Differentiating non-epileptic seizures from epileptic seizures in Glut1 deficiency syndrome.

AIM: To investigate the clinical characteristics of non-epileptic seizures due to transient brain dysfunction caused by energy deficiency after prolonged fasting or exercise in individuals with glucose transporter type 1 deficiency syndrome (Glut1DS), and then elucidate further the seizure features to distinguish non-epileptic seizures from epileptic seizures. METHOD: This retrospective case-control study included 57 non-epileptic seizures and 23 epileptic seizures (control group) in 14 individuals (11 males, three females; aged 5-44 years, median = 20 years) with Glut1DS, all with a heterozygous pathogenic SLC2A1 mutation. RESULTS: Non-epileptic seizures were classified as paroxysmal altered consciousness (n = 8), movement disorders (n = 35) (eye-head movements, ataxia, spasticity, weakness, involuntary movement), dysaesthesia (n = 8), and vomiting (n = 6) at the peak ages at onset of 5 to 10 years. Ketogenic diet therapy was effective in 33 of 43 (77%) non-epileptic seizures. Providing supplementary food before high-impact exercise or during attacks prevented or mitigated non-epileptic seizures in some individuals. Glut1DS-associated non-epileptic seizures are fundamentally situation-related seizures with specific provoking and ameliorating factors. Non-epileptic seizures can be distinguished from epileptic seizures by the absence of complete consciousness loss and rapid postictal recovery despite prolonged seizures. INTERPRETATION: Non-epileptic seizures are not well recognized but require different therapeutic approaches compared to epileptic seizures. Awareness of the differentiation of non-epileptic seizures from epileptic seizures is essential when performing preventive or therapeutic decision-making for acute exacerbation seizures.

Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy.

BACKGROUND: In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis. METHODS: Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds ratios in case-control associations, and allele frequencies in the Genome Aggregation Database. We performed functional tests of the effects of variants on mitosis, apoptosis, and radial neuroblast migration in vitro and conducted video-EEG studies in mice lacking a copy of Ick. RESULTS: A variant, K305T (c.914A→C), cosegregated with epilepsy or polyspikes on EEG in 12 members of the family affected with juvenile myoclonic epilepsy. We identified 21 pathogenic ICK variants in 22 of 310 additional patients (7%). Four strongly linked variants (K220E, K305T, A615T, and R632X) impaired mitosis, cell-cycle exit, and radial neuroblast migration while promoting apoptosis. Tonic-clonic convulsions and polyspikes on EEG resembling seizures in human juvenile myoclonic epilepsy occurred more often in knockout heterozygous mice than in wild-type mice (P=0.02) during light sleep with isoflurane anesthesia. CONCLUSIONS: Our data provide evidence that heterozygous variants in ICK caused juvenile myoclonic epilepsy in 7% of the patients included in our analysis. Variant ICK affects cell processes that help explain microdysgenesis and polyspike networks observed on EEG in juvenile myoclonic epilepsy. (Funded by the National Institutes of Health and others.).

Recurrent NUS1 canonical splice donor site mutation in two unrelated individuals with epilepsy, myoclonus, ataxia and scoliosis - a case report.

BACKGROUND: We encountered two unrelated individuals suffering from neurological disorders, including epilepsy and scoliosis. CASE PRESENTATION: Whole-exome sequencing identified the same recurrent, de novo, pathogenic variant in NUS1 [NM_138459.4:c.691 + 1C > A] in both individuals. This variant is located in the conserved cis-prenyltransferase domain of the nuclear undecaprenyl pyrophosphate synthase 1 gene (NUS1), which encodes the Nogo-B receptor, an essential catalyst for protein glycosylation. This variant was confirmed to create a new splice donor site, resulting in aberrant RNA splicing resulting in a 91-bp deletion in exon 3 in both individuals. The mutant mRNA was partially degraded by nonsense mediated mRNA decay. To date, only four de novo variants and one homozygous variant have been reported in NUS1, which cause developmental and epileptic encephalopathy, early onset Parkinson's disease, and a congenital disorder of glycosylation. Seven patients, including our two patients, have presented with epileptic seizures and intellectual disabilities. CONCLUSIONS: Our study strongly supports the finding that this recurrent, de novo, variant in NUS1 causes developmental and epileptic encephalopathy with involuntary movement, ataxia and scoliosis.

Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts.

BACKGROUND: Leukoencephalopathy with brain calcifications and cysts (LCC) is neuroradiologically characterized by leukoencephalopathy, intracranial calcification, and cysts. Coats plus syndrome is also characterized by the same neuroradiological findings together with defects in retinal vascular development. Indeed, LCC and Coats plus were originally considered to be the same clinical entity termed cerebroretinal microangiopathy with calcifications and cysts, but evidence suggests that they are genetically distinct. Mutations in CTS telomere maintenance complex component 1 (CTC1) and small nucleolar RNA, C/D box 118 (SNORD118) genes have been found to cause Coats plus and LCC, respectively. MATERIALS AND METHODS: Eight unrelated families with LCC were recruited. These patients typically showed major neuroradiological findings of LCC with no signs of extra-neurological manifestations such as retinal abnormality, gastrointestinal bleeding, or hematological abnormalities. SNORD118 was examined by Sanger sequencing in these families. RESULTS: Seven out of eight probands carry compound heterozygous mutations, suggesting that SNORD118 mutations are the major cause of LCC. We identified a total of eight mutation, including four that were novel. Some of the variants identified in this study present heterozygously in public databases with an extremely rare frequency (<0.1%). CONCLUSION: Biallelic SNORD118 mutations were exclusively found in most unrelated families with LCC.

[Treatment of pediatric epilepsy].

Recently, the treatment strategy for pediatric epilepsy has been dramatically changed in Japan, because of the approval of new-generation antiepileptic drugs. Since 2006, a total of 6 new antiepileptic drugs, including gabapentin (GBP; adults/pediatric patients: 2006/2011 [year of approval]), topiramate (TPM; 2007/2013), lamotrigine (LTG; 2008/2008), levetiracetam (LEV; 2010/2013), stiripentol (STP; 2012/2012), and rufinamide (RUF; 2013/2013), have been introduced. Thus far, valproate (VPA) and carbamazepine (CBZ) have been first indicated for "generalized" epilepsy and "focal" epilepsy syndromes/types, respectively, in Japan. However, the approval of these new drugs could allow us to choose more effective and less toxic ones at an early stage of treatment. In this chapter, we describe the latest domestic and foreign guidelines for the treatment of pediatric epilepsy.

A cryptic microdeletion including MBD5 occurring within the breakpoint of a reciprocal translocation between chromosomes 2 and 5 in a patient with developmental delay and obesity.

The 2q23.1 deletion syndrome has been recently recognized as a neurodevelopmental disorder associated with intellectual disability, epilepsy, and autism spectrum disorder. Recently, methyl-CpG-binding domain 5 gene (MBD5), located in the 2q23.1 region, has been considered as a single causative gene of this syndrome. We report on a female patient with a de novo reciprocal translocation between chromosomes 2 and 5. Chromosomal microarray testing revealed a cryptic 896 kb deletion that included MBD5. Although clinical manifestations of this patient are compatible with those of patients with 2q23.1 deletion syndrome, a focal pachygyria revealed by brain magnetic resonance imaging has never been observed in the previously reported cases. Obesity caused by hyperphagia was observed in our patient and 28% of the previously reported patients with the 2q23.1 deletion syndrome. For better medical management, appropriate dietary guidance against hyperphagia should be given to the patients' family.

Mutations in EFHC1 cause juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.

A reappraisal of interictal EEG characteristics in self-limited epilepsy with autonomic seizures, formerly known as Panayiotopoulos syndrome or early-onset benign occipital epilepsy.

