate • Ca channel phenytoin • GABA potentiation Barbiturates • Glutamate uptake Lamotrigine

32. New vs old drugs • The new ones are found to be • as effective as those of the old • expensive • not time tested

33. Side effects of AEDS

34. Current recommendation(American Academy Of Neurology) • Patients with newly diagnosed epilepsy Who require treatment can be initiated on standard AEDs such as carbamazepine, valproic acid,phenobarbital OR • The new AEDs lamotrigine,gabapentin,oxcarbazine,or topiramate (evidence level A/B)

35. Status epilepticus • Continues or repititive discreet szs without regaining consciousness in between which lasts 5 or more minutes • Medical emergency • As many statuses as epilepsies • Ass with mortality rate of 20% • The mechanism which normally aborts a sz is lost

36. Etiology • Drug discontinuation or incompliance • Acute structural injuries • Remote >> abnormalities • Metabolic abnormalities • Drugs intoxications

37. …con • Status is Cx by • self sustenance • Pharmaco-resistance • Neuronal damage Which tends to worsen as time passes without Being controlled

38. Pathophysiology • Milliseconds to secs ionchannel opening/closing Neurotransmitter modulation • Secs to minutes Receptor trafficing • Minutes to Hrs Plastic changes in neuropeptide modulators • Hrs to days change in gene expression partly explains how sz becomes self sustaining and Pharmaco resistant

39. complications • Hyperthermia • Aspiration • Rahbdomyolysis • Lactic acidosis • Brain injury • Pulmonary edema

40. Treatment • Supportive Airways BP Fast neurological examn Draw blood/secure iv line • Ideal situations this should take <4’ • INITIATE Rx as fast as possible

41. Rx

42. …con Diazepam/Lorazepm IV stat Repeat another dose Secure 2nd iv line Phenytoin 20mg/kg 50mg/min 10mg/kg

43. ..cont. Phenobarb 20mg/kg 50mg/min Repeat 10mg/kg If controlled taper for 24 hrs but maintain higher serum levels G/A Propofol When the bp is low consider midazolam drip .

45. References • Harrisons 16th edt • Uptudate 14.1 • Lancet (vol 5 march 2006) • Nejm(349;13 sep 25,2003) • Nejm(2005,Tales of temporal lobe • www.neurology.com