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Home , Epileptologist

10/21/2020

Outcome of Pediatric in Adulthood No financial disclosure

Suad Khalil, MD Pediatric Neurologist and Epileptologist MSU- Assistant Professor

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What does the term Objectives “outcome” mean ??

• History of (remission or persistence of seizures, evolution of pattern throughout life and response to AEDs) • Discuss global aspects of outcome of pediatric • The natural course of the disease causing the seizures epilepsies during adulthood • The comorbidities (changes in cognition, psychiatric • Discuss specific aspects of outcome in some symptoms, and sometimes of the neurological condition), epileptic syndromes, and focus on epilepsies that • The risk of mortality begin during infancy, childhood and adolescence • The familial and social impact of a disease that has started in childhood

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Epilepsy Syndromes

Age Seizure semiology EEG data Comorbidities

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The Syndrome Solar System Focal Generalized Unknown Idiopathic onset onset onset Etiology JAE Epilepsy with Primary reading JME epilepsy 10 yr grand-mal Structural seizures upon awakening Epilepsies with BECTS 1 yr specific modes Genetic Childhood of activation Childhood 1 mo absence epilepsy types epilepsy with BMEI occipital BNC Combined Infectious paroxysms BNFC Focal Generalized Unknown West Generalized EME EIEE Syndrome & Focal Cryptogenic or Symptomatic Focal Lennox-Gastault Epilepsies Neonatal Seizures Syndrome

Metabolic Focal Epilepsy with myoclono-astatic Rasmussen’s

Comorbidities seizures Syndrome Severe myoclonic Immune epilepsy in infancy Epilepsy with ESESS myoclonic Landau-Kleffner absences Syndrome Unknown Non-idiopathic

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In general…. In general….

• 50% of patients with pediatric epilepsies are going into remission as they age • Some epilepsies are characterized by the evolution of the • This percentage varies greatly according to epileptic seizure pattern (type, severity or frequency, remission or syndromes and etiologies of epilepsies no remission, etc) • Generally, children with idiopathic focal or generalized epilepsies show better prognosis and evolution as many outgrow their seizures and are relatively unaffected from the • While in others, the evolution is better characterized by cognitive point of view the occurrence of comorbidities (cognition and psychiatric manifestations) that appear and progress over time overtaking the seizures themselves Camfield et al.,1993

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In general… Neonatal Epilepsies

• In symptomatic epilepsies, the etiology itself has a • Etiology…Etiology…and Etiology great impact on the overall prognosis in adulthood Self-limited neonatal seizures Self- limited familial neonatal epilepsy Seizures Progressive lesional brain processes • Start in the neonate between day 4 and 7 of life • Unilateral clonic events that recur and may Fixed brain lesion alternate sides from seizure to seizure • Seizures remit by 4-6 months of age. • May have seizures in later life, normal developmental milestones

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Early myoclonic encephalopathy (EME)

Epileptic Early Myoclonic Encephalopathy (EME) Early Infantile Epileptic Encephalopathy (EIEE) ● Most often associated w inborn errors of metabolism, less common are Encephalopathies congenital brain abnormalities West Syndrome ● EEG showing during sleep Lennox Gastuate Syndrome ● Clinical: encephalopathy + myoclonic (usu segmental) jerks in first few hours of  life, also have focal clonic seizures, later on tonic spasms ● Poor prognosis, depends on etiology

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Early infantile epileptic encephalopathy (EIEE)

● , usually related to structural abnormalities ● Onset w/in 2-3 months, frequent tonic spasms, developmental delay, spasticity. Can also have hemi-. ● EEG burst suppression at all stages ● Poor prognosis, 50% die in infancy, if survive severe impairment

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West Syndrome

● Epileptic infantile spasms ● Triad: spasms, psychomotor arrest, ● 90% affect by 1 yo, between 3-7 mo ● Etiology: brain dysfunction of some sort (migrational, neurocutaneous, metabolic, congenital malformation, etc) ● Treatment: ACTH, occ prednisone. Vigabitrin w 2/2 TS. ● prognosis: usually progresses to LGS, w/cognitive impairment

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Dravet Syndrome (SMEI)

• Severe of infancy, epileptic encephalopathy • Also has hypotonia, ataxia, pyramidal signs, dysautonomia • Mutation in SCN1A gene • Also in? (GEFS+) • Sz w/in 1 year of life, typically febrile clonic • Also get win 1-5 yo GTC Hypsarrhythmia • Hemiclonic, alternating (classic) • Absence, myoclonus, focal motor, dyscognitive

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Dravet Syndrome (SMEI)- Prognosis Severe seizures in childhood, onset prior to age 8 • Many cases evolve into LGS from other epilepsy • Initial catastrophic period; epilepsy is very active and status epilepticusis syndromes (West) common Lennox- Cause: genetic, neurocutaneous, hypoxia, • The seizure frequency tends to diminish during adolescence Gastaut meningitis, head injuries, etc etc etc. • 25% have hx West syndrome • The seizures remain frequent for most patients despite AED polytherapy Syndrome • In adults, generalized or unilateral tonic clonic seizures become frequent often (LGS) Clinical: nonspecific, however preceded by myoclonic characterized by: • They occur predominantly or exclusively during sleep >> SUDEP • Multiple sz types (tonic, atonic, atypical absence, myoclonic) • Developmental regression and psychomotor retardation • Interictal EEG: <2.5 Hz spike-wave/atypical spike- wave, most predominant in frontal regions • Mental retardation/developmental delay

