Possible Role of High-Dose Barbiturates and Early Administration of Parenteral Ketogenic Diet for Reducing Development of Chronic Epilepsy in Febrile Infection-Related Epilepsy Syndrome: A Case Report.

We describe the efficacy of high-dose barbiturates and early administration of a parenteral ketogenic diet (KD) as initial treatments for acute status epilepticus (SE) in an 8-year-old girl with febrile infection-related epilepsy syndrome (FIRES). The patient was admitted to our hospital with refractory focal SE. Abundant epileptic discharges over the left frontal region were observed on electroencephalogram (EEG). Treatment with continuous infusion of thiamylal for 4 hours, increased incrementally to 40 mg/kg/h, successfully ended the clinical SE, and induced a burst-suppression coma. The infusion rate was then gradually decreased to 4 mg/kg/h over the next 12 hours. Parenteral KD was administered from days 6 to 21 of illness. Continuous infusion of thiamylal was switched to midazolam on day 10 without causing seizures or EEG exacerbations. The patient has remained seizure free in the 15 months since hospital discharge. The effectiveness of KD for the treatment of FIRES has attracted attention amongst clinicians, but KD treatment may need to last for 2 to 4 days before it can stop SE, a time period that could cause irreversible brain damage. Considering the severity of SE in our patient and the dose of barbiturates needed to treat it, we consider this case to have had a good clinical outcome. The results suggest that rapid termination of seizure using high-dose barbiturates in conjunction with early administration of parenteral KD could reduce the development of chronic epilepsy in patients with FIRES.

Higher intelligence may be a risk factor for postoperative transient disturbance of consciousness after corpus callosotomy.

INTRODUCTION: Corpus callosotomy (CC) is an established surgical option for palliative treatment of medically intractable epilepsy, especially for seizures with drop attacks. We postulated that specific risk factors for post-CC transient disturbance of consciousness (pCTDC) are associated with CC. The purpose of this study was to review patients with intractable epilepsy who underwent CC and to statistically analyze risk factors for pCTDC. METHODS: Inclusion criteria for patients who underwent CC between January 2009 and November 2019 were: (1) ≥2 years old and (2) followed up for more than 8 months. The state of consciousness before and after CC was evaluated with the Glasgow coma scale. We statistically assessed predictors for pCTDC as the primary outcome. RESULTS: Fifty-six patients (19 females, 37 males) were enrolled, and the age range was 2-57 years old. Thirty-seven (66.1%) patients developed pCTDC. The mean period from the beginning of the state of pCTDC to recovery to their baseline conscious level was 4.9 days (range: 2-25 days). All three (100%) normal intelligence level patients, 13 (81%) of 16 patients with a moderately impaired level of intelligence, and 21 (57%) of 37 patients with a severely impaired level of intelligence exhibited pCTDC. Univariate (p = 0.044) and multivariate (p = 0.006) logistic regression analyses for predictors of pCTDC showed that intellectual function was statistically significant. CONCLUSION: Two-thirds of patients developed pCTDC. One risk factor for pCTDC may be higher intellectual function.

Epilepsy in patients with focal cortical dysplasia may be associated with autism spectrum disorder.

INTRODUCTION: Patients with epilepsy associated with focal cortical dysplasia (FCD) may be associated with autism spectrum disorder (ASD). Therefore, the purpose of this study was to compare surgically treated patients with epilepsy secondary to FCD and normal volunteers without epilepsy and to review the neuropathological findings of patients with FCD. METHODS: This study involved 38 patients with medically intractable focal onset epileptic seizures who underwent epilepsy surgery (Group 1). All patients had epilepsy associated with FCD. These patients and 38 normal volunteers without epilepsy (Group 2) were administered the autism spectrum quotient (AQ) test, and the groups were compared. RESULTS: The 38 patients in Group 1 included 16 females and 22 males (age range 20-60, mean age, 33.0; standard deviation (SD), 11.8 years). The normal volunteers in Group 2 included 22 females and 16 males (age range 20-57, mean age, 30.6 years; SD, 8.8 years). Total AQ scores were significantly higher in Group 1 than Group 2 (p = 0.027). Patients with FCD I showed a higher AQ score than those with FCD II in the AQ test (p ≤ 0.001). CONCLUSION: Patients with epilepsy secondary to FCD were associated with higher ASD score than normal volunteers. This tendency was seen more strongly in patients with FCD I than FCD II.

