The impact of myasthenia gravis severity on work and daily activities.

INTRODUCTION/AIMS: People with myasthenia gravis (MG) experience impaired quality of life. However, the impact of MG symptoms on work productivity has not been well-studied. We aimed to evaluate this impact and to examine associations between disease severity and the degree of impairment. METHODS: Data were drawn from the Adelphi MG Disease-Specific Programme™, a multinational (USA, France, Germany, Italy, Spain, UK) survey completed by physicians and their patients with MG in 2020. Patient-reported measures included the Work Productivity and Activity Impairment (WPAI): Specific Health Problem questionnaire. RESULTS: The WPAI questionnaire was completed by 330 patients. Among those currently employed, the mean percentage of work time missed (absenteeism) was 13.3% (N = 116), percentage impairment of productivity at work (presenteeism) was 26.7% (N = 121), and overall work impairment was 30.0% (N = 110). Across all patients, impairment of non-work-related activities due to health problems (ADL impairment) was 39.2% (N = 330). Regression analysis indicated that impairment differed according to MG Foundation of America (MGFA) class (p = .0147, p < .0001, p < .0001 and p < .0001 for absenteeism, presenteeism, overall work impairment and ADL impairment, respectively). Being MGFA class III/IV was a predictor of presenteeism, overall work impairment and ADL impairment in a predictor model. DISCUSSION: Patients with MG experience substantial work impairment particularly those with more severe symptoms, highlighting an important way in which patient quality of life is negatively affected. More effective treatment strategies would enable patients to lead more productive lives and could impact decisions relating to work and career.

Parkinson's Disease Dementia Patients: Expression of Glia Maturation Factor in the Brain.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease characterized by the presence of dopaminergic neuronal loss and motor disorders. PD dementia (PDD) is a cognitive disorder that affects many PD patients. We have previously demonstrated the proinflammatory role of the glia maturation factor (GMF) in neuroinflammation and neurodegeneration in AD, PD, traumatic brain injury (TBI), and experimental autoimmune encephalomyelitis (EAE) in human brains and animal models. The purpose of this study was to investigate the expression of the GMF in the human PDD brain. We analyzed the expression pattern of the GMF protein in conjunction with amyloid plaques (APs) and neurofibrillary tangles (NFTs) in the substantia nigra (SN) and striatum of PDD brains using immunostaining. We detected a large number of GMF-positive glial fibrillary acidic protein (GFAP) reactive astrocytes, especially abundant in areas with degenerating dopaminergic neurons within the SN and striatum in PDD. Additionally, we observed excess levels of GMF in glial cells in the vicinity of APs, and NFTs in the SN and striatum of PDD and non-PDD patients. We found that the majority of GMF-positive immunoreactive glial cells were co-localized with GFAP-reactive astrocytes. Our findings suggest that the GMF may be involved in the pathogenesis of PDD.

Safety and outcomes with efgartigimod use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice.

INTRODUCTION/AIMS: Multiple novel therapies have been approved for patients with myasthenia gravis. Our aim is to describe the early experience of efgartigimod use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG). METHODS: This multicenter retrospective study included AChR+ve gMG patients from five major neuromuscular centers who were treated with efgartigimod and had both pre- and post-efgartigimod myasthenia gravis activities of daily living (MG-ADL) scores. Information regarding MG history, concomitant treatment(s), MG-ADL and other MG-specific measures, laboratory data, and adverse events were recorded. RESULTS: A total of 37 patients (M:23, F:14) with a mean age of 65.56 (±14.74) y were included in this cohort. A total of 36/37 patients completed at least one cycle and 28 patients completed at least two cycles of efgartigimod. A total of 72% (26/36) of patients had a clinically meaningful reduction (≥2 point change) in MG-ADL after the completion of the first cycle of efgartigimod (mean pre-efgartigimod 8.02) (±3.09) versus post-efgartigimod 4.33 (±3.62). Twenty-five percent (9/36) achieved minimal symptom expression status after one cycle and 25% (7/28) after the second cycle. Treatment benefit was sustained after cycle 2. Three out of four patients with thymoma in this cohort had clinically significant reductions in MG-ADL scores. Immunoglobulin G (IgG) levels decreased by about 60% (n = 10). One patient had a relapse of Clostridium difficile infection resulting in the discontinuation of therapy. Four patients had mild side effects. DISCUSSION: Efgartigimod led to clinically meaningful improvement in MG-ADL in diverse AChR+ve gMG patients but treatment frequency to achieve optimal symptom control needs to be explored.

