Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
J Neurol Neurosurg Psychiatry ; 86(12): 1337-46, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25535305

RESUMO

OBJECTIVE: Mutations in one of the 3 genes encoding collagen VI (COLVI) are responsible for a group of heterogeneous phenotypes of which Bethlem myopathy (BM) represents the milder end of the spectrum. Genotype-phenotype correlations and long-term follow-up description in BM remain scarce. METHODS: We retrospectively evaluated the long-term clinical evolution, and genotype-phenotype correlations in 35 genetically identified BM patients (23 index cases). RESULTS: Nineteen patients showed a typical clinical picture with contractures, proximal weakness and slow disease progression while 11 presented a more severe evolution. Five patients showed an atypical presentation, namely a limb girdle muscle weakness in 2 and a congenital myopathy pattern with either no contractures, or only limited to ankles, in 3 of them. Pathogenic COL6A1-3 mutations were mostly missense or in frame exon-skipping resulting in substitutions or deletions. Twenty one different mutations were identified including 12 novel ones. The mode of inheritance was, autosomal dominant in 83% of the index patients (including 17% (N=4) with a de novo mutation), recessive in 13%, and undetermined in one patient. Skipping of exon 14 of COL6A1 was found in 35% of index cases and was mostly associated with a severe clinical evolution. Missense mutations were detected in 39% of index cases and associated with milder forms of the disease. CONCLUSIONS: Long-term follow-up identified important phenotypic variability in this cohort of 35 BM patients. However, worsening of the functional disability appeared typically after the age of 40 in 47% of our patients, and was frequently associated with COL6A1 exon 14 skipping.


Assuntos
Colágeno Tipo VI/genética , Contratura/genética , Distrofias Musculares/congênito , Adolescente , Adulto , Idade de Início , Envelhecimento , Biópsia , Criança , Pré-Escolar , Estudos de Coortes , Contratura/patologia , Progressão da Doença , Éxons/genética , Feminino , Seguimentos , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Debilidade Muscular/etiologia , Distrofias Musculares/genética , Distrofias Musculares/patologia , Mutação , Mutação de Sentido Incorreto/genética , Exame Neurológico , Fenótipo , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
2.
Clin Genet ; 85(2): 178-83, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23495813

RESUMO

Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients with polymicrogyria (five unilateral) were tested for mutations in TUBB2B by Sanger sequencing. We identified two novel de novo mutations, c.743C>T (p.Ala248Val) and c.1139G>T (p.Arg380Leu) in exon 4 of TUBB2B in three unrelated families. Brain magnetic resonance images showed polymicrogyria involving predominantly the perisylvian regions. In addition, there was a dysmorphic appearance of the basal ganglia, thin corpus callosum, enlargement of the ventricles, thinning of the white matter and hypoplasia of pons and cerebellar vermis. This combination of associated features was absent in all 17 patients with polymicrogyria in whom no mutation was identified. This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function.


Assuntos
Gânglios da Base/patologia , Modelos Moleculares , Fenótipo , Polimicrogiria/genética , Polimicrogiria/patologia , Tubulina (Proteína)/genética , Sequência de Bases , Análise Mutacional de DNA , Dineínas/química , Dineínas/metabolismo , Genes Dominantes/genética , Humanos , Imageamento por Ressonância Magnética , Dados de Sequência Molecular
3.
Neuromuscul Disord ; 33(6): 476-483, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37207382

