Management Strategies in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic, proximal and distal, asymmetrical or symmetrical, motor and sensory demyelinating polyneuropathy with a progressive course for at least 2 months. The accurate diagnosis is crucial as CIDP is amenable to treatment. Recent advances have provided new strategies and options for management of this syndrome. In this article, we review the clinical and diagnostic features as well as discuss recent insights and treatment strategies along with our experience in the management of patients with CIDP

Ravulizumab use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice

PurposeTo describe the early experience of ravulizumab use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG).MethodsThis multicenter retrospective study included AChR+ve gMG patients who were treated with ravulizumab and had both pre- and post-ravulizumab myasthenia gravis activities of daily living (MG-ADL) scores. Clinical information regarding MG history, concomitant treatment(s), MG-ADL, other MG-specific measures, and adverse events were recorded.ResultsA total of 18 patients with mean age of 61.83 (±16.08, n = 18) years were included in this cohort. In 10 complement inhibitor naive patients, a clinically meaningful reduction in mean Mg-ADL (baseline: 6.6 (±3.58) vs. 4.4 (±2.28), post ravulizumab) was seen. 6 out of 10 patients (60%) had clinically meaningful reduction post ravulizumab and two achieved minimum symptom expression (MSE). In 8 patients switched from eculizumab to ravulizumab, further reduction was noted in post ravulizumab mean MG-ADL (Baseline: 3.25 (±3.34) vs. 1.5 (±2.34) post ravulizumab). None of the patients who switched from eculizumab to ravulizumab experienced worsening symptoms. Eleven out of 14 (78.5%) patients on prednisone therapy were able to reduce their prednisone dose post-ravulizumab. None of the patients experienced any major side effects.ConclusionIn our clinical practice, 60% of AChR+ve gMG complement inhibitor naive patients experienced a clinically meaningful improvement in MG-ADL scores with ravulizumab. Patients were safely switched from eculizumab to ravulizumab and had further improvement in their mean MG-ADL scores. Of those on prednisone therapy, the majority were able to reduce their prednisone dosage

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Diabetic and non-diabetic lumbosacral radiculoplexus neuropathy

Background: Lumbosacral radiculoplexus neuropathy (LRPN) originally described in diabetic patients is a distinct clinical condition characterized by debilitating pain, weakness and atrophy most commonly affecting the proximal thigh muscles asymmetrically. The syndrome is usually monophasic and preceded by significant weight loss (at least more than 10 lbs). Though a self-limited condition, recovery is gradual with some residual weakness. Recent advances and research has provided new insights in the pathogenesis and thereby management of this syndrome. In this paper, we review the clinical and diagnostic features as well as discuss recent insights and treatment strategies along with our experience in the management of patients with diabetic and non-diabetic LRPN. Materials and Methods: Literature in English published between 1953 and 2008 was searched in the MEDLINE and Pubmed database, maintained by the US National library of medicine and National institutes of health, using key words of diabetic amyotrophy, lumbosacral radiculoplexus neuropathy, diabetic proximal neuropathy, diabetic radiculopathy and diabetic lumbosacral plexopathy. In addition, literature reported in various textbooks on peripheral neuropathy was reviewed as well. Observation: The diagnosis relies mostly on clinical suspicion and characteristic electromyographic findings. The exact pathogenesis of the illness remains unknown, but there seems to be a component of immune-mediated inflammatory microvasculitis which causes secondary ischemia of the lumbosacral plexus. This has prompted a trial of immunosuppressive agents (like steroids) with an attempt to alter the course of the illness. A few reports have noted that immunosuppression when instituted early in the course of the illness (within three months of symptom onset) may hasten the recovery and improve symptoms. Conclusion: Though the exact mechanism of LRPN in diabetic and non-diabetic patients remains unknown, new evidence alludes to an underlying inflammatory vasculitic process. Early treatment with immunosuppressants may be beneficial in some cases, although the data available at this time is limited to a small cohort of patients. The decision is individualized weighing the risks and benefits in a given patient. Future research in this direction with double-blinded case-controlled studies is required to investigate this further

