RESUMO
PURPOSE: Coherence analysis in electroencephalography (EEG) allows measurement of the degree of consistency of amplitude between pairs of electrodes. Theoretically, disconnective epilepsy surgery should decrease coherence between corresponding areas. The study aimed to evaluate postoperative changes in interhemispheric coherence values after corpus callosotomy (CC). METHODS: Non-lesional, drug-resistant, generalized epilepsy patients who underwent total CC were retrospectively collected. To evaluate coherence, we divided the scalp interictal EEG into "baseline" and "discharge" states after excluding periods with artifacts. Interhemispheric coherence values were obtained between eight pairs of symmetrically opposite scalp electrodes in six different frequency bands. We analyzed both pre- and postoperative EEG sessions and calculated the percentage of difference (POD) in coherence values. RESULTS: We collected 13 patients and analyzed 2496 interhemispheric coherence values. Preoperative coherence values differed significantly between baseline and discharge states (p = 0.0003), but postoperative values did not (p = 0.11). For baseline state, coherence values were decreased after CC and median POD was - 22.3% (p < 0.0001). Delta frequency showed the most decreased POD (-44.3%, p = 0.0009). Median POD was lowest in the Fp1-Fp2 pair of electrodes. For discharge state, coherence values were decreased after CC and median POD was - 24.7% (p < 0.0001). Delta frequency again showed the most decreased POD (-55.9%, p = 0.0016). Median POD was lowest in the F7-F8 pair. CONCLUSION: After total CC, interhemispheric coherence decreased significantly in both baseline and discharge states. The most decreased frequency band was the delta band, which may be used as a representative frequency band in future studies.
Assuntos
Corpo Caloso , Eletroencefalografia , Epilepsia Generalizada , Couro Cabeludo , Humanos , Feminino , Eletroencefalografia/métodos , Masculino , Corpo Caloso/cirurgia , Corpo Caloso/fisiopatologia , Criança , Adolescente , Estudos Retrospectivos , Pré-Escolar , Epilepsia Generalizada/cirurgia , Epilepsia Generalizada/fisiopatologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/fisiopatologiaRESUMO
PURPOSE: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects. METHODS: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated. RESULTS: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. CONCLUSION: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.
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Exoma , Malformações do Sistema Nervoso , Criança , Humanos , Exoma/genética , Mutação , Malformações do Sistema Nervoso/genética , Atrofia/genética , Receptor 1 de Folato/genética , CinesinasRESUMO
BACKGROUND: Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear. METHODS: We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail. RESULTS: Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly. CONCLUSIONS: Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.
Assuntos
Colágeno Tipo IV/genética , Mutação/genética , Síndrome de Dandy-Walker/genética , Feminino , Humanos , Masculino , Gravidez , Ultrassonografia Pré-Natal/métodosRESUMO
PURPOSE: Subependymal giant cell astrocytomas (SEGAs) are tumors that usually arise in the wall of one or the other lateral ventricle near a foramen of Monro, most often on a background of tuberous sclerosis complex (TSC). TSC has a variety of clinical manifestations caused by germline mutations of the TSC complex subunit 1 or 2 (TSC1, TSC2) genes. SEGAs without clinical manifestations of TSC are termed solitary SEGAs, which are hypothesized to be caused by tumor-only TSC1/2 mutations, or "forme fruste" of TSC with somatic mosaic mutations. However, it is difficult to distinguish between the two. Here, we report three patients with genetically investigated solitary SEGAs and review this rare manifestation. METHODS: SEGA was completely removed in two patients and partially removed in one. Genetic analyses were performed on the tumor tissue and on peripheral blood via DNA microarray, reverse-transcriptase polymerase chain reaction, and next-generation sequencing with ultra-deep sequencing of mutation points. RESULTS: All three patients had tumors with TSC2 somatic mutations and loss of heterozygosity (LOH). In one patient, the same TSC2 mutation was also detected in 1% of leukocytes in his blood. The tumors did not recur, and clinical manifestations of TSC did not develop during the 4-year follow-up. CONCLUSIONS: The genetic cause of solitary SEGAs may be a TSC2 mutation with LOH. In patients with solitary SEGA, mosaic mutations may present in other organs, and TSC may clinically manifest later in life; therefore, patients should be followed up for prolonged periods.
