RESUMO
An electron microscopic study revealed disruption of capillary endothelial tight junctions (TJs) in both biopsied muscle, taken at 5 years and 1 month of age, and the autopsied brain, taken at 13 years and 6 months of age, in a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) and mitochondrial DNA (mtDNA) point mutation A3243G. This endothelial barrier disruption might result in vasogenic edema and systemic lactic acidosis, possibly the critical pathology of MELAS.
Assuntos
Encéfalo/patologia , Síndrome MELAS/patologia , Junções Íntimas/patologia , Adolescente , Encéfalo/ultraestrutura , DNA Mitocondrial/genética , Progressão da Doença , Feminino , Humanos , Síndrome MELAS/genética , Microscopia Eletrônica de Transmissão/métodos , Mutação Puntual/genética , Junções Íntimas/diagnóstico por imagem , UltrassonografiaRESUMO
N-acetyltransferase (NAT2) is an enzyme involved in detoxification of various carcinogens. The gene is highly polymorphic with a number of alleles, and is also known as acetylator phenotypes: the fast, intermediate and slow acetylators. In this report, we describe a novel NAT2 allele, which was found in the allele typing with 109 Japanese individuals using conventional restriction fragment length polymorphism (RFLP) method. The sequence analyses of the entire amino acid coding region of the novel allele showed that it possessed a 190C>T variation leading to an amino acid substitution from arginine to tryptophan at position 64 (R64W). Consequently, the novel allele we found has been given the name of NAT2*19 by the arylamine N-acetyltransferase nomenclature committee.
Assuntos
Alelos , Substituição de Aminoácidos/genética , Arilamina N-Acetiltransferase/genética , Cisteína/genética , Treonina/genética , Frequência do Gene , HumanosRESUMO
The ependyma was examined in eight children with neuroblast migratory disorders of diverse origin: three cases of lissencephaly type 1 with severe to mild degrees of agyria/pachygyria, four cases of lissencephaly type 2 in Fukuyama muscular dystrophy and the Walker-Warburg syndrome, and one case of hemimegalencephalic pachygyria. Morphological and immunohistochemical abnormalities of the ependyma were strikingly similar in all. Discontinuities were disproportionate to the degree of ventriculomegaly. In some regions, the ependyma remained a pseudostratified columnar epithelium, though basal processes were absent. The poles of the horns of the lateral ventricles were replaced by extensive heterotopic ependymal rosettes. Rosettes and rows of ependyma also were in other subventricular sites. Subependymal nodules of large astrocytes and their processes bulged into the ventricular lumen after infancy. Ependymal cells did not express glial fibrillary acidic protein, but showed persistent expression of S-100 protein, cytokeratin CK-904 and sometimes vimentin long after these proteins normally disappear. An abnormal ependyma in lissencephaly/pachygyria may contribute to disturbances in neuronogenesis, guidance of axonal projections and neuroblast migrations; it may be a primary factor in pathogenesis.
Assuntos
Encefalopatias/patologia , Encéfalo/anormalidades , Encéfalo/patologia , Epêndima/patologia , Córtex Cerebral/anormalidades , Córtex Cerebral/patologia , Ventrículos Cerebrais/patologia , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Distrofias Musculares/patologia , Lobo Occipital/patologia , SíndromeRESUMO
We report the first case to our knowledge of chronic pancreatitis associated with mitochondrial encephalopathy with the A8344G mitochondrial DNA (mtDNA) mutation. This 10-year-old-girl had suffered from recurrent abdominal pain with elevated serum amylase and lipase since the age of 6, and easy fatigability, tremor and astatic seizures since the age of 8. A biopsy of quadriceps muscle revealed ragged-red-fibers and cytochrome c oxidase deficiency. Analysis of mtDNA in peripheral blood identified an A8344G mutation in the mitochondrial tRNA(Lys) gene. Taken together with physical signs of myoclonic seizures and cerebellar dysfunction, we diagnosed her as myoclonic epilepsy with ragged-red fibers associated with chronic pancreatitis. Although no association between mitochondrial disease and pancreatitis has yet been established, this case suggests it is necessary to consider the participation of mitochondrial abnormality in the pathogenesis of recurrent pancreatitis.