RESUMO

Eteplirsen is FDA-approved for the treatment of Duchenne muscular dystrophy (DMD) in exon 51 skip-amenable patients. Previous studies in boys > 4 years of age indicate eteplirsen is well tolerated and attenuates pulmonary and ambulatory decline compared with matched natural history cohorts. Here the safety, tolerability and pharmacokinetics of eteplirsen in boys aged 6-48 months is evaluated. In this open-label, multicenter, dose-escalation study (NCT03218995), boys with a confirmed mutation of the DMD gene amenable to exon 51 skipping (Cohort 1: aged 24-48 months, n = 9; Cohort 2: aged 6 to < 24 months, n = 6) received ascending doses (2, 4, 10, 20, 30 mg/kg) of once-weekly eteplirsen intravenously over 10 weeks, continuing at 30 mg/kg up to 96 weeks. Endpoints included safety (primary) and pharmacokinetics (secondary). All 15 participants completed the study. Eteplirsen was well tolerated with no treatment-related discontinuations, deaths or evidence of kidney toxicity. Most treatment-emergent adverse events were mild; most common were pyrexia, cough, nasopharyngitis, vomiting, and diarrhea. Eteplirsen pharmacokinetics were consistent between both cohorts and with previous clinical experience in boys with DMD > 4 years of age. These data support the safety and tolerability of eteplirsen at the approved 30-mg/kg dose in boys as young as 6 months old.


Assuntos
Distrofia Muscular de Duchenne , Masculino , Humanos , Pré-Escolar , Lactente , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/genética , Morfolinos/uso terapêutico , Éxons , Mutação , Distrofina/genética
4.
Nat Med ; 4(12): 1441-4, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9846586

RESUMO

Duchenne muscular dystrophy (DMD) is a lethal, progressive muscle wasting disease caused by a loss of sarcolemmal bound dystrophin, which results in the death of the muscle fiber leading to the gradual depletion of skeletal muscle. The molecular structure of dystrophin is very similar to that of the related protein utrophin. Utrophin is found in all tissues and is confined to the neuromuscular and myotendinous junctions in mature muscle. Sarcolemmal localization of a truncated utrophin transgene in the dystrophin-deficient mdx mouse significantly improves the dystrophic muscle phenotype. Therefore, up-regulation of utrophin by drug therapy is a plausible therapeutic approach in the treatment of DMD. Here we demonstrate that expression of full-length utrophin in mdx mice prevents the development of muscular dystrophy. We assessed muscle morphology, fiber regeneration and mechanical properties (force development and resistance to stretch) of mdx and transgenic mdx skeletal and diaphragm muscle. The utrophin levels required in muscle are significantly less than the normal endogenous utrophin levels seen in lung and kidney, and we provide evidence that the pathology depends on the amount of utrophin expression. These results also have important implications for DMD therapies in which utrophin replacement is achieved by delivery using exogenous vectors.


Assuntos
Proteínas do Citoesqueleto/biossíntese , Proteínas de Membrana/biossíntese , Distrofia Muscular Animal/metabolismo , Animais , Proteínas do Citoesqueleto/genética , Expressão Gênica , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos mdx , Camundongos Transgênicos , Distrofia Muscular Animal/genética , Transgenes , Utrofina
5.
Nat Med ; 3(11): 1216-21, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9359695

RESUMO

Dystrophin-deficient mice (mdx) expressing a truncated (trc) utrophin transgene show amelioration of the dystrophic phenotype. Here we report a multifunctional study demonstrating that trcutrophin expression leads to major improvements of the mechanical performance of muscle (that is, force development, mechanical resistance to forced lengthenings and maximal spontaneous activity) and of the maintenance of the intracellular calcium homeostasis. These are two essential functions of muscle fibers, known to be impaired in mdx mouse muscles and Duchenne muscular dystrophy (DMD) patients. Our results bring strong support to the hypothesis that muscle wasting in dystrophin-deficient DMD patients could be prevented by upregulation of utrophin.


Assuntos
Proteínas do Citoesqueleto/fisiologia , Distrofina/deficiência , Proteínas de Membrana/fisiologia , Contração Muscular , Músculos/fisiopatologia , Animais , Cálcio/metabolismo , Proteínas do Citoesqueleto/biossíntese , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/genética , Expressão Gênica , Terapia Genética , Homeostase , Contração Isométrica , Proteínas de Membrana/biossíntese , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos mdx , Camundongos Transgênicos , Músculos/química , Músculos/patologia , Distrofia Muscular Animal/terapia , Transgenes , Utrofina
6.
Diabetes Metab ; 33(2): 135-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17320448

