Clin. Transl. Neurosci., Volume 2, Issue 2 (July 2018) – 16 articles

Prospective memory (PM) is the ability to remember to carry out intentions within a certain delay. PM tasks require a large degree of self-initiated retrieval, and in the absence of a prompt to recall, people must ‘remember to remember’ by their own volition. Thus, PM is a challenge – especially in old age with increasing health-related PM demands. Surprisingly, older adults show less pronounced impairment in naturalistic PM tasks (e.g., call the experimenter twice a day) than in the laboratory (e.g., press button × when a specific word appears). In fact, the age-PM paradox states that older individuals regularly outperform younger participants in naturalistic PM approaches. In these tasks, older individuals might experience better time management, better planning abilities, or a more efficient use of PM cues. Alternatively, elderly people might be more motivated when performing naturalistic tasks rather than abstract tasks. Here, we review the literature on the impact of motivation on the age-PM paradox by highlighting different methods used to manipulate motivation. We applied a systematic literature search on the Medline/PubMed database and reference lists of articles. Main findings suggest that depending on the type of modulation and the task setting, motivation enhances PM performance in older adults: Increasing importance (either by the experimenter or personally) boosted PM performance in older adults both in the laboratory and in naturalistic settings, while offering a monetary reward did not. Conversely, providing a social motive enhanced PM performance in the laboratory but not in naturalistic approaches. Although these results are encouraging, they also highlight the need for additional research on the impact of motivation on PM performance. Future studies should particularly focus on investigating the effect of non-financial reward on PM performance and elucidate the role of personality traits in the relation between motivation and PM. Full article

Introduction: Narcolepsy is a chronic neurological sleep disorder, the diagnosis of which is based upon clinical evaluation and additional paraclinical assessments. Awareness of narcolepsy is low and screening tools needed. The Epworth Sleepiness Scale (ESS), the Ullanlinna Narcolepsy Scale (UNS), and more recently the Swiss Narcolepsy Scale (SNS) were used as screening tools for narcolepsy. The aims of the present study are (1) to assess the value of the SNS in a new series of patients with narcolepsy with cataplexy (NC), and (2) to compare its sensitivity and specificity with the ESS and UNS. Patients and Methods: We prospectively assessed by questionnaire patients with NC (n = 80, all with assessment of cerebrospinal fluid (CSF) hypocretin-1 levels) and patients with excessive daytime sleepiness (EDS) of other origin (n = 111) in Zurich and Leiden. Causes of EDS included idiopathic hypersomnia (n = 12), behaviorally induced sleep insufficiency syndrome (n = 32), restless legs syndrome (n = 7), sleep-disordered breathing (n = 22), and hypersomnia due to medical disorders (n = 9). Diagnoses were made according to the International Classification of Sleep Disorders (third edition). Cutoff values of UNS and SNS for diagnosis of narcolepsy were those suggested in the literature. Results: For the diagnosis of narcolepsy, the following sensitivities and specificities were found: SNS (89% and 88%), UNS (100% and 62%), and ESS (91% and 54%). For the diagnosis of narcolepsy with low or non-detectable CSF hypocretin-1, the sensitivities and specificities were: SNS (93% and 88%), UNS (100% and 62%), and ESS (93% and 54%). Discussion: In conclusion, the SNS is accurate and superior to the ESS and the UNS for the screening/diagnosis of NC and allows, in addition, the identification of hypocretin-1 deficient patients. Full article

The Center for Neuro-Oncology of the University Hospital in Turin is hosted by the Division of Neuro-Oncology/Neurology and coordinates the Multidisciplinary Brain Tumor Board (MTB; which includes neuro-oncologists, neurosurgeons, neuroradiologists, neuropathologists, medical and radiation oncologists, and hematologists). The MTB guarantees the continuity of care from diagnosis to the end of life support. The Division of Neuro-Oncology/Neurology has an in- and outpatient clinic. In addition to daily clinical practice, major activities consist of clinical trials, translational studies, and teaching. This neurology-centered model of brain tumor care is similar to other brain tumor centers in the United States and Europe. Full article

