ABSTRACT
Introduction: There have been 15 formal sets of criteria published for the diagnosis of CIDP. No study to date has compared the sensitivity and specificity of all published criteria in the ...same patient population. Methods: We conducted a retrospective chart review of patients with CIDP (n = 56) and controls with diabetic polyneuropathy (n = 37) or amyotrophic lateral sclerosis (n = 39) who were followed in an academic neuromuscular practice. The sensitivity and specificity of each CIDP criterion was calculated, including clinical, laboratory, and electrodiagnostic components. Results: Sensitivities ranged from 1.8% to 87.5%; the Dyck (87.5%), Neuropathy Association (75%), and European Federation of Neurological Societies (EFNS; 73.2%) criteria ranked highest. Specificities ranged from 65.6% to 100% and, among the 3 most sensitive criteria, the EFNS (90.8%) and Neuropathy Association (82.9%) criteria were most specific. Conclusions: In our patient population, the EFNS and Neuropathy Association criteria stand out due to high sensitivity and specificity. Muscle Nerve 50: 40–46, 2014
ABSTRACT
Introduction: The etiology of neuropathy was idiopathic in 20%–30% of patients despite thorough investigation, based on results from the 1980s and 1990s. Since then, new etiologies have been ...recognized, and skin biopsy has been used to confirm small‐fiber neuropathy. Methods: The authors reviewed the charts of 373 patients with idiopathic neuropathy who were referred to a neuropathy center between 2002 and 2012. Results: Among the 284 eligible patients, 93 (32.7%) remained idiopathic. The most common cause was impaired glucose metabolism (72 patients, 25.3%), including diabetes in 26 and prediabetes in 46. Other etiologies were chronic inflammatory demyelinating polyneuropathy (CIDP) in 57 (20%) and monoclonal gammopathy in 20 (7%), as well as toxic, Sjögren disease, celiac disease, other immune‐mediated diseases, vitamin B12 deficiency, amyloidosis, vitamin B1 and B6 deficiency, vasculitis, hypothyroidism, hereditary, Lyme disease, and anti‐sulfatide antibody. Conclusions: The major causes of undiagnosed neuropathies were impaired glucose metabolism, CIDP, and monoclonal gammopathies. Despite thorough evaluation 32.7% remained idiopathic. Muscle Nerve 53: 856–861, 2016
BACKGROUND:Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive, multisystem disease that presents with cardiomyopathy or polyneuropathy. The APOLLO study assessed the ...efficacy and tolerability of patisiran in patients with hATTR amyloidosis. The effects of patisiran on cardiac structure and function in a prespecified subpopulation of patients with evidence of cardiac amyloid involvement at baseline were assessed.
METHODS:APOLLO was an international, randomized, double-blind, placebo-controlled phase 3 trial in patients with hATTR amyloidosis. Patients were randomized 2:1 to receive 0.3 mg/kg patisiran or placebo via intravenous infusion once every 3 weeks for 18 months. The prespecified cardiac subpopulation comprised patients with a baseline left ventricular wall thickness ≥13 mm and no history of hypertension or aortic valve disease. Prespecified exploratory cardiac end points included mean left ventricular wall thickness, global longitudinal strain, and N-terminal prohormone of brain natriuretic peptide. Cardiac parameters in the overall APOLLO patient population were also evaluated. A composite end point of cardiac hospitalizations and all-cause mortality was assessed in a post hoc analysis.
RESULTS:In the cardiac subpopulation (n=126; 56% of total population), patisiran reduced mean left ventricular wall thickness (least-squares mean difference ± SEM–0.9±0.4 mm, P=0.017), interventricular septal wall thickness, posterior wall thickness, and relative wall thickness at month 18 compared with placebo. Patisiran also led to increased end-diastolic volume (8.3±3.9 mL, P=0.036), decreased global longitudinal strain (–1.4±0.6%, P=0.015), and increased cardiac output (0.38±0.19 L/min, P=0.044) compared with placebo at month 18. Patisiran lowered N-terminal prohormone of brain natriuretic peptide at 9 and 18 months (at 18 months, ratio of fold-change patisiran/placebo 0.45, P<0.001). A consistent effect on N-terminal prohormone of brain natriuretic peptide at 18 months was observed in the overall APOLLO patient population (n=225). Median follow-up duration was 18.7 months. The exposure-adjusted rates of cardiac hospitalizations and all-cause death were 18.7 and 10.1 per 100 patient-years in the placebo and patisiran groups, respectively (Andersen–Gill hazard ratio, 0.54; 95% CI, 0.28–1.01).