RESUMO

AIMS: To facilitate the transition from urine ketones (acetoacetate) to capillary blood ketones (3-beta-hydroxybutyrate), we studied the correlation between these two tests. METHODS: Retrospective study of all patients with blood glucose greater than or equal to 2.5 g/l on arrival in the Emergency Department. We studied the correlation between urine ketones (Clinitek 50, Bayer) and capillary blood ketones (Optium, Abbott). We then compared the relative risks (RR) of ketoacidosis and hospitalization associated with each of these tests. RESULTS: In 33 months, 529 adult patients with both urine and blood testing for ketones were enrolled (ketoacidosis 8%, admission rate 49%). Urine ketones scored as +, ++ and +++ corresponded to median capillary blood ketone levels of 0.5 mmol/l (IQR: 0.1-0.9), 0.7 mmol/l (IQR: 0.2-1.8) and 3 mmol/l (IQR: 1.4-5.2), respectively. RRs of ketoacidosis or hospitalization associated with blood ketones greater than or equal to 3 mmol/l were higher than those associated with +++ urine ketones: 74 (95% confidence interval [CI]: 48-88) and 2.9 (95% CI: 2.5-3) versus 31 (95% CI: 18-45) and 2 (95% CI: 1.7-2.1), respectively. CONCLUSIONS: In hyperglycaemic patients in the Emergency Department, a good correlation was observed between urine ketones and capillary blood ketones for low values, but a poor correlation was observed for high values. Either test can therefore be used to exclude ketosis, but the capillary blood ketones test is more accurate to confirm ketoacidosis.


Assuntos
Ácido 3-Hidroxibutírico/sangue , Acetoacetatos/urina , Hiperglicemia/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperglicemia/urina , Cetonas/sangue , Cetonas/urina , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
7.
J Mass Spectrom ; 52(6): 372-377, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28444691

RESUMO

Congenital disorders of glycosylation (CDG) are due to defective glycosylation of glycoconjugates. Conserved oligomeric Golgi (COG)-CDG are genetic diseases due to defects of the COG complex subunits 1-8 causing N-glycan and O-glycan processing abnormalities. In COG-CDG, isoelectric focusing separation of undersialylated glycoforms of serum transferrin and apolipoprotein C-III (apoC-III) allows to detect N-glycosylation and O-glycosylation defects, respectively. COG5-CDG (COG5 subunit deficiency) is a multisystem disease with dysmorphic features, intellectual disability of variable degree, seizures, acquired microcephaly, sensory defects and autistic behavior. We applied matrix-assisted laser desorption/ionization-MS for a high-throughput screening of differential serum O-glycoform and N-glycoform in five patients with COG5-CDG. When compared with age-matched controls, COG5-CDG showed a significant increase of apoC-III0a (aglycosylated glycoform), whereas apoC-III1 (mono-sialylated glycoform) decreased significantly. Serum N-glycome of COG5-CDG patients was characterized by the relative abundance of undersialylated and undergalactosylated biantennary and triantennary glycans as well as slight increase of high-mannose structures and hybrid glycans. Using advanced and well-established MS-based approaches, the present findings reveal novel aspects on O-glycan and N-glycan profiling in COG5-CDG patients, thus providing an increase of current knowledge on glycosylation defects caused by impairment of COG subunits, in support of clinical diagnosis. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/sangue , Defeitos Congênitos da Glicosilação/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Defeitos Congênitos da Glicosilação/diagnóstico , Glicosilação , Ensaios de Triagem em Larga Escala/métodos , Humanos , Polissacarídeos/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
8.
Rev Med Brux ; 27 Spec No: Sp33-7, 2006.
Artigo em Francês | MEDLINE | ID: mdl-21818891

RESUMO

Cerebral palsy was recently redefined as a group of disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication or behaviour, by epilepsy or by secondary musculoskeletal problems (Bax et al. 2005). It has an estimated incidence of 0.2 %, i.e., 200 new cases per year in Belgium and a total of about 18,000 patients (in a population of 10 millions). Over the last few years, interest has risen in issues pertaining to learning, social participation, services, some assessment modalities (including gait analysis), some therapeutic modalities (including orthotics and antispastic treatment). The Department of Neurology of the H6pital Universitaire des Enfants Reine Fabiola has taken an active part in several aspects of these developments, including research on pathophysiology, neurophysiology, motor control and management (including intrathecal baclofen) as well as setting up the Interuniversity Reference Centre for Cerebral Palsy ULB-VUB-ULg. The 20th anniversary of the hospital offers an opportunity to review this important topic.


