Childhood Seizure Disorders.pdf

Childhood Seizure Disorders Ayalew Moges ,M.D. Pediatrician & Pediatric Neurologist June 28,2024 1  Definition of Seizure A transient occurrence of Sns and/or Sxs due to abnormal, excessive or synchronous...

Childhood Seizure Disorders Ayalew Moges ,M.D. Pediatrician & Pediatric Neurologist June 28,2024 1  Definition of Seizure A transient occurrence of Sns and/or Sxs due to abnormal, excessive or synchronous neuronal activity in the brain. - i.e. during a seizure, large numbers of brain cells are activated abnormally at the same time. - It is like an "electrical storm" in the brain. ** Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsiadoi 10.1111/epi.13671. 2  Clinical Vs Electrical/electrographic seizures Convulsion: the motor act of seizure Status Epilepticus (SE): - Continuous convulsion lasting for > 5 min OR - Serial convulsions for >5 min b/n which there is no return of consciousness. - Convulsive and non-convulsive status epilepticus ** t1: for generalized tonic-clonic seizures 5 min ; for focal seizures with impaired awareness SE 10min & for for absence SE 10-15 min. Aura : suggests a focal origin of the epileptiform discharge Seizure Semiology : preictal state (premonitory or 3 prodromal state), aura, ictus/ictal state,& postictal state.  Acute symptomatic seizures (provoked seizures) - Secondary to an acute problem affecting brain excitability such as electrolyte imbalance. - Most children do well. - May signify major structural, inflammatory, or metabolic disorders of the brain, such as meningitis, encephalitis, acute stroke, or brain tumor. Unprovoked seizures - One that is not an acute symptomatic seizure. First Unprovoked seizure: - 30% of patients later develop epilepsy; the risk is 20% if the neurologic exam, EEG,and neuroimages are normal. Remote symptomatic seizure - Secondary to a distant brain injury, such as an old stroke. Seizure Disorder - Epilepsy, febrile seizures, single unprovoked seizures and acute symptomatic seizures. 4  Reflex seizures - Precipitated by a sensory stimulus such as visual (flickering lights , patterns, reading),auditory(music), somatosensory, or proprioceptive stimuli; praxis ; eating; bathing in hot water, or being startled. Epilepsy : Two or more unprovoked seizures which occur >24 hr apart or at least one unprovoked epileptic seizure with enough EEG (epileptiform discharges) and clinical information to convincingly demonstrate an enduring predisposition to develop recurrences. Epileptic syndrome - Disorder that manifests with one or more specific seizure types - Specific age of onset , EEG findings and specific prognosis - Several types of epileptic syndromes 5  Epileptic Encephalopathy - Epilepsy syndrome with severe EEG abnormality - Results in cognitive & other impairments Developmental encephalopathy: - The underlying etiology (e.g. a specific gene mutation) contributes to developmental delay independent of the patient’s seizure burden and/or EEG abnormalities. Developmental epileptic encephalopathy - Both the EEG abnormalities and the underlying etiology contribute to the patients developmental delay 6  Diagnostic and Classification Scheme of Epilepsies by ILAE Level 1: Determine if the event was an epileptic seizure and, if so, characterize the seizure type or types based on available clinical information as focal, generalized, or unknown. Level 2: Determine the type of epilepsy the patient has (focal, generalized, focal and generalized, or unknown). Level 3: Determine if the epilepsy fits into a particular epilepsy syndrome. Level 4: Establish a unifying diagnosis that takes into account the epilepsy syndrome, underlying etiologies, and associated comorbidities.  Cont’d ……Diagnostic and Classification Scheme of Epilepsies by ILAE Etiology for epileptic seizures : 1. Genetic 2. Structural 3. Metabolic 4. Immune 5. Infectious 6. Unknown Comorbidities should be considered at all levels of an epilepsy diagnosis: - Developmental delay, psychiatric sxs, behavioral issues, academic difficulties, movement abnormalities,etc.  Etiology of Epileptic Seizures Genetic epilepsy (idiopathic epilepsy) - The direct result of a known or presumed genetic defect(s) that is not causative of a brain structural or metabolic disorder other than the epilepsy. 