Epilepsy Dr Desiree Fernandez UCC 7 th March 2010

1. Epilepsy Dr Desiree Fernandez UCC 7th March 2010

2. Definitions • Seizure: manifestation of an abnormal and excessive synchronised discharge of a set of cerebral neurones • Epilepsy: a condition in which the sufferer is prone to experience recurrent seizures (eg person having had 2 or more seizures) • Status epilepticus: traditionally defined as a condition in which epileptic seizures continue, or are repeated without regaining conciousness, for a period of 30 mins or more (different authorities debate time range of 5-60 mins) • Provoked seizures: seizures which have an obvious and immediate preceding cause (eg acute systemic, metabolic or toxic insult; or acute cerebral event such as stroke, trauma, infections)

3. Seizure Types • International League Against Epilepsy (ILAE) • Partial onset seizures • Generalised onset seizures • Unclassified epileptic seizures

4. Partial (Focal) Seizures • Simple partial seizures • Complex partial seizures • Partial seizures evolving to secondarily generalised seizures

5. Partial (Focal) Seizures • Simple partial seizures • Focal motor with or without march • clonus (jerking) is the commonest; • usually occur in epilepsy arising from frontal or central regions • Somatosensory or special sensory symptoms: • Tingling/ numbness/ electric shock-like feeling (less common)/ burning/ pain/ feeling of heat • Visual, auditory, gustatory, olfactory, vertiginous • Simple hallucinations • Autonomic symptoms • Changes in skin colour, blood pressure, heart rate, pupil size, piloerection • Usually occurs as part of generalised or complex partial seizures of frontal or temporal origin

6. Partial (Focal) Seizures • Simple partial seizures • Psychic symptoms (auras), are more common in complex partial than in simple partial seizures. • Dysphasic symptoms: cortical speech areas (dominant frontal/ temporoparietal cortex). Repetitive vocalisation with formed words may occur with complex partial seizure originating from non-dominant temporal lobe. • Dysmnestic symptoms (disturbance of memory): flash backs, deja vu, jamais vu, panoramic experiences (recollections of previous experiences, former life or childhood memory). Most common in mesial temporal lobe seizures • Cognitive symptoms: dreamy states/ sensations of unreality/ depersonalisation. Most common in temporal lobe seizures. • Affective symptoms: fear (commonest), depression, anger, elation,irritability, erotic thoughts, serenity. Most commonly seen in mesial temporal lobe seizures. Laughter without mirth occurs in epilepsy of frontal origin. • Illusions: of size, shape, weight, distance, sound. Usually features in temporal or parieto-occipital epileptic foci. • Structured hallucinations (visual, auditory, gustatory, olfactory): crude/ elaborate hallucinations caused by temporal or parieto-occipital epileptic foci.

7. Partial (Focal) Seizures • Complex partial seizures • Aura (as in simple partial seizures): usually lasting few seconds; only rarely prolonged • Altered conciousness: follows the aura or occur simultaneously. This may occur as an absence and motor arrest. The patient may have no outward sign apart from appearing vacant or glazed. There may be associated spasm, posturing or mild tonic jerking • Automatisms: defined as involuntary motor actions which occur during or in the aftermath of epileptic seizures, in a state of unconciousness. There is total amnesia for the event. Most commonly occurs in temporal or frontal lobe seizures.

8. Partial (Focal) Seizures • Complex partial seizures • Types of automatisms: • Oro-alimentary: orofacial movements such as lip smacking, chewing, swallowing or drooling. Most common in mesial temporal lobe seizures • Mimicry: displays of laughter/ fear/ anger/ excitement • Gestural: fiddling movements with hands, tapping, patting, rubbing, ordering, tidying movements. Complex actions eg undressing, genitally directed actions • Ambulatory: walking, circling, running • Verbal: meaningless sounds, humming, whistling, grunting, repeated words, formed sentences • Responsive: quasi-purposeful behaviour, seemingly responsive to environmental stimuli • Violent behaviour: these are never premeditated, never remembered, never highly coordinated or skilful and never goal directed