Assuntos
Pesquisa Biomédica , Paralisia Cerebral/fisiopatologia , Transtornos Neurológicos da Marcha/fisiopatologia , Bélgica , Paralisia Cerebral/epidemiologia , Criança , Eletromiografia , Hospitais Pediátricos , Hospitais Universitários , Humanos , Equipe de Assistência ao Paciente
9.
Neuromuscul Disord ; 8(3-4): 186-92, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9631400

RESUMO

Acute myopathy occurs in critically ill patients, receiving neuromuscular blocking agents or corticosteroids during intensive care hospitalisation. We report three patients with acute quadriplegic myopathy, two of whom were not exposed to corticosteroids or neuromuscular blocking agents. The first of these latter two patients had a history of generalised anoxia with coma related to surgery, complicated by multiple organ failure and sepsis. The second patient, suffering from acute leukaemia, developed sepsis and acute respiratory distress syndrome with the need for mechanical ventilation in the intensive care unit. Electrophysiological studies and muscle biopsy findings were consistent with the diagnosis of critical illness myopathy with loss of myosin filaments. Selective loss of myosin was confirmed by biochemical analysis of muscle. These findings demonstrate that acute myopathy with loss of myosin filaments may occur in patients with severe systemic illness without exposure to corticosteroids or neuromuscular blocking agents.


Assuntos
Estado Terminal , Doenças Musculares/complicações , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/patologia , Actinas/metabolismo , Idoso , Biópsia , Eletrodiagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Doenças Musculares/diagnóstico , Doenças Musculares/patologia , Miosinas/metabolismo
10.
Neuromuscul Disord ; 8(6): 362-70, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9713852

RESUMO

The mechanical properties and the myosin isoform composition were studied in three isolated muscles (EDL, soleus, diaphragm) of mutant mice lacking both dystrophin and utrophin (dko). They were compared with the corresponding muscles of the normal and the dystrophin-deficient (mdx) and the utrophin-deficient (uko) mice. In comparison with mdx muscles, dko muscles show a significant reduction of the normalized isometric force, confirmed by the reduced muscular activity of the whole animal. Kinetics parameters (twitch time-to-peak and half-relaxation time) were slightly reduced, and the maximal speed of shortening of soleus, Vmax, was reduced by 30%. The maximal power output (muW/mm3) was reduced by 50% in dko soleus. In the three muscles studied, the relative myosin heavy chains (MHC) composition showed a shift towards slower isoforms. dko EDL presented a dramatic decrease of the resistance ot tetanic contraction with forced lengthenings (eccentric contractions), while muscle lacking only utrophin (uko mutants) display a normal resistance to this exacting mechanical challenge. These experiments suggest that lack of both dystrophin and utrophin is very detrimental to the mice and that mechanical properties of the muscles may explain the overall phenotype. Moreover these results bring some support to the idea that the expression of utrophin in mdx muscle compensates, to some extent, for the lack of dystrophin.


