RESUMO
Diffuse leucoencephalopathy with axonal spheroids (DLS) is a rare disease affecting the white matter leading to dementia and progressive motor impairment. The neuropathological hallmark includes axonal swelling and spheroids as well as myelin loss. We report a case of a 46-year-old man with memory deficit and behavioral changes followed by a rapid cognitive decline and pyramidal syndrome. Head magnetic resonance imaging showed cortical atrophy of the brain and symmetric corticospinal tract involvement. He died 4 years after the first symptoms. Autopsy was performed and the brain revealed cortical and corpus callosum atrophy, a grayish granular appearance of the white matter and ventricular enlargement. Myelin stains showed a significant demyelination of the centrum ovale and corticospinal tract. Such degeneration was accompanied by axonal loss, axonal swelling, and numerous spheroids. There was no pigment overload or inflammation. We discuss this new DLS case with bilateral, severe, and rapid cortical-spinal involvement.
Assuntos
Axônios/patologia , Córtex Cerebral/patologia , Leucoencefalopatias/complicações , Doenças da Coluna Vertebral/complicações , Precursor de Proteína beta-Amiloide/metabolismo , Humanos , Leucoencefalopatias/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/metabolismo , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismoRESUMO
BACKGROUND: Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLA2, the gene encoding a ß subunit of succinate-CoA ligase, have been reported in 17 patients until now. Mutations in SUCLG1, encoding the α subunit of the enzyme, have been described in two pedigrees only. METHODS AND FINDINGS: In this study, two unrelated patients harbouring three novel pathogenic mutations in SUCLG1 were reported. The first patient had a severe disease at birth. He was compound heterozygous for a missense mutation (p.Pro170Arg) and a c.97+3G>C mutation, which leads to the complete skipping of exon 1 in a minigene expression system. The involvement of SUCLG1 was confirmed by western blot analysis, which showed absence of SUCLG1 protein in fibroblasts. The second patient has a milder phenotype, similar to that of patients with SUCLA2 mutations, and is still alive at 12 years of age. Western blot analysis showed some residual SUCLG1 protein in patient's fibroblasts. CONCLUSIONS: Our results suggest that SUCLG1 mutations that lead to complete absence of SUCLG1 protein are responsible for a very severe disorder with antenatal manifestations, whereas a SUCLA2-like phenotype is found in patients with residual SUCLG1 protein. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.
Assuntos
Ácido Metilmalônico/urina , Encefalomiopatias Mitocondriais/genética , Encefalomiopatias Mitocondriais/fisiopatologia , Mutação , Índice de Gravidade de Doença , Succinato-CoA Ligases/genética , Sequência de Aminoácidos , Criança , Evolução Fatal , Humanos , Lactente , Masculino , Ácido Metilmalônico/sangue , Encefalomiopatias Mitocondriais/mortalidade , Modelos Moleculares , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Fenótipo , Succinato-CoA Ligases/química , Succinato-CoA Ligases/deficiência , Succinato-CoA Ligases/metabolismoRESUMO
Mutations of mitochondrial genome are responsible for respiratory chain defects in numerous patients. We have used a strategy, based on the use of a mismatch-specific DNA endonuclease named " Surveyor Nuclease", for screening the entire mtDNA in a group of 50 patients with neuromuscular features, suggesting a respiratory chain dysfunction. We identified mtDNA mutations in 20% of patients (10/50). Among the identified mutations, four are not found in any mitochondrial database and have not been reported previously. We also confirm that mtDNA polymorphisms are frequently found in a heteroplasmic state (15 different polymorphisms were identified among which five were novel).
