Myxovirus resistance protein A (MxA) expression in myositides: Sarcoplasmic expression is common in both dermatomyositis and lupus myositis.

INTRODUCTION/AIMS: Myxovirus resistance protein A (MxA) is a type I interferon (IFN1) pathway activation marker and MxA sarcoplasmic expression is currently recognized as a highly specific marker for dermatomyositis (DM). However, we have frequently observed endothelial tubuloreticular inclusions (TRI), another surrogate IFN1 activation marker, in a variety of overlap myositides. The aim of this study was to examine MxA expression in those myositides. METHODS: We retrospectively performed MxA immunostaining on a wide range of myositides. RESULTS: MxA sarcoplasmic expression was present in DM (94.4%, 17/18), active lupus myositis (LM, 80%,16/20), inactive LM (36%, 4/11), antisynthetase syndrome (ASyS, 20%, 2/10), systemic sclerosis (13%, 2/15), Sjogren's syndrome (7.7%, 1/13), and human immunodeficiency virus (HIV) myositis (5.6%, 1/18) and was absent in immune-mediated necrotizing myopathy (IMNM, 0/16) and hydroxychloroquine myopathy (0/5). The sensitivity and specificity of MxA sarcoplasmic expression for LM and DM combined compared with all other myositides were 84.6% (95% CI: 69.5-94.1) and 92.1 (95% CI: 83.6-97.0), respectively, and superior to TRIs. MxA capillary expression was nonspecific. Histologically, 35% of LM cases demonstrated a unique panfascicular necrotizing myopathy pattern. The remainder of the LM cases had significant morphological overlap with DM/ASyS (20%), IMNM (20%), or polymyositis (15%). DISCUSSION: MxA sarcoplasmic expression is highly prevalent in LM and DM and is a useful marker in differentiating DM and LM from other myositides. LM can manifest in various pathology patterns that need to be differentiated from DM, IMNM, ASyS, and polymyositis.

An Unusual Presentation of Dermatomyositis With Muscle Hypertrophy.

Peripheral nerve hyperexcitability is a rare disorder characterized by spontaneous motor unit activity. Although peripheral nerve hyperexcitability is seen in multiple immune-mediated neurological conditions, an association with dermatomyositis has rarely been reported. We present a 65-year-old woman with serological and muscle biopsy features of dermatomyositis who also developed marked muscle hypertrophy, stiffness, and delayed relaxation along with electrodiagnostic features of peripheral nerve hyperexcitability such as that seen in Isaacs syndrome.

Phase 2 trial in acetylcholine receptor antibody-positive myasthenia gravis of transition from intravenous to subcutaneous immunoglobulin: The MGSCIg study.

BACKGROUND AND PURPOSE: Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody-positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2. METHODS: This multicenter North American open-label prospective investigator-initiated study had two components: the IVIg Stabilization Period (ISP) enrolling patients already on IVIg as part of routine clinical care (Weeks -10 to -1), followed by transition of stable MG subjects to SCIg in the Experimental Treatment Period (ETP; Weeks 0 to 12). We hypothesized that >65% of patients entering the ETP would have a stable Quantitative Myasthenia Gravis (QMG) score from Week 0 to Week 12. Secondary outcome measures included other efficacy measures, safety, tolerability, IgG levels, and treatment satisfaction. RESULTS: We recruited 23 patients in the ISP, and 22 entered the ETP. A total of 12 subjects (54.5%) were female, and 18 (81.8%) were White, with mean age 51.4 ± 17 years. We obtained Week 12 ETP QMG data on 19 of 22; one subject withdrew from ETP owing to clinical deterioration, and two subjects withdrew due to dislike of needles. On primary analysis, 19 of 22 participants (86.4%, 95% confidence interval = 0.72-1.00) were treatment successes using last observation carried forward (p = 0.018). Secondary efficacy measures supported MG stability. SCIg was safe and well tolerated, and IgG levels were stable. Treatment satisfaction was comparable between ISP and ETP. CONCLUSIONS: MG patients on IVIg as part of their routine clinical care remained stable on monthly IVIg dosage, and most maintained similar disease stability on SCIg.

Rapidly Progressive Paraneoplastic Neuropathy Associated with Renal Cell Carcinoma: A Case Report.

Background: Paraneoplastic neurological disorders are rare syndromes that occur with various malignancies including renal cell carcinoma. Symptoms of paraneoplastic neurological disorders are diverse and involve either the central nervous system, peripheral nervous system, or both. Case Presentation: We present a patient with diffuse limb pain, rapidly progressive asymmetric motor and sensory symptoms and distal upper limb atrophy. Electrodiagnostic testing was suggestive of mononeuritis multiplex. Initial empiric treatment with corticosteroids did not lead to improvement. Further diagnostic studies revealed bilateral clear cell renal carcinoma. Treatment with plasmapheresis led to significant and rapid improvement in pain and limb strength. Conclusions: This case highlights the rare occurrence of paraneoplastic neuropathy in renal cancer and emphasizes the importance of screening for malignancy in patients presenting with rapidly progressive multifocal neuropathy.

Excellent response to therapeutic plasma exchange in myasthenia gravis patients irrespective of antibody status.

