Seizures & Epilepsy

1. Seizures & Epilepsy MBBS IV Group C Tutor: Prof. V. Wong 16th Feb 2004

2. Outline • Definitions • Pathophysiology • Aetiology • Classification • Video demonstration • Diagnostic approach • Treatment • Quiz

3. Definition • Seizure (Convulsion) • Clinical manifestation of synchronised electrical discharges of neurons • Epilepsy • Present when 2 or more unprovoked seizures occur at an interval greater than 24 hours apart

4. Definition • Provoked seizures • Seizures induced by somatic disorders originating outside the brain • E.g. fever, infection, syncope, head trauma, hypoxia, toxins, cardiac arrhythmias

5. Definition • Status epilepticus (SE) • Continuous convulsion lasting longer than 30 minutes OR occurrence of serial convulsions between which there is no return of consciousness • Idiopathic SE • Seizure develops in the absence of an underlying CNS lesion/insult • Symptomatic SE • Seizure occurs as a result of an underlying neurological disorder or a metabolic abnormality

6. Aetiology of seizures • Epileptic • Idiopathic (70-80%) • Cerebral tumor • Neurodegenerative disorders • Neurocutaneous syndromes • Secondary to • Cerebral damage: e.g. congenital infections, HIE, intraventricular hemorrhage • Cerebral dysgenesis/malformation: e.g. hydrocephalus

7. Aetiology of seizures • Non-epileptic • Febrile convulsions • Metabolic • Hypoglycemia • HypoCa, HypoMg, HyperNa, HypoNa • Head trauma • Meningitis • Encephalitis • Poisons/toxins

8. Aetiology of Status Epilepticus • Prolonged febrile seizure • Most common cause • Idiopathic status epilepticus • Non-compliance to anti-convulsants • Sudden withdrawal of anticonvulsants • Sleep deprivation • Intercurrent infection • Symptomatic status epilepticus • Anoxic encephalopathy • Encephalitis, meningitis • Congenital malformations of the brain • Electrolyte disturbances, drug/lead intoxication, extreme hyperpyrexia, brain tumor

9. Pathophysiology • Still unknown • Some proposals: • Excitatory glutamatergic synapses • Excitatory amino acid neurotransmitter (glutamate, aspartate) • Abnormal tissues — tumor, AVM, dead area • Genetic factors • Role of substantia nigra and GABA

10. Pathophysiology • Excitatory glutamatageric synapses • And, excitatory amino acid neurotransmitter (glutamate, aspartate) • These are for the neuronal excitation • In rodent models of acquired epilepsy and in human temporal lobe epilepsy, there is evidence for enhanced functional efficacy of ionotropic N-methyl-D-aspartate (NMDA) and metabotropic (Group I) receptors Chapman AG. Glutatmate and Epilepsy. J Nutr. 2000 Apr; 130(4S Suppl): 1043S-5S

11. Pathophysiology • Abnormal tissues — tumor, AVM, dead area • These regions of the brain may promote development of novel hyperexcitable synapses that can cause seizures

12. Pathophysiology • Genetic factors • At least 20 % • Some examples • Benign neonatal convulsions--20q and 8q • Juvenile myoclonic epilepsy--6p • Progressive myoclonic epilepsy--21q22.3

13. Pathophysiology • Role of substantia nigra • Studies with 2-deoxyglucose indicate that a marked increase in metabolic activity in SN is a common feature of several types of generalized seizures; it is possible that some of this increased activity is associated with GABAergic nerve terminals that become activated in an attempt to suppress seizure spread. • Because GABA has been shown to inhibit nigral efferents, it is likely that GABA terminals inhibit nigral projections that are permissive or facilitative to seizure propagation From Gale K. Role of the substantia nigra in GABA-mediated anticonvulsant actions. Adv Neurol.1986;44:343-364

14. Pathophysiology • Premature brain • It is more susceptible to specific seizures than is the brain in older children and adults • Kindling • Repeated subconvulsive stimulation (e.g. to the amygdala) will lead to generalized convulsion • This may explain the development of epilepsy after injury to the brain • One temporal lobe seizure -> contralateral lobe

15. Classification of seizures

16. Seizures • Partial • Electrical discharges in a relatively small group of dysfunctional neurones in one cerebral hemisphere • Aura may reflect site of origin • + / - LOC Generalized • Diffuse abnormal electrical discharges from both hemispheres • Symmetrically involved • No warning • Always LOC

17. Partial Seizures Simple Secondary generalized Complex 1. w/ motor signs 2. w/ somato-sensory symptoms 3. w/ autonomic symptoms 4. w/ psychic symptoms 1. simple partial --> loss of consciousness 2. w/ loss of consciousness at onset 1. simple partial --> generalized 2. complex partial --> generalized 3. simple partial --> complex partial --> generalized

18. Simple partial seizureswith motor signs • Focal motor w/o march • Focal motor w/ march • Versive • Postural • Phonatory

19. Simple partial seizures with motor signs • Sudden onset from sleep • Version of trunk • Postural • Left arm bent • Forcefully stretched fingers • Looks at watch • Note seizure

20. Simple partial seizures with sensory symptoms • Somato-sensory • Visual • Auditory • Olfactory • Gustatory • Vertiginous

21. Simple partial seizures with sensory symptoms • Vertiginous symptoms “Sudden sensation of falling forward as in empty space” • No LOC • Duration: 5 mins

22. Simple partial seizures with autonomic symptoms • Vomiting • Pallor • Flushing • Sweating • Pupil dilatation • Piloerection • Incontinence

23. Simple partial seizures with autonomic symptoms • Stiffness in L cheek • Difficulty in articulating • R side of mouth is dry • Salivating on the L side • Progresses to tongue and back of throat