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Astrocitoma , Proteína 2 do Complexo Esclerose Tuberosa/genética , Esclerose Tuberosa , Astrocitoma/diagnóstico por imagem , Astrocitoma/genética , Humanos , Mutação/genética , Recidiva Local de Neoplasia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genéticaRESUMO
The leukodystrophies cause severe neurodevelopmental defects from birth and follow an incurable and progressive course that often leads to premature death. It has recently been reported that abnormalities in aminoacyl t-RNA synthetase (ARS) genes are linked to various unique leukodystrophies and leukoencephalopathies. Aminoacyl t-RNA synthetase proteins are fundamentally known as the first enzymes of translation, catalysing the conjugation of amino acids to cognate tRNAs for protein synthesis. It is known that certain aminoacyl t-RNA synthetase have multiple non-canonical roles in both transcription and translation, and their disruption results in varied and complicated phenotypes. We clinically and genetically studied seven patients (six male and one female; aged 2 to 12 years) from five unrelated families who all showed the same phenotypes of severe developmental delay or arrest (7/7), hypotonia (6/7), deafness (7/7) and inability to speak (6/7). The subjects further developed intractable epilepsy (7/7) and nystagmus (6/6) with increasing age. They demonstrated characteristic laboratory data, including increased lactate and/or pyruvate levels (7/7), and imaging findings (7/7), including calcification and abnormal signals in the white matter and pathological involvement (2/2) of the corticospinal tracts. Through whole-exome sequencing, we discovered genetic abnormalities in lysyl-tRNA synthetase (KARS). All patients harboured the variant [c.1786C>T, p.Leu596Phe] KARS isoform 1 ([c.1702C>T, p.Leu568Phe] of KARS isoform 2) either in the homozygous state or compound heterozygous state with the following KARS variants, [c.879+1G>A; c.1786C>T, p.Glu252_Glu293del; p.Leu596Phe] ([c.795+1G>A; c.1702C>T, p.Glu224_Glu255del; p.Leu568Phe]) and [c.650G>A; c.1786C>T, p.Gly217Asp; p.Leu596Phe] ([c.566G>A; c.1702C>T, p.Gly189Asp; p.Leu568Phe]). Moreover, similarly disrupted lysyl-tRNA synthetase (LysRS) proteins showed reduced enzymatic activities and abnormal CNSs in Xenopus embryos. Additionally, LysRS acts as a non-canonical inducer of the immune response and has transcriptional activity. We speculated that the complex functions of the abnormal LysRS proteins led to the severe phenotypes in our patients. These KARS pathological variants are novel, including the variant [c.1786C>T; p.Leu596Phe] (c.1702C>T; p.Leu568Phe) shared by all patients in the homozygous or compound-heterozygous state. This common position may play an important role in the development of severe progressive leukodystrophy. Further research is warranted to further elucidate this relationship and to investigate how specific mutated LysRS proteins function to understand the broad spectrum of KARS-related diseases.
Assuntos
Leucodistrofia de Células Globoides/genética , Leucodistrofia de Células Globoides/fisiopatologia , Lisina-tRNA Ligase/genética , Aminoacil-tRNA Sintetases/genética , Aminoacil-tRNA Sintetases/fisiologia , Animais , Criança , Pré-Escolar , Modelos Animais de Doenças , Feminino , Homozigoto , Humanos , Leucoencefalopatias/genética , Lisina-tRNA Ligase/fisiologia , Masculino , Mutação , Linhagem , Fenótipo , Sequenciamento do Exoma , Xenopus laevisRESUMO
KCNT1 mutations are gain-of-function mutations in potassium channels resulting in severe infantile epilepsy. Herein we describe 3 infants with malignant migrating partial seizures with KCNT1 mutations accompanied by massive systemic to pulmonary collateral arteries with life-threatening hemoptysis and heart failure.