Following the creation of the first university chair for neurology (Zurich 1894), the Swiss Neurological Society (SNG) was founded in 1908.. In 1932, neurology was recognized in Switzerland as an independent specialty and included in the medical (undergraduate) curriculum. The postgraduate training (residency program) in neurology lasted first 4 years (including 1 year of internal medicine, 0.5 years of psychiatry and 2.5 years of clinical neurology as mandatory rotations). In 1985, it grew to 5 years, and in 1996 to 6 years (including 1 year of internal medicine, 3 years of clinical neurology, and 1 year of clinical neurophysiology). Considering the results of a survey among young neurologists and “landscape changes” such as the increasing subspecialization, economic pressure, requirements for research, number of foreign doctors, and restrictions of working hours, the SNG undertook a revision which was approved in 2016. Today, the Swiss neurology postgraduate training includes 1 year of internal medicine, a “common trunk” of 3 years of general neurology (with 1 year of clinical neurophysiology including sleep), and 2 years of “fellowships” with rotations in different subspecialties and up to 12 months of research. Full article

Spontaneous intracranial hypotension (SIH) has gained more attention in the eyes of clinicians in the past years and is now recognized as an important cause of headaches. While usually self-limiting and benign, some patients suffer from debilitating symptoms that interfere significantly with their social and professional life. Thus, recognition and adequate treatment of SIH is of paramount importance. Recent refinements in imaging techniques combined with modern microneurosurgical techniques offer many diagnostic and therapeutic possibilities today. The aim of this review is to give the reader an updated review on the state-of-the art in the challenging diagnosis and treatment of SIH as well as an insight into recent developments of pathophysiological concepts and affiliations with other enigmatic diseases. Full article

Network oscillations in the brain are routinely recorded in the clinic and in the research lab. Here we outline a new paradigm in which network oscillations serve as treatment targets for noninvasive brain stimulation. We show how transcranial alternating current stimulation (tACS) can be used to modulate network oscillations that are impaired in disorders of the central nervous system (CNS). Using rational design, a structured process of target identification, target engagement, and target validation can be deployed to develop effective noninvasive brain stimulation paradigms for the treatment of neurological and psychiatric illnesses. We conclude by outlining how this approach could be applied to two disorders of the CNS, depression and epilepsy, for which there already exist clinical brain stimulation treatment options. Full article

Narcolepsy type 1 (NT1) and, to a lesser extent, neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy, entail the loss of the hypothalamic neurons that release the hypocretin/orexin (H/O) neuropeptides. NT1 has been associated with autonomic anomalies including alterations in temperature regulation and cardiovascular control, particularly during sleep. A spectrum of autonomic dysfunctions also characterizes neurodegenerative diseases. The central autonomic network (CAN) is an interconnected set of brain structures that are critical for the control of autonomic preganglionic neurons. The H/O neurons include pre-autonomic neurons that directly target preganglionic sympathetic neurons in the intermediolateral column of the spinal cord and parasympathetic neurons in the dorsal motor nucleus of the vagus nerve. The H/O neurons also project to and modulate the activity of other CAN structures that include pre-autonomic neurons, such as the rostral ventromedial medulla and caudal raphe nuclei, the rostral ventrolateral medulla and the hypothalamic paraventricular nucleus. In addition, the H/O neurons project to and modulate the activity of neurons in the nucleus of the solitary tract in the medulla, which receives and relays visceral afferent information, and in higher order structures of the CAN, such as the dorsomedial nucleus of the hypothalamus and the extended amygdala. The H/O neurons should, therefore, be regarded as a key component of the CAN. Functional alterations of the CAN due to H/O neuron deficiency might contribute to autonomic anomalies in patients with neurodegenerative diseases and are likely to underlie autonomic anomalies in patients with NT1. Full article

