Epilepsy and seizure disorders

1. EPILEPSY AND SEIZURE DISORDERS Presenters: Luyimbazi IvaN Nansubuga Carol 1

2. Introduction-Seizures Seizures - paroxysmal events due to abnormal excessive or hypersynchronous neuronal activity in the brain cortex. The clinical characteristics of a seizure are the result of the area of the brain that is abnormally stimulated 5-10% of the population will have at least one seizure in their lifetime Highest incidence is in childhood and late adulthood. 2

3. Seizure terms Ictal= seizure Post-ictal= confusion following seizure Aura= abnormal sensation preceding loc Automatisms= nonsensical involuntary movements Tonic=contraction producing extension and arching Clonic= alternating muscle contraction-relaxation 3

4. Etiology CNS Head trauma Seizure in 1 week of injury not predictive of epilepsy Stroke Mass (tumor/abscess) Meningitis/encephalitis Congenital malformations/ cortical dysplasias Idiopathic Systemic Hypo/hyperglycemia Hypo/hypernatremia Hypocalcemia Uremia Hepatic encephalopathy Hypoxia Hyperthermia Drug overdose or withdrawal EtOH withdrawal sz occurs within 48h 4

5. CLASSIFICATION Focal seizures originate within network limited to one cerebral hemisphere Generalized seizures - arise within and rapidly engage networks across both cerebral hemispheres, result from biochemical or structural abnormalities 5

6. FOCAL SEIZURES Focal seizures without cognitive impairment Motor symptoms Involves motor strip, Manifested by abnormal movement of an extremity, Somatosensory symptoms Involves sensory strip, temporal(hearing and smell) or occipital(visual) lobe Autonomic symptoms i nvolves temporal lobe (tachycardia, pallor, flushing, sweating) Psychic symptoms Involve frontal or temporal lobe (limbic system): affective disturbances, cognitive deficits, hallucinations 6

7. FOCAL SEIZURES……. b) Focal seizures with cognitive impairment Typically frontal or temporal lobe onset Often stereotyped for the individual patient Average duration 1-3 minutes O nset can be followed by impaired consciousness Many times will progress to a generalized seizure Frequently seen in adult onset epilepsy Automatisms: coordinated involuntary movements, typically orobuccolingual or non-purposeful hand movements 7

8. Generalised Seizures Typical Absence seizure Characterized by brief sudden loss of consciousness without loss of postural control Lasts secs , consciousness returns suddenly, No post ictal confusion Genetically determined, onset at 4-8yrs, Main seizure type in 15-20% of children with epilepsy. Can occur hundreds of times in a day but child unaware, 1 st clues;- day dreaming, decline in school performance 8

9. Generalised Seizures Atypical Absence Seizure Longer duration of loss of consciousness, Less abrupt onset and cessation More obvious focal signs Less responsive to drugs 9

10. Generalised Tonic Clonic Seizures Main seizure in 10% of people with epilepsy Commonly results from metabolic derangements Usually abrupt onset, no auras, Tonic phase Clonic phase Post-ictal phase Post-ictal confusion can last hours-days especially in alcoholics 10

11. Generalised Seizures Atonic seizures Sudden losses of postural muscle tone, lasts 1-2 secs , Consciousness briefly impaired, No post ictal confusion . Myoclonic Seizure Sudden brief muscle contraction involving one part or entire body A normal physiological form- Is sudden jerk while falling asleep. Caused by cortical dysfunction. 11

12. Classification Pseudoseizures Non-epileptic seizures May be manifestation of conversion disorder, factitious disorder or malingering Features that may distinguish from epileptic seizures Pre-attack preparation, absence of post-ictal confusion “Disorganized” movements, pelvic thrusting, thrashing Bilateral convulsions without loss of consciousness Violent or goal-directed behavior, obscene language, Video EEG may help to diagnose 12

13. Seizure Mechanisms Involves 2 phases-initiation and propagation Initiation involves 2 concurrent events-high frequency bursts of Action potential, hypersynchronisation Ca2+ influx depolarising neuronal mem Opening of N a+ channels, Na entry Hyperpolarizing of GABA. 13

14. Mechanisms of Anti Epileptic Drugs Antiepileptic drugs appear to act primarily by blocking the initiation or spread of seizures. The mechanisms include; inhibition of Na + -dependent action potentials (e.g., phenytoin, carbamazepine, lamotrigine, topiramate, zonisamide), inhibition of voltage-gated Ca 2+ channels (phenytoin, gabapentin, pregabalin) attenuation of glutamate activity (lamotrigine, topiramate, felbamate) potentiation of GABA receptor function (benzodiazepines and barbiturates) increase in the availability of GABA (valproic acid, gabapentin, tiagabine) modulation of release of synaptic vesicles (levetiracetam). act by inhibiting T-typ e Ca 2+ channels in thalamic neurons.( valproic -absence seizures) 14

