• Journal of Interdisciplinary Genomics
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• 제3권1호
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• pp.13-20
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• 2021

Developmental and epileptic encephalopathies are the most devastating early-onset epilepsies, characterized by early-onset seizures that are often intractable, electroencephalographic abnormalities, developmental delay or regression, and various comorbidities. A large number of underlying genetic variants of developmental and epileptic encephalopathies have been identified over the past few decades. However, the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. This review explores the genetic basis of developmental and epileptic encephalopathies that start within the first year of life, including Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, infantile spasms, and Dravet syndrome. The purpose of this review is to give an overview and encourage the clinicians to start considering genetic testing as an important investigation along with electroencephalogram for better understanding and management of developmental and epileptic encephalopathies.

• Clinical and Experimental Pediatrics
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• 제58권11호
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• pp.407-414
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• 2015

Early-onset epileptic encephalopathies are one of the most severe early onset epilepsies that can lead to progressive psychomotor impairment. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects, and an increasing number of novel genetic causes continue to be uncovered. A typical diagnostic approach includes documentation of anamnesis, determination of seizure semiology, electroencephalography, and neuroimaging. If primary biochemical investigations exclude precipitating conditions, a trial with the administration of a vitaminic compound (pyridoxine, pyridoxal-5-phosphate, or folinic acid) can then be initiated regardless of presumptive seizure causes. Patients with unclear etiologies should be considered for a further workup, which should include an evaluation for inherited metabolic defects and genetic analyses. Targeted next-generation sequencing panels showed a high diagnostic yield in patients with epileptic encephalopathy. Mutations associated with the emergence of epileptic encephalopathies can be identified in a targeted fashion by sequencing the most likely candidate genes. Next-generation sequencing technologies offer hope to a large number of patients with cryptogenic encephalopathies and will eventually lead to new therapeutic strategies and more favorable long-term outcomes.

• BMB Reports
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• 제52권5호
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• pp.304-311
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• 2019

The cytoplasmic FMR1-interacting protein family (CYFIP1 and CYFIP2) are evolutionarily conserved proteins originally identified as binding partners of the fragile X mental retardation protein (FMRP), a messenger RNA (mRNA)-binding protein whose loss causes the fragile X syndrome. Moreover, CYFIP is a key component of the heteropentameric WAVE regulatory complex (WRC), a critical regulator of neuronal actin dynamics. Therefore, CYFIP may play key roles in regulating both mRNA translation and actin polymerization, which are critically involved in proper neuronal development and function. Nevertheless, compared to CYFIP1, neuronal function and dysfunction of CYFIP2 remain largely unknown, possibly due to the relatively less well established association between CYFIP2 and brain disorders. Despite high amino acid sequence homology between CYFIP1 and CYFIP2, several in vitro and animal model studies have suggested that CYFIP2 has some unique neuronal functions distinct from those of CYFIP1. Furthermore, recent whole-exome sequencing studies identified de novo hot spot variants of CYFIP2 in patients with early infantile epileptic encephalopathy (EIEE), clearly implicating CYFIP2 dysfunction in neurological disorders. In this review, we highlight these recent investigations into the neuronal function and dysfunction of CYFIP2, and also discuss several key questions remaining about this intriguing neuronal protein.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.100-104
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• 2022

The gene encoding solute carrier family 9 member 6 (SLC9A6) on Xq26.3 is associated with Christianson syndrome (CS) mimicking Angelman syndrome. In CS, developmental and epileptic encephalopathy (DEE) appears in about 20%, and DEE with spike-and-wave activation in sleep (SWAS) is reported only in several cases. A 10-year-old boy with DEE showed multidrug resistant focal seizures from 6 months of age. He had progressive microcephaly, regression, global developmental delay without speech, hyperkinesia, and truncal ataxia; he had a long thin face, esotropia, and happy demeanor. Brain magnetic resonance imaging demonstrated cerebellar atrophy. Electroencephalogram at 7.5 years of age showed nearly continuous diffuse paroxysms in slow wave sleep. The seizures were responsive to corticosteroids for a while. Trio whole exome sequencing exhibited a likely pathogenic variant of SLC9A6 in the proband and his asymptomatic mother: c.1194dup (p.Leu399AlafsTer12). This is a rare case report of CS with DEE-SWAS in a Korean patient.

