RESUMO
Juvenile myasthenia gravis (JMG) exhibits a more favorable response to glucocorticoids and has a better prognosis than adult myasthenia gravis. However, no established treatment exists for refractory JMG. Although thymectomy has been performed in several patients with refractory systemic JMG, there are few detailed clinical descriptions of patients who underwent thymectomy. Here, we present the case of a 10-year-old boy with refractory systemic JMG who was successfully treated with thymectomy. The patient developed symptoms, including dysphagia, malaise, diurnal ptosis, and weakness in the trunk muscles, and he was diagnosed with generalized JMG. Despite undergoing various treatments, including steroids, tacrolimus, steroid pulse therapy, intravenous immunoglobulin, azathioprine (AZT), and rituximab, his symptoms did not improve. Therefore, he underwent a thoracoscopic thymectomy 24 months after disease onset. Thymectomy led to remission, as demonstrated by a significant reduction in the quantitative myasthenia gravis score and anti-acetylcholine receptor antibody levels, which persisted for 43 months after surgery. Our case demonstrates the effectiveness of thymectomy in systemic JMG patients with positive anti-acetylcholine receptor antibodies, despite therapeutic failure with AZT and rituximab, within 2 years of disease onset.
Assuntos
Miastenia Gravis , Timectomia , Criança , Humanos , Masculino , Autoanticorpos , Progressão da Doença , Glucocorticoides/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/cirurgia , Rituximab , Resultado do TratamentoRESUMO
Human metapneumovirus (hMPV) is a common cause of upper and lower respiratory tract infections in children. A few case reports have described hMPV encephalitis or encephalopathy. Neuroimaging data on patients with hMPV encephalitis are scarce. We report a patient with trisomy 13 who developed severe hMPV pneumonia, multifocal cerebral and cerebellar hemorrhagic infarctions and extensive cerebral white matter demyelination. Although adult respiratory distress syndrome and disseminated intravascular coagulation contributed to the devastating central nervous system (CNS) lesions, endothelial dysfunction of the CNS caused by hMPV infection probably also played a pathophysiological role in this case.
Assuntos
Encefalite , Metapneumovirus , Infecções por Paramyxoviridae , Pneumonia Viral , Infecções Respiratórias , Substância Branca , Adulto , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Criança , Encefalite/complicações , Humanos , Lactente , Infecções por Paramyxoviridae/complicações , Pneumonia Viral/complicações , Síndrome da Trissomia do Cromossomo 13/complicações , Substância Branca/diagnóstico por imagemRESUMO
Cerebellar ataxia, mental retardation, and disequilibrium syndrome 4 (CAMRQ4) is early onset neuromotor disorder and intellectual disabilities caused by variants of ATP8A2. We report sibling cases and systematically analyze previous literature to increase our understanding of CAMRQ4. Japanese siblings presented with athetotic movements at 1 and 2 months of age. They also had ptosis, ophthalmoplegia, feeding difficulty, hypotonia, and severely delayed development. One patient had retinal degeneration and optic atrophy. Flattening of the auditory brainstem responses and areflexia developed. At the last follow-up, neither patient could sit or achieve head control, although some nonverbal communication was preserved. Whole exome sequencing revealed compound heterozygous variants of ATP8A2: NM_016529.6:c.[1741C>T];[2158C>T] p.[(Arg581*)];[(Arg720*)]. The p.(Arg581*) variant has been reported, while the variant p.(Arg720*) was novel. The symptoms did not progress in the early period of development, which makes it difficult to distinguish from dyskinetic cerebral palsy, particularly in solitary cases. However, visual and hearing impairments associated with involuntary movements and severe developmental delay may be a clue to suspect CAMRQ4.
