[Big data and deep learning in preventive and rehabilitation medicine]. / Big Data und maschinelles Lernen bei Prävention und Rehabilitation.

The digitalization in medicine has led to almost universal availability of information to different healthcare professionals and accelerated clinical pathways. Fast-track concepts and short hospital stays require intelligent and practicable systems in preventive and rehabilitation medicine. This includes optimization of movement analysis by innovative tools such as detectors sensing skin movements, portable feedback systems for monitoring, robot-assisted devices, and prevention programs based on reliable data. Finally, clinical structures are needed to exploit the maximal potential of artificial intelligence (AI) and deep learning. One example is the establishment of inter- and transdisciplinary professional teams such as a RehaBoard. In contrast to other cost-intensive disciplines such as oncology, the introduction of AI into rehabilitation orthopedics and trauma surgery with the support of cross-sectoral cooperation has great potential for performing well in patient benefit-orientated competition (value-based competition).

Age effects in storage and extinction of a naturally acquired conditioned eyeblink response.

Acquisition of conditioned eyeblink responses is known to decline with age, and age-related decline has been related to a reduction of cerebellar size and function. The aim of the present study was to investigate age-related effects on storage-related processes and extinction of visual threat eyeblink responses (VTERs), conditioned responses which are naturally acquired in early childhood. Storage and extinction of VTERs were tested in 34 healthy participants with an age range from 21 to 74 years (mean age 41.6±16.3 years). High-resolution structural magnetic resonance images (MRI) were acquired in all subjects. Conventional volumetric measures and voxel-based morphometry (VBM) were performed at the level of the cerebellum. Storage and extinction of VTERs showed a significant age-dependent decline. Likewise, cerebellar volume decreased with age. Storage, but not extinction showed a significant positive correlation with age-dependent reduction of total cerebellar volume. VBM analysis showed that gray matter volume in circumscribed areas of intermediate lobules VI, and Crus I and II bilaterally were positively correlated with VTER storage (p<0.05, FWE corrected). Considering extinction, no significant correlations with gray matter cerebellar volume were observed. The present findings show that reduction of storage of learned eyeblink responses with age is explained at least in part by age-dependent decline of cerebellar function. Future studies need to be performed to better understand which brain areas contribute to age-dependent reduction of extinction.

Humor, laughter, and the cerebellum: insights from patients with acute cerebellar stroke.

Extent of cerebellar involvement in cognition and emotion is still a topic of ongoing research. In particular, the cerebellar role in humor processing and control of laughter is not well known. A hypermetric dysregulation of affective behavior has been assumed in cerebellar damage. Thus, we aimed at investigating humor comprehension and appreciation as well as the expression of laughter in 21 patients in the acute or subacute state after stroke restricted to the cerebellum, and in the same number of matched healthy control subjects. Patients with acute and subacute cerebellar damage showed preserved comprehension and appreciation of humor using a validated humor test evaluating comprehension, funniness and aversiveness of cartoons ("3WD Humor Test"). Additionally, there was no difference when compared to healthy controls in the number and intensity of facial reactions and laughter while observing jokes, humorous cartoons, or video sketches measured by the Facial Action Coding System. However, as depression scores were significantly increased in patients with cerebellar stroke, a concealing effect of accompanying depression cannot be excluded. Current findings add to descriptions in the literature that cognitive or affective disorders in patients with lesions restricted to the cerebellum, even in the acute state after damage, are frequently mild and might only be present in more sensitive or specific tests.

fMRI reveals cognitive and emotional processing in a long-term comatose patient.

We report on a 41-year old woman with prolonged comatose unresponsiveness following traumatic head injury. Structural MRI showed bilateral midbrain damage and ventriculomegalia. Functional MRI revealed robust cortical responses to visual, auditory and tactile stimulation. Speech stimuli moreover consistently elicited activation in Broca's and Wernicke's areas. Familiar speakers and direct addressing evoked significantly stronger amygdala activation than unfamiliar speakers and neutral phrases. This study hence demonstrates the potential of functional neuroimaging in the investigation of residual higher cortical functions in unresponsive comatose patients.