Assuntos
DNA Mitocondrial/genética , Endonucleases , Testes Genéticos/métodos , Doenças Neuromusculares/genética , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/genética , LinhagemRESUMO
INTRODUCTION: Pompe's disease, also called glycogen storage disease type II or acid maltase deficiency, is an autosomal recessive disease caused by an enzymatic deficiency of acid-alpha-glucosidase (GAA). This deficiency causes an accumulation of intralysosomal glycogen in different organs. The classic form appears in the newborn with a very severe hypotonia and cardiomyopathy, which lead to death before age two. Less frequently, the disease appears only in childhood or in adult life, so called late-onset Pompe's disease. This form causes a very progressive limb-girdle myopathy and restrictive respiratory failure. The diagnosis is based on a low level of GAA either in the muscle biopsy or in the leucocytes. We report six cases of late-onset Pompe's disease from the Languedoc-Roussillon district. METHOD: Our work was a retrospective analysis of all cases of Pompe disease diagnosed in adults between 1975 and 2006 at the Montpellier and Nîmes University Hospital. We describe the clinical presentation and course of this form and explain the diagnostic approach. Results. The mean age at onset was 44.3 years (range: 36-60 years). The first symptom was fatigability (50%), gait difficulty (50%) and dyspnea (16%). The mean delay from symptom onset to diagnosis was 8.4 years (range: 17 years). Fatal outcome due to respiratory failure was noted in three patients. The mean time between symptom onset and death (four patients) was 20.75 years (range: 37 years). The diagnosis was made on the muscle biopsy showing a low level of GAA. Muscle was strictly normal on the morphologic study in one patient, pointing out the requirement for enzymatic analysis. Molecular confirmation was available in one patient. DISCUSSION: Late-onset Pompe's disease is a possible cause of limb-girdle myopathy. Respiratory involvement is a characteristic feature. Enzymatic assay of GAA activity on the muscle biopsy is required for certain diagnosis. CONCLUSION: It is very important to recognize the adult form of Pompe's disease, a possible cause of limb-girdle myopathy, in order to search for respiratory failure and propose non-invasive ventilation if necessary. Moreover, substitutive therapy (recombinant acid-alpha-glucosidase) has shown efficiency for the classical infantile form of Pompe's disease and such treatment could be proposed for the adult form if larger studies confirm its efficacy.
Assuntos
Doença de Depósito de Glicogênio Tipo II/patologia , Adulto , Idade de Início , Biópsia , Progressão da Doença , Dispneia/etiologia , Dispneia/fisiopatologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Fadiga Muscular/fisiologia , Músculos/patologia , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , alfa-Glucosidases/metabolismoRESUMO
CONTEXT: Progressive supranuclear palsy (PSP) is classically characterized by supranuclear ophthalmoplegia, paroxysmal imbalance with backward falling, axial dystonia, rigidity, pseudobulbar palsy and cognitive dysfunction. However, incomplete or atypical clinical presentation has been previously reported, but in all these cases, the patients had at least one of the main clinical features of the disease (ophthalmoplegia, parkinsonian syndrome or cognitive dysfunction). CASE REPORT: A 60-year-old woman presented with nocturnal agitation and choreiform movements. A few months later she developed severe swallowing disorders, caused by achalasia of the upper esophageal sphincter, and responsible for recurrent acute respiratory distress and pneumonia, prevailing to tracheotomy and gastrostomy. She died suddenly two years after the onset of the symptoms. RESULTS: Postmortem examination of brain revealed a tauopathy, with deposition of abnormal phosphorylated tau in threads and in coiled-shaped as well as globose tangles in the brainstem, subthalamic nuclei and hippocampus. Nuclei of the medulla, including the vagus/solitarius complex and the region of the nucleus ambiguous were especially rich in tau positive inclusions. Ultrastructural analysis of globoid-shaped tangles in the brainstem revealed the presence of straight and paired helicoidal filaments compatible with a PSP. CONCLUSIONS: This case contributes to improve knowledge of the clinical phenotypic range of PSP. In this case, the neuropathological lesions accounted for most of the symptoms. However, the early death of the patient was probably related to the particular distribution of the neuropathological lesions. This case suggests that the initial neuropathological changes in PSP is located in the dorsal brainstem.
