Recurrent brachial plexopathy as initial presentation of systemic lupus erythematosus: A case report and review of the literature.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects many organs of the body including the peripheral nervous system (PNS) which has potential significant impact. Plexopathy is rare but one of the serious PNS manifestations of lupus. CASE: A 41-year-old female presented with recurrent attacks of painful brachial plexopathy and right hemi-diaphragmatic paralysis. After extensive workup, she was diagnosed with SLE and started on hydroxychloroquine and mycophenolate mofetil. The frequency and severity of the attacks of plexopathy has significantly improved after starting the immune suppressive therapy for SLE. Whole exome sequencing unveiled previously unreported mutations encoding non-synonymous amino acids in titin and minichromosome maintenance 3-associated protein. CONCLUSION: Recurrent attacks of painful brachial plexopathy may warrant careful evaluation for underlying SLE with a premise of therapeutic benefit.

Autonomic Reflex Screen Test Abnormalities in Cold-Induced Sweating Syndrome Type 1.

Cold-induced sweating syndrome (CISS) is a rare autosomal recessive disease due to mutation in the Cytokine receptor-like factor 1 (CRLF1). The characteristic symptom of CISS is the tendency to sweat profusely especially in the upper body and hands when the patient is exposed to cold temperature. We sought to first report the findings of autonomic reflex screen in a case of CISS type 1 with Cytokine receptor-like factor 1 mutation. Valsalva morphology, Valsalva ratio, and heart rate response to deep breathing were normal for the patient's age. Quantitative sudomotor axon reflex test showed nonlength dependent decrease in the sweat volume. Tilt table revealed evidence of reflex (vasovagal) "syncope," however, the patient was asymptomatic without loss of consciousness.

Histopathologic Findings in 5 Patients With Hypomyopathic Dermatomyositis: The Importance of MHC-1 Expression on Myofibers.

Muscle histopathologic findings in hypomyopathic dermatomyositis (HDM) have not been adequately characterized. We sought to determine the results of conventional and immunohistopathology in HDM. Light microscopic and immunohistochemical analysis was performed on muscle from 5 patients with HDM without muscle weakness. Ages ranged from 49 to 56 years. Creatine kinase level was normal. Electromyography showed mild "myopathic" changes in 2. The median duration of skin disease before biopsy was 18 months. Abnormal major histocompatibility (MHC) class I immunoreactivity was noted in myofibers in all specimens even when conventional histopathology was normal (1 patient) or only mildly abnormal (3 patients). One specimen had the characteristic findings of dermatomyositis. Patchy MHC-1 expression on myofibers was a consistent finding in HDM in the absence of other histopathologic abnormalities. The presence of MHC-1 expression could indicate a degree of endoplasmic reticulum stress even in the absence of clinical muscle weakness, muscle enzyme abnormalities, or significant inflammatory infiltrate.

Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: development of an imaging biomarker.

Previous diffusion tensor imaging (DTI) studies have shown white matter pathology in amyotrophic lateral sclerosis (ALS), predominantly in the motor pathways. Further these studies have shown that DTI can be used longitudinally to track pathology over time, making white matter pathology a candidate as an outcome measure in future trials. DTI has demonstrated application in group studies, however its derived indices, for example fractional anisotropy, are susceptible to partial volume effects, making its role questionable in examining individual progression. We hypothesize that changes in the white matter are present in ALS beyond the motor tracts, and that the affected pathways and associated pattern of disease progression can be tracked longitudinally using automated diffusion connectometry analysis. Connectometry analysis is based on diffusion spectrum imaging and overcomes the limitations of a conventional tractography approach and DTI. The identified affected white matter tracts can then be assessed in a targeted fashion using High definition fiber tractography (a novel white matter MR imaging technique). Changes in quantitative and qualitative markers over time could then be correlated with clinical progression. We illustrate these principles toward developing an imaging biomarker for demonstrating individual progression, by presenting results for five ALS patients, including with longitudinal data in two. Preliminary analysis demonstrated a number of changes bilaterally and asymmetrically in motoric and extramotoric white matter pathways. Further the limbic system was also affected possibly explaining the cognitive symptoms in ALS. In the two longitudinal subjects, the white matter changes were less extensive at baseline, although there was evidence of disease progression in a frontal pattern with a relatively spared postcentral gyrus, consistent with the known pathology in ALS.