CONCLUSIONS:Patisiran decreased mean left ventricular wall thickness, global longitudinal strain, N-terminal prohormone of brain natriuretic peptide, and adverse cardiac outcomes compared with placebo at month 18, suggesting that patisiran may halt or reverse the progression of the cardiac manifestations of hATTR amyloidosis.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT01960348.
Intravenous immune globulin (IVIG) is an immune‐modulating biologic therapy that is increasingly being used in neuromuscular disorders despite the paucity of high‐quality evidence for various ...specific diseases. To address this, the AANEM created the 2009 consensus statement to provide guidance on the use of IVIG in neuromuscular disorders. Since then, there have been several randomized controlled trials for IVIG, a new FDA‐approved indication for dermatomyositis and a revised classification system for myositis, prompting the AANEM to convene an ad hoc panel to update the existing guidelines.New recommendations based on an updated systemic review of the literature were categorized as Class I‐IV. Based on Class I evidence, IVIG is recommended in the treatment of chronic inflammatory demyelinating polyneuropathy, Guillain‐Barré Syndrome (GBS) in adults, multifocal motor neuropathy, dermatomyositis, stiff‐person syndrome and myasthenia gravis exacerbations but not stable disease. Based on Class II evidence, IVIG is also recommended for Lambert‐Eaton myasthenic syndrome and pediatric GBS. In contrast, based on Class I evidence, IVIG is not recommended for inclusion body myositis, post‐polio syndrome, IgM paraproteinemic neuropathy and small fiber neuropathy that is idiopathic or associated with tri‐sulfated heparin disaccharide or fibroblast growth factor receptor‐3 autoantibodies. Although only Class IV evidence exists for IVIG use in necrotizing autoimmune myopathy, it should be considered for anti‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase myositis given the risk of long‐term disability. Insufficient evidence exists for the use of IVIG in Miller‐Fisher syndrome, IgG and IgA paraproteinemic neuropathy, autonomic neuropathy, chronic autoimmune neuropathy, polymyositis, idiopathic brachial plexopathy and diabetic lumbosacral radiculoplexopathy.
Patients with anti-MAG neuropathy present with distal demyelinating polyneuropathy, IgM monoclonal gammopathy, and elevated titers of anti-MAG antibodies.
This paper reviews what is known about the ...clinical presentation, course, pathophysiology, and treatment of anti-MAG neuropathy, with considerations for the design of therapeutic trials.
A literature review of the medical and scientific literature related to anti-MAG neuropathy, and the design of therapeutic clinical trials in peripheral neuropathy.
Anti-MAG neuropathy can remain indolent for many years but then enter a progressive phase. Highly elevated antibody titers are diagnostic, but intermediate titers can also occur in chronic inflammatory demyelinating polyneuropathy (CIDP). The peripheral nerves can become inexcitable, thereby masking the demyelinating abnormalities. There is good evidence that the anti-MAG antibodies cause neuropathy. Reduction of the autoantibody concentration by agents that target B-cells was reported to result in clinical improvement in case series and uncontrolled trials, but not in controlled clinical trials, probably due to inadequate trial design.
We propose that therapeutic trials for anti-MAG neuropathy include patients with the typical presentation, some degree of weakness, highly elevated anti-MAG antibody titers, and at least one nerve exhibiting demyelinating range abnormalities. Treatment with one or a combination of anti-B-cell agents would aim at reducing the autoantibody concentration by at least 60%. A trial duration of 2 years may be required to show efficacy. The neuropathy impairment score of the lower extremities (NIS-LL) plus the Lower Limb Function (LLF) score would be a suitable primary outcome measure.
Objective
To examine the impact on quality of life (QOL) of patients with hATTR amyloidosis with polyneuropathy treated with inotersen (Tegsedi™) versus placebo.
Methods
Data were from the NEURO-TTR ...trial (ClinicalTrials.gov Identifier: NCT01737398), a phase 3, multinational, randomized, double-blind, placebo-controlled study of inotersen in patients with hATTR amyloidosis with polyneuropathy. At baseline and week 66, QOL measures—the Norfolk-QOL-Diabetic Neuropathy (DN) questionnaire and SF-36v2
®
Health Survey (SF-36v2)—were assessed. Treatment differences in mean changes in QOL from baseline to week 66 were tested using mixed-effect models with repeated measures. Responder analyses compared the percentages of patients whose QOL meaningfully improved or worsened from baseline to week 66 in inotersen and placebo arms. Descriptive analysis of item responses examined treatment differences in specific activities and functions at week 66.
