1. Epilepsy BY RUTENDO GANYANI AND SARAH FOLKERTS

2. Case  52 yr man brought to A&E  Wife witnessed: while standing at bus stop he fell to the ground & she was unable to rouse him  Breathing stopped for about 20s -> after that jerking movements affecting his arms & legs ~ 2mins  There was some urinary incontinence & his face became blue  After regaining consciousness he remained drowsy with a headache  No symptoms prior to episode  What are your main DDs?  What investigations would you perform?

3. -Syncope & epileptic fit are the main DDs -Syncope often while standing, stressful events & associated w/ arrythmia -Try to assess for prodromal & postictal symptoms -Syncope -> dizziness & lightheadedness before -Epileptic fit -> confusion & sleepiness after -Investigations: -FBC -U&E (exclude uraemia, hyponatraemia, hypoglycaemia & hypocalcaemia) -Also check gamma-GT for possible alcohol abuse -CT scan to exclude mass lesion or cerebrovascular event -Refer to neurologist for EEG

4. What is epilepsy?  Epilepsy is the most common neurological disorder.  Characterised by abnormal electrical activity in the brain.  Can be focal or generalised

5. What is it’s aetiology? Changes in neuronal excitability!!!!  Reduction in GABA  Increase in Ach transmission  Increase in Na+ transmission  Decrease in K+ transmission  Mutations found in K+, Na+, Ach and GABA receptors (channelopathies)

6. How does it present?

7.  PARTIAL SEIZURES!

8. Symptoms depend on site of origin No loss of consciousness or post-ictal confusion What symptoms would you see if the seizure originated in the: 1.Temporal region? 2.Parietal region? 3.Frontal region? 4.Occipital region? ANSWERS Temporal : aura-smell/taste, déjà vu, jamais vu, emotional changes, oral automatisms, gestures eg dystonic or fidgeting Frontal : mainly motor, often bilateral e.g. kicking, cycling, violent. Parietal : Sensory, nausea, choking, sinking sensations, Illusions of body distortion Occipital : Visual hallucinations – simple or complex (shapes to scenes),Vision may black out, Visuo-spatial distortions, headache, nausea

9. Altered consciousness, but may seem fully aware Symptoms: automatisms (chewing, swallowing, repeated displacement behaviour) Generally temporal lobe in origin, can progress to generalised Prior to onset may experience sense of déjà vu/jamais vu, perceptual changes, auras May have some post-ictal confusion Question So where is the main difference between this type of seizure and a simple partial seizure?

10.  GENERALISED SEIZURES!

11. Also called Grand Mal seizures Easiest to diagnose No warning of onset Whole brain involved Tonic phase -:  whole body stiffness  breathing may stop (cyanosis ) ask about this when taking a collateral Hx  loss of bladder control patient may report that they were wet when they regained consciousness. Ask about this when taking Hx. Also tongue biting Clonic phase –:  muscle jerks Post-ictal-: unconsciousness, muscle relaxation, slow regain of consciousness, confusion, sleepy, headaches and aching limbs, no recall of episode ask about post-ictal symptoms when taking Hx eg tiredness

12. Also called Petit Mal Rare in adults Generally start between 6-12 yrs Affect Girls > Boys Symptoms: seem to ‘switch-off’ (~10 s) but cannot be alerted or woken up

13. The in-betweener!  Partial with secondary generalised  Simple partial seizure, patient conscious and aware progressing to generalised (Grand-Mal)  Seizures becomes generalised when abnormal electrical activity hits the thalamus  The ‘simple’ part of the seizure depends on site of origin

14. ‘Other’  psychogenic non-epileptic seizures  Myoclonic – sudden jerks (like when falling asleep), possibly familial  Clonic – repeated twitches and jerks no stiffness  Tonic – all muscle contract, whole body stiffness  Atonic – ‘drop attacks,’ muscle tone lost

15. TREATMENT OF EPILEPSY

16. Options  Pharmacological :  First line approach for seizures  Anticonvulsants  Surgical  removal of aberrant areas (found by MRI/CAT/electrical stim)  Implants  VNS – vagal nerve stimulation

17. Seizure type1 st line2 nd line Simple Partial Complex partial Partial with secondary generalised Carbimazepine Sodium Valproate Lamotrigine Oxcarbazepine Gabapentin Pregabalin Tiagabine Topiramate etc Tonic-Clonic Seizure (Grand Mal) Sodium Valproate Lamotrigine Carbimazepine Clobazam Levetiracetam Oxcarbazepine Topiramate Absence Seizures (Petit Mal) Ethosuximide Sodium Valproate Clonazepam Lamotrigine Status Epilepticus (medical emergency) IV Lorazepam (repeated after 10 mins) After 25 mins: phenytoin sodium, fosphenytoin, or phenobarbital sodium After 45 mins: Anaesthetize with thiopental, midazolam or propofol Buccal Midazolam/Rectal diazepam (if resusc facilities not available, e.g. at home) Secure airway!

18. Anti-epileptic hypersensitivity syndrome -1-8 weeks from treatment initiation -Initial signs: fever, rash, swollen lymph nodes -Severe signs: Blood, liver, kidney abnormality, vasculitis & organ failure -Withdraw drugs immediately -Topical steroids & antihistamines -Systemic corticosteroids? -Beware of rebound seizures activity Be aware of this!

20. GABAa targets Enhance activation of GABA A mediated channels via:  Action at co-agonist sites  Inhibition of GABA breakdown  Inhibition of GABA uptake  GABA mimetics Benzodiazepines: Act on GABAa receptor (γ subunit) to increase activity, thereby reducing neuronal transmission by enhancing inhibition. Barbiturates : as above but bind the β- subunit of the GABAa receptor GABA transporter inhibitors e.g. Tiagabine GABA transaminase inhibitors e.g. Vigabatrin Side effects of Benzodiazepines and barbiturates Short-term use only (< 12 weeks) Tolerance and dependency can develop Impaired motor coordination (↓muscle tone) Impaired cognitive performance Sedation Disturbed sleep patterns Retrograde amnesia Withdrawal on termination Benzo overdose: use flumazenil

22. 1.Sodium Valproate 2.Ethosuximide 3.Diazepam 4.Carbamazepine a.Ca-channel blocker b.Na-channel blocker c.GABA receptor modulator 1. Sodium Valproate – b. Na-channel blocker 2. Ethosuximide – a. Ca-channel blocker 3. Diazepam – c. GABA receptor modulator 4. Carbarmazepine – b. Na-channel blocker

23.  Any Questions???