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.

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.

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.

Phenotypic Variability Leads to Under-recognition of HNPP.

OBJECTIVE: To determine the range of phenotypic expression in individuals with hereditary neuropathy with liability to pressure palsy (HNPP) with the chromosome 17 deletion. METHODS: Twenty-one patients from 10 families were studied. Genetic testing was performed in at least one member of each family. Every patient was examined clinically, electrophysiological data was available in 18 patients, and a sural nerve biopsy was performed on 4 patients. In addition, a patient symptom questionnaire was administered over the telephone to identify symptomatic individuals from the at-risk population. RESULTS: The identified phenotypes were those of compressive neuropathy, symmetric peripheral neuropathy (often misdiagnosed as Charcot-Marie-Tooth neuropathy), acute brachial paralysis, and confluent mononeuropathy multiplex. Many individuals were oligosymptomatic and these formed the majority of undiagnosed patients. CONCLUSIONS: The presence of mild symptoms and the marked phenotypic variability of the disease result in underdiagnosis of HNPP.