Assuntos
Coreia/patologia , Acalasia Esofágica/patologia , Transtornos do Sono-Vigília/patologia , Paralisia Supranuclear Progressiva/patologia , Coreia/complicações , Transtornos de Deglutição/etiologia , Diagnóstico Diferencial , Acalasia Esofágica/complicações , Acalasia Esofágica/diagnóstico por imagem , Feminino , Humanos , Nervo Hipoglosso/patologia , Corpos de Inclusão/patologia , Pessoa de Meia-Idade , Radiografia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/cirurgia , Transtornos do Sono-Vigília/complicações , Substância Negra/patologia , Paralisia Supranuclear Progressiva/diagnóstico , TraqueostomiaRESUMO
INTRODUCTION: The most frequent acute and sub-acute complications of chronic alcoholism are delirium tremens, hepatic encephalopathy and Gayet-Wernicke encephalopathy. Morel laminar sclerosis is a rare and less known complication, often reported with Marchiafava-Bignami disease. CASE REPORT: A 57-year-old alcoholic man presented delirium after surgery. Anterograde and retrograde amnesia as well as wrong recognitions appeared progressively and one generalized seizure occurred. He then developed mutism and became bedridden. Magnetic resonance imaging (MRI) showed high-intensity bilateral temporoparietal signals from white matter on T2-weighted images and high-intensity signals from the parietal cortex on T1-weighted images. The patient died four months after the onset of the delirium. Post-mortem examination of the brain showed cortical laminar necrosis with Alzheimer Type II gliosis but without demyelinisation of the corpus callosum. CONCLUSION: Cortical laminar necrosis with chronic ethylism is usually called Morel's laminar sclerosis. Nevertheless, histology is not typical of this diagnosis, because of necrosis especially of the second (and not the third) layer of the cortex, and because of the absence of lesion of the corpus callosum. MRI data are of interest here because they were rarely reported in cases of Morel's laminar sclerosis.
Assuntos
Amnésia/etiologia , Encéfalo/patologia , Córtex Cerebral/patologia , Complicações Pós-Operatórias/patologia , Delírio/etiologia , Hérnia Umbilical/complicações , Humanos , Hipóxia Encefálica/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , NecroseRESUMO
Among neuroeosinophilic syndromes, neuromuscular disorders are considered as a special group, including perimyosistis, polymyositis and fasciitis. These three disorders are considered as a continuum. They usually without a recognized cause, and are considered to be spontaneous or exercise-induced. We report the case of a 43 year-old woman who experienced angioedema followed by an histologically proven-fasciitis with eosinophilia after Ramipril (Triatec) use. Causal attribution to Ramipril was considered "plausible". To our knowledge this side effect has never been reported with this drug.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Eosinofilia/induzido quimicamente , Fasciite/induzido quimicamente , Ramipril/efeitos adversos , Adulto , Angioedema/induzido quimicamente , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Toxidermias/etiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Obesidade/complicações , Ramipril/uso terapêuticoRESUMO
We report the observation of an 18-year-old girl, whose clinical presentation was very suggestive of a congenital myopathy with neonatal onset. A congenital myopathy had been already diagnosed in her brother and in addition her half-cousin died diagnosed with a severe nemaline myopathy at age 4 years. A muscle biopsy performed on both siblings revealed histological and ultrastructural features of 'cap myopathy'. This case report suggests that 'cap myopathy' and some cases of nemaline myopathy with neonatal onset might be two phenotypic expressions of the same genetic disorder. These two entities could therefore, perhaps, be regarded as 'Z-line disorders' possibly caused by defective myofibrillogenesis.
Assuntos
Doenças Musculares/congênito , Doenças Musculares/genética , Miopatias da Nemalina/diagnóstico , Miopatias da Nemalina/genética , Actinas/genética , Adolescente , Adulto , Biópsia , Pré-Escolar , Feminino , Humanos , Masculino , Músculos/patologia , Doenças Musculares/diagnóstico , Mutação , Cadeias Pesadas de Miosina/genética , LinhagemRESUMO
Leigh syndrome is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Mutations in SURF1 gene have been identified in patients with cytochrome c oxidase deficiency. We report a homozygous splice site deletion [516-2_516-1delAG] in a young girl presenting with cytochrome c oxidase-deficient Leigh syndrome. Identification of molecular defect is indispensable for genetic counselling and prenatal diagnosis.
