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1.
Seizure ; 66: 26-30, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30776697

RESUMO

PURPOSE: This study aimed to investigate the genetic etiology of epilepsy in a cohort of Chinese children. METHODS: Targeted next-generation sequencing (NGS) was performed for 120 patients with unexplained epilepsy, including 71 patients with early-onset epileptic encephalopathies, and 16 patients with Dravet syndrome (including three patients with a Dravet-like phenotype) but without SCN1A pathogenic variants. RESULTS: Pathogenic variants of 14 genes were discovered in 22 patients (18%). A de novo KCND3 pathogenic variant (c.1174G > A, p.Val392Ile) was identified in a boy with refractory epilepsy, psychomotor regression, attention deficit, and visual decline. Pathogenic variants in other coding genes were excluded via whole exome sequencing. This KCND3 variant was previously confirmed to be pathogenic by Giudicessi, et al. However, the clinical profile was different: sudden death at 20 years old without any medical history of neurological disorders, nor with any diseases typically caused by KCND3 pathogenic variants such as Brugada syndrome, spinocerebellar ataxia type 19/22 or ataxia accompanied by epilepsy. This indicates that we have identified a new KCND3 phenotype. In addition, we also uncovered a GRIN1 pathogenic variant and a novel HCN1 pathogenic variant in the Dravet cohort. CONCLUSION: Our study highlights the significant utility of NGS panels in the genetic diagnosis of pediatric epilepsy. Our findings indicate that KCND3 pathogenic variants may be responsible for a wider phenotypic spectrum than previously thought, by including childhood epileptic encephalopathy. Furthermore, this study provides evidence that GRIN1 and HCN1 are candidate genes for Dravet and Dravet-like phenotypes.


Assuntos
Epilepsias Mioclônicas/genética , Mutação/genética , Canais de Potássio Shal/genética , Análise de Variância , Pré-Escolar , China , Estudos de Coortes , Análise Mutacional de DNA , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Frequência do Gene , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Lactente , Imagem por Ressonância Magnética , Masculino , Proteínas do Tecido Nervoso/genética , Canais de Potássio/genética , Receptores de N-Metil-D-Aspartato/genética
2.
Epileptic Disord ; 20(3): 214-218, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897043

RESUMO

We describe a 10-month-old boy with early-onset epileptic encephalopathy who was found to have a hemizygous deletion in 9q33.3-q34.11 involving STXBP1 and SPTAN1 genes. He presented at the age of 2.5 months with frequent upper extremity myoclonus, hypotonia, and facial dysmorphisms. Interictal EEG showed multifocal polyspike and wave during wakefulness and sleep. Ictal EEG revealed low-amplitude generalized sharp slow activity, followed by diffuse attenuation. Metabolic testing was unrevealing. Brain MRI showed thinning of the corpus callosum with an absence of rostrum. This patient is the second reported case with 9q33.3-q34.11 deletion involving STXBP1 and SPTAN1 genes associated with epileptic encephalopathy and myoclonic seizures. Larger case series are needed to better delineate this association.


Assuntos
Proteínas de Transporte/genética , Epilepsias Mioclônicas/genética , Proteínas dos Microfilamentos/genética , Proteínas Munc18/genética , Espasmos Infantis/genética , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Deleção Cromossômica , Eletroencefalografia , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/fisiopatologia , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Espasmos Infantis/diagnóstico por imagem , Espasmos Infantis/fisiopatologia
3.
Biochem Biophys Res Commun ; 500(2): 158-162, 2018 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-29625105

RESUMO

We sequenced the mitochondrial genome from a 40-year-old woman with myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications. Histological and biochemical features of mitochondrial respiratory chain dysfunction were present. Direct sequencing showed a novel heteroplasmic mutation at nucleotide 5513 in the MT-TW gene that encodes tRNATrp. Restriction Fragment Length Polymorphism analysis confirmed that about 80% of muscle mtDNA harboured the mutation while it was present in minor percentages in mtDNA from other tissues. The mutation is predicted to disrupt a highly conserved base pair within the aminoacyl acceptor stem of the tRNA. This is the 17° mutation in MT-TW gene and expands the known causes of late-onset mitochondrial diseases.