What's in the literature?

In amyotrophic lateral sclerosis (ALS), a recent double-blind placebo-controlled trial of acetyl-L-carnitine along with riluzole showed probable benefit in 42 patients compared with 40 patients who received placebo. Using an electrophysiologic measure devised to differentiate ALS from other neuromuscular conditions, a "splint-hand index" was devised and is reviewed. Analysis of skin in ALS may also be of interest, and there was a report of accumulation of fused in sarcoma protein in the epidermis of ALS patients. With regard to myasthenia gravis, there is another report that early treatment of ocular symptoms with corticosteroids may prevent the development of generalized symptoms. A new study of thymus histopathology in muscle-specific tyrosine kinase (MuSK) myasthenia gravis is covered and another article on the use of thymectomy. In Duchenne muscular dystrophy, the best method of administrating corticosteroids is still being debated, and a long-term study of daily versus intermittent prednisolone is reviewed. The study showed less sustained benefit from the intermittent prednisolone but with a better side effect profile. According to 2 recent reports, it seems that titin mutations may be an underrecognized cause of myopathy with early respiratory failure in adults. Keeping with the respiratory failure theme, there was also an interesting article on the long-term benefits and side effects of cyclosporine in patients with interstitial lung disease from antisynthetase syndrome. Finally, the spectrum of small fiber neuropathy may be expanding to include a causative role in some patients with fibromyalgia syndrome and in juveniles with diffuse pain and a possible autoimmune predisposition.

Multifocal radiculoneuropathy during ipilimumab treatment of melanoma.

INTRODUCTION: Ipilimumab, a monoclonal anti-CTLA-4 antibody, is used to treat melanoma. Neuromuscular side effects, possibly autoimmune, may occur. METHODS: In this investigation we undertook a retrospective review of patient records. RESULTS: After 3 doses of ipilimumab, a 31-year-old man developed asymmetric, severe weakness involving all limbs, respiration, and cranial nerves, which was progressive over 2 weeks. EMG/NCS showed an axonal polyradiculoneuropathy with multifocal motor conduction blocks. CSF protein was 749 mg/dl. Nerve pathology showed inflammation around the endoneurial microvessels and subperineurial edema and inflammation. Spine MRI showed leptomeningeal and anterior and posterior root enhancement. Strength improved slowly over months after ipilimumab discontinuation and immunomodulating treatment. CONCLUSIONS: Ipilimumab toxicity presented as a monophasic, multifocal, asymmetric polyradiculoneuropathy involving roots and peripheral and cranial nerves. Ipilimumab may produce a polyradiculoneuropathy with disruption of the blood-nerve barrier due to a microvasculopathy.

Undiagnosed patent foramen ovale presenting as a cryptogenic brain abscess: case report and review of the literature.

A 43-year-old man with no significant medical history but poor oral hygiene presented with fever and new-onset tonic-clonic seizures secondary to a left parieto-occipital brain abscess defined by computed tomography, magnetic resonance imaging, and surgical evacuation. A comprehensive workup looking for a source of infection was unremarkable including computed tomography of the chest, abdomen, and pelvis; blood cultures; and a tagged white blood cell scan. A transesophageal echocardiogram bubble study revealed the presence of a patent foramen ovale (PFO) but no other abnormalities. Culture of the material obtained at surgery revealed flora commonly found in the oropharynx that responded to antibiotic therapy. A review of the literature revealed three other cases in which a brain abscess from flora commonly found in the oropharynx was associated with a PFO. We hypothesize that the underlying mechanism is a significant bacterial load from poor dentition that enters the arterial circulation through a PFO and forms the nidus for a brain abscess. Surgical evacuation is the preferred method for diagnosis and initial treatment. If a brain abscess is identified without any adjacent source of infection, a recent head trauma, or a neurosurgical procedure, then a transesophageal echocardiogram is indicated to exclude a PFO. If a PFO is found, then hematogenous spread of flora normally found in the oropharynx through a right to left shunt should be suspected. Surgical evacuation followed by intravenous antibiotics specific to the identified organisms is warranted. Once the infection is eliminated, anatomic closure of the PFO with good oral hygiene practices may be the best course of action for preventing recurrences.