Analysis of length of stay and treatment emergent complications in hospitalized myasthenia gravis patients with exacerbation.

INTRODUCTION: AIMS Myasthenia Gravis (MG) is an autoimmune neuromuscular disease in which patients suffer from recurrent exacerbation. There are insufficient data measuring the effects of the resources employed before and during acute exacerbation on subsequent disease outcomes. This study aims to identify factors which lead to lengthened hospital stay. METHODS: This is a retrospective chart review of acute MG exacerbations requiring hospitalization. Exacerbations were identified using ICD-9/ICD-10 codes and considered the following variables: age and Myasthenia Gravis Foundation of America (MGFA) class at initial MG diagnosis, age and MGFA class at exacerbation, sex, thymectomy, cause of exacerbation, treatment regimen at time of exacerbation, inpatient treatment regimen, length of hospital stay (LOS), intubation, use of noninvasive ventilation, complications, and disposition. RESULTS: Seventy patients with 141 hospitalizations were identified. Crisis management characterized by intubation and plasmapheresis positively correlated with LOS (both p < .001). Almost 1/5 hospitalizations required intubation. Previous thymectomy negatively correlated with LOS (p < .05). In contrast, male sex correlated with longer LOS (p < .05). One-third of hospital stays were followed by discharge to a post-acute care facility, 7% home with home health, and 1 hospitalization resulted in death. DISCUSSION: Plasmapheresis, intubation, and male sex were associated with increased LOS in acute MG exacerbation. Intubation appears to be the strongest predictor of LOS. Those with previous thymectomy had shorter hospital stays. The role of thymectomy in the acute setting merits further analysis.

Impact of COVID-19 infection among myasthenia gravis patients- a Cerner Real-World DataTM study.

BACKGROUND: Myasthenia gravis (MG) is an auto-immune disease, and the mainstay of therapy is immunomodulation. Such patients are at high risk of acquiring any infections. Hence, we sought to determine the impact of the current global pandemic COVID-19 infection in MG patients. METHODS: For our study, we used Cerner Real-World DataTM that was provided through Cerner's HealtheDataLab research tool. We ran a database query from January 2019 to July 2020 in our study and identified myasthenia patients with and without COVID-19 infection. To extract these patients' data, we used ICD 9-CM, ICD-10, and SNOMED-CT codes. We reported the data using means, range, and prevalence rates, and the p-values were calculated using the two-sample t-test and Pearson's chi-squared test. RESULTS: In the COVID-19 data set, a total of twenty-seven myasthenia patients were identified with a positive COVID-19 infection, and four were diagnosed with an exacerbation. The male to female ratio was equal and one unknown gender (3.7%) with a mean (± SD) age of 64.33 ± 18.42 years. This study group was compared with a non-COVID-19 data set in which a total of sixty-four myasthenia patients were identified, and twenty-three had an exacerbation. Among the 13 hospitalized patients in the two groups, the mean length of hospitalization for the myasthenia patients in the COVID-19 data set was 8.28 days (n = 7), and the non-COVID-19 set was 4.33 days (n = 6), and it was statistically significant (p-value= 0.007). CONCLUSIONS: The mean length of hospital stay is prolonged in myasthenia patients who tested positive for COVID-19.

Real-Time Noninvasive Bioluminescence, Ultrasound and Photoacoustic Imaging in NFκB-RE-Luc Transgenic Mice Reveal Glia Maturation Factor-Mediated Immediate and Sustained Spatio-Temporal Activation of NFκB Signaling Post-Traumatic Brain Injury in a Gender-Specific Manner.