Posttraumatic epilepsy may be a state in which underlying epileptogenicity involves focal cortical dysplasia.

INTRODUCTION: The occurrence rate of posttrauma epilepsy ranges widely from 1% to 30%. Little is known about the underlying epileptogenesis of traumatic brain injury (TBI)-related epilepsy (TRE), because no comparison between TRE and TBI without epilepsy has been performed in terms of neuropathology. Therefore, we postulated that different neuropathological factors may be present between TRE and TBI without epilepsy. The purpose of this study was to clarify differences between TRE and TBI without epilepsy. METHODS: We studied patients who experienced severe head trauma and underwent brain surgery. The age range of the patients was 9-71 years old. Patients with medically resistant epilepsy were included in the Epilepsy group, and patients without epilepsy were included in the nonepilepsy group. Pathological findings, age, sex, and cause of head trauma were statistically compared between these two groups. RESULTS: This study involved 10 patients, nine of whom met the inclusion criteria. Pathological findings for all patients in the Epilepsy group included focal cortical dysplasia (FCD) (p = 0.012). CONCLUSION: The difference between TRE and TBI without epilepsy was underlying FCD in patients with TRE.

Seizure focus in the frontal interhemispheric fissure leads to ipsilateral isolated eye deviation.

OBJECTIVE: Few studies have examined the localization of seizures presenting with ictal eye deviation (ED) in the absence of other motor symptoms. We aimed to investigate differences in the localization of the ictal onset zone (IOZ) between patients with isolated ED and those with ED plus head turning (HT) during focal seizures. METHODS: We reviewed intracranial video-EEG data for 931 seizures in 80 patients with focal onset epilepsy in whom the IOZ could be confirmed. The 233 seizures in 49 patients with ED were classified into two semiological groups based on initial ED and the presence/absence of HT: (1) isolated ED (i.e., ED without HT), and (2) ED + HT (i.e., ED with HT). We analyzed the localization and lateralization of IOZs in each semiological group. We performed multivariate logistic regression analysis using a mixed-effects to determine the associations between IOZs and isolated ED/ED + HT. RESULTS: A total of 183 IOZs in 24 patients were included in the isolated ED group, while a total of 143 IOZs in 31 patients were included in the ED + HT group. Sixty-eight IOZs of eight patients in the isolated ED group were located in the ipsilateral frontal interhemispheric fissure (F-IHF). Only ipsilateral F-IHF was significantly associated with isolated ED (odds ratio [OR], 2.43; 95% confidence interval [CI], 0.37-4.49; P = 0.021). The contralateral lateral frontal cortex (latF) (P = 0.007) and ipsilateral mesial temporal region (mT) (P = 0.029) were significantly associated with ED + HT. CONCLUSION: The present study is the first to demonstrate that seizures with an F-IHF focus tend to present with initial ipsilateral isolated ED. This finding may aid in identifying the seizure focus in patients with isolated ED prior to resection.

Postoperative persistent fever may be a risk factor for hydrocephalus in hemispherical disconnection surgery.

INTRODUCTION: Hemispherical disconnection surgery such as hemispherotomy or posterior quadrant disconnection (PQD) surgery sometimes induces hydrocephalus. We postulated that some risk factors for postoperative hydrocephalus can be managed perioperatively. The purpose of this study was to clarify and statistically analyze perioperative risk factors for postoperative progressive hydrocephalus. METHODS: We reviewed patients who underwent hemispherotomy or PQD. We compared patients with and without progressive hydrocephalus with multivariate and univariate logistic regression analysis to identify risk factors for hydrocephalus. RESULTS: Twenty-four patients underwent hemispherectomy or PQD (age: 25 days-45 years old, mean: 13.3 years, median: 8 years, standard deviation: 13.9 years, 14 males). Among them, five patients (21%) required hydrocephalus treatment. Persistent fever was a risk factor for progressive hydrocephalus (multivariate analysis: p = 0.024, univariate analysis: p < 0.001). CONCLUSION: Postoperative persistent fever may be a manageable risk factor for postoperative hydrocephalus in hemispherotomy and PQD surgery.

