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

Purpose: To describe the early experience of ravulizumab use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG). Methods: This 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. Results: A 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. Conclusion: In 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.

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.

A Rare Case of Burkitt's Lymphoma Presenting With Features Mimicking Vogt-Koyanagi-Harada Disease.

Here, we report a case of Burkitt's lymphoma in an HIV-positive patient presenting with features suggestive of Vogt-Koyanagi-Harada disease (VKHD), which in retrospect was likely a misdiagnosis. We hope to describe a rare presentation of lymphoma in order to prevent misdiagnosis and promote early recognition. The patient was a 25-year-old male who initially presented with right eye pain and blurry vision. He was found to have bilateral serous retinal detachments and was diagnosed with VKHD and started on prednisone. He stopped taking the prednisone, and his vision worsened. He then developed right eye ptosis, restricted eye movements, nausea, vomiting, headache, dysphagia, tongue deviation, and slurred speech. MRI showed diffuse cranial nerve enhancement. He was found to be positive for HIV and Hepatitis A with CD4 count of 41. Lumbar puncture showed WBC 83 (94% lymphocytes), RBC 1460, glucose 62, and protein 195, with Epstein-Barr virus (EBV) positivity and negative cytology. Gd1a antibody was positive (72). He underwent empiric treatment with IV solumedrol for possible VKHD exacerbation, followed by empiric intravenous immune globulin (IVIG) for possible acute inflammatory demyelinating polyneuropathy (AIDP). He subsequently developed diffuse limb weakness and loss of reflexes, and he was treated with plasma exchange (PLEX). He demonstrated minimal response to treatment. Electromyography (EMG) was unrevealing, and the MRI of the cervical and lumbar spine showed diffuse nerve root thickening and enhancement. He underwent an esophagogastroduodenoscopy (EGD) for continued dysphagia, and the biopsy was positive for an aggressive B-cell lymphoma strongly favoring Burkitt's lymphoma. VKHD is a rare condition diagnosed based on retinal exam findings. Few cases of lymphoma report findings suggestive of VKHD. This is a rare case of lymphoma initially presenting with these retinal findings. Understanding this potential presentation of lymphoma is essential for early diagnosis and treatment and for optimizing patient outcomes.

The use of eculizumab in ventilator-dependent myasthenia gravis patients.

INTRODUCTION/AIMS: Eculizumab has been shown to be efficacious in acetylcholine receptor antibody-positive (AChR+ ) Myasthenia Gravis Foundation of America (MGFA) class II, III, and IV generalized myasthenia gravis (gMG) patients. However, it has not been studied in MGFA class V gMG patients. METHODS: We report three AChR+ , refractory, MGFA class V gMG patients treated with eculizumab. MGFA class, MG-Composite (MGC) score and MG Activities of Daily Living (MG-ADL) score were assessed before and after eculizumab. RESULTS: Two of three gMG patients, refractory to intravenous immunoglobulin, plasmapheresis, prednisone, and (in one case) rituximab, showed a robust response to eculizumab with marked improvement in MGFA, MG-ADL, and MGC measures. The third patient showed a partial response to eculizumab but remained on noninvasive ventilation and gastrostomy intubation. Patients 1 and 2 achieved minimal manifestation status at week 4 and week 6, respectively, and showed continued improvement on MG-ADL and MGC scores through weeks 55 and 43, respectively, with eculizumab. The third patient showed a partial response at week 10, followed by a slight decline in his MG-ADL score, but noted a slow but an incomplete improvement afterward on MG-ADL and MGC scores, possibly due to delayed eculizumab infusion. DISCUSSION: Eculizumab may play a role in the treatment of patients with MGFA class V, refractory gMG. Larger studies are required to provide further evidence.

Rituximab in refractory chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a disorder in which early effective treatment is important to minimize disability from axonal degeneration. It has been suggested that some patients with CIDP may benefit from rituximab therapy, but there is no definitive evidence for this. METHODS: Baseline and post-rituximab-therapy neuromuscular Medical Research Council (MRC) sum scores, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, and functional status were assessed in 11 patients with refactory CIDP. RESULTS: The MRC sum score, INCAT disability score, and functional status improved in all patients after rituximab therapy. DISCUSSION: Our study provides evidence of the efficacy of rituximab therapy in at least some patients with CIDP. A placebo-controlled study to assess the effectiveness of rituximab therapy in CIDP with and without nodal antibodies is required to identify disease markers that predict responsiveness.

Immunohistochemistry and electrophysiological findings in swine abattoir workers with immune-mediated polyradiculoneuropathy.

