Epilepsy

DR ZAKI NOAH HASAN Professor of neurology

Seizure
An epileptic seizure : is any clinical event caused by an abnormal electrical discharge in the brain EPILEPSY : is the tendency to have recurrent seizures


FIRST UNPROVOKED SEIZURE : recurrence rate = 70 % Epilepsy Incidence rate: 50 and 120 per 100,000 per yearEpilepsy Prevalence rate has been found to be 4–10 cases per 1000 persons Standardized mortality rates are 2–3

NORMALLY inhibitory circuits limit synchronous discharge amongst neighboring groups of neurons. The inhibitory transmitter gamma-aminobutyric acid (GABA)
inhibitory transmitter
Excitatory transmitter

Excitatory transmitter

inhibitory transmitter
Reduction in inhibitory systems and excessive excitation play a part in the genesis of seizure activity
excitatory neurotransmitters: acetylcholine glutamate aspartate
gamma-aminobutyric acid (GABA)



The chief division of seizure types on physiological grounds is between
generalized seizures where the electrophysiological abnormality involves both hemispheres simultaneously and synchronously
partial (focal) seizures in which paroxysmal neuronal activity is limited to one part of the cortex

Secondary generalized

Generalized seizures (convulsive and non-convulsive)A. Absence seizures 1. Absence seizures 2. Atypical absence seizuresB. Myoclonic seizuresC. Clonic seizuresD. Tonic seizuresE. Tonic–clonic seizuresF. Atonic seizures CLASSIFICATION OF EPILEPSY


11-- Partial (focal, local) seizures A. Simple partial seizures 1. With motor signs 2. With somatosensory or special sensory symptoms 3. With autonomic symptoms or signs 4. With psychic symptoms B. Complex partial seizures 1. Simple partial onset followed by impairment of consciousness 2. With impairment of consciousness at onset C. Partial seizures evolving to secondarily generalized seizures 1. Simple partial seizures evolving to generalized seizures 2. Complex partial seizures evolving to generalized seizures 3. Simple partial seizures evolving to complex partial seizures evolving to generalized seizures. 111-- Unclassified epileptic seizures
CLASSIFICATION OF EPILEPSY

Partial seizuresSimple partial seizures

1--Motor : jerking, spasm or posturing, speech arrest, dysartheria, choking sensations, version of the head or eyesTodd’s paralysis can occur after a seizure 2-- Sensory : tingling or numbness or pain. Visual phenomena such as flashing lights and colors
4--Autonomic symptoms occur such as changes in skin color, blood pressure, heart rate, pupil size and piloerection.
4--psychic symptoms: such as fear d javu james vu



Complex partial seizures
three distinct components:The aura The loss of consciousness: characterized by motor and speech arrest, during which the patient appears vacant (the ‘motionless stare’). The automatism. Automatisms are defined as involuntary motor actions that occur during or in the aftermath of epileptic seizures,[chewing, lip smacking, swallowing or drooling , fiddling movements , Verbal automatisms , Violent behavior

Automatisms

Tonic–clonic seizure (grand mal seizure) prodromal period during which an attack is anticipated, [ an ill-defined vague feeling or increasing myoclonic jerking
Aura: then occurs (in fact a simple or complex partial seizure) in the seconds before attack, this indicates that the tonic–clonic seizure is secondarily generalized Generalized seizures

Tonic seizure

Tonic stiffening : Cry (a loud guttural sound), then patient will fall if standing) initially in flexion but then in axial extension, with the eyes rolled up, the jaw shut, the limbs stiff, adducted and extended, and the fists clenched. Respiration ceases and cyanosis is common. The eyes remain open with the dilated and unreactive pupils upturning of the eyeballsTachycardia or bradycardia and even asystole. This tonic stage lasts on average 10–30 seconds

The clonic phase

during which convulsive movements, usually of all four limbs, jaw, and facial muscles occur; breathing can be stertorous and arrest of respiration can occur saliva (sometimes bloodstained owing to tongue biting) may froth from the mouth. The convulsive movements decrease in frequency (eventually to about four clonic jerks per second), and increase in amplitude as the attack progresses. The attack is usually followed by a period of flaccidity of the muscles and consciousness is slowly regained. Confusion is invariable in the post-ictal phase.

