Priya S. Dhawan

Disrupted daytime activity and altered sleep-wake patterns may predict transition to mild cognitive impairment or dementia: a critically appraised topic.

Background:There is a well-known relationship between neurodegenerative disease, disrupted sleep, and cognition. Pathologic and imaging studies have shown that regions in the brain shown to regulate sleep and circadian rhythm are abnormal in Alzheimer disease. Most of these studies have been cross-sectional, and often look at patients already with dementia. This leaves uncertainty with regard to the temporal relationship of circadian disruption and cognitive decline. Objective:To determine whether disrupted daytime activity and altered sleep patterns predict development of mild cognitive impairment (MCI) or dementia. Methods:The objective was addressed through the development of a structured, critically-appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, and behavioral neurology and sleep medicine content experts. Results:A prospective cohort study of 1282 cognitively normal women demonstrated that when peak circadian activity, as measured by wrist actigraphy, occurred later than average, there was an increased risk of MCI or dementia [odds ratio (OR), 1.83; 95% confidence interval (CI), 1.29-2.61]. Increased odds for dementia or MCI also existed for those with decreased circadian rhythm amplitude (OR, 1.57; 95% CI, 1.09-2.25) and robustness (OR, 1.57; 95% CI, 1.29-2.61). Conclusions:Disrupted circadian rhythm measures, including lower amplitude, a less robust rhythm, and delayed timing of peak activity on wrist actigraphy, were predictive of future development of MCI or dementia in cognitively normal women.

IVIG versus PLEX in the treatment of worsening myasthenia gravis: What is the evidence? A critically appraised topic

Background:Immune therapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are first line in the treatment of worsening myasthenia gravis. Although PLEX is favored in myasthenic crisis, IVIG is increasingly used in exacerbations due to cost and ease of administration. Objectives:To review and critically assess current evidence on the effects of IVIG and PLEX on functional outcomes in patients with worsening myasthenia gravis. Methods:A structured critical appraisal was conducted on the objective topic. This included a creation of a structured question based on a clinical scenario, comprehensive literature search, selection of evidence for review, and critical appraisal of selected evidence. Evidence was summarized and commentary provided. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neuromuscular neurology. Results:A single-blinded, randomized-controlled trial that compared IVIG and PLEX in 84 patients with worsening myasthenia gravis was selected for review. Primary outcome measure was functional status at 14 days after treatment, as assessed by the Quantitative Myasthenia Gravis Score. Change in Quantitative Myasthenia Gravis Score at day 14 for all subjects was 4.0, without statistically significant differences between IVIG and PLEX groups. Conclusions:IVIG and PLEX are equally effective in worsening myasthenia gravis. Treatment decisions may depend on several variables, including presence of respiratory distress, medical comorbidities, access to medication, and cost. PLEX will likely remain the treatment of choice in true myasthenic crisis.

Spectrum of Autonomic Nervous System Impairment in Sjögren Syndrome

Objective: To describe the spectrum of autonomic dysfunction in a uniformly evaluated cohort of patients with Sjögren syndrome. Methods: A series of 13 patients underwent a comprehensive evaluation for suspected autonomic impairment, including a neurological examination, autonomic testing, and laboratory studies. A diagnosis of Sjögren syndrome was established as the cause of autonomic dysfunction in all. Clinical features, findings on autonomic testing, and laboratory results are described. Results: All patients in this series reported postural lightheadedness and syncope or near-syncope. Autonomic testing confirmed the presence of orthostatic hypotension on tilt-table testing in 5 patients and an excessive postural tachycardia and/or hypertensive response in 8 patients. Only 2 of the patients with orthostatic hypotension had a significant sensory neuropathy. Symptoms suggestive of gastrointestinal and genitourinary impairment were seen in nearly all patients, with abnormal motility testing (most frequently esophageal dysmotility) in 5 of 6 patients who underwent formal testing. Patients in this series treated with immune-modulating therapy experienced significant improvement. Conclusions: A diagnosis of Sjögren syndrome should be aggressively pursued in patients with signs and symptoms suggestive of autonomic nervous system impairment. Although the spectrum of adrenergic failure is variable, ranging from orthostatic hypotension to an excessive postural tachycardia, most patients do have symptoms of more generalized autonomic failure. Patients who were treated with immune-modulating therapy did improve.

