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Escalating drug costs place patients at risk for financial toxicity and demand that physicians understand and act on the ethical and economic principles related to drug pricing. This manuscript reviews these principles and provides clinicians with a framework to think about the value of the drugs prescribed for patients with neuromuscular diseases. A key component of addressing the drug pricing crisis will be establishing a value based (benefit/cost) drug pricing framework. Determining the value of a drug is difficult and requires estimating the benefit and costs to patients and society while integrating indirect and contextual variables. Other considerations in drug pricing include "externality," the value to society derived from innovation. The Institute for Clinical and Economic Review (ICER) is a leading independent research organization providing clinicians with value-based price "benchmarks." All physicians must educate themselves in drug pricing principles and be prepared to have conversations regarding individual and societal value with the patients they serve. [ABSTRACT FROM AUTHOR]

Drug prices in the United States have reached astounding heights, negatively impacting patients and society. The vast majority of prescription drug spending is on brand name drugs, which are protected from typical market pressures by FDA exclusivity and intellectual property patents. Drugs to treat "orphan" diseases, of particular relevance to neuromuscular clinicians, are some of the most expensive in all of medicine. The Orphan Drug Act's original intent was to incentivize the creation of drugs that would otherwise provide little economic payoff. While it has facilitated incredible, life-changing drugs for our patients, it has also become a source of abuse. Many expensive drugs approved under the Orphan Drug Act were previously available for compassionate use or for another indication at much lower prices. As patients increasingly face high drug prices, it is important for clinicians to understand a drug's risk for inducing financial toxicity, as the financial and emotional consequences of an overpriced low-value drug may outweigh its intended benefit. [ABSTRACT FROM AUTHOR]

Introduction: The MG-QOL15 is a validated, health-related quality of life (HRQOL) measure for myasthenia gravis (MG). Widespread use of the scale gave us the opportunity to further analyze its clinimetric properties.Methods: We first performed Rasch analysis on >1,300 15-item Myasthenia Gravis Quality of Life scale (MG-QOL15) completed surveys. Results were discussed during a conference call with specialists and biostatisticians. We decided to revise 3 items and prospectively evaluate the revised scale (MG-QOL15r) using either 3, 4, or 5 responses. Rasch analysis was then performed on >1,300 MG-QOL15r scales.Results: The MGQOL15r performed slightly better than the MG-QOL15. The 3-response option MG-QOL15r demonstrated better clinimetric properties than the 4- or 5-option scales. Relative distributions of item and person location estimates showed good coverage of disease severity.Conclusions: The MG-QOL15r is now the preferred HRQOL instrument for MG because of improved clinimetrics and ease of use. This revision does not negate previous studies or interpretations of results using the MG-QOL15. Muscle Nerve 54: 1015-1022, 2016. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is an autoimmune neuromuscular disease caused by antibodies directed against the postsynaptic muscle membrane. The clinical hallmark of the disease is fluctuating and fatigable weakness that affects the ocular muscles (resulting in diplopia and ptosis), the bulbar muscles (causing dysphagia, dysarthria, and dyspnea), and extremity muscles. The diagnosis is most often made with serological testing that identifies either acetylcholine receptor antibodies or muscle-specific tyrosine kinase antibodies. Electrodiagnostic testing has a role in supporting the diagnosis. There are many available treatments that result in improvement of function and quality of life. Treatment should be individualized after consideration of many factors, including disease distribution and severity, patient comorbidities, age, serological status, and what is known about the efficacy and safety of the various treatments. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: The objective of this study is to determine if change in acetylcholine receptor antibody (AChR-ab) levels reflects change in clinical severity in patients with myasthenia gravis (MG). Methods: We reviewed results from a prospective trial in MG and from all 85 patients in an MG Clinic who had AChR-ab determinations performed at least twice by the same commercial laboratory. Results: Change in AChR-ab levels correlated only weakly with change in clinical severity. AChR-ab levels fell in 92% of patients who improved and in 63% who did not. A fall in AChR-ab level had a positive predictive value for clinical improvement of 83% and a negative predictive value of only 59%. Conclusions: AChR-ab levels fell in almost all patients who improved, but also in most patients who did not. Thus, we do not recommend commercially available AChR-ab levels as a biomarker of improvement in MG. However, antibody levels might be useful as a marker for inadequate immunotherapy. Muscle Nerve 49:483-486, 2014 [ABSTRACT FROM AUTHOR]

