Myoimaging in the NGS era: the discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features--a case report

Myosin heavy chain 7 related myopathies are rare disorders characterized by a wide phenotypic spectrum and heterogeneous pathological features. In the present study, we performed clinical, morphological, genetic and imaging investigations in three relatives affected by autosomal dominant distal myopathy. Whilst earlier traditional Sanger investigations had pointed to the wrong gene as disease causative, next-generation sequencing allowed us to obtain the definitive molecular genetic diagnosis in the family

Electrophysiological abnormalities in iatrogenic botulism: Two case reports and review of the literature

Therapeutic use of botulinum neurotoxin type A (BoNT/A) is effective, and generally safe. Nevertheless, iatrogenic botulism (IB) is rarely reported as a result of systemic spread of the BoNT/A, causing general weakness, bulbar symptoms and dysautonomia. Suggestive clinical feature are decisive to raise the diagnostic suspicion, which however needs a confirmation in the electrodiagnostic (EDX) study, above all to exclude other treatable diseases. In this study, we report 2 patients who developed IB after receiving therapeutic doses of BoNT/A, assessing the EDX changes, and reviewing the literature on EDX in IB. Although there is not enough data to draw solid conclusions we propose that, in a subject with suggestive clinical features and recent exposure to BoNT/A, the absence of a decremental or incremental response to repetitive nerve stimulation in muscles showing acute denervation changes, is a suggestive finding for the diagnosis of IB

Nefl-Related Charcot-Marie tooth disease due to P440L mutation in two italian families: expanding the phenotype and defining modulating factors

Mutations in the neurofilament polypetide light chain (NEFL) gene account for <1 % of all forms of Charcot-Marie-Tooth (CMT) diseases, and present with different phenotypes, including demyelinating, axonal and intermediate neuropathies and with diverse pattern of transmission, with dominant and recessive inheritance being described. Here we present clinical and molecular data in two new unrelated Italian families, affected with CMT. We studied fifteen subjects (11 women, 4 men), age range 23-62 year. Onset of symptoms was mainly in childhood, with running/walking difficulties; some patients were pauci-asymptomatic; almost all shared variably distributed features of absent/reduced deep tendon reflexes, impaired gait, reduced sensation and distal weakness in the legs. Skeletal deformities were seldom documented and were of mild degree. Additional features included sensorineural hearing loss in three patients, underactive bladder in two patients and cardiac conduction abnormalities, requiring pacemaker implantation, in one child. Central nervous system impairment was not documented in any subject. Neurophysiological investigation disclosed feature suggestive of demyelinating sensory-motor polyneuropathy in one family and resembling an intermediate form in the other. Multigene panel analysis of all known CMT genes revealed two heterozygous variants in NEFL: p.E488K and p.P440L. Whilst, the latter change segregated with the phenotype, the p.E488K variant appeared to act as a modifier factor being associated to axonal nerve damage. Our study expands the array of clinical features associated with NEFL- related CMT

Idiopathic pes cavus in adults is not associated with neurophysiological impairment in the lower limbs

The nerve conduction characteristics of adults with idiopathic pes cavus/hammer toes have not been studied extensively. Among 2048 out-patients (59.5 ± 13.9 years) referring to a laboratory of Neurophysiology in Rome, we recruited 18 patients with idiopathic pes cavus (61.3 ± 12.5 years). Fifty-four age/sex-matched controls were also studied. No nerve conduction differences were observed between patients with and without cavus foot (p > 0.05). The absence of deep tendon reflexes and slight muscle weakness and hypotrophy in the lower limbs were more common in subjects with cavus foot deformity than in controls (p < 0.001). Adult patients with idiopathic pes cavus/hammer toes do not differ from healthy controls from a neurophysiological standpoint, but they could show minor signs of clinical impairment, such as lower limb weakness, hypotrophy and areflexia

Impact of Mézières Rehabilitative Method in Patients with Parkinson’s Disease: A Randomized Controlled Trial

The aim of this study was to assess the efficacy of Mézières method in improving trunk flexibility of the back muscles and balance in patients with Parkinson’s disease (PD). Materials and Methods. Thirty-six patients were randomized into 2 groups: the Mézières treatment group and the control group (home exercise group). The primary outcome was the improvement in balance per the Berg Balance Scale (BBS) and the trunk flexibility of the back for the anterior flexion trunk test. Also, we evaluated pain, gait balance for the Functional Gait Assessment (FGA), disease-related disability for the Modified Parkinson’s Activity Scale and the Unified Parkinson’s Disease Rating Scale (UPDRS), the quality of life, and the functional exercise capacity. All the measures were evaluated at baseline (T0), at the end of the rehabilitative program (T1), and at the 12-week follow-up (T2). Results. In the Mézières group, the BBS (p<.001) and trunk flexion test (p<.001) improved significantly at T1 and remained the same at T2. Between groups, significant changes were reported in FGA (p=.027) and UPDRS Total (p=.007) at T1 and in FGA (p=.03) at T2. Conclusion. The Mézières approach is efficacious in improving the flexibility of the trunk and balance in PD patients

Additional file 1: Figure S1. of Myoimaging in the NGS era: the discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features – a case report

Light microscopy of muscle sections stained with ATPASE (pH 4.3 [a], 4.6 [b], and 9.4 [c]) showing a slight predominance of type I fiber. Several type I fibers are atrophic. Hematoxylin-Eosin stain reveals muscle fiber size variability and an increased number of internal nuclei. (TIF 771 kb

Loss-of-function mutations in the SIGMAR1 gene cause distal hereditary motor neuropathy by impairing ER-mitochondria tethering and Ca2+ signaling

Distal Hereditary Motor Neuropathies (dHMNs) are clinically and genetically heterogeneous neurological conditions characterized by degeneration of the lower motor neurons. So far, 18 dHMN genes have been identified, however about 80% of dHMN cases remain without a molecular diagnosis.By a combination of autozygosity mapping, identity-by-descent segment detection and whole-exome sequencing approaches we identified two novel homozygous mutations in the SIGMAR1 gene (p.E138Q and p.E150K) in two distinct Italian families affected by an autosomal recessive form of HMN.Functional analyses in several neuronal cell lines strongly support the pathogenicity of the mutations and provide insights into the underlying pathomechanisms involving the regulation of ER-mitochondria tethering, Ca(2+) homeostasis and autophagy. Indeed, in\ua0vitro, both mutations reduce cell viability, the formation of abnormal protein aggregates preventing the correct targeting of sigma-1R protein to the mitochondria-associated ER membrane (MAM) and thus impinging on the global Ca(2+) signaling.Our data definitively demonstrate the involvement of SIGMAR1 in motor neuron maintenance and survival by correlating, for the first time in the Caucasian population, mutations in this gene to distal motor dysfunction and highlight the chaperone activity of sigma-1R at the MAM as a critical aspect in dHMN pathology