[Mobile computing systems in preclinical care of stroke. Results of the Stroke Angel initiative within the BMBF project PerCoMed]. / Einsatz mobiler Computing-Systeme in der präklinischen Schlaganfallversorgung. Ergebnisse aus der Stroke-Angel-Initiative im Rahmen des BMBF-Projekts PerCoMed.

BACKGROUND: Telemedical networks that apply innovative mobile information technologies (IT) are an innovative approach to improve stroke care in community settings. Within the German Stroke Angel initiative and the research project PerCoMed (Pervasive Computing in Medical Care, funded by the Federal Ministry of Education and Research, http://www.percomed.de) the effects of such a solution were assessed by an interdisciplinary research approach. The main goal of the team of researchers and practitioners was to provide clear evidence of improvements in intersectional processes of the stroke chain survival, namely in the acute stroke processes between prehospital rescue services and hospital stroke units. MATERIAL AND METHODS: Between October 2005 and October 2007 the paramedical staff of five rescue service transporters in a rural area of northern Bavaria was included in a network with the stroke unit of the Neurological Clinic Bad Neustadt. Telemedical support by the Stroke Angel computing system - a software running on a personal digital assistant (PDA) to transmit patient data from the rescue team to the hospital during patient transporting time - was established. As procedural guidance, the Stroke Angel system suggests a predefined path through the necessary emergency procedures according to the structure of the mandatory protocol and the implemented Los Angeles Prehospital Stroke Screen (LAPSS). RESULTS: In the empirical study the authors obtained a complete data set of 226 consecutively admitted patients for analysis in Bad Neustadt and LAPSS data of 217 patients from a second scenario in Düsseldorf. Medical, economic and technical analyses were applied. The technological robustness of the Stroke Angel system could be proven and information entered was transmitted fully and correctly. Concerning medical research questions, for both scenario locations LAPSS with a sensitivity of 68.3% and a specificity of 85.1% has to be deemed insufficient. Hence, alternative algorithms will have to be used in the next steps of evaluation. The system significantly influenced the clinical process of acute stroke management more than the preclinical ones (door-to-CT: 32 min. before and 16 min. at the end of the project). Lysis treatment rose from 6.12% (2005) to 11.17% (2007) of patients with acute stroke. CONCLUSIONS: From the set of perspectives taken, the study illustrates that mobile computing technologies offer new and innovative approaches to improve intersectional acute stroke care. It also teaches the participants that interdisciplinary research can significantly deepen the understanding of such technologies and projects, which can lead to better decision making concerning solution implementation, management and improvements. The approach will be brought into daily practice in Bad Neustadt/Saale within the next months.

GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition.

The Striatum is involved in the regulation of movements and motor skills. We have shown previously, that the osmolyte and neuromodulator taurine plays a role in striatal plasticity. We demonstrate now that hereditary taurine deficiency in taurine-transporter knock-out (TAUT KO) mice results in disinhibition of striatal network activity, which can be corrected by taurine supplementation. Modification of GABAA but not glycine receptors (taurine is a ligand for both receptor types) underlies this disinhibition. Whole-cell recordings from acutely isolated as well as cultured striatal neurons revealed a decreased agonist sensitivity of the GABAA receptor in TAUT KO neurons in the absence of changes in the maximal GABA-evoked current amplitude. The striatal GABA level in TAUT KO mice was unchanged. The amplitude enhancement of spontaneous IPSCs by zolpidem was stronger in TAUT KO than in wild-type (WT) animals. Tonic inhibition was absent in striatal neurons under control conditions but was detected after incubation with the GABA-transaminase inhibitor vigabatrin: bicuculline induced a larger shift of baseline current in WT as compared to TAUT KO neurons. Lack of taurine leads to reduced sensitivity of synaptic and extrasynaptic GABAA receptors and consequently to disinhibition. These findings help in understanding neuropathologies accompanied by the loss of endogenous taurine, for instance in hepatic encephalopathy.