1. Genetic generalized epilepsies (idiopathic generalized epilepsies) e.g. childhood absence epilepsy (CAE),JAE,JME 2. Epilepsies caused by a known gene defect e.g. Dravet syndrome (mutations in the SCN1A gene). Metabolic epilepsy  Structural epilepsy (symptomatic epilepsy) - Caused by an underlying structural brain disorder that may or may not be genetic. E.g. old stroke or hypoxic ischemic injury, epilepsy 2ry to tuberous sclerosis (which is also genetic in etiology). Immune-mediated epilepsy - Secondary to immune-mediated CNS inflammation. - Immunotherapies such as steroids and IVIG may be the first- line treatments. e.g. Autoimmune encephalitides such as anti-NMDA receptor encephalitis and anti-LG1 limbic encephalitis. 10  Infectious epilepsy - Secondary to chronic infections such as TB and HIV rather than acute infections such as bacterial meningitis or HSV encephalitis. Unknown epilepsy - Cryptogenic epilepsy and presumed symptomatic epilepsy were the older terms - Epilepsy syndrome in which there is a presumed underlying brain disorder causing the epilepsy and affecting neurologic function but the underlying disorder (cause of epilepsy) is still unknown  Seizure Type and Epilepsy Syndrome Seizure types , age of onset , cause , severity , co-morbid conditions , response to medication ,and clinical course vary widely. 1) Age at onset of seizures 2) Cognitive development and neurologic examination 3) Description of seizure type 4) EEG findings, including the background rhythm, help to classify ≈50% of childhood seizures into specific syndromes. Two main ways of grouping patients to bring an ordered approach of classification , treatment and prognosis : 1) Seizure type 2) Epilepsy syndrome 12  Pathophysiology of Epilepsy 1. Underlying etiology - Any process that can disrupt neuronal function & connectivity …. process of making the brain epileptic (epileptogenesis). - Underlying etiologies of epilepsy : brain tumors, strokes, scarring, or mutations of specific genes, etc. 2. Kindling - Animal model for human temporal lobe epilepsy - Repeated electrical stimulation of selected areas of the brain with a low-intensity current initially causes no apparent changes but with repeated stimulation results in epilepsy. 13 3. Epileptic state of increased excitability - Present in all patients irrespective of the underlying etiology or mechanism of epileptogenesis. 4. Seizure-related neuronal injury - As demonstrated by MRI in patients after prolonged febrile and afebrile status epilepticus. - Acute swelling in the hippocampus & long-term hippocampal atrophy with sclerosis on MRI. ?? apoptosis and necrosis of neurons in the involved regions. 14  In a seizure focus, each neuron has a stereotypic synchronized response called paroxysmal depolarization shift (PDS) PDS consists of: 1. Sudden depolarization phase - Glutamate & calcium channel activation 2. Series of action potentials at its peak followed by an after-hyperpolarization phase - Potassium channels & GABA receptors activation 15  Epidemiology Cumulative lifetime incidence of epilepsy: 3% - More than ½ of cases begin in childhood - Genetic factors : 20 % of all cases of epilepsy Annual prevalence of epilepsy: 0.5-1 % 4-10% of children experience at least 1 seizure (febrile or afebrile) in the 1st 16 years of life < 1/3 of seizures in children are caused by epilepsy. 16  WHO : Key facts about Epilepsy Epilepsy is a chronic noncommunicable disorder of the brain that affects people of all ages. 50 million people worldwide have epilepsy - One of the most common neurological diseases globally. 80% of the people with epilepsy live in low- and middle-income countries(LMIC). 70% of people living with epilepsy could live seizure-free if properly diagnosed and treated. The risk of premature death in people with epilepsy is up to 3x higher than for the general population. ¾ of people with epilepsy living in LMIC do not get the Rx they need. In many parts of the world, people with epilepsy and their 17 families suffer from stigma and discrimination.  