PURPOSE: In the 2022 New International Classification of Epilepsy Syndromes, self-limited epilepsy with autonomic seizures (SeLEAS), formerly known as Panayiotopoulos syndrome is recognized as an electroclinical syndrome that is clinically characterized by autonomic seizures and electroencephalographically by multifocal EEG foci. EEG studies were reviewed herein and the suitability of the EEG definition to characterize SeLEAS was assessed. METHODS AND RESULTS: The EEG findings of SeLEAS studies published to date were reviewed and typical sites of EEG foci and their evolutionary changes with age were analyzed. Although previous studies investigated the details of interictal EEG characteristics in a sufficient number of SeLEAS cases, there were few systematically analyzing cross sectional and longitudinal EEG changes except one study. Despite these limited evidence, I propose the following practical and useful EEG definition. The interictal EEG characteristics of SeLEAS are multifocal EEG foci with age-dependent predominant locations; occipital (O) at 2-5 years old, and occipital and frontopolar (synchronous and independent O and Fp spikes) at 4-7 years old and centro-parieto-temporal (CPT) at 6-10 years old. O EEG foci evolve to multifocal EEG foci with a O-Fp or CPT predominance with age and disappear by 12∼16 years old. O-Fp EEG foci may further evolve to generalized spike-wave complexes and rarely to spike-wave activated in sleep. In rare cases, the EEGs do not have epileptic EEG foci. CONCLUSION: Interictal EEG foci in SeLAES may have different EEG patterns in terms of location and the mode of appearance depending on the age at which EEG is recorded. O-Fp EEG foci may be a specific EEG pattern indicating a diagnosis of SeLEAS.

[Epilepsy in Children].

Childhood epilepsy is characterized by specific epilepsy syndromes that occur during each developmental age. These "age-dependent" epilepsy syndromes are clinically categorized into a self-limited epilepsy group with good prognosis and high prevalence rate and a pharmacoresistant epilepsy group with poor prognosis despite low prevalence rates. Many children develop pharmacoresistant epilepsy beginning in early infancy and progress to developmental epileptic encephalopathy, which is associated with intellectual, behavioral, and/or motor disabilities. These children do not show remission in epilepsy and are transitioned to the adult service and require comprehensive medical care.

[A child with paroxysmal exertion-induced dyskinesia].

We experienced a 12-year-old boy with paroxysmal exertion (exercise)-induced dyskinesia (PED). His attacks, characterized by painless paralytic stiffness of the extremities during running or playing, developed at 4 years of age. He was initially diagnosed as having epilepsy based on epileptic discharges on interictal EEG. Although several anti-epileptic drugs were not effective, clorazepate was found to be very useful for complete control of attacks for 3 years. His attacks recurred at 8 years of age and appeared to be aggravated by psychological stress, fatigue and lack of sleep. His attacks were confirmed to be non-epileptic paroxysmal hypokinesia with rigid tetraplegia, by ictal video EEG recording, and he was diagnosed as having PED. They did not respond to various anti-epileptic drugs and L-dopa/carbidopa. His attacks were reduced to some extent by administration of hydroxyzine. PED is a very rare condition and similar to paroxysmal kinesigenic dyskinesia (PKD). There is a strong possibility that patients with PED have been misdiagnosed as PKD.

Epilepsy with myoclonic-atonic seizures, also known as Doose syndrome: Modification of the diagnostic criteria.

