[Henry Head (1861-1940) and his importance for neurology]. / Henry Head (1861­1940) und seine Bedeutung für die Neurologie.

Nowadays, Henry Head is best known for his Head zones. The concept was understood very differently by Head in comparison to what current medical books falsely describe them to be. In reality, there is no direct relationship between one particular skin zone and one single organ. It is certain that the drawings considered depictions of the Head zones in today's medical textbooks were actually not created by Head. From a neurological point of view, Head is important for two reasons: his self-experiment in 1909 to damage one of his own peripheral nerves followed by regeneration was heroic. It has helped generations of neurologists to have a better understanding of the pathophysiology of peripheral nerve damage and thus make a better assessment of the prognosis of such injuries. Head's second contribution pertains to the radicular organization at the level of the spinal cord. The pathophysiology of herpes zoster radiculitis enabled him to develop the concept of the dermatomes on the basis of preliminary work around 1900. Henry Head's contribution was the systematic compilation of the existing publications of the time and amendment of his own cases. As he was the most important neurologist at that time, at least in the English speaking world, and was well connected with people in the German neurology community, it was probably easy for him to make his dermatome maps well known. In retrospect, Head was less successful in neuropsychology with holistic concepts for higher cognitive functions which were in vogue during his lifetime. His late work on aphasia is now considered refuted. Head's criticism of the strict localization was well in syncronization with the zeitgeist of the early twentieth century. Establishing the fact that Broca's aphasia and Wernicke's aphasia are not easily diagnostically distinguishable from each other was more an achievement of subsequent generations of neurologists and neuropsychologists as well as technical advances.

Strengthening the occupational and social participation of multiple sclerosis patients - design of a multicenter, parallel-group randomized controlled trial (MSnetWork-study).

BACKGROUND: Multiple Sclerosis is an autoimmune inflammatory disease of the central nervous system that often leads to premature incapacity for work. Therefore, the MSnetWork project implements a new form of care and pursues the goal of maintaining or even improving the state of health of MS patients and having a positive influence on their ability to work as well as their participation in social life. A network of neurologists, occupational health and rehabilitation physicians, psychologists, and social insurance suppliers provide patients with targeted services that have not previously been part of standard care. According to the patient's needs treatment options will be identified and initiated. METHODS: The MSnetWork study is designed as a multicenter randomized controlled trial, with two parallel groups (randomization at the patient level with 1:1 allocation ratio, planned N = 950, duration of study participation 24 months). After 12 months, the patients in the control group will also receive the interventions. The primary outcome is the number of sick leave days. Secondary outcomes are health-related quality of life, physical, affective and cognitive status, fatigue, costs of incapacity to work, treatment costs, out-of-pocket costs, self-efficacy, and patient satisfaction with therapy. Intervention effects are analyzed by a parallel-group comparison between the intervention and the control group. Furthermore, the long-term effects within the intervention group will be observed and a pre-post comparison of the control group, before and after receiving the intervention in MSnetWork, will be performed. DISCUSSION: Due to the multiple approaches to patient-centered, multidisciplinary MS care, MSnetWork can be considered a complex intervention. The study design and linkage of comprehensive, patient-specific primary and secondary data in an outpatient setting enable the evaluation of this complex intervention, both on a qualitative and quantitative level. The basic assumption is a positive effect on the prevention or reduction of incapacity for work as well as on the patients' quality of life. If the project proves to be a success, MSnetWork could be adapted for the treatment of other chronic diseases with an impact on the ability to work and quality of life. TRIAL REGISTRATION: The trial MSnetWork has been retrospectively registered in the German Clinical Trials Register (DRKS) since 08.07.2022 with the ID DRKS00025451 .

[Data on multiple sclerosis in Germany and their representation in the ambulatory registry NeuroTransData (NTD) network]. / Daten zur Multiplen Sklerose in Deutschland und ihre Abbildung im Register des ambulanten Netzwerkes NeuroTransData (NTD).