History Seizure Semiology: 1. Preictal state: behavior of child immediately preceding seizure 2. Aura (ictal onset) - Epigastric discomfort or pain - Feeling of fear , head ache ,chest pain etc. 3. Ictal / Seizure characteristics - Seizure type , time of day ,frequency - Duration of seizure - State of consciousness (retained or impaired) - Posture of the patient, vocalizations - Presence and distribution of cyanosis - Loss of sphincter control (especially bladder) - Presence of fever 18 4. Postictal state :sleep,hemiparesis,dysphasia,confusion  Perinatal problems (asphyxia , jaundice, trauma, meningitis, etc.) Developmental milestones(motor ,speech , language) Headache ,vomiting Precipitating factors Past Hx of meningitis Past Hx of seizure & use of AEDs Trauma (TBI) Poisoning Previous therapy Family Hx of seizures Any evidence of active CNS infection 19  Physical examination Physical , ophthalmologic , and neurologic examination provides information about : 1) Increased ICP 2) Neurocutaneous syndromes 3) Structural brain abnormalities - Brain malformations , injuries , infections , tumors 20  BP HC, length,weight Fundoscopy - Papilledema , retinal hemmorrhages , coloboma , chorioretinitis , macular changes Unusual facial features & hepatosplenomegaly - Metabolic or storage diseases Skin lesions - Shagreen patch ,ash-leaf lesions, cafeau-lait spots Localizing neurologic signs 21  Classification of Seizures Clinical + EEG Classifying the seizure type : - Provides clue to cause of seizure - Helps in choosing the most appropriate treatment - Allows a firm basis for making prognosis 22  International Classification of Epileptic Seizures 1) PARTIAL SEIZURES - Simple partial, a) Simple partial followed by impaired (consciousness retained) consciousness - Motor - Consciousness - Sensory impaired at onset - Autonomic - Psychic c) Partial seizures with b) Complex partial 2ry generaliz. (consciousness (Jacksonian march) impaired) 23 2 ) GENERALIZED 3 ) UNCLASSIFIED SEIZURES - Neonatal seizures SEIZURES N.B. Classification of a) Absences(Petit mal) Epilepsies and Epileptic - Typical (simple) Syndromes in children - Atypical (complex) *** SPECIAL SYNDROMES b) GTC (grand mal) - Situation-related seizures - Febrile convulsions c) Tonic - Isolated seizures or d) Clonic isolated status epilepticus e) Myoclonic - Acute symptomatic f) Atonic seizures: g) Infantile spasms e.g., alcohol withdrawal seizures, eclampsia , uremia 24  ILAE 2017 Classification of Seizure Types Basic Version 1 25 ILAE 2017 Classification of Seizure Types Expanded Version1 26  Epileptic (Infantile) Spasms Age of onset : 2 – 12 months (peak age 4-8 months) Characterized by brief symmetric contractions of the neck , trunk , and extremities Types: Flexor,extensor ,or mixed (most common type) Clusters or volleys of seizures may persist for minutes with brief intervals b/n each spasm (during drowsiness or upon arousal) EEG : chaotic pattern of high voltage ,bilaterally asynchronous , slow-wave activity ( hypsarrhythmia) or modified hypsarrhythmia pattern West Syndrome: triad of infantile epileptic spasms ,developmental regression, and hypaarrhythmia Usually mistaken for startles caused by colic or other benign 27 paroxysmal syndromes Classification : 1) Cryptogenic/Idiopathic/Unknown etiology (10-20%) - uneventful pregnancy and birth history - normal dev’tal milestones before onset of seizures - normal neurologic examination , CT and MRI of brain - Medical emergency as delay in Dx of > 3 weeks can affect long term prognosis 2) Symptomatic (Structural/Metabolic) (80-90%) - Severe prenatal , perinatal and postnatal factors Prenatal and perinatal factors HIE with PVL Congenital infections Inborn errors of metabolism Neurocutaneous syndromes e.g. tuberous sclerosis Congenital brain anomalies ; Prematurity 28 Postnatal factors HIE,CNS infections,head trauma (subdural hematoma ,IVH) Treatment Exogenous ACTH & glucocorticoids suppress CRH synthesis ACTH ( preferred drug ): High dose IM Prednisolone : 10mg PO QID for 2 weeks then tapper & stop Vigabatrine PO : for TSC pts Other ASMs : Sodium valproate, clonazepam,levetiracetam Ketogenic diet Surgery Prognosis Cryptogenic - good Symptomatic: 80-90% chance of ID/MR;other neurologic sequelae based on underlying CNS disorder 29  Neonatal seizures 1) Clonic Seizures A. Focal clonic seizures - Rhythmic twitching of muscle groups, particularly extremities,trunk & face. - causes: Localized structural lesions, infections ,SAH B. Multifocal clonic seizures : Similar to focal clonic seizures but many muscle groups are involved. 2) Spasms (Flexor/Extensor/mixed) - May occur in clusters; cannot be provoked by stimulation or suppressed by restraint 3) Tonic seizures (Focal & generalized Flexor/Extensor/mixed ) - Focal tonic is epileptic & generalized tonic is non-epileptic - Rigid posturing of limbs, trunk & neck 30 - +/- fixed deviation of the eyes. 4) Myoclonic seizures - Brief focal or generalized jerks of extremities or body that tend to involve distal muscle groups. 5) Subtle seizures - Chewing motions, excessive salivation - Alterations in respiratory rate including apnea - Blinking, nystagmus - Bicycling or pedaling movements - Changes in color. 