Longitudinal evolution of diffusion metrics after left hemisphere ischaemic stroke.

White matter is often severely affected after human ischaemic stroke. While animal studies have suggested that various factors may contribute to white matter structural damage after ischaemic stroke, the characterization of damaging processes to the affected hemisphere after human stroke remains poorly understood. Thus, the present study aims to thoroughly describe the longitudinal pattern of evolution of diffusion magnetic resonance imaging metrics in different parts of the ipsilesional white matter after stroke. We acquired diffusion and anatomical images in 17 patients who had suffered from a single left hemisphere ischaemic stroke, at 24-72 h, 8-14 days and 6 months post-stroke. For each patient, we created three regions of interest: (i) the white matter lesion; (ii) the perilesional white matter; and (iii) the remaining white matter of the left hemisphere. We extracted diffusion metrics (fractional anisotropy, mean, axial and radial diffusivities) for each region and conducted two-way repeated measures ANOVAs with stage post-stroke (acute, subacute and chronic) × regions of interest (white matter lesion, perilesional white matter and remaining white matter). Fractional anisotropy values stayed consistent across time-points, with significantly lower values in the white matter lesion compared to the perilesional white matter and remaining white matter tissue. Fractional anisotropy values of the perilesional white matter were also significantly lower than that of the remaining white matter. Mean, axial and radial diffusivities in the white matter lesion were all decreased in the acute stage compared to perilesional white matter and remaining white matter, but significantly increased in both the subacute and chronic stages. Significant increases in mean and radial diffusivities in the perilesional white matter were seen in the later stages of stroke. Our findings suggest that various physiological processes are at play in the acute, subacute and chronic stages following ischaemic stroke, with the infarct territory and perilesional white matter affected by ischaemia at different rates and to different extents throughout the stroke recovery stages. The examination of multiple diffusivity metrics may inform us about the mechanisms occurring at different time-points, i.e. focal swelling, axonal damage or myelin loss.

Are unrefreshing naps associated with nocturnal sleep architecture specificities in idiopathic hypersomnia?

STUDY OBJECTIVES: Unrefreshing naps are supportive clinical features of idiopathic hypersomnia (IH) and are reported by more than 50% of IH patients. They are, however, not mandatory for the diagnosis, and their pathophysiological nature is not understood. This study aimed at verifying whether IH patients with and without unrefreshing naps constitute two subtypes of IH based on their demographic/clinical characteristics, and sleep architecture. METHODS: One hundred twelve IH patients underwent a polysomnography (PSG) followed by a multiple sleep latency test (MSLT). They completed questionnaires on excessive daytime sleepiness, mood, and sleep quality. They were met by sleep medicine physicians who conducted a semi-structured clinical interview and questioned them on refreshing aspects of their naps. Patients who reported unrefreshing naps were compared to patients reporting refreshing naps on questionnaires, MSLT and PSG variables, with age as a covariable. As sensitivity analyses, we performed the same comparisons in participants presenting objective markers of IH and those diagnosed with IH based only on clinical judgment (subjective IH), separately. RESULTS: In the whole sample, 61% of patients reported unrefreshing naps. These participants had less awakenings, a lower percentage of N1 sleep, less sleep stage transitions, and a higher percentage of REM sleep on the nighttime PSG compared to the refreshing naps subgroup. When subjective and objective IH patients were tested separately, more group differences were observed on PSG for subjective IH patients. CONCLUSIONS: Patients with unrefreshing naps have less fragmented sleep compared to those with refreshing naps. Future studies should investigate whether this group difference indicates a weaker arousal drive.

HLA in isolated REM sleep behavior disorder and Lewy body dementia.

Synucleinopathies-related disorders such as Lewy body dementia (LBD) and isolated/idiopathic REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. In this study, we examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA-DRB1*11:01 was the only allele passing FDR correction (OR = 1.57, 95% CI = 1.27-1.93, p = 2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR = 1.26, 95%CI = 1.12-1.41, p = 8.76e-05), 70Q (OR = 0.81, 95%CI = 0.72-0.91, p = 3.65e-04) and 71R (OR = 1.21, 95%CI = 1.08-1.35, p = 1.35e-03). Position 71 (pomnibus = 0.00102) and 70 (pomnibus = 0.00125) were associated with iRBD. Our results suggest that the HLA locus may have different roles across synucleinopathies.

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts.

NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement-sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies.

HLA in isolated REM sleep behavior disorder and Lewy body dementia.