INTRODUCTION: The primary objective of this study was to assess response to plasma exchange (PLEX) in myasthenia gravis (MG) patients with and without autoantibodies (Ab) to acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). Analysis was also done to determine if correlation existed between sex, early or late onset MG, thymoma, or thymectomy and response to PLEX. MATERIALS AND METHODS: Data was analyzed on 58 consecutive MG patients treated with PLEX. Responses were categorized as complete response, clinical improvement requiring maintenance PLEX, or no/minimal response to PLEX. RESULTS: Eighty-eight percent (51/58) of patients were Ab-positive; 44 had AChR and 7 had MuSK Ab. Complete response was seen in 26 patients (24 Ab+), 24 remain on maintenance PLEX (19 Ab+), and 2 had no/minimal response (both AChR Ab+). Ab status (P = 0.43), AChR Ab (P = 0.10), MuSK Ab (P = 0.45), early onset MG (P = 0.63), thymoma (P = 0.46), and thymectomy (P = 0.16) were not significantly associated with outcome. Patient sex did show significant association with outcome (P = 0.01), with men more likely to have complete response and women more likely to require maintenance. Late onset MG is significantly associated with higher likelihood of complete response (P = 0.03). Antibody titers declined after PLEX in 83% of patients with complete response, in whom pre- and post-PLEX titers were available (n = 6). CONCLUSIONS: In conclusion, our study showed 96% response rate to PLEX in MG; however, only patient gender and late onset MG were significantly associated with treatment response.

Treatment of painful peripheral neuropathy.

Neuropathic pain management is an important aspect in the management of painful peripheral neuropathy. Anticonvulsants and antidepressants have been studied extensively and are often used as first-line agents in the management of neuropathic pain. In this article, data from multiple randomized controlled studies on painful peripheral neuropathies are summarized to guide physicians in treating neuropathic pain. Treatment is a challenge given the diverse mechanisms of pain and variable responses in individuals. However, most patients derive pain relief from a well-chosen monotherapy or well-designed polypharmacy that combines agents with different mechanisms of action.

Clinical findings in MuSK-antibody positive myasthenia gravis: a U.S. experience.

We performed a retrospective chart review on 53 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients at nine university-based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9-79 years. Twenty-seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long-term (> or =3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG-related death. This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.

Von hippel-lindau disease associated with thymoma and myasthenia gravis.

Von Hippel-Lindau (VHL) disease is an autosomal-dominant disorder characterized by central nervous system hemangioblastomas, retinal angioma, and renal cell carcinoma. Thymoma and autoimmune neurologic disorders have not been reported in association with VHL disease. We report a unique concurrence of antibody-positive myasthenia gravis and thymoma in a patient with VHL disease. Although this may be coincidental, a possible genetic link between thymoma and VHL is described.

Painful peripheral neuropathy and its nonsurgical treatment.

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathy. Antidepressants and anticonvulsants are the two pharmacological classes most widely studied and represent first-line agents in the management of neuropathic pain. The number of pharmacological agents that have demonstrated effectiveness for neuropathic pain continues to expand. In the current review, we summarize data from randomized, controlled pharmacological trials in painful peripheral neuropathies. Although neuropathic pain management remains challenging because the response to therapy varies considerably between patients, and pain relief is rarely complete, a majority of patients can benefit from monotherapy using a well-chosen agent or polypharmacy that combines medications with different mechanisms of action.

Transverse myelitis in systemic sclerosis.

BACKGROUND: Neurological involvement occurs rarely with systemic sclerosis (SSc). Only a few cases of transverse myelopathy have been reported in the setting of SSc. OBJECTIVE: To describe a patient with SSc who developed transverse myelitis that improved during a course of immunosuppression. RESULTS: A 30-year-old woman with SSc presented with subacute onset of bilateral lower extremity weakness and numbness. Results of magnetic resonance imaging and cerebrospinal fluid studies supported a diagnosis of transverse myelitis. The patient responded favorably to a course of corticosteroids and cyclophosphamide. No overlapping autoimmune disorders were evident. Clinical follow-up showed significant recovery, with resolution of radiological abnormalities. CONCLUSION: Transverse myelitis can occur as a rare manifestation of SSc and may respond favorably to immunosuppressive therapy.

Adult polyglucosan body disease associated with lewy bodies and tremor.

BACKGROUND: Adult polyglucosan body disease (PGBD) is rare and typically presents with upper and lower motor neuron involvement and neurogenic bladder. Extrapyramidal features are unusual in PGBD and are presumed secondary to widespread pathology that includes the basal ganglia. There are no prior reports of Lewy bodies in PGBD. OBJECTIVE: To report a unique finding of Lewy bodies in a patient with PGBD. REPORT OF A CASE A 46-year-old woman initially presented with a 4-year history of resting tremor. The tremor responded to levodopa therapy. Several months later, she developed upper and lower motor neuron involvement and other clinical features of PGBD. A sural nerve biopsy specimen revealed intra-axonal polyglucosan bodies that confirmed the clinical diagnosis. Bulbar and limb weakness progressed, and she developed dementia. She died 6 years after onset. At autopsy, extensive polyglucosan body formation was found in many regions of the central nervous system. In addition, numerous alpha-synuclein staining Lewy bodies were observed in the substantia nigra, accompanied by marked neuron depopulation. CONCLUSIONS: To our knowledge, this is the first report of adult PGBD associated with Lewy bodies and levodopa-responsive tremor. Although polyglucosan bodies were seen in substantia nigra, it is most likely that our patient had coexisting Parkinson disease.