Michael Hehir

Mycophenolate mofetil in AChR‐antibody‐positive myasthenia gravis: Outcomes in 102 patients

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

Efficacy of prednisone for the treatment of ocular myasthenia (EPITOME): A randomized, controlled trial

Introduction: In this study we evaluated the safety, tolerability, and efficacy of prednisone in patients with ocular myasthenia gravis (OMG) concurrently treated with pyridostigmine. Methods: This investigation was a randomized, double‐blind, placebo‐controlled trial. Participants whose symptoms failed to remit on pyridostigmine were randomized to receive placebo or prednisone, initiated at 10 mg every other day, and titrated to a maximum of 40 mg/day over 16 weeks. The primary outcome measure was treatment failure. Results: Fewer subjects were randomized than the 88 planned. Of the 11 randomized, 9 completed 16 weeks of double‐blind therapy. Treatment failure incidence was 100% (95% CI 48%–100%) in the placebo group (n = 5) vs. 17% (95% CI 0%–64%) in the prednisone group, P = 0.02 (n = 6). Median time to sustained minimal manifestation status (MMS) was 14 weeks, requiring an average prednisone dose of 15 mg/day. Adverse events were infrequent and generally mild in both groups. Conclusions: A strategy of low‐dose prednisone with gradual escalation appears to be safe, well‐tolerated, and effective in treating OMG. Muscle Nerve 53: 363–369, 2016

Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review

Objective: To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG). Methods: This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs. Results: Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls (p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) (p = 0.001 and p = 0.005). Classification of evidence: This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.

Can mycophenolate mofetil be tapered safely in myasthenia gravis? A retrospective, multicenter analysis.

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. Muscle Nerve 52: 211–215, 2015

Electrodiagnosis of Myotonic Disorders

Clinical and electrical myotonia is caused by a small group of neuromuscular disorders. This article reviews myotonia and its differential diagnosis. The use of electrodiagnostic testing to evaluate the primary myotonic disorders (myotonic dystrophy and the nondystrophic myotonias) is also discussed.

Generalized Myasthenia Gravis: Classification, Clinical Presentation, Natural History, and Epidemiology

Myasthenia gravis (MG) is a rare disease, but the most common disorder of the neuromuscular junction. It is the prototypic autoimmune disease most commonly caused by antibodies to the acetylcholine receptor (AChR) leading to characteristic fatigable weakness of the ocular, bulbar, respiratory, axial, and limb muscles. The majority of patients with MG first present with ocular symptoms. Most patients with MG will experience at least 1 exacerbation of symptoms throughout the course of their illness. This article will cover the epidemiology, clinical presentation, classification, and natural history of MG.

Construction and validation of the chronic acquired polyneuropathy patient‐reported index, “CAP‐PRI:” a disease‐specific, health‐related quality of life instrument

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

Unexpected neuroimaging abnormalities in patients with apparent C8 radiculopathy: Broadening the clinical spectrum

Introduction: C8‐root impingement by C7/T1 lesions on neuroimaging studies is not consistently observed in C8 radiculopathy. We hypothesized that C7 or T1 root lesions (with a pre‐ or postfixed plexus) or cervical myelopathy might explain some “C8 radiculopathies” without C8 root compression. Methods: Retrospective analysis of cervical neuroimaging in 31 consecutive patients with EMG‐confirmed C8 radiculopathy. Results: Five patients (16%) had C8‐root compression at C7/T1. Of those without C8‐root compression, 5 (16%) had C7‐root compression at C6/7, one (3%) had T1‐root compression at T1/T2, 7 (23%) had cervical cord compression at or above the C6/7 level, 4 (13%) had intramedullary cervical lesions, and 9 (29%) had mild or nonspecific findings. Conclusions: C8 radiculopathy without C8‐root compression may be due to C7‐root compression in the setting of a “prefixed” brachial plexus, upper cervical cord compression with vascular compromise of the distal cervical spinal cord (“myelopathic hand”), or intramedullary cervical cord lesions. Muscle Nerve 45: 859–865, 2012

Double trouble in a patient with myotonia.

Non-dystrophic myotonias (NDM) are characterised by muscle stiffness during voluntary movement owing to delayed skeletal muscle relaxation caused by mutations in the chloride (CLCN1) and sodium (SCN4A) skeletal muscle channel genes. Late onset acid maltase deficiency (AMD) is characterised by progressive respiratory and proximal muscle weakness; electrical but not clinical myotonia can be observed. Case report of a unique patient with concurrent NDM and AMD. We describe the clinical presentation and management of a patient with two rare neuromuscular disorders. This case illustrates the importance of reopening the differential diagnosis in patients who do not conform to the typical natural history of a specific disease.

Validation of a simple disease-specific, quality-of-life measure for diabetic polyneuropathy: CAPPRI

Objective We studied the performance of a 15-item, health-related quality-of-life polyneuropathy scale in the clinic setting in patients with diabetic distal sensorimotor polyneuropathy (DSPN). Methods Patients with DSPN from 11 academic sites completed a total of 231 Chronic Acquired Polyneuropathy Patient-Reported Index (CAPPRI) scales during their clinic visits. Conventional and modern psychometric analyses were performed on the completed forms. Results Conventional and modern analyses generally indicated excellent psychometric properties of the CAPPRI in patients with DSPN. For example, the CAPPRI demonstrated unidimensionality and performed like an interval-level scale. Conclusion Attributes of the CAPPRI for DSPN include ease of use and interpretation; unidimensionality, allowing scores to be summed; adequate coverage of disease severity; and the scales ability to address relevant life domains. Furthermore, the CAPPRI is free and in the public domain. The CAPPRI may assist the clinician and patient with DSPN in estimating disease-specific quality of life, especially in terms of pain, sleep, psychological well-being, and everyday function. The CAPPRI may be most useful in the everyday clinical setting but merits further study in this setting, as well as the clinical trial setting.