AIMS AND METHODOLOGY: Description of basic data, common symptoms and their medical, non-drug and combined symptomatic treatment in a large sample of MS patients undergoing outpatient treatment of the German NeuroTransData (NTD) physician network. RESULTS: Currently there are 21,407 patients in the registry. Average age is 49.0 ± 13.0 years, 72,3 % of them female, average disease duration is 14.3 ± 8,9 years. Relapsing-remitting MS (RRMS) was present in 77 %, secondary-progressive MS (SPMS) 15 %, PPMS 5 %. The mean EDSS score of the total sample was 2.8 (range 0,5-8). Fatigue was the most common symptom in all subtypes (96 %), followed by spasticity (all 31 %, SPMS: 47 %; PPMS 36 %). Regarding symptomatic drug treatment, non-drug treatment and combined treatment, there was a wide range of variation. While spasticity was treated in 81 %, only 21 % of patients with fatigue receiving any form of therapy, Also, fecal and urine incontinence often remained untreated in 69 % resp. 56 % of cases. CONCLUSIONS: Setup, development and maintenance of a registry for a complex and chronic disease like MS represents an instrument to assess and improve patient care in the outpatient setting. Our results are hard to compare with the DMSG-registry, another German, more hospital-based data collection. However, both registries identify fatigue as the most common symptom in MS.

[Implementation and evaluation of a revised curriculum for psychiatry and psychotherapy]. / Einführung und Evaluation eines neuen Kurrikulums Psychiatrie und Psychotherapie.

BACKGROUND: Medical education in the discipline of psychiatry and psychotherapy at the University of Münster was traditionally focused on the transfer of knowledge via lectures. According to the current guidelines, the medical curriculum was modified as from the winter semester 2016/2017 to be more competency-based and the changes were evaluated. OBJECTIVE: Lectures and seminars were reduced to achieve a better linkage between theoretical and practical knowledge. Moreover, learning goals were formulated based on the German National Competence-based Catalogue of Learning Objectives in Medicine (NKLM) and entrustable professional activities (EPAs). MATERIAL AND METHODS: Almost all previous lectures are now replaced by an inverted classroom concept with e­learning. Theoretical knowledge is deepened by immediate multiple choice (MC) examinations and a seminar, which now focusses on specific practical EPAs. At the end of the semester, the students now undergo a practical, formative examination with simulated patients (actors) in addition to the former MC test. For evaluation, a representative sample of a semester cohort which took part in the previous curriculum and a similar cohort which attended the revised curriculum were investigated. Moreover, variables which might have an impact on the results were assessed, e. g. pre-existing psychiatric knowledge and motivation. RESULTS: Students taught by the modified curriculum showed a significantly better practical performance and no reduction of theoretical knowledge. Relevant influencing factors were not identified. CONCLUSION: The results show that a competency-based modification of the curriculum in the discipline of psychiatry and psychotherapy leads to more practical abilities and thus helps future physicians to be more self-determined.

Mental, Neurological, and Somatic Comorbidities and Their Treatment in Persons With Intellectual Disability.

BACKGROUND: Persons with intellectual disability (ID) often suffer from significant comorbidities. As data have been lacking until now, the present report is the first one containing outpatient data on the prevalence of ID in Germany, its comorbidities, and outpatient (drug) treatment. METHODS: This study is based on the nationwide outpatient billing data and drug prescription data of all SHI-insured adults (SHI, statutory health insurance) (age 18-109) who were seen at least once in an outpatient medical practice in 2018. Patients with at least two F70-F79 diagnoses in two quarters were included in the study group (SG) (n = 324 428). A random sample of patients without ID served as the control/comparison group (CG) (n = 648 856). The odds ratios (SG vs. CG) for comorbidities, prescriptions of selected classes of drugs, and involvement of medical specialties were each analyzed by multivariate logistic regression. RESULTS: The prevalence of ID was 0.55%. ID was found to be associated with a variety of comorbidities. The highest odds ratios [OR] were for infantile cerebral palsy (OR: 121.71; 95% confidence interval: [111.67; 132.67]), autism spectrum disorders (OR: 83.85 [75.54; 93.08]), and developmental disabilities (OR: 61.34 [58.86; 63.94]). The most frequently prescribed drug categories (as classified by the anatomic-therapeutic-chemical (ATC) convention) were psychoactive drugs (antipsychotic, anxiolytic, and hypnotic drugs and sedatives) and antiepileptic drugs (OR: 10.40 [10.27; 10.53] and 9.90 [9.75; 10.05], respectively). Both general practitioners (OR: 2.64 [2.59; 2.69]) and medical specialists were consulted by the SG more frequently than by the CG; the type of specialist most commonly consulted was in the neuropsychiatric field, i.e., a neurologist or psychiatrist (OR: 6.85 [6.77; 6.92]). CONCLUSION: A diagnosis of ID frequently appears in outpatient billing data. Future analyses should be devoted to the specific care of people with intellectual disability, who constitute an especially multimorbid and vulnerable patient group.

Development of Registry Data to Create Interactive Doctor-Patient Platforms for Personalized Patient Care, Taking the Example of the DESTINY System.

