Epilepsy the Essentials

INSTITUTE OF NEUROLOGY DCEE / NSE Epilepsy the Essentials Fergus Rugg-Gunn Consultant Neurologist Dept of Clinical and Experimental Epilepsy Institute of Neurology, University College London Epilepsy Society National Hospital for Neurology and Neurosurgery, UCLH

Overview Diagnosis Treatment General medical ward Status epilepticus

Definition the occurrence of recurrent and unprovoked transient paroxysms of excessive or uncontrolled discharges of neurons, which may be caused by a number of different aetiologies, leading to epileptic seizures

Epidemiology Prevalence 450,000 in UK (1/130) Incidence per 100,000 150 100 50 30,000 new cases / year in UK Peaks in first 15yr and 60yr+ 5,000 dead in 1 st year from cause 1,000 deaths/yr in UK directly as a result of epilepsy 0 10 20 30 40 50 60 70 80 Age (years) Lifetime incidence of a seizure 1/20 20-30% misdiagnosis rate

Tonic Clonic Tonic-clonic Absence Myoclonic Simple Complex Secondarily generalised Atonic

Vasovagal / Neurocardiogenic syncope Prevalence much higher than epilepsy Prodromal symptoms - sweaty, light headed, dizzy, loss of vision and hearing FEATURE SYNCOPE GTCS Duration Usually < 30s 1-2 min Precipitant 50% None Falls Flaccid/stiff Tonic Jerking 80% Always Hypersalivation None Common Incontinence Quite common Common Tongue bite Rare Common Post-ictal confusion <30s 2-30 min Myoclonic jerks: common Adapted from Lempert et al, 2000 multifocal, usually non-rhythmic

Types of Partial Epileptic Seizures Simple Temporal: epigastric rising, déjà-vu, fear, auditory, olfactory Frontal: less clear, motor, sensory, odd Parietal: sensory, vertigo Occipital: visual Complex Temporal. 2-4 minutes Frontal 15-30 seconds Head rotation & automatisms: face, limbs, speech

Dissociative seizures Epilepsy Non-epileptic attack disorder Precipitating cause Rare Common (emotion, stress) Onset Rapid Gradual Aura Various Panic, altered mental state Vocalisation Various Tearfulness, crying Consciousness Complete/incomplete Unresponsive (alpha on EEG) Movement Atonic, tonic, clonic Flailing, thrashing, pelvic thrusting, motor automatisms opisthotonus, wax and wane Injury Tongue bite, fall May tongue bite (tip), carpet burns Incontinence Common Sometimes Duration Few minutes Often prolonged, variable recovery

Differential diagnosis Syncope Cardiac arrhythmia Hyperventilation, panic attack, NEAD Migraine Metabolic - hypoglycaemia Drugs: E, A, C, L, M

Treatment

18 Perampanel No. of medications 16 14 12 10 8 6 4 2 0 Retigabine Stiripentol Date

Anti-epileptic drugs in the UK Acetazolamide Carbamazepine (1965) Clobazam Clonazepam Ethosuximide Phenobarbitone (1912) Phenytoin (1938) Primidone Sodium Valproate (1977) Vigabatrin Lamotrigine (1991) Gabapentin (1993) 1993 Piracetam 1995 Topiramate 1998 Tiagabine 2000 Oxcarbazepine 2000 Levetiracetam 2005 Pregabalin 2005 Zonisamide 2007 Rufinamide 2008 Lacosamide 2009 Eslicarbazepine 2011 Retigabine 2012 Perampanel 2016 - Brivaracetam

Carbamazepine Lamotrigine Oxcarbazepine Sodium Valproate Topiramate Levetiracetam Zonisamide Simple partial Complex partial Secondarily generalised

Carbamazepine Lamotrigine Oxcarbazepine Sodium Valproate Topiramate Levetiracetam Zonisamide Simple partial Complex partial Secondarily generalised

Tonic Clonic Tonic-clonic Absence Myoclonic Atonic Valproate Lamotrigine Topiramate Levetiracetam Zonisamide

Tonic Clonic Tonic-clonic Absence Myoclonic Atonic Valproate Lamotrigine Topiramate Levetiracetam Zonisamide

Prescribing Recommended dose may be inappropriate co-morbidity, age There are no specific dosages for AEDs Start low and go slow Therapeutic drug monitoring compliance, toxicity, illness, Rx Not a substitution for clinical surveillance Generic substitution Compliance simple regimes, labelling, aids, carers, education

Seizures On The General Medical Ward 1-2% of all emergency attendances & medical admissions 60% are in patients with known epilepsy Correct diagnosis? Correct classification? Correct AED and dose? Compliance? Comorbidity sepsis, sleep apnoea? Clear triggers? Covert lesion? Consistent with the truth? Correct approach to emergency care?

