MRI patterns of muscle involvement in type 2 and 3 spinal muscular atrophy patients.

Only few studies have reported muscle involvement in spinal muscular atrophy using muscle MRI but this has not been systematically investigated in a large cohort of both pediatric and adult patients with type 2 and type 3 spinal muscular atrophy. The aim of the present study was to define possible patterns of muscle involvement on MRI, assessing both fatty replacement and muscle atrophy, in a cohort of type 2 and type 3 spinal muscular atrophy children and adults (age range 2-45 years), including both ambulant and non-ambulant patients. Muscle MRI protocol consisted in T1-weighted sequences acquired on axial plane covering the pelvis, the thigh, and the leg with contiguous slices. Each muscle was examined through its whole extension using a grading system that allows a semiquantitative evaluation of fatty infiltration. Thigh muscles were also grouped in anterior, posterior, and medial compartment for classification of global atrophy. The results showed a large variability in both type 2 and type 3 spinal muscular atrophy, with a various degree of proximal to distal gradient. Some muscles, such us the adductor longus and gracilis were always selectively spared. In all patients, the involvement was a combination of muscle atrophy and muscle infiltration. The variability observed may help to better understand both natural history and response to new treatments.

VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype.

BACKGROUND: Mitochondrial respiratory chain consists of five complexes encoded by nuclear and mitochondrial genomes. Mitochondrial aminoacyl-tRNA synthetases are key enzymes in the synthesis of such complexes. Bi-allelic variants of VARS2, a nuclear gene encoding for valyl-tRNA (Val-tRNA) synthetase, are associated to several forms of mitochondrial encephalopathies or cardiomyoencephalopathies. Among these, the rare homozygous c.1100C > T (p.Thr367Ile) mutation variably presents with progressive developmental delay, axial hypotonia, limbs spasticity, drug-resistant epilepsy leading, in some cases, to premature death. Yet only six cases, of which three are siblings, harbouring this homozygous mutation have been described worldwide. CASE PRESENTATION: Hereby, we report two additional cases of two non-related young girls from Sardinia, born from non-consanguineous and healthy parents, carrying the aforesaid homozygous VARS2 variant. At onset both the patients presented with worsening psychomotor delay, muscle hypotonia and brisk tendon reflexes. Standard genetic tests were normal, as well as metabolic investigations. Brain MRI showed unspecific progressive abnormalities, such as corpus callosum hypoplasia (patient A) and cerebellar atrophy (patient A and B). Diagnosis was reached by adopting massive parallel next generation sequencing. Notably clinical phenotype of the first patient appears to be milder compared to previous known cases. The second patient eventually developed refractory epilepsy and currently presents with severe global impairment. Because no specific treatment is available as yet, both patients are treated with supporting antioxidant compounds along with symptomatic therapies. CONCLUSIONS: Given the paucity of clinical data about this very rare mitochondrial encephalopathy, our report might contribute to broaden the phenotypic spectrum of the disorder. Moreover, noteworthy, three out of five pedigrees so far described belong to the Northern Sardinia ethnicity.