"Real-world evidence (RWE)" is becoming increasingly important in order to integrate the results of randomized studies into everyday clinical practice. The data collection of RWE is usually derived from large-scale national and international registries, often driven by academic centers. We have developed a digitalized doctor-patient platform called DESTINY (DatabasE-assiSted Therapy decIsioN support sYstem) that is utilized by NeuroTransData (NTD), a network of neurologists and psychiatrists throughout Germany. This platform can be integrated into everyday practice and, as well as being used for scientific evaluations in healthcare research, can also serve as an individual, personalized treatment application. Its various modules allow for a timely identification of side-effects or interactions of treatments, can involve patients via the "My NTC Health Guide" portal, and can collect data of individual disease histories that are integrated into innovative algorithms, e.g., for the prediction of treatment response [currently available for multiple sclerosis (MS), with other indications in the pipeline]. Here, we describe the doctor-patient platform DESTINY for outpatient neurological practices and its contribution to improved treatment success as well as reduction of healthcare costs. Platforms like DESTINY may facilitate the goal of personalized healthcare.

Confirmation rate of blinded (99m)Tc-SPECT compared to neurochemical dementia biomarkers in CSF in patients with Alzheimer disease.

In Alzheimer disease, CSF biomarkers and nuclear imaging are of particular interest. Many studies investigated only one technique, limiting comparison. Here, in 76 patients blinded 99mTc-SPECT was compared to CSF. Sensitivity of CSF was 92%; and 51% for SPECT. Specificity favored SPECT (90 vs. 80%). Both techniques showed no coherence (p = 0.17-0.47). Our results confirm that CSF biomarkers show higher sensitivity. SPECT has higher specificity and can also be used for other dementias without established CSF biomarkers.

Automatic dementia screening and scoring by applying deep learning on clock-drawing tests.

Dementia is one of the most common neurological syndromes in the world. Usually, diagnoses are made based on paper-and-pencil tests and scored depending on personal judgments of experts. This technique can introduce errors and has high inter-rater variability. To overcome these issues, we present an automatic assessment of the widely used paper-based clock-drawing test by means of deep neural networks. Our study includes a comparison of three modern architectures: VGG16, ResNet-152, and DenseNet-121. The dataset consisted of 1315 individuals. To deal with the limited amount of data, which also included several dementia types, we used optimization strategies for training the neural network. The outcome of our work is a standardized and digital estimation of the dementia screening result and severity level for an individual. We achieved accuracies of 96.65% for screening and up to 98.54% for scoring, overcoming the reported state-of-the-art as well as human accuracies. Due to the digital format, the paper-based test can be simply scanned by using a mobile device and then be evaluated also in areas where there is a staff shortage or where no clinical experts are available.

Early and differential diagnosis of dementia and mild cognitive impairment: design and cohort baseline characteristics of the German Dementia Competence Network.

BACKGROUND: The German Dementia Competence Network (DCN) has established procedures for standardized multicenter acquisition of clinical, biological and imaging data, for centralized data management, and for the evaluation of new treatments. METHODS: A longitudinal cohort study was set up for patients with mild cognitive impairment (MCI), patients with mild dementia and control subjects. The aims were to establish the diagnostic, differential diagnostic and prognostic power of a range of clinical, laboratory and imaging methods. Furthermore, 2 clinical trials were conducted with patients suffering from MCI and mild to moderate Alzheimer's Disease (AD). These trials aimed at evaluating the efficacy and safety of the combination of galantamine and memantine versus galantamine alone. RESULTS: Here, we report on the scope and projects of the DCN, the methods that were employed, the composition and flow within the diverse groups of patients and control persons and on the clinical and neuropsychological baseline characteristics of the group of 2,113 subjects who participated in the observational and clinical trials. CONCLUSION: These data have an impact on the procedures for the early and differential clinical diagnosis of dementias, the current standard treatment of AD as well as on future clinical trials in AD.

Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke.

