[Quality indicators artificial intelligence]. / Qualitätsindikatoren künstliche Intelligenz.

The ability of some artificial intelligence (AI) systems to autonomously evolve and the sometimes very limited possibilities to comprehend their decision-making processes present new challenges to our legal system. At a European level this has led to reform efforts, of which the proposal for a European AI regulation promises to close regulatory gaps in existing product safety law through cross-sectoral AI-specific safety requirements. A prerequisite, however, would be that the EU legislator does not only avoid duplications and contradictions with existing safety requirements but also refrains from imposing exaggerated and unattainable demands. If this were to be taken into consideration, the new safety requirements could also be used to specify the undefined standard of care in liability law. Nevertheless, challenges in the context of provability continue to remain unresolved, posing a risk of rendering the legal protection efforts of the aggrieved party ineffective. It remains to be seen whether the EU legislator will address this need for reform with the recently proposed reform of product liability law by the Commission.

[Viral diseases of the nervous system-Selected new and old viruses]. / Virale Erkrankungen des Nervensystems ­ ausgewählte neue und alte Viren.

Viral diseases of the nervous system are ancient and poliomyelitis was described in Egypt as early as 2000 BC. They can cause a wide range of neurological symptoms, such as meningitis, encephalitis, meningoencephalitis, Guillain-Barré-like syndrome and stroke, often leaving mild to severe residuals. Depending on the pathogen, the symptoms appear quickly within hours, or lead to increasing chronic symptoms within 1 week or months. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was newly identified in January 2020 and occurs worldwide, illustrates the sequelae of a phenomenon that has been known for centuries, the possible rapid spread of pathogen-related infectious diseases. Due to vaccination programs some pathogens are becoming rarer or are considered to be eradicated. Nevertheless, vaccination programs, especially in the poorer regions, are repeatedly interrupted, for example by wars. The most recent example is the interruption of vaccination against poliomyelitis in Ukraine. As life expectancy continues to rise and years of life lost to infectious diseases decrease, the new infectious disease threat is likely to come from emerging and re-emerging infections; however, according to a recent analysis of population data from 29 countries, life expectancy during the corona pandemic has decreased, e.g., by 28 months in the USA and by 6 months in Germany. Climate change, rapid urbanization and changing land-use patterns could increase the risk in the coming decades. In particular, the climate change can alter the spectrum of global pathogens and especially vector-borne infections can spread to new areas. A sustained increase in travel, trade and mobility enables the pathogens to spread quickly.

[Multiple sclerosis treatment consensus group (MSTCG): position paper on disease-modifying treatment of multiple sclerosis 2021 (white paper)]. / Multiple Sklerose Therapie Konsensus Gruppe (MSTKG): Positionspapier zur verlaufsmodifizierenden Therapie der Multiplen Sklerose 2021 (White Paper).

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).

A Network-Wide Stroke Team Program Reduces Time to Treatment for Endovascular Stroke Therapy in a Regional Stroke-Network.

BACKGROUND AND PURPOSE: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. METHODS: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January - June 2015, n = 80 vs. July 2015 - June 2016, n = 184). RESULTS: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25-75% interquartile range [IQR] 231-381 min to 254 min, IQR 215.25-341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35-102 min to 43.5 min, IQR 27.75-81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5-170.5 min to 114.5 min, IQR 66.5-151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). CONCLUSIONS: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network.

Reduced white matter integrity in amateur boxers.