9. Partial (Focal) Seizures • Complex partial seizures • Arise from temporal lobe in 60% of cases • Arise from frontal lobe in 30% of cases • 10-50% of scalp EEG may be unchanged • EEG: localised spike and wave/ spikes/ sharp waves/ slow activity/ flattening may be seen • Partial seizures evolving to secondarily generalised seizures (tonic/ clonic/ tonic-clonic) • Simple partial to generalised • Complex partial to generalised • Simple partial to complex partial to generalised

10. Generalised Seizures (Non-Convulsive) • Typical absence seizures(petit mal) • Abrupt, sudden loss of conciousness (absence) and cessation of motor activity. • Patient is unaware (appears glazed/vacant) and is inaccessible. • Tone is usually preserved and there is no fall. • Attack ends abruptly and previous activity is resumed. • Patient has no recollection of event • There is no confusion • > 80% of attacks last < 10 sec., but attacks can be repeated and often cluster • Attacks are often worse when the patient is awakening or drifting to sleep • Attacks may be precipitated by fatigue, drowsiness, photic stimulation, hyperventilation, relaxation. • Typically develop in childhood or adolescence • EEG: 3 Hz spike and wave. Interictal EEG is normal • Other phenomena eg blinking, slight clonic movements, alterations in tone, brief automatisms can occur in longer attacks

11. Generalised Seizures • Atypical absence seizures. Differ from typical absence seizures: • Longer seizure duration, attacks may wax and wane • Incomplete loss of awareness • Incomplete amnesia of event • Onset and cessation of attacks are not as abrupt • Tone changes are more severe and there may be atonic/ clonic/ tonic phenomena, automatisms, autonomic disturbance • EEG: Diffuse, but assymetrical and irregular spike and wave bursts (2-2.5 Hz), but may be variable also. Interictal EEG is abnormal: continuous slowing, spikes or irregular spike and wave activity. • Seizures often not induced by hyperventilation or photic stimulation • Associated learning diificulties or other neurological abnormalities may be present • Patients may also have other (multiple) seizure types • May manifest at any age

12. Generalised Seizures • Myoclonic seizures • Brief contraction of a muscle, muscle group, or several muscle groups caused by cortical discharge • Can be single or repetitive • Severity range from imperceptible twitch to severe jerking (may result in propulsion of hand-held objects/ fall) • Recovery is immediate and conciousness is not lost • Myoclonus can be induced by action, noise, startle, photic stimulation or percussion • If occuring as part of idiopathic generalised seizures, myoclonus occurs on waking or on dropping off to sleep • May occur at any age • EEG: generalised spike/ spike and wave/ polyspike and wave, often assymmetrical and irregular, frequently predominant in frontal area. Interictal EEG varies depending on underlying epilepsy aetiology.

13. Generalised Seizures • Clonic seizures • Clonic jerks, which are often asymmetrical and irregular • Most frequent in neonates, infants or young children • Always symptomatic • EEG: fast activity (10 Hz)/ fast activity mixed with larger amplitude slow waves/ rarely, polyspike and wave or spike and wave discharges

14. Generalised Seizures • Tonic seizures • Tonic muscle contraction with altered conciousness without a clonic phase • There is extension of the neck, contraction of facial muscles,eyes opening widely with upturning of eyeballs; contraction of respiratory muscles; and spasm of the proximal upper limb muscles, which causes abduction and elevation of shoulders and semiflexed arms. • If the tonic contraction spreads distally, the arms rise up and are held as if defending the head against a blow and the lower limbs become forcibly extended or contracted in triple flexion. • The spasm may fluctuate causing head nodding, or slight alterations in limb posture. There may be a cry followed by apnoea. • Seizures usually last <60 secs • EEG: flattening (desynchronisation)/ fast activity (15-15 Hz) with increased amplitude as the attack progresses/ rhythmic discharges (10 Hz). Scalp EEG recording is also often obscured by artefacts from muscle contraction. Interictal EEG is seldom normal. • Occurs at all ages • Occurs in the diffuse cerebral damage and learning disability • Often associated with other seizure types

