E. St. Louis

Rapid eye movement sleep behavior disorder: Devising controlled active treatment studies for symptomatic and neuroprotective therapy-a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group

OBJECTIVES We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

Amiodarone-associated neuromyopathy: a report of four cases.

Amiodarone-associated neuromyopathy: a report of four cases E. P. Flanagan, C. M. Harper, E. K. St Louis M. H. Silber and K. A. Josephs Department of Neurology, Mayo Clinic, Rochester, MN, USA Correspondence: Dr Keith A. Josephs, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA (tel.: +15075380138; fax: +15072664752; e-mail: josephs.keith@mayo.edu).

INTRAMEDULLARY SJÖGREN SYNDROME

Sjogren syndrome (SS) is a systemic autoimmune disorder predominantly affecting the exocrine glands, involving the CNS in 20%–25% of cases. Previous neuropathologic specimens in Sjogren myelopathy have suggested a vasculitic pathophysiology. ### Case report. A 66-year-old woman developed sicca symptoms followed by subacutely evolving neck pain, paraparesis, and paresthesias below her neckline. She had 5 similar attacks over ensuing months, partially improved by IV methylprednisolone, but gradually became cane dependent and noted anesthesia below her chest. Her only regular medication was benazepril. One year later, her symptoms recurred, and she presented to our institution. On examination, there was flaccid hyporeflexic upper extremity paresis with areflexic paraplegia. A T5 sensory level was noted. There was no optic disc pallor, dysmetria, or dyssynergia. Brain MRI was unremarkable except for small vessel disease. Spinal MRI showed multiple patchily enhancing, longitudinal white matter lesions (several extending over 3 corresponding vertebral body segments) from the medullary spinal junction to the conus medullaris. CSF showed protein 208, glucose 79, 9 erythrocytes, and 9 leukocytes, including 6 lymphocytes, 2 histiocytes, and 1 neutrophil. CSF de novo immunoglobulin G (IgG) synthesis was 45.6 (−9.9 to 3.3 mg/day) and CSF IgG index was 0.8 (0.0–0.7). Possible matching IgG bands in serum and CSF were seen. SSA, SSB, antinuclear antibodies (1:320, normal 1:40), Smith (1:50), and RNP (1:100) were positive. Serum NMO …

Treatment of Hypersomnia

Central nervous system (CNS) hypersomnia disorders such as narcolepsy and idiopathic hypersomnia significantly impair quality of life and lead to safety risks in driving and occupational abilities. Effectively and tolerably counteracting hypersomnia symptoms is thus a critical public health mandate. Pharmacological treatment with stimulants remains the mainstay of care for CNS hypersomnia patients. Traditional sympathomimetic stimulants including methylphenidate and amphetamines remain the most effective and commonly used options for most patients, although the advent of the nonsympathomimetic stimulant agents modafinil and armodafinil has provided effective yet safer and more tolerable treatment options for many narcolepsy patients. Anticataplectic treatments for narcolepsy patients include tricyclic and selective serotonin reuptake inhibitor antidepressants and sodium oxybate, the sodium salt of γ-hydroxybutyrate. Important adjunctive treatments for hypersomnia include caffeine and several nonpharmacologic measures such as prescribed napping, sleep hygiene education, relaxation training, cognitive behavioral therapy, and bright light therapy. Effective and tolerable treatment strategies for hypersomnia patients first requires an accurate diagnosis of the underlying cause or causes, expert knowledge of the complex clinical pharmacology of available stimulant and anticataplectic treatments, and familiarity with nonpharmacologic options with tailoring of the most appropriate combination of treatments to the individual patient.