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Introduction: Charcot-Marie-Tooth type 4C (CMT4C) is an autosomal recessive dysmyelinating neuropathy characterized by precocious and rapidly progressive scoliosis., Methods: Patients in a French-Canadian kindred were evaluated with clinical examination, electrophysiologic study, and genomic DNA extraction., Results: Six of 10 siblings were clinically symptomatic with supportive electrophysiologic features. The proband presented with regional side-to-side sensorimotor asymmetry, typical pes cavus without obvious scoliosis, and unremarkable plain films of the spine. Affected siblings all share symptoms of foot deformity but have variable onset of neuropathic symptoms, degree of extremity weakness, progression of symptoms, and, most notably, evidence of scoliosis. DNA sequence analysis revealed a novel combination of 2 known recessive mutations, p.R904X and p.R954X, in the SH3TC2 gene., Conclusions: A broad spectrum of phenotypes should be considered in the possible diagnosis of CMT4C. The absence of scoliosis or late-onset symptoms should not exclude SH3TC2 from the list of candidate genes under consideration. Age of onset and clinical features were variable and suggest that polygenic factors contribute to the final phenotype., (© 2015 Wiley Periodicals, Inc.)

Introduction: Diagnostic nerve ultrasound is becoming more commonly used by both radiologists and clinicians. The features of different neuromuscular conditions must be described to broaden our understanding and ability to interpret findings., Methods: Our study examines the sonographic features of 7 subjects with hereditary neuropathy with liability to pressure palsies (HNPP) in comparison to 32 controls by measuring the nerve cross-sectional area (CSA) of the median, ulnar and tibial nerves., Results: Significant differences (P < 0.05) in nerve size were found. The HNPP group had a larger CSA for the median nerve at the wrist and ulnar nerve at the elbow (entrapment sites), but not the forearms. The tibial nerve at the ankle was also larger in the HNPP group, suggesting possible concomitant tibial neuropathy at the ankle., Conclusion: These results will help shape imaging protocols to better detect conditions with non-uniform nerve enlargements., (Copyright © 2011 Wiley Periodicals, Inc.)

Muscle stretch reflexes (MSRs) are fundamental to the neurologic examination. Although the fifth, sixth, and seventh cervical roots have appropriate and easily elicited MSRs, the C8 level does not. The C8 reflex is obtained by tapping the thenar eminence, which produces flexion at the interphalyngeal joints of the fingers. To confirm that finger flexion represented an MSR, an externally triggered hammer-skin contact set-up was employed. Surface recording electrodes were placed at one third of the distance between the medial epicondyle and ulnar styloid. This montage produced distinct T-waves with latencies compatible with a reflex arc. Normative data were collected for 75 healthy subjects (150 arms), including 15 from each of five age groups (20-29, 30-39, 40-49, 50-59, > or =60 years). Distance 1 (D1) was measured from the FPL to the C7 spinous process and distance 2 (D2) from C7 to the G1 electrode. A high median neuropathy abolished the T-wave. A distal median nerve block at the carpal tunnel had no effect. Mean latencies (+/- SD) from the respective age groups were as follows: 21.73 +/- 1.16 ms; 22.50 +/- 1.70 ms; 22.19 +/- 1.52 ms; 22.66 +/- 2.13 ms; and 23.97 +/- 1.91 ms. Reflex latencies significantly correlated with age (r = 0.33, P = 0.004), height (r = 0.51, P < 0.0001), and D1 + D2 or arc length (r = 0.74, P < 0.0001). This novel MSR is generated from the FPL tendon and stimulates contraction of the long finger flexors. It therefore represents a clinically useful C8 MSR.

