Denervation In Distal Muscles Research Articles

A novel MFN2 mutation causes variable clinical severity in a multi-generational CMT2 family

Dominant mutations in MFN2 cause a range of phenotypes, including severe, early-onset axonal neuropathy, “classical CMT2”, and late-onset axonal neuropathy. We found a novel MFN2 mutation - c.283A>G (p.Arg95Gly) - that results in an axonal neuropathy with variable clinical severity in a multigenerational family. In affected family members, electromyography showed moderate to severe, chronic denervation in distal muscles. Such variable clinical severity highlights the need to do careful assessments of at risk individuals when assessing MFN2 variants.

Case report: Auto-immune polymyositis secondary to EBV-infection

Introduction: Polymyositis is an immune-mediated syndrome secondary to defect in cellular immunity, frequently associated with other autoimmune diseases, maybe idiopathic, or known etiology which have the most frequent cancer or infection. In the case of viral infections, an agent can cause an injury uprightly muscle tissue, also damaging the vascular endothelium to release cytokines, which leads to a defect in expression of major histocompatibility complex and the susceptibility of muscle to destruction. In the clinical case which is described below, as an etiological factor for polymyositis arises an acute Epstein–Barr virus. Case report: Man, 45 years old, leucodermic firefighter with a history of chronic sinusitis and a former smoker. Without chronic medication. Appealed to the U.S. by frame with a month of evolution of generalized and progressive myalgia, generalized decrease in muscle strength with predominantly distal, anorexia, night sweats and weight loss quantified in about 10 kg. No fever or other symptoms. On admission he had noted the general decline in muscle mass, flaccid tetraparesia 3/3 predominantly distal — grade 3 in lower limbs, sensitively maintained. AST 708 UI/L, ALT 577 UI/L, LDH 4015 UI/L, and rhabdomyolysis with CK 25,129 UI/L. Serial serology for EBV was indicative of recent infection, TC-chest revealed consolidated nonspecific changes and pathological results of muscle biopsy revealed an extensive area of necrosis with inflammatory infiltrate with eosinophils and B lymphocytes. Described neurogenic EMG signs of active denervation in distal muscles of the lower limbs. The study to autoimmunity, Ac. Anti-SRP positive and initially positive ANA,with subsequent negative. Microbiological, serological to zoonoses, thyroid function and neoplasm were negative. For worsening muscle atrophy, the patient developed a restrictive ventilatory framework, diffusion of CO2 decreased and elevated markers of myocardial necrosis (without electrocardiographic or ecocardiographic changes) was transferred to Unit of Intensive Therapy and was subjected to non-invasive ventilation and initiated therapy 3 mg/kg/day with methylprednisolone. Despite on the poor prognosis associated with anti-SPR, the patient had a good clinical outcome in physical rehabilitation program, with the interference myopathy secondary to corticosteroids; did complete weaning of corticosteroids. Complaints about pain remained reasonably controlled with pregabalin. She was discharged with diagnosis of polymyositis with Ac anti-SRP secondary to EBV infection, followed in Outpatient Internal Medicine and Autoimmune Diseases.

New findings in the ataxia of Charlevoix–Saguenay

The aim of the study was to enhance our understanding of the pathogenesis of the ataxia of Charlevoix-Saguenay, based on the findings presented herein. Five patients with a molecular diagnosis of this disease underwent clinical, radiological, ophthalmologic and electrophysiological examinations. Five novel mutations, which included nonsense and missense variants, were identified, with these resulting in milder phenotypes. In addition to the usual manifestations, a straight dorsal spine was found in every case, and imaging techniques showed loss of the dorsal kyphosis. Cranial MRI demonstrated hypointense linear striations at the pons. Tensor diffusion MRI sequences revealed that these striations corresponded with hyperplastic pontocerebellar fibres, and tractographic sequences showed interrupted pyramidal tracts at the pons. Ocular coherence tomography demonstrated abnormal thickness of the nerve fibre layer. Electrophysiological studies showed nerve conduction abnormalities compatible with a dysmyelinating neuropathy, with signs of chronic denervation in distal muscles. The authors suggest that the hyperplastic pontocerebellar fibres compress the pyramidal tracts at the pons, and that the amount of retinal fibres traversing the optic discs is enlarged. These facts point to the contribution of an abnormal developmental mechanism in the ataxia of Charlevoix-Saguenay. Accordingly, spasticity would be mediated by compression of the pyramidal tracts, neuromuscular symptoms by secondary axonal degeneration superimposed on the peripheral myelinopathy, while the cause of the progressive ataxia remains speculative. The distinctive aspect of the dorsal spine could be of help in the clinical diagnosis.

