Clinical and Translational Neuroscience

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

Multiple sclerosis (MS) is an inflammatory neurological illness common in young adults. The prevalence and incidence of MS are regionally and globally increasing. Recent data from Saudi Arabia (SA) estimate the prevalence to be 40.40 cases per 100,000 population, and 61.95 cases per 100,000 population for Saudi nationals. With the increasing availability of treatment options, new challenges for treatment selection and approaches have emerged. There is a clear need for national guidelines to standardize practice, guide the personalization of decisions, and contain increasing costs. A multidisciplinary expert panel was formed to develop evidence-based Saudi consensus recommendations on the diagnosis and clinical care of MS, to aid healthcare practitioners in advising patients on treatment decisions. The recommendations were agreed upon after a thorough review, an evaluation of existing international guidelines, and the latest emerging evidence. Full article

Cognitive performance is negatively affected by the presence of noise, which is seen as a distractor and a stressor, especially in hazardous occupational environments. The addition of musculoskeletal fatigue that commonly accompanies occupational work due to noise interruption can further elevate risk and compromise safety. The purpose of the study was to investigate the impact of both individual and a combination of noise interference and physical workload on simple and choice response time tasks. Sixteen healthy male and female participants (age: 20 ± 1 years; height: 169.48 ± 8.2 cm; weight: 67.93 ± 12.7 kg) performed a simple (SRT) and choice response task (CRT) with three Blazepod™ light response time systems by striking with the dominant lower extremity from a seated position while listening to noises from a construction site (65–85dB) through headphones. Participants then performed a low-intensity musculoskeletal fatigue task and completed the above measures again. Response times (RT) (ms) from three trials of SRT and CRT, both without and with noise interference, before (PRE) and after the workload (POST), were averaged, and a 2 (Noise) × 2 (workload) × 2 (task) repeated measure ANOVA and a 2 (Noise) × 2 (workload) repeated measure ANOVA were performed for SRT and CRT, respectively, using JASP at an alpha level of 0.05. Results revealed a significant interaction between workload task (p = 0.041), as well as a main effect significance for the workload (p = 0.007) and noise (p = 0.044). The main effect significance also existed for workload in SRT (p = 0.009) and for noise in CRT (p = 0.002). In SRT, RT was significantly faster during the POST fatigue measure, suggesting a possible cognitive arousal and a learning effect improvement rather than a negative fatigue effect. In both SRT and CRT, as well as individually in CRT, RT was significantly slower due to noise interruption, negatively impacting performance, especially in the more challenging CRT compared to SRT. Thus, findings from the current study suggest that the impact of noise interruption is significant when the complexity of the response task is greater, and the potential cognitive arousal due to the workload and potential learning effects may influence response time performances. Finally, a lower extremity cognitive–motor task demonstrates response time behavior similar to such upper extremity cognitive–motor tasks. Full article

Virtual reality (VR) is seen by some as a tool that may greatly improve, or even revolutionize cognitive rehabilitation. VR offers distinct advantages compared to classic rehabilitation using paper-and-pencil or computer-based training, such as immersion, the feeling of presence, embodiment of virtual players, ecological and multisensory stimulation. We here review recent clinical studies examining the effects of VR training in patients with stroke-induced cognitive deficits. Several trials reported evidence that VR training improves general cognition compared to standard cognitive training. However, the evidence remains controversial, as some of these studies had a high risk of bias. Regarding mood, there is some indication that immersive training improves depression scores in stroke patients, but the number of studies examining mood changes is very low. Finally, in the domain of spatial cognition the development of specific intervention techniques such as virtual prism adaptation provide avenues for clinical interventions, though well-controlled clinical trials are lacking. Together, the available evidence suggests that VR has the potential to improve rehabilitation particularly in domains requiring repetitive training in an immersed, ecological setting, or when a mismatch between body frames and the environment is created. Controlled clinical studies are required to examine the specific advantages of VR compared to classic interventions. Full article