Generalized seizures Absence seizure

sudden loss of consciousness (the absence) cessation of all motor activity. Tone is usually preserved, and there is no fall last less than 10 seconds repeated, sometimes hundreds of times a day Absences may be precipitated by fatigue, drowsiness, relaxation, photic stimulation or hyperventilation. Poor schooling

EEG : showing high voltage, regular, symmetric and synchronous 3 Hz spike-wave paroxysms

Absence seizure

Generalized seizures Myoclonic seizure

twitch to a severe jerking, resulting, for instance, in a sudden fall or the propulsion of handheld objects. consciousness was not lost. Treatment of myoclonic epilepsies (1) Clonazepam: (2) VPA (3) Topiramate (4) Zonisamide:


Atonic seizure The most severe form is the classic drop attack (astatic seizure) in which all postural tone is suddenly lost causing collapse to the ground
Clonic seizure Clonic seizures are most frequent in neonates, infants or young children, and are always symptomatic.

An epileptic syndrome

an epileptic disorder characterized by a cluster of signs and symptoms customarily occurring together, and the ILAE classification scheme attempts to categorize epilepsy according to syndrome into : Generalized Localization-related epilepsies 3. Epilepsies and syndromes undetermined as to whether focal or generalized 4. Special syndromes

Generalized

Idiopathic generalized epilepsies with age-related onset (in order of age)Benign neonatal familial convulsionsBenign neonatal convulsionsBenign myoclonic epilepsy in infancyChildhood absence epilepsyJuvenile absence epilepsyJuvenile myoclonic epilepsyEpilepsy with generalized tonic–clonic seizures on awakeningOther generalized idiopathic epilepsys not defi ned aboveEpilepsies with seizures precipitated by specific modes of activationCryptogenic or symptomatic generalized epilepsies (in order of age)West’s syndromeLennox–Gastaut syndromeEpilepsy with myoclonic astatic seizuresEpilepsy with myoclonic absencesSymptomatic generalized epilepsiesNon-specifi c aetiology• Early myoclonic encephalopathies• Early infantile encephalopathy with burst suppression• Other symptomatic epilepsies not defi ned aboveSpecifi c syndromesEpilepsies in other disease states Localization-related epilepsies
Idiopathic with age-related onset Benign epilepsy with centrotemporal spikes Childhood epilepsy with occipital paroxysms Primary reading epilepsy Symptomatic Epilepsia partialis continua Syndromes of specific modes of precipitation Temporal lobe epilepsies Frontal lobe epilepsies Parietal lobe epilepsies Occipital lobe epilepsies Reflex epilepsies Idiopathic
ILAE classification

Epilepsies and syndromes undetermined as to whether focal or generalized

With both generalized and focal seizures Neonatal seizures Severe myoclonic epilepsy in infancy Electrical status epilepticus in slow-wave sleep Acquired epileptic aphasia Other undetermined epilepsies (not defi ned above) with unequivocal generalized or focal features
Special syndromes
Febrile convulsions Isolated seizures or isolated status epilepticus Seizures occurring only when there is an acute metabolic or toxic event due to factors such as alcohol, drugs, eclampsia, non-ketotic hyperglycinaemia

Childhood absence epilepsy

more common in girlsappears in childhood (peak age 6–7 years), and is not associated with learning disability or other neurological problems.abrupt sudden loss of consciousness and the cessation of all motor activity. Tone is preserved, and there is no fall.ends as abruptly as it started, and previous activity is resumed as if nothing had happenedAbout one-third of patients also develop generalized tonic–clonic seizures80% got remission 20% of previously diagnosed patients are still having seizuresa regular 3-Hz spike-wave.

Juvenile myoclonic epilepsy

the most common subtype of Idiopathic Generalized Epilepsy Age of onet [12 and 18 years]Types of seizures in JME = myoclonic -+-generalized tonic-+– clonic seizures-+- typical absence seizuresGenetically localized to chromosome 6pbrief myoclonic jerks, occurring in the first hour or so after awakening Bursts of sudden, shock-like jerks, affecting mainly the shoulders and arms, usually but not always symmetricallyThe myoclonic seizures (and other seizures) can be precipitated by photic stimuli, lack of sleep, alcohol, hypoglycaemia and poor compliance with medicationTreatment of choice for JME is valproate (VPA), recurrence is likely if treatment is stopped.