Neurotrauma especially traumatic brain injury (TBI) is the leading cause of death and disability worldwide. To improve upon the early diagnosis and develop precision-targeted therapies for TBI, it is critical to understand the underlying molecular mechanisms and signaling pathways. The transcription factor, nuclear factor kappa B (NFκB), which is ubiquitously expressed, plays a crucial role in the normal cell survival, proliferation, differentiation, function, as well as in disease states like neuroinflammation and neurodegeneration. Here, we hypothesized that real-time noninvasive bioluminescence molecular imaging allows rapid and precise monitoring of TBI-induced immediate and rapid spatio-temporal activation of NFκB signaling pathway in response to Glia maturation factor (GMF) upregulation which in turn leads to neuroinflammation and neurodegeneration post-TBI. To test and validate our hypothesis and to gain novel mechanistic insights, we subjected NFκB-RE-Luc transgenic male and female mice to TBI and performed real-time noninvasive bioluminescence imaging (BLI) as well as photoacoustic and ultrasound imaging (PAI). Our BLI data revealed that TBI leads to an immediate and sustained activation of NFκB signaling. Further, our BLI data suggest that especially in male NFκB-RE-Luc transgenic mice subjected to TBI, in addition to brain, there is widespread activation of NFκB signaling in multiple organs. However, in the case of the female NFκB-RE-Luc transgenic mice, TBI induces a very specific and localized activation of NFκB signaling in the brain. Further, our microRNA data suggest that TBI induces significant upregulation of mir-9-5p, mir-21a-5p, mir-34a-5p, mir-16-3p, as well as mir-155-5p within 24 h and these microRNAs can be successfully used as TBI-specific biomarkers. To the best of our knowledge, this is one of the first and unique study of its kind to report immediate and sustained activation of NFκB signaling post-TBI in a gender-specific manner by utilizing real-time non-invasive BLI and PAI in NFκB-RE-Luc transgenic mice. Our study will prove immensely beneficial to gain novel mechanistic insights underlying TBI, unravel novel therapeutic targets, as well as enable us to monitor in real-time the response to innovative TBI-specific precision-targeted gene and stem cell-based precision medicine.

Anti-calcitonin gene-related peptide monoclonal antibodies for neuropathic pain in patients with migraine headache.

INTRODUCTION: There is increasing evidence that calcitonin gene-related peptide (CGRP) plays a role in the development of neuropathic pain, a common feature of peripheral neuropathy. Although clinical studies have shown that anti-CGRP monoclonal antibodies are highly efficacious for migraine headache prophylaxis, their effects on nonheadache chronic pain conditions, including neuropathic pain, in humans are unknown. Therefore, the aim of this study was to assess the effectiveness of anti-CGRP monoclonal antibodies for neuropathic pain in patients with coexisting chronic migraine. METHODS: A retrospective chart review was conducted of 14 patients with chronic migraine and peripheral neuropathy. All patients were treated with anti-CGRP monoclonal antibodies. We collected data on patient-reported scores on the Neuropathy Pain Scale (NPS) and the frequency of migraine headache days (MHDs) per month. Data were collected 3 and 0 months before and 3, 6, 9, and 12 months after treatment with anti-CGRP medications. RESULTS: With treatment of anti-CGRP monoclonal antibodies, patients reported a 41.7% decrease in NPS scores from 89.3 at baseline to 52.1 at 12 months posttreatment (P < .05). In addition, there was a 33.3% decrease in MHDs per month from 19.8 at baseline to 13.2 at 12 months posttreatment (P < .05). DISCUSSION: Administration of anti-CGRP medications significantly improved neuropathic pain in patients who also had chronic migraine. To confirm these promising outcomes, it would be worthwhile to conduct a blinded, randomized study with a larger population of patients.

Relative effects of forced vital capacity and ALSFRS-R on survival in ALS.

INTRODUCTION/AIM: Amyotrophic lateral sclerosis (ALS) is a degenerative neuromuscular disease with marked clinical heterogeneity. This heterogeneity can be partly captured by clinical measures, such as the forced vital capacity (FVC) and ALS Functional Rating Scale-Revised (ALSFRS-R). We aimed to further characterize the performance of these clinical measures, including their independence and additivity, in predicting mortality. METHODS: We leveraged the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT ALS) database, which includes data from 23 clinical trials (n = 2050). The primary exposures were baseline FVC and ALSFRS-R. The primary outcome was 1-y mortality. We performed correlation analyses, survival analyses and assessed classification performance using receiver operator characteristic (ROC) curves. RESULTS: FVC and ALSFRS-R were weakly correlated (r = 0.31, p < .001). A 1-SD increase in FVC (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.59-0.74) and ALSFRS-R (HR: 0.75; 95% CI: 0.68-0.82) were associated with reduced risk of 1-y mortality. ROC analyses showed optimal predictive cutoffs at 80% for FVC (area under the curve [AUC]: 0.69) and 38 for ALSFRS-R (AUC: 0.67). After stratifying patients based on these cutoffs, we found a marked reduction (HR: 0.25; 95% CI: 0.19-0.33) in incident mortality for patients in the high FVC and high ALSFRS-R group relative to the low FVC and low ALSFRS-R group. DISCUSSION: ALSFRS-R and FVC are comparable predictors of survival that are only weakly correlated. When considered together, they synergistically predict survival. As such, consideration of both measures should be a routine part of prognostication in care of patients with ALS.

