Seizures/status epilepticus (evaluation and management) Seizures: Definition: temporary alteration in brain function due to excessive synchronized neuronal

activity Epidemiology: 10% people will have one seizure in lifetime 2 million in US and 50 million worldwide have epilepsy high incidence rates in early childhood and second peak in people over 65; incidence of epilepsy highest in the elderly 30-40% of patients with epilepsy continue to experience occasional seizures despite treatment recurrence rate after single generalized tonic-clonic seizure is 30-70% within 3-4 years in untreated patients Description: Partial: Focal seizures involving only part of the brain Partial-simple: No alteration in consciousness. Usually associated with positive symptoms (e.g. tingling rather than numbness). Manifestation depends on localization - can include motor, sensory, visual, gustatory, olfactory, auditory, psychic phenom. (deja vu, fear, panic, euphoria) Partial-complex: Alteration in consciousness - can include automatisms (lip smacking, chewing, picking at clothing) differentiated from absence by presence of aura, longer duration (90secs vs 15 secs) and postictal confusion Secondarily generalized: convulsion preceded by focal onset (the focal onset is sometimes not apparent clinically) Generalized: seizures involving both hemisphere of the brain at the same time, with abrupt loss of consciousness Myoclonic: shortest generalized seizure, may consist of single jerk, shows generalized spike or polyspike wave discharge on EEG Clonic: Rhythmic jerking Tonic: Sustained muscle contraction; may drop seizures Absence, typical: 3Hz spike and wave discharges on EEG associated with brief (usually <30 seconds) episode of unresponsiveness, may be accompanied by eyelid fluttering, decreased tone, increased tone, or automatisms (petit mal Absence, atypical: 1.5-2.5Hz spike wave discharges on EEG; longer in duration and associated with more automatisms and motor signs than typical absence Atonic (astatic): loss of muscle tone; may drop seizures

Epilepsy: Definition: group of disorders characterized by tendency toward recurrent unprovoked seizures and can typically be diagnosed only after two or more unprovoked seizures Classification: Idiopathic: no identifiable cause, no associated neurological abnormalities, although genetic mutations are increasingly being discovered to underlie many of these disorders; often begins in childhood or young adulthood, there is NO well defined aura Symptomatic

Cryptogenic: presumed symptomatic due to other neurological abnormalities, but cause is unknown

Localization related epilepsies and syndromes: Idiopathic with age-related onset Benign epilepsy with centrotemporal spikes (BECTS) (Rolandic epilepsy) school-age, otherwise healthy children and resolves by puberty most common partial epilepsy of children (2/3 of all idiopathic partial epilepsy) onset at 3-16 years (peak 5-8) complex genetic inheritance Sx/exam Nocturnal seizures with excessive salivation, gurgling or choking sounds, clonic contractions of upper face and upper extremity 20% of patients will have only one seizure; will have infrequent seizures; can be treated with antiepileptic drugs used for partial seizures (carbamezapine) pts neurologically normal, outgrow the disorder Childhood epilepsy with occipital paroxysms panayiotopolous syndrome onset at 1-14 years, peak age 5, girls/boys equally affected principle seizure type is autonomic and autonomic status epilepticus child conscious but feeling sick, turns pale, vomits (headaches may occur at onset) 20% progress into LOC and ictal syncope neuro exam/imaging normal, multifocal spike and slow waves, misdx common, prognosis benign Idiopathic childhood occipital epilepsy range 3-16; average 8 years equal gender 50% have family hx of epilepsy sx of episodic blindness, colored luminous discs, visual hallucinations lasting seconds or minutes; postictal migraine in one third interictal EEG shows high amplitude spike and wave complexes occurring with eyes closed treated with meds for partial seizures carbamezapine good prognosis Cryptogenic and symptomatic Rasmussens encephalitis presents in childhood 6-10 years of age with uncontrollable focal seizures may present with epilepsia partialis continua (EPC) - focal motor status epilepticus progressive; usually involves only one hemisphere antiglutamate receptor antibodies seen in some cases neuropathology: perivascular lymphocystic infiltrates with vascular injury, astrogliosis, neuronal loss, and cortical atrophy hemispherectomy is the best established treatment; high dose IVIG may be helpful