Benign partial epilepsy with centrotemporal spikes[benign epilepsy with rolandic spikes)

the most common ‘idiopathic’ partial epilepsy syndrome[15% of all epilepsies]age of onset is at 4–10 years.characteristic EEG feature is the high-amplitude rolandic spikespasm and clonic jerking of one side of the face and throat muscles, then speech arrest and guttural vocalizationsThe epilepsy ceases in almost all cases, usually by the age of 12 years, without long-term sequalae. There is an excellent response to therapy with carbamazepine or other antiepileptic drugs.

West syndrome

The infantile spasms take the form of sudden, generally bilateral and symmetrical contractions of the muscles of the neck, trunk or limbs cluster and may occur hundreds of times a day. In the most common type, the flexor muscles are predominantly affected, and the attack takes the form of sudden flexion with arms and legs held in adduction (the so-called salaam attacks). develop in the first year of life The most common cause is tuberous sclerosis AND neonatal ischemia severe epilepsy, intellectual and psychomotor deterioration. EEG: hypsarrhythmia Treatment: adrenocorticotropic hormone The prognosis is poor


Lennox–Gastaut syndrome The age of onset is between 1 and 7 yearsIn one-third of cases no cause is identifiable (cryptogenic Lennox–Gastaut syndrome). About one-third of cases are caused by malformations of brain development.atypical absence, tonic, myoclonic, tonic and tonic–clonic seizures, and later complex partial50% of cases have an (IQ) below 50.Response to treatment is often poorCarbamazepine and benzodiazepines may exacerbate tonic or atonic seizures

Febrile seizures

children between 3 months and 5 years of agethe seizures are generalized and briefpre-existing neurodevelopmental in 1-5%febrile convulsions can sometimes cause hippocampal sclerosis, and by this mechanism subsequent temporal lobe epilepsy13% incidence of epilepsy if at least two factors a. Family history of nonfebrile seizures b. Abnormal neurologic examination or development c. Prolonged febrile seizure d. Focal febrile seizure with Todd’s paralysis

Frontali. Approximately 20% of partial seizuresii. Unilateral or bilateral (asymmetric) tonic posturing (bicycling and fencing posture)iii. Short duration (20–30 seconds) with minimal postictal confusioniv. Awareness and memory may be retained unless temporal spread presentPosterior frontal may have focal clonic movements but no loss of awarenessvii. Prominent nocturnal pattern—often 5–10 or more seizures in one nightViii Versive seizures frontal epileptic focus may involve the frontal eye field, causing forced deviation of the eyes and sometimes turning of the head to the opposite side



Temporal i. Approximately 70% of partial seizuresii. Aura of deja vu, epigastric sensation (rising), fear/anxiety, or olfactory sensationiii. Stare and nonresponsiveiv. Oral and manual automatismsv. Usually 60–90 secondsvi. Contralateral, early dystonic upper extremity posturing has lateralizing valuevii. Postictal language disturbance when seizures originate in dominant hemisphere

TRIGGER FACTORS FOR SEIZURES

Sleep deprivation Alcohol (particularly withdrawal) Recreational drug misuse Physical and mental exhaustion Flickering lights, including TV and computer screens (primary generalised epilepsies only) Intercurrent infections and metabolic disturbances Uncommonly: loud noises, music, reading, hot baths

PRIMARY GENERALISED EPILEPSIES

Incidence
Age of onset
Type of seizure
EEG features
Provoking factors
Treatment
Prognosis
Childhood absence epilepsy
6-8/100 000
4-8 yrs
Frequent brief absences
3/s spike and wave
Hyperventilation, fatigue
EthosuximideSodium valproate
40% develop tonic clonic seizures, 80% remit in adulthood
Juvenile absence epilepsy
1-2/100 000
10-15 yrs
Less frequent absences than childhood absence
Poly-spike and wave
Hyperventilation, sleep deprivation
Sodium valproate
80% develop tonic clonic seizures, 80% seizure-free in adulthood
Juvenile myoclonic epilepsy
25-50/100 000
15-20 yrs
GTCS, absences, morning myoclonus
Poly-spike and wave, photosensitivity
Sleep deprivation, alcohol withdrawal
Sodium valproate
90% remit with sodium valproate but relapse onAED withdrawal
GTCS on awakening
Common
10-25 yrs
GTCS, sometimes myoclonus
Spike and wave on waking and sleep onset
Sleep deprivation
Sodium valproate
65% controlled with AEDs but relapse off treatment