Assuntos
Deficiência de Citocromo-c Oxidase/genética , Doença de Leigh/genética , Mutação , Proteínas/genética , Feminino , Homozigoto , Humanos , Lactente , Proteínas de Membrana , Proteínas MitocondriaisRESUMO
Neural cell adhesion molecules (NCAM) are known to play a pivotal role in regulating cell-cell interactions in various tissues. The diversity of NCAM is made by alternative splicing of a single gene and by post-translational modifications. The spatio-temporal expression of the various isoforms is developmentally regulated and may modulate cell interactions. We investigated the expression of NCAM isoforms, in particular polysialylated and phosphatidylinositol-anchored isoforms, in developing psoas and quadriceps human muscle from 15 weeks of gestation to term. In parallel, we examined the expression of the myosin heavy chain phenotype (another developmentally regulated system) to determine whether polysialylated-NCAM molecules (the so-called embryonic NCAM) and developmental myosin heavy chains are coexpressed. Our results showed an expression of polysialylated-NCAM and phosphatidylinositol-anchored isoforms during the early stages of myotube maturation. The expression of polysialylated-NCAM on developing myotube was always associated with the expression of developmental myosin heavy chains. However, the loss of polysialylated-NCAM from maturing myotubes was not correlated with the disappearance of the developmental myosin heavy chains, but rather with the appearance of an adult myosin heavy chain phenotype. The relationship between polysialylated-NCAM and myosin heavy chain phenotype was similar in psoas and in quadriceps muscles. We observed that maturation of quadriceps muscle takes place earlier than psoas. Biochemical analysis showed that phosphatidylinositol-anchored molecules were never polysialylated; this indicates different roles of these isoforms in muscle development.
Assuntos
Moléculas de Adesão Celular Neuronais/análise , Idade Gestacional , Músculos/embriologia , Miosinas/análise , Envelhecimento , Anticorpos , Anticorpos Monoclonais , Moléculas de Adesão Celular Neuronais/genética , Humanos , Immunoblotting , Imuno-Histoquímica , Recém-Nascido , Desenvolvimento Muscular , Músculos/química , Músculos/citologia , Miosinas/genética , Splicing de RNARESUMO
Multiple mitochondrial DNA (mtDNA) deletions have been reported in patients with autosomal dominant and recessive disorders. We studied several affected and one non-affected individuals belonging to a pedigree in which the inheritance of the pathological trait was compatible with an autosomique dominant transmission. Affected members had late-onset multisystem disorders with multiple mtDNA deletions in skeletal muscle. But this family presented a striking difference from previously described cases, because none of the patients had progressive external ophthalmoplegia (PEO). We also studied one young boy with a no contributary family history. He had a cerebellar ataxia with PEO and multiple mtDNA deletions in muscle. Molecular analysis revealed that in the first family, repeated sequences were present at the breakpoint junctions, whereas such motifs were not found in the young patient's case. In the first family, we evidenced mtDNA point mutations in clones containing breakpoint junctions and a 9-bp motif triplication in the intergenic COII/tRNA(Lys) region, whereas this sequence is repeated twice in the wild type mtDNA. Our results suggest that multiple deletions observed in the two pedigrees result from different molecular mechanisms and point out the role of repeated sequences in the first pedigree. No mtDNA repair system has been described in mammals so far, but the molecular abnormalities found in the first family suggest that a defect in an mtDNA repair system, homologous to the E. coli MutHLS pathway, could be responsible for such a phenotype.
Assuntos
DNA Mitocondrial/genética , Deleção de Genes , Criança , DNA Mitocondrial/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Sequências Repetitivas de Ácido Nucleico , Análise de Sequência de DNARESUMO
X-linked myopathy with excessive autophagy (XMEA, MIM 310440) is a rare inherited mild myopathy. We have used 32 polymorphic markers spanning the entire X chromosome to exclude most of the chromosome except the Xq28 region in a large XMEA family. Using three additional families for linkage analysis, we have obtained a significant two-point lod score with marker DXS1183 (Z = 2.69 at theta = 0). Multipoint linkage analysis confirmed the assignment of the disease locus with a maximal lod score of 2.74 obtained at recombination fraction zero. Linkage of XMEA to the Xq28 region is thus firmly established. In addition, we have ruled out the Emery-Dreifuss muscular dystrophy to be allelic with XMEA by direct sequencing of the emerin gene in three of our families.