15. Epilepsy Epilepsy - Is a clinical condition in which they are recurrent(2 or more) un provoked seizures. Provoked seizures Seizures induced by somatic disorders originating outside the brain E.g. fever, infection, syncope, head trauma, hypoxia, toxins, cardiac arrhythmias Status epilepticus Continuous convulsion lasting longer than 30 minutes OR occurrence of serial convulsions between which there is no return of consciousness 15

16. Mechanism of epileptogenesis Refers to transformation of a normal neuronal network into one that is chronically hyperexcitable . CNS injuries ( trauma,stroke,infections ) initiate a process that gradually lowers the seizure threshold in the affected region. It can also be mediated by developmentally regulated events(in genetic & idiopathic epilepsy) 16

17. Epilepsy in Uganda Epilepsy is the most common neurological condition Prevalence is 2-5 persons/100 people High predominance in areas endemic with onchocerciasis(15-20 cases/1000 people) in Kabalore and Nebbi districts Etiology is birth trauma, accidents and untreated malaria. 60 % of mental illness is a result of epilepsy; poorly managed disease Study done by Epilepsy support Association of Uganda 17

18. 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 18

19. Investigations I. Exclusion of differentials: urinalysis Hematological: CBC Biochemical: U&Es, Calcium, glucose, ABGs Radiological: CXR, CT head Toxicological: screen Microbiological: Lumbar Puncture (Always used with justification) 19

20. Investigations II. Confirmation of epilepsy: Dynamic investigations : result changes with attacks E.g. EEG Static investigations : result same between and during attacks E.g. Brain scan 20

21. Electroencephalography (EEG) Uses of EEG in epilepsy Diagnostic: support diagnosis, classify seizure, localize focus, quantify Prognostic: adjust anti-epileptic treatment 21

22. EEG Normal EEG doesn’t rule out epilepsy Always abnormal in a GTC Use of video EEG telemetry to detect seizure activity on 24hrs Interictal EEG maybe normal 60% of times in known epileptics Can classsify seizure disorders. MRI recommended to r/o structural lesions. 22

23. Neuroimaging Structural neuroimaging Functional neuroimaging 23

24. Structural Neuroimaging Who should have a structural neuroimaging? Status epilepticus Develop seizures when > 20 years old Focal epilepsy (unless typical of benign focal epilepsy syndrome) Refractory epilepsy Evidence of neurocutaneous syndrome 24

25. Structural Neuroimaging Modalities available: Magnetic Resonance Imaging (MRI) Computerized Tomography (CT) What sort of structural scan? MRI better than CT CT usually adequate if to exclude large tumor MRI not involve ionizing radiation I.e. not affect fetus in pregnant women (but nevertheless avoided if possible) 25

26. Functional Neuroimaging Principles in diagnosis of epilepsy: When a region of brain generates seizure, its regional blood flow, metabolic rate and glucose utilization increase. After seizure, there is a decline to below the level of other brain regions throughout the inter-ictal period. 26

27. Functional Neuroimaging Modalities available: Positron Emission Tomography (PET) Single Photon Emission Computerized Tomography (SPECT) Functional Magnetic Resonance Imaging (fMRI) Mostly used in: Planning epilepsy surgery Identifying epileptogenic region Localizing brain function 27

28. Treatment of epilepsy Emergency treatment and long term seizure control Rx underlying condition Avoid precipitating factors; alcohol, lack of sleep, lights Prevent recurrence with drugs Address psychological and social issues Note ; advised to continue AEDs for 1yr after removal of structural lesion 28

29. Anticonvulsants Cabamazepine Phenytoin Valproic acid Tonic- clonic and focal Ethosuximide Valproic acid Clonazepam Absence seizures Valproic acid Clonazepam Myoclonic seizures Diazepam Lorazepam Short term control Phenytoin Phenobarbital Prolonged therapy Status Epilepticus Drugs used in seizure disorders 29

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31. Epilepsy - Treatment The treatment target is seizure-freedom and improvement in quality of life! Basic rules for drug treatment: Drug treatment should be simple, preferably using one anticonvulsant (monotherapy). “Start low, increase slow“. Add-on therapy is necessary in some patients . 31

32. Treatment withdrawal If patient is seizure-free for three years, withdrawal of pharmaco therapy should be considered. Withdrawal should be carried out only if patient is satisfied that a further attack would not ruin employment etc. (e.g. driving license). It should be performed very carefully and slowly! 20% of pts will suffer a further sz within 2 yrs. 32

33. Status Epilepticus 33

34. Algorithm of patient with Seizures 34