Causes of epilepsy . Primary generalized Idiopathic (30%) Secondary generalized 1-Vascular (ischemia, hemorrhage), subarachnoid hemorrhage, arteriovenous malformation, cavernous malformation, venous sinus thrombosis 2-Congenital: Inborn erros: eg., gangliosidoses, glycogen storage diseases 3-Neurodegenerative/ neurological conditions 4-Hippocampal sclerosis 5-Neoplasm 6-Trauma 7-metabolic hyponatremia, hypocalcemia, hypomagnesemia, hypophosphatemia, hypoglycemia , hyperglycemia, hyperthyroidism, thyrotoxicosis, uremia, 8-Genetic (single gene disorder) 9-Infections and Inflammation 10-Drugs, alcohol and toxins

Infection :Meningitis . Encephalitis i. Herpes simplex virus 1: most commonly causes temporal lobe seizures ii. Herpes simplex virus 2: infection acquired in birth canal iii. Human immunodeficiency virus c. Brain abscess Toxic : Alcohol toxicity or withdrawal Barbiturate toxicity or withdrawal Benzodiazepine toxicity or withdrawal Cocaine Common medications that cause seizures i. Antidepressants (tricyclic antidepressants, bupropion) ii. Antipsychotics (chlorpromazine, thioridazine, trifluoperazine, perphenazine, haloperidol) iii. Analgesics (fentanyl, meperidine, pentazocine, propoxyphene, tramadol iv. Local anesthetics (lidocaine, procaine) v. Sympathomimetics (terbutaline, ephedrine, phenylpropanolamine) vi. Antibiotics (penicillin, ampicillin, cephalosporins, metronidazole, isoniazid, pyrimethamine) vii. Antineoplastic agents (vincristine, chlorambucil, methotrexate,cytosine arabinoside : cyclosporine,) viii. Bronchodilators (aminophylline, theophylline) x. Others (insulin, antihistamines, atenolol, baclofen, cyclosporine)
Causes of epilepsy

Genetic

hypomelanotic macules
facial angiofibromas
shagreen patches
subungual fibromas
autosomal dominant
Epilepsy ALL FORMS SKIN delay or mental retardation
(MRI) studies and comprise: subependymal glial nodules subependymal giant cell astrocytomas, renal tumors


Sturge–Weber syndromeSPORADIC port wine naevus in the distribution of the trigeminal nerveThe epilepsy can be focal or generalized.hemiplegia and mental impairment

Genetic

Seizure
-
+
Aura (e.g. olfactory)
-
+
Cyanosis
-
+
Tongue-biting
-
+
Post-ictal confusion
-
+
Post-ictal amnesia
-
+
Post-ictal headache
+
-
Rapid recovery
FEATURES HELPFUL IN DISTINGUISHING SEIZURES FROM FAINTS



Basic labsa. Electrolytes:↓Na+, Ca2+, Mg2+b. or ↓ glucosec. Platelets (thrombotic thrombocytopenic purpura, disseminated intravascular coagulopathy)d. Toxicology screen e. AED levelsf. vasculitis screen g. Infection: urinalysis, chest X-ray H- Lumbar puncture (LP) (perform if recent fever, atypical mental status changes Investigations

Epileptic nature of attacks?

Ambulatory EEG Videotelemetry
Standard EEG Sleep EEG EEG with special electrodes (foramen ovale, subdural
Type of epilepsy?
INVESTIGATION OF SUSPECTED EPILEPSY
CT MRI
Structural lesion?
Urea and electrolytes Liver function tests Blood glucose Serum calcium, magnesium
Metabolic disorder?
Full blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) Chest X-ray Serology for syphilis, HIV, collagen disease CSF examination
Inflammatory or infective disorder?

Investigations

the diagnosis of epilepsy is made primarily on the history, Any videotape recording the role of the EEG is to assist in the subsequent classification of the type of epileptic seizures and the epilepsy syndrome. The role of MRI is not to diagnose epilepsy, but to identify any underlying structural cerebral abnormality in those with diagnosed epilepsy.

Investigation of epilepsy

Electroencephalography (EEG) Is the paroxysmal event an epileptic seizure? Probability of recurrence after single unprovoked seizure Is seizure onset focal or generalized? For Syndromic classification To diagnose non-convulsive status?