Results
Statistically significant mean differences between treatment arms were observed for three of five Norfolk-QOL-DN domains and five of eight SF-36v2 domains, with better outcomes for inotersen than placebo in physical functioning, activities of daily living, neuropathic symptoms, pain, role limitations due to health problems, and social functioning. A larger percentage of patients in the inotersen arm than the placebo arm showed preservation or improvement in Norfolk-QOL-DN and SF-36v2 scores from baseline to week 66. Responses at week 66 showed more substantial problems with daily activities and functioning for patients in the placebo arm than in the inotersen arm.
Conclusion
Patients with hATTR amyloidosis with polyneuropathy treated with inotersen showed preserved or improved QOL at 66 weeks compared to those who received placebo.
Neuromuscular diseases such as polymyositis, dermatomyositis, peripheral neuropathy, and disorders of neuromuscular transmission are reported to be complications of hematopoietic stem cell ...transplantation (HSCT). Although cases have been reported with allogeneic HSCT in the setting of chronic graft versus host disease, they are also known to occur without evidence thereof and even occur in the setting of autologous HSCT. The 2005 National Institutes of Health Consensus Criteria classify polymyositis and dermatomyositis as “distinctive” features, and neuropathy and MG as “other” features. These neuromuscular complications present very similarly to the idiopathic autoimmune disorders and respond to similar treatment modalities. Muscle Nerve, 2015 Muscle Nerve 52: 480–487, 2015
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and anti–myelin‐associated glycoprotein (anti‐MAG) neuropathy are three demyelinating acquired ...neuropathies, with distinct responses to immunotherapy. In placebo‐controlled, double‐blind, randomized trials, intravenous immunoglobulin (IVIg) has been effective for CIDP and MMN, and plasmapheresis has been effective for CIDP. Corticosteroids have been beneficial in controlled trials for CIDP. Other agents, including cyclophosphamide, rituximab, azathioprine, cyclosporine, interferons, fludarabine, mycophenolate mofetil, and etanercept, have been reported to benefit some patients with inflammatory demyelinating neuropathies in case series and case reports. This review examines the use and toxicity associated with these immunotherapy medications in treating patients with chronic immune‐mediated demyelinating neuropathies. Muscle Nerve, 2009
Intravenous immunoglobulin (IVIG) is a therapeutic biologic agent that has been prescribed for over two decades to treat various neuromuscular conditions. Most of the treatments are given off‐label, ...as little evidence from large randomized trials exists to support its use. Recently, IGIV‐C has received an indication for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP). Because of the lack of evidence, an ad hoc committee of the AANEM was convened to draft a consensus statement on the rational use of IVIG for neuromuscular disorders. Recommendations were categorized as Class I–IV based on the strength of the medical literature. Class I evidence exists to support the prescription of IVIG to treat patients with Guillain–Barré syndrome (GBS), CIDP, multifocal motor neuropathy, refractory exacerbations of myasthenia gravis, Lambert–Eaton syndrome, dermatomyositis, and stiff person syndrome. Treatment of Fisher syndrome, polymyositis, and certain presumed autoimmune neuromuscular disorders is supported only by Class IV studies, whereas there is no convincing data to substantiate the treatment of inclusion body myopathy (IBM), idiopathic neuropathies, brachial plexopathy, or diabetic amyotrophy using IVIG. Treatment with IVIG must be administered in the context of its known adverse effects. There is little evidence to advise the clinician on the proper dosing of IVIG and duration of therapy. Muscle Nerve, 2009
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic neuropathy characterized by symmetrical proximal and distal weakness, with large‐fiber sensory loss, impaired balance, and ...areflexia. This condition is often underdiagnosed due to the frequent absence of these classical clinical features as well as abnormalities that arise during confirmatory tests. Current diagnostic tests involve the measurement of cerebrospinal fluid protein levels, nerve biopsy, electrodiagnostic testing, and treatment response. Due to the clinical heterogeneity of the condition and a lack of a consistent confirmatory test, a variety of diagnostic criteria were developed. At least 14 different sets of diagnostic criteria have been proposed that each have varying diagnostic sensitivities. Although the diagnostic tests used within these criteria are useful, they individually offer evidence to support, rather than definitively confirm, the diagnosis of CIDP. Currently, there is no biomarker that can reliably identify all patients with CIDP, but it is evident that such a biomarker is urgently needed to ensure effective disease management.
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