The Role of Mutations on HLA Genes in Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, posttetanic potentiation, and autonomic changes. [1] The initial presentation can be similar to that of myasthenia gravis (MG), but the progressions of the 2 diseases have some important differences. LEMS disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca2+ channels involved with neurotransmitter release.

The Significance of Autoantibodies in Juvenile Dermatomyositis

Juvenile dermatomyositis is a chronic and rare autoimmune disorder classified into the spectrum of idiopathic inflammatory myopathies. Although this entity is mainly characterized by the presence of pathognomonic cutaneous lesions and proximal muscle weakness, the clinical manifestation can be highly heterogeneous; thus, diagnosis might be challenging. Current treatment recommendations for juvenile dermatomyositis, based mainly upon case series, include the use of corticosteroids, immunomodulatory, and immunosuppressive agents. Recently, several specific autoantibodies have been shown to be associated with distinct clinical phenotypes of classic dermatomyositis. There is a need to further evaluate their relevance in the formation of various clinical features. Furthermore, while providing more personalized treatment strategies, one should consider diversity of autoantibody-related subgroups of juvenile dermatomyositis.

Isolated proximal weakness of the legs due to neuroborreliosis

Proximal muscle weakness of the legs is a symptom with a broad differential diagnosis. It is mainly caused by neuromuscular disorders and is often a diagnostic challenge. Here, we present a 73-year-old man with isolated proximal weakness of the legs due to lumbar root involvement on the basis of neuroborreliosis. After treatment with intravenous antibiotics he recovered completely. This is the first described case with isolated proximal muscle weakness of the legs due to neuroborreliosis. Despite the fact neuroborreliosis is a rare cause of proximal muscle weakness of the legs, clinicians should include it in their differential diagnosis, especially since it is a treatable condition.

A case of motor and sensory polyneuropathy induced by primary hyperparathyroidism

Primary hyperparathyroidism (PHP) is a disease in which excessive amounts of parathyroid hormone (PTH) are secreted and calcium levels in the blood increase. Hypercalcemia caused by PHP has a major influence on the peripheral nervous system and produces symptoms such as muscle cramps, paresthesia, and proximal muscle weakness. Here we report a rare case of sensory-dominant polyneuropathy caused by PHP, which improved after surgery.

Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes

Background and Objective:Multiple studies highlighting diagnostic utility of neurofascin 155 (NF155)-IgG4 in chronic demyelinating inflammatory polyradiculoneuropathy (CIDP) have been published. However, few studies comprehensively address the long-term outcomes, or clinical utility of NF155-IgM or NF155-IgG, in the absence of NF155-IgG4. In this study we evaluate phenotypic and histopathological specificity, and differences in outcomes between these NF155 antibody isotypes or IgG subclasses. We also compare NF155-IgG4 seropositive cases to other seropositive demyelinating neuropathies.Methods:In this study, neuropathy patient sera seen at Mayo Clinic were tested for NF155-IgG4, NF155-IgG and NF155-IgM autoantibodies. Demographic and clinical data of all seropositive cases were reviewed.Results:We identified 32 NF155 patients (25 NF155-IgG positive [20 NF155-IgG4 positive], 7 NF155-IgM seropositive). NF155-IgG4 seropositive patients clinically presented with distal more than proximal muscle weakness, positive sensory symptoms (prickling, asymmetric paresthesia, neuropathic pain) and gait ataxia. Cranial nerve involvement (11/20, 55%) and papilledema (4/12, 33%) occurred in many. Electrodiagnostic testing (EDX) demonstrated demyelinating polyradiculoneuropathy (19/20, 95%). Autonomic involvement occurred in 45% (n=9, median CASS score 3.5, range 1-7). Nerve biopsies from the NF155-IgG4 patients (n=11) demonstrated grouped segmental demyelination (50%), myelin reduplication (45%) and paranodal swellings (50%). Most patients needed 2nd and 3rd line immunosuppression but had favorable long-term outcomes (n=18). Among 14 patients with serial EDX over 2 years, all except one demonstrated improvement after treatment. NF155-IgG positive NF155-IgG4 negative (NF155-IgG positive) and NF155-IgM positive patients were phenotypically different from NF155-IgG4 seropositive patients. Sensory ataxia, neuropathic pain, cerebellar dysfunction and root/plexus MRI abnormalities were significantly more common in NF155-IgG4 positive compared to MAG-IgM neuropathy. Chronic immune sensory polyradiculopathy (CISP)/CISP-plus phenotype was more common among Contactin-1 neuropathies compared to NF155-IgG4 positive cases. NF155-IgG4 positive cases responded favorably to immunotherapy compared to MAG-IgM seropositive cases with distal acquired demyelinating symmetric neuropathy (p<0.001) and had better long-term clinical outcomes compared to contactin-1 IgG (p=0.04).Discussion:We report long-term follow-up and clinical outcome of NF155-IgG4 patients. NF155-IgG4 but not IgM or IgG patients have unique clinical-electrodiagnostic signature. We demonstrate NF155-IgG4 positive patients, unlike classical CIDP with neuropathic pain and dysautonomia common at presentation. Long-term outcomes were favorable.Classification of Evidence:This study provides Class III evidence that NF155-IgG4 seropositive patients, compared to typical CIDP patients, present with distal more than proximal muscle weakness, positive sensory symptoms, and gait ataxia.