Palliative care in amyotrophic lateral sclerosis clinics: A survey of NEALS consortium membership.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition managed with a multidisciplinary approach. Palliative care is important for this approach, but there is a lack of recommendations for the role and involvement of palliative medicine (PM) specialists in multidisciplinary ALS care. METHODS: This questionnaire-based survey assessed the state of palliative care in selective sites that are a part of Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS). RESULTS: Twenty-seven percent of the sites included palliative care specialists as a part of their ALS clinics and they were introduced to the patients and family by ALS specialists (75.94%) usually at an advanced stage of ALS. DISCUSSION: Our study when compared with other study results having a similar aim showed that there is a variability in the practice of palliative care specialists in ALS clinics. Having evidence-based guidelines will help in the management of ALS patients more effectively.

Approach to Limb Weakness.

"Approach to limb weakness" provides an overview of the pathways of the motor system and the type of weakness seen with pathology at each level from the cortex to the muscle. This article provides the clinical pearls needed to identify different patterns of weakness and accurately localize the level of weakness. It offers important pointers that help distinguish among the different etiologies of weakness at each level, as well as various diagnostic approaches and treatments of diseases that lead to limb weakness. The diagnoses discussed are meant to be representative and not exhaustive, as a complete differential for each pattern of weakness is beyond the scope of this article.

Clinical features with anti fibroblast growth factor receptor 3 (FGFR3) antibody-related polyneuropathy: a retrospective study.

BACKGROUND: Despite its initial association with sensory neuropathies, anti-fibroblast growth factor receptor 3 (FGFR3) antibodies have been since reported with a broad range of neuropathies and clinical features. The aim of the study is to report the clinical and electro diagnostic findings in a cohort of patients with sensory or sensorimotor polyneuropathy and anti-FGFR3 antibodies. METHODS: We performed a retrospective chart review to assess the clinical characteristics of patients with sensory or sensorimotor neuropathy related to FGFR3 antibodies. Descriptive statistics were reported using frequencies and percentages for categorical variables and median and interquartile range (IQR) for continuous variables. RESULTS: This study included 14 patients (9 women) with a median age of 51.9 years (IQR 48-57). The most common presenting symptoms were painful paresthesia (100%), gait instability (42.9%), constitutional symptoms (42.9%), and autonomic symptoms (28.6%). Onset of symptoms was chronic (≥12 weeks) in eight patients (57.1%). Examination showed a distal loss of sensation to pin prick (100%), as well as impaired vibration sensation (78.6%) and proprioception (35.7%), in the distal extremities. We also observed mild weakness in the distal lower-extremities (42.9%). Three patients (21.4%) had trigeminal neuralgia, three patients (21.4%) had co-existing autoimmune disease, and one patient (7.1%) had a history of renal cell carcinoma. The mean titer of FGFR3 antibody was 14,285.71 (IQR 5000-16,750). All 14 patients produced normal results in the neuropathy workup. Nerve conduction study and electromyography showed sensory axonal neuropathy in four patients (28.6%), sensorimotor axonal neuropathy in seven patients (50%), and a normal result in three patients (21.4%). For those with a normal NCS/EMG, a skin biopsy showed a non-length-dependent small fiber neuropathy. CONCLUSIONS: Neuropathy related to FGFR3 antibodies can potentially involve small and large fibers, sensory and motor fibers, and even the trigeminal nerve, which contributes to a highly variable clinical presentation.

Adverse Side Effects Associated with Corticosteroid Therapy: A Study in 39 Patients with Generalized Myasthenia Gravis.

BACKGROUND The tolerability of high-dose oral corticosteroids in patients with generalized myasthenia gravis (gMG) has not been systematically assessed. We evaluated adverse side effects (ASEs) of corticosteroid treatment in patients with gMG. MATERIAL AND METHODS Retrospective analysis was conducted of ASEs reported as being related to corticosteroid treatment in 39 patients with gMG who were treated with oral corticosteroids for ≥1 year. RESULTS Median (interquartile range [IQR]) age was 60 (21) years, 53.8% of patients were women, and 66.7% were aged ≤65 years. Median (IQR) prednisone treatment duration was 14 (2) months; median (IQR) daily dose was 40 (15) mg. The median number of ASEs reported as corticosteroid-related was 2/patient (IQR, 1). Pre-diabetes and weight gain were most common (each 43.6% of patients). Bruising, insomnia, and osteoporosis were more prevalent in patients aged >65 years, while irritability, osteopenia, and pre-diabetes were more common in patients aged £65 years, although differences were not statistically significant. Irritability and weight gain were more prevalent in women (P=0.010 for irritability); osteoporosis and pre-diabetes more common in men (P=0.015 for osteoporosis). ASEs were generally more common in the high-dose prednisone group (>30 mg/day), but were only statistically significant for irritability (P=0.001). CONCLUSIONS Corticosteroid-related ASEs were common in patients with gMG. Some of these ASEs can have serious medical consequences, and certain ASEs appeared to be associated with specific patient characteristics. Demographics and comorbidities of patients with gMG must be carefully considered before corticosteroid initiation. Potential ASEs, such as unanticipated osteoporosis in men, require extra vigilance.