The myasthenia gravis composite (MGC) was constructed by selecting the best performing items from three commonly used, MG-specific scales. The response categories of the items were subsequently weighted for importance. The MGC, which takes less than five minutes to complete, is made up of three ocular, three bulbar, one respiratory, one neck, and two limb items. After its construction, the MGC was validated in an 11-center scale validity study. During the validation study, which included test-retest analysis, it was determined that a 3-point improvement in MGC score reliably indicates clinical improvement. A 3-point improvement in MGC also appears to be meaningful to the patient. Rasch analysis of the MGC confirmed that all 10 items belong and can be summed to provide a total score, and that the weights given to the response categories of the items are appropriate. [ABSTRACT FROM AUTHOR]

In this review we present an overview of quality of life (QOL) and QOL measures in neuromuscular disorders. We discuss the characteristics of QOL measures used in neuromuscular research, highlighting differences between generic versus disease-specific and global versus health-related QOL instruments. The phenomenon of response shift is reviewed. Commonly used QOL instruments are reviewed for amyotrophic lateral sclerosis, muscle diseases, myasthenia gravis, and polyneuropathy. We also review some of what is known about QOL for patients with these neuromuscular disorders. Muscle Nerve 46: 9-25, 2012 [ABSTRACT FROM AUTHOR]

The MG-QOL15 is helpful in informing the clinician about the patient's perception of the extent of and dissatisfaction with myasthenia gravis (MG)-related dysfunction. The aims of this study were to determine the usefulness of the MG-QOL15 for following individuals with MG and to guide clinical researchers who plan to use the MG-QOL15. We assessed sensitivity and specificity for detecting clinical change and evaluated test-retest reliability. Sensitivities and specificities of various cut-points of change in scores are presented. Also presented are means and standard deviations of MG-QOL15 scores for all patients and for subgroups of patients. The test-retest reliability coefficient was 98.6%. The MG-QOL15 has an acceptable longitudinal construct validity. We consider this instrument to be most useful for informing the clinician about the patient's perception and tolerance of MG-related dysfunction. More objective measures, such as the MG Composite, should also be used to follow disease severity. Muscle Nerve, 2011 [ABSTRACT FROM AUTHOR]

This review illustrates how measurements of clinical status in patients with myasthenia gravis have evolved from clinical descriptions and estimates of mortality rates to more sophisticated evaluative instruments, including numerical rating scales that measure strength, endurance, quality of life, and activities of daily living. The rationale and use of weighting and the importance of patient-reported outcomes are also discussed. The measurement of the steroid-sparing effect of an immunosuppressant is also reviewed. Muscle Nerve 42: 5-13, 2010 [ABSTRACT FROM AUTHOR]

Two recent randomized, controlled trials failed to demonstrate a benefit of mycophenolate mofetil (MMF) over prednisone in the treatment of myasthenia gravis (MG). We reviewed our experience with MMF in MG to determine whether these trials may have been unsuccessful because of their short duration and the unpredicted benefit of prednisone. We reviewed outcomes and prednisone dosage for all our acetylcholine-receptor (AChR)-antibody positive MG patients treated with MMF alone or with prednisone for at least 3 months. The percentage of patients with a desirable outcome (MG-specific Manual Muscle Test score <4 or Myasthenia Gravis Foundation of America post-invention status of minimal manifestations or better) began to increase after 6 months; 80% of those followed for >24 months had a desirable outcome. Prednisone dose decreased after 12 months; after 25 months, 54.5% of patients took no prednisone and 75% took <7.5 mg/day. This retrospective analysis provides class IV evidence that MMF begins to improve AChR-positive MG after 6 months, both with prednisone and as monotherapy. Muscle Nerve 41: 593-598, 2010 [ABSTRACT FROM AUTHOR]

