- Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy. [Journal Article]
- JNJ Neurol 2018 Dec 04
- CONCLUSIONS: PYROXD1 variants can cause an adult-onset slowly progressive LGMD-type phenotype.
- Pompe Disease Could Mimic Exam Findings of Amyloidosis: Two Rare Diagnoses Bona Fide. [Journal Article]
- CRCase Rep Hematol 2018; 2018:9615834
- A 70-year-old female presented with a three-year history of evolving macroglossia causing dysphagia and dysarthria, with proximal muscle weakness. Given the classic physical finding of macroglossia, ...
A 70-year-old female presented with a three-year history of evolving macroglossia causing dysphagia and dysarthria, with proximal muscle weakness. Given the classic physical finding of macroglossia, the patient underwent extensive evaluation for amyloidosis which proved to be negative apart from a bone marrow biopsy which stained positive for transthyretin without amino acid sequence abnormality, thus giving wild-type transthyretin amyloidosis. Since the wild-type transthyretin amyloidosis could not entirely explain her clinical presentation and evaluation, further studies were conducted in a sequential manner, thus leading to a diagnosis of Pompe disease explaining her presenting signs and symptoms including her macroglossia. Through this fascinating case, we attempt to highlight the approach for the diagnoses of two rare diseases in a patient by emphasizing the importance of having a broad differential diagnosis when presented with findings which may have been thought as pathognomonic for certain diseases.
- Long-term outcomes of a patient with late-onset multiple acyl-CoA dehydrogenase deficiency caused by novel mutations in ETFDH: A case report. [Journal Article]
- MMedicine (Baltimore) 2018; 97(48):e13153
- CONCLUSIONS: Muscle biopsy was the main method used to determine LSM. Treatment with riboflavin should be started when the diagnosis of LSM is definitive. Furthermore, ETFDH gene tests should be performed for further classification. Moreover, coenzyme Q10 may be another effective drug for MADD.
- Tacrolimus inhibits Th1 and Th17 responses in MuSK-antibody positive myasthenia gravis patients. [Journal Article]
- ENExp Neurol 2018 Nov 22; 312:43-50
- Muscle specific tyrosine kinase antibody positive myasthenia gravis (MuSK- MG) is characterized by autoantibodies against the MuSK protein of the neuromuscular junction resulting in weakness of bulba...
Muscle specific tyrosine kinase antibody positive myasthenia gravis (MuSK- MG) is characterized by autoantibodies against the MuSK protein of the neuromuscular junction resulting in weakness of bulbar and proximal muscles. We previously demonstrated that patients with MuSK-MG have increased pro-inflammatory Th1 and Th17 responses. Tacrolimus, an immunosuppressant used in AChR-MG and transplantation patients, inhibits T cell responses through interference with IL-2 transcription. The therapeutic efficacy and immunological effect of tacrolimus in MuSK-MG is unclear. In the current study we examined the proliferation, phenotype and cytokine production of CD4+ and CD8+ T cells in peripheral blood mononuclear cells of MuSK-MG following a 3-day in vitro culture with or without tacrolimus. We determined that tacrolimus profoundly suppressed CD4 and CD8 T cell proliferation and significantly suppressed Th1 and Th17 responses, as demonstrated by a reduced frequency of IFN-γ, IL-2, and IL-17 producing CD4 T cells and reduced frequencies of IFN-γ and IL-2 producing CD8 T cells. Tacrolimus also inhibits pathogenic Th17 cells coproducing IL-17 and IFN-γ. In addition, tacrolimus suppressed follicular T helper cell (Tfh) and regulatory T helper cell (Treg) subsets. These findings provide preliminary support for tacrolimus as a potential alternative immunosuppressive therapy for MuSK-MG.
- Management of Myasthenia Gravis in Pregnancy. [Review]
- NCNeurol Clin 2019; 37(1):113-120
- Myasthenia gravis is an autoimmune disorder characterized by fluctuating weakness of extraocular and proximal limb muscles. It occurs in 1 in 5000 in the overall population and is 2 times more common...
