A case of type 1 facioscapulohumeral muscular dystrophy (FSHD) with restrictive ventilatory defect and congestive heart failure

[Background] Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease characterized by asymmetric involvement of muscles in the face, upper extremity, trunk, and lower extremity regions, with variable severity. It was recently reported that restrictive respiratory involvement is more frequent and severe than previously recognized, while cardiac dysfunction other than arrhythmia is still considered extremely rare in FSHD. [Case report] A 59-year-old man presenting with marked muscle atrophy in the trunk and asymmetrical muscle atrophy in the legs was hospitalized because of dyspnea and edema in the face and limbs. Shortness of breath with body movement started from approximately 40 years of age. Muscle biopsy revealed myopathic change with mild to moderate variation in fiber size. The diagnosis of FSHD was made by D4Z4 contraction to three repeats on genetic testing. A pulmonary function test revealed a decline of forced vital capacity (FVC) and a preserved FEV1/FVC indicating restrictive ventilatory defect (RVD). Ultrasonic echocardiogram (UCG) showed diffuse left ventricular hypokinesis, ventricular septum thickening, pericardial effusion, and decreased ejection fraction (LVEF 30%). [Conclusion] Although restrictive ventilatory defect and congestive heart failure are uncommon in FSHD, respiratory and cardiac evaluation may be necessary in patients with FSHD

Impaired response of hypoxic sensor protein HIF-1 alpha and its downstream proteins in the spinal motor neurons of ALS model mice

We have recently reported spinal blood flow-metabolism uncoupling in an amyotrophic lateral sclerosis (ALS) animal model using Cu/Zn-superoxide dismutase 1 (SOD1)-transgenic (Tg) mice, suggesting a relative hypoxia in the spinal cord. However, the hypoxic stress sensor pathway has not been well studied in ALS. Here, we examined temporal and spatial changes of the hypoxic stress sensor proteins HIF-1 alpha and its downstream proteins (VEGF, HO-1, and EPO) during the normcodccourse of motor neuron (MN) degeneration in the spinal cord of these ALS model mice. We found that HIP-1 alpha protein expression progressively increased both in the anterior large MNs and the surrounding glial cells in Tg mice from early symptomatic 14 week (W) and end stage 18W. Double immunofluorescence analysis revealed that HIP-1 alpha, plus GFAP and Iba-1 double-positive surrounding glial cells, progressively increased from 14 W to 18 W, although the immunohistochemistiy in large MNs did not change. Expression levels of VEGF and HO-1 also showed a progressive increase but were significant only in the surrounding glial cells at 18W. In contrast, EPO protein expression was decreased in the surrounding glial cells of Tg mice at 18W. Because HIF1-alpha serves as an important mediator of the hypoxic response, these findings indicate that MNs lack the neuroprotective response to hypoxic stress through the HIF-1 alpha system, which could be an important mechanism of neurodegeneration in ALS

Effect of intravenous immunoglobulin therapy on anti-NT5C1A antibody-positive inclusion body myositis after successful treatment of hepatitis C: A case report

Inclusion body myositis (IBM) is the commonest idiopathic inflammatory myopathy of older persons. Pathophysiological mechanism of IBM remains unknown; however, an association of IBM with chronic hepatitis C virus (HCV) infection and serum autoantibodies against skeletal muscle protein 5′-nucleotidase 1A (NT5C1A) has recently been reported. No effective treatment for IBM has yet been developed. We here present a 70-year-old man who was anti-NT5C1A antibody-positive in association with IBM and chronic hepatitis C. The initial treatment of ombitasvir/paritaprevir/ritonavir for his chronic hepatitis C was successful; however, his symptoms of IBM did not improve. On the contrary, his quadriplegic paralysis became more severe and he developed dysphagia. Next, steroid pulse therapy was initiated for IBM and, although his hyper-creatine phosphokinase-emia improved, his symptoms did not; indeed, they worsened. Subsequent intravenous immunoglobulin therapy (IVIg) resulted in obvious improvement in his dysphagia. Thereafter IVIg therapy was repeated at approximately 2-monthly intervals. His dysphagia remained improved for more than 1 year; however, his quadriplegia continued to progress slowly. Although IBM can reportedly be associated with hepatitis C, we inferred that there was no direct relationship between these conditions in our patient because his IBM did not improve after treatment of his hepatitis C. Although his IBM-associated quadriplegia did not improve, IVIg therapy did result in improvement in his dysphagia