15. Generalised Seizures • Tonic-clonic seizures (Grand mal seizures) • Seizure is initiated with loss of conciousness, patient will fall if standing and there is a brief period of tonic flexion, followed by a longer phase of rigidity and axial extension. The eyes would rolled up, jaw clamped shut, limbs stiff, adducted and extended with the fist clenched or held in the main d'accoucheur position. Respiration ceases and cyanosis is common. This tonic stage lasts 10-30 secs. • Clonic phase follows, involving generalised convulsions of limbs, jaw, facial muscles. Breathing may be stertorous. Tongue biting may occur. Mouth frothing may occur. Autonomic features (flushing, BP changes, pulse rate changes, increased salivation) are common. This clonic phase lasts 30-60 secs and is followed by a brief tonic muscle contraction during which urinary incontinence may occur. The final phase is characterised by muscle flaccidity and lasts between 2-30 mins. Consciousness is slowly regained. Plantar responses are usually extensor and tendons are diminished. Patient may fall asleep. Muscle soreness and headache may occur post-ictally. • Occurs at any age • Occurs in many variety of epilepsy syndromes, including idiopathic generalised epilepsy • Pre-ictal EEG: spike and wave/ spike paroxysms • Interictal EEG variable dependent on underlying pathology.

16. Generalised Seizures • Tonic-clonic seizures (Grand mal seizures) • EEG:Tonic phase: generalised flattening, followed by low voltage activity, which increase in amplitude. These are followed by slow waves with increasing amplitude and decreasing frequency (3->1 Hz) • EEG: Clonic phase: Slow waves are interrupted by bursts of faster activity (10 Hz) corresponding to clonic jerks. As the phase progresses, the slow waves widen and these bursts become less frequent. Readings are often obscured by muscle artefacts. • Post-ictal EEG: silent for few seconds, then slow delta activity develops. This can last from minutes to hours.

17. Generalised Seizures • Atonic seizures • The classic drop attack is the most severe form, in which all postural tone is suddenly lost, causing the patient to collapse like a rag doll. • Tone change can be limited with sagging at knee, bowing of knees, nodding of head, or can develop in a stepwise fashion. • Seizures are short-lasting and recovery is immediate. • Occurs at any age • Are always associated with diffuse cerebral damage, learning disability and are common in severe symptomatic epilepsies • EEG: irregular spike and wave/ polyspike and wave/ slow wave/ low amplitude fast activity/ a mixture • Interictal EEG: diffuse abnormalities

18. Management of 1st Seizure • History taking • Witness account of event • Seizure risk • prenatal/ perinatal history (eg infection during pregnancy, premature birth etc) • family history of epilepsy, • history of head injury/ meningitis/ encephalitis/ intracranial pathology(stroke/ tumour/ AVM) • previous febrile convulsions • excessive alcohol use • illicit drug use • sleep deprivation • Drug history • antidepressants eg bupropion, tricyclics • antipsychotic medications eg chlorpromazine, haloperidol, clozapine • aminophylline • high doses of penicillin • lithium • Analgesic (eg tramadol)

19. Management of 1st Seizure • Investigations • Blood/ urine test • Electrolyte imbalance (Na, Ca, Mg) • Renal failure/ Uremia • Liver failure • Hypo/ Hyperglycaemia • Hypoxia • Illicit drug levels • EEG • CT / MRI brain • Points to note: • 1st seizure may present as status epilepticus • Usually, no AED is required unless present as status epilepticus or if there is pathology that would cause seizure recurrence • Advice need to be given re: driving/ lifestyle

20. Management of Status Epilepticus • General resuscitation • Protection of cardiopulmonary function • Protect airways • Give oxygen • +/- intubation • Monitoring • Regular neurological observation (eg GCS) • ECG/ BP/ temperature/ oximetry • Glucose/ electrolytes/ ABG • Emergency investigations • FBC/ U&E/ LFT/ Ca/ Mg/ blood glucose/ clotting screen/ ABG/ serum anti-convulsant levels • Emergency drug treatment

