[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.

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.

[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.

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.

Immunologically induced electrophysiological dysfunction: implications for inflammatory diseases of the CNS and PNS.

During inflammation of the central or peripheral nervous system, a high number of immunologically active molecules, including bacterial or viral products as well as host-derived cytokines, are released. Patients suffering from inflammatory CNS or PNS diseases often develop transient symptoms with a rapid recovery, which obviously cannot be accounted for by immunologically induced tissue damage. These observations led to the hypothesis that immunologically active molecules can affect directly the electrophysiological functions of neurons and glial cells. Evidence for this hypothesis came from in vitro studies showing that cytokines, such as interleukins or tumor necrosis factors, arachidonic acid and its metabolites, interfere with electrophysiological properties of neurons or glial cells. These molecules affect ion currents, intracellular Ca2+ homeostasis, membrane potentials, and suppress or enhance the induction and maintenance of long-term potentiation. Similarly, virus proteins from human immunodeficiency virus type I were found to alter intracellular Ca2+ concentrations of neurons and astrocytes by modulating either transmitter receptors and channels or membrane transporters. Cerebrospinal fluid from MS patients contains factors which increase Na+ current inactivation and thereby reduce neuronal excitability. Immunoglobulins in sera of patients suffering from multifocal motor neuropathy and from acquired neuromyotonia interfere with nerve fibers, inducing alterations of conduction. Increased knowledge of these mechanisms will help to explain the pathogenesis of neurological symptoms and may provide a rationale for new therapeutic strategies.

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.

Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization.

BACKGROUND AND PURPOSE: The procoagulant protein tissue factor (TF) has been implicated in thromboembolic complications associated with advanced atherosclerosis. In this study, we investigated whether TF expression in high-grade stenoses of the internal carotid artery (ICA) is associated with clinical features of plaque destabilization and addressed the relationship between TF expression and plaque inflammation. METHODS: In 36 consecutive patients undergoing surgery for high-grade ICA stenosis, clinical evidence of plaque instability was provided by the recent occurrence of ischemic symptoms attributable to the stenosis and the detection of cerebral microembolism by means of transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. Endarterectomy specimens were stained immunocytochemically for TF expression as well as macrophage (CD68) and T cell (CD3) infiltration. RESULTS: Morphologically, TF immunoreactivity was codistributed with plaque inflammation and predominantly localized to CD68+ macrophages. Accordingly, statistical analysis revealed a significant association of TF expression with plaque infiltration by macrophages (P<0.0001) and T cells (P=0.013). Plaques extensively stained for TF (median of TF+ total section area >40% in semiquantitative assessment) were more frequent in symptomatic (12/27) than in asymptomatic patients (1/9). Conversely, plaques exhibiting little TF expression (median of TF+ section area <20%) were more frequent in asymptomatic (3/9) than in symptomatic (1/27) patients (P=0.016). Likewise, we found a highly significant association of TF expression with the occurrence of cerebral microembolism (P=0.008). CONCLUSIONS: Induction of TF at sites of plaque inflammation may play an important role in the destabilization of high-grade ICA stenosis.

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.

Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours.