Assuntos
Doenças Musculares/genética , Cromossomo X/genética , Biópsia , Mapeamento Cromossômico , DNA/química , DNA/genética , Saúde da Família , Feminino , Ligação Genética , Haplótipos , Humanos , Escore Lod , Masculino , Proteínas de Membrana/genética , Repetições de Microssatélites , Músculo Esquelético/patologia , Doenças Musculares/patologia , Mutação , Proteínas Nucleares , Linhagem , Análise de Sequência de DNA , Timopoietinas/genéticaRESUMO
A patient who had a two-month history of nonspecific inflammatory disease experienced symptoms of raised intracranial pressure and meningitis. Computed tomographic scan showed multiple, small ring-enhancing hypodensities consistent with cerebral abscesses. The infective agent proved to be Hemophilus paraphrophilus, a fastidious, particularly slow-growing organism that was identified on blood cultures. An autopsy disclosed disseminated microabscesses and demonstrated typical pathologic changes of endocarditis complicating mitral valve prolapse.
Assuntos
Abscesso Encefálico/etiologia , Infecções por Haemophilus/complicações , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/patologia , Feminino , Infecções por Haemophilus/diagnóstico por imagem , Infecções por Haemophilus/patologia , Humanos , Pessoa de Meia-Idade , RadiografiaRESUMO
Two patients with mitochondrial encephalomyopathy due to complexes I and IV deficiencies received 150 mg/d of coenzyme Q10 (CoQ). We studied them with a bicycle ergometer exercise test and 31P NMR spectroscopy before and after 10 months of treatment. Before treatment, we observed a low phosphocreatine/inorganic phosphate (PCr/P(i)) resting value along with abnormally high resting lactate concentration. During exercise, there was a pronounced acidosis with delayed kinetics of postexercise recovery for blood lactate, pH, PCr, and PCr/P(i) ratio. Oxygen uptake during exercise was reduced while the lowering of the ventilatory threshold indicated an early activation of glycolysis. After treatment, the bicycle ergometer exercise test indicated a significant improvement with a decrease in resting blood lactate level, an increase in oxygen consumption during exercise, and an increase in the kinetics of lactate disappearance during the recovery period. A shift of the ventilatory threshold to higher workload was present. 31P NMR spectroscopy confirmed the improvement, showing a significant increase in the PCr/P(i) ratio at rest and in the kinetics of recovery for pH, PCr, and PCr/P(i) ratio following exercise in patient 1. For patient 2, we observed a less pronounced acidosis correlated with a lesser amount of Pi produced during exercise. These observations indicate an improvement of mitochondrial function and a shift from high to low glycolytic activity in both patients consequent to CoQ treatment.
Assuntos
Teste de Esforço , Espectroscopia de Ressonância Magnética , Mitocôndrias Musculares , Músculos/metabolismo , Doenças Musculares/tratamento farmacológico , Ubiquinona/uso terapêutico , Adolescente , Adulto , Humanos , Masculino , Doenças Musculares/diagnóstico , Doenças Musculares/metabolismo , Oxirredução , FósforoRESUMO
PURPOSE: The coexistence of mitochondrial myopathy and polymyalgia rheumatica without giant cell arteritis is an interesting association. The frequency of this association was assessed in a prospective study. PATIENTS AND METHODS: Muscle biopsy specimens were obtained from 15 patients with polymyalgia rheumatica. When ragged red fibers (RRF) were observed, histochemical, ultrastructural, and biochemical studies were performed. RESULTS: In five cases, we found the typical appearance of mitochondrial myopathy, with the presence of numerous RRF. Histochemical and biochemical results confirmed these mitochondrial myopathies, showing miscellaneous deficiencies of mitochondrial respiratory chain enzymes. CONCLUSION: Persistence of histologic and biochemical abnormalities after steroid treatment in two patients seems to indicate that a subclinical mitochondrial myopathy preceded polymyalgia rheumatica. How a mitochondrial myopathy could induce or facilitate the emergence of a polymyalgia rheumatica remains unknown.