Assuntos
Circulação Colateral , Epilepsias Parciais/genética , Mutação com Ganho de Função , Proteínas do Tecido Nervoso/genética , Canais de Potássio/genética , Artéria Pulmonar/fisiopatologia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/fisiopatologia , Evolução Fatal , Feminino , Marcadores Genéticos , Humanos , Recém-Nascido , Masculino , Canais de Potássio Ativados por SódioRESUMO
Neuroblastic tumors (NT) with opsoclonus-myoclonus syndrome (OMS) display characteristic histological features, such as lymphocytic infiltration with lymphoid follicles, indicating an underlying immune response. We retrospectively assessed NT patients from 2001 to 2016. Five cases of NT with OMS and 76 cases of NT without OMS were histopathologically reviewed in this study. The grade of lymphocytic infiltration was evaluated. The number of follicles was counted and the presence or absence of lymphoid follicles was recorded for each case. We also confirmed the presence or absence of follicular dendritic cells (FDCs). We investigated the relationship between the histopathological and clinical findings of NT with OMS. Lymphocytic infiltration was observed in all cases; however, the precise follicular structure was occasionally unclear. Patients with clear follicular structures displayed germinal centers including tingible body macrophages and FDCs. All patients without neurological sequelae demonstrated a clear follicular structure with a FDC meshwork pattern. The interval between OMS onset and the detection and initial treatment of NT was typically longer in patients with neurological sequelae compared to those without neurological sequelae. Early detection and treatment of NT with OMS at the phase of a clear follicular formation with multiple FDC may provide favorable neurological outcomes.
Assuntos
Neuroblastoma/complicações , Neuroblastoma/patologia , Síndrome de Opsoclonia-Mioclonia/etiologia , Feminino , Humanos , Lactente , MasculinoRESUMO
BACKGROUND: Electrocorticogram (ECoG) spike activity is enhanced under general anesthesia with 1.5 minimum alveolar concentration (MAC) sevoflurane compared with lower concentrations in adult patients with epilepsy. However, the effect of concentration of sevoflurane on ECoG in children with epilepsy is less known. AIMS: The primary endpoint was to investigate the effects of sevoflurane on ECoG spike activity in pediatric patients undergoing epilepsy surgery. The secondary endpoint was to examine its effects on baseline ECoG including burst suppression. METHODS: Children of age 3-18 years with medically intractable epilepsy undergoing corpus callosotomy or resection of the epileptic foci (n = 11) were enrolled. Electrodes were placed on the brain surface and ECoG was recorded under anesthesia with endtidal carbon dioxide tension at 30 mmHg and sevoflurane at 2.5%, followed by age-adjusted 1.5 MAC (3.1-3.4%) for 10 min. The number of leads with spikes, the average number of spikes per lead per minute, median frequency of ECoG, and duration of suppression of ECoG ≥ 1 s were compared between 2.5% and 1.5 MAC sevoflurane. RESULTS: The number of leads with spikes increased [11 vs 14, P = 0.003, difference in mean (95% CI) is 3 (2-5)], and the average number of spikes increased [9 vs 14·lead-1 ·min-1 , P = 0.003, difference in mean (95% CI) is 5 (2-8) lead-1 ·min-1 ] under anesthesia with 1.5 MAC compared with 2.5% sevoflurane. Median frequency was decreased [2.8 Hz vs 2.0 Hz, P = 0.003, difference in mean (95% CI) is 0.8 (0.4-1.2) Hz], and the duration of suppression was increased [105 s vs 262 s, P < 0.001, difference in mean (95% CI) is 156 (90-223) s] with 1.5 MAC compared with 2.5% sevoflurane. CONCLUSIONS: Sevoflurane at 1.5 MAC significantly increased the extent and the number of spikes, prolonged the duration of suppression, and decreased median frequency of ECoG compared with those at 2.5% sevoflurane.