Epilepsy surgery reduced seizure frequency for patients with severe motor and intellectual disorders.

INTRODUCTION: Little is known about epilepsy surgery for patients with severe motor and intellectual disorders (SMIDs). We hypothesized that epilepsy surgery could reduce epileptic seizure frequency in these patients. The purpose of this study was to compare pre- and postoperative seizure frequency in patients with SMIDs. METHODS: A total of 288 surgeries were performed for pediatric patients, including those with SMIDs, from 2009 to 2018. Inclusion criteria were as follows: Oshima classification 1 (intelligence quotient <20 and bedridden), ≥2 years old, proven ictal events evaluated by long-term video electroencephalography, and ≥1-year follow-up. Seizure frequency and the number of antiseizure medications (ASMs) were compared between pre- and postepilepsy surgery. Patients' respiratory and feeding conditions were also examined to determine comorbidities. RESULTS: Nineteen patients (5 girls, 14 boys; age: 2 to 12 years) fulfilled the inclusion criteria. One patient underwent focus resection, 2 patients underwent total corpus callosotomy, and 16 patients underwent vagus nerve stimulation therapies. Of 19 patients, 16 (84.2%) had daily seizures, and 3 (15.8%) had weekly seizures before surgery. Epilepsy surgery significantly reduced seizure frequency (p = 0.029). Five patients (26.3%) had status epilepticus (SE) before surgery, which disappeared in all but one after surgery (p = 0.046). The number of ASMs did not change between before and after surgery (p = 0.728). CONCLUSION: Epilepsy surgery reduced the frequency of epileptic seizures and improved SE even among patients with compromised respiratory function and compromised food intake.

De novo PHACTR1 mutations in West syndrome and their pathophysiological effects.

Trio-based whole exome sequencing identified two de novo heterozygous missense mutations [c.1449T > C/p.(Leu500Pro) and c.1436A > T/p.(Asn479Ile)] in PHACTR1, encoding a molecule critical for the regulation of protein phosphatase 1 (PP1) and the actin cytoskeleton, in unrelated Japanese individuals with West syndrome (infantile spasms with intellectual disability). We then examined the role of Phactr1 in the development of mouse cerebral cortex and the pathophysiological significance of these two mutations and others [c.1561C > T/p.(Arg521Cys) and c.1553T > A/p.(Ile518Asn)], which had been reported in undiagnosed patients with intellectual disability. Immunoprecipitation analyses revealed that actin-binding activity of PHACTR1 was impaired by the p.Leu500Pro, p.Asn479Ile and p.Ile518Asn mutations while the p.Arg521Cys mutation exhibited impaired binding to PP1. Acute knockdown of mouse Phactr1 using in utero electroporation caused defects in cortical neuron migration during corticogenesis, which were rescued by an RNAi-resistant PHACTR1 but not by the four mutants. Experiments using knockdown combined with expression mutants, aimed to mimic the effects of the heterozygous mutations under conditions of haploinsufficiency, suggested a dominant negative effect of the mutant allele. As for dendritic development in vivo, only the p.Arg521Cys mutant was determined to have dominant negative effects, because the three other mutants appeared to be degraded with these experimental conditions. Electrophysiological analyses revealed abnormal synaptic properties in Phactr1-deficient excitatory cortical neurons. Our data show that the PHACTR1 mutations may cause morphological and functional defects in cortical neurons during brain development, which is likely to be related to the pathophysiology of West syndrome and other neurodevelopmental disorders.

Corpus callosotomy for drug-resistant spasms associated with tuberous sclerosis complex.