To increased yield of EEG :1- additional electrodes2- combination of wake and sleep records3- activation procedures of hyperventilationand photic stimulation4- Ambulatory EEG monitoring5- In-patient video EEG telemetry units

MRI is generally the imaging modality of first choice for epilepsy.

computed tomography (CT) is useful in acute situations when MRI is not appropriate. CT is also helpful to identify focal cortical calcification and in diagnosing tuberous sclerosis and Sturge–Weber syndrome. CT is also helpful where there are contraindications to MRI, such as a cardiac pacemaker or cochlear implants. MRI is MORE sensitive and specific for identifying common epileptogenic abnormalities, such as indolent gliomas, cavernomas, malformations of cortical development (MCD) lesions in the medial temporal lobe.

Functional magnetic resonance imaging Functional MRI (fMRI) can visualize regional brain activity. The areas detected with changes in blood oxygenation level The most important clinical application of fMRI is in the localization and lateralization of cognitive functions prior to surgery in order to minimize the risk of causing a fixed deficit.
Magnetic resonance spectroscopy (MRS) provides measurements of specific brain metabolites. Metabolites that are detectable with MRS include N-acetylaspartate , choline, creatine, lactate, γ-aminobutyric acid and glutamate.There is evidence that NAA is located primarily within neurones and precursor cells. Creatine and choline are found in both neurones and glia. Accurate definition of brain anatomy and the identification of structural abnormalities .

Single-photon emission computed tomography (SPECT) allows measurements of regional cerebral blood flow changes in the areas affected by epileptic activity. IT is sensitive and specific in localizing seizure onset in intractable TLE subtraction ictal SPECT co-registered to MRI (SISCOM) improves the rate of localization used mainly in Extratemporal seizures particularly valuable in patients with normal MRI


Positron emission tomography (PET) maps cerebral glucose metabolism using 18F-deoxyglucose (18FDG). Interictally, PET shows areas of reduced glucose metabolism that usually include the seizure focus but are more extensive is in determining the lateralization of epileptic focus, especially in the presurgical assessment

Treatments for epilepsy

Anti-epileptic drugs (AEDs) Dietary therapy Vagus nerve stimulation Epilepsy surgery

First aid (by relatives and witnesses)

Move person away from danger (fire, water, machinery, furniture) After convulsions cease, turn into 'recovery' position (semi-prone) Ensure airway is clear Do NOT insert anything in mouth (tongue-biting occurs at seizure onset and cannot be prevented by observers) If convulsions continue for more than 5 minutes or recur without person regaining consciousness, summon urgent medical attention Person may be drowsy and confused for some 30-60 minutes and should not be left alone until fully recovered
IMMEDIATE CARE OF SEIZURES



Ensure airway is patent Give oxygen to offset cerebral hypoxia Give intravenous anticonvulsant (e.g. diazepam 10 mg) ONLY IF convulsions are continuous or repeated (if so, manage as for status epilepticus) Consider taking blood for anticonvulsant levels (if known epileptic) Investigate cause
Immediate medical attention

Treatment principles

Use one drug at a time (monotherapy), at least initially Initial titration should be to low maintenance doses Further upward titration will depend on response and side-effects If first drug fails, alternative monotherapies should be tried Upward and downward titration should be in slow, stepped doses Polytherapy should be used only if monotherapy will at least three first choice drugs has failed to control seizures Patients should be fully counseled about goals, role, risk, outcome and logistics of drug treatment

1st choice

2ed choice
Contraindicated
Myoclonic
Sodium valproate Topiramate Levetiracetam
Clobazam Clonazepam Lamotrigine Piracetam Zonisamide
Carbamazepine Gabapentin Oxcarbazepine Pregabalin Tiagabine Vigabatrin
Tonic
Lamotrigine Sodium valproate
Clobazam Clonazepam Levetiracetam Topiramate
Carbamazepine Oxcarbazepine
Atonic
Lamotrigine Sodium valproate
Clobazam Clonazepam Levetiracetam Topiramate
Carbamazepine Oxcarbazepine Phenytoin
Focal with/without secondary generalization
Carbamazepine Lamotrigine Levetiracetam Oxcarbazepine Sodium valproate Topiramate
Clobazam Gabapentin Pregabalin Tiagabine Zonisamide


CHRONIC Side-effects cognitive impairment –Tremor- obesity ovarian cyst visual field defectweight gain, weight lossbone marrow suppression, liver dysfunction dermatologic reactions +-- hair loss+ hairsutismbone disease stone formation poly neuropathy cerebellar degeneration Allergy Central nervous system side effects (dose dependent) drowsiness, headache dizziness, dysequilibrium cognitive dysfunction (memory)
Side-effects
Idiosynchratic reactions