The Swiss Neurological Society (SNG) was founded in 1908. In the 1930s, a pre- and postgraduate neurological curriculum and the recognition of neurology as medical specialty followed. In the 1950–1960s, first independent university departments were created in the country. On the occasion of the 110th anniversary of the SNG, the biosketches of its first 42 presidents (including C. von Monakow, R. Bing, M. Minkowski, H. Krayenbühl and M. Mumenthaler) are presented. The multidisciplinary and international influences that contributed to the development of neurology in Switzerland are discussed in the context of the national and international scientific, medical and political history. Full article

Primary headaches, especially migraine, are common disabling neurological disorders with recurrent headache attacks that affect approximately 12–60% of the population. Depending on headache frequency, migraine is often associated with a high socioeconomic burden and a low quality of life. In order to provide adequate treatment for severely affected headache patients, integrated headache care has been established in Germany. It is based on a multimodal and multidisciplinary approach assessing headache diagnosis and offering therapy that has been shown to be effective. This article provides an overview of the structure of integrated headache care at the outpatient headache center at the Munich University Hospital (Upper Bavarian Headache Center). We present different modules of outpatient, day hospital, and inpatient care and discuss clinical outcome for patients utilizing integrated care at our center. Full article

Background and Purpose: Sleep apnea (SA) is highly prevalent in the stroke population. Testing and treating SA in stroke patients is challenging due to inaccessibility to testing and impaired mobility. To address this problem, we designed and implemented an inpatient diagnosis and treatment program for managing SA in patients with stroke. Our main aim in this article is to assess the feasibility of this program. Methods: We tested 83 patients with a portable SA testing device and initiated treatment with auto-titrating continuous positive airway pressure (A-CPAP) for those who were diagnosed with SA during their stay in an inpatient stroke rehabilitation unit (SRU). Patients diagnosed with SA were given a 2- to 4-week trial of A-CPAP in their hospital bed with close follow-up from a sleep medicine service. Results: Of the 83 patients tested, 54 (67.5%) had SA and 46 (85%) agreed to a trial of A-CPAP therapy. Of the 46 patients, who trialed A-CPAP, 32 (70%) achieved average daily use of four or more hours and went home with it. Conclusions: This program provides a feasible and convenient means of testing and treating SA among stroke patients undergoing inpatient stroke rehabilitation. Full article

Introduction: Imaging-based diagnosis of intra-axial contrast-enhancing brain tumors is frequently challenging. We show that the diagnosis of medulloblastoma (MDB) versus pilocytic astrocytoma (PA) and ependymoma (EPM) profit from computational analyses, based on quantitative image properties (i.e. textural features from apparent diffusion coefficient (ADC)-maps) and an automated machine learning classification (random forests (RF)). Methods: Forty patients who were diagnosed with three types of brain tumors were included in this study: 16 with MDB, 4 with PA, and 10 EPM. Based on the analysis of multi parametric preoperative magnetic resonance images, neuroradiologists gave a clear-cut diagnosis if they were sure of the diagnosis; however, most diagnoses comprise several possible tumor types. To distinguish between the named tumor types, a computer-based differential diagnosis (DD) tool was developed. Tumor lesion volumes were manually defined using ADC-maps only. From the demarked ADC-map, texture-parameters were extracted to train RF classifiers for pairwise DD. Performance of the RF models and reproducibility of the manual segmentation were evaluated. Results: Neuroradiologists gave correct and clear-cut diagnoses for 31% of MDB, 14.3% of PA, and 10% of EPM. Most diagnoses comprised several tumor types and altogether diagnoses containing the right tumor were given in 69% of true MDB, 64% of true PA, and 30% of true EPM. Ambiguous diagnoses could be improved by RF classifiers showing the following PA versus MDB performance: sensitivity 0.888 ± 0.031, specificity 0.886 ± 0.036; EPM versus MDB: sensitivity: 0.938 (95% CI = (0.677, 0.997)) and specificity: 0.7 (95% CI = (0.354, 0.919)); EPM versus PA: sensitivity: 0.786 (95% CI = (0.488, 0.942) and specificity: 0.100 (95% CI = (0.005, 0.458). An inter- and intra-rater analysis (three human raters) was performed and the Fleiss’ kappa test revealed high inter-rater agreement of κ = 0.821 (p value << 0.001) and an intra-rater agreement of κ = 0.822 (p value << 0.001). Conclusion: In the frequent case of ambiguous neuroradiologist diagnoses, a subsequent differential RF classification improves the diagnoses in all cases. The largest benefit is gained for the discrimination PA versus MDB with an accuracy of 88.0 ± 3.0% followed by EPM versus MDB with an accuracy of 84.6%. Full article