BACKGROUND AND PURPOSE: The goals of this study were to examine MRI baseline characteristics of patients with acute ischemic stroke (AIS) and to study the influence of intravenous tissue plasminogen activator (tPA) on MR parameters and functional outcome using a multicenter approach. METHODS: In this open-label, nonrandomized study of AIS patients with suspected anterior circulation stroke, subjects received a multiparametric stroke MRI protocol (diffusion- and perfusion-weighted imaging and MR angiography) within 6 hours after symptom onset and on follow-up. Patients were treated either with tPA (thrombolysis group) or conservatively (no thrombolysis group). Functional outcome was assessed on day 90 (modified Rankin Score; mRS). RESULTS: We enrolled 139 AIS patients (no thrombolysis group, n=63; thrombolysis group, n=76). Patients treated with tPA were more severely affected (National Institutes of Health Stroke Scale score, 10 versus 13; P=0.002). Recanalization rates were higher in the thrombolysis group (Thrombolysis in Myocardial Infarction criteria 1 through 3 on day 1; 66.2% versus 32.7%; P<0.001). Proximal vessel occlusions resulted in larger infarct volumes and worse outcome (P=0.02). Thrombolysis was associated with a better outcome regardless of the time point of tPA treatment (< or =3 hours or 3 to 6 hours) (univariate analysis: mRS < or =2, P=0.017; mRS < or =1, P=0.023). Age (P=0.003), thrombolytic therapy at 0 to 6 hours (P=0.01), recanalization (P=0.016), lesion volume on day 7 (P=0.001), and initial National Institutes of Health Stroke Scale score (P=0.001) affected functional outcome (mRS on day 90) positively (multivariate analysis). The time point of tPA therapy affected the recanalization rate (P=0.024) but not final infarct volume. CONCLUSIONS: In this pilot study, tPA therapy had a beneficial effect on vessel recanalization and functional outcome. Multiparametric MRI delineates tissue at risk of infarction in AIS patients, which may be helpful for the selection of patients for tPA therapy. tPA therapy appeared safe and effective beyond a 3-hour time window. This study delivers the rationale for a randomized, MR-based tPA trial.

Cerebral microembolism in patients with Sneddon's syndrome.

BACKGROUND: The pathogenesis of Sneddon's syndrome is unclear. This study addresses the question whether cerebral thromboembolism may be involved in the pathogenesis of the neurologic complications of the disorder. The study consisted of 13 patients with Sneddon's syndrome defined by both generalized livedo reticularis and a history of one or more cerebrovascular ischemic events; none had clinical or Doppler ultrasonographic evidence of atherosclerosis. METHODS: Transcranial Doppler microembolic monitoring of the middle cerebral artery; blood screening for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies). RESULTS: Five patients (38%) showed clinically silent microembolism at transcranial Doppler monitoring, with individual microembolic event rates of the middle cerebral artery between 2 per hour and 33 per hour. In this group, the time since the last ischemic symptom was significantly shorter than in the eight patients without microemboli. Antiphospholipid antibodies were detected in three patients (23%), all of whom belonged to the microemboli-positive group. CONCLUSIONS: These data suggest that the detectability of both clinically silent cerebral microembolism and antiphospholipid antibodies may provide paraclinical evidence of active disease in patients with Sneddon's syndrome. The results support the notion that an immune-mediated prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization, and/or triggering in situ thrombosis of cerebral vessels, plays a pathogenetic role in the neurologic manifestations of this disorder.

Cheyne-Stokes respiration in ischemic stroke.

We monitored breathing pattern and arterial oxygen saturation in 32 conscious patients with acute ischemic stroke. Seventeen (53%) had Cheyne-Stokes respiration with concomitant drops in oxygen saturation, unrelated to infarct location. The ventilatory disturbance promptly reversed after intravenous theophylline ethylenediamine or oxygen inhalation. The therapy is a simple way of improving arterial oxygenation in a large subgroup of patients with acute ischemic stroke.

Cerebral microembolism in symptomatic and asymptomatic high-grade internal carotid artery stenosis.

Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (> or = 70%) internal carotid artery (ICA) stenosis, we examined the relation between the rate of TCD-detected silent microembolism of the ipsilateral middle cerebral artery and a history of recent (< 121 days) ischemic symptoms attributable to the diseased ICA. In the so-defined neurologically symptomatic group (n = 33 patients), silent microembolic events occurred in 27 subjects (overall mean rate, 14/h +/- 29). Among 56 neurologically asymptomatic patients matched for the degree of ICA stenosis, only nine showed such events (overall mean rate, 0.35/h +/- 1.4). Across all 89 patients studied, an individual microembolic event rate > or = 2/h had a positive predictive value of 0.88 for a history of recent symptoms. Our data suggest that TCD monitoring can provide reliable paraclinical evidence of "unstable ICA disease."

Cerebral blood flow velocity alterations during obstructive sleep apnea syndrome.