Background and Objectives: Isolated/idiopathic REM sleep behavior disorder (iRBD) and Lewy body dementia (LBD) are synucleinopathies that have partial genetic overlap with Parkinson's disease (PD). Previous studies have shown that neuroinflammation plays a substantial role in these disorders. In PD, specific residues of the human leukocyte antigen ( HLA ) were suggested to be associated with a protective effect. This study examined whether the HLA locus plays a similar role in iRBD, LBD and PD. Methods: We performed HLA imputation on iRBD genotyping data (1,072 patients and 9,505 controls) and LBD whole-genome sequencing (2,604 patients and 4,032 controls) using the multi-ethnic HLA reference panel v2 from the Michigan Imputation Server. Using logistic regression, we tested the association of HLA alleles, amino acids and haplotypes with disease susceptibility. We included age, sex and the top 10 principal components as covariates. We also performed an omnibus test to examine which HLA residue positions explain the most variance. Results: In iRBD, HLA-DRB1 *11:01 was the only allele passing FDR correction (OR=1.57, 95% CI=1.27-1.93, p =2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR=1.26, 95%CI=1.12-1.41, p =8.76e-05), 70Q (OR=0.81, 95% CI=0.72-0.91, p =3.65e-04) and 71R (OR=1.21, 95% CI=1.08-1.35, p =1.35e-03). In HLA-DRB1 , position 71 ( p omnibus =0.00102) and 70 ( p omnibus =0.00125) were associated with iRBD. We found no association in LBD. Discussion: This study identified an association between HLA-DRB1 11:01 and iRBD, distinct from the previously reported association in PD. Therefore, the HLA locus may play different roles across synucleinopathies. Additional studies are required better to understand HLA's role in iRBD and LBD.

Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects.

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention.

Timing stroke: A review on stroke pathophysiology and its influence over time on diffusion measures.

Diffusion imaging (DWI) is considered an optimal technique to detect hyperacute cerebral ischemia and has thus enriched the clinical management of patients with suspected stroke. Researchers have taken this technique beyond with Diffusion Tensor Imaging (DTI)-extracted measures, which have been proposed as biomarkers of stroke progression. A large body of literature report on the correlates between pathophysiological events, such as cytotoxic and vasogenic edema, and diffusion changes in the brain. However, a unified picture of these changes, and their exploration as stroke pathology progression biomarkers, remains to be done. We present here a narrative review on the different pathophysiological events underlying stroke from onset until late subacute stages and its relation to different brain edema forms. Studies included in this review used either DWI and/or DTI analysis in hyperacute (<24 h), acute (1-7 days), early subacute (7-30 days) and/or late subacute (1-6 months) phase of stroke, including human and animal models. Our conclusions are that diffusion measures should be considered as a potential proxy measure for stroke neuroinflammation status, specially in early stages of the disease. Furthermore, we suggest that the choice of diffusion measures and the interpretation of their changes, in both research and clinical settings, need to be linked to the different stroke phases to account correctly for the progression, and eventual resolution, of neuroinflammation.

Self-reported developmental changes in the frequency and characteristics of somnambulistic and sleep terror episodes in chronic sleepwalkers.

BACKGROUND: Far from being benign, somnambulistic episodes can be frequent and/or severe and potentially injurious. Episodes may also be accompanied by sleep mentation with variable degrees of retrograde amnesia. The present study investigated how somnambulistic episodes unfold from childhood through adulthood, a topic that remains understudied. METHODS: Adult sleepwalkers with a diagnosis of primary somnambulism and a childhood onset of the disorder (n = 113) were assessed for changes in frequency of their episodes, recall of episode-related sleep mentation and aggressive episodes during childhood, adolescence and adulthood. In addition, sleepwalkers (n = 52) with childhood-onset of sleep terrors were assessed for developmental changes in sleep terror frequency. RESULTS: Results indicate that the frequency of somnambulistic episodes remains unchanged during childhood and adolescence before increasing during adulthood. An opposite trend was observed for sleep terrors. The frequency of aggressive somnambulistic episodes and of sleep mentation associated with somnambulism increased from childhood to adolescence and into adulthood. By contrast, the recall of sleep mentation associated with sleep terrors did not change over time. Additionally, a higher frequency of aggressive somnambulistic episodes predicted a higher frequency of sleep mentation associated with somnambulism. These patterns were similar across men and women. CONCLUSION: Our study demonstrates that in chronic sleepwalkers, sleep mentation associated with somnambulistic episodes increases with age while episodes worsen in frequency and severity from childhood to adulthood. These findings add to the limited literature in the field and provide valuable insights into how key clinical characteristics of somnambulism evolve across the lifespan.

Word-finding in confrontation naming and picture descriptions produced by individuals with early post-stroke aphasia.