Causes of drug failure:1- poor compliance 2- wrong diagnosis 3- incorrect classification4- wrong treatment modality dosing and combination

Seizure free : patient has to be free of seizure for at least 1 year or 3 times the longest interseizure interval
1 year freedom

Seizure free : patient has to be free of seizure for at least 1 year or 3 times the longest interseizure interval
1 year freedom

Status epilepticus (SE) is usually defined as seizure activity lasting for 30 minutes or more Manifesting either as continuous clinical seizure activity, or intermittent seizures without recovery of consciousness in between.
Types Tonic-Clonic Status Epilepticus (TCSE) Absence Status Epilepticus Epilepsia Partialis Continua (EPC) Myoclonic Status Epilepticus Complex Partial Status Epilepticus
associated with significant mortality and morbidity in terms of cognitive and neurological deficit

Stage of early status (0–30 min)Lorazepam 4 mg IV bolus (can be repeated once)Ш (if seizures continue after 30 min)Stage of established status (30–60/90 min)Phenobarbital IV infusion 10 mg/kg at 100 mg/minorPhenytoin IV infusion 15 mg/kg at 50 mg/minorFosphenytoin IV infusion 15 mg PE/kg at 100 mg PE/minorValproate IV infusion 25 mg/kg at 3–6 mg/kg/minШ (if seizures continue after 30–90 min)Stage of refractory status (>60/90 min – general anaesthesia)Propofol: IV bolus 2 mg/kg,

congenital malformations is 2–3Ч normal risk; but continuing AEDs during pregnancy Valproate: higher incidence of congenital malformation ;higher rate of cleft palate. Seizure frequency may increase during pregnancy.Follow anticonvulsant levels every 4–6 weeks. Initiate folic acid, 4 mg/day, preconceptually Breast-feeding is not contraindicated, Valproic acid have been associated with an increased frequency of polycystic ovary syndrome.
Difficulties with conception
Women and Epilepsy

Epilepsy and driving

Driving is prohibited after a seizure with loss of consciousness Driving is permitted: 2-3 years of seizure free interval with patients on AEDs 2-3 years of seizure free interval after withdrawal of AEDs

Epilepsy

DR ZAKI NOAH HASAN PROFESSOR OF NEUROLOGY

An epileptic syndrome

an epileptic disorder characterized by a cluster of signs and symptoms customarily occurring together, and the ILAE classification scheme attempts to categorize epilepsy according to syndrome into : Generalized Localization-related epilepsies 3. Epilepsies and syndromes undetermined as to whether focal or generalized 4. Special syndromes

PRIMARY GENERALISED EPILEPSIES

Incidence
Age of onset
Type of seizure
EEG features
Provoking factors
Treatment
Prognosis
Childhood absence epilepsy
6-8/100 000
4-8 yrs
Frequent brief absences
3/s spike and wave
Hyperventilation, fatigue
EthosuximideSodium valproate
40% develop tonic clonic seizures, 80% remit in adulthood
Juvenile absence epilepsy
1-2/100 000
10-15 yrs
Less frequent absences than childhood absence
Poly-spike and wave
Hyperventilation, sleep deprivation
Sodium valproate
80% develop tonic clonic seizures, 80% seizure-free in adulthood
Juvenile myoclonic epilepsy
25-50/100 000
15-20 yrs
GTCS, absences, morning myoclonus
Poly-spike and wave, photosensitivity
Sleep deprivation, alcohol withdrawal
Sodium valproate
90% remit with sodium valproate but relapse onAED withdrawal
GTCS on awakening
Common
10-25 yrs
GTCS, sometimes myoclonus
Spike and wave on waking and sleep onset
Sleep deprivation
Sodium valproate
65% controlled with AEDs but relapse off treatment

West syndrome

The infantile spasms take the form of sudden, generally bilateral and symmetrical contractions of the muscles of the neck, trunk or limbs cluster and may occur hundreds of times a day. In the most common type, the flexor muscles are predominantly affected, and the attack takes the form of sudden flexion with arms and legs held in adduction (the so-called salaam attacks). develop in the first year of life The most common cause is tuberous sclerosis AND neonatal ischemia severe epilepsy, intellectual and psychomotor deterioration. EEG: hypsarrhythmia Treatment: adrenocorticotropic hormone The prognosis is poor

