A systematic review on the definition of rhabdomyolysis

Journal of Neurology - Rhabdomyolysis (RML) is an interdisciplinary condition due to muscle cell injury followed by the release of cell components into circulation. Etiology of RML has a broad...     

Angeborene und endogene endokrine Myopathien

Disorders in endocrinological pathways rarely lead to manifest acquired or endogenous myopathy so that an interdisciplinary evaluation between neurology and endocrinology is essential for these disorders. Asymptomatic or forme fruste variants may be more common and even underdiagnosed in these circumstances. Dysbalance disorders of protein synthesis, electrolytes and carbohydrates can lead to several rare forms of myopathy due to the dependence on hormonal metabolism. In general, the main neuromuscular symptom is proximal weakness, sometimes in addition to myalgia and muscle atrophy. Endocrine myopathies are usually reversible by treatment of the underlying disease. The severity of the endocrinopathy is of fundamental importance for the long-term clinical outcome.     

Acetyl-dl-leucine improves restless legs syndrome: a case report

Journal of Neurology -     

Congenital and endogenous endocrine myopathy

Disorders in endocrinological pathways rarely lead to manifest acquired or endogenous myopathy so that an interdisciplinary evaluation between neurology and endocrinology is essential for these disorders. Asymptomatic or forme fruste variants may be more common and even underdiagnosed in these circumstances. Dysbalance disorders of protein synthesis, electrolytes and carbohydrates can lead to several rare forms of myopathy due to the dependence on hormonal metabolism. In general, the main neuromuscular symptom is proximal weakness, sometimes in addition to myalgia and muscle atrophy. Endocrine myopathies are usually reversible by treatment of the underlying disease. The severity of the endocrinopathy is of fundamental importance for the long-term clinical outcome.     

Immune-mediated rippling muscle disease with myasthenia gravis: A report of seven patients with long-term follow-up in two

We report seven patients with immune-mediated rippling muscle disease (iRMD) and AChR-antibody positive myasthenia gravis (MG) without germline caveolin-3 gene mutations. We describe the follow-up of two patients and the clinical features of five new patients (1 female, 4 male, aged 32 to 69 years). These presented with significant generalized, exercise-induced and electrically-silent muscle rippling with myalgia, combined with generalized MG. In two of the seven patients, MG appeared before iRMD. Mediastinal imaging excluded thymic alterations in all, although two had other coincident tumours. Myalgia and rippling were aggravated by acetylcholinesterase-inhibitor treatment. Generalized MG and iRMD were successfully treated with plasma exchange, steroids and azathioprine in the two patients followed long-term. Muscle morphology of five patients showed a minimal myopathic pattern with rare lymphohistiocytic infiltration. In four patients, sarcolemmal caveolin-3, and dysferlin immunofluorescence staining was moderately reduced in a mosaic pattern, but caveolin-3 protein on Western blots was clearly reduced only in two. Notably, electron microscopy showed that caveolae were almost completely lost at the sarcolemma in the three biopsies examined but not in endothelium. Antibodies targeting high molecular weight muscle proteins, likely associated with the neuromuscular endplate and sarcolemma, were found in the iRMD patients but also in age-matched MG patients without iRMD. Since the generalized MG and iRMD improved with immunosuppressive treatments, it is likely that both are caused by autoantibodies, but the target for pathogenic antibodies in iRMD requires further study.     

Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disorder characterized by a defect in synaptic transmission at the neuromuscular junction causing fluctuating muscle weakness with a decremental response to repetitive nerve stimulation or altered jitter in single-fiber electromyography (EMG). Approximately 80% of all myasthenia gravis patients have autoantibodies against the nicotinic acetylcholine receptor in their serum. Autoantibodies against the tyrosine kinase muscle-specific kinase (MuSK) are responsible for 5–10% of all myasthenia gravis cases. The autoimmune target in the remaining cases is unknown. Recently, low-density lipoprotein receptor-related protein 4 (LRP4) has been identified as the agrin receptor. LRP4 interacts with agrin, and the binding of agrin activates MuSK, which leads to the formation of most if not all postsynaptic specializations, including aggregates containing acetylcholine receptors (AChRs) in the junctional plasma membrane. In the present study we tested if autoantibodies against LRP4 are detectable in patients with myasthenia gravis. To this end we analyzed 13 sera from patients with generalized myasthenia gravis but without antibodies against AChR or MuSK. The results showed that 12 out of 13 antisera from double-seronegative MG patients bound to proteins concentrated at the neuromuscular junction of adult mouse skeletal muscle and that approximately 50% of the tested sera specifically bound to HEK293 cells transfected with human LRP4. Moreover, 4 out of these 13 sera inhibited agrin-induced aggregation of AChRs in cultured myotubes by more than 50%, suggesting a pathogenic role regarding the dysfunction of the neuromuscular endplate. These results indicate that LRP4 is a novel target for autoantibodies and is a diagnostic marker in seronegative MG patients.