Assuntos
Síndrome MERRF/complicações , Pancreatite/genética , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Doença Crônica , Feminino , Humanos , Síndrome MERRF/genética , Síndrome MERRF/patologia , Imageamento por Ressonância Magnética , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Pâncreas/fisiopatologia , Pancreatite/patologia , Pancreatite/fisiopatologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vitaminas/uso terapêuticoRESUMO
Administration of ACTH at two different doses (0.05 and 0.5 microgram/g/day) to suckling rats resulted in the suppression of both the body and brain weight gains and the developmental increase in brain CNPase activity, and the suppression of the brain CNPase activity persisted for 3 weeks (up to the end of the experiment) after the cessation of ACTH administration in the suckling period, while the suppression of the body and brain weight gains was noticed only during the administration period. The authors emphasized the possibility that long-term therapy with massive doses of ACTH for infantile spasms may be hazardous to the developing brain in many ways.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Encéfalo/enzimologia , Crescimento/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Animais , Animais Lactentes , Encéfalo/crescimento & desenvolvimento , Depressão Química , Bainha de Mielina/fisiologia , Ratos , Ratos EndogâmicosRESUMO
A 13-year-old boy with the juvenile type of acid alpha-glucosidase deficiency is presented. Muscle CT scans performed before muscle biopsy revealed high image density over the entire rectus femoris, and partial high density over the iliopsoas, adductor magnus and tibialis anterior. MRI of the rectus femoris in the transaxial plane showed high image intensity over the entire length of the muscle in both T1- and T2-weighted images. A biopsy revealed a surprising histological difference between the rectus femoris, which showed pronounced vacuolar myopathy with excessive glycogen, and the vastus lateralis, in which deposition of glycogen was minimal and the CT image indicated a normal muscle density. The findings in this case suggest that CT scanning and MRI are useful in recognizing muscle involvement in acid alpha-glucosidase deficiency, which is characterized by images of increased density compared to normal muscle, presumably because excessive deposition of glycogen and lysosomal membranes cause high X-ray absorption on CT and high signal intensity on MRI.
Assuntos
Músculos/diagnóstico por imagem , Músculos/patologia , alfa-Glucosidases/deficiência , Adolescente , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/patologia , Tomografia Computadorizada por Raios XRESUMO
We report a 3-year-11-month-old boy who manifested action myoclonus only. Histochemical analysis of the quadriceps muscle revealed subsarcolemmal hyperactivity. The administration of 5-hydroxytryptophan and carbidopa dramatically improved the action myoclonus and reduced an amplitude of giant somatosensory evoked potentials. A nosological relation of this case with "essential myoclonus" and mitochondrial encephalomyopathy was discussed.
Assuntos
5-Hidroxitriptofano/uso terapêutico , Carbidopa/uso terapêutico , Doenças Musculares/tratamento farmacológico , Mioclonia/tratamento farmacológico , Pré-Escolar , Humanos , Masculino , Músculos/patologia , Músculos/ultraestrutura , Doenças Musculares/complicações , Doenças Musculares/patologia , Mioclonia/etiologiaRESUMO
A 28-month-old male with generalized hypotonia and muscle weakness, a myopathic face, skeletal dysmorphism and delayed motor milestones from birth is reported. He gradually developed the ability of sitting and rolling over, but could not stand without support until 28 months. There was no intellectual impairment or seizures. Deep tendon reflexes were absent. The serum CK value, peripheral nerve conduction velocity and EMG were within normal limits. A muscle biopsy specimen showed mild variation in fiber size, and an increased number of type 2C fibers on histochemical examination, but no apparent abnormalities on electron microscopy. The baby was tentatively diagnosed as having minimal change myopathy or nonspecific congenital myopathy which is thought to be one of the congenital nonprogressive myopathies.