TRIGGER FACTORS FOR SEIZURES 

Sleep deprivation Alcohol (particularly withdrawal) Recreational drug misuse Physical and mental exhaustion Flickering lights, including TV and computer screens (primary generalized epilepsies only) Intercurrent infections and metabolic disturbances Uncommonly: loud noises, music, reading, hot baths

Causes of epilepsy . Primary generalized Idiopathic (30%) Secondary generalized 1-Vascular (ischemia, hemorrhage), subarachnoid hemorrhage, arteriovenous malformation, cavernous malformation, venous sinus thrombosis 2-Congenital: Inborn erros: eg., gangliosidoses, glycogen storage diseases 3-Neurodegenerative/ neurological conditions 4-Hippocampal sclerosis 5-Neoplasm 6-Trauma 7-metabolic hyponatremia, hypocalcemia, hypomagnesemia, hypophosphatemia, hypoglycemia , hyperglycemia, hyperthyroidism, thyrotoxicosis, uremia, 8-Genetic (single gene disorder) 9-Infections and Inflammation 10-Drugs, alcohol and toxins

Infection :Meningitis . Encephalitis i. Herpes simplex virus 1: most commonly causes temporal lobe seizures ii. Herpes simplex virus 2: infection acquired in birth canal iii. Human immunodeficiency virus c. Brain abscess Toxic : Alcohol toxicity or withdrawal Barbiturate toxicity or withdrawal Benzodiazepine toxicity or withdrawal Cocaine Common medications that cause seizures i. Antidepressants (tricyclic antidepressants, bupropion) ii. Antipsychotics (chlorpromazine, thioridazine, trifluoperazine, perphenazine, haloperidol) iii. Analgesics (fentanyl, meperidine, pentazocine, propoxyphene, tramadol iv. Local anesthetics (lidocaine, procaine) v. Sympathomimetics (terbutaline, ephedrine, phenylpropanolamine) vi. Antibiotics (penicillin, ampicillin, cephalosporins, metronidazole, isoniazid, pyrimethamine) vii. Antineoplastic agents (vincristine, chlorambucil, methotrexate,cytosine arabinoside : cyclosporine,) viii. Bronchodilators (aminophylline, theophylline) x. Others (insulin, antihistamines, atenolol, baclofen, cyclosporine)
Causes of epilepsy

Epileptic nature of attacks?

Ambulatory EEG Videotelemetry
Standard EEG Sleep EEG EEG with special electrodes (foramen ovale, subdural
Type of epilepsy?
INVESTIGATION OF SUSPECTED EPILEPSY
CT MRI
Structural lesion?
Urea and electrolytes Liver function tests Blood glucose Serum calcium, magnesium
Metabolic disorder?
Full blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) Chest X-ray Serology for syphilis, HIV, collagen disease CSF examination
Inflammatory or infective disorder?


EEG
may help to establish a diagnosis characterize the type of epilepsy (i.e. primary generalised or partial with or without secondary generalisation). Inter-ictal records patients so the EEG is not a sensitive test for the presence or absence of epilepsy. It is abnormal in only about 50% ; However, 'epileptiform changes' (sharp waves or spikes) are fairly specific (falsely positive in 1/1000). The sensitivity can be increased to about 85% by prolonging recording time and including a period of natural or drug-induced sleep. Ambulatory EEG recording or video/EEG monitoring may provide helpful information when attacks are frequent.

Brain imaging

1-Functional magnetic resonance imaging Functional MRI (fMRI) can visualize regional brain activity. The areas detected with changes in blood oxygenation level The most important clinical application of fMRI is in the localization and lateralization of cognitive functions prior to surgery in order to minimize the risk of causing a fixed deficit.
2- Magnetic resonance spectroscopy (MRS) provides measurements of specific brain metabolites. N-acetylaspartate , choline, creatine, lactate, γ-aminobutyric acid and glutamate. 3- PET SCAN4- SPECT SCAN 5- subtraction ictal SPECT co-registered to MRI (SISCOM)

Treatments for epilepsy

Anti-epileptic drugs (AEDs) Dietary therapy Vagus nerve stimulation Epilepsy surgery

First aid (by relatives and witnesses)