Clinical experience with maintenance therapeutic plasma exchange in refractory generalized myasthenia gravis.

BACKGROUND: Despite the availability of several immunomodulatory therapies, about 20% of myasthenia gravis (MG) patients remain refractory to conventional treatments. There is limited evidence to support the use of maintenance therapeutic plasma exchange (TPE) therapy for refractory generalized MG. METHODS: Retrospective chart review of 14 patients with refractory generalized MG treated for 12 months with maintenance TPE therapy. Outcome measures were myasthenia gravis composite (MGC) score, myasthenia gravis activities of daily living (MG-ADL), number of acute exacerbations, medication changes, and adverse events. Data were collected at 3 monthly intervals for 12 months before and after initiation of TPE therapy. RESULTS: Clinically meaningful reductions in mean MG-ADL (>2 points) (mean MG-ADL score: 9.9 ± 0.5; 12-month pre-TPE to 5.2 ± 0.9; 12-month post-TPE) and MGC (>3 points) (mean MGC score: 25.2 ± 1.6; 12-month pre-TPE to 11.7 ± 1.4; 12-month post-TPE) were observed at 3 months following initiation of TPE and were maintained up to 12 months in all patients. After 12 months of TPE therapy, all patients had a significant reduction in daily prednisone and pyridostigmine use. Patients previously on IVIG or rituximab therapy were successfully weaned off both treatments. There was a significant reduction in acute MG exacerbations; 7.8 ± 1.1 mean exacerbations/patient (12-month pre-TPE) to 2 ± 1.1 mean exacerbations/patient (12-month post-TPE). CONCLUSION: Over a period of 12 months, maintenance TPE therapy improved MG-ADL, and MGC with decreased immunosuppressant requirement, while being well-tolerated.

Expanding medical student interaction in neurology with a redesigned student interest group in neurology (sign) chapter.

BACKGROUND: Student Interest Group in Neurology (SIGN) chapters across the medical schools in the United States provide opportunities for medical students to participate in clinical, research, and service activities in neurology. Despite these, applicants for the field of neurology have traditionally been low. METHODS: Following changes were introduced: an open board style SIGN chapter executive committee with greater active engagement of first and second year students. New activities included journal clubs, hands on workshops, celebration/cause events (example ALS walk). In addition, a free neurology clinic was introduced. Activities were planned in consultation with office of medical education, and were organized during 'down times'. Data on student enrollment, activities successfully carried out, students interested in neurology residency, number of neurology-related research projects with student involvement were collected prior to changes and compared to values after changes were introduced. RESULTS: Post intervention, student engagement in neurology activities and projects increased significantly. However, a similar increase in applications to neurology residency was not yet observed. CONCLUSIONS: An open chapter with early engagement and involvement of first and second year medical students, creating a variety of chapter activities with greater hands on involvement, planned in conjunction with office of medical education has reinvigorated our SIGN chapter.

AANEM survey of training in electrodiagnostic medicine in U.S. residency programs.

BACKGROUND: Little literature exists describing resident training in peripheral electrodiagnosis (EDX). METHODS: U.S. residency programs in neurology and physical medicine and rehabilitation (PM&R) were surveyed by the AANEM (American Association of Neuromuscular and Electrodiagnostic Medicine) on specific features of EDX training. RESULTS: Ninety-seven programs responded to the survey. Training duration was 4-8 weeks in most neurology programs; training averaged 22 weeks in PM&R programs. EDX experience was required in all PM&R and in 90% of neurology programs. Results varied greatly for the residency years of training, pulling of residents for other responsibilities, participation in continuity clinics, number of teaching physicians, number of needle examinations performed, organization of nerve conduction training, written/oral examinations, muscle/nerve biopsy reviews, and training materials. CONCLUSIONS: This survey demonstrated large variability in training of neurology and PM&R residents in peripheral EDX.