Assuntos
Doenças Musculares/congênito , Humanos , Lactente , Masculino , Músculos/patologia , Doenças Musculares/patologiaRESUMO
A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes, in which a pituitary growth hormone (GH) secretion deficiency of hypothalamic origin was revealed through neuro-endocrinological examinations, was described. The case was a 10-year-old girl, who had been suffering from generalized tonic seizures since age 5, four episodes of alternating hemiplegia since age 6, stunted growth since age 7, and simple partial motor seizures as well as gelastic seizures since age 8. Marked elevation of lactate and pyruvate in both serum and CSF, abundant ragged red fibers in biopsied muscle, and low density areas in the left occipital lobe and bilateral globus pallidus in addition to diffuse brain atrophy on CT scan and MRI of the head were demonstrated, although the activities of muscle enzymes complex I-IV were within normal ranges. Pituitary GH secretion was deficient under the loadings with insulin, L-DOPA, sleep, and a single growth hormone releasing factor (GRF) administration, but normal GH response was registered under the repetitive stimulation with GRF. Activities of other hormonal axes were normal. It is likely that short stature commonly observed in MELAS patients is due to hypothalamic dysfunction, which might be brought out by chronic ischemia and energy deficiency of the diencephalon based upon mitochondrial abnormality of that region. It is likely that gelastic seizure in this case is due to hypothalamic dysfunction.
Assuntos
Acidose Láctica/fisiopatologia , Encefalopatias/fisiopatologia , Hormônio do Crescimento/deficiência , Hipotálamo/metabolismo , Convulsões/fisiopatologia , Transtornos Cerebrovasculares/fisiopatologia , Criança , Feminino , Humanos , Riso , Mitocôndrias Musculares/patologiaRESUMO
A high-dose intravenous gamma-globulin (IVGG) therapy was given to two children; one with intractable dermatomyositis (case 1) and the other with polymyositis (case 2). Case 1, a 3-year-6-month-old girl, only poorly responded to the standard oral prednisolone therapy and a pulse therapy with high-dose methyl-prednisolone. This patient showed a complete remission after a course IVGG therapy, 100 mg/kg/day iv. for 5 days, which has been maintained for 6 months up to the present. Case 2, a 13-year-6-month-old girl, also showed little improvement after the oral prednisolone therapy, and transient improvement during plasma exchange therapy. This patient showed fairly good response after three repeated courses of IVGG therapy, but not complete remission.
Assuntos
Dermatomiosite/terapia , Miosite/terapia , gama-Globulinas/administração & dosagem , Adolescente , Pré-Escolar , Feminino , Humanos , Injeções IntravenosasRESUMO
The cDNA probes for the Duchenne muscular dystrophy (DMD) gene can detect deletions in over 50% of affected males and provide a highly accurate diagnostic test in the affected families. We present the results of our recent molecular genetic studies of five DMD families (six affected males and 16 non-affected family members) by using the dystrophin cDNA. Five molecular deletions were identified in the DNA samples of six affected males by studying abnormalities of Hind III and Bgl II fragments detected by the entire dystrophin cDNA. We could not find any abnormality in a family by the same DNA analysis. Deletion was found at two different loci; in two of six probands, it was located near 5' region of the gene seen by cDNA segment 1-2 a, while in the other three, near the center of the gene covered by cDNA segment 8. In three females of the five families, we detected novel fragments, the size of which was altered due to molecular deletion. These results greatly facilitated diagnosis of the carrier status in females. We studied also the dystrophin location in the biopsied skeletal muscle (femoral muscle) in a family, by means of indirect immunofluorescence staining using antiserum against dystrophin. Dystrophin was positive in the surface membrane of muscles from a non-affected brother, mother and sister, but it was absent in the muscle from a DMD proband.
