Sporadic late-onset nemaline myopathy (SLONM) is a rare acquired myopathy characterized by rapid-onset proximal weakness in late adulthood, and the presence of nemaline bodies on muscle biopsy. In recent years, several therapeutic interventions, including immunomodulating agents and autologous stem cell transplantation, have shown variable degrees of efficacy in different patients, but no consensus has been reached to allow an effective tailoring of treatments in this severe disease. We performed a retrospective evaluation of clinical, pathological, laboratory, muscle MRI, and follow-up data of SLONM patients diagnosed in the period 2010-2015 in our neuromuscular center. Six patients (three males and three females) were identified. Average time elapsed from the onset of symptoms to referral to the neuromuscular specialist was 23.7 months. Monoclonal gammopathy was detectable in five patients. Nemaline bodies were detected in all the patients, and their abundance correlated with clinical severity. Signs of cardiac involvement were present in all the patients to different extents. Muscle MRI showed a preferential involvement of neck extensors, paraspinal, gluteal, hamstring and soleus muscles. All patients were treated with prednisone and repeated courses of intravenous immunoglobulins, and a favorable outcome was reached in five patients. Our experience confirms that SLONM is clinically characterized by subacute proximal and axial muscle weakness. Time to referral was relatively long and should be reduced with increasing awareness of the disease. Muscle MRI could be of help as a diagnostic tool to identify this potentially treatable myopathy. Cardiac evaluation should be warranted in all SLONM patients to detect subclinical heart involvement.

The objective of the study was to better characterize the clinical phenotype associated with the A8344G "MERRF" mutation of mitochondrial DNA. Fifteen mutated patients were extensively investigated. The frequency of main clinical features was: exercise intolerance and/or muscle weakness 67 %, respiratory involvement 67 %, lactic acidosis 67 %, cardiac abnormalities 53 %, peripheral neuropathy 47 %, myoclonus 40 %, epilepsy 40 %, ataxia 13 %. A restrictive respiratory insufficiency requiring ventilatory support was observed in about half of our patients. One patient developed a severe and rapidly progressive cardiomyopathy requiring cardioverter-defibrillator implantation. Five patients died of overwhelming, intractable lactic acidosis. Serial muscle MRIs identified a consistent pattern of muscle involvement and progression. Cardiac MRI showed non-ischemic late gadolinium enhancement in the left ventricle inferolateral part as early sign of myocardial involvement. Brain spectroscopy demonstrated increased peak of choline and reduction of N-acetylaspartate. Lactate was never detected in brain areas, while it could be documented in ventricles. We confirm that muscle involvement is the most frequent clinical feature associated with A8443G mutation. In contrast with previous reports, however, about half of our patients did not develop signs of CNS involvement even in later stages of the disease. The difference may be related to the infrequent investigation of A8344G mutation in 'pure' mitochondrial myo-cardiomyopathy, representing a bias and a possible cause of syndrome's underestimation. Our study highlights the importance of lactic acidosis and respiratory muscle insufficiency as critical prognostic factors. Muscle and cardiac MRI and brain spectroscopy may be useful tools in diagnosis and follow-up of MERRF.

In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis.

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