Assuntos
Anestésicos Inalatórios/farmacologia , Encéfalo/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Epilepsia/cirurgia , Éteres Metílicos/farmacologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , SevofluranoRESUMO
A male infant suffered from partial seizures at four months of age, and developed West syndrome at eight months of age. ACTH therapy was effective for the West syndrome. However, partial seizures recurred at 14 months of age, which could not be sufficiently controlled with an anti-epileptic drug. A characteristic facial appearance, great toe abnormalities, and developmental retardation were noted. An interstitial deletion of 2q was detected by chromosomal G-banding and array comparative genomic hybridization (CGH) confirmed the deletion as arr 2q24.3q31.3 (166,303,447-180,982.972) ×1 (build19). He presented with clinical findings similar to those of the recently defined 2q31.1 deletion syndrome. The deletion extended to the SCN1A gene, a gene responsible for Dravet syndrome, mapped to the 2q24.3 region. No deletion was noted in the adjacent SCN2A gene. Thus, for interstitial deletions, detailed breakpoints should be identified by array CGH. The frequency of epilepsy varies with deletion ranges in the 2q24-q31 region, suggesting that deletions in the SCN1A gene deletion, as well as in the 2q31.1 region, are involved in the development of West syndrome.
Assuntos
Cromossomos Humanos Par 2 , Espasmos Infantis/genética , Deleção Cromossômica , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Espasmos Infantis/diagnóstico por imagemRESUMO
Objective: Patients with childhood-onset epilepsy often need continued epilepsy treatment into adulthood. We investigated parents' opinions of the changes in their children's epilepsy treatment during the transition from childhood to adulthood using questionnaires and formulated agendas to build the appropriate medical treatment system for epilepsy. Methods: We distributed questionnaires to parents of patients with epilepsy who were 12 to 18 years old. Results: We distributed 176 questionnaires, and analyzed 79 (45%) questionnaires. Most parents (59%) wanted their child to continue treatment for epilepsy in the pediatrics department because of confidence in the current treatment environment. Most parents (73%) were anxious about their child not being treated in the pediatrics department during future epilepsy medical treatments because of concerns about whether a proper handover from the pediatrics department to other departments is possible. No parent was recommended the departmental transition by the primary pediatrician to other courses for future epilepsy treatment, while 19% of par-ents had a sense of incongruity regarding epilepsy treatment at the current pediatrics department. Parents who were anxious about future epilepsy treatments had significantly fewer general-school students than parents without anxiety. In addition, their children had more seizures than children of parents who were not anxious. Furthermore, they wanted their child to continue treatment for epilepsy in the pediatrics department more than the parents without anxiety. Conclusions: Approximately 70% of the parents were anxious about obtaining future epilepsy treatment in clinical departments other than the pediatrics department. To build a satisfactory medical treatment system for patients with epilepsy having different backgrounds and requiring continued treatment in adulthood, it is important to create a cooperating network consisting of pediatricians, neurologists, neurosurgeons, psychiatrists, and epileptologists.
Assuntos
Epilepsia/terapia , Pais , Adolescente , Adulto , Atitude , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Whole-exome sequencing (WES) is becoming a standard tool for detecting nucleotide changes, and determining whether WES data can be used for the detection of copy-number variations (CNVs) is of interest. To date, several algorithms have been developed for such analyses, although verification is needed to establish if they fit well for the appropriate purpose, depending on the characteristics of each algorithm. Here, we performed WES CNV analysis using the eXome Hidden Markov Model (XHMM). We validated its performance using 27 rare CNVs previously identified by microarray as positive controls, finding that the detection rate was 59%, or higher (89%) with three or more targets. XHMM can be effectively used, especially for the detection of >200 kb CNVs. XHMM may be useful for deletion breakpoint detection. Next, we applied XHMM to genetically unsolved patients, demonstrating successful identification of pathogenic CNVs: 1.5-1.9-Mb deletions involving NSD1 in patients with unknown overgrowth syndrome leading to the diagnosis of Sotos syndrome, and 6.4-Mb duplication involving MECP2 in affected brothers with late-onset spasm and progressive cerebral/cerebellar atrophy confirming the clinical suspect of MECP2 duplication syndrome. The possibility of an 'exome-first' approach for clinical genetic investigation may be considered to save the cost of multiple investigations.