Myofibrillar myopathy due to dominant LMNA mutations: A report of 2 cases

Ana€ıs Chanut, MSc Pascal Laforêt, MD, PhD Angeline Madelaine, MSc François Petit, PharmD, PhD Norma B. Romero, MD, PhD Edoardo Malfatti, MD, PhD 1 Myology Institute, Neuromuscular Pathology Reference Center, Groupe Hospitalier Universitaire La Piti e-Salpêtrière; Sorbonne Universit es UPMC Univ Paris 06, Paris, France 2 Myology Institute, Neuromuscular Morphology Unit, Groupe Hospitalier Universitaire La Piti e-Salpêtrière; Sorbonne Universit es UPMC Univ Paris 06, Paris, France 3 Assistance Publique-Hôpitaux de Paris (APHP), Hôpitaux Universitaires Paris Sud, Antoine B eclère Hospital, Department of Molecular Genetics, Clamart, France

King-Devick Test identifies real-time concussion and asymptomatic concussion in youth athletes

Background: Sports concussion has an annual incidence of approximately 3.8 million. Over half go unreported and a substantial number may be asymptomatic. A rapid, cost-effective, and reliable tool that facilitates diagnosis of concussion is needed. The King-Devick (K-D) test is a vision-based tool of rapid number naming for assessment of concussion. In this study, we evaluated the utility of the K-D test in real time for identification of symptomatic concussion in youth athletes and to determine if similar impairment (subclinical concussion) exists in youth athletes without an obvious head injury or symptoms. Methods: Youth hockey players underwent K-D testing preseason, postseason, and immediately after suspected concussion. Additional testing was performed in a subgroup of nonconcussed athletes immediately before and after a game to determine effects of fatigue on K-D scores. Results: Among 141 players tested, 20 had clinically diagnosed concussion. All 20 had immediate postconcussion K-D times >5 seconds from baseline (average 7.3 seconds) and all but 2 had worse postseason scores (46.4 seconds vs 52.4 seconds, p < 0.05, Wilcoxon signed rank test). Nonconcussed athletes saw minimal improvement postseason (43.9 seconds vs 42.1 seconds, p < 0.05) and 51 nonconcussed players assessed before and after a game revealed no significant time change as a result of fatigue. Conclusions: Rapid number naming using the K-D test accurately identifies real-time, symptomatic concussion in youth athletes. Scores in concussed players may remain abnormal over time. Athletes should undergo preseason and postseason K-D testing, with additional evaluation real time to inform the assessment of suspected concussion. Classification of Evidence: This study provides Class III evidence that the K-D test accurately identifies real-time concussions in youth athletes.

Systemic vasculitis with dermatomyositis, hearing loss, neuropathy, and multiorgan dysfunction

A 39-year-old woman presented with 10 months of steadily progressive weakness, myalgia, weight loss, and intermittent feet tingling. During the course of her illness, she developed refractory atrial fibrillation, left followed by right-sided hearing loss, amenorrhea, and hematuria. She had been on rituximab for years for “polyarthralgias,” which was stopped at symptom onset. Examination showed severe proximal weakness and mildly decreased toe proprioception. Deltoid biopsy (figure) was diagnostic of dermatomyositis. Liver and enteric biopsies showed lymphocytosis. Suspicion for vasculitis led to sural nerve biopsy (figure), showing large-arteriole vasculitis. Despite treatment with high-dose prednisone and cyclophosphamide, the patient died. This is a unique case of systemic vasculitis associated with dermatomyositis, hearing loss, neuropathy, and multiorgan dysfunction. The histologic findings and the relentless progression despite stopping rituximab argue against a role for rituximab in the pathogenesis.

Neurologic Manifestations of Nutritional Disorders

Maintenance of medical and neurologic health requires adequate ingestion, absorption, and storage of vitamins and minerals. Nutritional deficiency disorders are prevalent worldwide and result primarily from malnourishment, chronic alcoholism, malabsorption, bariatric surgery, eating disorders, and chronic diseases. The neurologic complications of nutritional deficiencies are often severe, and potentially reversible. Recognition of characteristic signs and symptoms of these disorders requires a careful history and examination, as radiologic and other diagnostic testing may often be normal or only minimally abnormal, at least initially. Early treatment can halt progression or potentially reverse associated neurologic manifestations.