Clinical and Translational Neuroscience

Background: Laser-evoked potentials (LEPs) constitute an objective clinical diagnostic method used to investigate the functioning of the nociceptor system, including signaling in thin peripheral nerve fibers: Aδ and C fibers. There is preliminary evidence that phase locking LEPs with the breathing cycle can improve the parameters used to evaluate LEPs. Methods: We tested a simple breathing protocol as a low-cost improvement to LEP testing of the hands. Twenty healthy participants all underwent three variants of LEP protocols: following a video-guided twelve-second breathing instruction, watching a nature video, or using the classic LEP method of focusing on the hand being stimulated. Results: The breath protocol produced significantly shorter latencies as compared with the nature or classic protocol. It was also the least prone to artifacts and was deemed most acceptable by the subjects. There was no difference between the protocols regarding LEP amplitudes. Conclusions: Using a breathing video can be a simple, low-cost improvement for LEP testing in research and clinical diagnostics. Full article

Patients with migraine often isolate themselves during their attacks. This disease-related loneliness seems to reverberate interictal, as some patients report failing relationships, losing jobs, or suffering from reduced social contacts. We developed a 10-item self-report questionnaire, the loneliness of migraine scale (LMS), and conducted an online survey. The questionnaire comprised diagnostic questions for migraine, the loneliness of migraine scale, the Generalized Anxiety Disorder Scale (GAD-7), the Patient Health Questionnaire (PHQ-8), and the Headache Attributed Lost Time Index (HALT-90). We computed item statistics, the psychometric properties of the LMS and assessed correlations between loneliness, migraine days, anxiety, and depression. We included 223 participants with (probable) migraine, reporting 8 ± 6 headache days with a disease duration of 11 ± 11 years. The mean scores of the HALT were 88 ± 52, of the GAD-7 10 ± 5, for PHQ-8 11 ± 6, and of the LMS 28.79 ± 9.72. Cronbach’s alpha for all ten items was 0.929. The loneliness scale correlated with the GAD-7 (r = 0.713, p < 0.001), with the PHQ-8 scale (r = 0.777, p < 0.001) and with migraine days (r = 0.338, p < 0.001). The LMS is a reliable and valid questionnaire measuring the loneliness of migraine patients. Feelings of loneliness were common and correlated highly with migraine days, anxiety, and depression. Full article

In March 2021, cerebral venous sinus thrombosis and thrombocytopenia after vaccination with adenovirus-based vaccine against SARS-CoV-2 were first reported. The underlining condition has been termed vaccine-induced immune thrombocytopenia (VITT). Anti-platelet factor 4 antibodies have been proposed as a central component of the pathomechanism. Treatment recommendations entailed immunomodulation with intravenous immunoglobulins, avoidance of heparins and avoidance of platelet transfusions. Although mortality from VITT-associated cerebral venous sinus thrombosis has decreased over time, it remains high. The aim of this narrative review is to describe different aspects of this disease according to the current state of knowledge. Full article

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may lead to acute and chronic neurological symptoms (NeuroCOVID-19). SARS-CoV-2 may spread from the respiratory tract to the central nervous system as the central nervous system (CNS) of certain patients dying from COVID-19 shows virus-related neuropathological changes. Moreover, a syndrome found in many patients having passed a SARS-CoV-2 infection, which is termed long COVID and characterized by lasting fatigue and other diverse clinical features, may well have some of its pathological correlates inside the CNS. Although knowledge on the routes of SARS-CoV-2 neuroinvasion and the pathophysiology of NeuroCOVID have increased, the molecular mechanisms are not yet fully understood. This includes the key question: to understand if observed CNS damage is a direct cause of viral damage or indirectly mediated by an overshooting neuroimmune response. Full article

There is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, even in its mild or moderate respiratory forms, can include long-term neuropsychological deficits. Standardized neuropsychological, psychiatric, neurological, and olfactory tests were administered to 45 patients 236.51 ± 22.54 days after hospital discharge following severe, moderate, or mild respiratory severity from SARS-CoV-2 infection (severe = intensive care unit hospitalization, moderate = conventional hospitalization, mild = no hospitalization). Deficits were found in all domains of cognition, and the prevalence of psychiatric symptoms was relatively high in the three groups. The severe infection group performed more poorly on long-term episodic memory tests and exhibited greater anosognosia than did the other two groups. Those with moderate infection had poorer emotion recognition, which was positively correlated with persistent olfactory dysfunction. Individuals with mild infection were more stressed, anxious, and depressed. The data support the hypothesis that the virus targets the central nervous system (notably the limbic system) and the notion that there are different neuropsychological phenotypes. Full article