Assuntos
Variações do Número de Cópias de DNA , Exoma , Sequenciamento de Nucleotídeos em Larga Escala , Cadeias de Markov , Modelos Genéticos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Algoritmos , Atrofia , Encefalopatias/genética , Encefalopatias/patologia , Pontos de Quebra do Cromossomo , Duplicação Cromossômica , Biologia Computacional/métodos , Feminino , Gigantismo/genética , Histona Metiltransferases , Histona-Lisina N-Metiltransferase , Humanos , Deficiência Intelectual/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteína 2 de Ligação a Metil-CpG/genética , Proteínas Nucleares/genética , Sensibilidade e Especificidade , Deleção de SequênciaRESUMO
OBJECTIVE: We performed high-dose erythropoietin therapy (hEPO) for acute encephalopathy or encephalitis (AE), and evaluated its safety and efficacy. METHODS: We performed hEPO in AE patients with widespread lesions demonstrated by diffusion-weighted imaging, and prospectively investigated changes in hemoglobin levels, adverse events, changes in images, and developmental quotients. RESULTS: All four patients showed neither an increase in the hemoglobin level nor adverse event possibly related to hEPO. One patient with acute encephalitis showed resolution of the lesion and normal developmental quotient. Two patients who had acute encephalopathy with febrile convulsive status epilepticus showed mild cerebral atrophy in the recovery phase;one had a normal developmental quotient. The patient with acute necrotizing encephalopathy including a brainstem lesion avoided acute-phase death. CONCLUSION: Two patients showed no sequelae despite images indicating widespread abnormality. hEPO could be performed safely in patients with AE, however further trials are necessary concerning its efficacy.
Assuntos
Encefalite/tratamento farmacológico , Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Doença Aguda , Pré-Escolar , Imagem de Difusão por Ressonância Magnética , Eletroencefalografia , Encefalite/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Resultado do TratamentoRESUMO
We encountered two patients with acquired Kanji dysgraphia in whom continuous spikes and waves, dominant in the occipito-temporal region, were recorded during slow-wave sleep. Electrical status epileptics during sleep (ESES) was demonstrated on overnight electroencephalography, and dipoles clustered in and around the posterior inferior temporal cortex on magnetoencephalography. Functional neuroimaging suggested dysfunction in the left posterior temporal lobe, including the posterior inferior temporal cortex. The patients had normal intelligence with no problems in reading and writing Kana, as well as copying, reading aloud, and identifying Kanjis, but showed Kanji dysgraphia (morphological, phonemic, and semantic error) accompanied by impaired visual processing. ESES was resolved by sodium valproate, clonazepam, and acetazolamide in Patient 1, and by adrenocorticotropic hormone, sodium valproate, and clorazepate in Patient 2. The present cases had the unique cognitive dysfunction of Kanji dysgraphia, which is distinct from that of Landau-Kleffner syndrome and continuous spikes and waves during slow-wave sleep. However, the present cases also share common features with these two encephalopathies in terms of the clinical course, pathophysiology, neuroimaging, and response to steroids and antiepileptic drugs. In the context of the Japanese language, acquired Kanji dysgraphia may occur due to electrical dysfunction of left posterior inferior temporal cortex in patients with ESES.