Assuntos
Epilepsias Mioclônicas/genética , Predisposição Genética para Doença , Leucoencefalopatias/genética , Mutação/genética , RNA de Transferência de Triptofano/genética , Retinite Pigmentosa/genética , Calcificação Vascular/genética , Adulto , Sequência de Bases , Epilepsias Mioclônicas/sangue , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Humanos , Leucoencefalopatias/sangue , Leucoencefalopatias/diagnóstico por imagem , Retinite Pigmentosa/sangue , Retinite Pigmentosa/diagnóstico por imagem , Análise de Sequência de DNA , Tomografia Computadorizada por Raios X
4.
Brain Dev ; 40(2): 126-129, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28823645

RESUMO

BACKGROUND: Epilepsy with myoclonic absences (EMAs) is a rare epileptic disorder characterized by a predominant type of seizures, myoclonic absences (MAs). The pathophysiology of MAs in patients with EMAs remains unknown. Here, we report the first characterization of the ictal phase of MAs by single photon emission computed tomography (SPECT). METHODS: We evaluated 1 male (Patient 1) and 1 female (Patient 2) patient with EMAs, aged 8 and 4years at first SPECT investigation, respectively. We performed ictal and interictal 99 mTc-ethyl cysteinate dimer (ECD) SPECT. We then generated images of subtraction ictal SPECT co-registered to MRI (SISCOM) from the interictal and ictal data to evaluate topographic changes in cerebral blood flow (CBF) during MAs as compared to the interictal state. RESULTS: In Patient 1, the CBF increased in the perirolandic areas, thalamus, caudate nucleus, and precuneus, and decreased in the middle frontal gyrus and bilateral orbitofrontal regions. In Patient 2, CBF increased in the thalamus, putamen, and globus pallidus. In contrast to the CBF in Patient 1, CBF was decreased in the precuneus. CONCLUSIONS: Using SPECT, we showed that, in addition to the thalamus and basal ganglia, the perirolandic cortical motor area is involved in MAs. We hypothesize that in MAs the blood perfusion in the perirolandic cortical motor area might have changed under the influence of the cortico-thalamic network oscillation features. The CBF properties observed by means of our SPECT procedure may represent key features of the pathophysiological mechanisms underlying MAs.


Assuntos
Encéfalo/diagnóstico por imagem , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsia Tipo Ausência/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Encéfalo/fisiopatologia , Mapeamento Encefálico , Circulação Cerebrovascular , Criança , Pré-Escolar , Epilepsias Mioclônicas/fisiopatologia , Epilepsia Tipo Ausência/fisiopatologia , Feminino , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/fisiopatologia , Masculino , Fluxo Sanguíneo Regional
5.
Brain Dev ; 40(2): 130-133, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28927557

RESUMO

We report a one-year-old boy with early-onset myoclonic epilepsy, developmental arrest, and hyperekplexia during early infancy. He presented with refractory myoclonic/tonic seizures since birth. Electroencephalography revealed multifocal spikes, and rhythmic activities that occurred simultaneous with aggravation of myoclonus accompanied by tonic upper limb elevation. Brain magnetic resonance imaging revealed progressive cerebral atrophy with periventricular signal change and thin corpus callosum at one year of age. A de novo heterozygous missense mutation in the CACNA1A gene was confirmed. This patient was the most severe phenotype of CACNA1A-related early-onset encephalopathy among previous reports.


Assuntos
Encéfalo/diagnóstico por imagem , Canais de Cálcio/genética , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/genética , Mutação de Sentido Incorreto , Encéfalo/fisiopatologia , Epilepsias Mioclônicas/fisiopatologia , Humanos , Hiperecplexia/diagnóstico por imagem , Hiperecplexia/genética , Hiperecplexia/fisiopatologia , Lactente , Masculino , Fenótipo , Índice de Gravidade de Doença
6.
Ann Ist Super Sanita ; 53(2): 167-169, 2017 Apr-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28617265

RESUMO

The neurologic sequelae post-measles are less common than other complications measles-related and can lead to severe disability or death: primary measles encephalitis (PME), acute post-infectious measles encephalomyelitis (APME), measles inclusion body encephalitis (MIBE), and subacute sclerosing panencephalitis (SSPE). SSPE syndrome can affect people years from the acute measles virus infection, as result of the persistence of defective viral particles in brain cells. Clinical onset typically manifests with progressive intellectual deterioration, behavioral changes, and myoclonic jerks. The course of SSPE in the majority of affected children is that of a progressive worsening with fatal outcome within two years. This report described an Italian case of fulminant SSPE syndrome that led to death within few months from the initial onset.