INTRODUCTION: Professional boxing can lead to chronic traumatic encephalopathy, a variant of traumatic brain injury (TBI). Its occurrence in amateur boxers is a matter of debate since amateur boxing is considered to be less harmful due to more strict regulations. However, several studies using different methodological approaches have revealed subtle signs of TBI even in amateurs. Diffusion tensor imaging (DTI) is sensitive to microscopic white matter changes and has been proven useful in TBI when routine MR imaging often is unrevealing. METHODS: DTI, with tract-based spatial statistics (TBSS) together with neuropsychological examination of executive functions and memory, was used to investigate a collective of 31 male amateur boxers and 31 age-matched controls as well as a subgroup of 19 individuals, respectively, who were additionally matched for intellectual performance (IQ). RESULTS: All participants had normal findings in neurological examination and conventional MR. Amateur boxers did not show deficits in neuropsychological tests when their IQ was taken into account. Fractional anisotropy was significantly reduced, while diffusivity measures were increased along central white matter tracts in the boxers group. These changes were in part associated with the number of fights. CONCLUSIONS: TBSS revealed widespread white matter disturbance partially related to the individual fighting history in amateur boxers. These findings closely resemble those in patients with accidental TBI and indicate similar histological changes in amateur boxers.

The weepy nerve-different sensitivity of left and right recurrent laryngeal nerves under tensile stress in a porcine model.

PURPOSE: Recurrent laryngeal nerve palsy in thyroid surgery is still a threatening complication. Our aim was to analyze the impact of prolonged tensile stress on the recurrent laryngeal nerve (RLN) in an animal model using continuous intraoperative neuromonitoring (C-IONM). METHODS: Constant tensile stress was applied to left and right RLNs in 20 pigs (40 RLN). In a pilot study, five animals were subjected to a tensile force of 0.34 ± 0.07 N for 10 min and changes in amplitude were documented using C-IONM. In the main study, a force of 1.2 N was applied until the signal amplitude was reduced by 85 %, in 15 pigs. Nerve conductivity was analyzed by threshold current measurements. RESULTS: Good correlation was found between stress and amplitude decrease in the pilot study as well as between signal decrease and duration of trauma in the main study. Great variations were found inter- and intra-individually. These variations were most prominent at 85 % signal reduction (median 36 min, range 0.3-171 min). There was no side specificity (left 0.3-171 min, right 0.3-168 min, respectively, p = 0.19). However, in each individual animal, there was a sensitive (0.3-98.9 min) and less sensitive nerve (26.8-171 min). These differences became highly significant at 85 % of signal reduction (p = 0.008), where the vulnerability is 1.4 to 146.4 times higher on one side (mean 4.3). CONCLUSIONS: Our study demonstrates the presence of a sensitive RLN that was 4.3 times more vulnerable than the contralateral nerve (range 1.4-146.4 times, p = 0.008). Thus, the right and the left nerves cannot be assumed to be of equal sensitivity to trauma. In our data, the more sensitive nerve does not occur predominantly on one side and was named the "weepy nerve."

Trends in stroke severity at hospital admission and rehabilitation discharge before and during the COVID-19 pandemic in Hesse, Germany: a register-based study.

BACKGROUND: The COVID-19 pandemic has affected acute stroke care, resulting in a decrease in stroke admissions worldwide. We examined trends in stroke severity at hospital admission, including (1) probable need for rehabilitation (National Institutes of Health Stroke Scale score > 6 points) and (2) probable need for assistance (modified Rankin Scale score > 2 points), and discharge to rehabilitation after acute care among inpatients with acute ischemic stroke and intracerebral hemorrhage. METHODS: We compared quality assurance data for acute ischemic stroke and intracerebral hemorrhage during the pandemic with the period before the pandemic in Hesse, Germany, using logistic regression analyses. RESULTS: Fewer inpatients with a probable need for rehabilitation were present at the beginning of the second wave of the COVID-19 pandemic in September 2020 (adjusted OR (aOR) 0.85, 95% CI [0.73, 0.99]), at the end of the second national lockdown in May 2021 (aOR 0.81, 95% CI [0.70, 0.94]), and at the approaching peak of COVID-19 wave 4 in November 2021 (aOR 0.79, 95% CI [0.68, 091]). Rates of probable need for assistance were significantly lower at the beginning of COVID-19 wave 2 in August 2020 (aOR 0.87, 95% CI [0.77, 0.99]) and at the beginning of COVID-19 wave 3 in March 2021 (aOR 0.80, 95% CI [0.71, 0.91]). Rates of discharge to rehabilitation were lower from the beginning in October 2020 to the peak of COVID-19 wave 2 in December 2020 (aOR 0.83, 95% CI [0.77, 0.90]), at the beginning and end of COVID-19 wave 3 in March 2021 and May 2021 (aOR 0.86, 95% CI [0.79, 0.92]), respectively, and at the beginning of COVID-19 wave 4 in October 2021 (aOR 0.86, 95% CI [0.76, 0.98]). CONCLUSIONS: The results suggest that the COVID-19 pandemic had an impact on stroke management during the pandemic, but the absolute difference in stroke severity at hospital admission and discharge to rehabilitation was small.