BACKGROUND AND PURPOSE: The sulfonylurea receptor 1-regulated NC(Ca-ATP) channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume. We hypothesized that patients with type 2 diabetes mellitus taking sulfonylurea agents both at the time of stroke and during hospitalization would have superior outcomes. METHODS: We reviewed medical records of patients with diabetes mellitus hospitalized within 24 hours of onset of acute ischemic stroke in the Neurology Clinic, Charité Hospital, Berlin, Germany, during 1994 to 2000. After exclusions, the cohort comprised 33 patients taking a sulfonylurea at admission through discharge (treatment group) and 28 patients not on a sulfonylurea (control group). The primary outcome was a decrease in National Institutes of Health Stroke Scale of 4 points or more from admission to discharge or a discharge National Institutes of Health Stroke Scale score of 0. The secondary outcome was a discharge modified Rankin Scale score < or =2. RESULTS: No significant differences, other than stroke subtype, were observed among baseline variables between control and treatment groups. The primary outcome was reached by 36.4% of patients in the treatment group and 7.1% in the control group (P=0.007). The secondary outcome was reached by 81.8% versus 57.1% (P=0.035). Subgroup analyses showed that improvements occurred only in patients with nonlacunar strokes and were independent of gender, previous transient ischemic attack, and blood glucose levels. CONCLUSIONS: Sulfonylureas may be beneficial for patients with diabetes mellitus with acute ischemic stroke. Further investigation of similar cohorts and a prospective randomized trial are recommended to confirm the present observations.

Delayed Transcranial Echo-Contrast Bolus Arrival in Unilateral Internal Carotid Artery Stenosis and Occlusion.

Some patients with internal carotid artery (ICA) occlusion or stenosis are at risk of developing a hemodynamic stroke. Transcranial ultrasonography using an echo-contrast bolus technique might be able to assess the extent of hemodynamic compromise. We describe a transcranial Doppler sonographic method that analyzes the differences in echo-contrast bolus arrival between both middle cerebral arteries after intravenous echo-contrast application. Ten patients with 50%-79% ICA stenosis, 10 patients with 80%-99% ICA stenosis and 22 patients with ICA occlusion were studied and compared with 15 age-matched controls. There were significant increases in delayed filling of the middle cerebral artery in both 80%-99% stenoses and occlusions compared with controls. The extent of the observed delays did not correlate with vasomotor reactivity. Echo-contrast bolus arrival time can be used to gain additional information on the intracranial hemodynamic effects of extracranial carotid artery disease that seems to be independent of the established ultrasound indices.

Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study.

BACKGROUND AND PURPOSE: We investigated whether transient ischemic attacks (TIAs) before stroke can induce tolerance by raising the threshold of tissue vulnerability in the human brain. METHODS: Sixty-five patients with first-ever ischemic territorial stroke received diffusion- and perfusion-weighted MRI within 12 hours of symptom onset. Epidemiological and clinical data, lesion volumes in T2, apparent diffusion coefficient (ADC) maps and perfusion maps, and cerebral blood flow and cerebral blood volume values were compared between patients with and without a prodromal TIA. RESULTS: Despite similar size and severity of the perfusion deficit, initial diffusion lesions tended to be smaller and final infarct volumes were significantly reduced (final T2: 9.1 [interquartile range, 19.7] versus 36.5 [91.2] mL; P=0.014) in patients with a history of TIA (n=16). This was associated with milder clinical deficits. CONCLUSIONS: The beneficial effect of TIAs on lesion size in ADC and T2 suggests the existence of endogenous neuroprotection in the human brain.

The future of graduate medical education in Germany - position paper of the Committee on Graduate Medical Education of the Society for Medical Education (GMA).

The German graduate medical education system is going through an important phase of changes. Besides the ongoing reform of the national guidelines for graduate medical education (Musterweiterbildungsordnung), other factors like societal and demographic changes, health and research policy reforms also play a central role for the future and competitiveness of graduate medical education. With this position paper, the committee on graduate medical education of the Society for Medical Education (GMA) would like to point out some central questions for this process and support the current discourse. As an interprofessional and interdisciplinary scientific society, the GMA has the resources to contribute in a meaningful way to an evidence-based and future-oriented graduate medical education strategy. In this position paper, we use four key questions with regards to educational goals, quality assurance, teaching competence and policy requirements to address the core issues for the future of graduate medical education in Germany. The GMA sees its task in contributing to the necessary reform processes as the only German speaking scientific society in the field of medical education.

Web-based application to eliminate five contraindicated multiple-choice question practices.

Multiple-choice questions (MCQs) evaluate factual knowledge in medical education and have a high reliability, if performed appropriately. However, many MCQs contain formal errors leading to reduced validity. The authors developed a Web application capable of recognizing and eliminating five frequent contraindicated practices in MCQs: negative stem, unfocused stem, cueing words, longest item = right item flaw, and stem/item similarities. The authors used simple string algorithms and dynamic comparisons with keywords. The system was successfully validated with a sample of approximately 800 continuous medical education (CME) questions, showing that our system automatically detects 60% of all formal didactic errors. Flaws not detected by the software can easily be avoided using quick manuals on item wording or clear instruction to the authors. The authors conclude that it is feasible to improve the quality of MCQs by designing a Web application that is capable of detecting common flaws by simple string operations.