Assuntos
Epilepsias Mioclônicas/etiologia , Panencefalite Esclerosante Subaguda/complicações , Pré-Escolar , Diagnóstico Diferencial , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/diagnóstico por imagem , Evolução Fatal , Feminino , Humanos , Imagem por Ressonância Magnética , Panencefalite Esclerosante Subaguda/diagnóstico , Panencefalite Esclerosante Subaguda/diagnóstico por imagem
7.
Ann Neurol ; 81(5): 677-689, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28380698

RESUMO

OBJECTIVE: To comprehensively describe the new syndrome of myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK), including cellular electrophysiological characterization of observed clinical improvement with fever. METHODS: We analyzed clinical, electroclinical, and neuroimaging data for 20 patients with MEAK due to recurrent KCNC1 p.R320H mutation. In vitro electrophysiological studies were conducted using whole cell patch-clamp to explore biophysical properties of wild-type and mutant KV 3.1 channels. RESULTS: Symptoms began at between 3 and 15 years of age (median = 9.5), with progressively severe myoclonus and rare tonic-clonic seizures. Ataxia was present early, but quickly became overshadowed by myoclonus; 10 patients were wheelchair-bound by their late teenage years. Mild cognitive decline occurred in half. Early death was not observed. Electroencephalogram (EEG) showed generalized spike and polyspike wave discharges, with documented photosensitivity in most. Polygraphic EEG-electromyographic studies demonstrated a cortical origin for myoclonus and striking coactivation of agonist and antagonist muscles. Magnetic resonance imaging revealed symmetrical cerebellar atrophy, which appeared progressive, and a prominent corpus callosum. Unexpectedly, transient clinical improvement with fever was noted in 6 patients. To explore this, we performed high-temperature in vitro recordings. At elevated temperatures, there was a robust leftward shift in activation of wild-type KV 3.1, increasing channel availability. INTERPRETATION: MEAK has a relatively homogeneous presentation, resembling Unverricht-Lundborg disease, despite the genetic and biological basis being quite different. A remarkable improvement with fever may be explained by the temperature-dependent leftward shift in activation of wild-type KV 3.1 subunit-containing channels, which would counter the loss of function observed for mutant channels, highlighting KCNC1 as a potential target for precision therapeutics. Ann Neurol 2017;81:677-689.


Assuntos
Ataxia , Disfunção Cognitiva/etiologia , Epilepsias Mioclônicas , Temperatura Alta , Canais de Potássio Shaw/metabolismo , Adolescente , Adulto , Idade de Início , Ataxia/complicações , Ataxia/diagnóstico por imagem , Ataxia/genética , Ataxia/fisiopatologia , Eletroencefalografia , Epilepsias Mioclônicas/complicações , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/fisiopatologia , Feminino , Células HEK293 , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Canais de Potássio Shaw/genética , Síndrome , Adulto Jovem
8.
Neurologia ; 32(2): 69-73, 2017 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25661268

RESUMO

INTRODUCTION: Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. METHOD: We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. RESULTS: In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. CONCLUSIONS: The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment.


Assuntos
Doença de Alzheimer/complicações , Síndrome de Down/complicações , Epilepsias Mioclônicas/complicações , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/tratamento farmacológico , Feminino , Humanos , Levetiracetam , Masculino , Pessoa de Meia-Idade , Piracetam/análogos & derivados , Piracetam/uso terapêutico , Estudos Retrospectivos , Ácido Valproico/uso terapêutico
9.
Brain Dev ; 39(1): 75-79, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27523882