Objective: The present study aims to assess the relationship between quantitative measures of connected speech production and performance in confrontation naming in early post-stroke aphasia (8-14 days post-stroke). Method: We collected connected speech samples elicited by a picture description task and administered a confrontation naming task to 20 individuals with early post-stroke aphasia and 20 healthy controls. Transcriptions were made in compliance with the CHAT format guidelines. Several micro- (i.e. duration, total number of words, words per minute, mean length of utterances, ratio of open- to closed-class words and noun-to-verb ratio, VOC-D, repetitions, self-corrections, and phonological and semantic errors) and macrolinguistic (i.e. informativeness and efficiency) measures were extracted. Results: We provide evidence for the presence of impairments in an array of micro- and macrolinguistic measures of speech in individuals with early post-stroke aphasia. We show that in the patient group, confrontation naming abilities most strongly relate to informativeness in a picture description task. Conclusion: Our findings contribute to a better understanding of the relationship between performance in confrontation naming and in connected speech production in the first days after stroke onset and also suggest that discourse analysis may provide unique, possibly more complex information.

Rare PSAP Variants and Possible Interaction with GBA in REM Sleep Behavior Disorder.

BACKGROUND: PSAP encodes saposin C, the co-activator of glucocerebrosidase, encoded by GBA. GBA mutations are associated with idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of synucleinopathy. OBJECTIVE: To examine the role of PSAP mutations in iRBD. METHODS: We fully sequenced PSAP and performed Optimized Sequence Kernel Association Test in 1,113 iRBD patients and 2,324 controls. We identified loss-of-function (LoF) mutations, which are very rare in PSAP, in three iRBD patients and none in controls (uncorrected p = 0.018). RESULTS: Two variants were stop mutations, p.Gln260Ter and p.Glu166Ter, and one was an in-frame deletion, p.332_333del. All three mutations have a deleterious effect on saposin C, based on in silico analysis. In addition, the two carriers of p.Glu166Ter and p.332_333del mutations also carried a GBA variant, p.Arg349Ter and p.Glu326Lys, respectively. The co-occurrence of these extremely rare PSAP LoF mutations in two (0.2%) GBA variant carriers in the iRBD cohort, is unlikely to occur by chance (estimated co-occurrence in the general population based on gnomAD data is 0.00035%). Although none of the three iRBD patients with PSAP LoF mutations have phenoconverted to an overt synucleinopathy at their last follow-up, all manifested initial signs suggestive of motor dysfunction, two were diagnosed with mild cognitive impairment and all showed prodromal clinical markers other than RBD. Their probability of prodromal PD, according to the Movement Disorder Society research criteria, was 98% or more. CONCLUSION: These results suggest a possible role of PSAP variants in iRBD and potential genetic interaction with GBA, which requires additional studies.

Does the adenosine deaminase (ADA) gene confer risk of sleepwalking?

Sleepwalking is a common non-rapid eye movement (NREM) parasomnia and a significant cause of sleep-related injuries. While evidence suggest that the occurrence of this condition is partly determined by genetic factors, its pattern of inheritance remains unclear, and few molecular studies have been conducted. One promising candidate is the adenosine deaminase (ADA) gene. Adenosine and the ADA enzyme play an important role in the homeostatic regulation of NREM sleep. In a single sleepwalking family, genome-wide analysis identified a locus on chromosome 20, where ADA lies. In this study, we examined if variants in the ADA gene were associated with sleepwalking. In total, 251 sleepwalking patients were clinically assessed, and DNA samples were compared to those from 94 unaffected controls. Next-generation sequencing of the whole ADA gene was performed. Bio-informatic analysis enabled the identification of variants and assessed variants enrichment in our cohort compared to controls. We detected 25 different coding and non-coding variants, of which 22 were found among sleepwalkers. None were enriched in the sleepwalking population. However, many missense variants were predicted as likely pathogenic by at least two in silico prediction algorithms. This study involves the largest sleepwalking cohort in which the role of a susceptibility gene was investigated. Our results did not reveal an association between ADA gene and sleepwalking, thus ruling out the possibility of ADA as a major genetic factor for this condition. Future work is needed to identify susceptibility genes.

Autonomic Modulation During Baseline and Recovery Sleep in Adult Sleepwalkers.