IMPORTANCE: Workers exposed to aerosolized brain in a swine-processing plant developed immune-mediated polyradiculoneuropathy (IP) possibly triggered by an immune response. OBJECTIVE: Immunohistochemistry results were correlated with electrophysiological variables to examine the immunopathogenesis of this disorder. DESIGN/SETTING: Laboratory studies used normal nerve tissue that was exposed to sera from 12 IP patients; 10 exposed controls; and 10 unexposed controls. Clinical and electrophysiological data from IP patients were obtained from medical record reviews. MAIN OUTCOME MEASURES: Analysis included electromyography results of IP patients and nerve conduction studies examining CMAP amplitude, distal motor latency, motor conduction velocity, F-wave latency, sensory nerve action potential amplitude, and sensory nerve conduction velocity. Case and control results were compared relative to distance from exposure. RESULTS: Electrodiagnostic findings revealed prolongation of the distal and f-wave latencies suggestive of demyelination at the level of the nerve root and distal nerve terminals. Immunohistochemical results identified an antibody to the peripheral nerve, with staining at the level of the axolemma. Thus, IP may be a primary axonopathy with secondary paranodal demyelination causing the conduction changes. Staining of the distal and proximal portions of the nerve appears consistent with easier access through the blood-nerve barrier. CONCLUSIONS AND RELEVANCE: IP is an immune-mediated neuropathy related to antibodies to an axon-based antigen on peripheral nerves. Secondary paranodal demyelination is likely. Further studies to identify the primary axonal antigenic target would be useful.

Engineered agrin attenuates the severity of experimental autoimmune myasthenia gravis.

INTRODUCTION: Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG). METHODS: EAMG was induced in female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR) and complete Freund's adjuvant (CFA). NT-1654 was dissolved in phosphate-buffered saline (PBS) and injected daily subcutaneously into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days. RESULTS: We showed that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMG rats. DISCUSSION: We demonstrated that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMG rats. Muscle Nerve 57: 814-820, 2018.

Multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) was first described in 1988 as a purely motor neuropathy affecting multiple motor nerves. The diagnosis was based entirely on demonstrating electrophysiological evidence of a conduction block (CB) that selectively affected motor axons, with sparing of sensory axons even through the site of motor CB. Subsequently, a similar disorder was reported but with absence of demonstrable CB on routine nerve conduction studies and there is still some debate as to whether MMN without CB is related to MMN. MMN is thought to be an inflammatory neuropathy related to an immune attack on motor nerves. The conventional hypothesis is that the primary pathology is segmental demyelination, but recent research raises the possibility of a primary axonopathy. Anti-GM1 antibodies can be found in some patients but it is unclear whether these antibodies are pathogenic. Intravenous immunoglobulin is the mainstay of treatment but other immunosuppressive treatments can also be effective.

Post-streptococcal vasculopathy with evolution to Degos' disease.

Degos' disease or malignant atrophic papulosis is a rare disseminated occlusive vasculopathy affecting the skin, gastrointestinal tract, central nervous system, and less often other organ systems. The exact etiology of this vasculopathy has not been established. Infections, autoimmune disease and coagulation defects have been proposed as underlying pathogenic mechanisms, but none have been confirmed. Here, we report the clinical, radiological and histopathologic features of Degos' disease in a 41-year-old man following streptococcal throat infection. Prior postulated hypothesis as post-infectious immunologic mechanism may be further supported by this case.

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.

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.

Treatment of chronic inflammatory demyelinating polyneuropathy with pulsed oral steroids.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy that responds to various immunosuppressive treatments. Oral daily prednisone therapy is effective and inexpensive, but the long-term treatment that is usually necessary leads to serious adverse effects. Consequently, intravenous immunoglobulin and plasma exchange have been widely used to treat CIDP, making treatment expensive and inconvenient. A steroid regimen that reduces adverse effects but preserves efficacy would simplify treatment. Pulsed steroids have nongenomic actions not seen with low-dose steroids, including rapid inhibition of arachidonic acid release and of calcium and sodium cycling across plasma membranes of immune cells. OBJECTIVE: To study the efficacy, safety, and tolerability of pulsed oral methylprednisolone therapy in patients with CIDP. DESIGN: Open-label prospective study. SETTING: University of Minnesota Neuropathy Center, Minneapolis. PATIENTS: Ten patients (3 women and 7 men) with CIDP followed up for at least 22 months. MAIN OUTCOME MEASURES: Neuromuscular score and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score were used as outcome measures for efficacy; weight, blood pressure, changes in bone density, and steroid-related adverse effect questionnaire were used as outcome measures for safety. RESULTS: This steroid regimen leads to significant improvement in weakness and disability in all patients treated and to off-treatment remission in 60% of patients. Treatment was fairly well tolerated, and only 1 patient discontinued treatment because of adverse effects. Steroid-induced osteoporosis remained a problem, especially in older patients. CONCLUSIONS: Pulsed oral methylprednisolone may be efficacious in the long-term treatment of CIDP and is relatively well tolerated. Remission can be induced in most patients, especially those with a shorter duration of disease.

Response to oral supplementation in copper deficiency myeloneuropathy.

Neurological manifestations due to copper deficiency include ataxic myeloneuropathy that resembles subacute combined degeneration due to B12 deficiency. We report our experience in the treatment of 10 patients with copper deficiency myeloneuropathy and conclude that copper supplementation leads to stabilization rather than improvement in the neurological deficits.

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.