BACKGROUND: Corpus callosotomy (CC) has recently been adopted for the treatment of drug-resistant epileptic spasms and tonic spasms. In the present study, we investigated CC outcomes among patients with drug-resistant epileptic spasms or tonic spasms associated with tuberous sclerosis complex (TSC). METHODS: We retrospectively collected data from seven patients (3 women, 4 men) with diagnosed TSC and who were treated using CC at Seirei Hamamatsu General Hospital in Japan. All patients had experienced drug-resistant epileptic spasms (<3 s of muscular contraction) or tonic spasms (>3 s) prior to CC, which were confirmed via video-electroencephalogram monitoring. RESULTS: All patients exhibited multiple bilateral cortical tubers on brain magnetic resonance imaging. The main seizure types were epileptic spasms in four, tonic spasms in one, and both seizure types in two patients. Patients underwent total CC between the ages of 25 months and 21.5 years. Additional resection or disconnection was performed in two patients. The follow-up period after CC ranged between 9 months and 3.5 years. Three patients achieved remission from spasms following CC alone. Two other patients became free from spasms several months after CC but required an additional focus disconnection or medical treatment. The remaining two patients continued to show spasms or asymmetrical tonic seizures. CONCLUSION: Total CC resulted in freedom from drug-resistant epileptic or tonic spasms in several patients with TSC. Stepwise progression from CC to additional resection or disconnection surgery may aid in the treatment of spasms secondary to TSC.

Double match of 18F-fluorodeoxyglucose-PET and iomazenil-SPECT improves outcomes of focus resection surgery.

BACKGROUND: When the results of electroencephalography (EEG), magnetic resonance imaging (MRI), and seizure semiology are discordant or no structural lesion is evident on MRI, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are important examinations for lateralization or localization of epileptic regions. We hypothesized that the concordance between interictal 2-[18F]fluoro-2-deoxy-D-glucose (18FDG)-PET and iomazenil (IMZ)-SPECT could suggest the epileptogenic lobe in patients with non-lesional findings on MRI. METHOD: Fifty-nine patients (31 females, 28 males; mean age, 29 years; median age, 27 years; range, 7-56 years) underwent subdural electrode implantation followed by focus resection. All patients underwent 18FDG-PET, IMZ-SPECT, and focus resection surgery. Follow-up was continued for ≥ 2 years. We evaluated surgical outcomes as seizure-free or not and analyzed correlations between outcomes and concordances of low-uptake lobes on PET, SPECT, or both PET and SPECT to the resection lobes. We used uni- and multivariate logistic regression analyses. RESULTS: In univariate analyses, all three concordances correlated significantly with seizure-free outcomes (PET, p = 0.017; SPECT, p = 0.030; both PET and SPECT, p = 0.006). In multivariate analysis, concordance between resection and low-uptake lobes in both PET and SPECT correlated significantly with seizure-free outcomes (p = 0.004). The odds ratio was 6.0. CONCLUSION: Concordance between interictal 18FDG-PET and IMZ-SPECT suggested that the epileptogenic lobe is six times better than each examination alone among patients with non-lesional findings on MRI. IMZ-SPECT and 18FDG-PET are complementary examinations in the assessment of localization-related epilepsy.

Disruption of the Photoreceptor Inner Segment-Outer Segment Junction in a 6-Year-Old Girl with Joubert Syndrome.

Joubert syndrome (JS) is a spectrum of genetic disorders characterised by cerebellar and brainstem malformation called "molar tooth sign", resulting in hypotonia, developmental delay, and intellectual disability. Here we describe a young female JS patient with "salt-and-pepper" fundus and inner segment-outer segment junction (IS/OS line) discontinuity, with a lack of external limiting membrane. Ocular coherence tomography (OCT) detected blurred external retinal layers in the macula centre. Although JS patients often have retinal degeneration with varying severity, few investigators have utilised OCT in their investigations. Our findings will help clarify the precise mechanisms of retinal involvement in JS.

Steroid-Responsive Involuntary Movements as a Remote Symptom of Febrile Infection-Related Epilepsy Syndrome.

Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic encephalopathy that occurs in children or adolescents. To date, evidence for the management of the post-acute phase of FIRES is focused on drug-resistant epilepsy that continues from the acute phase. Information on involuntary movements, which are newly developed in the chronic phase, is limited. We report a 13-year-old boy, who had a history of FIRES at nine years of age and experienced worsening seizure control that was accompanied by unremitting involuntary　movements after two years of a fairly controlled period. The involuntary movements resulted in motor deterioration and forced him to be bedridden. Although no neuronal autoantibodies were detected, we hypothesized that the boy's neurological deterioration was triggered by an autoimmune response based on the elevation of serum anti-glutamic acid decarboxylase and serum anti-thyroid peroxidase antibodies and hypermetabolism of bilateral lenticular nuclei on 18-fluorodeoxyglucose positron emission tomography that resembled those reported in patients with other types of autoimmune encephalitis. Serial methylprednisolone pulse therapy and intravenous immunoglobulin therapy ameliorated involuntary movements and improved his activities of daily living. Late-onset involuntary movements, along with seizure exacerbation, may appear in the chronic phase of FIRES. Immunotherapy could be effective in treating these symptoms.

Epidemiological study on pediatric-onset dystonia in Japan: A questionnaire-based survey.

OBJECTIVE: This study aimed to investigate the clinical characteristics of pediatric-onset dystonia in Japan, addressing the diagnostic challenges arising from symptom variations and etiological diversity. METHODS: From 2020 to 2022, questionnaires were distributed to 1218 board certified child neurologists (BCCNs) by Japanese Society of Child Neurology. In the primary survey, participants were asked to report the number of patients with pediatric-onset dystonia under their care. Subsequently, the follow-up secondary survey sought additional information on the clinical characteristics of these patients. RESULTS: The primary survey obtained 550 responses (response rate: 45 %) from BCCNs for their 736 patients with dystonia. The predominant etiologies included inherited cases (with DYT10   being the most prevalent, followed by DYT5 and ATP1A3-related neurologic disorders), acquired cases (with perinatal abnormalities being the most common), and idiopathic cases. The secondary survey provided clinical insights into 308 cases from 82 BCCNs. Infancy-onset dystonia presented as persistent and generalized with diverse symptoms, primarily linked to ATP1A3-related neurologic disorders and other genetic disorders resembling acquired dystonia. Conversely, childhood/adolescent-onset dystonia showed paroxysmal, fluctuating courses, predominantly affecting limbs. The most common etiologies were DYT5 and DYT10 , leading to therapeutic diagnoses. CONCLUSION: Pediatric-onset dystonia in Japan was treated by 28 % of BCCNs. The majority of cases were inherited, with high prevalence rates of DYT5 and DYT10 . Infancy-onset dystonia exhibits diverse etiologies and symptoms, emphasizing the utility of various examinations, including genetic testing. These findings significantly contribute to our understanding of pediatric-onset dystonia in Japan, although this study has the limitation of questionnaire survey.

Treatment odyssey to epilepsy surgery in children with focal cortical dysplasia: Risk factors for delayed surgical intervention.

OBJECTIVE: To elucidate the patient's journey to epilepsy surgery and identify the risk factors contributing to surgical delay in pediatric patients with drug-resistant epilepsy (DRE) due to focal cortical dysplasia (FCD). METHODS: A retrospective review was conducted of 93 pediatric patients who underwent curative epilepsy surgery for FCD between January 2012 and March 2023 at a tertiary epilepsy center. The Odyssey plot demonstrated the treatment process before epilepsy surgery, including key milestones of epilepsy onset, first hospital visit, epilepsy diagnosis, MRI diagnosis, DRE diagnosis, and surgery. The primary outcome was surgical delay; the duration from DRE to surgery. Multivariate linear regression models were used to examine the association between surgical delay and clinical, investigative, and treatment characteristics. RESULTS: The median age at seizure onset was 1.3 years (interquartile range [IQR] 0.14-3.1), and at the time of surgery, it was 6 years (range 1-11). Notably, 46% experienced surgical delays exceeding two years. The Odyssey plot visually highlighted that surgical delay comprised a significant portion of the patient journey. Although most patients underwent MRI before referral, MRI abnormalities were identified before referral only in 39% of the prolonged group, compared to 70% of the non-prolonged group. Multivariate analyses showed that delayed notification of MRI abnormalities, longer duration from epilepsy onset to DRE, older age at onset, number of antiseizure medications tried, and moderate to severe intellectual disability were significantly associated with prolonged surgical delay. CONCLUSION: Pediatric DRE patients with FCD experienced a long journey until surgery. Early and accurate identification of MRI abnormalities is important to minimize surgical delays.

