Clinical and Translational Neuroscience

This systematic review and meta-analysis of global peer-reviewed neuroimaging findings preliminarily assessed the magnitude of effect sizes (ES) of the influences of family poverty/low socioeconomic status (SES) on children’s neurocognition and whether these were consistently detrimental. The literature search (Web of Science; PUBMED; MEDLINE: PSYCNET; GOOGLE SCHOLAR; SCIENCEDIRECT) included 66 studies from 1988 to 2022; 85% of the studies included were conducted in Western, high-income nations. Bayesian models, corrected by study sizes and variances, revealed ESs were heterogeneous across countries and measurements. Bayesian and standard hypothesis testing indicated high and low SES groups showed similar behavioral performances in neuroimaging-concurrent tasks. Except for Magnetic Resonance Imaging studies, ESs were small-to-intermediate with modest reliability. The strongest ESs were found for attention, mathematical performance, language, and cortical volume, followed by intermediate ESs for reading and socioemotional processes. Differentials in resting activity and connectivity, working memory, and executive functions yielded small effects. A bibliometric analysis showed a significant proportion of the literature attributed neurocognitive deficits to low SES, despite overlooking the under-representativity of non-Western and low-income countries, potential influences of racial/ethnic differences, and measurement sensitivity/specificity discrepancies. To reach United Nations Sustainable Development Goals, policies and interventions should consider regional, structural, or environmental ecologies beyond the individual, critically probing implicit deficit attributions. Full article

Neuromuscular disorders (NMDs) encompass a highly diverse group of conditions that affect the skeletal muscles, peripheral nervous system, or motor endplate. Depending on the underlying disease, common characteristics include progressive muscle weakness and sensory disturbances, both of which can contribute to sleep disruption. Disorders of sleep are extremely frequent in NMDs and substantially co-determine overall morbidity, quality of life, and survival. As many NMDs currently lack a cure, supportive therapy is mandatory and includes appropriate management of sleep-related symptoms. Specific sleep disorders that may arise in NMDs include insomnia due to pain or leg muscle cramps, restless legs syndrome, and sleep-disordered breathing, notably obstructive sleep apnea and hypoventilation. This review article aims to comprehensively outline the clinical spectrum of sleep disorders and sleep properties associated with NMDs. Full article

Study objectives: Sleep and circadian rhythms disorders are frequent in the acute stroke. Sleep modifications are likely to contribute to the development of stroke-related delirium, a common neuropsychiatric complication of acute stroke. This systematic review aimed to clarify the association between sleep modifications and the occurrence of delirium in patients with acute stroke. Methods: The current systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The search was performed on PubMed and Scopus databases. Only studies that provided data concerning sleep, or pre-existing sleep disorders, in acute stroke and performed a formal evaluation of delirium were included. Results: The literature search enabled the identification of 15 studies, which exhibited high heterogeneity in terms of study design, settings, sleep assessments, delirium measures, and types of sleep intervention. In the study quality assessment, the majority of the studies were rated as weak or moderate. In most of the cases, sleep was subjectively assessed by the patients or rated by clinicians. None of the studies performed polysomnography for the evaluation of sleep. Only four of the studies assessed the impact of a sleep intervention on delirium, suggesting the potentially protective role of sleep promotion in reducing the prevalence and severity of stroke-related delirium. Conclusions: The evidence arising from the present systematic review supports that sleep disruption is a potential promoting factor for stroke-related delirium. We suggest that a formal sleep assessment and sleep promotion should be included in routine stroke care. Full article

Severe traumatic brain injury (TBI) may cause disorders of consciousness (DoC) in the form of coma, unresponsive wakefulness syndrome (UWS), or minimally conscious state (MCS). Despite significant advancements made over the last two decades in detecting, predicting, and promoting the recovery of consciousness in TBI patients with DoC, the available diagnostic and treatment choices remain limited. In cases of severe TBI, the dissolution of consciousness both in the acute and post-acute phases constitutes one of the major clinical findings and challenges. In clinical settings, neurologists and neurorehabilitation specialists are called on to discern the level of consciousness in patients who are unable to communicate, and to project outcomes and recommend approaches to treatment. Standards of care are not available to guide clinical decision-making for this population, often leading to inconsistent, inaccurate, and inappropriate care. Recent studies refer to network-based mechanisms of consciousness as a more promising method to predict outcomes and functional recovery. A further goal is the modulation of neural networks underlying awareness and arousal as the main components of consciousness. This review centers on the difficulties in characterizing individuals experiencing post-traumatic DoC and on the recent advancements made in the identification and prognostication of consciousness recovery through the utilization of advanced neuroimaging and electrophysiological techniques as well as biomarkers. Moreover, we discuss new treatment approaches and summarize recent therapeutic recommendations. Full article

