Twenty-eight consecutive patients with multiple sclerosis (MS) were clinically evaluated to determine the presence of sleep-related disorders. There were 12 males and 16 females aged between 22 and 67 with disability ranging between 1.5 and 8.5 on Kurtzke extended disability status score (EDSS). Fifteen patients (54%) reported sleep-related problems. These included difficulties initiating sleep and/or frequent awakenings due to spasms or discomfort in the legs (8 patients), difficulty in initiating or maintaining sleep (3), habitual snoring (4) and nocturia (1). All-night oximetry was performed and the tracings analysed for the number of dips in oxygen saturation (SaO₂) or more than 4%. Three patients showed significant sleep-related oxygen desaturation (>5 dips of >4% SaO₂/h). Subsequent polysomnography performed in 2 of the 3 patients with significant oxygen desaturation confirmed the presence of sleep apnoea. MRI analysis of brain stem regions showed abnormalities in 20/22 cases. The 3 patients showing nocturnal oxygen desaturation had MRI brain stem lesions, but their locations were variable and their general appearance not different from that seen in the 17 without sleep apnoea. Sleep disturbance in MS is common but poorly recognised. It is usually due to leg spasms, pain, immobility, nocturia or medication. It is much less commonly associated with nocturnal respiratory insufficiency.

Although the clinical presentation of PLA2G6-associated neurodegeneration was reported to be homogeneous, our findings suggest patients with PLA2G6 mutation could show heterogeneous phenotype such as dystonia-parkinsonism, dementia, frontotemporal atrophy/hypoperfusion, with or without brain iron accumulation. Based on the clinical heterogeneity, the functional roles of PLA2G6 and the roles of PLA2G6 variants including single heterozygous mutations should be further elucidated in patients with atypical parkinsonism, dementia, or Parkinson disease. PLA2G6 mutations should be considered in patients with early-onset l-dopa-responsive parkinsonism and dementia with frontotemporal lobar atrophy.

This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P < 0.000001), constipation, (P < 0.000001) and age over 70 years (P = 0.0002). Combined features obtained from the generalized logistic regression achieved a hazard ratio of 5.71 (95% confidence interval 2.85–11.43). Bayesian classifier suggested that patients with higher Mini-Mental State Examination score and lower caudate SBR asymmetry were more likely to develop parkinsonism, while patients with the opposite pattern were more likely to develop dementia. This study shows that iRBD patients older than 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.

TRAF6 is essential for RANK-mediated NF-κB activation and is involved in the development of several types of cells. Kanaya et al. demonstrate that RANK–TRAF6-mediated NF-κB is essential for the development of M cells and FAE.

A number of situational and behavioural individual differences moderate the impact of shift and night work. The aims of this study were to identify individual differences correlates of sleep and fatigue-related shiftwork outcomes and examine their potential relative causal impact. Power company shiftworkers completed a questionnaire that measured age/experience, number of dependents, shiftwork locus of control, morningness-eveningness, workload and sleep/health-related behaviours. Shiftwork sleep and fatigue outcome variables were also measured. Hierarchical multiple regression was used to examine predictive contributions of the individual difference variables and to generate path coefficients from situational and psychological predictors through behavioural variables to the outcome variables. Shiftwork-specific internality showed the most systematic significant causal relationships with sleep and fatigue outcomes. While not having as strong a direct causal influence on sleep and fatigue outcomes as internality, the other predictors did show more significant causal effects upon sleep-related behaviours than did internality. Behavioural variables made little contribution to the total causal effects of the predictors on the outcome variables. The results suggest control beliefs to be a moderating factor in shiftwork exposure and the potential utility of this construct in aiding more effective targeting of interventions.

Eighteen amyotrophic lateral sclerosis (ALS) patients having neither respiratory complaints nor subjective symptoms of sleep disturbance were studied by using an ambulatory multi-parameter monitoring system during sleep. They were divided into two groups: 11 patients with predominantly bulbar form and seven with non-bulbar form. After performing daytime pulmonary function tests, the presence of sleep-disordered breathing (SDB) was evaluated by using a portable device. ALS patients did not show significant SDB as a whole, and the respiratory disturbance index (RDI) was not significantly different between the bulbar group and the non-bulbar group. However, three patients of the bulbar group showed significant SDB, and the patterns of apnea/hypopnea suggested that both bulbar weakness and minimal diaphragmatic weakness might cause SDB in ALS patients at an early clinical stage. Multi-parameter respiratory monitoring during sleep should be included in the routine evaluation of ALS patients at an early clinical stage, especially those with predominantly bulbar involvement, in order to predict early respiratory failure.

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