Waning humoral responses to SARS-CoV-2 vaccination have been reported arguing for booster vaccinations even in healthy populations. Multiple sclerosis (MS) immunotherapy with anti-CD20 monoclonal antibodies may negatively influence morbidity and mortality of COVID-19. The opportunity to treat patients at risk for a severe COVID-19 course with specific monoclonal antibodies targeting SARS-CoV-2 represents an important novel measure for patient safety. We report a patient with waning humoral vaccination response around five months after two mRNA vaccination doses upon initiation of ocrelizumab treatment. Symptomatic COVID-19 infection was treated with casirivimab/imdevimab with rapid symptom recovery. Full article

As the COVID-19 pandemic progresses, reports of neurological manifestations are increasing. However, despite a high number of case reports and case series on COVID-19 and Guillain-Barré-Syndrome (GBS), a causal association is still highly debated, due to the lack of case-control studies. In this opinion paper, we focus on a few clinically relevant questions regarding the possible link between GBS and SARS-CoV-2 infection or vaccination based on our personal clinical experience and literature review. Full article

The COVID-19 pandemic specifically affects the management and treatment of patients with autoimmune neurological disorders. Major concerns include potentially higher risks of infection or severe disease course under certain immunotherapies used to treat those disorders and the influence of COVID-19 on the underlying disease. We present data of the neuroimmunological outpatient department of the University Hospital of Bern (Switzerland). 24 cases were analyzed, 19 of them suffered from Multiple Sclerosis. Of these 24 patients, 6 were hospitalized, 2/6 were treated in the Intensive Care Unit. Possible risk factors for severe course (defined as need for hospitalization) observed in our cohort included cardiovascular risk factors, treatment with B-cell depleting agents, Sphingosine-1 Phosphate Receptor Modulators, and oral steroid therapies. These data are based on a small, retrospective observational cohort and should be interpreted with caution, although they are in line with several other cohort studies. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the degeneration of cortical and spinal motor neurons. With no effective treatment available to date, patients face progressive paralysis and eventually succumb to the disease due to respiratory failure within only a few years. Recent research has revealed the multifaceted nature of the mechanisms and cell types involved in motor neuron degeneration, thereby opening up new therapeutic avenues. Intriguingly, two key features present in both ALS patients and rodent models of the disease are cortical hyperexcitability and hyperconnectivity, the mechanisms of which are still not fully understood. We here recapitulate current findings arguing for cell autonomous and non-cell autonomous mechanisms causing cortical excitation and inhibition imbalance, which is involved in the degeneration of motor neurons in ALS. Moreover, we will highlight recent evidence that strongly indicates a cardinal role for the motor cortex as a main driver and source of the disease, thus arguing for a corticofugal trajectory of the pathology. Full article

Background: An early treatment start with disease modifying therapies (DMT) and long-term adherence is crucial in the treatment of people with multiple sclerosis (PwMS) to prevent future disability. Objectives: To gain information on the diagnostic process, decision making, treatment start and adherence with regard to DMT as well as satisfaction in PwMS in Switzerland to optimize management of PwMS. Methods: A survey was conducted between June 2017 and March 2018 in six hospital-based MS centres and eight private practices in Switzerland. PwMS according to the 2010 McDonald criteria, aged 18–60 years, having a clinical isolated syndrome, relapsing remitting MS, or secondary progressive MS were eligible. The survey contained 40 questions, covering participants’ background and circumstances, treatment decisions, therapy start, treatment adherence, and satisfaction (EKNZ Req-2016-00701). Results: 212 questionnaires were returned for analysis. Of these, 125 (59.0%) were answered by patients treated by practice-based neurologists and 85 (40.1%) by patients treated in hospitals. That PwMS were satisfied overall with current medical care, that they were free of relapses and disease progression, and that they were able to live independently were the main goals of patients. Satisfaction was reflected by an early therapy start and a high adherence to DMT in our cohort. The treating neurologist played a major role in this regard. Furthermore, a satisfactory first diagnostic consultation (FDC) was crucial for successful long-term patient care positively influencing an early treatment start, longer duration of the initial therapy, as well as adherence to treatments and general satisfaction. Conclusion: The treating neurologist and especially a satisfactory FDC play a major role for the successful long-term treatment of PwMS. Detailed information on various aspects of the disease and time with the treating neurologist seems to be of major importance. Full article