Health-related quality of life (HRQOL) estimates can play an important role in patient care by providing information about the patient's perception of impairment and disability and the degree to which the patient tolerates disease manifestations. The 15-item myasthenia gravis quality of life scale (MG-QOL15) is an HRQOL evaluative instrument specific to patients with myasthenia gravis (MG) that was designed to be easy to administer and interpret. In this multicenter study we demonstrate the construct validity of the MG-QOL15 in the practice setting. To assess the construct validity, score distributions were examined for test items in different MG patient groups that represent the clinical spectrum of the disease. For example, patients in remission more frequently scored test items as normal than did patients in other groups. Patients with lower (better) MG composite scores also more frequently scored items as normal than did patients with higher (worse) scores. There was also appropriate correlation between the MG-QOL15 and the other MG-specific scales studied. The study findings shed light on what troubles MG patients. The MG-QOL15 has construct validity in the clinical practice setting and represents an efficient and valuable tool for assessing HRQOL for patients with MG. Muscle Nerve, 2010 [ABSTRACT FROM AUTHOR]

We assessed the performance of items from the Quantitative Myasthenia Gravis (QMG), MMT (Manual Muscle Test), and MG-ADL (Myasthenia Gravis - Activities of Daily Living) scales, using data from two recently completed treatment trials of generalized MG. Items were selected that were relevant to manifestations of MG, meaningful to both the physician and the patient, and responsive to clinical change. After the 10 items were chosen, they were weighted based on input from MG experts from around the world, considering factors such as quality of life, disease severity, risk, prognosis, validity, and reliability. The MG Composite is easy to administer, takes less than 5 minutes to complete, and requires no equipment. Weighting of the response options of the 10 items should result in ordinal scores that better represent MG status and are more responsive to meaningful clinical change. To better determine its suitability for clinical use and for treatment trials, the MG Composite will be tested prospectively at several academic medical centers and will be used as a secondary measure of efficacy in pending clinical trials of MG. Muscle Nerve 38: 1553-1562, 2008 [ABSTRACT FROM AUTHOR]

We describe the process whereby a recently developed myasthenia gravis (MG)-specific quality-of-life (QOL) instrument was reduced from 60 items to 15 items while maintaining potential usefulness in the clinic and in prospective treatment trials. In data from a recently completed prospective trial of mycophenolate mofetil (MMF) in MG, the MG-QOL15 correlated as highly as the 60-item MG-QOL for physical and social domains of the 36-item health survey of the Medical Outcomes Study Short Form (SF-36). Correlation coefficients for the MG-QOL15 were similar to the 60-item MG-QOL for the Quantitative Myasthenia Gravis (QMG), MG-specific Manual Muscle Testing (MG-MMT), and the MG-specific Activities of Daily Living (MG-ADL) scores at week 0 and for change in scores from week 0 to week 12 in the MMF trial. Using the physician global impression at week 12 of the trial as the 'gold standard,' the MG-QOL15 demonstrated high sensitivity. Because the MG-QOL15 instrument can be quickly and easily administered and interpreted, it is a potential QOL measure for treatment trials and the clinical evaluation of patients with MG. Muscle Nerve, 2008 [ABSTRACT FROM AUTHOR]

Supportive care, symptomatic treatment, and patient education should be provided for patients with inherited or acquired polyneuropathies. In addition, specific treatment is available for many of the acquired polyneuropathies. Genetic counseling is valuable for many patients with inherited polyneuropathies, but only rarely is specific treatment an option for these patients. However, specific treatments are available for many of the rare and devastating systemic disorders associated with polyneuropathies. Thus, clinicians must promptly diagnose these inherited disorders so that specific treatment may be initiated. The clinical features of these rare inherited disorders are emphasized. [ABSTRACT FROM AUTHOR]