Intraventricular hemorrhage volume and younger age at surgery may be risk factors for postoperative hydrocephalus after hemispherotomy in children.

OBJECTIVE: Hemispherotomy is an effective treatment for intractable hemispheric epilepsy; however, hydrocephalus remains a common complication of the procedure. The causes of hydrocephalus following hemispherotomy have not been fully elucidated; therefore, the purpose of this study was to identify the risk factors associated with the condition. METHODS: The authors investigated the records of all patients aged < 18 years who underwent hemispherotomy at their institution between 2003 and 2020 and were monitored for hydrocephalus for at least 1 year after the procedure. To identify the risk factors for hydrocephalus, the following information about each patient was collected: sex, corrected age at surgery, body weight at surgery, previous intracranial surgery, etiology of epilepsy, results of PET for hypermetabolism, side of surgery, type of operation (vertical or horizontal approach), operation time, blood loss during surgery, use of intraventricular drainage, occurrence of intraventricular hemorrhage (IVH) on the 1st postoperative day, duration of postoperative fever of > 38°C, and maximum C-reactive protein level after the operation. Multivariate logistic regression analyses were performed. RESULTS: This study included 51 children who underwent hemispherotomies for drug-resistant epilepsy at our hospital. Seven patients (13.7%) experienced hydrocephalus and were treated with ventricular or subdural peritoneal shunts or fenestration. Multivariate logistic analysis using the Bayesian information criterion revealed that 3 factors were associated with the occurrence of hydrocephalus: age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C. CONCLUSIONS: This study showed that younger age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C might be risk factors for hydrocephalus after hemispherotomy. The risk of hydrocephalus should be considered in cases of early surgical indication in children. Intraoperative hemostasis and postoperative use of anti-inflammatory measures may reduce the risk of hydrocephalus.

Synchronous heart rate reduction with suppression-burst pattern in KCNT1-related developmental and epileptic encephalopathies.

Suppression-burst (SB) is an electroencephalographic pattern observed in neonatal- and infantile-onset developmental and epileptic encephalopathies (DEEs), which are associated with high mortality in early life. However, the relation of SB electroencephalogram (SB-EEG) with autonomic function requires clarification. We investigated the relationship between heart rate (HR) and phasic transition during SB-EEG in DEEs to explore the mechanism of early death. Seven patients (two with KCNT1-DEE) with neonatal- and infantile-onset DEE who presented with SB-EEG were retrospectively identified. Five-minute SB-EEGs were analyzed with simultaneous recording of electrocardiograms. Mean HR, suppression duration, and burst period were calculated by measuring RR intervals. Two patients with KCNT1-DEE exhibited synchronous HR fluctuations, with an HR decrease during suppression and an increase during burst. The HR decrease was larger (-6.1% and -7.7%) and the median duration of suppression was longer (4.0 and 8.2 s) in patients with KCNT1-DEE than the other five (range: -2.9% to 0.9% and 0.7-1.7s, respectively). A strong negative correlation was confirmed between suppression duration and HR reduction rates in one patient with KCNT1-DEE. SB phases may influence HR regulation in patients with KCTN1-DEE.

An integrated genetic analysis of epileptogenic brain malformed lesions.