24. Simple partial seizures with psychicsymptoms • Dysphasia • Dysmnesic • Cognitive • Affective • Illusions • Structured hallucinations

25. Simple partial seizure with pyschic symptoms • Dysmnesic symptoms • “déjà-vu” • Affective symptoms • fear and panic • Cognitive • Structured hallucination • living through a scene of her former life again

26. Complex Partial Seizures • Simple partial onset followed by impaired consciousness • with or without automatism • With impairment of consciousness at onset • with impairment of consciousness only • with automatisms

27. Simple Partial Seizures followed by Complex Partial Seizures • Seizure starts from awake state • Impairment of consciousness • Automatisms • lip-smacking • right leg

28. Complex Partial Seizures with impairment of consciousness at onset • Suddenly sit up • Roll about with vehement movement

29. Partial Seizures evolving to Secondarily Generalised Seizures • Simple Partial Seizures to Generalised Seizures • Complex Partial Seizures to Generalised Seizures • Simple Partial Seizures to Complex Partial Seizures to Generalised Seizures

30. Simple Partial Seizures to Generalised Seizures • Turns to his R with upper body and bends his L arm • Stretches body • LOC • Tonic-clonic seizure • Relaxation phase • Postictal sleep

31. Simple Partial Seizures to Complex Partial Seizures to Generalised Seizures • Initially unable to communicate but understands • Automatism • Smacking • Hand-rubbing • Abolished communication • Generalised tonic-clonic seizure

32. Generalized seizures • Absence • Myoclonic • Clonic • Tonic • Tonic-clonic • Atonic

33. Absence seizures • Sudden onset • Interruption of ongoing activities • Blank stare • Brief upward rotation of eyes • Duration: a few seconds to 1/2 minute • Evaporates as rapidly as it started

34. Absence seizures • Stops hyperventilating • Mild eyelid clonus • Slight loss of neck muscle tone • Oral automatisms

35. Myoclonic seizures • Sudden, brief, shock-like • Predominantly around the hours of going to or awakening from sleep • May be exacerbated by volitional movement (action myoclonus)

36. Myoclonic seizures • Symmetrical myoclonic jerks

37. Clonic seizures • Repetitive biphasic jerky movements • Repetitive vocalisation synchronous with clonic movements of the chest (mechanical) • Venous injection of diazepam • Passes urine

38. Tonic seizures • Rigid violent muscle contraction • Limbs are fixed in strained position • patient stands in one place • bends forward with abducted arms • deep red face • noises - pressing air through a closed mouth

39. Tonic seizures • Elevates both hands • Extreme forward bending posture • Keeps walking without faling • Passes urine

40. Tonic Phase Sudden sharp tonic contraction of respiratory muscle: stridor / moan Falls Respiratory inhibition cyanosis Tongue biting Urinary incontinence Clonic Phase Small gusts of grunting respiration Frothing of saliva Deep respiration Muscle relaxation Remains unconscious Goes into deep sleep Awakens feeling sore, headaches Tonic-clonic seizures(grand mal)

41. Tonic-clonic seizures • Tonic stretching of arms and legs • Twitches in his face and body • Purses his lips and growls • Clonic phase

42. Atonic seizures • Sudden reduction in muscle tone • Atonic head drop

43. Epilepsy syndrome • Epilepsy syndromes may be classified according to: • Whether the associated seizures are partial or generalized • Whether the etiology is idiopathic or symptomatic/ cryptogenic • Several important pediatric syndromes can further be grouped according to age of onset and prognosis • EEG is helpful in making the diagnosis • Children with particular syndromes show signs of slow development and learning difficulties from an early age

44. Table 1. Modified ILAE Classification of Epilepsy Syndromes

45. Table 1. Modified ILAE Classification of Epilepsy Syndromes (cond’)

46. Three most common epilepsy syndromes: • Benign childhood epilepsy • Childhood absence epilepsy • Juvenile myoclonic epilepsy Three devastating catastrophic epileptic syndromes: • West syndrome • Lennox-Gastaut syndrome • Landau Kleffner Syndrome

47. Benign childhood epilepsy with centrotemporal spike (Benign Rolandic Epilepsy) • Typical seizure affects mouth, face, +/- arm. Speech arrest if dominant hemisphere, consciousness often preserved, may generalize especially when nocturnal, infrequent and easily controlled • Onset is around 3-13 years old, good respond to medication, always remits by mid-adolescence

48. Childhood absence epilepsy • School age ( 4-10 years ) with a peak age of onset at 6-7 years • Brief seizures, lasting between 4 and 20 seconds • 3Hz Spike and wave complexes is the typical EEG abnormality • Sudden onset and interruption of ongoing activity, often with a blank stare. • Precipitated by a number of factors i.e. fear, embarrassment, anger and surprise. Hyperventilation will also bring on attacks. Juvenile myoclonic seizure • Around time of puberty • Myoclonic ( sudden spasm of muscles ) jerks → generalized tonic clonic seizure without loss of consciousness • Precipitated by sleep deprivation

49. West’s syndrome (infantile spasms) Triad: • infantile spasms • arrest of psychomotor development • hypsarrhythmia • Spasms may be flexor, extensor, lightning, nods, usually mixed. Peak onset 4-7 months, always before 1 year. Lennox-Gastaut syndrome Characterized by seizure, mental retardation and psychomotor slowing Three main type: • tonic • atonic • atypical absence Landau- Kleffner syndrome ( acquired aphasia )

50. Diagnosis in epilepsy • Aims: • Differentiate between events mimicking epileptic seizures • E.g. syncope, vertigo, migraine, psychogenic non-epileptic seizures (PNES) • Confirm the diagnosis of seizure (or possibly associated syndrome) and the underlying etiology