Abstract In 3 large cohorts (total of 787 patients), clinical vibration impairment (CVI) of the great toe using a tuning fork was compared with quantitative vibration threshold (QVT). Using a stepwise multivariate analysis, we assessed demographic and anthropomorphic patient characteristics associated with the difference between CVI and QVT for the various cohorts and the chosen QVT ranges of percentile abnormality. We also compared CVI or QVT abnormality with a composite score of nerve conduction abnormality to confirm that QVT is a valid measure of severity of neuropathy. Highly significant associations between CVI and QVT were found in all 3 cohorts studied, regardless of the chosen QVT percentile level of abnormality. However, in the 2 cohorts evaluated by many different physicians, CVI overestimated QVT much more often than underestimated it. The discordance between CVI and QVT in all QVT abnormality percentile levels was associated with age, height and body surface area (BSA) in 1 cohort, with age and BSA in another cohort, and with age in the third cohort. In the third cohort, the correlation between QVT and the composite score of nerve conduction abnormality was significantly higher than the correlation between CVI and the composite score. Using a tuning fork, neuromuscular physicians overestimate vibration sensation loss more often than when QVT testing is done, which employs quantitative stimuli, a broad range of stimulus magnitudes, null stimuli, validated algorithms of testing and validated reference values. To improve assessment of vibration sensation, physicians should take into account age, height and weight (or body surface area) when judging vibration abnormalities. Applying some useful approaches to quantitative sensory testing might improve the accuracy of clinical sensory testing. [ABSTRACT FROM AUTHOR]

The article focuses on the diagnosis and treatment of stiff-person syndrome. A brief of history of the syndrome's discovery is presented. The characteristics of the syndrome and the diagnostic criteria for the classic syndrome are discussed. Some neurological diseases that must be ruled out before making the diagnosis of stiff-person syndrome, or its variants are listed. Several lines of evidence suggesting that stiff-person syndrome has an autoimmune basis are also highlighted.

Abstract: We present a patient with acute onset painful polyneuropathy found to have a novel MPZ mutation (Arg36Trp). The Arg36Trp mutation described in this report occurs at a putative adhesion interface. An alternative explanation for his polyneuropathy was not found and his mother was identified to have polyneuropathy and carry the same mutation. Two hundred normal controls were without this base alteration. The temporal profile of the index case may provide further indirect evidence suggesting an immune mechanism contributing to the pathogenesis of some cases of MPZ mutations. We predict that other rapid symptom onset polyneuropathies will be found to have direct genetic susceptibility. [Copyright &y& Elsevier]

Discusses stiff-person syndrome. Description of this disease and how it affects the body; Association of the disease with high levels of serum and cerebrospinal fluid autoantibodies; Details of a study in this issue by Claudia Sommer and others; Limitations of the study; Assertion that advances in the understanding of the clinical features and pathophysiological mechanisms of paraneoplastic and primary autoimmune neurological disorders allow clinicians to more effectively diagnose and manage these conditions.

Introduction/Aims: We developed a patient‐ and physician‐weighted consensus unit called the adverse event unit (AEU) that quantifies and compares adverse event (AE) burden among any group of medications in neurological patients. In this study we evaluated preliminary validity and feasibility of measuring AE burden with the AEU in myasthenia gravis (MG). Methods: This is a single‐center, prospective, 1‐year, observational study of adult MG patients presenting for routine care between April 1, 2021 and March 31, 2022. The MG Activities of Daily Living (MG‐ADL), the 15‐item MG Quality of Life revised (MG‐QOL15r), MG‐Composite, and AEU scores were obtained at all visits. A priori primary feasibility metric was AEU completion rate equal to (within 3.8%, one‐sided 95% confidence interval [CI]) or better than MG‐ADL completion rate. Time to administer AEU and MG‐ADL/MG‐QOL15r, correlation between AEU total score and MG‐QOL15r, and median AEU scores for each MG medication were evaluated. Results: Fifty‐four patients completed 67 study visits; side effects were reported at 75% of the visits. The study met the primary feasibility endpoint; AEU and MG‐ADL were recorded at all visits. Times to administer the AEU (median 5 minutes) and MG‐ADL/MG‐QOL15r were similar. We observed a weak correlation of 0.29 (95% CI 0.03 to 0.51, P =.032) between AEU and MG‐QOL15r scores. Non–statistically significant differences in median AEU scores were observed among MG medications. Discussion: Our data demonstrate preliminary feasibility and validity of using the AEU to measure AE burden in MG. Future studies will compare AE burden among MG treatments and evaluate clinically meaningful AEU scores in MG. See Editorial on pages 1–3 in this issue. [ABSTRACT FROM AUTHOR]