Assuntos
Ataxia Cerebelar , Deficiência Intelectual , Adenosina Trifosfatases , Humanos , Deficiência Intelectual/genética , Hipotonia Muscular , Náusea , Proteínas de Transferência de Fosfolipídeos , Irmãos , SíndromeRESUMO
Variants of SCN1A represent the archetypal channelopathy associated with several epilepsy syndromes. The clinical phenotypes have recently expanded from Dravet syndrome. CASE REPORT: We present a female patient with the de novo SCN1A missense variant, c.5340G > A (p. Met1780Ile). The patient had various clinical features with neonatal onset SCN1A epileptic encephalopathy, arthrogryposis multiplex congenita, thoracic hypoplasia, thoracic scoliosis, and hyperekplexia. CONCLUSION: Our findings are compatible with neonatal developmental and epileptic encephalopathy with movement disorders and arthrogryposis; the most severe phenotype probably caused by gain-of-function variant of SCN1A. The efficacy of sodium channel blocker was also discussed. Further exploration of the phenotype-genotype relationship of SCN1A variants may lead to better pharmacological treatments and family guidance.
Assuntos
Artrogripose , Epilepsias Mioclônicas , Síndromes Epilépticas , Transtornos dos Movimentos , Feminino , Humanos , Artrogripose/genética , Epilepsias Mioclônicas/genética , Mutação de Sentido Incorreto , Transtornos dos Movimentos/genética , Fenótipo , Canal de Sódio Disparado por Voltagem NAV1.1/genética , MutaçãoRESUMO
BACKGROUND: Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that causes lactic acidosis and neurodevelopmental changes. Five causative genes have been identified: PDHA1, PDHB, DLAT, DLD, and PDHX. Four neurological phenotypes have been reported: neonatal encephalopathy with lactic acidosis, non-progressive infantile encephalopathy, Leigh syndrome, and relapsing ataxia. Of these, neonatal encephalopathy has the worst mortality and morbidity and there is no effective treatment. SUBJECTS AND METHODS: We studied two girls who were clinically diagnosed with PDHC deficiency as neonates; they were subsequently found to have PDHA1 mutations. The clinical diagnosis was based on white matter loss and a lateral ventricular septum on fetal MRI, spasticity of the lower extremities, and lactic acidosis worsening after birth. Intravenous ketogenic diets were started within 24 h after birth. The ketogenic ratio was increased until the blood lactate level was controlled, while monitoring for side effects. RESULTS: In both cases, the lactic acidosis improved immediately with no apparent side effects. Both children had better developmental outcomes than previously reported cases; neither exhibited epilepsy. CONCLUSIONS: Intravenous ketogenic diet therapy is a treatment option for neonatal-onset PDHC deficiency. Further studies are needed to optimize this therapy.
Assuntos
Dieta Cetogênica , Doença da Deficiência do Complexo de Piruvato Desidrogenase/dietoterapia , Feminino , Humanos , Lactente , Recém-Nascido , Nutrição ParenteralRESUMO
OBJECTIVE: To describe clinical and genetic studies on a patient with early-onset spinal muscular atrophyX3 (SMAX3) with novel variant of ATP7A. METHODS: Clinical, neurophysiological, neuroimaging and pathological examinations were performed. Whole exome sequencing was applied to search genetic bases of this patient. RESULTS: The patient had gait abnormality from early infantile period. Muscle imaging at 42 years old showed predominant involvement of proximal muscles as compared to the distal muscles. The patient had a novel variant of ATP7A, which was the fourth genotype of ATP7A exhibited as SMAX3. Contrary to previous reports of distal motor neuropathy, the clinical and neuroimaging findings in this case revealed dominant involvement in the proximal portion of the extremities and trunk, which is similar to patients with type III SMA. CONCLUSION: The dominant involvement of proximal motor system in this patient may expand the phenotypic variability of SMAX3. We need to be aware of this disorder in differential diagnosis of patients with type III SMA-like phenotype.
Assuntos
ATPases Transportadoras de Cobre/genética , Atrofias Musculares Espinais da Infância/diagnóstico , Atrofias Musculares Espinais da Infância/genética , Adulto , Humanos , Masculino , Atrofias Musculares Espinais da Infância/patologia , Atrofias Musculares Espinais da Infância/fisiopatologiaRESUMO
People with severe motor and intellectual disabilities syndrome (SMIDS) have multiple comorbidities and high mortality rates. This study examined whether there is a difference in the efficacy and tolerability of perampanel (PER) between patients with drug-resistant epilepsy with or without SMIDS. The study identified 65 patients with drug-resistant epilepsy who underwent PER treatment as adjunctive therapy. The 50 % responder rate was 22 % (14/65) overall and 11 % (5/44) in patients with SMIDS versus 43 % (9/21) in patients without SMIDS (p <0.01). Although the overall 50 % responder rate was similar to those of previous reports, PER was less efficacious in the patients with SMIDS; nevertheless, PER was tolerated in the patients with SMIDS.