• Annals of Clinical Neurophysiology
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• 제9권2호
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• pp.63-68
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• 2007

The EEG plays an important diagnostic role in epilepsy and provides supporting evidence of a seizure disorder as well as assisting with classification of seizures and epilepsy syndromes. There are a variety of electroclinical syndromes that are really defined by the EEG such as Lennox-Gastaut syndrome, benign rolandic epilepsy, childhood absence epilepsy, juvenile myoclonic epilepsy and also for localization purposes, it is vitally important especially for temporal lobe epilepsy. The sensitivity of first routine EEG in diagnosis of epilepsy has been known about 20-50%, but this proportion rises to 80-90% if sleep EEG and repetitive recording should be added. Convincing evidences suggest that the EEG may also provide useful prognostic information regarding seizure recurrence after a single unprovoked attack and following antiepileptic drug (AED) withdrawal. Moreover, patterns in the EEG make it possible to disclose an ictal feature of nonconvulsive status epilepticus, separate epileptic from other non-epileptic episodes and clarify the clues predictive of the cause of the encephalopathy (i.e., triphasic waves in metabolic encephalopathy). Therefore, regardless of its low sensitivity and other pitfalls, EEG should be considered not only in the situation of new onset episode such as a newly developed, unprovoked seizure or a condition manifesting decreased mentality from obscure origin, but also as a barometer of the long-term outcome following AED withdrawal.

• Journal of Korean Neurosurgical Society
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• 제58권2호
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• pp.159-162
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• 2015

Neurological deficits after brain surgery are not uncommon, and correct and prompt differential diagnosis is essential to initiate appropriate treatment. We describe a patient suffering from loss of consciousness due to hyperammonemia, following valproic acid treatment after surgery for an unruptured cerebral aneurysm. A 57-year-old female patient underwent successful aneurysmal neck clipping to correct an unruptured aneurysm. Her postoperative course was good, and she received anti-epileptic therapy (valproic acid) and a soft diet. Within a few days the patient experienced mental deterioration. Her serum valproic acid reached toxic levels (149.40 mg/L), and serum ammonia was fifteen times the upper normal limit (553 mmol/L; normal range, 9-33 mmol/L). After discontinuation of valproic acid and with conservative treatment, the patient recovered without any complications. Valproate-induced hyperammonemic encephalopathy is an unusual but serious neurosurgical complication, and should not be disregarded as a possible cause of neurological deficits after neurovascular surgery. Early diagnosis is crucial, as discontinuation of valproic acid therapy can prevent serious complications, including death.

• Journal of Genetic Medicine
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• 제18권2호
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• pp.137-141
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• 2021

Genetic causes of developmental and epileptic encephalopathy (DEE) have been rapidly uncovered from mid-2010s. The mutations of gene enconding calcium channel, voltage-dependent, P/Q type, alpha 1A subunit (CACNA1A) are recently detected in DEE, which gene is already known well in familial hemiplegic migrine type 1 or episodic ataxia type 2. Ketogenic diet therapy (KDT) is effective in some DEE, which data is short in CACNA1A encephalopathy. A 3-month-old male with global developmental delay and multidrug-resistant focal seizures was diagnosed as epilepsy of infancy with migrating focal seizures (EIMFS). Brain magnetic resonance imaging and metabolic screening were all normal. Whole exome sequencing revealed two variants of CACNA1A: c.899A>C, and c.2808del that is from his mother. His seizures disappeared within 3 days whenever on KDT, which recurred without it. To our knowledge, this rare case of EIMFS with novel mutations of CACNA1A, is the first report in CACNA1A encephalopathy becoming seizure-free on KDT.

