Epilepsy and seizures Notes

NOTES NOTES EPILEPSY & SEIZURES GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Seizure: brain neurons → abnormal, excessive, synchronized electrical activity period ▫ Clusters of brain neurons temporarily impaired (seconds-minutes) → paroxysmal electrical discharges → disordered awareness, behavior, movement ▫ → too much excitatory, too little inhibitory activity CAUSES ▪ Many unknown causes; some known causes (e.g. brain infection): ▫ ↑ excitation: long-lasting/fast activation of NMDA receptor via glutamate ▫ ↓ inhibition: genetic mutations → dysfunctional GABA receptors ▪ Causation → classification Provoked seizures ▪ Triggers → abnormal brain activity; subside once trigger removed ▪ Medication ▫ Aminophylline, bupivacaine, bupropion, butyrophenones ▪ Recreational drugs ▫ Amphetamines, cocaine, methylphenidate, psilocybin, psilocin ▪ Alcohol consumption/ withdrawal ▪ Flashing lights ▫ Photosensitive epilepsy ▪ Fever ▫ Febrile seizures Epileptic seizures ▪ Recurring, unpredictable seizures; brain dysfunction → abnormal brain activity; seizures triggered 576 OSMOSIS.ORG ▪ Idiopathic seizures/epilepsy disorder ▫ Most common ▪ Disorders ▫ Brain injury, brain abscess, brain tumors, eclampsia, encephalitis, Angelman syndrome ▪ Cerebrovascular disease ▫ Intracranial bleeding; perinatal hypoxia, ischemia; ischemic stroke ▪ Systemic disorders ▫ Uremic encephalopathy, hepatic encephalopathy, electrolyte imbalances, hypoglycemia, thiamine deficiency, vitamin B12 deficiency Nonepileptic seizures ▪ → fainting spell, psychological conditions, stress, not epileptic brain activity SIGNS & SYMPTOMS ▪ Subtle signs ▫ Spacing out, unusual sensations, brief muscle jerks ▪ Life-threatening ▫ Generalized muscle contractions > five minutes DIAGNOSIS DIAGNOSTIC IMAGING MRI/CT scan ▪ Detects structural brain abnormalities (brain tumors or vascular disorders) LAB RESULTS ▪ Electrolytes; blood glucose; complete blood cell count; liver, renal function; serum calcium; urinalysis

Chapter 75 Epilepsy & Seizures MNEMONIC: SICK DRIFT3R ▫ Assess possible underlying infection, genetic condition, metabolic disorder, other causes Differential diagnosis for seizures Substrates: sugar, oxygen Isoniazid Cations: Na, Ca, Mg Kids: pregnancy/eclampsia Drugs Rum: alcohol withdrawal Illnesses: chronic Fever Trauma 3 “antis”: antihistamine, antidepressant, anticonvulsants Rat poison OTHER DIAGNOSTICS Electroencephalogram (EEG) ▪ Detects abnormal, epileptiform brain electrical activity Clinical history ▪ Assess type of seizure; differentiate between primary, secondary seizures Neurological exams ▪ Assess behavior, motor abilities, mental functions → underlying seizure cause, type TREATMENT MEDICATIONS Epilepsy ▪ Antiepileptic medication ▫ Depends on type of seizures, age, lifestyle, and comorbidities OTHER INTERVENTIONS Provoked seizures ▪ Address trigger ABSENCE SEIZURE osms.it/absence-seizure PATHOLOGY & CAUSES ▪ Formerly called petit mal seizures ▪ Generalized seizure; brief loss of awareness/responsiveness; sudden onset, termination; usually no postictal state ▪ Most common in children; can occur 50–100 times/day; often misdiagnosed as inattentiveness, daydreaming CAUSES ▪ Cause → abnormal neuronal activity unknown COMPLICATIONS ▪ May progress into generalized tonic-clonic seizures ▪ Learning difficulties ▪ Behavior problems OSMOSIS.ORG 577