Myasthenia gravis is an autoimmune disorder characterized by fluctuating weakness of extraocular and proximal limb muscles. It occurs in 1 in 5000 in the overall population and is 2 times more common in women than men. The onset in women is most common in the third decade, and risk of severe exacerbation occurs most frequently in the year after presentation. The disease does not have an impact on fertility and overlap with pregnancy is expected. This article provides a description of the disease process and its impact on the expecting mother, fetus, and newborn. Management options in pregnancy and lactation are discussed.
- Coexistence of anti-HMGCR and anti-MDA5 identified by an unlabeled immunoprecipitation assay in a chinese patient cohort with myositis. [Journal Article]
- MMedicine (Baltimore) 2018; 97(47):e13236
- Myositis-specific autoantibodies are important diagnostic and prognostic markers. The aim of our study is to detect anti-3-hydroxy 3-methylutaryl coenzyme A reductase (anti-HMGCR) antibody using nove...
Myositis-specific autoantibodies are important diagnostic and prognostic markers. The aim of our study is to detect anti-3-hydroxy 3-methylutaryl coenzyme A reductase (anti-HMGCR) antibody using novel unlabeled immunoprecipitation (IP) assay and immunoblotting in Chinese patients with myositis and to clarify the features of anti-HMGCR-positive patients. In the present study, we established novel unlabeled IP assay and immunoblotting of HMGCR C-terminus for anti-HMGCR detection. The presence of anti-HMGCR was screened in 181 Chinese patients with myositis. The sera from 12 of 181 patients were positive for anti-HMGCR. The prevalence of anti-HMGCR autoantibody in our cohorts is about 6.6%. Unexpected, coexistence of anti-HMGCR and anti-melanoma differentiation-associated protein (anti-MDA5) were identified in 4 patients with characteristic rash and interstitial lung disease (ILD), but without myasthenia and elevated serum creatine kinase (CK) levels. Other anti-HMGCR positive patients without anti-MDA5 presented with severe proximal muscle weakness. Mean serum CK levels and lactate dehydrogenase (LDH) were significantly higher in anti-HMGCR-positive patients than in antibody-negative patients (P <.05). Muscle biopsies available from 6 anti-HMGCR-positive patients were characterized with prominent myofiber necrosis and regeneration, little or none of inflammatory cell infiltrates. None of anti-HMGCR positive patients in our cohort was exposed to statins. Our data suggested that anti-HMGCR were found to coexist frequently with anti-MDA5 identified by the established unlabeled IP assay and statin exposure is rare in Chinese myositis patients with anti-HMGCR.
- Severe necrotizing myositis associated with long term anti-neoplastic efficacy following nivolumab plus ipilimumab combination therapy. [Journal Article]
- CRClin Rheumatol 2018 Nov 19
- Immune-related adverse events (irAEs), have been reported under immune checkpoint inhibitors. Nivolumab plus ipilimumab (N + I) demonstrated meaningful improvements in key patient-reported outcomes, ...
Immune-related adverse events (irAEs), have been reported under immune checkpoint inhibitors. Nivolumab plus ipilimumab (N + I) demonstrated meaningful improvements in key patient-reported outcomes, in patients with pretreated microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). We report a case of severe necrotizing myositis which occurred in a patient treated with N + I combination for mCRC MSI-H. A 61-year-old woman was diagnosed with mCRC MSI-H and BRAFV600E mutated with synchronous liver, pleural, and lymph nodes metastases. After she failed to respond to standard chemotherapy (two lines with 5-fluorouracil, oxaliplatin, and irinotecan + bevacizumab), she received in a clinical trial (CheckMate 142), nivolumab 3 mg/kg, and ipilumumab 1 mg/kg every 3 weeks . One week after the second infusion, she developed rapidly extending proximal muscles weakness associated with diffuse erythematous rash with grade 2/5 strength on abdominal, dorsal, and proximal limb muscles and impressive muscular edema. The creatine kinase level was at 14827 U/L (0-160 U/L), without any detectable autoantibodies. The electromyogram showed a severe myogenic syndrome, and muscular histological analysis demonstrated extensive muscular necrosis, with scarce lymphocytic infiltrates and pathological expression of class I HLA and C5b9 complement deposits with severe endomysial edema. N-I therapy was discontinued. Intravenous methylprednisolone was initiated for 3 days followed by 1 mg/kg/day orally, combined with intravenous immunoglobulins (2 g/kg/day for 2 days). At 3 years of first infusion of N + I, patient is without any new progressive disease, in partial response on the liver, pleural, and nodes metastasis, with only persistent minor psoas weakness.