Assuntos
Mitocôndrias Musculares/patologia , Doenças Musculares/complicações , Polimialgia Reumática/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Mitocôndrias Musculares/enzimologia , Doenças Musculares/enzimologia , Doenças Musculares/patologia , Polimialgia Reumática/enzimologia , Polimialgia Reumática/patologia , Estudos ProspectivosRESUMO
We report a primary histiocytic tumor involving the cerebellum. Microscopically, the tumor was composed of nests of pleomorphic cells surrounded by thin vascular septa invaded by lymphocytes. Immunocytochemistry and electron microscopy confirmed the histiocytic origin of the tumor. Although we considered several diagnoses, we ultimately concluded that "atypical inflammatory histiocytic tumor of the cerebellum" best characterized the lesion. This case represents another example of the diversity of histiocytic tumors and shows that they can occur in the central nervous system.
Assuntos
Neoplasias Cerebelares/patologia , Histiocitoma Fibroso Benigno/patologia , Adulto , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/ultraestrutura , Diagnóstico Diferencial , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Histiocitoma Fibroso Benigno/metabolismo , Histiocitoma Fibroso Benigno/ultraestrutura , Humanos , Imuno-Histoquímica , Microscopia Eletrônica , Proteínas S100/metabolismo , Vimentina/metabolismo , alfa 1-Antiquimotripsina/metabolismo , alfa 1-Antitripsina/metabolismoRESUMO
We report herein the clinical and pathological features of 20 patients with central neurocytomas. Investigations for various differentiation antigens and cell type-specific markers were performed by immunohistochemistry using paraffin-embedded tissue. In addition, the expression of L1 adhesion molecule and of the various N.CAM (neural cell adhesion molecule) isoforms were investigated by immunoblotting studies in two frozen specimens. Central neurocytomas are clinically characterized by their intraventricular localization, occurrence in young adults, and good prognosis. It rarely occurs in patients over 50, but such cases have a poor prognosis. Total surgical excision is the best treatment. Radiotherapy is appropriate if surgery is incomplete or contraindicated. Histologically, central neurocytomas display the following features: an oligo-like pattern, usually associated with large fibrillary rosettes or perivascular arrangement, and a rich endocrine-type vasculature. Central neurocytomas have a remarkably homogeneous antigenic profile. GFAP expression is only found in scattered reactive astrocytes, S100 protein in reactive astrocytes and rare tumor cells. Among the pan-neuroendocrine markers, central neurocytomas always express neuron-specific enolase; they frequently express synaptophysin but never chromogranin A. Synaptophysin is the most reliable immunohistological marker for central neurocytomas; however, immunoreactivity could be lost with long formalin fixation. In these cases, electron microscopy is used to support the neuronal nature of the tumor cells. The expression of L1 adhesion molecule and the isoform 180 of N.CAM, indicates that central neurocytomas are formed by cells committed to neuronal phenotype. Nevertheless, advanced neuronal differentiation may be absent, as suggested by the persistence of embryonic N.CAM, the nonexpression of neurofilament proteins, and the absence of mature synapses in numerous cases. Central neurocytomas and neuroblastomas share some biochemical properties, but their respective clinicopathological features and biological behavior are dramatically different.
