Global synergistic actions to improve brain health for human development.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization's new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022-2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a 'neurological revolution' across four key pillars - surveillance, prevention, acute care and rehabilitation - termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

Sleep Disorders in Parkinson Disease.

Sleep disorders in Parkinson disease have attracted the attention of clinicians and researchers for decades. Recently, major advances in their clinical characterization, polysomnographic description, pathophysiologic understanding, and treatment took place. Parkinson disease encompasses the whole spectrum of sleep medicine: every category of sleep disorder can be observed in these patients. Video polysomnography frequently is indicated, sometimes followed by multiple sleep latency/maintenance of wakefulness tests. Additional studies may include actigraphy, cardiorespiratory polygraphy, and dim light melatonin assessment. Treatment needs to be specific to the underlying sleep disorder and can include medications and nondrug treatments, for example, behavioral therapy and light therapy.

Nightmare Disorder and Isolated Sleep Paralysis.

Nightmare disorder and recurrent isolated sleep paralysis are rapid eye movement (REM) parasomnias that cause significant distress to those who suffer from them. Nightmare disorder can cause insomnia due to fear of falling asleep through dread of nightmare occurrence. Hyperarousal and impaired fear extinction are involved in nightmare generation, as well as brain areas involved in emotion regulation. Nightmare disorder is particularly frequent in psychiatric disorders and posttraumatic stress disorder. Nonmedication treatment, in particular imagery rehearsal therapy, is especially effective. Isolated sleep paralysis is experienced at least once by up to 40% of the general population, whereas recurrence is less frequent. Isolated sleep paralysis can be accompanied by very intense and vivid hallucinations. Sleep paralysis represents a dissociated state, with persistence of REM atonia into wakefulness. Variations in circadian rhythm genes might be involved in their pathogenesis. Predisposing factors include sleep deprivation, irregular sleep-wake schedules, and jetlag. The most effective therapy consists of avoiding those factors.

Effects of singing bowl exposure on Karolinska sleepiness scale and pupillographic sleepiness test: A randomised crossover study.

BACKGROUND: The aim of this study was to investigate the effects on subjective and objective sleepiness of a stay above a large struck singing bowl compared to a relaxation period in a silent singing bowl. METHODS: Fifty-eight healthy subjects were recruited for the study, 48 participated on two days, one week apart, during the same timeslot. The Karolinska sleepiness scale was used to evaluate current subjective sleepiness, and the relative pupillary unrest index to assess objective sleepiness. In this randomized cross-over study, the intervention consisted of a 20-minute stay in a hammock while the singing bowl, positioned beneath, was struck seven times. The controlled comparator was a 20-minute stay in the same hammock above the singing bowl, but without being struck. After these two interventions subjective and objective sleepiness were re-evaluated. RESULTS: The mean relative pupillary unrest index values after relaxation in the struck and silent singing bowl groups were 0.74 and respectively 0.71 (p = 0.460). The median Karolinska sleepiness scale value after relaxation with the struck singing bowl was 3 compared with 4 (p = 0.041) for the silent singing bowl. DISCUSSION: This study evaluated the influence of a struck singing bowl on sleepiness during daytime. Subjective sleepiness was significantly lower after relaxation above a struck singing bowl. After gender stratification, the difference was still significant in women. Objective sleepiness was not different in both groups. Finally, we can only speculate if women may be more susceptible to subjective improvements in case of sleepiness and show another perception of relaxation in a struck singing bowl compared to men.

Multimodal Magnetic Resonance Imaging reveals alterations of sensorimotor circuits in restless legs syndrome.

STUDY OBJECTIVES: Integrated information on brain microstructural integrity and iron storage and its impact on the morphometric profile is not available in restless legs syndrome (RLS). We applied multimodal magnetic resonance imaging (MRI) including diffusion tensor imaging, the transverse relaxation rate (R2*), a marker for iron storage, as well as gray and white matter volume measures to characterize RLS-related MRI signal distribution patterns and to analyze their associations with clinical parameters. METHODS: Eighty-seven patients with RLS (mean age 51, range 20-72 years; disease duration, mean 13 years, range 1-46 years, of those untreated n = 30) and 87 healthy control subjects, individually matched for age and gender, were investigated with multimodal 3T MRI. RESULTS: Volume of the white matter compartment adjacent to the post- and precentral cortex and fractional anisotropy (FA) of the frontopontine tract were both significantly reduced in RLS compared to healthy controls, and these alterations were associated with disease duration (r = 0.25, p = 0.025 and r = 0.23, p = 0.037, respectively). Corresponding gray matter volume increases of the right primary motor cortex in RLS (p < 0.001) were negatively correlated with the right FA signal of the frontopontine tract (r = -0.22; p < 0.05). Iron content evaluated with R2* was reduced in the putamen as well as in temporal and occipital compartments of the RLS cohort compared to the control group (p < 0.01). CONCLUSIONS: Multimodal MRI identified progressing white matter decline of key somatosensory circuits that may underlie the perception of sensory leg discomfort. Increases of gray matter volume of the premotor cortex are likely to be a consequence of functional neuronal reorganization.

Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation.

A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) in conjunction with the European Restless Legs Syndrome Study Group (EURLSSG) and the RLS Foundation (RLS-F) to develop evidence-based and consensus-based recommendations for the prevention and treatment of long-term pharmacologic treatment of dopaminergic-induced augmentation in restless legs syndrome/Willis-Ekbom disease (RLS/WED). The Task Force made the following prevention and treatment recommendations: As a means to prevent augmentation, medications such as α2δ ligands may be considered for initial RLS/WED treatment; these drugs are effective and have little risk of augmentation. Alternatively, if dopaminergic drugs are elected as initial treatment, then the daily dose should be as low as possible and not exceed that recommended for RLS/WED treatment. However, the physician should be aware that even low dose dopaminergics can cause augmentation. Patients with low iron stores should be given appropriate iron supplementation. Daily treatment by either medication should start only when symptoms have a significant impact on quality of life in terms of frequency and severity; intermittent treatment might be considered in intermediate cases. Treatment of existing augmentation should be initiated, where possible, with the elimination/correction of extrinsic exacerbating factors (iron levels, antidepressants, antihistamines, etc.). In cases of mild augmentation, dopamine agonist therapy can be continued by dividing or advancing the dose, or increasing the dose if there are breakthrough night-time symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. For severe augmentation the patient can be switched either to an α2δ ligand or rotigotine, noting that rotigotine may also produce augmentation at higher doses with long-term use. In more severe cases of augmentation an opioid may be considered, bypassing α2δ ligands and rotigotine.

Narcolepsy is strongly associated with the T-cell receptor alpha locus.

Narcolepsy with cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals. Narcolepsy was first shown to be tightly associated with HLA-DR2 (ref. 3) and later sublocalized to DQB1*0602 (ref. 4). Following studies in dogs and mice, a 95% loss of hypocretin-producing cells in postmortem hypothalami from narcoleptic individuals was reported. Using genome-wide association (GWA) in Caucasians with replication in three ethnic groups, we found association between narcolepsy and polymorphisms in the TRA@ (T-cell receptor alpha) locus, with highest significance at rs1154155 (average allelic odds ratio 1.69, genotypic odds ratios 1.94 and 2.55, P < 10(-21), 1,830 cases, 2,164 controls). This is the first documented genetic involvement of the TRA@ locus, encoding the major receptor for HLA-peptide presentation, in any disease. It is still unclear how specific HLA alleles confer susceptibility to over 100 HLA-associated disorders; thus, narcolepsy will provide new insights on how HLA-TCR interactions contribute to organ-specific autoimmune targeting and may serve as a model for over 100 other HLA-associated disorders.

Auditory startle reaction is disinhibited in idiopathic restless legs syndrome.

STUDY OBJECTIVES: Because the auditory startle reaction is abnormal in disorders with substantia nigra pathology, we hypothesized that auditory startle responses (ASRs) might also be altered in restless legs syndrome (RLS). DESIGN: Neurophysiologic study of the auditory startle reaction. SETTING: Neurology departments of a university hospital and an affiliated local hospital. PATIENTS AND PARTICIPANTS: Fifteen patients with idiopathic RLS (6 de novo, 9 untreated after a 7-day wash-out period of levodopa, mean duration of RLS [corrected] symptoms 21.2 +/- 17.9 years, mean IRLS [corrected] severity score 23.5 +/- 6.7) and 15 sex- and age-matched healthy controls were investigated. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: ASRs were elicited by 8 high-intensity auditory stimuli differing randomly in tonal frequency and intensity. Reflex electromyographic activity was simultaneously recorded with surface electrodes from 8 facial, neck, arm, and leg muscles. In RLS patients, ASRs were significantly more frequent (541 of 960 possible responses; controls, 430 of 960), and ASR area under the curve was significantly larger (3812 +/- 450 microVms; controls, 1756 +/- 226 microVms). Analysis per body region revealed that ASRs were significantly more frequent in RLS patients than in controls in leg muscles (138/360 vs 55/360); ASR latencies to leg muscles were significantly shorter in RLS patients (129 +/- 6 ms vs 160 +/- 11 ms); ASR area under the curve was significantly larger in RLS patients in facial (7547 +/- 1326 mmicroVms vs 2982 +/- 448 microVms) and leg muscles (1373 +/- 308 microVms vs 541 +/- 193 microVms). CONCLUSIONS: Our data demonstrate disinhibition of reticulospinal pathways in RLS patients as compared to normal controls, likely originating from dysfunction rostral to the lower brainstem.