Nine days after left ophthalmic-distribution zoster, a 47-year-old man developed SUNCT headaches (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing). In contrast to two prior cases of SUNCT that developed after varicella zoster virus (VZV) meningoencephalitis without rash, this case describes an association of SUNCT with overt zoster, thus adding to the spectrum of headache and facial pain syndromes caused by VZV reactivation. [ABSTRACT FROM AUTHOR]

Health-related quality of life measures have become an important tool in measuring clinical outcomes. Disease-specific health-related quality of life scales, particularly in diseases that might fluctuate, can draw attention to non-motor symptoms and guide symptom management. The following review provides an overview of quality of life ( QOL) with a focus of disease-specific QOL measures for myasthenia gravis. We also review the current understanding of non-motor symptoms in myasthenia gravis and suggest that QOL measures might be a useful way of accounting for these symptoms. After reading the review, the reader will have a better understanding of QOL measures and how they can be used for patient care and clinical research. [ABSTRACT FROM AUTHOR]

Objective: To design a physician and patient derived tool, the Adverse Event Unit (AEU), akin to currency (e.g. U.S. Dollar), to improve AE burden measurement independent of any particular disease or medication class. Patients/Methods: A Research Electronic Data Capture (REDCap) online survey was administered to United States physicians with board certification or board eligibility in general neurology, subspecialty neurology, primary care internal medicine or family medicine, subspecialty internal medicine, general pediatrics, and subspecialty pediatrics. Physicians assigned value to 73 AE categories chosen from the Common Terminology Criteria of Adverse Events (CTCAE) relevant to neurologic disorder treatments. An online forced choice survey was administered to non-physician, potential patients, through Amazon Mechanical Turk (MTurK) to weight the severity of the same AE categories. Physician and non-physician data was combined to assign value to the AEU. Surveys completed between 1/2017 and 3/2019. Results: 363 physicians rated the 73 AE categories derived from CTCAE. 660 non-physicians completed forced choice experiments comparing AEs. The AEU provides 0–10, weighted values for the AE categories studied that differ from the ordinal 1–4 CTCAE scale. For example, CTCAE severe diabetes (category 4) is assigned an AEU score of 9. Although non-physician input changed physician assigned AEU values, there was general agreement among physicians and non-physicians about severity of AEs. Conclusion: The AEU has promise to be a useful, practical tool to add precision to AE burden measurement in the clinic and in comparative efficacy research with neurology patients. AEU utility will be assessed in planned comparative efficacy clinical trials. [ABSTRACT FROM AUTHOR]

The recommendations for clinical research standards published in 2000 by a task force of the Medical Scientific Advisory Board (MSAB) of the Myasthenia Gravis Foundation of America (MGFA) were largely successful in introducing greater uniformity in the recording and reporting of MG clinical trials. Recognizing that changes in clinical trial design and implementation may increase the likelihood that new therapies are developed for MG, the MGFA MSAB Task Force here presents updated recommendations for the design and implementation of clinical trials in MG, including (a) the use of a quantitative measure, such as the MG-Composite, that is weighted for clinical significance and incorporates patient reported outcomes; (b) consideration of nontrial strategies; and (c) development of biomarkers that support mechanistic studies of pharmacotherapies. The hope is that these updated task force recommendations will expedite the development and acceptance of more effective and less noxious therapies for MG. Muscle Nerve 45: 909-917, 2012 [ABSTRACT FROM AUTHOR]

The article focuses on polyneuropathy that presents with widespread sensory or sensorimotor symptoms and signs. The fundamental step of determining whether the polyneuropathy is a distal, symmetrical, sensory or sensorimotor polyneuropathy is emphasized. Patients with acquired polyneuropathies usually complain of positive neuropathic sensory symptoms while patients with inherited polyneuropathies rarely do. Most polyneuropathies warrant additional electrodiagnostic evaluation in an electromyography laboratory.