Background: The relationship between sleep and creativity is a topic of much controversy. General benefits of napping have been described not only in sleep-deprived individuals and in shift workers, but also in people with sufficient night sleep. However, only few studies have investigated the relationship between nap and creativity. Methods: Forty-two native German speakers (29 females, mean age = 24 years, SD = 3.3 years) took part in two experimental sessions (i.e., baseline and intervention). In both sessions, divergent and convergent verbal and figural creativity tasks were administered at the same time of the day. While the baseline session was identical for all the participants, in the second session participants were randomized into either a sixty-minute nap or a sixty-minute rest group. Results: No significant group differences were found for neither divergent nor convergent creativity thinking tasks, suggesting that the interventions had similar effects in both groups. Interestingly, the analysis of the pooled data (i.e., pooled nap and rest groups) indicated differential effects of figural versus verbal creativity tasks, such that significant post-intervention improvements were found for the figural, but not for the verbal divergent and convergent thinking tasks. Conclusions: While further studies are needed to confirm these findings, to the best of our knowledge, such a dissociation between performance of verbal and figural creativity tasks after nap/rest interventions has not been described to date. Full article

REM sleep behavior disorder (RBD) is a parasomnia in which the customary generalized skeletal muscle atonia of REM sleep, “REM-atonia”, is compromised, allowing for the injurious acting-out of dreams. RBD can be idiopathic/isolated (iRBD) or symptomatic of neurological disorders, and can be triggered by most antidepressants. RBD mainly affects middle-aged and older adults, and is strongly linked with alpha-synucleinopathies, mainly Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). iRBD is now known to be the earliest and strongest predictor of future PD/DLB, which has stimulated a major international clinical and basic science research effort to enroll iRBD patients for upcoming neuroprotective/disease-modifying trials and to identify the most promising interventions to test in these cohorts. This review will provide the latest pertinent information on the rapidly expanding field of RBD. The methods included a PubMed literature search that included PubCrawlers, which utilizes the NCBI (National Center for Biotechnology Information) E-utils tools for publication retrieval, using the keywords “REM sleep behavior disorder” and “RBD”. The results yielded the latest updates on iRBD as prodromal PD/DLB, with the most promising biomarkers for phenoconversion provided, along with a presentation of three clinical research consortiums that are systematically gathering patients in preparation for enrollment in upcoming clinical trials: (i) The International RBD Study Group; (ii) The North American Prodromal Synucleinopathy (NAPS and NAPS2) Consortium; and (iii) The FARPRESTO Italian multicenter RBD research consortium. In addition, updates on the Parasomnia Overlap Disorder (RBD + NREM parasomnia) and on narcolepsy-RBD are provided, along with new epidemiologic data, the latest RBD management guidelines, and updates on animal models of RBD. Emerging areas of critical RBD research are also highlighted. In conclusion, RBD is a notable example of clinical and translational neuroscience research. Full article

In the last few years, restless sleep has been described as the key element of many clinical issues in childhood, leading to the recognition of “restless sleep disorder” (RSD) as a new proposed diagnostic category. The essential aid of video-polysomnographic recordings enables detection and quantification of the “large muscle group movements” (such as limb movements and repositioning) frequently described by parents of children with RSD. Strong evidence links iron deficiency to the pathophysiology of sleep-related movement disorders such as RSD, restless legs syndrome, periodic limb movement disorder, and attention deficit hyperactivity disorder (ADHD) due to the important role played by the brain dopamine production system. Serum ferritin is the main parameter used to evaluate iron deficiency in patients with sleep-related movement disorders. Iron supplementation is recommended when the serum ferritin level is <50 ng/mL, since the literature emphasizes the correlation between lower levels of serum ferritin, serum iron, and cerebrospinal fluid ferritin, and increased symptom severity. Moreover, several studies report an improvement in symptoms when ferritin levels are kept above 50 ng/mL. In this narrative review, we discuss the role of iron in sleep-related movement disorders, as well as ADHD, highlighting not only the connection between these two conditions, but also the relevance of iron supplementation for symptom improvement. Full article