Inflammatory demyelinating neuropathies

Early and effective treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) is important to minimize axonal degeneration that occurs secondary to demyelination. The disease course is invariably chronic, so long-term treatment is often required, and adverse effects and costs are important considerations in devising a treatment plan. CIDP responds to prednisone, but long-term treatment can result in significant adverse effects. Azathioprine, mycophenolate mofetil, and cyclosporine can be used as steroid-sparing agents and may facilitate more rapid and successful tapering of prednisone. Intravenous immunoglobulin (IVIg) and plasma exchange are also effective in the treatment of CIDP and can be used in patients who are unresponsive to prednisone or develop steroid-related adverse effects. IVIg may also be used as a first-line treatment, but its cost can be a limiting factor. A few uncontrolled studies have suggested that pulsed weekly methylprednisolone is both effective and well tolerated in the long-term treatment of CIDP. Treatments based on rituximab or cyclophosphamide have also been used in resistant disease. Variants of CIDP have been described on the basis of their association with specific antibodies or immunoglobulins and their response to specific immunomodulatory treatments. Multifocal motor neuropathy with conduction block responds to IVIg in the majority of patients. However, weakness may slowly worsen over time, and some patients become unresponsive. Anecdotal reports suggest that rituximab may be useful in patients who develop progressive disease. Placebo-controlled trials in anti-myelin-associated glycoprotein neuropathy suggest that rituximab is effective and, with a combination of prednisone and cyclophosphamide, numbness and strength may improve. Other treatments that may be effective include plasma exchange and IVIg. Treatment is generally started with prednisone, IVIg, or plasma exchange. Rituximab and cyclophosphamide are used only in progressive, treatment-resistant disease because of the potential for serious adverse effects. © Current Medicine Group, LLC 2009

Diabetic and non-diabetic lumbosacral radiculoplexus neuropathy

Background: Lumbosacral radiculoplexus neuropathy (LRPN) originally described in diabetic patients is a distinct clinical condition characterized by debilitating pain, weakness and atrophy most commonly affecting the proximal thigh muscles asymmetrically. The syndrome is usually monophasic and preceded by significant weight loss (at least more than 10 lbs). Though a self-limited condition, recovery is gradual with some residual weakness. Recent advances and research has provided new insights in the pathogenesis and thereby management of this syndrome. In this paper, we review the clinical and diagnostic features as well as discuss recent insights and treatment strategies along with our experience in the management of patients with diabetic and non-diabetic LRPN. Materials and Methods: Literature in English published between 1953 and 2008 was searched in the MEDLINE and Pubmed database, maintained by the US National library of medicine and National institutes of health, using key words of diabetic amyotrophy, lumbosacral radiculoplexus neuropathy, diabetic proximal neuropathy, diabetic radiculopathy and diabetic lumbosacral plexopathy. In addition, literature reported in various textbooks on peripheral neuropathy was reviewed as well. Observation: The diagnosis relies mostly on clinical suspicion and characteristic electromyographic findings. The exact pathogenesis of the illness remains unknown, but there seems to be a component of immune-mediated inflammatory microvasculitis which causes secondary ischemia of the lumbosacral plexus. This has prompted a trial of immunosuppressive agents (like steroids) with an attempt to alter the course of the illness. A few reports have noted that immunosuppression when instituted early in the course of the illness (within three months of symptom onset) may hasten the recovery and improve symptoms. Conclusion: Though the exact mechanism of LRPN in diabetic and non-diabetic patients remains unknown, new evidence alludes to an underlying inflammatory vasculitic process. Early treatment with immunosuppressants may be beneficial in some cases, although the data available at this time is limited to a small cohort of patients. The decision is individualized weighing the risks and benefits in a given patient. Future research in this direction with double-blinded case-controlled studies is required to investigate this further