Sleepwalking has been conceptualized as deregulation between slow-wave sleep and arousal, with its occurrence in predisposed patients increasing following sleep deprivation. Recent evidence showed autonomic changes before arousals and somnambulistic episodes, suggesting that autonomic dysfunctions may contribute to the pathophysiology of sleepwalking. We investigated cardiac autonomic modulation during slow-wave sleep in sleepwalkers and controls during normal and recovery sleep following sleep deprivation. Fourteen adult sleepwalkers (5M; 28.1 ± 5.8 years) and 14 sex- and age-matched normal controls were evaluated by video-polysomnography for one baseline night and during recovery sleep following 25 h of sleep deprivation. Autonomic modulation was investigated with heart rate variability during participants' slow-wave sleep in their first and second sleep cycles. 5-min electrocardiographic segments from slow-wave sleep were analyzed to investigate low-frequency (LF) and high-frequency (HF) components of heart rate spectral decomposition. Group (sleepwalkers, controls) X condition (baseline, recovery) ANOVAs were performed to compare LF and HF in absolute and normalized units (nLF and nHF), and LF/HF ratio. When compared to controls, sleepwalkers' recovery slow-wave sleep showed lower LF/HF ratio and higher nHF during the first sleep cycle. In fact, compared to baseline recordings, sleepwalkers, but not controls, showed a significant decrease in nLF and LF/HF ratio as well as increased nHF during recovery slow-wave sleep during the first cycle. Although non-significant, similar findings with medium effect sizes were observed for absolute values (LF, HF). Patterns of autonomic modulation during sleepwalkers' recovery slow-wave sleep suggest parasympathetic dominance as compared to baseline sleep values and to controls. This parasympathetic predominance may be a marker of abnormal neural mechanisms underlying, or interfere with, the arousal processes and contribute to the pathophysiology of sleepwalking.

Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder.

OBJECTIVE: To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated REM sleep behavior disorder (iRBD). METHODS: We fully sequenced 25 genes previously identified in GWASs of PD in a total of 1,039 patients with iRBD and 1,852 controls. The role of rare heterozygous variants in these genes was examined with burden tests. The contribution of biallelic variants was further tested. To examine the potential effect of rare nonsynonymous BST1 variants on the protein structure, we performed in silico structural analysis. Finally, we examined the association of common variants using logistic regression adjusted for age and sex. RESULTS: We found an association between rare heterozygous nonsynonymous variants in BST1 and iRBD (p = 0.0003 at coverage >50× and 0.0004 at >30×), driven mainly by 3 nonsynonymous variants (p.V85M, p.I101V, and p.V272M) found in 22 (1.2%) controls vs 2 (0.2%) patients. All 3 variants seem to be loss-of-function variants with a potential effect on the protein structure and stability. Rare noncoding heterozygous variants in LAMP3 were also associated with iRBD (p = 0.0006 at >30×). We found no association between rare heterozygous variants in the rest of genes and iRBD. Several carriers of biallelic variants were identified, yet there was no overrepresentation in iRBD. CONCLUSION: Our results suggest that rare coding variants in BST1 and rare noncoding variants in LAMP3 are associated with iRBD. Additional studies are required to replicate these results and to examine whether loss of function of BST1 could be a therapeutic target.

Childhood restless legs syndrome: A longitudinal study of prevalence and familial aggregation.

Restless legs syndrome is a relatively common neurological disorder in adults. In childhood, however, its prevalence and genetic contribution are still largely unknown. The objectives of this study were to assess the prevalence of restless legs syndrome (RLS) during childhood and adolescence in a large population-based cohort and evaluate the degree of association with parental history. Data from a large, prospective longitudinal cohort from the Quebec Longitudinal Study of Child Development of 1,856 children born in 1997-1998 were studied from 2005 to 2013. The prevalence of RLS was assessed at ages 7, 8, 12, 13 and 15 years through a questionnaire completed by the mother. Parental history of RLS was also queried. Between 7 and 15 years of age, the yearly prevalence of RLS ranged from 2.4% to 3.1%, with a higher prevalence in boys than girls at 12 years old. The prevalence of RLS at any time during this period was 8.6% but only 1.8% of parents answered positively at least twice during the longitudinal study. This low persistent rate could be explained by remissions or the use of parental report. The prevalence was higher when there was at least one parent affected with RLS (13.0%) compared to children without a parental history (6.9%). Findings from this population-based study confirm the high prevalence of RLS in children aged 7-15 years and corroborate the strong familial aggregation for RLS. Parents should be encouraged to inform the paediatrician about the presence of RLS in the family to help the diagnostic process.

Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder.

BACKGROUND: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). OBJECTIVE: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. METHODS: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. RESULTS: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. CONCLUSION: Our results do not support a major role for variants in these genes in the risk of iRBD. © 2020 International Parkinson and Movement Disorder Society.

Spindles insufficiency in sleepwalkers' deep sleep.

OBJECTIVES: Sleepwalkers have consistently shown N3 sleep discontinuity, especially after sleep deprivation. In healthy subjects, sleep spindles activity has been positively correlated to sleep stability. We aimed to compare spindles density during N3 sleep between sleepwalkers and healthy controls. METHODS: Two cohorts of 10 and 21 adult sleepwalkers respectively controlled with 10 and 18 healthy volunteers underwent one baseline and one recovery sleep recording after 38h (cohort 1) and 25h (cohort 2) of sleep deprivation. For the two recordings, we performed an automatic detection of spindles (11-16Hz) from EEG signal during N3 sleep, restricted to the first sleep cycle and repeated for all cycles. For better interpretation of results, we extended the analysis to N2 sleep and we also measured the density of slow waves oscillation (SWO) (0.5-4Hz) during the same periods. RESULTS: Compared to controls, sleepwalkers showed significantly lower spindle densities during N3 sleep considering the first sleep cycle (both cohorts) or all cycles (cohort 1). SWO densities did not differ (cohort 1) or were lower (cohort 2) for sleepwalkers. The effect of sleep deprivation did not interact with the effect of group on spindles and SWO densities. CONCLUSION: This work suggests that the instability of N3 sleep inherent to sleepwalkers may be underpinned by a specific alteration of spindles activity.

GBA variants in REM sleep behavior disorder: A multicenter study.

OBJECTIVE: To study the role of GBA variants in the risk for isolated REM sleep behavior disorder (iRBD) and conversion to overt neurodegeneration. METHODS: A total of 4,147 individuals were included: 1,061 patients with iRBD and 3,086 controls. GBA was fully sequenced using molecular inversion probes and Sanger sequencing. We analyzed the effects of GBA variants on the risk of iRBD, age at onset (AAO), and conversion rates. RESULTS: GBA variants were found in 9.5% of patients with iRBD compared to 4.1% of controls (odds ratio, 2.45; 95% confidence interval [CI], 1.87-3.22; p = 1 × 10-10). The estimated OR for mild p.N370S variant carriers was 3.69 (95% CI, 1.90-7.14; p = 3.5 × 10-5), while for severe variant carriers it was 17.55 (95% CI, 2.11-145.9; p = 0.0015). Carriers of severe GBA variants had an average AAO of 52.8 years, 7-8 years earlier than those with mild variants or noncarriers (p = 0.029). Of the GBA variant carriers with available data, 52.5% had converted, compared to 35.6% of noncarriers (p = 0.011), with a trend for faster conversion among severe GBA variant carriers. However, the results on AAO and conversion were based on small numbers and should be interpreted with caution. CONCLUSIONS: GBA variants robustly and differentially increase the risk of iRBD. The rate of conversion to neurodegeneration is also increased and may be faster among severe GBA variant carriers, although confirmation will be required in larger samples. Screening for RBD in healthy carriers of GBA variants should be studied as a potential way to identify GBA variant carriers who will develop a synucleinopathy in the future.

SMPD1 variants do not have a major role in rapid eye movement sleep behavior disorder.

Mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson's disease and dementia with Lewy bodies. In the current study, we aimed to evaluate the role of SMPD1 variants in isolated rapid eye movement sleep behavior disorder (iRBD). SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1287 controls from European descent. Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.

Predicting Early Post-stroke Aphasia Outcome From Initial Aphasia Severity.

Background: The greatest degree of language recovery in post-stroke aphasia takes place within the first weeks. Aphasia severity and lesion measures have been shown to be good predictors of long-term outcomes. However, little is known about their implications in early spontaneous recovery. The present study sought to determine which factors better predict early language outcomes in individuals with post-stroke aphasia. Methods: Twenty individuals with post-stroke aphasia were assessed <72 h (acute) and 10-14 days (subacute) after stroke onset. We developed a composite score (CS) consisting of several linguistic sub-tests: repetition, oral comprehension and naming. Lesion volume, lesion load and diffusion measures [fractional anisotropy (FA) and axial diffusivity (AD)] from both arcuate fasciculi (AF) were also extracted using MRI scans performed at the same time points. A series of regression analyses were performed to predict the CS at the second assessment. Results: Among the diffusion measures, only FA from right AF was found to be a significant predictor of early subacute aphasia outcome. However, when combined in two hierarchical models with FA, age and either lesion load or lesion size, the initial aphasia severity was found to account for most of the variance (R 2 = 0.678), similarly to the complete models (R 2 = 0.703 and R 2 = 0.73, respectively). Conclusions: Initial aphasia severity was the best predictor of early post-stroke aphasia outcome, whereas lesion measures, though highly correlated, show less influence on the prediction model. We suggest that factors predicting early recovery may differ from those involved in long-term recovery.