21. Management of Status Epilepticus • Emergency drug treatment • 50 ml of 50% glucose, if suspected hypoglycaemia • 250 mg thiamine in alcoholics / poor nutrition state (IV glucose alone can precipitate Wernicke's encephalopathy in such individuals) • Pre-hospital setting: 10 mg diazepam (rectal) or 10 mg midazolam (buccal) • IV lorazepam 4mg (2mg/min), if seizure continues or recurs, repeat dose • IV phenytoin infusion (load at 15-20 mg/kg at 50mg/min), watch for cardiac arrhythmias and hypotension OR IV fosphenytoin infusion (15-20mg/kg at 100-150mg/min) • General anaesthesia with IV propofol (loading dose 2mg/kg, maintenance dose 0.1-0.2 mg/kg/min) OR phenobarbital 15-20mg/kg (max infusion rate: 100mg/min) • ICU monitoring is required • Other points to note: • Valproate is useful in non-convulsive status epilepticus • IV levatiracetam (keppra) may be useful in some refractory status epilepticus (anecdotal evidence based on few case reports)

22. Diagnosis and implications of epilepsy • Epilepsy is defined if there are 2 or more seizures • Epilepsy impacts on: • Driving (see later slides) • Work: unable to perform work at heights (eg builder on scaffolding), or near high voltage cables, or where there is a risk of falling into water, or which involves driving • Social: epileptics may have relationship difficulties, social life may be curtailed due to seizure triggers, drugs/ epilepsy syndromes may slow mentation/ learning and impact on school performance

23. New Irish Driving Regulations December 2010 • Group 1: Cars, Light Vans and Motorcycles • The main seizure freedom period for personal driving in categories A1, A, B, EB, M or W (car, light van or motorcycle) remains the same at one year of seizure freedom. • Provoked seizures: a person who has had a provoked epileptic seizure due to a recognizable provoking factor that is unlikely to recur at the wheel may be declared able to drive on an individual basis subject to neurological opinion. (Previously six months) • Sleep seizures: For persons who have seizures exclusively in sleep they may be declared fit to drive once this pattern has been established for no less than one year. (Previously 2 years). If a further occurrence of a seizure happens in waking a one year seizure freedom period is required. • Seizures without influence on consciousness or the ability to act – persons with who have never had any seizures other than seizures which have been demonstrated to affect neither consciousness nor cause any functional impairment can be declared fit to drive once this pattern has been established for no less than one year (was previously subject to neurological opinion). If there is an occurrence of any other kind of seizure then a one year seizure freedom period is required. • Initial or isolated seizures: a person who has had an initial seizure or loss of consciousness should be advised not to drive and a specialist report is required regarding the period of driving prohibition and follow up to be undertaken. • First or single unprovoked seizures: a person who has had a first unprovoked epileptic seizure may be declared fit to drive after a period of six months seizure freedom with an appropriate medical assessment preferably a Neurological assessment.

24. New Irish Driving Regulations December 2010 • Seizures associated with a physician directed change or reduction of anti‐epileptic therapy: in such cases the person may be advised not to drive from the beginning of the period of withdrawal and for six months after stopping of treatment. Seizures which occur during the physician advised change or withdrawal of medication require three months off driving if previously effective treatment is reinstated. • Surgery In cases where a person has had curative epilepsy surgery the seizure freedom period prior to licensing is the same as the main seizure freedom period for epilepsy i.e.1 year. The new regulations provide definitions of epilepsy and provoked seizures. • Epilepsy: common medical disorder characterised by recurrent seizures, as defined by having had 2 or more epileptic seizures less than five years apart. • Provoked epileptic seizure: seizure which has a recognisable causative factor that is avoidable. The new regulations state that all drivers with epilepsy should be under annual licence review until they have been seizure free for a period of at least five years. Persons with epilepsy will not meet the criteria for unconditional licencing (10 year licence) and notification should be given to the licensing authority.