PURPOSE: The aim of this review is to propose the updated diagnostic criteria of epilepsy with myoclonic-atonic seizures (EMAS), which is a recent subject of genetic studies. Although EMAS has been well known as Doose syndrome, it is often difficult to diagnose due to a lack of consensus regarding some of the inclusion criteria. Along with progress in molecular genetic study on the syndrome, it becomes important to recruit electroclinical homogeneous EMAS patients, hence the validity of the clinical criteria should be verified based on recent clinical researches. At present, the most updated ILAE diagnostic manual of EMAS includes: (1) normal development and cognition before the onset of epilepsy; (2) onset of epilepsy between 6 months and 6 years of age (peak: 2-4 years); (3) myoclonic-atonic seizures (MAS) are mandatory (4) presence of generalized spike-wave discharges at 2-3 Hz without persistent focal spike discharges; and (5) exclusion of other myoclonic epilepsy syndromes. In the criteria, we should emphasize that the age at onset of MAS is between 2-5 years in (2), presence of myoclonic-atonic, atonic or myoclonic-flexor seizures (MASs) causing drop attacks associated with generalized spike-wave discharges is mandatory in (3), and epileptic spasms causing drop attacks must be excluded in (5). In the modified criteria, I propose that EMAS is redesignated as genetic generalized epilepsy with MASs, consistent with the familial genetic study conducted by Doose and the recent identification of candidate genes. It should also be noted that EMASs evolves to transient or long-lasting epileptic encephalopathy.

Non-lesional late-onset epilepsy in the elderly Japanese patients: Presenting characteristics and seizure outcomes with regard to comorbid dementia.

The objective of the present retrospective study was analysis of clinical, radiological, and electrophysiological characteristics of the non-lesional late-onset epilepsy (NLLOE) in the elderly Japanese patients, and comparison of the seizure outcomes in this population with regard to presence of comorbid dementia. The study cohort comprised 89 consecutive patients with NLLOE aged ≥ 65 years. In 49 cases (55%), NLLOE manifested with a single type of seizure. Focal impaired awareness seizures (FIAS) were encountered most often (in 69 patients; 78%). Ten patients (11%) had a history of the status epilepticus. Comorbid dementia was diagnosed in 31 patients (35%). Localized or diffuse white matter hyperintensity was the most common imaging finding (66 cases). Epileptiform discharges in the temporal area represented the most frequent abnormality on interictal EEG (24 cases). Seizure-free status for ≥ 12 months was attained in 46 out of 64 patients (72%), who were followed for ≥ 12 months (range, 12 - 110 months), and 42 of them received monotherapy, mainly with levetiracetam (21 patients), carbamazepine (10 patients), or lacosamide (8 patients). In comparison to their counterparts, the rate of seizure-free status for ≥ 12 months was significantly lower in patients with comorbid dementia (81% vs. 52%; P = 0.0205). In conclusion, the NLLOE among Japanese patients aged ≥ 65 years has variable presenting characteristics, and comorbid dementia is diagnosed in one-third of cases. Seizure-free status for ≥ 12 months may be attained in more than two-thirds of treated patients, but comorbid dementia is associated with significantly worse response to antiseizure therapy.

CUX2 deficiency causes facilitation of excitatory synaptic transmission onto hippocampus and increased seizure susceptibility to kainate.

CUX2 gene encodes a transcription factor that controls neuronal proliferation, dendrite branching and synapse formation, locating at the epilepsy-associated chromosomal region 12q24 that we previously identified by a genome-wide association study (GWAS) in Japanese population. A CUX2 recurrent de novo variant p.E590K has been described in patients with rare epileptic encephalopathies and the gene is a candidate for the locus, however the mutation may not be enough to generate the genome-wide significance in the GWAS and whether CUX2 variants appear in other types of epilepsies and physiopathological mechanisms are remained to be investigated. Here in this study, we conducted targeted sequencings of CUX2, a paralog CUX1 and its short isoform CASP harboring a unique C-terminus on 271 Japanese patients with a variety of epilepsies, and found that multiple CUX2 missense variants, other than the p.E590K, and some CASP variants including a deletion, predominantly appeared in patients with temporal lobe epilepsy (TLE). The CUX2 variants showed abnormal localization in human cell culture analysis. While wild-type CUX2 enhances dendritic arborization in fly neurons, the effect was compromised by some of the variants. Cux2- and Casp-specific knockout mice both showed high susceptibility to kainate, increased excitatory cell number in the entorhinal cortex, and significant enhancement in glutamatergic synaptic transmission to the hippocampus. CASP and CUX2 proteins physiologically bound to each other and co-expressed in excitatory neurons in brain regions including the entorhinal cortex. These results suggest that CUX2 and CASP variants contribute to the TLE pathology through a facilitation of excitatory synaptic transmission from entorhinal cortex to hippocampus.