Move person away from danger (fire, water, machinery, furniture) After convulsions cease, turn into 'recovery' position (semi-prone) Ensure airway is clear Do NOT insert anything in mouth (tongue-biting occurs at seizure onset and cannot be prevented by observers) If convulsions continue for more than 5 minutes or recur without person regaining consciousness, summon urgent medical attention Person may be drowsy and confused for some 30-60 minutes and should not be left alone until fully recovered
IMMEDIATE CARE OF SEIZURES


Ensure airway is patent Give oxygen to offset cerebral hypoxia Give intravenous anticonvulsant (e.g. diazepam 10 mg) ONLY IF convulsions are continuous or repeated (if so, manage as for status epilepticus) Consider taking blood for anticonvulsant levels (if known epileptic) Investigate cause
Immediate medical attention


Treatment principles
Use one drug at a time (monotherapy), at least initially Initial titration should be to low maintenance doses Further upward titration will depend on response and side-effects If first drug fails, alternative monotherapies should be tried Upward and downward titration should be in slow, stepped doses Polytherapy should be used only if monotherapy will at least three first choice drugs has failed to control seizures Patients should be fully counseled about goals, role, risk, outcome and logistics of drug treatment

1st choice

2ed choice
Contraindicated
Myoclonic
Sodium valproate Topiramate Levetiracetam
Clobazam Clonazepam Lamotrigine Piracetam Zonisamide
Carbamazepine Gabapentin Oxcarbazepine Pregabalin Tiagabine Vigabatrin
Tonic
Lamotrigine Sodium valproate
Clobazam Clonazepam Levetiracetam Topiramate
Carbamazepine Oxcarbazepine
Atonic
Lamotrigine Sodium valproate
Clobazam Clonazepam Levetiracetam Topiramate
Carbamazepine Oxcarbazepine Phenytoin
Focal with/without secondary generalization
Carbamazepine Lamotrigine Levetiracetam Oxcarbazepine Sodium valproate Topiramate
Clobazam Gabapentin Pregabalin Tiagabine Zonisamide


CHRONIC Side-effects cognitive impairment –Tremor- obesity ovarian cyst visual field defectweight gain, weight lossbone marrow suppression, liver dysfunction dermatologic reactions +-- hair loss+ hairsutismbone disease stone formation poly neuropathy cerebellar degeneration Allergy Central nervous system side effects (dose dependent) drowsiness, headache dizziness, dysequilibrium cognitive dysfunction (memory)
Side-effects
Idiosynchratic reactions

. Childhood-onset epilepsy, particularly classical absence seizures, carries the best prognosis for successful drug withdrawal. Other primary generalised epilepsies, such as juvenile myoclonic epilepsy, have a marked liability to recur after AED withdrawal. Seizures that begin in adult life, particularly those with partial features, are also likely to recur, especially if there is an identified structural lesion. Overall, the recurrence rate of seizures after drug withdrawal is about 40%


Status epilepticus defined as seizure activity lasting more than 5 minutes or more Manifesting either as continuous clinical seizure activity, or intermittent seizures without recovery of consciousness in between.
Types Tonic-Clonic Status Epilepticus (TCSE) Absence Status Epilepticus Epilepsia Partialis Continua (EPC) Myoclonic Status Epilepticus Complex Partial Status Epilepticus
associated with significant mortality and morbidity in terms of cognitive and neurological deficit

Stage of early status (0–30 min)Lorazepam 4 mg IV bolus (can be repeated once)Ш (if seizures continue after 30 min)Stage of established status (30–60/90 min)Phenobarbital IV infusion 10 mg/kg at 100 mg/minorPhenytoin IV infusion 15 mg/kg at 50 mg/minorFosphenytoin IV infusion 15 mg PE/kg at 100 mg PE/minorValproate IV infusion 25 mg/kg at 3–6 mg/kg/minШ (if seizures continue after 30–90 min)Stage of refractory status (>60/90 min – general anaesthesia)Propofol: IV bolus 2 mg/kg,

congenital malformations is 2–3Ч normal risk; but continuing AEDs during pregnancy Valproate: higher incidence of congenital malformation ;higher rate of cleft palate. Seizure frequency may increase during pregnancy.Follow anticonvulsant levels every 4–6 weeks. Initiate folic acid, 4 mg/day, preconceptually Breast-feeding is not contraindicated, Valproic acid have been associated with an increased frequency of polycystic ovary syndrome.
Difficulties with conception
Women and Epilepsy