[Indication for emergent revascularisation of acute carotid occlusion]. / Stellenwert der Revaskularisation eines akuten Karotisverschlusses.

BACKGROUND AND PURPOSE: We examined indications for emergent revascularisation of acutely occluded internal carotid artery (ICA) using current diagnostic methods. MATERIAL AND METHODS: From 1997 to 2006 we prospectively followed 34 consecutive patients undergoing emergency revascularisation due to acute extracranial ICA occlusion and acute ischaemic stroke within 72 h after symptom onset (mean 25) and within 36 h after admission (mean 16). Exclusion criteria were occlusion of the intracranial ICA or ipsilateral middle cerebral artery (MCA), ischaemic infarction of more than one third of the MCA perfusion area, or reduced level of consciousness. All patients underwent duplex sonography, cerebral CT, and/or MRI and angiography (MRA and/or DSA). We performed endarterectomy and thrombectomy of the ICA. RESULTS: Confirmed by postoperative duplex sonography at discharge, ICA revascularisation was successful in 30 (88%) of 34 cases. Postoperative intracranial haemorrhage was detected in two patients (6%) and perioperative reinfarction in one (3%). Compared to the preoperative status, 20 patients (59%) showed signs of clinical improvement by at least one point on the Rankin scale, ten patients (29%) remained stable, and two patients (6%) had deteriorated. The 30-day mortality was 6% (two patients). CONCLUSION: After careful diagnostic workup, revascularisation of acute extracranial ICA occlusion is feasible with low morbidity and mortality.

Intracranial bilateral vertebral artery dissection during anticoagulation after cerebral venous and sinus thrombosis (CSVT).

A 37-year-old woman presented with cerebral venous and sinus thrombosis (CVST). During the period of anticoagulation she developed asymptomatic dissection of the intracranial segments of both vertebral arteries with an enlarging false aneurysm on the right side. Endovascular occlusion of the pathological segment of the right vertebral artery including the dissecting aneurysm and conservative management of the other side resulted in complete recovery without neurological complications.

[Post-stroke-depression. Algorithm for a standardized diagnostic approach in clinical routine]. / Post-Stroke-Depression. Algorithmus für ein standardisiertes diagnostisches Vorgehen in der klinischen Routine.

Depression is a frequent and important complication after stroke. The occurrence of a post-stroke-depression (PSD) has a significant impact on the functional and cognitive deficit, on mortality and on quality of life after stroke. In contrast to the clinical importance, PSD is often ignored in routine management of stroke patients and remains often untreated if diagnosed. The diagnostic uncertainty is aggravated by the lack of appropriate diagnostic criteria for PSD in the International Classification of Diseases (ICD-10) used in Germany. For the first time, we present an algorithm, which allows for a standardized examination of stroke patients on the presence of PSD. All stroke patients should be examined initially by a short and simple screening tool and are subjected to more extensive procedures only if PSD is assumed based on the screening result. Furthermore potentials and limitations to convert the diagnosis of PSD into a diagnostic related group (DRG) that is used to calculate the hospital's reimbursement are highlighted. Finally pharmacological treatment options for PSD are discussed.

Episodic respiratory failure due to focal epileptic activity.

We report on a patient with a complicated course after surgical abdominal intervention and episodic life threatening respiratory failures successfully treated with carbamazepine after diagnosis of a ponto-medullary lesion in the MRI.

The pentapeptide QYNAD does not inhibit neuronal network activity.