Introduction: The Myasthenia Gravis Patient Registry (MGR) is a voluntary, patient-submitted database dedicated to improve understanding of care/burden of myasthenia gravis (MG).Methods: In this study we present analyses of baseline records through July 2017 (n = 1140) containing data on the MG-Activities of Daily Living (MG-ADL) and the MG 15-item Quality of Life (MG-QOL15) instruments, two validated scales assessing quality of life in MG patients at sign-up into the MGR.Results: Most registrants reported moderate to severe impairment of health-related quality of life, with a median MG-ADL score of 6 and a median MG-QOL15 score of 21. Seventy-one percent of the patients had received pyridostigmine. Corticosteroids, mycophenolate mofetil, and azathioprine were the most common immunomodulators/immunosuppressants, with 85% of participants having ever using one of these agents. Forty-seven registrants reported receiving intravenous immunoglobulin, and 30% received plasma exchange. Twelve percent reported other treatments, and 40% were unsure whether they received less common therapies. Forty percent had undergone thymectomy.Discussion: The MGR data correlate well with other MG cohorts. Many MG patients remain negatively impacted despite treatment. [ABSTRACT FROM AUTHOR]

To date there are only two validations on the Chronic Acquired Polyneuropathy Patient‐Reported Index (CAPPRI) questionnaire, both originated from the North America. We sought to translate and validate CAPPRI for use in Serbian patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We included 109 CIDP patients. CAPPRI, short form (36) health survey (SF‐36), Medical Research Council Sum Score (MRC‐SS), Inflammatory Neuropathy Cause and Treatment (INCAT) sensory and disability scores, Beck Depression Inventory (BDI), and Krupp's Fatigue Severity Scale (FSS) were used. Serbian CAPPRI questionnaire was understandable and the language was appropriate and simple. Calculation demonstrated good person (0.9) and item (0.9) reliability with adequate item (4.1), and person (2.9) separation indices. There was a minor floor effect (13.8%), and no ceiling effect. All items had good fit, except items 2 (pain), 5 (sleeping), and 14 (eating) to some degree. Category responses were well ordered and organized, except item 14 (eating). The CAPPRI score did not vary regarding gender, age, or education. Patients with worse scores on MRC‐SS, INCAT sensory score, INCAT disability score, FSS, and BDI had worse scores on CAPPRI (P < .01). The CAPPRI score showed strong correlation with the SF‐36 score (rho = −0.76, P < .01). The Serbian version of the CAPPRI is reliable and valid patient‐reported index for patients with CIDP, able to differentiate between levels of impairment and disability in this disease. [ABSTRACT FROM AUTHOR]

Introduction: The Inclusion Body Myositis Functional Rating Scale (IBMRFS) is a 10-item clinician-rated ordinal scale developed for people with inclusion body myositis.Methods: Single observations of the IBMFRS were collected from 132 patients. After Rasch analysis, modifications were made to the scale to optimize fit to the Rasch model while maintaining clinical validity and utility.Results: The original IBMFRS did not fit the assumptions of the Rasch model because of multidimensionality of the scale. Items assessed local dependence, disordered step thresholds, and differential item functioning. Deconstructing the scale into upper limb (IBMFRS-UL) and lower limb (IBMFRS-LL) scales improved fit to the Rasch model. A 9-item scale with the swallowing item removed (IBMFRS-9) remained multidimensional but demonstrated the ability to discriminate patients along the severity continuum. IBMFRS-UL, IBMFRS-LL, and IBMFRS-9 scores were transformed to a 0-100 scale for comparability.Discussion: This analysis has led to the development of 3 optimized versions of the IBMFRS. Muscle Nerve 60: 161-168, 2019. [ABSTRACT FROM AUTHOR]

Introduction: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy.Methods: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients.Results: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001).Discussion: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019. [ABSTRACT FROM AUTHOR]

Introduction: A randomized trial demonstrated benefit from thymectomy in nonthymomatous acetylcholine receptor (AChR)-antibody positive myasthenia gravis (MG). Uncontrolled observational and histologic studies suggest thymectomy may not be efficacious in anti-muscle-specific kinase (MuSK)-MG.Methods: The therapeutic impact of thymectomy was evaluated from data collected for a multicenter, retrospective blinded review of rituximab in MuSK-MG.Results: Baseline characteristics were similar between thymectomy (n = 26) and nonthymectomy (n = 29) groups, including treatment with rituximab (42% vs. 45%). At last visit, 35% of thymectomy subjects reached the primary endpoint, a Myasthenia Gravis Foundation of America (MGFA) post-intervention status (PIS) score of minimal manifestations (MM) or better, compared with 55% of controls (P = 0.17). After controlling for age at onset of MG, rituximab, prednisone, and intravenous immunoglobulin/plasma exchange treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome (odds ratio = 0.43, 95% confidence interval 0.12-1.53, P = 0.19).Discussion: Thymectomy was not associated with additional clinical improvement in this multicenter cohort of MuSK-MG patients. Muscle Nerve 59:404-410, 2019. [ABSTRACT FROM AUTHOR]