31  GTC convulsions tend not to occur in ,1st mo of life: - Arborization of axons and dendritic processes as well as myelination is incomplete in the neonatal brain; So, seizure discharge cannot readily be propagated throughout the neonatal brain to produce a generalized seizure. Investigations Lumbar puncture - Indicated in virtually all neonates with seizures except for metabolic disorders (hypoglycemia or hypocalcemia) EEG is indicated in all cases 32  Febrile seizures Most common cause of seizures in childhood Excellent prognosis Dx by exclusion Incidence : ≈ 2-5% of young children Recurrence : in 30% of cases after 1st episode & 50 % after 2 or more episodes or age < 1year Genetic predisposition (AD) Types 1) Simple (Typical) 2) Complex or complicated (atypical) 33  Simple Febrile Seizures 1) Age 6 months – 60 months (5 years) 2) Core T0 ≥ 38 0C 3) Primary generalized (usually GTC) Sz 4) Duration : few seconds -15 minutes 5) Not recurrent in 24 hour period 6 )R/o.CNS infections (bacterial ,viral) ( Do LP if any doubt !!!!! ) e.g. Age < 12-18 months.Any metabolic imbalance * Risk of epilepsy = 1% ; No EEG is needed 34  Complex Febrile Seizures 1) Duration >15 min 2) Repeated convulsions in 24 hrs 3) Focal seizure activity 4) Focal findings during postictal period ** LP must be done if no C/I ! ; EEG should be done ** Risk of epilepsy: 6-33 % based on risk factors EEG in complex febrile seizures: - Done after 2 weeks of a febrile seizure - In the 1st two weeks it may show non-speicfic slowing ,usually posteriorly. 35 *15% children with epilepsy have had febrile seizures * Only 5% (range 1–33%,dependent on risk factors) of febrile seizures pts proceed to develop epilepsy later in life. * Febrile Status Epilepticus: > 30 minutes * Febrile infection-related (or refractory) epilepsy (FIRES): - Older (>5 year) usually male children & associated with encephalitis-like illness but 36 without an identifiable infectious agent.  Risk Factors for Recurrence of Febrile Seizures MAJOR MINOR Age 30 sec No postictal state (resume preseizure activity) Too frequently daily No loss of body tone ; head may fall forward slightly. 43  Automatic behaviors are frequent Hyperventilation for 3–4 min routinely produces absence seizure. EEG: 3/sec generalized spike and wave discharge. 2) Complex (atypical) absence seizures Associated motor components: - Myoclonic mov’t of face, fingers, or extremities &, on occasion, loss of body tone. EEG: Atypical spike and wave discharges at 2–2.5/sec 44  GENERALIZED TONIC-CLONIC (Grand mal) SEIZURES Common Occur de novo or follow partial seizure with a focal onset (secondary generalization) +/- aura : focal origin of epileptiform discharge. Sudden LOC - +/- shrill, piercing cry. Eyes roll back, entire body musculature undergoes tonic contractions, - rapidly become cyanotic with apnea. Clonic phase is heralded by rhythmic clonic contractions alternating with relaxation of all muscle groups. 45  Clonic phase slows toward the end of the seizure - usually persists for a few minutes - often sigh as seizure abruptly stops. Bite their tongue but rarely vomit. Loss of sphincter control (esp. bladder) is common Postictally - Semicomatose & typically remain in deep sleep from 30 min to 2 hr.. - Often vomiting & intense bifrontal headache. 46  MYOCLONIC EPILEPSIES OF CHILDHOOD Characterized by repetitive seizures consisting of : - brief, - symmetric muscular contractions with loss of body tone & falling or slumping forward Include a heterogeneous group of conditions with multiple causes and variable outcomes. At least five distinct subgroupings Could be benign in children but serious in adolescents/adults 47  Laboratory Tests Serum electrolytes (Na , K, Ca , Mg) Toxicology screening (urine and serum ) Metabolic testing (urine & serum ) Serum glucose * * EEG * * Lumbar puncture Skull X-Ray Neuroimaging (CT/MRI) - Focal neurologic deficits - MRI of the brain is recommended over CT 48  Indications for CT or MRI Brain in children with seizures: 1. Focal seizure 2. Postictal focal deficits on neurologic exam 3. Patient's status is not returning to baseline 4. Trauma preceding the seizure 5. Patients with a high-risk medical history.  