BACKGROUND: Controversial data was published about the sodium channel-blocking effect of the endogenous pentapeptide QYNAD, which is elevated in patients with multiple sclerosis and Guillain-Barré-syndrome. In some experiments with single cells and nerve preparations QYNAD inhibited sodium currents to the same extent as the known sodium channel blocker lidocaine whereas in other laboratory testing QYNAD failed to show any effect at all. METHODS: Micro-electrode arrays with cultured neuronal networks are highly suitable to determine neuroactive activity of applied substances. The impact on electrophysiological parameter changes was compared between QYNAD and the established sodium channel blockers lidocaine and tetrodotoxin (TTX). RESULTS: QYNAD did not alter network activity whereas the sodium channel blockers lidocaine (IC50 14.9 micorM) and tetrodotoxin (IC50 1.1 nM) reversibly decreased network activity in similar concentrations as in patch-clamp experiments. This decrease of spontaneous electrophysiological activity was achieved by prolonging the interburst-interval. CONCLUSION: Although QYNAD might have mild effects on single-cell sodium currents, there is no significant effect on neuronal network function. These results raise concerns about QYNAD exhibiting a relevant impact on functional disability of the central nervous system in patients.

Chlamydia pneumoniae, herpes simplex virus and cytomegalovirus in symptomatic and asymptomatic high-grade internal carotid artery stenosis. Does infection influence plaque stability?

BACKGROUND: Current debates are focused on inflammatory processes in atherosclerotic lesions as a possible pathomechanism for destabilization and thrombembolism. In this prospective study the role of systemic and local infection in patients with high-grade internal carotid artery stenosis (ICA) was evaluated. PATIENTS AND METHODS: Serum antibody titers of 109 consecutive patients, who underwent surgery for ICA stenosis (asymptomatic n = 40, symptomatic n = 69) were prospectively measured for Chlamydia pneumoniae (Cpn) (IgA and IgG), Herpes simplex virus (HSV) (IgG, IgM) and Cytomegalovirus (CMV) (IgG, IgM) respectively. 53 carotis plaques of this group (asymptomatic n = 17, symptomatic n = 36) could be analyzed by polymerase chain reaction (PCR) for Cpn-, HSV- and CMV-DNA presence. RESULTS: Seropositivity was found in 61,5% for Cpn, 91,7% for HSV and 72,5% CMV respectively. No significant relation was found between symptomatic and asymptomatic patients as well as no difference was seen for presence of IgA antibodies against Cpn comparing both groups. Plaque-PCR revealed Cpn in 7 cases (13,2%), HSV in 2 cases (3,8%) and no CMV had been detected. Again, no significant relationship was found concerning symptomatic and asymptomatic patients. All 9 PCR-positive plaques displayed lesions of "complicated atherosclerosis" as central fibrous necrosis and calcification or plaque bleeding and surface thrombosis. CONCLUSIONS: Our results do not support the hypothesis that systemic Cpn, HSV or CMV- infection or evidence of Cpn-, HSV- or CMV-DNA in carotid plaques causes plaque destabilization and cerebral thromboembolism. Plaque infection could only be observed in cases with advanced atherosclerosis.

IV thrombolysis in patients with acute stroke due to spontaneous carotid dissection.

The authors reviewed the histories of 33 patients (ages 44 to 50 years) treated with IV thrombolysis for acute stroke due to spontaneous cervical carotid artery dissection. Median NIH Stroke Scale (NIHSS) score on admission was 15. No new or worsened local signs, subarachnoid hemorrhage, pseudoaneurysm formation, or rupture of the cervical ICA were observed. At 3 months, median NIHSS was 7 and median modified Rankin Scale (mRS) 2.5; mRS < or = 2 was observed in 17 patients.

Influence of D-arabitol and ribitol on neuronal network activity.

To date, two new defects in the pentose phosphate pathway have been identified in patients with abnormalities in their polyol profiles. Some of them presented with neurological symptoms of so far unknown aetiology. The pathophysiological role of polyols, e.g. in the brain, is relatively unknown. We tested the neurotoxicity of polyols using a 'neurochip' model. After exposure of cortical rat neurons to D-arabitol and ribitol in increasing concentrations up to 10 mmol/L, the electrophysiological activity was measured. No acute effect on the spontaneous network activity of cortical neurons was observed. We speculate that polyols have only secondary effects on brain dysfunction.

