Prevention of Adverse Outcomes and Treatment Side Effects in Patients with Neuromuscular Disorders.

In this article, we review prevention of serious adverse clinical outcomes and treatment side effects in patients with neuromuscular disorders including myopathies and myasthenia gravis. While neither of these entities is preventable, their course can often be modified, and severe sequelae may be prevented, with the identification of risk factors and proactive attention toward treatment planning.

Myasthenia gravis and pregnancy.

Myasthenia gravis (MG) is an autoimmune disorder with bimodal age of presentation, occurring in young women of reproductive age and at an older age in men. Occasionally, MG is diagnosed during pregnancy. Management of MG includes symptomatic treatment with cholinesterase inhibitors and immunosuppressive therapy for controlling the disease activity. Treatment of MG in women of reproductive age, who may be contemplating pregnancy, requires discussion regarding the choice of medication as well as the understanding of risks/adverse effects involved with various treatments. During the peripartum period, it is essential to ensure careful monitoring of the disease state along with the well-being of the mother and fetus and to coordinate neonatal monitoring overseen by a multidisciplinary team comprising a high-risk maternal fetal medicine specialist, a neurologist familiar with these complex issues, and a neonatologist.

Value of terminal latency index and sensory electrophysiology in idiopathic and diabetic chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVES: To evaluate sensory electrophysiology, terminal latency index (TLI), and treatment response in idiopathic and diabetic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We performed a retrospective review of 147 patients with CIDP who underwent electrodiagnostic evaluation (January 2000-December 2015). Eighty-nine patients fulfilled electrophysiological criteria described by the Ad hoc Subcommittee of the American Academy of Neurology and Albers et al. Fifty-eight patients were divided into idiopathic (N = 40) and diabetic (N = 18) groups. These groups were compared for age, sex, cerebrospinal fluid protein, response to treatment, sensory response abnormalities, and TLI measurements using chi-square tests for binary and categorical variables and using t-tests and mixed-effects models for continuous variables. RESULTS: The difference in abnormal rates of sensory responses was significant for the sural nerve, with the idiopathic group having a lower rate than the diabetic group (80% vs. 100%, p < 0.001). No group differences in the TLI measurements were significant. CONCLUSIONS: Sural sensory responses may have some value in differentiating idiopathic CIDP from diabetic CIDP. Larger prospective studies are needed to confirm our findings. SIGNIFICANCE: Our study suggests that abnormal sural sensory potentials may have some significance in differentiating idiopathic CIDP from diabetic CIDP.

Suprascapular neuropathy: A review of 87 cases.

INTRODUCTION: Suprascapular neuropathy (SSN) is rare, with an estimated prevalence of 4.3% in patients with shoulder pain. METHODS: This retrospective chart review included patients with SSN seen during a 16-year period. Demographics and clinical information were recorded. Descriptive statistics, including percentages, means, and standard deviations, were computed for the variables of interest for all patients. RESULTS: Of 87 patients included in this study, trauma (n = 27) was the most common cause of SSN, followed by neuralgic amyotrophy (n = 21). Fifty-seven patients had isolated SSN. Others had SSN associated with axillary neuropathy (23 patients), brachial plexopathy (3 patients), and long thoracic, radial, or spinal accessory neuropathy (1 patient each). DISCUSSION: SSN is commonly associated with axillary neuropathy. Trauma remains the most common cause of SSN. Electrodiagnostic findings aid in the initial diagnosis and may indicate the need for close clinical follow-up based on the severity of the axonal injury.

Oculopalatal tremor, facial myokymia and truncal ataxia in a patient with neurosarcoidosis.

Symptomatic palatal tremor (SPT) is the result of a structural lesion, in the form of stroke, trauma or demyelinating disease. SPT is due to contractions of the levator veli palatini and can be accompanied by simultaneous movements of the facial and ocular muscles. Facial myokymia (FM) is a persistent quivering of the facial muscles. FM is usually encountered with conditions involving the pontine tegmentum. We report, to our knowledge, the first patient with neurosarcoidosis with simultaneous SPT and FM. A 49-year-old African American woman, with non-caseating granulomas in a paratracheal lymph node biopsy, presented with progressive gait disturbances for the last 3 years. Neurological examination revealed ataxic speech, bilateral rotatory nystagmus, myokymia of the chin and perioral muscles, palatal tremor without ear click and marked truncal ataxia. MRI demonstrated a lesion involving the facial nucleus and the right middle cerebellar peduncle. Based on exclusion of alternative etiologies, a diagnosis of neurosarcoidosis was made and the patient was started on methotrexate for 9 months, with minimal improvement. She was then switched to intravenous infliximab without major adverse events. The patient's speech and gait ataxia improved and follow up MRI demonstrated resolution of the enhancing lesions. To our knowledge, this is the first reported case of the combination of palatal tremor and FM due to neurosarcoidosis. Methotrexate may fail to produce clinical or radiographic response in up to 39% of patients. Tumor necrosis factor-α inhibitors, such as infliximab, should be considered in refractory cases.

Muscle-specific kinase-antibody-positive myasthenia gravis after autologous bone marrow transplantation.

A 44-year-old man presented with oculobulbar weakness approximately 5 years after autologous bone marrow transplantation (BMT). His workup led to the diagnosis of muscle-specific kinase-antibody-related myasthenia gravis (MG). There has been only one case report of muscle-specific kinase-antibody-positive MG after BMT, which was allogeneic. We report the first case of autologous BMT-associated MG with muscle-specific kinase antibody. The pathogenic mechanisms of immune dysregulation leading to MG after BMT are discussed.

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.

INTRODUCTION: Of the nearly 38 million people in the USA who receive statin therapy, 0.1-0.5% experience severe or life-threatening myopathic side effects. METHODS: We performed a genome-wide association study (GWAS) in a group of patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci. RESULTS: Replication studies in independent groups of severe statin myopathy (n = 190) and statin-tolerant controls (n = 130) resulted in the identification of three single-nucleotide polymorphisms (SNPs), rs9342288, rs1337512, and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (P = 0.0003-0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. CONCLUSION: Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle.

Genetic risk factors associated with lipid-lowering drug-induced myopathies.

Lipid-lowering drugs produce myopathic side effects in up to 7% of treated patients, with severe rhabdomyolysis occurring in as many as 0.5%. Underlying metabolic muscle diseases have not been evaluated extensively. In a cross-sectional study of 136 patients with drug-induced myopathies, we report a higher prevalence of underlying metabolic muscle diseases than expected in the general population. Control groups included 116 patients on therapy with no myopathic symptoms, 100 asymptomatic individuals from the general population never exposed to statins, and 106 patients with non-statin-induced myopathies. Of 110 patients who underwent mutation testing, 10% were heterozygous or homozygous for mutations causing three metabolic myopathies, compared to 3% testing positive among asymptomatic patients on therapy (P = 0.04). The actual number of mutant alleles found in the test group patients was increased fourfold over the control group (P < 0.0001) due to an increased presence of mutation homozygotes. The number of carriers for carnitine palmitoyltransferase II deficiency and for McArdle disease was increased 13- and 20-fold, respectively, over expected general population frequencies. Homozygotes for myoadenylate deaminase deficiency were increased 3.25-fold with no increase in carrier status. In 52% of muscle biopsies from patients, significant biochemical abnormalities were found in mitochondrial or fatty acid metabolism, with 31% having multiple defects. Variable persistent symptoms occurred in 68% of patients despite cessation of therapy. The effect of statins on energy metabolism combined with a genetic susceptibility to triggering of muscle symptoms may account for myopathic outcomes in certain high-risk groups.