Focal cortical dysplasia is the most common malformation during cortical development, sometimes excised by epilepsy surgery and often caused by somatic variants of the mTOR pathway genes. In this study, we performed a genetic analysis of epileptogenic brain malformed lesions from 64 patients with focal cortical dysplasia, hemimegalencephy, brain tumors, or hippocampal sclerosis. Targeted sequencing, whole-exome sequencing, and single nucleotide polymorphism microarray detected four germline and 35 somatic variants, comprising three copy number variants and 36 single nucleotide variants and indels in 37 patients. One of the somatic variants in focal cortical dysplasia type IIB was an in-frame deletion in MTOR, in which only gain-of-function missense variants have been reported. In focal cortical dysplasia type I, somatic variants of MAP2K1 and PTPN11 involved in the RAS/MAPK pathway were detected. The in-frame deletions of MTOR and MAP2K1 in this study resulted in the activation of the mTOR pathway in transiently transfected cells. In addition, the PTPN11 missense variant tended to elongate activation of the mTOR or RAS/MAPK pathway, depending on culture conditions. We demonstrate that epileptogenic brain malformed lesions except for focal cortical dysplasia type II arose from somatic variants of diverse genes but were eventually linked to the mTOR pathway.

Long-term changes in electroencephalogram findings in a girl with a nonsense SMC1A variant: A case report.

INTRODUCTION: Pathogenic truncating variants in SMC1A, which is located on chromosome Xp11.2, are known to cause infantile-onset epilepsy and severe intellectual disability in girls. Several studies have reported a correlation between SMC1A truncations and seizure clustering; however, the associated electroencephalogram (EEG) patterns remain largely unknown. CASE PRESENTATION: We investigated an 12-year-old girl who had developed epilepsy at the age of 4 months. The patient experienced unknown onset, tonic-clonic seizures that occurred in clusters several times a week. Her interictal EEG at the age of 2 years showed paroxysmal, generalized, high-amplitude slow waves, whereas epileptiform discharges were scarce. The patient's interictal EEG gradually deteriorated; at the age of 11 years, diffuse continuous spike-and-wave discharges were predominantly observed in the left temporal region and were particularly obvious in the awake state. Although the unknown onset, tonic seizures occurring weekly persisted under multiple antiepileptic medications, the patient did not experience seizure clustering since the age of 9 years. Whole-genome sequencing revealed a de novo known nonsense variant in SMC1A (c.2923C > T, p.R975*). CONCLUSION: Our patient presented with a mild abnormality in the interictal EEG during infancy and early childhood despite frequent seizure clustering. Notably, the patient's EEG findings gradually deteriorated over time, which was inconsistent with the amelioration of seizure clustering.

Successful Hemispherotomy in a Patient with Encephalopathy with Continuous Spikes and Waves during Sleep Related to Neonatal Thalamic Hemorrhage: A Case Report with Intracranial Electroencephalogram Findings.

Neonatal thalamic hemorrhage is a strong risk factor for developing encephalopathy with continuous spikes and waves during sleep (ECSWS), even when not accompanied by widespread cortical destruction. The efficacy and indication of resective epilepsy surgery in such patients has not yet been reported. A 4-year-old boy was diagnosed with ECSWS based on strong epileptiform activation during sleep and neurocognitive deterioration. He had a history of left thalamic hemorrhage related to a straight sinus thrombosis during the newborn period. He presented with daily absence seizures that were refractory to medical treatment. At age 5, he underwent intracranial electroencephalogram (EEG) recording using depth and subdural strip electrodes placed in the left thalamus and over bilateral cortex, respectively. Interictal and ictal epileptiform discharges were observed in the thalamus, always preceded by discharges in the left or right parietal lobe. Left hemispherotomy successfully normalized the EEG of his unaffected hemisphere and extinguished his seizures. This is the first case report documenting resective epilepsy surgery in a patient with ECSWS due to neonatal thalamic injury without widespread cerebral destruction. Based on intracranial EEG findings, his injured thalamus did not directly generate the EEG abnormalities or absence seizures on its own. Patients with ipsilateral neonatal thalamic injury and even mild lateralized cortical changes may be candidates for resective or disconnective surgery for ECSWS.