Headaches can be nociplastic, neuropathic, and nociceptive. Pain related to the latter two categories occurs in the presence of nerve lesions and nociceptive stimuli; attributing pain to the last category requires a list of potential causes and arguments supporting the causal claim. Taking a history and examining patients serves to assess diagnostic criteria and screen for disorders whose diagnosis requires additional examinations. Screening information occurs in two types: one indicates that patients have a headache due to another condition; the other suggests they are at risk. Aspiring to make causal claims for a headache is reasonable because if underlying disorders appear independently and randomly, it is probable that there is only one cause. Thus, having found a cause often implies having found the cause. The prerequisites for causal claims are temporal sequencing, correlation, and elimination of alternate causes. Mechanistic, manipulative, and probabilistic evidence supports the second criterion. The importance of headaches lies in their frequent appearance as an early symptom of an incipient disorder (“sentinel symptom”). Hence, they provide the opportunity to diagnose early diseases with potentially deleterious consequences. Thus, it is sensible to assess each attack carefully and systematically. Full article

Background: The clinical evaluation of a patient complaining of excessive daytime sleepiness is of crucial importance for the diagnosis of narcolepsy. The Swiss Narcolepsy Scale (SNS) was developed in 2004 as a screening tool for patients with narcolepsy and shown in three different studies to have a high sensitivity and specificity for narcolepsy type 1 (NT1). The aim of this study was to assess the validity and reliability of the Turkish version of SNS (SNS-TR). Patients and Methods: Twenty-one healthy controls, 26 patients with idiopathic hypersomnia, and 27 patients with narcolepsy were recruited from five accredited sleep centers in Turkey. Pearson’s correlation coefficient and degree of freedom were used to determine the validity of each question. Cronbach’s alpha was calculated to assess the internal consistency or reliability of Likert-type questions. The inter-rater reliability was tested using Cohen’s kappa analysis, and the intra-class correlation coefficient (ICC) was used to evaluate the validity and reliability between two evaluations with a one-month interval. Results: Sensitivity and specificity of SNS-TR were 90.5% and 100%, respectively, for diagnosing NT1. Cronbach’s alpha was 0.976, showing a highly reliable level of internal consistency. The inter-rater reliability of the questions and the validity and reliability between two evaluations were moderate or above. Conclusion: This study provides evidence for the validity and reliability of SNS-TR in diagnosing and discriminating NT1 from other disorders of hypersomnolence with a very high sensitivity and specificity. Full article

Unilateral head and neck pain is a hallmark of cervical artery dissection (CAD). While pain is conceived as an alarming sign for patients and often leads to discovery of the dissection, it is not known if persistence of pain is associated with the course of CAD. Potentially, pain could indicate persisting vessel pathology and thus guide treatment decisions aimed at reducing risk of ischemic stroke in CAD. We performed a retrospective analysis of data from patients with CAD treated at the University Hospital Zurich (USZ). Only patients with information about the presence of pain, independence after CAD according to the modified Rankin scale (mRS), and imaging-based information on vessel status were included. Patients were grouped according to presence/absence of head and/or neck pain on admission and at a three-month follow-up. We used descriptive statistics and logistic regression to reveal a potential association between pain on admission and pain at follow-up with status of the dissected vessel at follow-up (open vs. stenosed or occluded). We screened 139 patients with CAD between 2014 and 2019 and included 68. Fifty-nine patients (86.8%) had pain on admission, which was resolved in 46 (68%) at follow-up. Our post hoc analysis revealed that more patients with headache or neck pain on admission had a migraine diagnosis in medical history (n = 7 (10.4%) vs. n = 0 (0%), p = 0.029) and that NIHSS on admission was higher in patients with no pain at presentation (group B NIHSS = 3, IQR 8 vs. group A NIHSS = 2, IQR 5, group C NIHSS = 0, IQR 2, p = 0.041). There were no other differences between the three patient groups in the descriptive analysis. Logistic regression analysis for vessel status at follow-up did not show an association with pain on admission or at follow-up. In our cohort of patients with CAD, headache was a common initial clinical presentation, which rarely persisted for three months. Headache on admission or at follow-up did not predict persisting vessel pathology in patients with CAD. Full article