Flank Pain as a First Symptom of a Diffuse Midline Glioma.

Diffuse midline gliomas are a new entity in the WHO Classification of Tumors of the Central Nervous System, corresponding to grade 4 gliomas. The diagnostic pathognomonic feature is the presence of a H3K27M mutation. Although mainly seen in children, cases in adults have also been reported. The symptoms are highly variable and usually dependent on the location and extent of spinal cord compression.

Deep Grey Matter Volume is Reduced in Amateur Boxers as Compared to Healthy Age-matched Controls.

PURPOSE: Mild traumatic brain injuries (mTBI) sustained during contact sports like amateur boxing are found to have long-term sequelae, being linked to an increased risk of developing neurological conditions like Parkinson's disease. The aim of this study was to assess differences in volume of anatomical brain structures between amateur boxers and control subjects with a special interest in the affection of deep grey matter structures. METHODS: A total of 19 amateur boxers and 19 healthy controls (HC), matched for age and intelligence quotient (IQ), underwent 3T magnetic resonance imaging (MRI) as well as neuropsychological testing. Body mass index (BMI) was evaluated for every subject and data about years of boxing training and number of fights were collected for each boxer. The acquired 3D high resolution T1 weighted MR images were analyzed to measure the volumes of cortical grey matter (GM), white matter (WM), cerebrospinal fluid (CSF) and deep grey matter structures. Multivariate analysis was applied to reveal differences between groups referencing deep grey matter structures to normalized brain volume (NBV) to adjust for differences in head size and brain volume as well as adding BMI as cofactor. RESULTS: Total intracranial volume (TIV), comprising GM, WM and CSF, was lower in boxers compared to controls (by 7.1%, P = 0.009). Accordingly, GM (by 5.5%, P = 0.038) and WM (by 8.4%, P = 0.009) were reduced in boxers. Deep grey matter showed statistically lower volumes of the thalamus (by 8.1%, P = 0.006), caudate nucleus (by 11.1%, P = 0.004), putamen (by 8.1%, P = 0.011), globus pallidus (by 9.6%, P = 0.017) and nucleus accumbens (by 13.9%, P = 0.007) but not the amygdala (by 5.5%, P = 0.221), in boxers compared to HC. CONCLUSION: Several deep grey matter structures were reduced in volume in the amateur boxer group. Furthermore, longitudinal studies are needed to determine the damage pattern affecting deep grey matter structures and its neuropsychological relevance.

Diabetes, Hypertension, Atrial Fibrillation and Subsequent Stroke-Shift towards Young Ages in Brunei Darussalam.