Diagnosis Clinical features : seizure semiology ( Eye witness/video recording of events) EEG abnormalities: ictal or interictal period - Interictal EEG : normal in 40% of patients - Activation procedures ( to increase yield of EEG) : 1- Hyperventilation 2- Sleep deprivation 3- Photic stimulation 4- Eye closure 5- Special electrode placement (zygomatic leads) Video-Telemetry /Video EEG Recording Imaging (CT or MRI of brain) Routine lab 50  PAROXYSMAL NONEPILEPTIC DISORDERS (PNEDs) or SEIZURE MIMICS Based on age : In neonates ,infants, and children & adolescents 1. Syncope and other generalized paroxysms e.g. Syncope, breath-holding spells, functional seizures 2. Movement disorders and other abnormal movements e.g. Tics, tremor, jitteriness, hyperekplexia, gratification d/o 3. Oculomotor and visual abnormalities e.g. Paroxysmal tonic upgaze, spasmus nutans, OMA 4. Sleep disorders 51 e.g. Sleep myoclonus, narcolepsy, somnambulism, night terrors  Disorders that Mimic Childhood Epilepsy 1) Confused with GTC seizure - Pallid syncope (reflex anoxic seizure) - Vasodepressor syncope (reflex anoxic seizure) - Cyanotic breath-holding attacks - Collapsing attacks with cardiac dysrhythmias - Cataplexy 2) Confused with generalized absence seizure - Behavioral staring attacks - Day dreaming - Focal impaired awareness seizures - Tic disorder 52 3) Confused with focal impaired awareness seizures - Self-stimulatory behavior , especially in children with autistic spectrum disorders - Sleep walking (somnambulism) - Night terrors - Temper tantrums with amnesia for the rage event - Benign paroxysmal vertigo - Migraine-related disorders 4) Confused with epileptic myoclonus - Physiologic hypnagogic myoclonus - Benign infantile sleep myoclonus 53 - Startle disease (hyperekplexia)  Management 1) Establish diagnosis - Correctly determine seizure type , epileptic syndrome , etiology & precipitating factors. 2) Principles of pharmacologic therapy a) Begin monotherapy with drug of choice - Monotherapy should be tried best b) Push the first drug tried c) Add additional drugs - Polytherapy can be used 54 3) Drugs of choice Focal seizures: - Oxcarbazepine, carbamazepine, levetiracetam , phenytoin , phenobarbitone , primidone , clonazepam , valproic acid, lamotrigine, GTC seizure : - Valproic acid, , lamotrigine, phenytoin , phenobarbitone , primidone ,, carbamazepine Absence seizures : - Ethosuximide , valproic acid, lamotrigine, clonazepam , Nitrazepam, Myoclonic : - Clonazepam , nitrazepam , valproic acid ,levetiracetam Infantile spasms : - ACTH , prednisolone , clonazepam , nitrazepam , vigabatrin55 Akinetic : valproic acid , clonazepam  Other ASMs : - Lamotrigine - Topiramate - Gabapentin - Clobazam - Tiagabine - Vigabatrin - Lacosamide - Zonisamide 56  Factors increasing risk of recurring seizures 1) Evidence of structural lesion - strongest predictor 2) Abnormal EEG 3) Partial seizure type 4) Positive family Hx 5) Postictal motor paralysis N.B. - Persons with no risk factor have < 50% (usually 30%) chance of 2nd seizure within 2 yrs - Persons with 2 or more risk factors have a 100% chance of seizure recurrence within 2 yrs….Need 57 Rx. 4) Drug interactions a) B/n ASMs b) B/n ASMs & other drugs 5) ASMs plasma concentration 6) Discontinuing therapy - ASMs could be discontinued after 2 years of seizure free period - Tapper drugs slowly: elimination of one pill per day (or 25% of daily dosage) every five elimination half-lives - May take 2-3 months up to 3-6 months ( benzodiazepines e.g. clonazepam & barbiturates e.g. phenobarbitone ) - Rapid tapering of therapy precipitates seizures 58 7) Drug resistant epilepsy (Medically Intractable Epilepsy) - Causes : a) Improper Dx of seizure type (results in improper ASMs ) b) Failure to push the ASMs used to the maximal dosage c) Failure to use all available ASMs 59 8) Ketogenic diet -Lennox-Gastaut syndrome refractory to standard drug therapy -Progressive myoclonic epilepsy Diet contains a high proportion of fats & small amounts of CHO & protein(typically ratio of 4:1 ) Brain uses ketone bodies as primary fuel when it is deprived of glucose as an energy source(Ketosis)….acetoacetate & b-hydroxy butiric acid act as anticonvulsant drugs Effective in 1/3 -1/2 of children 60 9) Vagus Nerve Stimulation (VNS) Exact mechanism of action for seizure control remains unknown. Adjunctive treatment of partial seizures - In patients 12 years and older (FDA approval in 1997) Programmable NeuroCybernetic Prosthesis (NCP) generator is placed on patient's chest (upper left side). Lead is attached to left vagus nerve (midcervical portion) and delivers a biphasic current that continuously cycles b/n on and off periods. Electrical stimuli (