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Lennox-Gastaut LGS-Prognosis Syndrome (LGS)  The Lennox Gastaut syndrome (LGS) is among the most severe forms of childhood epilepsy and many adult • The course of the syndrome is not homogeneous depending on whether LGS is cryptogenic or ● Treatment: uncertain, however symptomatic, Epilepsy remains active and intractable can use VPA, LTG, TPX, • Seizures tend to become less frequent with age but cognitive and behavioral problems increase in most rufinamide, felbamate, clobazam patients ○ Do not use partial sz drugs eg • Cognition and behavioral problems usually aggravate with age carbamazepine • The proportion of severely retarded adult patients is around 50%, and is more important among ○ Others: Ketogenic diet, VNS, symptomatic than cryptogenic cases • The cognitive decline is continuous all along the course of the disease, but fluctuations with transient surgery phases of psychomotor worsening are seen in adult patients and are not always correlated with the frequency or severity of seizures • risk of mortality is high in adult patients with LGS, around 17%

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Long-term outcome of idiopathic generalized Juvenile Myoclonic Epilepsy (JME) epilepsies

Idiopathic Generalized Epilepsies ● Adolescence Childhood ● Triad of myoclonic jerks, GTC, absence sz ○ Usually upon awakening, or w sleep deprivation Absence ○ Myoclonus (100%), GTC (85-100%), Absence (20-40%) Epilepsy ○ Absence predates other types, up to 5 years ○ Classic is clonic-tonic-clonic ● Often FH positive sz (33%) Juvenile Juvenile ● Epidemiology: 25-30% of idiopathic generalized epilepsies, 10% of all epilepsy Myoclonic Absence ○ Maybe slightly higher female preponderance Epilepsy Epilepsy ○ Age ~15yo

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JME - Prognosis Childhood Absence Epilepsy (CAE)

○ The prognosis for JME is generally considered excellent as the majority of ● Benign generalized epilepsy, in otherwise healthy patients are able to be treated successfully with AEDs childhood ● Epidemiology: 6.3/1000 in study w/Swedish children, ○ Seizure-free rates of 60% to 90% have been reported more in female vs male ● ○ Achieving seizure freedom often involves lifestyle modifications as well as Seizure: typical is short, frequent spell of compliance with AEDs impairment of consciousness, lasting avg 10 seconds, ○ Cognition: Generally normal, however frontal lobe dysfunction common without change in muscle tone. Abrupt onset/offset ○ ○ Psychiatric: up to 50% have either anxiety or mood disorder Provoked by hyperventilation ○ Can occur 100s/day ○ ○ Multiple studies in the past have suggested that JME is a lifelong condition Can have first signs include eyelid movements, and the medications were not to be discontinued. eye opening, automatisms ○ Other seizure types RARE

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CAE-Prognosis Benign

● BECTS (Benign epilepsy with centro-temporal spikes) • CAE is one the relatively benign childhood epilepsies, but not all patients ● 10-20% of all childhood epilepsies, mean age 7-9yo become seizure-free. ● EEG: ...centrotemporal spikes. Normal PDR. ○ Characteristics: biphasic, negative followed by positive • Approximately 50% of patients with CAE will have a spontaneous remission ○ Bilateral, independent ○ by the age of 10 to 12 years, with a range of 21% to 89% remission. Occur almost exclusively during sleep (non-REM) ● If do not fit above, need to look further into other partial • In patients with absence seizures only, the seizure- free rate is epilepsies approximately 80%, while patients with GTC seizures and absence were only ● facial/oropharyngeal sz (twitching, hypersalivation, drooling, 30% seizure-free vocalizations • A Dutch study with long- term follow up (12 to 17 years) indicated that ● secondary generalizations, nocturnal seizure free-dom in the first 6 months of treatment predicted outcome ● Rx: only when disruptive/harmful ○ • Cognition: generally normal Carbamazepine (or derivatives thereof) is classic, prn BZD • Common to have psychiatric disease (ADHD, anxiety)

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Benign childhood epilepsy with centrotemporal spikes

• The long-term prognosis of BECTS is excellent, even in those with initially frequent, troublesome seizures, with all patients achieving remission by mid-adolescence • learning and behavior problems may be seen in the acute phase, long-term psychosocial outcome is excellent with no increase in Questions?? psychiatric problems or personality problems, and excellent occupational status

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References Referances

• Holopainen IE (2008). Seizures in the developing brain: cellular and molecular mechanisms of • https://www.epilepsydiagnosis.org neuronal damage, neurogen- esis and cellular reorganization. Neurochem Int 52: 935–947. • Hommet C, Billard C, Motte J et al. (2001). Cognitive function in adolescents and young adults in • complete remission from benign childhood epilepsy with centro-temporal spikes. Epileptic Disord • https://www.ilae.org 3: 207–216. • Hurst DL (1987). Severe myoclonic epilepsy of infancy. Pediatr Neurol 3: 269–272 • Wyllie's Treatment of Epilepsy: Principles and Practice 7th Edition • Dravet C, Bureau M, Oguni H et al. (2005). Severe myoclonic epilepsy in infants. In: J Roger, M Bureau, C Dravet et al. (Eds.), Epileptic Syndromes in Infancy, Childhood and Adolescence. 4th by Elaine Wyllie MD edn. John Libbey Eurotext, London, pp. 89–114. • Dulac O (2001). Epileptic encephalopathy. Epilepsia 42: 23–26. • Fastenau PS, Johnson CS, Perkins SM et al. (2009). Neuropsychological status at seizure onset in children: risk factors for early cognitive deficits. 73: 526–534. • Galanopoulou AS, Bojko A, Lado F et al. (2000). The spec- trum of neuropsychiatric abnormalities associated with electrical in sleep. Brain Dev 22: 279–295

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