Assuntos
Proteínas do Citoesqueleto/deficiência , Distrofina/deficiência , Proteínas de Membrana/deficiência , Músculo Esquelético/fisiologia , Miosinas/metabolismo , Músculos Respiratórios/fisiologia , Animais , Proteínas do Citoesqueleto/genética , Distrofina/genética , Extremidades , Contração Isométrica/fisiologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Camundongos Knockout/genética , Fadiga Muscular/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Miosinas/química , Músculos Respiratórios/metabolismo , Utrofina
11.
Neuromuscul Disord ; 8(6): 371-9, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9713853

RESUMO

31P NMR spectroscopy was used to study the energy metabolism of dystrophin-deficient skeletal muscle of mdx mice, an animal model of Duchenne muscular dystrophy, in which expression of a truncated form of utrophin has been obtained through transgenesis technology. Measurements of ATP, phosphocreatine (PCr), inorganic phosphates (Pi) and intracellular pH (pHi) were made at rest, during a fatigue protocol and during the subsequent recovery. Mechanical fatigue of transgenic muscles was similar to normal muscle, while mdx muscle showed larger force loss. At rest, muscles of all groups had similar values for [ATP], [PCr], [Pi] and pHi. During fatigue, [PCr] decreases mirrored [Pi] increases and were similar in all groups. The major difference between mdx muscles and the group of normal and trc-utrophin muscles concerned the values and evolution of pHi. The mdx muscles showed a more severe intracellular acidosis during exercise and a slower and incomplete post-exercise recovery of normal pHi. In contrast, in trc-utrophin muscles, the kinetics and amplitude of pHi changes were remarkably close to normal behaviour. We conclude that the impaired proton washout which is present in mdx muscles, is corrected to a great extent by the expression of trc-utrophin.


Assuntos
Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Hidrogênio/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Atividade Motora/fisiologia , Distrofia Muscular Animal/fisiopatologia , Animais , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx/metabolismo , Camundongos Endogâmicos mdx/fisiologia , Camundongos Transgênicos , Distrofia Muscular Animal/diagnóstico , Distrofia Muscular Animal/metabolismo , Fósforo , Utrofina
12.
Brain Res ; 707(2): 206-12, 1996 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-8919297

RESUMO

The medullary raphe nuclei, wherein serotonin (5-HT) coexists with substance P (SP) and thyrotropin-releasing hormone (TRH), innervate lower motor neurons in the spinal cord ventral horn by means of the ventral raphe-spinal pathway. Destruction of the ventral raphe-spinal pathway is associated with deficient recovery of denervated muscle, indicating that it may exert a trophic effect upon lower motor neurons. To determine whether SP could be a trophic factor for lower motor neurons within the ventral raphe-spinal pathway, the effect of muscle denervation with botulinum toxin type A on SP-encoding beta-preprotachykinin mRNA in the rat medullary raphe was examined by in situ hybridization histochemistry. Silver grain density over hybridized medullary raphe neurons was increased by up to 11%, although the number of hybridized neurons did not change in denervated as compared to control rats. Increased SP gene expression in the medullary raphe in response to motor unit lesioning suggests that raphe-spinal SP may be trophic to lower motor neurons.


Assuntos
Denervação Muscular , Núcleos da Rafe/metabolismo , Medula Espinal/metabolismo , Substância P/biossíntese , Animais , Células do Corno Anterior/metabolismo , Autorradiografia , Membro Posterior/inervação , Membro Posterior/fisiologia , Processamento de Imagem Assistida por Computador , Hibridização In Situ , Masculino , Vias Neurais/metabolismo , Ratos , Ratos Wistar , Coloração pela Prata
13.
Acta Neurol Belg ; 100(1): 34-40, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10779860

RESUMO

A 47-year-old female developed proximal limb weakness after hysterectomy for uterine fibromatosis. Muscle strength slowly improved, but relapse occurred at age 52. She presented with progressive gait difficulty, proximal limb weakness, and painful calves. Family history was not contributory. Cranial nerves, deep tendon reflexes, and sensation were normal. Serum creatine kinase was normal. An IgG kappa monoclonal protein was found. Nerve conduction studies were normal, but EMG showed brief small polyphasic motor unit action potentials with early recruitment in proximal muscles. Muscle biopsy showed abundant rods, atrophic muscle fibres, and type 1 fibre predominance. The sarcolemma was immunoreactive for IgG kappa. Plasmapheresis was unsuccessful, but methylprednisolone and azathioprine led to moderate improvement of muscle strength, associated with reduced monoclonal protein levels. This is the third case report, describing the association of monoclonal gammopathy and late-onset nemaline myopathy. Presence of a monoclonal protein at the sarcolemma and responsiveness to immunosuppressive treatment are suggestive of a dys-immune origin.


Assuntos
Miopatias da Nemalina/complicações , Paraproteinemias/complicações , Idade de Início , Anti-Inflamatórios/administração & dosagem , Feminino , Humanos , Metilprednisolona/administração & dosagem , Microscopia Eletrônica , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Miopatias da Nemalina/tratamento farmacológico , Miopatias da Nemalina/patologia , Paraproteinemias/tratamento farmacológico , Paraproteinemias/patologia
14.
Acta Neurol Belg ; 113(4): 477-85, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23797351

RESUMO

This study compares behavioral and electrophysiological (P300) responses recorded in a cued continuous performance task (CPT-AX) performed by children with attention deficit hyperactivity disorder-combined subtype (ADHD-com) and age-matched healthy controls. P300 cognitive-evoked potentials and behavioral data were recorded in eight children with ADHD (without comorbidity) and nine control children aged 8-12 years while performing a CPT-AX task. Such task enables to examine several kinds of false alarms and three different kinds of P300 responses: the "Cue P300", the "Go P300" and the "NoGo P300", respectively, associated with preparatory processing/attentional orienting, motor/response execution and motor/response inhibition. Whereas hit rates were about 95% in each group, ADHD children made significantly more false alarm responses (inattention- and inhibition-related) than control children. ADHD children had a marginally smaller Cue P300 than the control children. Behavioral and electrophysiological findings both highlighted inhibition and attention deficits in ADHD-com children in the CPT-AX task. A rarely studied kind of false alarm, the "Other" FA, seems to be a sensitive FA to take into account, even if its interpretation remains unclear.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Atenção/fisiologia , Encéfalo/fisiopatologia , Criança , Comportamento Infantil , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia
15.
Neuromuscul Disord ; 23(2): 139-48, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23219352

RESUMO

Upper limb assessment in non-ambulant patients remains a challenge. We have designed new tools to precisely assess pinch (MyoPinch), grip (MyoGrip), wrist flexion and extension (MyoWrist) strength. We have also designed a new tool to assess the ability of patients to produce repetitive flexion/extension movements of wrist and fingers (MoviPlate). We have assessed the feasibility and reliability of these new tools in 30 non-ambulant patients with Duchenne muscular dystrophy and in 30 age-matched male controls. Existing measures, such as Motor Function Measure, Tapping, and the Brooke Upper Extremity Functional Rating Scale were also performed. Results demonstrated that assessments were feasible in nearly all upper limbs tested for MyoGrip, MyoPinch and MoviPlate. The reliability of all tests, including MyoWrist which was not feasible in the patients presenting with contractures, was excellent in patients as in controls. Motor capacities decrease with the number of months spent in the wheelchair. The scores in the tests were partially correlated with each other, and with clinical measures such as vital capacity, Motor Function Measure, functional hand scale and Brooke score. This study validates a panel of upper limb muscle strength and function measures for Duchenne Muscular Dystrophy which can be applied from controls to extremely weak patients.


Assuntos
Testes Diagnósticos de Rotina/métodos , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/fisiopatologia , Extremidade Superior/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Estudos de Viabilidade , Força da Mão/fisiologia , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Amplitude de Movimento Articular/fisiologia , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Articulação do Punho/fisiopatologia , Adulto Jovem
16.
J Clin Neurosci ; 17(3): 410-1, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20071180

RESUMO

Miller Fisher syndrome (MFS) is characterized by gait ataxia, external ophthalmoplegia and areflexia. Immunohistochemical studies suggest a pathophysiological role for anti-GQ1b antibodies at the paranodal regions of the oculomotor nerves, at some neurons of the dorsal root ganglia (DRG) and at motor nerve terminals. The variability of abnormal electrophysiological findings reported is significant. Nerve conduction studies, H reflex and F waves were performed in three pediatric patients with MFS. The H reflex was absent in all three patients. It was the sole abnormality in two patients whereas the third patient also had extended motor and sensory nerve conduction impairments. The transient character of this isolated absence has been confirmed in one patient. These data point to a proximal demyelinating process near the DRG. This may involve selective demyelination of Ia spinocerebellar afferent fibers originating in muscle spindles. In a pediatric practice, the H reflex seems to be a useful tool in the diagnostic approach to MFS.


Assuntos
Reflexo H/fisiologia , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/fisiopatologia , Pediatria , Criança , Pré-Escolar , Feminino , Humanos , Condução Nervosa/fisiologia
17.
Neuromuscul Disord ; 20(8): 517-23, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20576434

RESUMO

Bethlem myopathy and Ullrich congenital muscular dystrophy are part of the heterogeneous group of collagen VI-related muscle disorders. They are caused by mutations in collagen VI (ColVI) genes (COL6A1, COL6A2, and COL6A3) while LMNA mutations cause autosomal dominant Emery-Dreifuss muscular dystrophy. A muscular dystrophy pattern and contractures are found in all three conditions, making differential diagnosis difficult especially in young patients when cardiomyopathy is absent. We retrospectively assessed upper and lower limb muscle CT scans in 14 Bethlem/Ullrich patients and 13 Emery-Dreifuss patients with identified mutations. CT was able to differentiate Emery-Dreifuss muscular dystrophy from ColVI-related myopathies in selected thigh muscles and to a lesser extent calves muscles: rectus femoris fatty infiltration was selectively present in Bethlem/Ullrich patients while posterior thigh muscles infiltration was more prominently found in Emery-Dreifuss patients. A more severe fatty infiltration particularly in the leg posterior compartment was found in the Emery-Dreifuss group.


Assuntos
Doenças do Colágeno/diagnóstico por imagem , Colágeno Tipo VI , Distrofia Muscular de Emery-Dreifuss/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Adolescente , Adulto , Idade de Início , Doenças do Colágeno/genética , Colágeno Tipo VI/genética , DNA/genética , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Distrofia Muscular de Emery-Dreifuss/genética , Mutação/genética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
19.
Proc Natl Acad Sci U S A ; 93(8): 3570-4, 1996 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-8622977

RESUMO

Fast skeletal muscles of mdx (X chromosome-linked muscular dystrophy) mice were injected after birth with a recombinant adenovirus containing a minidys- trophin gene, a 6.3-kbp cDNA coding for the N- and C-terminal ends of dystrophin. Adult muscles were challenged by forced lengthening during tetanic contractions. Stretch-induced mechanical and histological damages were much reduced in injected muscles, in direct proportion of the Miniber of fibers expressing minidystrophin. Damaged fibers were preferentially found among minidystrophin-negative regions. Minidystrostrophin confers an important functional and structural protection of limb muscles against high mechanical stress, even after a partial somatic gene transfer.


Assuntos
Distrofina/genética , Técnicas de Transferência de Genes , Terapia Genética , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/terapia , Adenoviridae/genética , Animais , Vetores Genéticos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos mdx , Contração Muscular , Fibras Musculares de Contração Rápida/fisiologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular Animal/fisiopatologia , Estresse Mecânico
20.
Neuropediatrics ; 34(3): 146-8, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12910438

RESUMO

A father and his daughter displayed strictly similar focal brain dysplasia at MR examination, characterized by regional medial posterior laminar sub-cortical grey matter heterotopia. To our knowledge, no family presenting such anomalies has yet been described. LIS1 and DCX gene defects were excluded. Collecting patients with such inherited dysplasia should improve our knowledge of the genetic basis of cortical malformations.


Assuntos
Encefalopatias/genética , Coristoma/genética , Lateralidade Funcional , Proteínas Associadas aos Microtúbulos/genética , Neuropeptídeos/genética , Lobo Occipital , Lobo Parietal , 1-Alquil-2-acetilglicerofosfocolina Esterase , Adulto , Encefalopatias/patologia , Pré-Escolar , Coristoma/patologia , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA