Immunolocalization of tenascin-C in human type II fiber atrophy

Tenascin-C is a multifunctional extracellular matrix glycoprotein with stimulatory and anti-adhesive or inhibitory properties for axon growth. Its location and discontinuous expression are restricted in innervated muscle tissues. Tenascin-C accumulated interstitially among human denervated muscle fibers and close to normal-sized fibers. To expand our knowledge of the expression of tenascin-C in human neuromuscular disorders, we investigated immunohistologically 20 human muscle specimens with type II myofiber atrophy of children and adults. Tenascin-C immunoreactivity in adult type II atrophy was frequent, and accumulation in children was sparse and weak. In both groups, tenascin-C immunoreactivity was found: 1. Interstitially around normal-sized type II muscle fibers. 2. Around atrophic type II muscle fibers. 3. Around small-caliber myofibers with centrally located nuclei. These results indicate that tenascin-C immunoreactivity: (1) is detectable around early denervated and reinnervated muscle fibers and, therefore, (2) may reflect in part the molecularly ongoing process of denervation and reinnervation in human type II fiber atrophy.     

STIG study: real-world data of long-term outcomes of adults with Pompe disease under enzyme replacement therapy with alglucosidase alfa

Journal of Neurology - Pompe disease is one of the few neuromuscular diseases with an approved drug therapy, which has been available since 2006. Our study aimed to determine the real-world...     

A role for cannabinoids in the treatment of myotonia? Report of compassionate use in a small cohort of patients

Journal of Neurology - The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory. Some patients anecdotally report...     

Matrix metalloproteinases in inflammatory myopathies: enhanced immunoreactivity near atrophic myofibers

OBJECTIVES: To further examine the role of proteolytic enzyme expression of matrix metalloproteinases (MMP) and T-cell markers in inflammatory myopathies and controls. MATERIAL AND METHODS: We studied the expression of MMP-2, MMP-7, and MMP-9 in 19 cases of inflammatory myopathies and controls using immunocytochemistry. RESULTS: Inflammatory myopathies showed distinct patterns of up-regulation of MMP. MMP-9 was strongly expressed in atrophic myofibers in all inflammatory myopathies. MMP-2 immunoreactivity was similar in its distribution, however, to a weaker intensity. In dermatomyositis the perifascicular atrophy showed pronounced MMP-9 immunoreactivity, probably reflecting denervated patterns of myofibers. Moreover, MMP-7 strongly immunolabeled invaded myofibers in polymyositis cases only. CONCLUSION: These patterns confirm, that MMP-7 up-regulation is prominent in PM, while MMP-2 immunoreactivity is only slightly elevated in inflamed muscle. In general, MMP-9 up-regulation appears to be an important additional molecular event in the multistep process of all inflammatory myopathies.     

Myoadenylate-deaminase gene mutation associated with left ventricular hypertrabeculation/non-compaction

BACKGROUND: Left ventricular hypertrabeculation (LVHT)/non-compaction, a rare myocardial abnormality and frequently associated with neuromuscular disorders, has not been reported in primary myoadenylate-deaminase (MAD) deficiency (MADD). CASE REPORT: In a 53-year-old man with easy fatigability and myalgia since boyhood, primary MADD was diagnosed based upon slightly, but recurrently elevated creatine-kinase, absent staining for MAD on muscle biopsy, markedly reduced MAD activity in the muscle homogenate, and the C34T mutation within exon 2 of the AMPD1 gene. An ambulatory ECG showed nocturnal sinus bradycardia and echocardiography thickening of the interventricular septum (20 mm) and the posterior wall (16 mm) and additionally LVHT. Cardiac MRI confirmed myocardial thickening and LVHT. Myocardial thickening and LVHT were regarded as causally related to the C34T mutation. CONCLUSION: Cardiac involvement in MADD may manifest as left ventricular myocardial thickening and LVHT. MADD should be included in the list of neuromuscular disorders which are associated with LVHT.     

Muscle pathology in 57 patients with myotonic dystrophy type 2

We evaluated muscle biopsies from 57 patients with genetically confirmed myotonic dystrophy type 2/proximal myotonic myopathy (DM2/PROMM). Light microscopy showed myopathic together with "denervation-like" changes in almost all biopsies obtained from four different muscles: increased fiber size variation, internal nuclei, small angulated fibers, pyknotic nuclear clumps, and predominant type 2 fiber atrophy. Quantitative morphometry in 18 biopsies that were immunostained for myosin heavy chain confirmed a predominance of nonselective type 2 fiber atrophy. These histological changes were similar in all patients regardless of the site of biopsy, the predominant clinical symptoms and signs, and the clinical course. It is likely that, in a number of undiagnosed patients, DM2 is the underlying disorder. With a better understanding of the histopathological pattern in DM2, biopsies from patients with undiagnosed neuromuscular disorders can now be reevaluated.     

Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease

Heterozygous missense mutations in the caveolin-3 gene (CAV3) cause different muscle disorders. Most patients with CAV3 alterations present with rippling muscle disease (RMD) characterized by signs of increased muscle irritability without muscle weakness. In some patients, CAV3 mutations underlie the progressive limb-girdle muscular dystrophy type 1C (LGMD1C). Here, we report two unrelated patients with novel homozygous mutations (L86P and A92T) in CAV3. Both presented with a more severe clinical phenotype than usually seen in RMD. Immunohistochemical and immunoblot analyses of muscle biopsies showed a strong reduction of caveolin-3 in both homozygous RMD patients similar to the findings in heterozygous RMD. Electron microscopy studies showed a nearly complete absence of caveolae in the sarcolemma in all RMD patients analyzed. Additional plasma membrane irregularities (small plasmalemmal discontinuities, subsarcolemmal vacuoles, abnormal papillary projections) were more pronounced in homozygous than in heterozygous RMD patients. A stronger activation of nitric oxide synthase was observed in both homozygous patients compared with heterozygous RMD. Like in LGMD1C, dysferlin immunoreactivity is reduced in RMD but more pronounced in homozygous as compared with heterozygous RMD. Thus, we further extend the phenotypic variability of muscle caveolinopathies by identification of a severe form of RMD associated with homozygous CAV3 mutations.