- GeneReviews® [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- SPTLC1-related hereditary sensory neuropathy (HSN) is an axonal form of hereditary motor and sensory neuropathy distinguished by prominent early sensory loss and later positive sensory phenomena incl...
SPTLC1-related hereditary sensory neuropathy (HSN) is an axonal form of hereditary motor and sensory neuropathy distinguished by prominent early sensory loss and later positive sensory phenomena including dysesthesia and characteristic "lightning" or "shooting" pains. Loss of sensation can lead to painless injuries, which, if unrecognized, result in slow wound healing and subsequent osteomyelitis requiring distal amputations. Motor involvement is present in all advanced cases and can be severe. After age 20 years, the distal wasting and weakness may involve proximal muscles, possibly leading to wheelchair dependency by the seventh or eighth decade. Sensorineural hearing loss is variable.
- Two cases of glutaric aciduria type II: how to differentiate from inflammatory myopathies? [Journal Article]
- ACActa Clin Belg 2018 Nov 19; :1-5
- Muscle weakness is a nonspecific finding of myopathy of any etiology that include iatrogenic, toxic, endocrinological, infectious, immunologic, and metabolic disorders. Among the metabolic myopathies...
Muscle weakness is a nonspecific finding of myopathy of any etiology that include iatrogenic, toxic, endocrinological, infectious, immunologic, and metabolic disorders. Among the metabolic myopathies glutaric aciduria type II (GAII) is an autosomal recessively inherited rare disorder of fatty acid and amino acid metabolisms. The late onset form is heterogeneous in terms of symptomatology and severity and for the cases that chronic manifestations of lipid storage myopathy are the only clues for the disease, differential diagnosis can be challenging. Here we report two cases of GAII: the first one was 18-year old boy who presented with proximal muscle weakness and in another center, he was diagnosed as polymyositis and treated with immunosuppressive therapies. He admitted to our clinic with ongoing muscle weakness and symptoms that were related to the side effects of immunosuppressive therapies. The second case was also presented with muscle weakness. For both cases, muscle biopsies and urinary organic acid analyses were consistent with the diagnosis of GAII. To differentiate inflammatory myositis from non-inflammatory myopathies; rheumatic symptoms, accompanying complaints of the patient and autoantibody positivity can be helpful. To our knowledge this is the first report to underline the differential diagnosis of inflammatory myopathies from metabolic myopathies.
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- Toxic Myopathy due to Antidopaminergic Medication Without Neuroleptic Malignant Syndrome. [Journal Article]
- JCJ Clin Neuromuscul Dis 2018; 20(2):94-98
- Severe recurrent proximal muscle weakness without neuroleptic malignant syndrome secondary to antidopaminergic medication has rarely been reported. We report a 29-year-old man with history of obsessi...
Severe recurrent proximal muscle weakness without neuroleptic malignant syndrome secondary to antidopaminergic medication has rarely been reported. We report a 29-year-old man with history of obsessive compulsive disorder and Tourette syndrome who presented with 2 months of worsening dyspnea 3 weeks after starting ziprasidone 40 mg daily that required mechanical ventilation. A year before, after an increased risperidone dose from 0.5 to 1 mg daily, he had developed proximal muscle weakness that spontaneously improved 2 months after discontinuation of risperidone. On this admission, his creatine kinase (CK) was 3318 units/L, and ziprasidone was discontinued. He fully recovered 2 months after discontinuation of ziprasidone, and his CK was 62 units/L. Genetic testing for limb-girdle muscular dystrophy was negative. This case highlights the importance of evaluating CK level in patients taking antidopaminergic medication with any suggestion of muscle weakness to prevent potentially life-threatening complication.