Charcot-Marie-Tooth disease (CMT) is among the most common inherited disorders of the peripheral nervous system, and it is broadly categorized as demyelinating type 1 or axonal type 2 based on nerve conduction studies. Mutations in discrete genes usually segregate into a single phenotype. However, mutations in connexin 32 (Cx32) can produce both axonal and demyelinating CMT phenotypes. Although over 300 mutations have been described in Cx32, somatic mosaicism has only been reported once previously. We report a 39-year-old man who was referred for electrodiagnostic evaluation due to a history of bilateral carpal tunnel syndrome. His physical examination and electrodiagnostic findings demonstrated a mild sensorimotor axonal peripheral neuropathy. Sequencing of his Cx32 (GJB1) gene identified a guanine-to-adenine (G>A) transition at nucleotide position 95. This transition mutation involved approximately one-third of leukocyte-derived genomic DNA. This is the second reported case of somatic mosaicism, and it highlights the phenotypic diversity among CMTX patients.

This case report describes a young man referred for electrodiagnostic evaluation for hand stiffness and intermittent numbness. His needle electromyography revealed diffusely increased insertional and spontaneous motor activity in the form of myotonic discharges. Given the finding of symptomatic myotonia also in his mother, Thomsen myotonia was suspected. Investigations not only confirmed Thomsen myotonia, but also led to the identification of a previously reported heterozygous Becker mutation in both the proband and his mother.

We report 2 cases of Lewis-Sumner syndrome (LSS) diagnosed in patients suffering from rheumatoid arthritis undergoing treatment with the antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody infliximab. While experiencing clinical improvement in their arthritic symptoms, both patients experienced sensory deficits and weakness in multiple nerve distributions. They had electrodiagnostic evidence of motor conduction block and subsequent improvement with intravenous immunoglobulin (IVIg). We describe the details of the cases and review the literature on immune-mediated neuropathies associated with anti-TNF-alpha therapy.

We report a 53-year-old-man who developed rippling muscle disease (RMD) 2 months after starting simvastatin therapy for hypercholesterolemia. He experienced stiffness, myalgias, and classic rippling, which was confirmed on clinical examination. Discontinuation of the statin improved his symptoms. Simvastatin therapy was resumed and resulted in a prompt and severe return of his symptoms. Approximately 1 year after symptom onset he developed mild seropositive oculobulbar myasthenia gravis, which spontaneously remitted after 5 months. We postulate that an immune-mediated disruption of caveolar function was exacerbated by statin exposure. We are unaware of any previous cases of statin-mediated unmasking of RMD.

The pathophysiology of statin-mediated muscle dysfunction is poorly defined. Reductions in skeletal muscle membrane cholesterol were initially thought to account for the range of myopathic reactions, e.g., myalgia, elevated serum creatine kinase, or rhabdomyolysis. This assumption however, does not consider a potential role of the isoprenoids in the pathophysiology of statin myopathy. The observation that derangements in mevalonate kinase (MK), but not more distal enzymes of cholesterologenesis, are associated with a skeletal myopathy suggests a critical role for the isoprenoids in the maintenance of muscle. Statins also deplete the isoprenoid pool by inhibiting the enzyme, beta-hydroxy-beta-methylglutaryl coenzyme A reductase, which is upstream of MK. Identifying candidate proteins that are both dependent on isoprenoid-mediated modification and associated with muscle disease, when genetically mutated, offers further insight into potential mechanisms of statin myopathy. For example, lamin A/C, selenoprotein N, alpha- and beta-dystroglycan, and cytoskeletal G-proteins all require isoprenylation for optimal function. Understanding the pleiotropic effects of protein prenylation, and the potential consequences of a generalized insufficiency of this form of protein modification, may help clarify the molecular pathogenesis of statin myopathy.

We report the case of a 79-year-old man with mild chronic renal failure who developed severe rhabdomyolysis after combined exposure to simvastatin and colchicine. Colchicine induces myopathy through disruption of microtubular function with subsequent vacuolization and pseudomyelinic body accumulation. Statin therapy is associated with myonecrosis, membranous myeloid bodies, and vacuolization, presumably as a function of impaired isoprenoid metabolism. Vesicle trafficking requires small G-protein prenylation and statins can disrupt cytoskeletal integrity. We propose that synergistic cytoskeletal myotoxicity may account for the extreme elevation of serum creatine kinase not previously reported in pure colchicine myopathy.