• Clinical and Experimental Pediatrics
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• 제52권9호
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• pp.964-970
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• 2009

Neonatal seizures are generally not only brief and subtle but also not easily recognized and are usually untreated. In sick neonates, seizures are frequently not manifested clinically but are detected only by electroencephalography (subclinical EEG seizures). This phenomenon of electroclinical dissociation is fairly common in neonates. On the other hand, neonates frequently show clinical behaviors such as stiffening, apnea, or autonomic manifestations that mimic seizures, which is usually associated with underlying encephalopathy and non-epileptic seizures. Therefore, it might be difficult to confirm the diagnosis of neonatal seizures. Early recognition of neonatal seizures is important to minimize poor neurodevelopmental outcomes, including cognitive, behavioral, and learning disabilities, as well as the development of postnatal epilepsy. EEG is a reliable tool in the determination of neonatal seizures. Continuous EEG monitoring is essential for the identification of seizures, evaluation of treatment efficacy, and prediction of the neurodevelopmental outcome. However, there is not yet a wide consensus on the optimal "standard" lead montage for the continuous EEG monitoring.

• Journal of Yeungnam Medical Science
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• 제2권1호
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• pp.103-111
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• 1985

저자들은 1983년 5월부터 1985년 11월까지 만 30개월간 본원 소아과를 통해 진료받은 100명의 소아간질환아를 대상으로 관찰한 결과 다음과 같은 성적을 얻었다. 1. 남녀별 발생빈도는 1.2:1로 남아에서 약간 많았다. 2. 경련발생 연령은 6개월 미만이 13예(12.6%), 6개월~3세군이 34예(33.0%), 3~5세군이 16예(15.5%), 5~10세군이 24예(23.3%), 10~15세군이 16예 (15.5%)였다. 3. 간질경련 양상은 generalized tonic-clonic, tonic, clonic seizure가 49.5%, 간대성 근경련이 5.8%, 비전형 소발작이 5.8%, 이완성발작이 1%였고, simple P.S.가 7.8%, complex P.S.가 3.9%, simple P.S. $\overline{c}$ 2nd G.이 17.5%, complex P.S. $\overline{c}$ 2nd G.이 2.9%, 미분류가 5.8%였다. 4. 간질의 원인으로 추정이 가능했던 경우가 17예(16.5%)였는데 주산기 저산소증(4.9%), 뇌막염(3.9%), 미숙아분만(1.9%) 등이 많은 원인이었다. 5. 간질과 동반된 질환은 30예(29%)에서 보였는데 지능장애, 과다행동증, 운동발달지연, 뇌성마비 등이 많았다. 6. 42예에서 행한 뇌 전산화단층촬영에서 14예의 이상소견을 보였는데 뇌 위축이 6예, 뇌경색이 3예, 수두증 및 뇌부종소견이 각각 2 예씩 나타났다.

• 대한임상검사과학회지
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• 제49권3호
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• pp.294-299
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• 2017

이 연구의 목적은 중첩성 뇌전증을 발견하고, 처음 기록된 30분 뇌파 패턴을 통하여 경련 가능성을 알아보고자 한다. 국제표준 10~20법을 통하여 전극을 부착하였다. 2014년 1월부터 2015년 12월까지 중환자실에 입원한 경련 의심 환자를 대상으로 하였다. 뇌파의 패턴은 주기적 방전파, 전반적 주기적 방전파, 버스트 억제파, 초점 뇌전증파, 비대칭 배경파, 전반적 서파, 삼상성 형태의 일반화 된 주기적 방전파 등 7 가지 범주로 분류하였다. 원인별 분류는 5가지 범주로 구분하였다. 전체 128명 중 평균 나이는 $56.9{\pm}17.5$였고, 남:여 비율은 74:54명이였다. 평균 뇌파검사 기간은 $5.5{\pm}5.1$일 이었고 최장 33일 이였다. 주기적 방전파(N=7), 전반적 주기적 방전파(N=10), 버스트 억제파(N=6), 초점 뇌전증파(N=19), 비대칭 배경파(N=24), 전반적 서파(N=51), 3상 형태의 일반화 된 주기적 방전파(N=11)이었다. 중첩성 뇌전증 환자의 원인은 원발성 증상성(N=4), 급성원발성 증상성(N=9), 급성 증상성(N=6), 진행성 뇌병증(N=2), 열성경련(N=1)이었다. 지속적 뇌파모니터링 검사는 중첩성 뇌전증을 발견하는데 유용한 검사이고, 뇌파 패턴을 통하여 경련 발생 유무를 확인할 수 있었다.