Assuntos
Epilepsia Resistente a Medicamentos , Deficiência Intelectual , Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Quimioterapia Combinada , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/tratamento farmacológico , Japão , Nitrilas , Piridonas/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The coexistence of falcine and occipital sinuses is rare and its natural course has not been reported. CASE REPORTS: Two patients with persistent falcine and occipital sinuses are described. Both patients had straight sinuses. In one, both the transverse and sigmoid sinuses were hypoplastic and the patient had an acquired Chiari I malformation. The other patient had no other venous anomalies and had a normal posterior cranial fossa. CONCLUSION: The coexistence of falcine and occipital sinuses can lead to an acquired Chiari I malformation. These cases suggest the importance of checking other venous and brain anomalies in this situation.
Assuntos
Cavidades Cranianas/anormalidades , Dura-Máter/anormalidades , Lobo Occipital/anormalidades , Adolescente , Malformação de Arnold-Chiari/fisiopatologia , Humanos , Lactente , Japão , MasculinoRESUMO
BACKGROUND: The clinical severity of Sandhoff disease is known to vary widely. Furthermore, long-term follow-up report is very limited in the literature. CASE PRESENTATION: We present a long-term follow-up report of a patient with juvenile-onset Sandhoff disease with a motor neuron disease phenotype. The patient had compound heterozygous variants of HEXB (p.Trp460Arg, p. Arg533His); the Trp460Arg was a novel variant. Long-term follow-up revealed no intellectual deterioration, swallowing dysfunction, or respiratory muscle dysfunction despite progressive weakness of the extremities and sensory disturbances. CONCLUSION: We need to be aware of Sandhoff disease in patients with juvenile-onset motor neuron disease.
Assuntos
Doença dos Neurônios Motores/etiologia , Doença de Sandhoff/genética , Adulto , Idade de Início , Seguimentos , Humanos , Fenótipo , Doença de Sandhoff/complicaçõesRESUMO
BACKGROUND: Generalized epilepsy and tremor phenotypes have been reported in some genetic disorders. Among them benign adult familial myoclonus epilepsy (BAFME) has been confirmed as a clearly defined clinical and genetic entity. On the other hand, non-progressive tremor and generalized epilepsy phenotypes have also been reported in patients with DHDDS variants. CASE PRESENTATION: We report on a long term follow-up of patient with de novo missense variant of DHDDS, who revealed non progressive nature. This 18-year-old woman presented non-progressive tremor since her early infancy. She had rare seizures. Her tremor was considered as cortical myoclonic tremor with giant somatosensory evoked potentials. CONCLUSION: In patients with early onset, non-progressive tremor and rare generalized epilepsy phenotypes, DHDDS variants may be considered in the genetic differential diagnosis.
Assuntos
Alquil e Aril Transferases/genética , Epilepsias Mioclônicas/genética , Epilepsia Generalizada/genética , Adulto , Alquil e Aril Transferases/metabolismo , Eletroencefalografia , Epilepsias Mioclônicas/fisiopatologia , Epilepsia Generalizada/fisiopatologia , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Seguimentos , Humanos , Japão , Mutação de Sentido Incorreto/genética , Linhagem , FenótipoRESUMO
We report the first three Japanese patients with missense variants in the GNB1 gene. Patients exhibited severe dyskinetic quadriplegia with cortical blindness and epileptic spasms, West syndrome (but with good outcomes), and hypotonic quadriplegia that later developed into spastic diplegia. Whole-exome sequencing revealed two recurrent GNB1 variants (p.Leu95Pro and p.Ile80Thr) and one novel variant (p.Ser74Leu). A recent investigation revealed large numbers of patients with GNB1 variants. Functional studies of such variants and genotype-phenotype correlation are required to enable future precision medicine.