Assuntos
Agrafia , Eletroencefalografia , Epilepsia , Lobo Occipital/fisiopatologia , Lobo Temporal/fisiopatologia , Adolescente , Agrafia/diagnóstico , Agrafia/etiologia , Agrafia/fisiopatologia , Criança , Pré-Escolar , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Humanos , Lactente , Masculino , Sono/fisiologiaRESUMO
OBJECTIVE: We examined the clinical course and the prognosis of patients with anti-NMDAR encephalitis. METHODS: We retrospectively evaluated the patients who has distinctive clinical features as anti-NMDAR encephalitis based on their medical records. RESULTS: There were two male and four female patients with anti-NMDAR encephalitis. They were aged between 13 and 16 years. One of the six, 14 years female patient was negative for anti-NMDAR antibody. All four female patients with anti-NMDAR encephalitis had an ovarian tumor. Neurocognitive dysfunction and epilepsy remained in one female patient with right temporal lobe lesion and one male patient with celebellar abnormalities had mild mental impairment. In three patients including two patients who were examined abdominal MRI for the first time after recovery from the encephalitis, overian tumors became apparent during follow-up. In one of other patients, overian tumors had a tendency to increase in size after recovery. CONCLUSION: Sequellae were seen in two cases that have abnormalities in brain MRI. As to ovarian tumor, it was considered to be necessary to checkup pelvic MRI for at least four years after the onset of encephalitis.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos RetrospectivosRESUMO
We report a case of developmental and epileptic encephalopathy with spike-and-wave activation during sleep with 22q11.2 deletion syndrome in a patient who had undergone hemispherotomy and achieved developmental improvement. A four-year-old male child with paralysis on the left side of his body since birth had a mild developmental delay. An MRI of the brain revealed polymicrogyria diffusely throughout the right hemisphere. He was diagnosed with the 22q11.2 deletion syndrome at one year of age. Focal impaired awareness seizure in the right hemisphere origin and focal to bilateral tonic-clonic seizure appeared by two years of age. At three years of age, myoclonic seizures occurred, which induced frequent falls. Simultaneously, developmental and epileptic encephalopathy with spike-and-wave activation during sleep were observed. At four years and seven months of age, the patient underwent a right hemispherotomy. Epileptic seizures and spike-and-wave activation during sleep disappeared, and cognitive improvement was observed one year after surgery. In spite of chromosomal abnormalities being present, drug-resistant epilepsy with localized regions on MRI should be evaluated to determine surgical options to improve cognitive function and development.
RESUMO
Myoclonus-dystonia syndrome (MDS) presents with both rapid myoclonus and dystonia, which is caused by mutations in the sarcoglycan (SGCE) gene. However, its complications and management remain unclear. Here, we report a case involving a girl with MDS due to a 7q21.13-q21.3 microdeletion complicated by early-onset multiple cerebral cavernous malformations (CCMs). The patient presented with myoclonus and dystonia at two and eight years of age, respectively. In addition to MDS, the patient developed growth hormone (GH) deficiency and mild intellectual disability. Magnetic resonance imaging of the brain showed multiple CCMs. Array-based comparative genomic hybridization revealed 7q21.13-21.3 microdeletion. The deletion size was 4.11 Mb, which included SCGE and KRIT1. After the introduction of zonisamide, both myoclonus and dystonia showed improvement, and GH therapy led to an increase in patient height. In cases of MDS, multiple early-onset CCMs and GH deficiency may occur; moreover, careful follow-up management may be necessary.
RESUMO
BACKGROUND: Some patients with ATP1A3 variant-associated polymicrogyria have recurrent transient heart failure. However, effective treatment for the transient cardiac condition remains to be elucidated. CASE REPORT: The patient started experiencing focal motor onset seizures in 12 h after birth, revealing bilateral diffuse polymicrogyria. The patient also experienced transient bradycardia (sinus bradycardia) attacks from 15 days old. Echocardiography revealed a reduced ejection fraction; however, no obvious electrocorticogram or electroencephalogram abnormalities were observed during the attacks. Initially, the attacks occurred in clusters daily. They later decreased in frequency, occurring at monthly intervals. Repeated episodes of transient bradycardia attacks and polymicrogyria indicated possible ATP1A3 gene abnormality and genetic testing revealed a novel heterozygous ATP1A3 variant (NM_152296: exon22:c.2977_2982del:p.(Glu993_Ile994del)), which was not found in the patient's parents. Cilostazol was administered at 3 months old for recurrent transient bradycardia attacks. Cilostazol significantly shortened the duration of bradycardia episodes and prolonged the interval between attacks. Cilostazol also effectively treats transient symptomatic bradycardia. CONCLUSION: Cilostazol could be a treatment option for recurrent transient bradycardia attacks associated with ATP1A3 gene abnormalities and polymicrogyria.
