Steven Novella

The frequency of undiagnosed diabetes and impaired glucose tolerance in patients with idiopathic sensory neuropathy.

The aim of the study was to determine the frequency of undiagnosed abnormal glucose metabolism in patients with idiopathic sensory neuropathy. Patients were separated into two groups depending on presence or absence of painful symptoms, and an oral glucose tolerance test was performed. Of the 48 patients studied, those with painful symptoms had a higher frequency of abnormal glucose metabolism than literature‐based controls, whereas patients without painful symptoms showed no difference. Comparison of patients with and without painful symptoms had a P‐value of 0.02. The results indicate the need to consider undiagnosed abnormal glucose metabolism in patients with idiopathic sensory neuropathy.

Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III

Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative diseases other than ALS. Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial.

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 (≥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. Muscle Nerve, 2009

Use of fiberoptic endoscopic evaluation of swallowing (FEES) in patients with amyotrophic lateral sclerosis.

This study investigated the use of fiberoptic endoscopic evaluation of swallowing (FEES) to both diagnose pharyngeal dysphagia and make treatment recommendations in 17 consecutive patients with a new diagnosis of amyotrophic lateral sclerosis (ALS) and complaints of dysphagia. Ten of 17 (59%) patients exhibited pharyngeal dysphagia with aspiration or aspiration risk with clear liquids, i.e., 5 of 8 (63%) limb and 5 of 9 (56%) bulbar. If depth of bolus flow was a problem, thickened liquids and single, small bolus sizes were recommended. If bolus retention was a problem, a small clear liquid bolus after each puree or solid bolus was recommended to aid pharyngeal clearing. Five of 17 (30%) patients required multiple FEES evaluations because of disease progression. For the first time in patients with ALS, FEES was shown to be successful in assessing preswallow anatomy and physiology, diagnosing pharyngeal dysphagia, and providing objective data for appropriate therapeutic interventions to promote safer oral intake. Visual biofeedback provided by FEES was successful for both patient and family education and to investigate individualized therapeutic strategies that, if successful, can be implemented immediately. Serial FEES allows for objective monitoring of dysphagia symptoms and timely implementation of diet changes and/or therapeutic strategies to continue safer oral intake and maintain optimum quality of life.

Rituximab in the management of refractory myasthenia gravis.

Myasthenia gravis (MG) is an immune‐mediated disorder with a variable response to treatment. In this study, patients with refractory MG who were treated with rituximab were identified. A review of patients referred to the Yale Neuromuscular Clinic was performed. Patients with refractory MG who were treated with rituximab were reviewed for response to treatment. Patients who had muscle‐specific kinase (MuSK+) or acetylcholine receptor (AChR+) antibodies were included. Six patients were identified who met the criteria described. All patients tolerated rituximab without side effects and had a reduced need for immunosuppressants and/or improvement in clinical function. Patients with refractory MG appeared to respond to rituximab in this small, retrospective study. This result suggests that a larger, prospective trial is indicated. Muscle Nerve, 2009

A case of inherited erythromelalgia

Background A 15-year-old boy presented with recurrent episodes of erythema and burning pain in the distal extremities, which he had experienced since early childhood. The episodes were triggered by heat or exertion. His medical history revealed an extensive six-generation family history of similar symptoms.Investigations Neurological examination, MRI brain scan, electromyography, skin biopsy, laboratory blood testing, and DNA analysis.Diagnosis Juvenile onset primary erythromelalgia.Management Genetic counseling, and symptomatic management of neuropathic pain.

Clinical trials of integrative medicine: testing whether magic works?

Over the past two decades complementary and alternative medicine treatments relying on dubious science have been embraced by medical academia. Despite low to nonexistent prior probability that testing these treatments in randomized clinical trials (RCTs) will be successful, RCTs of these modalities have proliferated, consistent with the principles of evidence-based medicine, which underemphasize prior plausibility rooted in science. We examine this phenomenon and argue that what is needed is science-based medicine rather than evidence-based medicine.

ALS untangled no. 20: The Deanna protocol

ISSN 2167-8421 print/ISSN 2167-9223 online

ALSUntangled: Introducing the table of evidence

We found no precedent for grading the types of evidence we review, so we used a ‘ crowd sourcing ’ approach to create the TOE. One ALSUntangled reviewer (RB) constructed a fi rst draft. The rest of the review team then suggested edits via emails over two months. Finally a subset of reviewers met in person and validated the utility of the TOE by attempting to convert the evidence from all 26 prior ALSUntangled reviews into this.

Suboptimal Optics: Vision Problems as Scars of Evolutionary History

The human eye is an excellent example of suboptimal bottom-up design resulting from the constraints of evolutionary historical contingency. The resulting suboptimal optics manifests in a number of medical ophthalmological disorders.