Temporal lobe epilepsies (TLEs) mesial temporal seizures are most common form seizures may consist of rising epigastric discomfort, nausea, autonomic signs, fear, and olfactory hallucinations, followed by loss of awareness, oral and manual automatisms (ipsilateral to ictal focus), dystonic postures (contralateral to ictal focus) patients often have history of prolonged, severe, febrile seizures hippocampal sclerosis is most common pathology seen with gliosis and neuronal loss in the CA1 pyramidal cell layer autosomal dominant partial epilepsy with auditory features (ADPEAF) onset second decade of life, auditory hallucinations of monotonous buzzing, voices from the past, specific singers, or distortions of sounds in the environment. may have other partial seizure types; mutations in LGII gene mesial temporal lobe epilepsy and hippocampal sclerosis show MRI apparent hippocampal atrophy and increased T2 weighted signals Frontal lobe epilepsies frequent seizures, often stage 2 sleep short seizure duration minimal or no postictal confusion rapid secondary generalization prominent motor manifestations complex gestural automatisms (hyperkinetic) supplementary motor seizures: brief, lasting 10-40seconds, bilateral, tonic or clonic movements in association with preserved consciousness bicycling movements and other asynchronous bilateral movements may occur (pelvic thrusting and side-to-side head movements are sugestive of psychogenic nonepileptic seizures (PNES) autosomal dominant frontal lobe nocturnal epilepsy: onset in first two decades of life; usually occur during sleep, clinically similar to other types of frontal lobe seizures; mutans in gene encoding for neuronal nictonic Ach receptors Generalized epilepsies and symptoms Infantile spasms Jack-knifing with sudden flexion, extension, or mixed flexion-extension movements of the trunk and proximal muscles, often occur in clusters Often have mental retardation (West syndrome) EEG is diffusely abnormal with high-amplitude sharp and slow waves (hypsarrhythmia) Causes include inborn errors of metab, struc brain abnormalities, tuberous sclerosis treatment with ACTH or vigabatrin is often used in TS due to high frequency of visual loss; resection if there is focal lesion Lennox-Gastaut syndrome triad of multiple seizures refrac to AEDs, mental retardation, slow spike and wave activity on EEG between ages 1-10 years, de novo or following infantile spasm most mentally retarded, 70% have identifiable cause for retardation and epilepsy multiple seizure types (tonic, atypial absence, atonic) No single etiology

diffusely abnormal EEH, becomes more abnormal in sleep; slow spike and wave dischargs of 1.52.5Hz difficult to control; treat with broad spectrum agent; felbamate may be used, ruinamide is new drug for this syndrome; VNS may be helpful Progressive myoclonic epilepsies rare group disorders charac. by severe myoclonus and other gen. seizure types, progressive dementia, and ataxia Baltic myoclonus - AR, mutation cystatin B on chr 21, onset 8-13, ataxia and dementia ocur late and are mild, markedly photosensitive; may have giant somatosensory evoked potentials Lafora disease - AR, 80% cases due to mutations of laforin gene on chr 6, seizures begin 10-18; rapid progression resulting in quadriparesis, dementia, and death in 2-20 years, marked photosensitivity Myoclonic epilepsy with ragged red fibers - mito inheritance, wide phenotypic variability, sx may begin in childhood or adulthood. seizures, dementia, ataxia; may have myopathy, neuropathy, deafness, optic atrophy, exercise intolerance, short stature, lactic acidosis Epilepsies and syndromes undetermined as to whether focal or generalized Epilepsy with electrical status epilepticus in slow wave sleep (ESES) begins early childhood, peak 4-5 assoc. with cog. impairment, esp. language, behav. disturbances EEG dx with generalized spike and wave activity as dominant pattern during sleep (>85% of slow wave time) Acquired epileptic aphasia (Landau-Kleffner syndrome) rare childhood disorder acquired aphasia, epileptiform discharges usually dev. in healthy children who acutely or progressively lose receptive and expressive language ability coincident with the appearance of paroxysmal EEG changes usually in sleep Special syndromes/situation-related seizures *Not necessarily assoc with dx of epilepsy Febrile seizures fever in children 6mo-5 years without intracranial infection; average 18-22 months; boys > girls approx. 1 in 25 children will have febrile seizure and one third will have recurrence usually occurs first day of fever, sometimes before fever is reorganized can be seizures of any type, usually tonic-clonic or tonic complex if seizure lasts >15 minutes, more than one seizure in 24 hours, or focal features EEG is generally not useful; epileptiform activity is not predictive of eventual development of epilepsy Management: ID underlying illness and do LP if no concern about meningitis No neuroimaging unless exam points to structural lesion no treatment; children with frequent or proonged febrile seizures can take oral or rectal diazepam during fevers

increased risk of developing epilepsy (3% by age 7 vs 0.5% in gen. pop)

Alcohol withdrawal 90% occur 7-48 hours after stop drinking; 50% 13-24 hours after; can occur up to 7 days after drinking tremulousness and some myoclonic jerks of extremities risk of DTs and status epilepticus EEG: may show heightened excitability to photic stimulation that resolves with BZDs Management: administer thiamine before glucose, correct fluid and electrolyte abnormalities, administer magnesium. Lorazepam and additional doses every 4 hours as needed. Phenytoin has no value for alcohol withdrawal seizures Eclampsia Occurrence of partial or secondarily generalized seizures, not caused by another neurological disease, in a woman who meets criteria for preeclampsia (proteinuria, edema, after 20 weeks gestation) headache, confusion, hyperreflexia, visual hallucinations, blindness seizures may occur even when few signs of preeclampsia present occurs before during or after childbirth EEG with focal or diffuse slowing and epileptiform activity treat with magnesium sulfate Reflex seizures regularly elicited by specific stimulus or event (visual, thinking, music, eating, reading, exercise, somatosensory, praxis) flickering light, patterns treat: avoidance, desensitization therapy, AEDs