(e.g. lip smacking, chewing motions, eyelid flutters) ▪ Possible sign of coexisting seizure types ▪ No recollection of seizure DIAGNOSIS DIAGNOSTIC IMAGING MRI/CT scan ▪ To rule out brain abnormalities OTHER DIAGNOSTICS Figure 75.1 An EEG taken from an individual having an absence seizure. EEG ▪ Shows generalized spike-and-slow wave discharges ▪ Easily induced by hyperventilation (most reliable test) TREATMENT SIGNS & SYMPTOMS ▪ Sudden loss of awareness, responsiveness → from few seconds-half a minute ▪ Blank stare ▪ Preceding activity ceases ▪ Ends abruptly or followed by automatisms ▪ Usually resolves as child ages MEDICATIONS Anticonvulsant medication ▪ Valproic acid (drug of choice in case of other coexisting types of seizures), ethosuximide (only for absence seizures) EPILEPTIC SEIZURE osms.it/epileptic-seizure PATHOLOGY & CAUSES ▪ Recurrent, unprovoked seizures → epilepsy symptoms TYPES Focal (partial) seizures ▪ Affect one brain hemisphere ▫ Subcategories: Focal aware seizure; focal impaired awareness seizure 578 OSMOSIS.ORG Generalized seizures ▪ Affect both brain hemispheres ▫ Subcategories: tonic seizures, atonic seizures, clonic seizures, tonic-clonic seizures, myoclonic seizures, absence seizures CAUSES ▪ Seizures genetic/idiopathic ▪ Cerebrovascular disease ▫ Intracranial bleeding; perinatal hypoxia,

Chapter 75 Epilepsy & Seizures ischemia; cerebrovascular insult ▪ Neurological disorder/illness ▫ Brain tumors, metastases; brain injury; brain abscess; encephalitis; eclampsia; Angelman syndrome; multiple sclerosis; systemic lupus erythematosus ▪ Systemic disorders ▫ Uremic encephalopathy; hepatic encephalopathy; electrolyte imbalances (hypercalcemia, hyponatremia); hypoglycemia, hyperglycemia; thiamine, pyridoxine, vitamin B12 deficiency COMPLICATIONS ▪ Injury → falling, drowning, car crash during attack ▪ Pregnancy complications → seizures during pregnancy; → antiepileptic medication → teratogenic effects ▪ Status epilepticus ▫ Continuous seizure activity > five minutes → permanent brain damage, death ▪ Sudden unexpected death in epilepsy (SUDEP) → frequent tonic-clonic seizures, inadequate antiepileptic treatment SIGNS & SYMPTOMS Focal seizures ▪ Focal aware seizure ▫ No awareness impairment; motor, sensory, autonomic, psychological sensations ▪ Focal impaired awareness seizure ▫ May include automatisms (e.g. lip smacking, chewing, swallowing, unpurposeful walking, etc.) Generalized seizures ▪ Tonic seizures ▫ Sudden, continuous muscle contractions; causes falling, often backwards ▪ Atonic seizures ▫ Sudden muscle relaxation; causes falling, often forwards ▪ Clonic seizures ▫ Rhythmic muscle contractions (convulsions) ▪ Tonic-clonic seizures ▫ Tonic phase → muscles suddenly stiffen; clonic phase → muscles rapidly contract, relax ▪ Myoclonic seizures ▫ Short, one/multiple muscle twitches over short time ▪ Absence seizures ▫ Loss of awareness/responsiveness; staring spell Generalized seizures often → postictal state ▪ Confusion, drowsiness, sleepiness, total amnesia for hours Todd’s paralysis or paresis ▪ May follow; affects arms/legs, usually limited to one side ▫ Lasts about 15 hours; temporary, but severe suppression of brain activity in seizure-affected area DIAGNOSIS DIAGNOSTIC IMAGING MRI/CT scan ▪ Detect structural brain abnormalities (brain tumors, vascular disorders) LAB RESULTS ▪ Electrolytes, blood glucose and calcium levels ▫ Assess possible underlying infection, genetic condition, metabolic disorder, other causes OTHER DIAGNOSTICS ▪ ≥ two unprovoked seizures required for epilepsy diagnosis EEG ▪ Detect abnormal, epileptiform electrical brain activity Neurological exam ▪ Assess behavior, motor abilities, mental functions → underlying cause, type of seizure OSMOSIS.ORG 579

TREATMENT MEDICATIONS Anticonvulsant medications ▪ Depends on type of seizures, age, lifestyle, comorbidities ▫ Focal epilepsy: lamotrigine, oxcarbazepine, carbamazepine ▫ Generalized epilepsy: valproate, lamotrigine, ethosuximide (only for absence seizures) ▫ If unsure: broad spectrum anticonvulsants (effective for all types): valproate, lamotrigine, topiramate SURGERY ▪ Surgical resection in certain cases (e.g. brain tumors or vascular disorders) FEBRILE SEIZURE osms.it/febrile-seizure PATHOLOGY & CAUSES ▪ Triggered by fever ▪ Exact mechanism unknown; proposed explanations ▫ ↑ body temperature during fever → ↑ excitability of neurons ▫ Hyperventilation during fever → ↓ CO2 levels → respiratory alkalosis → ↑ neuronal excitability ▫ ↑ cytokine levels during fever → enhancement of NMDA receptors → ↑ neuronal excitability TYPES Simple febrile seizure (most common) ▪ Affects whole body (tonic-clonic seizures) ▪ Lasts < 15 minutes ▪ Does not repeat within 24 hours Complex febrile seizure ▪ If 1/3 criteria met ▫ Affects specific body part corresponding to specific brain part ▫ Lasts > 15 minutes ▫ Repeats within 24 hours 580 OSMOSIS.ORG RISK FACTORS ▪ Genetic susceptibility ▪ Age 6 months–5 years ▪ Infections ▫ Usually common infections, e.g. otitis media SIGNS & SYMPTOMS ▪ High body temperature: >38° C/100.4° F ▪ Simple febrile seizure ▫ Presents as tonic-clonic seizures ▫ Tonic phase (muscles stiffen, go rigid) → clonic phase (muscles rapidly contract, relax) → convulsions ▫ Followed by postictal state, residual arm/leg weakness DIAGNOSIS LAB RESULTS ▪ Laboratory studies ▪ Lumbar puncture to distinguish from other underlying causes of fevers, seizures (e.g. encephalitis, meningitis)

Chapter 75 Epilepsy & Seizures TREATMENT ▪ Simple febrile seizures usually resolve by themselves MEDICATIONS ▪ Anticonvulsant ▫ Complex febrile seizures ▪ Antipyretic medications (ibuprofen, acetaminophen) ▫ Fever management FOCAL SEIZURE osms.it/focal-seizure PATHOLOGY & CAUSES ▪ Seizure that initially stems from localized brain region; limited to one hemisphere TYPES Focal aware seizure ▪ Affects small brain area ▪ Individual awake, alert; remembers seizure Focal impaired awareness seizure ▪ Unilaterally affects larger area of one cerebral hemisphere ▪ Individual loses awareness, responsiveness; does not remember seizure ▪ May develop into a secondary generalized seizure (focal onset bilateral tonic-clonic seizure) SIGNS & SYMPTOMS Focal aware seizures ▪ Symptoms may be subtle, last ≥ two minutes, vary by affected lobe ▫ Preserved consciousness ▪ Motor symptoms ▫ Twitching, muscle jerking ▪ Sensory symptoms ▫ Unusual auditory, gustatory, tactile, olfactory sensations ▪ Autonomic symptoms ▫ Sweating, piloerection, dilation of pupils, incontinence, unusual feelings of nausea ▪ Psychological symptoms ▫ Sudden unusual feeling of sadness, happiness, fear, anger; feelings of derealization (environment is not real) or depersonalization (dissociation from the environment or self); feeling of déjà vu ▪ Speech difficult/impossible Focal impaired awareness seizure ▪ Impaired consciousness ▪ Often preceded by aura (symptoms of focal aware seizure) ▪ May involve automatisms (e.g. lip smacking, chewing, swallowing, unpurposeful walking, etc.) ▪ Amnesia (no recollection of seizure) DIAGNOSIS DIAGNOSTIC IMAGING MRI/CT scan ▪ Identify structural brain abnormalities (brain tumors, vascular disorders) LAB RESULTS ▪ Blood tests ▫ Detect possible underlying infection, genetic condition, metabolic disorder, other causes OSMOSIS.ORG 581

OTHER DIAGNOSTICS EEG ▪ Detect epileptiform, abnormal electrical brain activity Neurological exam TREATMENT MEDICATIONS ▪ Anticonvulsant medications ▫ E.g. lamotrigine, oxcarbazepine, carbamazepine SURGERY ▪ Treat underlying cause ▫ E.g. brain tumors, vascular disorders → surgical resection MYOCLONIC SEIZURE osms.it/myoclonic-seizure PATHOLOGY & CAUSES ▪ Type of generalized seizure; presents with myoclonus ▫ Sudden, brief, involuntary muscle jerks lasting 1–2 seconds ▪ Epileptic; non-epileptic, e.g. physiologic while falling asleep, waking up; myoclonic jerks → nervous system disorders, metabolic abnormalities, etc. ▪ Associated with epileptic syndromes: ▫ Juvenile myoclonic epilepsy ▫ Progressive myoclonus epilepsy ▫ Myoclonic epilepsy with ragged-red fibers (MERRF) ▫ Lafora disease ▫ Unverricht–Lundborg disease ▫ Neuronal ceroid lipofuscinosis COMPLICATIONS ▪ May become generalized tonic-clonic seizures 582 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Brief body jerks; most commonly facial muscles, limbs ▪ Preserved consciousness, recollection of seizure DIAGNOSIS OTHER DIAGNOSTICS EEG ▪ Detect abnormal, epileptiform electrical brain activity TREATMENT MEDICATIONS ▪ Anticonvulsant medication ▫ Clonazepam, valproate, levetiracetam; carbamazepine, oxcarbazepine, pregabalin, others contraindicated