N88S mutation in the BSCL2 gene in a Serbian family with distal hereditary motor neuropathy type V or Silver syndrome

BackgroundDistal hereditary motor neuropathy type V (dHMN-V) and Silver syndrome are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) gene or Seipin. AimTo report the first Serbian family with a BSCL2 mutation showing variable expression within the family. Patients and methodsA 55-year-old woman presented with weakness of both hands at the age of 45. At age 47, she noticed distal muscle weakness and atrophy in her legs. Physical examination revealed atrophy and weakness of small hand muscles and mild atrophy and weakness of the lower limbs. There was generalized hyperreflexia with the exception of ankle reflexes which were diminished. Her 25year-old son had only stiffness of both legs at the age of 22. Physical examination revealed only generalized hyporeflexia. The third affected member in this family was her 55year-old cousin who showed a more prominent involvement of leg muscles with mild asymmetrical weakness of hand muscles and no pyramidal tract features. ResultsIn all three patients sensory nerve conduction velocities (NCV) were normal in all extremities. Compound muscle action potential (CMAP) amplitudes were markedly reduced in all patients. Concentric needle EMG showed evidence of chronic denervation in distal muscles. DNA sequencing of BSCL2 was performed and a heterozygous N88S missense mutation in BSCL2 gene was detected in all three patients. ConclusionThis report is further confirmation of phenotypic heterogenity due to the N88S mutation of BSCL2 gene in the same family.

Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations

We describe clinical, electrophysiological, histopathological and molecular features of a unique disease caused by mutations in the glycyl-tRNA synthetase (GARS) gene. Sixty patients from five multigenerational families have been evaluated. The disease is characterized by adolescent onset of weakness, and atrophy of thenar and first dorsal interosseus muscles progressing to involve foot and peroneal muscles in most but not all cases. Mild to moderate sensory deficits develop in a minority of patients. Neurophysiologically confirmed chronic denervation in distal muscles with reduced compound motor action potentials were features consistent with both motor neuronal and axonal pathology. Sural nerve biopsy showed mild to moderate selective loss of small- and medium-sized myelinated and small unmyelinated axons, although sensory nerve action potentials were not significantly decreased. Based on the presence or absence of sensory changes, the disease phenotype was initially defined as distal spinal muscular atrophy type V (dSMA-V) in three families, Charcot-Marie-Tooth disease type 2D (CMT2D) in a single family, and as either dSMA-V or CMT2D in patients of another large family. Linkage to chromosome 7p15 and the presence of disease-associated heterozygous GARS mutations have been identified in patients from each of the five studied families. We conclude that patients with GARS mutations present a clinical continuum of predominantly motor distal neuronopathy/axonopathy with mild to moderate sensory involvement that varies between the families and between members of the same family. Awareness of these overlapping clinical phenotypes associated with mutations in GARS will facilitate identification of this disorder in additional families and direct future research toward better understanding of its pathogenesis.

Distal Myasthenia Gravis With a Decrement, an Increment, and Denervation

We present two patients with distal myasthenia gravis poorly responsive to immunomodulatory therapy. In addition to a typical decrement on slow repetitive nerve stimulation, both had borderline to low compound muscle action potential (CMAP) amplitudes, a large increment in CMAP amplitude and area after exercise, and active denervation in distal muscles. Both had elevated acetylcholine receptor antibody (AChR Ab) levels, but normal voltage-gated calcium channel antibody levels. We hypothesize that these electrophysiological findings represent a more severe form of myasthenia gravis.

Generator sites for spontaneous activity in neuromyotonia. An EMG study

A 16-year-old female patient with symptoms and signs compatible with neuromyotonia was studied with various neurophysiological tests and with muscle biopsy. Nerve conduction studies revealed signs of axonal motor neuropathy. EMG showed denervation in distal muscles, and moderate neurogenic changes in other muscles. Abundant spontaneous motor unit activity was recorded in all muscles. This activity did not disappear upon proximal nerve blockade with local anaesthetics. Based on the shape of spontaneous discharges and their behaviour on nerve stimulation and during voluntary effort, the site of generation was suggested. This varied for different discharges, from proximally in the nerve, to various sites along the intramuscular nerve tree. In some axons there were signs of conduction block proximal to the generation site for the spontaneous discharges. Different axons showed various degrees of abnormality; local hyperexcitability triggering new impulses only after the passage of a preceding impulse, increased hyperexcitability generating spontaneous activity, total impulse blocking, and finally axonal degeneration. Treatment with dihydantoin reduced the spontaneous activity with concomitant clinical improvement.