Borderline Dravet syndrome: a useful diagnostic category?

The term "borderline" severe myoclonic epilepsy of infancy (SMEIB) has been used to designate patients in whom myoclonic seizures or generalized spike and wave activity are absent. It has also been used loosely to indicate mild forms of the syndrome. It is now acknowledged that the course and outcome of patients with SMEIB are the same as in the core syndrome. The rate of patients exhibiting SCN1A gene mutations is also similar, and it has been observed that the same mutations can cause both typical and "borderline" forms, indicating causal homogeneity. Defining a borderline form of a syndrome would mean setting the criteria of semiology and severity whereby a given phenotype falls within and outside the core syndrome. Such process has never been made for Dravet syndrome and is of course unrealistic in view its polymorphic expression. The eponym Dravet syndrome has been preferred to designate a syndrome spectrum that also embraces SMEIB. Therefore the term "borderline" Dravet syndrome is improper. The definition "mild form" of Dravet syndrome would certainly be more suitable to indicate those patients exhibiting a less severe or incomplete form of the syndrome. Variability in severity favors the concept that SCN1A loss of function causes a spectrum of epilepsy phenotypes in which seizures, often prolonged and precipitated by fever, are the prominent feature and schematic subdivisions would be inappropriate, at least in the early stages. An initial definition of SCN1A gene-related epilepsy would perhaps be more suitable when a mutation of this gene is ascertained and the clinical picture is still ill defined.

Retrospective multiinstitutional study of the prevalence of early death in Dravet syndrome.

PURPOSE: A questionnaire survey was conducted in Japan to investigate the causes and prevalence of death related to Dravet syndrome. METHODS: A questionnaire was delivered to 246 hospitals at which physicians were treating childhood epilepsy to gain information about the total number of patients with Dravet syndrome and their prevalence of early death. KEY FINDINGS: Responses to the survey were collected from 91 hospitals, and a total of 63 of 623 patients with Dravet syndrome died. Data from 59 of these patients were analyzed. The patients' ages at death ranged from 13 months to 24 years and 11 months, with a median age of 6 years and 8 months. The analysis showed that the risk of mortality remained high up to approximately 12 years of age. The causes of mortality included sudden death in 31 patients (53%), acute encephalopathy with status epilepticus (SE) in 21 patients (36%), drowning in 6 patients (10%), and acute hepatopathy in one patient (1%). The incidence of sudden death reached a first peak at 1-3 years of age and reached a second peak at 18 years and older. In contrast, the incidence of acute encephalopathy with SE reached a sharp peak at 6 years of age. Seven of 10 patients who underwent an SCN1A mutation analysis exhibited positive mutations without a specific mutation site. SIGNIFICANCE: In the present study, the prevalence of Dravet syndrome-related mortality was 10.1%. The incidence of sudden death and acute encephalopathy with SE was the highest in infancy (1-3 years) and at early school ages (with a peak at 6 years), respectively. After approximately 12 years of age, the risk of mortality declined sharply. Neither the treatment nor the number of seizures was associated with any cause of mortality. In addition, it is difficult to predict which factors lead to a fatal outcome.

Mortality in Dravet syndrome: search for risk factors in Japanese patients.