Seizures On The General Medical Ward 1-2% of all emergency attendances & medical admissions 40% are acute symptomatic seizures Headache Meningism Foreign travel Alcohol, illicit drug use Review medication incl. over the counter

Seizures On The General Medical Ward 1-2% of all emergency attendances & medical admissions 40% are acute symptomatic seizures Headache Meningism Foreign travel Alcohol, illicit drug use Review medication incl. over the counter anti-malarials, antibiotics (beta lactams and quinolones), tacrolimus, cyclosporin, tramadol, rituximab, cisplatin

Seizures On The General Medical Ward 1-2% of all emergency attendances & medical admissions 40% are acute symptomatic seizures Headache Meningism Foreign travel Alcohol, illicit drug use Review medication incl. over the counter Relevant past medical Hx DM, malignancy Recent insult e.g stroke, brain injury

Investigations Standard blood tests: FBC, U+E, LFT, CRP, glc, Mg, Ca Consider: serum / urine toxicology screen alcohol, salicylate, lithium, theophylline, cocaine ammonia autoimmune screen (VGKC, NMDA, paraneoplastic) infective screen pregnancy test CSF examination if altered mental state, sepsis, low immunity EEG may be helpful Neuroimaging CT / MRI

Definition of Convulsive SE a condition characterised by prolonged or recurrent tonic clonic seizures for 30 minutes or more Ref.

Status Epilepticus is a staged process Normal physiology (compensation) Cardiorespiratory compromise (decompensation) Neuronal damage Refractoriness 0 mins 30 60 90

General measures 1st stage (0 10 minutes) 2nd stage (0 60 minutes) 3rd stage (0 60/90 minutes) 4th stage (30 90 minutes) Assess cardiorespiratory function Secure airway and resuscitate Administer oxygen Institute regular monitoring Emergency AED therapy Set up intravenous lines Emergency investigations Administer glucose and/or thiamine Treat acidosis if severe Establish aetiology Identify and treat medical complications Pressor therapy when appropriate Transfer to intensive care EEG monitoring ICP monitoring where appropriate FBC, liver and renal function, glucose, calcium, Mg, clotting, blood gases, AED and other drug levels, store 50mls

General measures 1st stage (0 10 minutes) 2nd stage (0 60 minutes) 3rd stage (0 60/90 minutes) 4th stage (30 90 minutes) Assess cardiorespiratory function Secure airway and resuscitate Administer oxygen Institute regular monitoring Emergency AED therapy Set up intravenous lines Emergency investigations Administer glucose and/or thiamine Treat acidosis if severe Establish aetiology Identify and treat medical complications Pressor therapy when appropriate Transfer to intensive care EEG monitoring ICP monitoring where appropriate CT MRI CSF blood cultures

Early phase (0 10/30 mins) Benzodiazepines - Lorazepam 4 mg (IV bolus; rate not critical) - Diazepam 10-20mgs (IV bolus; not more than 5mg/min) repeat after 10 mins if no response Ref.

Established phase (10/30 60/90 mins) Intravenous infusions Phenobarbitone 10mg/kg, max rate 100mg/min OR Phenytoin 15mg/kg, max rate 50mg/min OR Sodium Valproate 15-45mg/kg (75kg = 2250mg) OR Levetiracetam IV bolus 500 2000mg Ref.

Refractory phase (>60/90 mins) ITU Propofol IV bolus 2mg/kg, then 5-10mg/kg/hr, OR reduced to 1-3mg/kg/hr Thiopental IV bolus of 100-250mg over 20sec, with OR further 50mg boluses every 2-3min until seizures controlled, then 3-5mg/kg/hr Midazolam IV bolus 0.1-0.3 mg/kg, max rate 4mg/min, Ref. then infusion 0.05-0.4 mg/kg/hr Claasen J et al. Epilepsia. 2002;43(2):146-153