Database Evaluation for Muscle and Nerve Diseases - DEMAND: An academic neuromuscular coding system

Background: A database which documents the diagnosis of neuromuscular patients is useful for determining the types of patients referred to academic centers and for identifying participants for clinical trials and other studies. The ICD-9 or ICD-10 numeric systems are insufficiently detailed for this purpose. Objective: To develop a database for neuromuscular diagnoses Methods: We developed a detailed diagnostic coding system for neuromuscular diseases called DEMAND: Database Evaluation for Muscle and Nerve Diseases that has been adopted by neuromuscular clinics at University of Texas Health Science Center San Antonio (UTHSCSA), Ohio State University (OSU), University of Kansas Medical Center (KUMC), and University of Texas Southwestern (UTSW). At the initial visit, patients are assigned a diagnostic code which can be revised later if appropriate. Fields include patient’s name, date of birth, and diagnostic code. The neuromuscular database consisted of 457 codes. Each code has a prefix (MUS or PNS) followed by a three-digit number. Depending on whether muscle or nerve is primarily involved, there are eight broad groups: motor neuron disease (MUS codes 100-139); neuromuscular junction disorders (MUS 200-217); acquired and hereditary myopathies (MUS 300-600s); acquired and hereditary polyneuropathies (PNS 100-400); mononeuropathies (PNS 500s); plexopathies (PNS 600s); radiculopathies (PNS 700s); and mononeuritis multiplex (PNS 800s). Results: During a period of 10 years, 17,163 of patients were entered (1,752 at UTHSCSA, 1,840 at OSU, 3,699 at KUMC, 9,872 at UTSW). The number of patients in several broad categories are: 3,080 motor neuron disease; 1,575 neuromuscular junction disease; 1,851 muscular dystrophies; 633 inflammatory myopathies; 1,090 hereditary neuropathies; 1,001 immune-mediated polyneuropathies; 620 metabolic/toxic polyneuropathies; 535 mononeuropathies; 296 plexopathies; and 769 radiculopathies. Conclusion: A detailed diagnostic neuromuscular database can be utilized at multiple academic centers. The database should be simple without too many fields to complete, to ensure compliance during busy clinic operations. This database has been very useful in identifying groups of patients for retrospective, observational studies and for prospective treatment studies including trials for Amyotrophic Lateral Sclerosis (ALS), Muscular Dystrophies (MD), Myasthenia Gravis (MG), and retrospective studies of Primary Lateral Sclerosis (PLS), chronic inflammatory demyelinating neuropathy (CIDP), etc

Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis

Objective: To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. Methods: Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. Results: The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect 7.29 points, 95% confidence interval 2.26 to 12.32, p 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). Conclusions: DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. Classification of evidence: These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Clinical effects of irrigation with Saussurea lappa extract in the treatment of chronic periodontitis: A pilot randomized trial

Introduction: Periodontitis is a chronic inflammatory disease manifested as the destruction of tooth supporting tissues, which may progress to tooth loss. The chemical antimicrobial agents are often applied locally into the periodontal pocket as adjuncts to conventional mechanical periodontal therapy, but these have various adverse effects. Root extract of Saussurea lappa has shown anti-inflammatory and anti-bacterial properties. Hence, the present study was aimed to assess and compare the effect of root extract of S. lappa to chlorhexidine gluconate as subgingival irrigant as an adjunct to scaling and root planing (SRP). Materials and Methods: Thirty chronic periodontitis patients in the age group of 25-45 years were selected for the study. Five hundred and forty periodontal pockets were treated by three different procedures: Group1: Subjects treated by SRP only, Group 2: In addition to SRP, irrigation with S. lappa extract was done and Group 3: Chlorhexidine was used as irrigant along with SRP. Periodontal clinical recordings (modified sulcular bleeding index, probing pocket depth, clinical attachment level, and the presence of pus discharge) were done at 0, 7, 14, 28, and 42 days. Results: The periodontal parameters studied improved in all the three groups over the time period. In 4-5 mm pockets, S. lappa treated group showed significant improvement than chlorhexidine treated group. Furthermore, a dramatic decrease in periodontal pockets with pus discharge was seen in this group. Conclusion: Subgingival irrigation with S. lappa might be a promising adjunct to conventional treatment options in the management of periodontal infections

Aurora kinase A-mediated phosphorylation of mPOU at a specific site drives skeletal muscle differentiation

10.1093/jb/mvz088JOURNAL OF BIOCHEMISTRY1672195-20

Review of the Diagnosis and Treatment of Periodic Paralysis.

Periodic paralyses (PPs) are rare neuromuscular disorders caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes. PPs include hypokalemic paralysis, hyperkalemic paralysis, and Andersen-Tawil syndrome. Common features of PP include autosomal dominant inheritance, onset typically in the first or second decades, episodic attacks of flaccid weakness, which are often triggered by diet or rest after exercise. Diagnosis is based on the characteristic clinic presentation then confirmed by genetic testing. In the absence of an identified genetic mutation, documented low or high potassium levels during attacks or a decrement on long exercise testing support diagnosis. The treatment approach should include both management of acute attacks and prevention of attacks. Treatments include behavioral interventions directed at avoidance of triggers, modification of potassium levels, diuretics, and carbonic anhydrase inhibitors. Muscle Nerve 57: 522-530, 2018