A questionnaire survey was conducted in Japan to investigate the causes and prevalence of death related to Dravet syndrome. The questionnaire was delivered to 246 hospitals at which physicians were treating childhood epilepsy to gain information about the total number of patients with Dravet syndrome and the prevalence of early death due to the disorder. Responses to the survey were collected from 91 hospitals, and a total of 63 of 623 patients with Dravet syndrome had died. Data from 59 of these patients were analyzed. The age at death for these patients ranged from 13 months to 24 years and 11 months, with a median age of 6 years and 8 months. The causes of mortality included sudden death in 31 patients (53%), acute encephalopathy with status epilepticus (SE) in 21 patients (36%), drowning in 6 patients (10%), and other causes in one patient (1%). The incidence of sudden death reached a first peak at 1-3 years of age and a second peak at 18 years and older. In contrast, the incidence of acute encephalopathy with SE reached a peak at 6 years of age. Seven of the 10 patients who underwent SCN1A mutation analysis exhibited positive mutations but exhibited no consistent phenotype. The prevalence of Dravet syndrome-related mortality was 10.1%. The incidence of sudden death and acute encephalopathy with SE was higher in infancy (1-3 years) and at early school ages (with a peak at 6 years), respectively. Neither the treatment nor the number of seizures was associated with any cause of mortality. Factors leading to a fatal outcome are difficult to predict.

CDKL5 alterations lead to early epileptic encephalopathy in both genders.

PURPOSE: Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. METHODS: A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. KEY FINDINGS: One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. SIGNIFICANCE: We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients.

A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome.

AIM: Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a metabolic encephalopathy that can be effectively treated with a ketogenic diet. The aim of this study was to consolidate the effectiveness of the modified Atkins diet (MAD) as an alternative treatment for GLUT1-DS. METHOD: Six Japanese males with GLUT1-DS were selected for treatment with the MAD. Their age at the time the MAD was instituted ranged from 7 to 16 years and the duration of treatment ranged from 1 to 42 months. All participants had early-onset epilepsy. Each participant's neuropsychological activity, seizure frequency, neurological status, and electroencephalographic (EEG) findings were compared before and after the introduction of the MAD. RESULTS: After initiation of the treatment, all individuals showed +2 to +3 urinary ketosis on a ketostick test check. Epileptic seizures and other paroxysmal events decreased markedly in all individuals. Interictal EEG showed improvement in the background activity and disappearance of epileptic discharges. Along with an increased vigilance level, improvement in motivation and cognitive function was also achieved. Non-paroxysmal permanent ataxia, spasticity, dysarthria, and dystonia were moderately improved in four individuals and slightly improved in the remaining two. Preprandial transient aggravation of neurological symptoms completely disappeared in all participants. There were no significant side effects. INTERPRETATION: For the treatment of GLUT1-DS, the MAD is less restrictive, more palatable, and easier to maintain than the conventional ketogenic diet, but its effectiveness was similar. Thus, MAD treatment is promising for individuals with GLUT1-DS and their families.

[Three children with Rasmussen encephalitis showing marked improvement in daily life activity following the functional hemispherectomy].

We investigated seizure, intelligence quotient (IQ), and neurological outcomes including the process of motor function recovery after functional right hemispherectomy in 3 children with Rasmussen's encephalitis (RE). Before the procedure, they were unable to walk, nor sit without support due to progressive worsening of left hemiplegia and relentless epilepsia partialis continua (EPC) of the left extremities, which were refractory to antiepileptic drug and immunological treatment. After functional right hemispherectomy, EPC completely disappeared, although complete left hemiplegia was sustained. However, they recovered up to being able to walk independently with assistance devices, and to have an ordinary life with family support within 1.5 to 5 months through rehabilitation. At the same time, the interictal EEG improved on the unaffected side of hemisphere, exhibiting a posterior alpha rhythm. Their IQ also improved, and they were able to attend school. Early functional hemispherectomy should be considered before patients with RE are left in a serious condition due to progressive worsening of hemiplegia and seizures refractory to the available treatment.