Primary headaches are a common debilitating health condition. Proper diagnosis and treatment depend on patients’ communication. We wanted to explore differences in pain communication with a special interest in potential sex differences. Patients visiting our headache unit for the first time filled in two different questionnaires (one before entering the consultation and one directly after finishing the consultation), through which we captured patients’ descriptions of their pain, its potential impact on daily lives, the well-being of our patients and the satisfaction with our consultation. We included a total of 35 patients (22 female, 13 male). Women reported experiencing a greater loss of socially active days during the last 3 months because of headaches compared to men. Furthermore, women were more satisfied with our consultation. In addition, we revealed migraineurs characterize their pain differently than stated in the International Classification of Headache Disorders (ICHD-3) criteria. The adjective “pressing” (drückend) was used significantly more often by migraineurs compared to patients with tension-type headaches. Nevertheless, in the physicians’ written report, the characterization more often contained the ICHD-3 corresponding adjective “pulsating” (pulsierend). Since the typification of headaches and subsequent therapy depends predominantly on the patients’ communication, consideration of the individual pain description and further research on headache characterization are indispensable. Full article

Post-COVID-19 syndrome is an ongoing challenge for healthcare systems as well as for society. The clinical picture of post-COVID-19 syndrome is heterogeneous, including fatigue, sleep disturbances, pain, hair loss, and gastrointestinal symptoms such as chronic diarrhea. Neurological complaints such as fatigue, cognitive impairment, and sleep disturbances are common. Due to the short timeframe of experience and small amount of evidence in this field, the treatment of post-COVID-19 syndrome remains a challenge. Currently, therapeutic options for post-COVID-19 syndrome are limited to non-pharmaceutical interventions and the symptomatic therapy of respective symptoms. In this article, we summarize the current knowledge about therapeutic options for the treatment of neurological symptoms of post-COVID-19 syndrome. Full article

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with symptoms that greatly affect quality of life (QoL). One of the most prevalent symptoms of MS is fatigue, also one of the main factors reducing QoL. Low levels of vitamin D (VD) are associated with worse QoL and with increased risk of developing more severe forms of the disease. Methods: In this cross-sectional study, we compared perceptions of quality of life and fatigue in 324 patients, subdivided into four groups, according to their treatment: high-dose VD therapy only, disease-modifying therapy (DMT) only, both treatments, and no treatments. All subjects completed the MSQOL-54 and the FSS questionnaires via an online survey. Results: High-dose VD treatment was associated with an increased perception of physical QoL (83.60 vs. 66.92, p < 0.001), mental QoL (75.52 vs. 59.80, p < 0.001), and fatigue (1.89 vs. 2.98, p < 0.001), compared to the DMT-only group. Treatment with DMT was associated with a worse perception of physical QoL compared to no treatment (70.58 vs. 76.53, p = 0.024). Conclusions: high-dose VD treatment is well-tolerated and associated with an increased perception of QoL in people with MS. Full article

Background: Genetic and epigenetic modifiers of age at onset of Parkinson’s disease (PD) are largely unknown. It remains unclear whether DNA methylation (DNAm) age acceleration is linked to age at onset in PD patients of different ethnicities with a similar genetic background. We aim to characterize the clinical, genomic and epigenomic features of three pairs of Chinese monozygotic twins discordant for PD onset by up to 10 years. Methods: We conducted whole genome sequencing, multiplex ligation-dependent probe amplification and genome-wide DNAm array to evaluate the three pairs of Chinese monozygotic twins discordant for age at onset of PD (families A–C). Results: We identified two heterozygous PRKN mutations (exon 2–4 deletion and p.Met1Thr) in PD affected members of one family. Somatic mutation analyses of investigated families did not reveal any variants that could explain the phenotypic discordance in the twin pairs. Of note, our epigenetic study revealed that the twins with earlier-onset had a trend of faster DNAm age acceleration than the later-onset/asymptomatic twins, but without statistical significance. Conclusion: The link between DNAm age acceleration and PD onset in Chinese patients should be interpreted with cautious, and need to be further verified in an extended PD cohort with similar genetic background. Full article

This review article addresses the complex issues faced by individuals with Multiple Sclerosis (MS) who are planning a family, becoming pregnant, or wishing to breastfeed their baby. Recommendations and guidelines were discussed and agreed upon by neurologists, neuroradiologists, nurses, and pharmacists involved in the management of MS in the Kingdom of Saudi Arabia (KSA). MS itself does not harm a pregnancy, and people with MS of childbearing age can be encouraged to enjoy family life. Family planning should be a part of the initial conversation with a newly diagnosed patient of childbearing age. Interferons and glatiramer acetate can be continued throughout pregnancy and can be administered during breastfeeding if the benefits outweigh the risks. These DMTs may be considered for a woman with well-controlled MS who is planning a pregnancy or otherwise not using contraception, according to an individualized risk-benefit analysis. The use of contraception should be maintained during the administration of other disease-modifying therapies (DMTs). Natalizumab can be administered at a reduced administration frequency to women with high MS disease activity up to 30 weeks gestation (this agent may induce hematological abnormalities in the fetus). Other DMTs should be withdrawn for variable periods before contraception is stopped and immediately after the discovery of a pregnancy (beware of rebound disease activity after withdrawing natalizumab or fingolimod). Resumption of treatment should not be delayed in women at risk of relapse during the postpartum period and especially in those who do not wish to breastfeed. Full article

There is a general understanding that older adults suffering from a stroke have poorer outcomes and might benefit less from neurorehabilitation. This narrative review analyzes the conflicting evidence for the effect of aging on the success of neurorehabilitation after a stroke. While there is convincing evidence that functional outcomes are negatively impacted by age, functional gains made during rehabilitation are less clearly impacted, and the effect of age seems to be related to other factors such as prestroke independence and therapy intensity, as well as the population studied. There is no evidence that would justify withholding high-intensity neurorehabilitation on the sole basis of age. Full article

There is much controversy about the link between motor symptom progression and the plethora of reported brain atrophy patterns in idiopathic Parkinson’s disease (PD). The main goal of this study is to provide empirical evidence for unique and common contributions of clinical phenotype characteristics on the dynamic changes of brain structure over time. We analyzed the behavioral and magnetic resonance imaging (MRI) data of PD patients (n = 22) and healthy individuals (n = 21) acquired two years apart through the computational anatomy framework of longitudinal voxel-based morphometry (VBM). This analysis revealed a symmetrical bi-hemispheric pattern of accelerated grey matter decrease in PD extending through the insula, parahippocampal gyrus, medial temporal lobes and the precuneus. We observed a hemisphere-specific correlation between the established scores for motor symptoms severity and the rate of atrophy within motor regions, which was further differentiated by the clinical phenotype characteristics of PD patients. Baseline cerebellum anatomy differences between the tremor-dominant and akineto-rigid PD remained stable over time and can be regarded as trait rather than state-associated features. We interpret the observed pattern of progressive brain anatomy changes as mainly linked to insular areas that determine together with basal ganglia the motor and non-motor phenotype in PD. Our findings provide empirical evidence for the sensitivity of computational anatomy to dynamic changes in PD, offering additional opportunities to establish reliable models of disease progression. Full article

Memory disorders are common in clinical practice. This review focuses on the rehabilitation of anterograde amnesia, the inability to learn and retrieve new information, in non-degenerative brain disease. Diverse mnemonic strategies may be helpful in learning specific pieces of information. Their success also depends on the severity of associated cognitive failures, in particular, executive dysfunction. However, unless transfer to everyday activities is specifically trained, such strategies are of limited value in promoting independence in daily life. External memory aids are often necessary to allow for independent living. Learning to use them requires intact capacities such as procedural learning or conditioning. This review further discusses the rehabilitation of confabulation, that is, the emergence of memories of events that never happened. The rehabilitation of memory disorders needs to be tailored to patients’ individual capacities and needs. Full article

This article deals with recommendations on the management of symptoms of MS and on the provision of vaccinations in patients receiving disease-modifying therapies (DMTs). Symptoms of MS, such as fatigue, depression, urinary symptoms, spasticity, impairment of gait, and sexual dysfunction, are common in this population. Recognizing and addressing these symptoms is key to maintaining the quality of life of people with MS. Vaccination status should be reviewed and updated prior to initiation of DMTs. In general, vaccination should be avoided for variable periods after the initiation of some DMTs. Live attenuated vaccines are contraindicated and should be considered on a case-by-case basis. These consensus recommendations will present the best practices for vaccination in Saudi Arabia before, during, and after the COVID-19 pandemic. The recommendations will be updated periodically and as needed as new evidence becomes available. Full article