The objective of this article is to provide a comprehensive personal survey of all the major parasomnias with coverage of their clinical presentation, investigation, physiopathogenesis and treatment. These include the four major members of the slow-wave sleep arousal parasomnias which are enuresis nocturna (bedwetting), somnambulism (sleepwalking), sleep terrors (pavor nocturnus in children, incubus attacks in adults) and confusional arousals (sleep drunkenness). Other parasomnias covered are sleep-related aggression, hypnagogic and hypnopompic terrifying hallucinations, REM sleep terrifying dreams, nocturnal anxiety attacks, sleep paralysis, sleep talking (somniloquy), sexsomnia, REM sleep behavior disorder (RBD), nocturnal paroxysmal dystonia, sleep starts (hypnic jerks), jactatio capitis nocturna (head and total body rocking), periodic limb movement disorder (PLMs), hypnagogic foot tremor, restless leg syndrome (Ekbom syndrome), exploding head syndrome, excessive fragmentary myoclonus, nocturnal cramps, and sleep-related epileptic seizures. There is interest in the possibility of relationships between sleep/wake states and creativity. Full article

Functional neurological disorder (FND) represent a common disorder with significant socio-economic impact. In this context and alongside recent new neuroscientific insights, FND attracts a growing interest both in clinical practice and academic activities. New international recommendation and expert opinions suggest that therapy of FND should be a tailored multidisciplinary management involving the neurologist, the physiotherapist, and in most cases the psychotherapist/psychiatrist. A first decisive step is the establishment of a definitive diagnosis, based on the presence of clinical positive signs during neurological assessment together with a clear communication and explanation of the diagnosis by the neurologist. A second important step is based on individual therapeutic sessions, involving different disciplines (neurology and psychotherapy or neurology and physiotherapy). Comorbidities, such as pain or fatigue and psychiatric comorbidities (anxiety, depression, dissociation etc.) should be carefully evaluated, as they need an individualized treatment path. New FND clinics have been created worldwide over the last decades to offer such multidisciplinary settings and this article will present the experience of a first Swiss FND clinic created in 2016. The aim is to highlight in the form of a narrative review the current literature supporting the usefulness and importance of FND clinics, by reviewing the latest evidence on multidisciplinary interventions in FND. Full article

SARS-CoV-2 has an impact on the nervous system as a result of pathological cellular and molecular events at the level of vascular and neural tissue. Severe neurologic manifestations including stroke, ataxia, seizure, and depressed level of consciousness are prevalent in patients with SARS-CoV-2 infection. Although the mechanism is still unclear, SARS-CoV-2 has been associated with the pathogenesis of intravascular coagulation and angiotensin-converting enzyme-I, both exacerbating systemic inflammation and contributing to hypercoagulation or blood–brain barrier leakage, resulting in ischemic or hemorrhagic stroke. On the other hand, the SARS-CoV-2 spike protein in neural tissue and within the cerebrospinal fluid may induce neural dysfunction, resulting in neuroinflammation, which is exacerbated by peripheral and neural hypercytokinemia that can lead to neuronal damage and subsequent neuroinflammation. A deeper understanding of the fundamental biological mechanisms of neurologic manifestations in SARS-CoV-2 infection can pave the way to identifying a single biomarker or network of biomarkers to help target neuroprotective therapy in patients at risk for developing neurological complications. Full article

This narrative review provides a brief overview of the current literature on technology-based interventions for the neurorehabilitation of persons with Parkinson’s disease (PD). The role of brain–computer interfaces, exergaming/virtual-reality-based exercises, robot-assisted therapies and wearables is discussed. It is expected that technology-based neurorehabilitation will gain importance in the management of PD patients, although it is often not clear yet whether this approach is superior to conventional therapies. High-intensity technology-based neurorehabilitation may hold promise with respect to neuroprotective or neurorestorative actions in PD. Overall, more research is required in order to obtain more data on the feasibility, efficacy and safety of technology-based neurorehabilitation in persons with PD. Full article

On behalf of Swiss Neurological Society together with the Swiss Society for Behavioral Neurology, we are pleased to present the Abstracts of the 113th Annual Meeting, which was held from 18–19 November 2021. Fifteen (15) abstracts were selected for oral presentations and sixty-one (61) abstracts were selected as poster presentations. We congratulate all the presenters on their research work and contribution. Full article