Southeast Asia harbors a young population of more than 600 million people. Socioeconomic transition within the last decades, driven by globalization and rapid economic growth, has led to significant changes in lifestyle and nutrition in many countries of this region. Hence, an increase in the number of non-communicable diseases is seen in most populations of Southeast Asia. Brunei Darussalam is the smallest country in this region, with a population of around 400,000 inhabitants. Vast hydrocarbon resources have transformed Brunei into a wealthy industrialized country within the last few decades. We compared the age distribution and prevalence of cardiovascular risk factors in ischemic stroke patients between the only stroke unit in Brunei Darussalam and a tertiary stroke center from Frankfurt/Germany. Between 2011 and 2016, a total number of 3877 ischemic stroke patients were treated in both institutions. Even after adjusting for age due to different population demographics, stroke patients in Brunei were younger compared to their German counterparts. The prevalence of hypertension and diabetes mellitus was significantly higher in young age groups in Brunei, whereas no difference was observed for older patients. The rapid socioeconomic transition might be a significant risk factor for the development of non-communicable diseases, including stroke.

Better be prepared: the spectrum of neuropsychiatric impairment among Libyan war victims transferred to Germany for trauma rehabilitation.

BACKGROUND: The current Libyan civil war has originated many casualties, imposing medical challenges. War injuries are complex, requiring specialized knowledge and interdisciplinary assessment for adequate patient and intercultural management. METHODS: This retrospective study analyzed records of 78 Libyan patients admitted from July 2016 to November 2017 to neurological and trauma surgical departments of Krankenhaus Nordwest, Frankfurt, Germany. Issues of system preparation of the hospital, demographics, injury patterns and therapies were analyzed. The chi-squared test was used to analyze differences in injury patterns in explosion and gunshot injuries. RESULTS: Seventy-seven of seventy-eight patients were male (mean age 30.6 years). The patients received primary and secondary treatment in Tunisia (n = 39), Libya (n = 36) and Turkey (n = 23). Forty-eight patients had gunshot injuries, 37 explosion injuries, 11 both. Preparation for management of injuries included hygienic and isolation protocols, organization of interpreters and intercultural training. Patients presented with a broad variety of neurological, psychiatric and trauma surgical injuries. Fifty-six patients had sensory, 47 motor deficits. Nine reported headache, 5 vertigo, 13 visual impairment, 28 psychiatric symptoms. Eighteen patients had central nervous damage, 50 peripheral nervous damage. Central nervous damage was significantly more common in gunshot than explosion injuries (p = 0.015). Peripheral nervous damage was more common in explosion than gunshot injuries (p < 0.1). Fifty-one patients had polytrauma and 49 suffered from fractures. Therapy included surgical interventions (n = 56) and physiotherapy. Structured rehabilitation programs were often indicated. CONCLUSION: Specialized knowledge about war injuries and their management including hospital preparation and planning regarding infrastructure may be required anytime. Injuries include a broad variety of neurological, psychiatric and trauma surgical injuries. Therefore, an interdisciplinary approach is crucial.

Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper).

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

[Meningitis, Meningoencephalitis - A Chameleon in (Emergency) Medicine]. / Meningitis/Meningoenzephalitis ­ ein Chamäleon in der Medizin.

A wide range of pathogens can cause meningitis or meningoencephalitis.Guiding symptoms of meningitis are headache, fever, nausea, vomiting and meningism.Guiding symptoms of meningoencephalitis are headache, fever, qualitative or quantitative disturbances of consciousness, signs of meningism are possible, optional focal neurological signs can occur.Crucial prognostic factor in treatment of acute meningitis and meningoencephalitis is rapid diagnosis and early initiation of therapy. An early start of therapy is crucial. In addition to rapid pathogen-specific treatment, specialized neurological intensive care medicine is life-saving.

Emerging and re-emerging viruses affecting the nervous system.