Assuntos
Sondas de DNA , Distrofias Musculares/genética , Distrofina , Triagem de Portadores Genéticos , Aconselhamento Genético , Humanos , Proteínas Musculares/genéticaRESUMO
We report a pair of 1-year-5-month-old female monozygotic twins with generalized loss of pain sensation, but without impairment of other sensory modalities and the diaphoretic function. Routine electrophysiological investigations revealed no abnormalities. Morphometric analysis of biopsied sural nerve showed that the number of small myelinated fibers was reduced and that of unmyelinated fibers was normal or mildly reduced. On the basis of these findings, we suspected a diagnosis of a rare disorder, HSAN type V, which has not previously been reported in Japan.
Assuntos
Doenças em Gêmeos , Neuropatias Hereditárias Sensoriais e Autônomas/diagnóstico , Gêmeos Monozigóticos , Eletrofisiologia , Feminino , Neuropatias Hereditárias Sensoriais e Autônomas/classificação , Humanos , Lactente , Fibras Nervosas Mielinizadas/patologia , Nervo Sural/patologiaRESUMO
The computed tomography (CT) and ultrasound (US) imaging studies were performed on skeletal muscles of two siblings (5-year-old boy and 10-year-old girl) with central core disease. The appearance of low-density areas in muscles was remarkable at the levels of the 3rd lumbar vertebra (L3), the midthigh and the thickest part of legs. The muscles at the levels of L3 and thigh were more severely affected than those of legs. Especially, paravertebral muscles, m. vastus, m. sartorius, m. gracilis tended to be more severely affected. The muscles of the legs except m. soleus were well preserved. US imaging of the thigh revealed a marked increase of echogenicity of rectus muscle as well as opaque, indistinct changes of fascia and bone. In contrast, the CT finding of the rectus muscle was relatively well preserved.
Assuntos
Músculos/diagnóstico por imagem , Doenças Musculares/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Músculos/patologia , Doenças Musculares/genética , Tomografia Computadorizada por Raios X , UltrassonografiaAssuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/psicologia , Síndrome MELAS/metabolismo , Transtornos Mentais/genética , Transtornos Mentais/psicologia , Mitocôndrias/metabolismo , Mutação , RNA de Transferência de Leucina/genética , Idoso , Depressão/complicações , Depressão/genética , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Transtorno de Pânico/complicações , Transtorno de Pânico/genética , Transtornos Fóbicos/complicações , Transtornos Fóbicos/genéticaAssuntos
Antipsicóticos/efeitos adversos , Diazepam/uso terapêutico , Síndrome Maligna Neuroléptica/tratamento farmacológico , Catatonia/tratamento farmacológico , Diazepam/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Síndrome Maligna Neuroléptica/etiologia , Esquizofrenia/tratamento farmacológico , Terminologia como AssuntoRESUMO
Ophthalmoplegic migraine (OM) is a rare variant of migraine characterized by recurrent attacks of severe headache followed by oculomotor nerve palsy. The recent revision of the International Headache Classification has reclassified OM from a subtype of migraine, defined as a functional headache, to the neuralgia category. We describe a case of an 11-year-old girl with pathologically confirmed oculomotor nerve schwannoma who had been suffering from symptoms mimicking OM. For five years, she has been under treatment for OM, an initial diagnosis which was corroborated by brain magnetic resonance imaging (MRI). Usually, most OM attacks occur during one period in a lifetime and remit completely. In contrast, however, her attacks became more frequent and were not controlled by medication. After surgery, the frequency of OM attacks was reduced. From this experience, we hypothesize that optic nerve tumor is one condition that can mimic OM, without apparent signs suggestive of intracranial mass. To our knowledge, this is the first report to describe a pathologically confirmed case of oculomotor nerve schwannoma mimicking OM.