Background: Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial.Methods: We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229.Findings: Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy.Interpretation: The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed.Funding: Alexion Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Introduction: Generic health-related quality-of-life (HRQOL) patient-reported outcome measures have been used in patients with chronic immune-mediated polyneuropathies. We have created a disease-specific HRQOL instrument.Methods: The chronic acquired polyneuropathy patient-reported index (CAP-PRI) was developed and validated in multiple steps. Items were initially generated through patient and specialist input. The performance of the preliminary 20 items was analyzed via a prospective, 5-center study involving chronic immune-mediated polyneuropathy patients.Results: Data analysis suggested modification to a 15-item scale with 3 response categories rather than 5. The final CAP-PRI was validated in another prospective, 5-center study. The CAP-PRI appeared to be a unidimensional outcome measure that fit the Rasch model in our multicenter cohort. It correlated appropriately with outcome measures commonly used in this patient population.Conclusions: The CAP-PRI is a simple disease-specific HRQOL measure that appears to be useful for clinical care and possibly also for clinical trials. Muscle Nerve 54: 9-17, 2016. [ABSTRACT FROM AUTHOR]

Introduction: Mycophenolate mofetil (MMF) is frequently used to treat myasthenia gravis, but there is little information to guide clinicians on the safety of reducing the dose in well-controlled patients. Methods: This retrospective chart review at 3 institutions identified 92 patients who had undergone MMF taper after achieving either pharmacologic remission or minimal manifestations status. Statistical analysis was performed to assess differences in patient characteristics between patients who had successfully tapered MMF and those who relapsed. Results: Of 92 patients undergoing a taper, 30 relapsed. The relapses were mild, transient, and usually responded to increased MMF dose. MG crisis did not occur. The mean dose at time of relapse was 888 mg/day. Patients with relapses were tapered more quickly (8.4 vs. 62.4 months). Conclusions: Tapering MMF appears safe after years of disease stability. Reducing the dose at a dose of only 500 mg/day every 12 months is recommended. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: We explored the modified Rankin scale (mRS) as a tool to quantitate disability in myasthenia gravis (MG). Our aim was to correlate patients' perception of their disability with that of the care provider and determine its relationship with other MG-related scores. Methods: We evaluated 107 MG patients at 2 neurological centers. Patients were assessed over the telephone before and after clinic visits using the 15-item Myasthenia Gravis Quality-of-Life index (MG-QOL15) and mRS. At the clinic, patients were assessed using the MG-QOL15, MG Composite (MGC), and mRS. Results: The MG-QOL15 correlated with the MGC, mRS, and assessors' scores of patients. Assessors' perception of disease burden was in line with that of the patients' scoring. MG-QOL15 scores obtained over the telephone were consistent with those obtained in the clinic. Scores were generally higher in patients receiving steroids at >5 mg/day and in those receiving or seeking benefits. Conclusion: The MG-QOL15 and mRS are useful for estimating disability in MG. Muscle Nerve 50: 501-507, 2014 [ABSTRACT FROM AUTHOR]