Multiple sclerosis (MS), particularly relapsing MS (RMS), has become a treatable disease in recent decades, and immunotherapies are now able to influence long-term disease course. A wide range of disease-modifying drugs are available, which makes the choice of therapy in individual cases considerably more complex. Due to specific regulatory aspects (partly diverging approvals by Swissmedic compared to the European Medicines Agency (EMA), and an independent evaluation process for the Federal Office of Public Health (FOPH) specialities list (SL)), we issued a consensus recommendation regarding specific aspects of immunotherapy for MS in Switzerland in 2019. Here, we present revised recommendations with an update on newly approved drugs and new safety aspects, also in reference to the risk of COVID-19 infection and vaccination. Full article

Patients with cluster headache often report a long diagnostic delay. This study creates and validates a screening test that could help speed up the diagnostic process. We invited patients to enrol in this diagnostic case–control study if a trigeminal autonomic headache had been suspected or confirmed. Patients in whom the diagnosis of a cluster headache was not made were controls. First, all participants answered 22 diagnostic questions with “yes” or “no”. Next, we eliminated questions that did not distinguish well between the groups. Then, the variables entered a regression model with the headache diagnosis as the dependent variable. Finally, we combined the remaining variables into a diagnostic scale and tested its accuracy. Seventy-four patients participated, 45 of whom suffered from a cluster headache. The analyses identified five questions distinguishing cluster headache patients and controls. These addressed smoking, being awakened by the pain, restlessness during the attack, unilateral tearing, and duration of the attack (hence, the “SMARTED” scale). The area under the ROC curve was 0.938; sensitivity and specificity, the positive and negative predictive values were 98%, 65%, 81% and 94%, respectively. The SMARTED scale validly and accurately screens for cluster headache in patients suspected of a trigeminal autonomic headache. Full article

For the past 10 years, disease-modifying therapy (DMT) options for multiple sclerosis (MS) have grown remarkably where DMTs have been shown to reduce the risk of MS relapses. MS patients are advised to begin treatment with a DMT shortly after diagnosis to limit the possibility of disease progression over time. While patients with radiologically isolated syndrome do not require pharmacologic treatment, high-risk patients with clinically isolated syndrome are advised to start DMTs. This article provides evidence-based recommendations for DMT use in MS management, helping healthcare practitioners advise patients on treatment decisions. We aim to provide recommendations for the management of acute MS relapses. The recommendations herein were developed following the gathering of a panel of experts after evaluating international guidelines, and the latest evidence was collected through a comprehensive literature review. Full article

There is no disputing the role that background music plays in memory recall. Music has the power to activate the brain and trigger deeply ingrained memories. For dementia patients, background music is a common therapy because of this. Previous studies used music to recall lyrics, series of words, and long- and short-term memories. In this research, electroencephalogram (EEG) and electrodermal activity (EDA) data are collected from 40 healthy participants using wearable sensors during nine music sessions (three happy, three sad, and three neutral). A post-study survey is given to all participants after each piece of music to know if they recalled any autobiographical memories. The main objective is to find an EEG biomarker using the collected qualitative and quantitative data for autobiographical memory recall. The study finds that for all four EEG channels, alpha power rises considerably (on average 16.2%) during the memory “recall” scenario (F3: p = 0.0066, F7: p = 0.0386, F4: p = 0.0023, and F8: p = 0.0288) compared to the “no-recall” situation. Beta power also increased significantly for two channels (F3: p = 0.0100 and F4: p = 0.0210) but not for others (F7: p = 0.6792 and F8: p = 0.0814). Additionally, the phasic standard deviation (p = 0.0260), phasic max (p = 0.0011), phasic energy (p = 0.0478), tonic min (p = 0.0092), tonic standard deviation (p = 0.0171), and phasic energy (p = 0.0478) are significantly different for the EDA signal. The authors conclude by interpreting increased alpha power (8–12 Hz) as a biomarker for autobiographical memory recall. Full article

Familial hemiplegic migraine type 2 is a premonitory subtype of migraine caused by an ATP1A2 gene mutation. It is an autosomal dominant genetic disease. Here, we report a 51-year-old woman who had a migraine attack due to a pathogenic ATP1A2 gene mutation. With frequent attacks, the patient developed complete left hemiplegia, a confusion of consciousness and partial seizures. Magnetic resonance imaging showed extensive angiogenic edema in the right cerebral hemisphere. In this article, we review the latest literature and try to explain the above symptoms in our patient with cortical spreading depression (CSD) and ATP1A2 gene mutations. Full article

The impact of aphasia on the everyday life of Greek-speaking people with aphasia (PWA) is often underestimated by rehabilitation clinicians. This study explores the adaptation and psychometric properties of the Greek (GR) version of The Aphasia Impact Questionnaire-21 (AIQ-21-GR) to address this issue. The aim of this study is to determine the reliability and validity of the Greek version of the AIQ-21. The AIQ-21-GR was administered to 69 stroke survivors, 47 with aphasia and 22 without aphasia. The data were analyzed to determine reliability and validity. Content validity was based on the Consensus-based Standards for the selection of health Measurement Instruments guidelines. The AIQ-21-GR shows high levels of reliability and validity. The results confirmed high scores of internal consistency (Cronbach’s α = 0.91) and indicated good known—groups validity (Mann–Whitney U = 202, p < 001). Content validity achieved high scores with an overall median score of 4 [Q₂₅ = 4, Q₇₅ = 5]. The psychometric properties of the AIQ-21-GR support the reliability and validity of the tool for investigating the impact of aphasia on the quality of life of Greek-speaking PWA. The AIQ-21-GR can be used for setting functional goals in collaboration with PWA and as a patient reported outcome measure for functional communication training. Full article

Female sex has been shown to be associated with an unfavorable outcome after ischemic stroke. In this nationwide analysis, we evaluate a large dataset of patients suffering from acute ischemic stroke to elucidate the factors associated with an increased risk of mortality after stroke in women. We analyzed a nationwide dataset from the German Federal Bureau of Statistics including 1,577,884 (761,537 female sex, 48.3%) in-hospital cases admitted between 1 January 2014 and 31 December 2019 with a primary diagnosis of acute ischemic cerebral infarction. Patients were analyzed regarding morbidity, treatments and in-hospital mortality. A multiple logistic regression analysis was performed, adjusted by patients’ risk profile including age, to evaluate the association of sex and in-hospital mortality. According to the median, women were older than men (79 years vs. 73 years). The multiple logistic regression analysis however revealed female sex remained an independent factor for an increased in-hospital mortality (odds ratio [OR] 1.12; 95% confidence interval [CI] 1.11–1.14; p < 0.001). Women had a higher prevalence of relevant risk factors, namely arterial hypertension (77.0% vs. 74.7%), arterial fibrillation (33.3% vs. 25.6%), chronic heart failure (12.3% vs. 9.7%), chronic kidney disease (15.6% vs. 12.9%) and dementia (6.6% vs. 4.1%), but were less affected with respect to other relevant co-morbidities such as cerebrovascular disease (11.7% vs. 15.1%), coronary heart disease (11.7% vs. 18.8%), diabetes mellitus (26.4% vs. 29.6%), dyslipidemia (38.1% vs. 42.0%), ischemic heart disease (12.3% vs. 19.3%) and previous coronary artery bypass grafting (1.1% vs. 3.2%). Overall, therapeutic interventions were performed less frequently in women such as carotid endarterectomy (1.1% vs. 2.3%), carotid stent (0.7% vs. 1.4%), as well as hematoma drainage (0.1% vs. 0.2%), and renal replacement therapy (0.4% vs. 0.6%). Conclusions: Our nationwide analysis revealed a higher mortality rate after stroke in women. Nevertheless, women had fewer in-hospital complications and were also less likely to experience the severe effects of some important co-morbidities. The dataset, however, showed that women received surgical or interventional carotid treatments after stroke less often. It is important for research on sex disparities in stroke to keep these treatment frequency differences in mind. Full article