RESUMO

We report a female patient with Dravet syndrome (DS) with erratic segmental myoclonus, the origin of which was first identified in the cerebral cortex by the detection of myoclonus-associated cortical discharges. The discharges were disclosed through jerk-locked back-averaging of electroencephalogram (EEG) data using the muscle activity of myoclonus as triggers. The detected spikes on the contralateral parieto-central region preceded myoclonic muscle activity in the forearms by 28-46ms. The patient was six months old at the time of examination, and was developing normally before seizure onset at two months of age. She suffered from recurrent afebrile or febrile generalized tonic-clonic seizures that often developed into status epilepticus. Interictal EEG and brain magnetic resonance imaging (MRI) showed no significant findings. The amplitudes of the somatosensory-evoked potentials were not extremely large. She has a chromosomal microdeletion involving SCN1A and adjacent genes.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Eletroencefalografia/métodos , Epilepsias Mioclônicas/diagnóstico por imagem , Mioclonia/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Diagnóstico Diferencial , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/fisiopatologia , Feminino , Humanos , Lactente , Mioclonia/tratamento farmacológico , Mioclonia/genética , Mioclonia/fisiopatologia , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Deleção de Sequência , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/genética , Estado Epiléptico/fisiopatologia
10.
Neurogenetics ; 17(4): 251-257, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27631729

RESUMO

Cutis laxa syndromes are rare inherited disorders of skin and connective tissue metabolism associated with variable systemic involvement. The main clinical manifestation is loose, wrinkled, redundant, inelastic skin, hypotonia, typical facies including short nose and down-slanting palpebral fissures, and varying degrees of developmental delay. The aim of this report is to describe two siblings diagnosed with a moderate form of ATP6V0A2-related cutis laxa with polymicrogyria (cobblestone-like brain dysgenesis). One of the patients has myoclonic epilepsy which may have contributed to his more severe clinical presentation. The literature on cutis laxa syndromes is reviewed.


Assuntos
Cútis Laxa/patologia , Cútis Laxa/fisiopatologia , Epilepsias Mioclônicas/patologia , Epilepsias Mioclônicas/fisiopatologia , Polimicrogiria/patologia , Polimicrogiria/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Cútis Laxa/complicações , Cútis Laxa/diagnóstico por imagem , Epilepsias Mioclônicas/complicações , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Humanos , Masculino , Mutação , Polimicrogiria/complicações , Polimicrogiria/diagnóstico por imagem , Irmãos
11.
Seizure ; 41: 81-5, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27513994

RESUMO

PURPOSE: Familial cortical myoclonic tremor with epilepsy (FCMTE) is an epileptic syndrome with autosomal dominant inheritance, of which four genetic subtypes (FCMTE1-4) have been reported. In the present study, we described the clinical and neurophysiologic features of a newly diagnosed Chinese FCMTE family, and investigated the genetic cause for this disease. METHODS: Clinical information was obtained from affected and normal individuals of an FCMTE family comprising 41 members. Electroencephalographies were analyzed in five of six affected members (including the proband). Brain magnetic resonance imaging, somatosensory evoked potential with C-reflex analysis and magnetoencephalography was performed in the proband. Genomic DNA of three affected and two unaffected individuals was analyzed to detect the genetic mutations by using whole-exome sequencing. RESULTS: The inheritance pattern of the pedigree was autosomal dominant. A novel missense mutation c.475C>T (p.Ala159Thr) of PLA2G6 were identified in this family. The mutated locus is highly conserved among other species. The mutation is predicted to have a functional impact, and completely co-segregated with the phenotype. CONCLUSION: This study identifies a novel PLA2G6 mutation that is the possible genetic cause of FCMTE in this family. This mutation and associated clinical features expand the spectrum and phenotypes of PLA2G6-related disorders including neurodegenerative diseases.


Assuntos
Epilepsias Mioclônicas/genética , Fosfolipases A2 do Grupo VI/genética , Mutação de Sentido Incorreto/genética , Linhagem , Adulto , Grupo com Ancestrais do Continente Asiático , Análise Mutacional de DNA , Eletroencefalografia , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Epilepsia ; 57(6): 941-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27037791