25. New Irish Driving Regulations December 2010 • Group 2: Lorries, Buses, Heavy Goods Vehicles • In the case of applicants with epilepsy for licencing in respect of heavy goods vehicles C1, C, D1, D,EC1, EC, ED1 or ED the directive permits for persons to be licenced to drive in these categories provided 10 years of seizure freedom have been achieved without the aid of anti‐epileptic drugs. • A permit may be granted in less time in the case of those with good prognostic indicators and in similarly in cases of juvenile epilepsy. Appropriate medical follow up must be completed and satisfactory result on neurological investigations. All persons are to be under licence review until they have been seizure free for at least 5 years. • Persons who have had a provoked seizure due to a recognizable provoking factor that is unlikely to recur at the wheel may be declared eligible to drive on an individual basis subject to neurological opinion with appropriate assessments having been completed after the acute episode. • First or single unprovoked seizures the person may be declared fit to drive in these categories once 5 years seizure freedom has been achieved without the aid of anti‐epileptic drugs. Drivers with good prognostic indicators may drive sooner. • Seizures due to drug or alcohol misuse, sleep deprivation or structural abnormality are not considered provoked seizures for licensing purposes. • Reports of seizures due to side effects of prescribed medication do not automatically imply that such events will be considered as provoked. • Seizures which may be considered provoked include eclamptic seizures, reflex anoxic seizures, immediate seizure seconds after head injury, seizure in the first week post head injury not associated with damage on CT or MRI nor with post amnesia of more than 30 minutes, seizures at time of stroke/TIA or within 24 hours of same, seizures during inter‐cranial surgery or the ensuing 24 hours. • Seizures associated with acute exacerbation of Multiple Sclerosis or Migraine need to be assessed on an individual basis by a Neurologist.

26. SUDEP • SUDEP is defined as the sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death of patients with epilepsy, with or without evidence of a seizure, excluding documented status epilepticus, and in whom post mortem examination does not reveal a structural or toxicological cause of death. • Incidence: 0.09/1000 person years in newly diagnosed patients to 9.3/1000 person years in epilepsy surgery candidates • Risk factors: • Young age • Male gender • Untreated seizures • Nocturnal seizures • Poor compliance to AEDs • Poorly controlled seizures • Polytherapy • Tonic-clonic seizures

27. SUDEP • Mechanism of death thought to be cardiorespiratory (ictal bradycardia and asystole/ central apnoea). In few observed cases, ictal EEG slowing/ flattening has been noted prior to cardiorespiratory failure--> this was interpreted as 'CNS shut-down' • Prevention • Avoidance of seizure triggers eg avoid excessive alcohol/ sleep deprivation/ stress etc • Good seizure control • Supervision during sleep • Avoidance of prone position in sleep/ use of anti-smother pillow or no pillow • Use of permanent cardiac pacemakers in select few • None of the above are fail safe and are based on small studies

28. Epilepsy in women • Catamenial seizures • Use of acetazolamide/ clobazam • Interaction with contraceptive drugs • Metabolism of contraceptive hormones are affected by AEDs (via cytochrome P450 enzyme system) • Enzyme inducing AEDs: carbamazepine, oxcarbazepine, phenytoin, barbiturates (phenobarbital, mephobarbital and primidone),topiramate. • Enzyme inhibiting AEDs: valproate and felbamate • No effect on enzyme: gabapentin, lamotrigine, levetiracetam, tiagabine,lacosamide. • Oral contraceptives used by women with epilepsy taking cyP450-inducing AEDs may need to contain higher amounts of estrogen (50 mcg or more), and/ or taken without the 7 day pill free break. • Intramuscular medroxyprogesterone (DepoProvera) is usually given as 150 mg every 12 weeks. Women with epilepsy taking cyP450-inducing AEDs may need the dosage interval of this contraceptive decreased to every 6 to 8 weeks. • The reliability of progesterone only contraceptives may be compromised by AEDs affecting the cyP450 system. • Consider IUD/ barrier methods

29. Epilepsy in women • Fertility • Lower in epileptics (psychological/ biological factors) • Teratogenicity • Various pregnancy registries (North American, UK, Australian, Irish, Lamotrigine etc) • Valproate and barbiturates most teratogenic (although barbiturate teratogenic rates were more significant in North American Register compared to other registers) • Lamotrigine least teratogenic • Monotherapy vs polytherapy • Folic acid supplementation • Collaboration between neurologist and obstetrician • Pre-pregnancy planning (where possible) • Folic acid • Monotherapy, where possible • Advise women NOT to stop AED, if they discover that they are pregnant

30. Thank you