Assuntos
Insuficiência Cardíaca , Polimicrogiria , Humanos , Lactente , Cilostazol , Bradicardia/tratamento farmacológico , Bradicardia/genética , Polimicrogiria/tratamento farmacológico , Polimicrogiria/genética , Polimicrogiria/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/complicações , Convulsões/complicações , ATPase Trocadora de Sódio-Potássio/genéticaRESUMO
Dynamin-1 (DNM1) is involved in synaptic vesicle recycling, and DNM1 mutations can lead to developmental and epileptic encephalopathy. The neuroimaging of DNM1 encephalopathy has not been reported in detail. We describe a severe phenotype of DNM1 encephalopathy showing characteristic neuroradiological features. In addition, we reviewed previously reported cases who have DNM1 pathogenic variants with white matter abnormalities. Our case presented drug-resistant seizures from 1 month of age and epileptic spasms at 2 years of age. Brain MRI showed no progression of myelination, progression of diffuse cerebral atrophy, and a thin corpus callosum. Proton magnetic resonance spectroscopy showed a decreased N-acetylaspartate peak and diffusion tensor imaging presented with less pyramidal decussation. Whole-exome sequencing revealed a recurrent de novo heterozygous variant of DNM1. So far, more than 50 cases of DNM1 encephalopathy have been reported. Among these patients, delayed myelination occurred in two cases of GTPase-domain DNM1 encephalopathy and in six cases of middle-domain DNM1 encephalopathy. The neuroimaging findings in this case suggest inadequate axonal development. DNM1 is involved in the release of synaptic vesicles with the inhibitory transmitter GABA, suggesting that GABAergic neuron dysfunction is the mechanism of refractory epilepsy in DNM1 encephalopathy. GABA-mediated signaling mechanisms play important roles in axonal development and GABAergic neuron dysfunction may be cause of white matter abnormalities in DNM1 encephalopathy.
Assuntos
Encefalopatias , Epilepsia , Espasmos Infantis , Humanos , Dinamina I/genética , Imagem de Tensor de Difusão , Epilepsia/genética , Espasmos Infantis/genética , Mutação , Fenótipo , Ácido gama-Aminobutírico/genéticaRESUMO
Although epilepsy is the most common comorbidity of brain tumors, epileptic spasms rarely occur. Brain tumors associated with epileptic spasms are mostly low-grade gliomas. To date, few studies in the literature have reported on malignant (Grades 3-4) brain tumors associated with epileptic spasms. Thus, we aimed to investigate the characteristics of malignant brain tumor-associated epileptic spasms. We retrospectively reviewed patients with malignant brain tumors and epileptic spasms in our institution. Data on demographics, tumor histology, magnetic resonance imaging, epileptic spasm characteristics, electroencephalography, and treatment responsiveness were also collected. Six patients were included. In all cases, the brain tumors occurred in infancy in the supratentorial region and epileptic spasm onset occurred after the completion of brain tumor treatment. Anti-seizure medication did not control epileptic spasms; two patients were seizure-free after epileptic surgery. Although all patients had developmental delays caused by malignant brain tumors and their treatment, developmental regression proceeded after epileptic spasm onset. Two patients who achieved seizure-free status showed improved developmental outcomes after cessation of epileptic spasms. This is the first report of the characteristics of malignant brain tumor-associated epileptic spasms. Our report highlights a difficulties of seizure control and possibillity of efficacy of epileptic surgery in this condition. In malignant brain tumor-associated epileptic spasms, it is important to proceed with presurgical evaluation from an early stage, bearing in mind that epileptic spasms may become drug-resistant.
Assuntos
Neoplasias Encefálicas , Eletroencefalografia , Humanos , Masculino , Feminino , Neoplasias Encefálicas/complicações , Estudos Retrospectivos , Lactente , Pré-Escolar , Epilepsia/etiologia , Epilepsia/fisiopatologia , Imageamento por Ressonância Magnética , Glioma/complicações , Glioma/fisiopatologia , Espasmo/etiologia , Espasmo/fisiopatologia , Anticonvulsivantes/uso terapêutico , CriançaRESUMO
Purpose: To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. Methods: We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. Results: The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p < 0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Conclusion: Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings.