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Arthritis Res Ther ; 22(1): 5, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059


OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

Orphanet J Rare Dis ; 11: 8, 2016 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-26809617


BACKGROUND: Late-onset Pompe disease (LOPD) is a rare treatable lysosomal storage disorder characterized by progressive lysosomal glycogen accumulation and muscle weakness, with often a limb-girdle pattern. Despite published guidelines, testing for LOPD is often overlooked or delayed in adults, owing to its low frequency compared to other muscle disorders with similar muscle patterns. Next-generation sequencing has the capability to test concurrently for several muscle disorders. This could potentially lead to increased diagnosis of LOPD, disorders with non-specific muscle weakness or atypical patients. METHODS: We developed a gene panel to further study its clinical utility in a cohort of patients with suspected muscle disorders. We designed a gene panel to analyze the coding sequences and splice site junctions of GAA causing LOPD, along with 77 other genes causing muscle disorders with overlapping phenotypes. RESULTS: At a median coverage of ~200X (sequences per base), all GAA exons were successfully covered with >20X and only 0.3 % of exons across all genes were <20X. The panel showed an excellent sensitivity (100 %) and specificity (98 %) across all selected genes, using known variations in Pompe patients and controls. We determined its clinical utility by analyzing 34 patients with suspected muscle disorders of undetermined etiology and various muscle patterns, who were referred or followed in neuromuscular and genetics clinics. A putative diagnosis was found in up to 32 % of patients. The gene panel was instrumental in reaching a diagnosis in atypical patients, including one LOPD case. Acid alpha-glucosidase activity was used to confirm the molecular results in all patients. CONCLUSION: This work highlights the high clinical utility of gene panels in patients with suspected muscle disorders and its potential to facilitate the diagnosis of patients showing non-specific muscle weakness or atypical phenotypes. We propose that gene panels should be used as a first-tier test in patients with suspected muscle disorders of undetermined etiology, which could further increase overall diagnosis of muscle conditions, and potentially reduce diagnostic delay. Further studies are necessary to determine the impact of first-tier gene panels on diagnostic delay and on treatment outcome for LOPD.

Doença de Depósito de Glicogênio Tipo II/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Doenças Musculares/diagnóstico , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
BMC Musculoskelet Disord ; 15: 388, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25414144


BACKGROUND: Eosinophilic granulomatosis with polyangiitis is a complex multisystemic syndrome with heterogeneous presentation. Most often, there is a clinical history of asthma or other atopic conditions, and current presentation generally includes signs of cutaneous or pulmonary involvement. Very few reports described myalgia or weakness as the chief complaint. Of these, only a few included muscle biopsy evaluation and none showed convincing evidence of primary myositis. We believe this report is the first to demonstrate true myositis in the setting of early eosinophilic granulomatosis with polyangiitis. CASE PRESENTATION: This report describes a 74 year old Caucasian man, with no known allergies, presenting severe myalgia, muscle weakness, jaw claudication, and fever. Blood work showed marked eosinophilia and high creatine kinase levels. Biceps brachialis muscle biopsy revealed eosinophilic necrotizing vasculitis and true myositis with myophagocytosis of non-necrotic fibers and strong sarcolemmal MHC-1 overexpression by immunohistochemistry. This patient was successfully treated with prednisone and azathioprine. CONCLUSION: Our finding of true myositis in a case of eosinophilic granulomatosis with polyangiitis suggests that primary auto-immunity against muscle fibers, distinct from the secondary effects of vasculitis, can occur in this entity and may represent an overlap syndrome. Early recognition of eosinophilic granulomatosis with polyangiitis in patients presenting with myositis may provide an opportunity to treat the vasculitis before onset of severe multisystemic disease. We recommend the use of muscle biopsy with immunohistochemistry for MHC-1 to confirm the diagnosis of myositis in the setting of eosinophilic granulomatosis with polyangiitis.

Síndrome de Churg-Strauss/diagnóstico , Eosinófilos , Granulomatose com Poliangiite/diagnóstico , Miosite/diagnóstico , Idoso , Síndrome de Churg-Strauss/complicações , Diagnóstico Diferencial , Granulomatose com Poliangiite/complicações , Humanos , Masculino , Miosite/complicações
J Neurol Neurosurg Psychiatry ; 82(6): 674-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20562458


The authors report on four patients aged over 50 with chronic myopathy suggestive of sporadic inclusion body myositis. They present progressive and selective weakness of the quadriceps femoris muscles. Asymmetrical and selective atrophy of the forearm muscles were noted in all, with more severe involvement of the flexors than the extensors. Biopsy revealed granulomatous myositis. Histological features of sporadic inclusion body myositis were lacking. Evidence for systemic sarcoidosis was found in one patient. Corticosteroid treatment was associated with a partial but significant improvement in two patients. Granulomatous myositis may mimic inclusion body myositis and may be steroid-responsive.

Antebraço/patologia , Miosite de Corpos de Inclusão/diagnóstico , Miosite/diagnóstico , Músculo Quadríceps/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Debilidade Muscular/patologia , Miosite/patologia , Miosite de Corpos de Inclusão/patologia , Sarcoidose/diagnóstico , Sarcoidose/patologia
Rev Prat ; 58(17): 1887-9, 1892-4, 2008 Nov 15.
Artigo em Francês | MEDLINE | ID: mdl-19157204


Dysimmune neuropathies encompass an acute form, Guillain-Barré syndrome (GBS), and mainly 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy, and polyneuropathy associated with anti-MAG (myelin-associated-glycoprotein) IgM monoclonal gammopathy. Recent concepts have concerned both incidence and mortality rates, and better scoring system for predict outcome in GBS, but new therapeutical strategy is needed for the so-called "benign" forms and for relapsing forms after first-line IVIg therapy. In chronic forms, criteria for diagnosis and guidelines for management have been edited in the recent years, together with recommendations for outcome measures. However, there is still a need for knowing the better outcome measures, and to elaborate new trials, mainly focusing on the long-term management of the patients.

Polirradiculoneuropatia/diagnóstico , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/terapia , Humanos , Imunoglobulina M/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Gamopatia Monoclonal de Significância Indeterminada/terapia , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/terapia , Glicoproteína Associada a Mielina/imunologia , Polineuropatias/imunologia , Polineuropatias/terapia , Polirradiculoneuropatia/terapia
Can J Neurol Sci ; 33(2): 243-5, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16736740


BACKGROUND: Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is based on the classical triad of rapidly progressive dementia, myoclonus and abnormal EEG. The 200k mutation within the gene encoding PrP, located on the short arm of chromosome 20, accounts for more than 70% of families with CJD worldwide. CASE REPORT: Herein, we report a patient who developed persistent dry cough and classical signs of CJD, including severe cognitive decline, cerebellar signs, and myoclonic jerks, leading to death a few weeks after disease onset. Mutation screening showed that he had the 200k point mutation in the PRNP gene. His mother had died twenty years earlier with neuropathologically confirmed CJD. She had presented a rapidly progressive ataxia with myoclonus, dementia, visual hallucinations, and the same persistent dry cough. CONCLUSIONS: The clinical presentation of this familial CJD case with persistent dry cough is quite unusual. Therefore, a neurological etiology should be sought when confronted with an unexplained persistent cough.

Tosse/etiologia , Síndrome de Creutzfeldt-Jakob/complicações , Síndrome de Creutzfeldt-Jakob/genética , Encéfalo/patologia , Encéfalo/fisiopatologia , Doenças Cerebelares/genética , Doenças Cerebelares/fisiopatologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/fisiopatologia , Tosse/fisiopatologia , Síndrome de Creutzfeldt-Jakob/diagnóstico , Análise Mutacional de DNA , Demência/genética , Demência/fisiopatologia , Progressão da Doença , Evolução Fatal , Transtornos Neurológicos da Marcha/genética , Transtornos Neurológicos da Marcha/fisiopatologia , Predisposição Genética para Doença/genética , Genótipo , Alucinações/genética , Alucinações/fisiopatologia , Humanos , Padrões de Herança/genética , Judeus/genética , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Mioclonia/genética , Mioclonia/fisiopatologia , Príons/genética