(1) Background: To test the accuracy of a fully automated stroke tissue estimation algorithm (FASTER) to predict final lesion volumes in an independent dataset in patients with acute stroke; (2) Methods: Tissue-at-risk prediction was performed in 31 stroke patients presenting with a proximal middle cerebral artery occlusion. FDA-cleared perfusion software using the AHA recommendation for the Tmax threshold delay was tested against a prediction algorithm trained on an independent perfusion software using artificial intelligence (FASTER). Following our endovascular strategy to consequently achieve TICI 3 outcome, we compared patients with complete reperfusion (TICI 3) vs. no reperfusion (TICI 0) after mechanical thrombectomy. Final infarct volume was determined on a routine follow-up MRI or CT at 90 days after the stroke; (3) Results: Compared to the reference standard (infarct volume after 90 days), the decision forest algorithm overestimated the final infarct volume in patients without reperfusion. Underestimation was observed if patients were completely reperfused. In cases where the FDA-cleared segmentation was not interpretable due to improper definitions of the arterial input function, the decision forest provided reliable results; (4) Conclusions: The prediction accuracy of automated tissue estimation depends on (i) success of reperfusion, (ii) infarct size, and (iii) software-related factors introduced by the training sample. A principal advantage of machine learning algorithms is their improved robustness to artifacts in comparison to solely threshold-based model-dependent software. Validation on independent datasets remains a crucial condition for clinical implementations of decision support systems in stroke imaging. Full article

Introduction: Postural tachycardia syndrome (POTS) is a chronic form of autonomic dysfunction characterized by symptoms of orthostatic intolerance, often accompanied by sudomotor dysfunction and gastrointestinal dysmotility. In a subgroup of patients with POTS, autoantibodies against adrenergic or cholinergic receptors suggest an immune-mediated etiology. Antiphospholipid syndrome (APS) is a hypercoagulative autoimmune disorder associated with anti-phospholipid-antibodies that causes arterial and venous thromboses. Concurrent occurrence of APS and immune-mediated POTS is rare. Methods and Results: Here, we report a 28-year-old female that experiences symptoms of orthostatic intolerance, vasovagal syncopes, gastrointestinal dysmotility and sudomotor dysfunction. She fulfills the formal diagnostic criteria of POTS showing a heart rate increment of ≥30 beats per minute (bpm) within 10 m of head-up tilt in the absence of orthostatic hypotension, accompanied by symptoms of orthostatic intolerance. The thermoregulatory sweat test reveals severe patchy anhidrotic areas. Gastric emptying scintigraphy shows an impaired gastrointestinal motility. Plasma norepinephrine levels and a skin biopsy appear normal. Finally, serological persistence of anti-alpha-1-adrenergic autoantibodies suggest an immune-mediated pathogenesis. Several years after initial presentation of POTS symptoms, the patient develops APS with recurrent venous emboli and persistent anti-phospholipid-antibodies. Recently the patient is diagnosed with Hashimoto’s thyroiditis (HT) expressing high levels of thyroid-stimulating hormone and high titers of anti-thyroid antibodies. Conclusion: To our knowledge, this is the first report of consecutive immune-mediated POTS, APS and HT in a young woman, possibly displaying a unique combination of three disorders of autoimmune etiology. Full article

On behalf of Swiss Society of Neurosurgery together with Association of neurosurgical nursing staff Switzerland, we are pleased to present the Abstracts of the 2021 Annual Meeting, that was held virtually from 16–17 September 2021. Fifty-one (51) abstracts were selected for presentation as oral presentations and forty (40) abstracts were selected as poster presentations. We congratulate all the presenters on their research work and contribution Full article

Parkinson's disease (PD) is a chronic neurologic disease that has a great impact on the patient’s quality of life. The natural course of the disease is characterized by an insidious onset of symptoms, such as rest tremor, shuffling gait, bradykinesia, followed by improvement with the initiation of dopaminergic therapy. However, this “honeymoon period��? gradually comes to an end with the emergence of motor fluctuations and dyskinesia. PD patients need long-term treatments and monitoring throughout the day; however, clinical examinations in hospitals are often not sufficient for optimal management of the disease. Technology-based devices are a new comprehensive assessment method of PD patient’s symptoms that are easy to use and give unbiased measurements. This review article provides an exhaustive overview of motor complications of advanced PD and new approaches to the management of the disease using sensors. Full article