RESUMO

OBJECTIVE: The pathogenesis of benign adult familial myoclonic epilepsy (BAFME) remains unknown, although cerebellar pathologic changes and brain hyperexcitability have been reported. We used resting-state functional magnetic resonance imaging (fMRI) to examine the functional connectivity between the cerebellum and cerebrum in a Chinese family with BAFME for the first time. METHODS: Eleven adults with BAFME and 15 matched healthy controls underwent resting-state blood oxygen level-dependent (BOLD) fMRI scanning. The cerebellar seeds, including the bilateral crus I, lobule VIII, lobule VIIb, and lobule IV&V, were defined a priori. Next, regional time courses were obtained for each individual by averaging the BOLD time series over all voxels in each seed region. Then, seed-based functional connectivity z-maps were produced by computing Pearson's correlation coefficients (converted to z-scores by Fisher transformation) between each seed signal and the time series from all other voxels within the entire brain. Finally, a second-level random-effect two-sample t-test was performed on the individual z-maps in a voxel-wise manner. RESULTS: Reduced functional connectivity of the right cerebellar crus I with the left middle frontal gyrus and right cerebellar lobule IX was observed in the default network of BAFME. Enhanced functional connectivity of the left cerebellar lobule VIII with the bilateral middle temporal gyri, right putamen, and left cerebellar crus I was found in the dorsal attention network of BAFME. Enhanced functional connectivity between the left cerebellar lobule VIIb and right frontal pole was found in the control network of BAFME. SIGNIFICANCE: Altered cerebellar-cerebral functional connectivity may contribute to the understanding of the nosogenesis of BAFME and explain the cognitive dysfunction in this Chinese family with BAFME.


Assuntos
Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Epilepsias Mioclônicas/fisiopatologia , Vias Neurais/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Eletroencefalografia , Eletromiografia , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Testes Neuropsicológicos , Oxigênio/sangue , Adulto Jovem
13.
J Child Neurol ; 31(9): 1127-37, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27095821

RESUMO

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins.


Assuntos
Epilepsia Resistente a Medicamentos/genética , Epilepsias Mioclônicas/genética , Heterozigoto , Proteínas Mitocondriais/genética , Mutação , Fenilalanina-tRNA Ligase/genética , Adolescente , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/patologia , Epilepsias Mioclônicas/fisiopatologia , Evolução Fatal , Feminino , Humanos , Fenótipo
14.
Cerebellum ; 15(6): 696-704, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26519379

RESUMO

Essential tremor (ET) presumably has a cerebellar origin. Imaging studies showed various cerebellar and also cortical structural changes. A number of pathology studies indicated cerebellar Purkinje cell pathology. ET is a heterogeneous disorder, possibly indicating different underlying disease mechanisms. Familial cortical myoclonic tremor with epilepsy (FCMTE), with evident Purkinje cell degeneration, can be an ET mimic. Here, we investigate whole brain and, more specifically, cerebellar morphological changes in hereditary ET, FCMTE, and healthy controls. Anatomical magnetic resonance images were preprocessed using voxel-based morphometry. Study 1 included voxel-wise comparisons of 36 familial, propranolol-sensitive ET patients, with subgroup analysis on age at onset and head tremor, and 30 healthy controls. Study 2 included voxel-wise comparisons in another nine ET patients, eight FCMTE patients, and nine healthy controls. Study 3 compared total cerebellar volume between 45 ET patients, 8 FCTME patients, and 39 controls. In our large sample of selected hereditary ET patients and ET subgroups, no local atrophy was observed compared to healthy controls or FCMTE. In ET patients with head tremor, a volume increase in cortical motor regions was observed. In FCMTE, a decrease in total cerebellar volume and in local cerebellar gray matter was observed compared to healthy controls and ET patients. The current study did not find local atrophy, specifically not in the cerebellum in hereditary ET, contrary to FCMTE. Volume increase of cortical motor areas in ET patients with head tremor might suggest cortical plasticity changes due to continuous involuntary head movements.


Assuntos
Cerebelo/diagnóstico por imagem , Epilepsias Mioclônicas/diagnóstico por imagem , Tremor Essencial/diagnóstico por imagem , Imagem por Ressonância Magnética , Adulto , Idade de Início , Atrofia/diagnóstico por imagem , Tremor Essencial/tratamento farmacológico , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares/farmacologia , Tamanho do Órgão , Propranolol/farmacologia
15.
J Formos Med Assoc ; 113(4): 258-63, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23643463

RESUMO

Myoclonic astatic epilepsy (MAE) is characterized by multiple seizure types, which are often refractory. Although vagus nerve stimulation (VNS) is an alternative treatment for medically intractable seizures, its exact mechanism of action remains unclear. Herein, we report the case of a 4-year-old boy with intractable MAE who has been in a seizure-free status for 2 years and 3 months since 6 months after the implantation of a vagus nerve stimulator (Model 103, Cyberonics, Inc., Houston, TX). Various test results 6 months after VNS were compared with those before VNS. Results of an electroencephalograph revealed disappearance of epileptiform discharges and an increased beta-gamma spectrum rhythm. The brain diffusion-tensor imaging showed an increased ratio of fraction anisotropy in the right fimbria-fornix, indicating improved diffusion of the white matter tract, and (18)F-fluorodeoxyglucose positron emission tomography revealed globally improved cerebral glucose metabolism. His cognitive and social-emotional performances also improved at 2 years after VNS. To the best of our knowledge, this is the first report to describe the effects of VNS on fimbria-fornix and glucose metabolism in MAE.