Atypical presentation of anti-HMGCR myopathy

Immune-mediated necrotising myopathy is a subtype of idiopathic inflammatory myopathy characterised by muscle fibre necrosis without significant inflammatory infiltrate. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) myopathy is seen in 6%–10% of idiopathic inflammatory myopathy and is diagnosed in the context of elevated serum creatine kinase levels, proximal muscle weakness and anti-HMGCR autoantibodies. We recently encountered a 61-year-old man with anti-HMGCR myopathy with an atypical skin manifestation, partially responsive to triple therapy with steroids, intravenous immunoglobulin (IVIG) and rituximab. To our knowledge, there have been only four reported cases of skin rash associated with anti-HMGCR myopathy. Our case demonstrates the importance of recognising atypical manifestations of anti-HMGCR myopathy. Early addition of IVIG and rituximab is also critical in patients not responding to steroid monotherapy. Delay in achieving remission leads to prolonged steroid use, lower likelihood of beginning physical therapy and overall worse clinical outcomes.

Anasarca as the presenting symptom of juvenile dermatomyositis: a case series

Background Juvenile Dermatomyositis (JDM) is an autoimmune disease that typically presents with classic skin rashes and proximal muscle weakness. Anasarca is a rare manifestation of this disease and is associated with a more severe and refractory course, requiring increased immunosuppression. Early recognition of this atypical presentation of JDM may lead to earlier treatment and better outcomes. Case presentation We present two female patients, ages 11 years old and 4 years old, who presented to the ED with anasarca and were subsequently diagnosed with JDM. Both patients required ICU-level care and significant immunosuppression, including prolonged courses of IV methylprednisolone, IVIG, and Rituximab. Conclusions Anasarca is a rare presentation of Juvenile Dermatomyositis, but it is important for clinicians to recognize this manifestation of the disease. Early recognition and treatment will lead to better outcomes in these children and hopefully decrease the need for prolonged hospitalization and ICU level care.

Unusual organ involvement in sarcoidosis: sarcoid myopathy and peritoneal sarcoidosis

Myopathy and peritoneal involvement are rare complications of sarcoidosis, and the latter can mimic malignancy with peritoneal dissemination. In this case, a patient with a history of polyarthritis and positive rheumatoid factor presented with proximal muscle weakness and abdominal pain. Biopsies of muscle and peritoneum revealed non-caseating granuloma suggesting sarcoidosis. Ocular and pulmonary involvement later developed and confirmed the diagnosis of sarcoidosis.