In vivo imaging of autophagy in a mouse stroke model

Recent studies have suggested that autophagy is involved in a neural death pathway following cerebral ischemia. In vivo detection of autophagy could be important for evaluating ischemic neural cell damage for human stroke patients. Using novel green fluorescent protein (GFP)-fused microtubule-associated protein 1 light chain 3 (LC3) transgenic (Tg) mice, in vivo imaging of autophagy was performed at 1, 3 and 6 d after 60 min transient middle cerebral artery occlusion (tMCAO). Ex vivo imaging of autophagy, testing of the autophagy inhibitor 3-methyladenine (3-MA), estern blot analysis, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and fluorescent analyses were performed on brain sections following tMCAO. In vivo fluorescent signals were detected above the ischemic hemisphere through the skull bone at 1, 3 and 6 d after tMCAO, with a peak at 1 d. Similar results were obtained with ex vivo fluorescence imaging. western blot analysis revealed maximum LC3-I and LC3-II expression at 1 d after tMCAO and fluorescence immunohistochemistry demonstrated that GFP-LC3-positive cells were primarily neuronal, not astroglial or microglial, cells. The number of GFP-LC3/TUNEL double-positive cells was greater in the peri-ischemic area than in the core. These results provided evidence of in vivo autophagy detection, with a peak at 1 d, in a live animal model following cerebral ischemia. This novel technique could be valuable for monitoring autophagic processes in vivo in live stroke patients, as well as for clarifying the detailed role of autophagy in the ischemic brain, as well as in other neurological diseases

Recurrent rhabdomyolysis in a patient with a history of rhabdomyolysis due to severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever syndrome that is endemic to East Asia. Here, we describe a case of rhabdomyolysis, thought to have been caused by pemafibrate (which was prescribed for hyperlipidemia) or bacterial infection, in a patient who had experienced SFTS-induced rhabdomyolysis 4 years ago. This case suggests that SFTS causes muscle degeneration and can lead to recurrent rhabdomyolysis as a long-term complication

Cerebral syphilitic gumma mimicking a brain tumor that enlarged temporarily after commencing antibiotic treatment

In this case report, we describe a 60-year-old man who presented with headaches for 1 year and mild confusion for 3 weeks and was initially diagnosed as having a cerebral tumor on the basis of finding a round lesion in the right lenticular nucleus with ring enhancement on gadolinium-enhanced T1-weighted brain magnetic resonance imaging. However, the discovery of positive serology for Treponema pallidum infection on routine tests on admission prompted analysis of cerebrospinal fluid, which was also positive on Treponema pallidum hemagglutination (TPHA), rapid plasma reagin (RPR), and treponemal antibody absorption (FTA-ABS) tests. Thus, he was diagnosed as having an intracranial syphilitic gumma. After commencing treatment with penicillin G, the lesion temporarily increased in size, but subsequently resolved completely with continuing antibiotic treatment. In the present era of increasing prevalence of syphilitic infection and because they are eminently treatable, syphilitic gummas should be included in the differential diagnosis of apparent brain tumors. Additionally, temporary enlargement of a probable gumma after instituting antibiotic treatment should not prompt cessation or change of the antibiotics

Spreading brain lesions in a familial Creutzfeldt-Jakob disease with V180I mutation over 4 years

BACKGROUND: We report a female patient with familial Creutzfeldt-Jakob disease with V180I mutation (fCJD with V180I), who was serially followed up with magnetic resonance imaging (MRI) and electroencephalogram (EEG) for up to four years. CASE PRESENTATION: At 6 months after the onset, diffusion-weighted images (DWI) and fluid-attenuated inversion recovery (FLAIR) of brain MRI revealed an increased signal intensity in the bilateral frontal, temporal, and parietal cerebral cortex with left dominancy except for the occipital lobe. However, her follow-up MRI at four years showed the high-signal regions spreading to the occipital cerebral cortex in DWI and FLAIR images, and bilateral frontal cerebral white matter in FLAIR images. EEG showed a progressive and general slow high-voltage rhythm from 7–8 to 3–5 c/s over four years, without evidence of periodic synchronous discharge. These findings correspond to the symptom progression even after akinetic mutism at 18 months. CONCLUSION: We suggest that serial MRI and EEG examinations are useful for early diagnosis of fCJD with V180I and for monitoring disease progression