Charcot-Marie-Tooth Neuropathy Score second version ( CMTNSv2) is a validated clinical outcome measure developed for use in clinical trials to monitor disease impairment and progression in affected CMT patients. Currently, all items of CMTNSv2 have identical contribution to the total score. We used Rasch analysis to further explore psychometric properties of CMTNSv2, and in particular, category response functioning, and their weight on the overall disease progression. Weighted category responses represent a more accurate estimate of actual values measuring disease severity and therefore could potentially be used in improving the current version. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Electrical impedance myography (EIM), a non-invasive, electrophysiological technique, has preliminarily shown value as an ALS biomarker. Here we perform a multicenter study to further assess EIM's potential for tracking ALS. ALS patients were enrolled across eight sites. Each subject underwent EIM, handheld dynamometry (HHD), and the ALS Functional Rating Scale-revised (ALSFRS-R) regularly. Techniques were compared by assessing the coefficient of variation (CoV) in the rate of decline and each technique's correlation to survival. Results showed that in the 60 patients followed for one year, EIM phase measured from the most rapidly progressing muscle in each patient had a CoV in the rate of decline of 0.62, compared to HHD (0.82) and the ALSFRS-R (0.74). Restricting the measurements to the first six months gave a CoV of 0.55 for EIM, 0.93 for HHD, and 0.84 for ALSFRS-R. For both time-periods, all three measures correlated with survival. Based on these data, a six-month clinical trial designed to detect a 20% treatment effect with 80% power using EIM would require only 95 patients/arm compared to the ALSFRS-R, which would require 220 subjects/arm. In conclusion, EIM can serve as a useful ALS biomarker that offers the prospect of greatly accelerating phase 2 clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: The MG Composite (MGC) is a validated outcome measure of the clinical manifestations of myasthenia gravis. Methods: We performed Rasch analyses of the MGC to investigate additional properties, including its unidimensionality and the appropriateness of the weights assigned to the response categories for the MGC items. Results: The fit statistics indicated that the 10 items belong together and can be summated for a total score. There was an overall absence of item order distortion between response categories. The Rasch model's expected category response values were compatible with item weights previously assigned. Conclusions: Our analysis suggests that: (1) the score can be summated to estimate an overall disease severity score; (2) the response options of the 10 items are not significantly distorted; and (3) the assigned weights of the response options are appropriate. Muscle Nerve 45: 820-825, 2012 [ABSTRACT FROM AUTHOR]

Introduction: The aim of this analysis was to examine the performance of the Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) during a multicenter scale validation study. Methods: Consecutive MG patients were assessed with several MG outcome measures, including the MG-ADL. Statistical tests included descriptive analysis, Pearson correlation, and sensitivity/specificity. Results: Eighty-seven patients completed the MG-ADL, MG Composite (MGC), and MG 15-item Quality of Life scale (MG-QOL15) on the first visit, and 76 returned for the second visit. At the first visit, there was a strong positive correlation between MG-ADL and MGC ( r = 0.85, P < 0.0001) and MG-QOL15 ( r = 0.76, P < 0.0001). Correlation of the delta MG-ADL score and physician impression of change between the visits was strong ( r = 0.70, P < 0.0001). A 2-point improvement in the MG-ADL best predicted clinical improvement. Test-retest analysis demonstrated a high reliability coefficient. Conclusions: The MG-ADL correlates strongly with newer, validated MG outcome measures. A 2-point improvement in the MG-ADL indicates clinical improvement. The MG-ADL is useful as a research tool and in routine clinical management. Muscle Nerve, 2011 [ABSTRACT FROM AUTHOR]

The article presents a study that investigated the relation between the Oculobulbar Facial Respiratory (OBFR) score and the myasthenia gravis (MG) Activities of Daily Living (MG-ADL) score, MG Composite scale, and MG Quality-of-Life (MG-QOL 15) scale. The bulbar function in MG is objectively measured using the OBFR score. The study involved 42 patients, were assessed twice, approximately 6 months apart using the MG measurements. Results revealed that OBFR correlated significantly with the other MG scores.

We describe a patient in remission from acute lymphoblastic leukemia who developed a painless common peroneal neuropathy. Magnetic resonance imaging (MRI) revealed nerve thickening and enhancement, while a positron emission tomography (PET) scan demonstrated increased fluorodeoxyglucose uptake in a large segment of the neurovascular bundle, suggesting peripheral nerve infiltration. Both findings resolved following treatment with chemotherapy that crossed the blood-nerve barrier. In selected patients presenting with peripheral neuropathy, MRI and PET scan can be helpful in the diagnosis of peripheral nerve infiltration. Muscle Nerve, 2008 [ABSTRACT FROM AUTHOR]