Assuntos
Eletroencefalografia , Epilepsias Mioclônicas/fisiopatologia , Neuroimagem , Estimulação do Nervo Vago , Pré-Escolar , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/terapia , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia por Emissão de Pósitrons
16.
Gene ; 512(2): 450-2, 2013 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-23124037

RESUMO

Several neurodegenerative disorders are known to predominantly affect the white matter of the brain including vanishing white matter disease (VWMD), an autosomal recessive disorder characterized by leukodystrophy of varying severity in addition to variable systemic involvement. We report a consanguineous Arab family with three affected children, all of whom presented with severe neonatal epilepsy and profound neurodegenerative disease characterized by marked leukodystrophy with white matter cavitation mimicking VWMD. We combined autozygome and exome analysis to identify a novel variant in the gene encoding a member of the eIF2B-related family of proteins (MRI1). This is a poorly understood family of proteins of unclear function. Our results represent the first link between a variant in a member of this family and a human disease, and suggest that it converges with the highly homologous eIF2B, known to be mutated in VWMD, on the molecular pathogenesis of neurodegeneration.


Assuntos
Aldose-Cetose Isomerases/genética , Epilepsias Mioclônicas/genética , Loci Gênicos , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Leucoencefalopatias/genética , Adulto , Aldose-Cetose Isomerases/metabolismo , Árabes , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/enzimologia , Feminino , Transtornos Heredodegenerativos do Sistema Nervoso/diagnóstico por imagem , Transtornos Heredodegenerativos do Sistema Nervoso/enzimologia , Humanos , Lactente , Recém-Nascido , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/enzimologia , Masculino , Radiografia
17.
Epilepsy Behav ; 17(4): 561-4, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20181534

RESUMO

We describe a patient with seizures arising from right anterior-inferior frontal lobe presenting as myoclonic epilepsy. A 19-year-old man had experienced frequent paroxysmal bilateral myoclonic jerks involving his upper arms, shoulders, neck, and upper trunk since the age of 10. His baseline EEG showed intermittent right frontal spikes, and his ictal EEG showed rhythmic sharp theta discharges in the same area. MRI revealed cortical dysplasia in the right inferior frontal gyrus, and ictal-interictal SPECT analysis by SPM showed increased signal abnormality in this region. Diffusion tensor imaging (DTI) showed defects in fasciculi in the same area. These findings suggest that frontal lobe epilepsy should be considered in some patients with myoclonic seizures.


Assuntos
Epilepsias Mioclônicas/diagnóstico , Epilepsia do Lobo Frontal/diagnóstico , Anticonvulsivantes/uso terapêutico , Mapeamento Encefálico , Imagem de Difusão por Ressonância Magnética/métodos , Eletroencefalografia/métodos , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsia do Lobo Frontal/diagnóstico por imagem , Epilepsia do Lobo Frontal/tratamento farmacológico , Humanos , Masculino , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto Jovem
18.
Epilepsy Res ; 89(2-3): 220-6, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20133106

RESUMO

Negative myoclonus (NM) is a sudden brief atonia in muscle that causes jerky lapses of posture. This study employed an electrophysiological technique (silent-period-locked-averaging (SPLA) electroencephalography (EEG)) and a pharmacodynamic imaging technique (123I-IMZ-SPECT) to examine epileptic NM (ENM). Delayed-phase 123I-IMZ-SPECT images, which reflect the specific binding of the tracers to GABA-A receptors, exhibited significant decrease in the left medial frontal area. The deficit in GABA-A receptors indicated that abnormal synchronization was mediated by the lack of inhibitory postsynaptic mechanism. The SPLA-EEG recorded spike-like notches superimposed on the slope of negative slow activity in the contralateral fronto-central region. The slow activity started around 100 ms before and the peak of the spike-like component was 30 ms before the onset of ENM. Since the 123I-IMZ-SPECT shows the actual distribution of the tracers, the abnormal area associated with ENM in this particular patient was supposed to be on the left medial frontal lobe. Scalp EEG, though it cannot always accurately locate the abnormal area, was highly sensitive to be able to detect electrical activities transmitted through neuronal network or volume conductor. Combined use of the two methods provided high resolution both in spatial and temporal domain.