Emerging and re-emerging viruses may cause meningitis, encephalitis, meningoencephalomyelitis, encephalitis, Guillian-Barré-like-syndromes as well as strokes. Most important viruses belong to the family of Adenoviridae, Arbovirus, Arenaviridae, Herpesviridae, Picornaviridae, Paramyxoviridae as well as Togaviridae. Clinical presentation usually consists of a biphasic presentation. Non-specific febrile illnesses may be accompanied by rash, headache, arthralgia and myalgia. Thereafter focal neurological signs may evolve. Diagnostic strategies for the detection of emerging and re-emerging viruses may be difficult due to the short viraemic period. Pitfalls in serology may be due to antibody crossreactivity. Arboviruses are transmitted by arthropods. Aedes mosquitos are one of the vectors for arboviruses like Chikungunya-virus, Dengue-virus, Japanese-Encephalitis-B-virus and West-Nile-virus. Since the last centuries Aedes mosquitos have spread from their naturally habitat in Africa to America as well as Europe. The arboviruses risk profile depend essentially on the occurrence, the activity of the respective vector, this may be the key to fight the disease and its spread. Due to global shifts in the ecological balance but also as a result of more or less successful control measures, some diseases have become rarer, others are more common. The viruses persist in the respective vector months to years; in ticks they may persist for years and in mosquitoes 1 to 4 months. In order to survive bad climatic conditions unscathed, the viruses partially overwinter in arthropods.

Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933].

BACKGROUND: The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. DESIGN: GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. CONCLUSION: 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. TRIAL REGISTRATION: Current Controlled TrialsISRCTN45122933.

Effect of physical therapy management of nonspecific low back pain with exercise addiction behaviors: A case series.

This case series describes two patients, aged 35 and 45 years, respectively, who presented with chronic nonspecific low back pain (NSLBP) having exercise addiction (EA) behaviors. Diagnosis of EA was based on clinical findings, exercising patterns and withdrawal symptoms along with high scores in the EA inventory. This report is a potential first-time description of the successful physical therapy management of NSLBP associated with EA utilizing pain neuroscience education (with individualized curriculum), mindfulness, breathing, quota-based reduction in exercises and modification of exercises into social participation, pleasure activities and hobbies. Both the patients were seen once a week, for 8 weeks. At discharge, they were pain-free and fully functional, which was maintained at a six-month follow-up.

Clinical outcome and cerebrospinal fluid profiles in patients with tick-borne encephalitis and prior vaccination history.

BACKGROUND: Tick-borne encephalitis (TBE) is endemic in southern and eastern districts of Germany. Approximately 10-14% of the infected individuals suffer from long-term disability and in 1.5-3.6% the course is fatal. Two well-tolerated vaccines are available, which provide high protection and which have been confirmed in several field studies. Here we investigate clinical course, long-term outcome and cerebrospinal fluid (CSF) characteristics of TBE cases with a prior history of any vaccination as well as real vaccination breakthrough (VBT). METHODS: A case series of 11 patients with a prior history of vaccination, part of a recently published lager cohort of 111 TBE cases. Evaluation included clinical data, degree of disability (modified RANKIN scale, mRS) and analysis of CSF and serum samples. Furthermore, metadata for extended analysis on clinical outcome of TBE with VBT were analysed. RESULTS: One patient had a clear VBT and ten of them had irregular vaccinations schedules (IVS). Infection severity did not differ in patients with IVS as compared to a non-vaccinated control cohort (median mRS: both 3.0) but these patients showed a stronger cellular immune response as measured by CSF pleocytosis (IVS, 205 cells/µL versus non-vaccinated control, 114 cell/µL, P < 0.05) and by differential pattern of CSF (intrathecal) immunoglobulin synthesis. However, shift analysis of VBT metadata using linear-by-linear association revealed a more serious course of TBE in patients with VBT than in a non-vaccinated control cohort (χ2 = 9.95, P = 0.002). Furthermore, ordinal logistic regression analysis showed that VBT patients had an age-corrected, 2.65 fold (CI: 1.110-6.328; χ2 = 4.813; p = 0.028) significant higher risk to suffer from moderate or severe infections, respectively. CONCLUSION: A history of IVS surprisingly seems to have no impact on the clinical course of TBE but may leave marks in the specific brain immune response. VBT patients, however, carry an age-independent, significant risk to experience a severe infection.