The effect of combined thrombolysis with rtPA and tirofiban on ischemic brain lesions.

To determine the effect of systemic thrombolysis with low-dose recombinant tissue plasminogen activator (rtPA) and the body-weight adjusted platelet GPIIb/IIIa receptor antagonist tirofiban, the authors performed lesion volumetry on magnetic resonance perfusion and diffusion images recorded before thrombolysis and on T2-weighted magnetic resonance images on day 8. Treatment with rtPA and tirofiban (n = 13) resulted in a 50% lesion reduction (p < 0.03), while lesion reduction was less in rtPA treatment (n = 16) and absent in nontreated patients (n = 18).

Effect of incomplete (spontaneous and postthrombolytic) recanalization after middle cerebral artery occlusion: a magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Early reperfusion is one of the best predictors of good outcome after acute middle cerebral artery (MCA) occlusion. The purpose of this study was to analyze the frequency and relevance of incomplete recanalization for tissue and clinical outcome. METHODS: From a larger acute stroke database (Kompetenznetzwerk Schlaganfall B5), all patients (n=82) with MCA main stem occlusion (excluding carotid T-occlusions) were selected. These patients had received a multiparametric stroke MRI protocol including diffusion- and perfusion-weighted imaging (DWI, PWI) and MR angiography (MRA) within 6 hours after symptom onset, at day 1 and after 1 week. Recanalization status was determined with MRA on day 1 (according to Thrombolysis In Myocardial Infarction flow grades) and used to group patients into those with persistent occlusion (0) or minimal (1), partial (2), or complete (3) recanalization. RESULTS: Incomplete recanalization according to MRI criteria was found in 39 patients (grade 1: n=20; grade 2: n=19), complete recanalization in 10, and persistent occlusion in 33. There was no statistically significant difference in any of the clinical (National Institutes of Health Stroke Scale score) or MRI baseline parameters (DWI lesion, PWI deficit, mismatch volume, mismatch ratio). However, lesion growth was smaller in patients with recanalization (even in patients with only minimal recanalization) and outcome was related to the degree of recanalization (mean modified Rankin score at 90 days: 3.36, 2.70, 1.79, and 1.44 for the groups with no, minimal, partial, and complete recanalization, respectively). Both incomplete and complete recanalization was more frequent in patients receiving thrombolysis. CONCLUSIONS: Incomplete recanalization on day 1 is a frequent MR finding after MCA main stem occlusion, indicating a more favorable clinical course than persistent occlusion. MR indicators of early recanalization could be useful surrogates of efficacy in thrombolytic trials.

Carotid surgery in acute symptomatic patients.

OBJECTIVES: evaluation of urgent carotid artery surgery with new diagnostic techniques and changing surgical considerations at a university hospital. DESIGN, MATERIAL AND METHODS: prospective monitoring and assessment of outcome in 67 patients who underwent urgent carotid surgery because of symptomatic extracranial carotid artery involvement. Patients were examined via the stroke unit: duplex sonography was mandatory for diagnosis of extracranial carotid artery disease, as was proof of an open middle cerebral artery (MCA). Assessment of intracerebral damage followed CT or MR imaging procedures. Perioperative and surgical management was standardized. Neurological impairment was assessed pre-, postoperatively and at follow-up using the Rankin scale. "Urgent" was defined as "immediate" after the final diagnostic step had been performed. RESULTS: within a period of 26 months 67 symptomatic patients (58% stroke, 42% TIA) underwent urgent carotid surgery. Median time from admission to surgery was 2 days. In all but five cases flow through the ICA could technically be restored (93%). Thirty-day mortality was 3% and disease-related morbidity 13%. The one and two year survival rates were 92 and 90%, respectively. No ipsilateral recurrent stroke occurred during follow-up. CONCLUSIONS: clinical decision-making based on stratified diagnostic workup by means of extra- and intracranial as well as intracerebral hemodynamics using new imaging techniques may select patients who will benefit more from urgent surgery than from conservative management.