Assuntos
Neoplasias do Ventrículo Cerebral/patologia , Neuroblastoma/patologia , Adolescente , Adulto , Biomarcadores Tumorais/análise , Moléculas de Adesão Celular Neuronais/análise , Neoplasias do Ventrículo Cerebral/química , Neoplasias do Ventrículo Cerebral/ultraestrutura , Epitopos , Feminino , Proteína Glial Fibrilar Ácida/análise , Humanos , Immunoblotting , Imuno-Histoquímica , Complexo Antígeno L1 Leucocitário , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neuroblastoma/química , Neuroblastoma/ultraestrutura , Fenótipo , Proteínas S100/análise , Sinaptofisina/análiseRESUMO
The pathological findings in 165 patients explored for malignant hyperthermia (MH) susceptibility are reported. The first group of 120 subjects were patients investigated for MH. These patients had suffered an attack of MH under anaesthetic or were members of families in which a subject had died of MH. In vitro contracture tests revealed 25 malignant hyperthermia susceptible (MHS) subjects, with positive contracture tests for halothane and caffeine, 5 malignant hyperthermia subjects with reaction to caffeine only (MHC), 3 malignant hyperthermia subjects with reaction to halothane only (MHH) and 87 malignant hyperthermia negative (MHN) subjects with normal contracture tests. The second group of 45 subjects had exertional heat stroke. In vitro contracture tests performed at least 3 months after the exertional heat stroke revealed 11 MHS, 6 MHC, 2 MHH subjects and 26 MHN. In both groups, whatever the in vitro contracture test results, pathological findings were heterogeneous and revealed various changes: rhabdomyolysis, mitochondrial myopathy, denervation, type II atrophy, AMPase deficiency, non-specific findings or normal features. Central core myopathy was only observed in the first subgroup and was the only disease significantly associated with MH. In contrast to previous reports, this study demonstrates the absence of a specific malignant hyperthermia or exertional heat stroke myopathy. Furthermore, the discovery of MHS subjects among the EHS group of patients highlights the need for systematic exploration of all these patients.
Assuntos
Hipertermia Maligna/genética , Hipertermia Maligna/patologia , Músculos/patologia , Doenças Musculares/patologia , Doenças Neuromusculares/patologia , Predisposição Genética para Doença , Humanos , Doenças Musculares/genética , Doenças Neuromusculares/genéticaRESUMO
A 26-year-old man had proximal weakness in the shoulder and the pelvic girdle since infancy. His sister, aged 16 years, presented a similar phenotype with more pronounced pelvic weakness. His muscle biopsy showed dense non-reducing inclusions which had a lamellar pattern at the ultrastructural level. These structures showed the typical features of fingerprint inclusions which were widely distributed in the fibers. Several central cores and other structural changes such as Z-line streaming were also observed. In view of the central cores, the male patient was investigated for malignant hyperthermia susceptibility. After exposure to halothane or caffeine, unusual intense contractures were observed on fiber preparations. The coexistence of central cores associated with fingerprint inclusions is suggestive of mixed congenital myopathy, which is in our case associated with malignant hyperthermia susceptibility.
Assuntos
Hipertermia Maligna/patologia , Miopatia da Parte Central/patologia , Adulto , Anestésicos Inalatórios/farmacologia , Biópsia , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Halotano/farmacologia , Humanos , Técnicas In Vitro , Corpos de Inclusão/patologia , Masculino , Microscopia Eletrônica , Contração Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Miopatia da Parte Central/congênito , Núcleo FamiliarRESUMO
The clinico-pathological features of 17 patients displaying a myopathy with lobulated (trabeculated) fibers are reported. All these patients had a limb girdle phenotype and at least 20% of lobulated fibers in their muscle biopsies. There were ten females and seven males. The onset of symptoms ranged from 2 to 55 years (mean 24). The average age at the time of muscle biopsy was 39 (range 3-63). Interestingly, in six patients, high prevalence of lobulated fibers was observed at the second biopsy only, performed on average 11 years after the first or in another muscle. Six patients had a suggestively positive family history. Facial weakness was noted in two patients (genetic study confirmed FSH dystrophy). The course and the severity of weakness varied from one patient to another. Immunohistochemistry and Western blot analyses revealed one Duchenne carrier, one alpha-sarcoglycanopathy, no dysferlinopathy and four calpain deficiencies (including one patient with FSH dystrophy), but SSCP revealed mutation in the calpain gene in only one of the patients. These results show that (1) myopathies with lobulated fibers are clinically and genetically heterogeneous, (2) lack of calpain expression by Western blot analysis is not always associated with null mutation, (3) a molecular diagnosis is made in less than 40% of myopathy with lobulated fibers, (4) when observed, lobulated fibers are most prominent in proximal muscles and require time to appear.