A telephonic single breath count test for screening of exacerbations of myasthenia gravis: A pilot study.

BACKGROUND: Patients with myasthenia gravis (MG) may experience worsening symptoms outside of a clinical setting. A method of diagnosing and triaging such individuals would be valuable. This study gauged the viability of a nurse-administered single breath count test (SBCT) over the telephone for assessing MG exacerbations. METHODS: This was a retrospective, single-center review of a pilot study of 45 telephone calls from patients with MG who had worsening baseline symptoms. SBCTs were administered over the telephone to patients by trained nurses. Patients with a breath count of 25 or less were sent to the emergency department. RESULTS: Using a cutoff count of 25, the nurse-administered telephonic SBCT had a positive predictive value of 71%, sensitivity of 80%, and specificity of 60% in diagnosing an MG exacerbation. CONCLUSIONS: SBCT administered by trained nurses by means of telephone may be a useful screening tool for assessing decreased respiratory function in patients with MG.

Optimizing telemedicine to facilitate amyotrophic lateral sclerosis clinical trials.

Amyotrophic lateral sclerosis (ALS) has the largest drug pipeline among neuromuscular diseases, with over 160 companies actively involved in ALS research. There is a growing need to recruit trial participants, but ALS patients often have limited mobility and most ALS trials are conducted in a small number of major centers. These factors effectively limit patient participation, particularly for those in rural areas. The current coronavirus disease 2019 (COVID-19) pandemic has necessitated the more widespread use of telemedicine technology for clinical care, and has prompted consideration of its increased use for clinical trials. In this opinion piece, we describe the current state of telemedicine for recruitment, consenting, and screening of participants for clinical trials. We also summarize the available data on remote administration of outcome measures. Current challenges include validation of outcome measures for remote assessment, as well as technological, regulatory, and licensure barriers.

Factors associated with acute exacerbations of myasthenia gravis.

INTRODUCTION: The etiology of acute exacerbations of myasthenia gravis (MG) is not well understood and further characterization can lead to improved preventative measures. This study aims to characterize factors contributing to MG exacerbations. METHODS: A total of 127 MG patient charts were reviewed retrospectively (2011-2016) to obtain demographics, immunizations, pharmaceutical records, contributing factors of each MG exacerbation, emergency department (ED) visits, hospitalizations, and duration. RESULTS: There were 212 exacerbations requiring 106 ED visits and 141 hospitalizations (average admission 6.5 days). Highest contributors were infections (30%) and medications that may worsen MG (19%), with 24% unattributed. Infection related exacerbations were associated with 44.3% of ED visits and 39.7% of hospitalizations. Patients prescribed beta-blockers were associated with more exacerbations (P < .01). Patients prescribed medications that may worsen MG had a higher exacerbation frequency shortly after administration. DISCUSSION: Infections and cautioned medications are frequently factors in acute MG exacerbations needing urgent medical attention and warrant caution.

Malignant Hyperthermia.

Malignant Hyperthermia (MH) is a life-threatening pharmacogenetic disorder which results from exposure to volatile anesthetic agents and depolarizing muscle relaxants. It manifests as a hypermetabolic response resulting in tachycardia, tachypnea, hyperthermia, hypercapnia, acidosis, muscle rigidity and rhabdomyolysis. An increase in the end-tidal carbon dioxide is one of the earliest diagnostic signs. Dantrolene sodium is effective in the management of MH, and should be available whenever general anesthesia is administered. This review also aims to highlight the genetics and pathology of MH, along with its association with various inherited myopathy syndromes like central core disease, multi-mini core disease, Native-American myopathy, and King-Denborough syndrome.

Evidence-based medicine for every day, everyone, and every therapeutic study.

The rapid growth in published medical literature makes it difficult for clinicians to keep up with advances in their fields. This may result in a cursory scan of the abstract and conclusion of a study without critically evaluating study quality. The application of evidence-based medicine (EBM) is the process of converting the abstract task of reading the literature into a practical method of using the literature to inform care in a specific clinical context while simultaneously expanding one's knowledge. EBM involves 4 steps: (1) stating the clinical problem in a defined question; (2) searching the literature for the evidence; (3) critically appraising the evidence for its validity; and (4) applying the evidence in the context of the patient's situation, preferences, and values. In this review, we use the recently published trial of thymectomy in myasthenia gravis as an example and systematically go through the steps of assessing internal validity, precision, and external validity. Muscle Nerve 58: 486-496, 2018.