Chapter 75 Epilepsy & Seizures STATUS EPILEPTICUS osms.it/status-epilepticus PATHOLOGY & CAUSES ▪ Medical emergency involving one acute prolonged seizure ≥ five minutes or multiple seizures occurring close together without recovery between TYPES ▪ Convulsive status epilepticus (CSE) ▪ Nonconvulsive status epilepticus (NCSE) CAUSES ▪ Epilepsy ▫ Usually triggered by medication change/ inadequate treatment ▪ Alcohol consumption/fasting while on anticonvulsant ▪ Acute cerebral injury ▪ Brain disorders ▫ Brain tumors, brain injury, brain abscess, encephalitis ▪ Systemic process/illness ▫ Uremic encephalopathy, hepatic encephalopathy ▪ Cerebrovascular disease ▫ Intracranial bleeding, cerebrovascular insult ▪ Eclampsia COMPLICATIONS ▪ Delayed treatment → irreversible neurological damage ▪ Prolonged muscle activity → hyperpyrexia, acidosis SIGNS & SYMPTOMS ▪ CSE ▫ Prolonged/repeated tonic-clonic seizures ▫ Tonic phase (muscles stiffen and go rigid), followed by clonic phase (muscles rapidly contract, relax) → convulsions ▪ NCSE ▫ Prolonged/repeated absence or focal impaired awareness seizure ▫ Long-lasting stupor, staring; unresponsiveness DIAGNOSIS ▪ Continuous seizure lasting > five minutes or recurrent seizures without regaining consciousness in between them for > five minutes DIAGNOSTIC IMAGING MRI/CT scan ▪ Detect structural brain abnormalities LAB RESULTS ▪ Identify underlying cause OTHER DIAGNOSTICS EEG ▪ Detect abnormal, epileptiform electrical brain activity TREATMENT MEDICATIONS ▪ Immediate application of benzodiazepines followed by antiseizure drug phenytoin ▪ If uneffective ▫ Valproic acid, phenobarbital, propofol, or ketamine OTHER INTERVENTIONS ▪ Oxygen, intravenous fluids OSMOSIS.ORG 583

TONIC-CLONIC SEIZURE osms.it/tonic-clonic-seizure PATHOLOGY & CAUSES ▪ Formerly called grand mal seizure ▪ Characterized by tonic (rigid) stage and clonic (convulsion) stage ▪ Most common seizure type ▪ May occur as one or multiple episodes as part of epilepsy disorder ▪ Can initiate in both brain hemispheres (generalized tonic-clonic seizure) or initiate in one and spread to both (focal to bilateral tonic-clonic seizure) ▪ Episode > five minutes → status epilepticus DIAGNOSTIC IMAGING SIGNS & SYMPTOMS OTHER DIAGNOSTICS ▪ May be preceded by unusual sensations, e.g. visual, auditory, olfactory hallucinations; dizziness (called an aura) ▪ Characterized by two phases ▫ Tonic phase: rigid, stiffening muscles; contracting chest muscles → cry/groan; biting of tongue, cheeks ▫ Clonic phase: muscles rapidly, rhythmically contract, relax; elbows, hips, knees bend, relax; urinary/fecal incontinence ▪ Tonic-clonic seizure → postictal state ▫ Confusion, drowsiness, sleepiness, total amnesia for hours after seizure ▪ May be followed by Todd paralysis/paresis for minutes–hours following seizure 584 OSMOSIS.ORG DIAGNOSIS MRI/CT scan ▪ Detect structural brain abnormalities (brain tumors, vascular disorders) LAB RESULTS ▪ Electrolytes; blood glucose, calcium levels ▫ Identify possible underlying infection, genetic condition, metabolic disorder, other causes EEG ▪ Detect abnormal epileptiform electrical brain activity TREATMENT MEDICATIONS ▪ Antiepileptic medication ▫ Valproate, lamotrigine, topiramate, phenytoin SURGERY ▪ Surgical resection for brain tumors, vascular disorders