Muscle pain in mitochondrial diseases: a picture from the Italian network

Abstract

Muscle pain may be part of many neuromuscular disorders including myopathies, peripheral neuropathies and lower motor neuron diseases. Although it has been reported also in mitochondrial diseases (MD), no extensive studies in this group of diseases have been performed so far. We reviewed clinical data from 1398 patients affected with mitochondrial diseases listed in the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", to assess muscle pain and its features. Muscle pain was present in 164 patients (11.7%). It was commonly observed in subjects with chronic progressive external ophthalmoplegia (cPEO) and with primary myopathy without cPEO, but also-although less frequently-in multisystem phenotypes such as MELAS, MERFF, Kearns Sayre syndrome, NARP, MNGIE and Leigh syndrome. Patients mainly complain of diffuse exercise-related muscle pain, but focal/multifocal and at rest myalgia were often also reported. Muscle pain was more commonly detected in patients with mitochondrial DNA mutations (67.8%) than with nuclear DNA changes (32.2%). Only 34% of the patients showed a good response to drug therapy. Interestingly, patients with nuclear DNA mutations tend to have a better therapeutic response than patients with mtDNA mutations. Muscle pain is present in a significant number of patients with MD, being one of the most common symptoms. Although patients with a myopathic phenotype are more prone to develop muscle pain, this is also observed in patients with a multi system involvement, representing an important and disabling symptom having poor response to current therapy.

Chronic pain is common in mitochondrial disease

“…Curative treatments are currently lacking and management is largely based on symptomatic therapies and maximizing quality of life [2 , 3] . Pain has been reported in series of patients with mitochondrial disease, related to myopathy [4] , neuropathy [5] and headache [6] . However, the prevalence, severity, impact on the quality of life and the genetic predisposition of chronic pain in this population is not fully known.…”

Fondazione Telethon and Unione Italiana Lotta alla Distrofia Muscolare, a successful partnership for neuromuscular healthcare research of value for patients

“…Moreover, in 2018 this platform has been made available to clinicians for post-marketing SMA data collection. Another registry on mitochondrial disorders was started with a Telethon-UILDM grant and is managed directly by Mitocon, the Italian mitochondrial PO, on a different information technology platform [ 51 ]; its data already contributed to several studies and publications (see, for example, refs [ 15 ] and [ 52 ]).…”

“…With this particular investment, Telethon and UILDM meant to stimulate clinical researchers to approach medical research in a more person-centred manner. Some studies directly involved patients and caregivers, for instance, engaging them in surveys on QoL, disease burden and needs for psychosocial support [ 40 , 41 , 50 ], and collection of information on their medical requirements [ 15 , 49 , 52 ]. POs focused on DMD and their patient representatives participated in the development of a new functional scale that reflects patient mobility needs and daily life activities [ 33 , 34 ] and patient-reported functional OM [ 35 ].…”

Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases

“…We here report the findings of a multicenter study providing a cross-sectional assessment of clinical and genetic features of movement disorders in MD starting in childhood. The NICNMD registry used in this study has already helped to redefine the clinical phenotype of common mtDNA mutations in Italian mitochondrial patients (e.g., m.3243A > G [ 12 ], m.8344A > G [ 13 ], or single deletions [ 10 ]) and it has been used to investigate several features of MDs, including myoclonus [ 14 ], ocular myopathies [ 11 ], peripheral neuropathy [ 15 ], muscle pain [ 17 ], lipomatosis [ 18 ], and epilepsy [ 16 ]. As of the time of this writing, the registry contains complete information on 1467 patients (last accession date 1 September 2019).…”

“…The aim of the present study was to better investigate the clinical, neuroradiological, and genetic features of movement disorders in childhood-onset MDs on the basis of data collected through the Nationwide Italian Collaborative Network of Mitochondrial Diseases (NICNMD) [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”