Assuntos
Eletroencefalografia , Epilepsias Mioclônicas/metabolismo , Epilepsias Mioclônicas/fisiopatologia , Lobo Frontal/metabolismo , Lobo Frontal/fisiopatologia , Receptores de GABA-A/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Eletroencefalografia/métodos , Epilepsias Mioclônicas/diagnóstico por imagem , Flumazenil/análogos & derivados , Lobo Frontal/diagnóstico por imagem , Humanos , Radioisótopos do Iodo , Masculino , Tempo de Reação , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto Jovem
19.
Epilepsia ; 51(4): 699-702, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19922588

RESUMO

We, for the first time, used functional neuroimaging analyses for a girl with early myoclonic encephalopathy (EME). The interictal single photon emission computed tomography (SPECT) and [18F]-fluoro-D-deoxyglucose positron emission tomography (FDG-PET) at 1 month of age showed hypoperfusion and hypometabolism of bilateral basal ganglia, thalami, and the right parietooccipital cerebral cortices, showing that there is profound dysfunction of the basal ganglia and thalamus as well as cerebral cortex. On the other hand, subtraction ictal SPECT of tonic spasms clearly showed hyperperfusion of the bilateral basal ganglia, thalami, brainstem, and deep cortical layer of bilateral frontoparietal cortices. The present study suggests that functional deafferentation of the cortex from subcortical structures exists in EME, and that these imaging abnormalities may provide insight into the pathophysiology of suppression-burst pattern in EME.


Assuntos
Vias Aferentes/fisiopatologia , Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Epilepsias Mioclônicas/fisiopatologia , Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Vias Aferentes/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Criança , Dominância Cerebral/fisiologia , Eletroencefalografia , Metabolismo Energético/fisiologia , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Sinais Assistido por Computador , Técnica de Subtração
20.
J Neurol ; 255(4): 520-5, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18283401

RESUMO

PURPOSE: To investigate the regional cerebral blood flow (rCBF) changes in patients with idiopathic generalized epilepsy (IGE), we compared brain single photon emission computed tomography (SPECT) images of drug naïve IGE patients with those of age/sex matched healthy volunteers. METHODS: Brain interictal 99mTc-ethylcysteinate dimer SPECT was performed in 21 patients with IGE (M/F = 10/11, 21.3 +/- 2.7 years) and 21 normal controls. The seizure types were generalized tonic-clonic seizure in 14 patients and myoclonic seizures with rare generalized tonic-clonic seizures in seven. Differences of rCBF between an IGE group and a normal control group were examined by the statistical parametric mapping (SPM) of brain SPECT images using independent t test. RESULTS: The SPM analysis showed that the rCBF of the IGE patients was significantly reduced in the anterior and posterior cingulate gyri, bilateral anterior nuclei and right dorsolateral nucleus of the thalamus, right superior colliculus of the midbrain, and the cerebellum at the level of uncorrected p < 0.005. In the small volume correction analysis for the thalamus and brainstem, the rCBF was also significantly decreased in the same brain regions at the level of FDR corrected p < 0.05. No brain regions of the IGE patients had increased rCBF. CONCLUSION: Our study demonstrates that the interictal rCBF in drug naive IGE patients is reduced in the cingulate gyrus, thalamus, brainstem and cerebellum. This result suggests that dysfunctions in these brain regions are associated with IGE.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Epilepsia Generalizada/diagnóstico por imagem , Epilepsia Generalizada/fisiopatologia , Adolescente , Adulto , Encéfalo/irrigação sanguínea , Mapeamento Encefálico/métodos , Artérias Cerebrais/fisiopatologia , Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/etiologia , Cisteína/análogos & derivados , Regulação para Baixo/fisiologia , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/fisiopatologia , Epilepsia Tônico-Clônica/diagnóstico por imagem , Epilepsia Tônico-Clônica/fisiopatologia , Feminino , Humanos , Masculino , Compostos de Organotecnécio , Tomografia Computadorizada de Emissão de Fóton Único
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