There is increasing evidence about a link between migraine, cerebral artery dissection and reversible cerebral vasoconstriction syndrome. We present a case of a patient who had all three diagnoses. The clinical evaluation of this patient was further complicated by a post-dural puncture headache, which added to the three types of headache already known to the patient. This clinical case supports the association between migraine, cerebral artery dissection and reversible cerebral vasoconstriction syndrome and highlights the importance of a precise history taking in establishing the correct diagnosis in patients with headache. Full article

Interdisciplinary cooperation and interaction have grown extremely important and will soon become indispensable in clinical neuroscience. The constantly increasing degree of specialization may further compartmentalize the different clinical neuroscience disciplines, potentially altering a unified identity in the field. In 2016, the Swiss Federation of Clinical Neuro-Societies (SFCNS) encouraged the creation of the Young Clinical Neuroscientists (YouCliN) Network bringing together juniors from all specialties united in the SFCNS – that is, biological psychiatry, neurology, neuropathology, neuropediatrics, neuropsychology, neuroradiology and neurosurgery. The main YouCliN mission is to cultivate an interdisciplinary spirit among clinical neuroscience trainees – in order for them to be prepared to face future challenges in a shoulder-to-shoulder manner. Moreover, the YouCliN represents junior interests in current issues of Swiss clinical neuroscience and contributes to shaping interdisciplinary training and courses. Transversality, better integration between fundamental and clinical neuroscience as well as between psychiatry and clinical neuroscience, and equal gender opportunities are further important topics and fields of action. In this article, the YouCliN Steering Committee presents the Network, the disciplines’ specific concerns and hopes, and positions itself with respect to future challenges for clinical neuroscience. Full article

Cerebellar ataxia is a clinically heterogeneous group of disorders, which includes several well-characterized genetic diseases as well as sporadic ataxias. The pathophysiology of ataxia is being understood, and a mechanistic basis for the appearance of these disorders is progressively emerging. Novel genes associated with dominant and recessive ataxias are being steadily identified, and research on their pathomechanisms not only has led to understanding the etiology and underlying cause for the development of ataxia but also has steered the field towards future therapeutic regime, aiming to control and prevent some forms of these diseases. Nevertheless, lack of knowledge for the causation of disease in a sizeable proportion of patient remains, and this issue is further compounded by the rarity of some of these ataxias as well as their restricted geographical distribution. On the other hand, large collaborative studies are providing critical information on the clinical spectrum, progression, and pathophysiology of inherited and sporadic ataxias. In the following sections, we describe the epidemiology, symptoms, pathological progression, and clinical management of various forms of inherited cerebellar ataxias. Finally, we provide a perspective on the challenges faced by the field in translational research and the development of successful therapeutic modalities for patients. Full article

Here, I develop the argument that clinician-scientists crucially contribute to the translation of knowledge from basic neurosciences to understanding disease and eventually therapies. Invasive experimental approaches in humans are still limited. Therefore, the translation of insights provided by research in animals to applications in humans remains a formidable challenge and successes have been rare. In my own experience, my combined training as a clinician and as a cellular neurophysiologist have allowed me to work with animal and human models of brain function in which the neuron forms the basic unit. This has greatly facilitated me to conduct experimentation at a neuronal circuit level with the prospect of translating it to humans. I advocate, therefore, the creation of dedicated postgraduate programs in academic and clinical neurosciences to train the next generation of clinical-scientists. Such careers require a strong motivation, but will immerse trainees in a fascinating intellectual environment with a promise to contribute to fundamental insights that ultimately benefit patients. Full article