We recorded cerebral blood flow velocity (CBFV) for the assessment of CO2-regulated alterations during apnea by means of transcranial Doppler ultrasound in a patient with obstructive sleep apnea syndrome. CBFV increased up to doubled peak flow values during obstructive apneic phases. The results provide evidence for a normal CO2 regulation of CBFV leading to periodic vascular stress during the night.

Ischemic brain tissue salvaged from infarction by the GP IIb/IIIa platelet antagonist tirofiban.

In an open pilot study, the authors tested whether the nonpeptide glycoprotein (GP) IIb/IIIa antagonist tirofiban, a highly effective and selective blocker of platelet aggregation, prevents the transition of ischemic brain tissue into the infarct proper as defined by MRI (perfusion-weighted/T2-weighted) in patients with acute ischemic stroke. The infarct volume (T2 lesion after 1 week) was smaller in treated patients (n = 10) compared with matched control subjects (n = 10; p = 0.029) with similar initial perfusion deficit (TTP-maps). The authors conclude that GP IIb/IIIa antagonists have therapeutic potential in acute stroke therapy.

Lipopolysaccharides and leukotriene B4 induce independently regulated electrophysiological and immunological responses in cultured astrocytes.

Astrocytes play an important role in immunological processes within the central nervous system. They are able to produce cytokines like interleukin 6 (IL-6) and depolarize substantially after stimulation by lipopolysaccharides (LPS) or leukotriene B4 (LTB4). Therefore, we investigated the coupling between these immunological and electrophysiological processes. Amiloride (250 microM), a blocker of various Na+ transport systems, inhibited LPS (5 micrograms/ml)-induced depolarization, whereas the LPS-induced release of IL-6 was unaffected, indicating different intracellular regulatory mechanisms. LTB4 (1.0 microM) induced a depolarization of a similar degree but mediated by a different ionic mechanism and failed to induce a detectable IL-6 release. Dexamethasone (1.0 microM) and cycloheximide (2.0 microM) specifically reduced LTB4-induced depolarization, while LPS-induced depolarization was unaffected, providing further evidence for different regulatory pathways. Neither the depolarization nor the immunological stimuli served as a proliferation signal. These data demonstrate that independent immunological and electrophysiological responses with specific intracellular regulation are evoked after stimulation with LPS or LTB4. With respect to functional disturbance of depolarized glial cells, e.g. in maintaining local ionic homeostasis, neuronal excitability may be affected indirectly and by this way account for the appearance of neurological symptoms during inflammatory CNS diseases.

Impairment of electrophysiological function of astrocytes by cerebrospinal fluid from a patient with Waldenström's macroglobulinemia.

Patients with the Bing Neel type of Waldenström's macroglobulinemia often present with global neurological symptoms. In this case report, we investigated the effects of cerebrospinal fluid (CSF) of a such a patients (CSF-WM), who presented with seizures and psychomotor slowing, on the electrophysiological properties of cultured rat neurons and astrocytes. Membrane potential and Na+ and K+ currents of neurons were unaffected. Astrocytes, however, were significantly depolarized from -77.6 +/- 8.2 mV to -48.0 +/- 7.6 mV (38%) by CSF-WM. The depolarization was markedly reduced after CSF-WM heat inactivation or after pre-incubation of astrocytes with dexamethasone (1 microM). Astrocytes are electrophysiologically active cells, which control local ionic micro-environment. Therefore, we conclude that global neurological symptoms in the Bing Neel type of Waldenström's macroglobulinemia like generalized seizures can result from an impairment of glial cells electrophysiological functions.

Cerebral hemodynamics in obstructive sleep apnea.

We have investigated cerebral blood flow velocity (CBVF) in 14 patients with marked obstructive sleep apnea syndrome using transcranial Doppler ultrasonography during sleep. The CBFV increased during apnea, with a mean acceleration of 0.9 cm/s2, followed by a rapid decrease during snoring. The same effect was obtained by voluntary apnea in healthy subjects, showing a smaller acceleration rate (0.6 cm/s2). These results provide evidence for a normal CO2 regulation of cerebral vessels during sleep apnea and do not support the notion of cerebral hypoperfusion during sleep being a risk factor for stroke.