Status: Management Airway Breathing (give O2) Circulation Drugs (lorazepam and IV fosphenytoin) DEFG: Dont Ever Forget Glucose and Thiamine Definition: one continuous unremitting seizure lasting longer than 30 minutes, or recurrent seizures without regaining consciousness between seizures for >30 minutes Investigations of seizures: Eyewitness account! History: medication and drug exposure previous seizures; screen for myoclonus, odd behaviors, loss of time, staring spells risk factors: history of febrile seizures, developmental delay, head injury resulting in LOC, brain infection, brain lesions, family history of seizures

General physical exam: assess signs of other systemic diseases skin findings suggestive of tuberous sclerosis, neurofibromatosis, sturge-weber syndrome Complete neuro exam Blood tests: metabolic and toxic disorders EEG: positive in 20-59% of people with epilepsy--a normal EEG never excludes the diagnosis of seizure 95% abnormal in absence epilepsy repeated EEGs positive in 59-92% of people with epilepsy; three 30-minute EEGs should diagnose 90% of cases with epilepsy Photic stimulation, hyperventilation, and sleep are all activating procedures used to increase the yield of EEG in finding abnormalities sleep deprived EEG is a more sensitive measurement epilepsy is suggested by abnormal spikes, polyspike discharges, spike-and-wave complexes EEG may distinguish between partial and generalized epilepsies. The interictal EEG of generalized seizures is frontally predominant, generalized spike, or polyspike wave discharges Ambulatory EEG can be helpful to obtain a longer sample, monitor frequency of seizures, or diagnose events of unclear etiology video EEG for dx of events with unclear etiology or for surgical planning Neuroimaging: MRI within thin cuts through temporal lobes is preferred imaging technique in epilepsy

Psychiatric comorbidities 20-30% have psych comorbidity depression is most common dx and occurs in 30-40% of patients with epilepsy 5-10 fold increased risk of suicide anxiety and psychosis more common than gen. pop. neuropsychiatric sx reported with temporal lobe epilepsy include psychosis, fear, anziety, hypergraphia, hypermorality (Geschwind syndrome, temporal lobe epilepsy, left hemisphere), and altered sexual function Psychogenic nonepileptic seizures (PNES) paroxysmal changes in behavior that resemble epileptic seizures but are without organic cause and EEG changes, usually due to conversion disorder many have comorbid psych illness or history of abuse 10-30% of patients evaluated at tertiary referral centers for medically refrac. epilepsy have PNES ddx: frontal lobe seizures that have unusual movements and very brief postictal state video EEG monitoring necessary for dx Womens issues Conception up to 20% of women with epilepsy have abnormal ovarian function, incl. anovulatory menstrual cycles, polycystic ovaries

more common in women taking valproic acid some AEDs induce metabolism of female sex hormones, decreases the efficacy of hormonal contraception (OCP metabolism increased by phenytoin) Pregnancy most deliver pregnant babies and have uneventful pregnancies increased incidence of minor and major fetal malformations, even if untreated. risk is 2-3% in gen. pop. and 4-6% in women with epilepsy risk of birth defects increases with the use of more AEDs Bone health osteopenia and osteoporosis occur at higher freq in men and women with long term AED exposure induced vit. D metabolism may play a role calcium and vitamin D supplementation and DEXA screening Epilepsy in elderly most common time to dev. epilepsy seizures may be difficult to recognize, postictal confusion may be prolonged may be secondary to vascular events, neurodegenerative condition, other structural etiology; most idiopathic Neuroleptic disorders that mimic epilepsy Syncope: vasovagal/neurocardiogenic, decreased cardiac output, volume depletion, arrhythmia Migraine: classic, basilar, confusional, acephalgic Cerebrovascular: TIA, amyloid angiopathy Sleep disorder: REM behavior disorder, narcolepsy, cataplexy, parasomnia Movement disorder: Tics, nonepileptic myoclonus, tremor Transient global amnesia Psychiatric: panic, dissociation, conversion, malingering Common causes provoked seizures Metabolic - hyponatremia, hypoglycemia, hyperthyroidism, nonketotic hyperglycemia, hypocalcemia, hypomagnesia, renal failure Porphyria Hypoxia Medications - BZD withdrawal, Barb withdrawal, phenothiazines, buproprion, tramadol Substance abuse - alcohol withdrawal, cocaine, amphetamine, phencyclidine, MDMA (ecstasy)