Striatal dopamine transporters and cognitive function in Parkinson's disease

Background Idiopathic Parkinson’s disease (PD) is characterized by clinical motor symptoms including hypokinesia, rigidity and tremor. In addition to the movement disorder, cognitive deficits are commonly described. In the present study, we applied FP‐CIT SPECT to investigate the impact of nigrostriatal dopaminergic degeneration on cognitive function in PD patients. Methods Fifty‐four PD patients underwent [123I]FP‐CIT SPECT and CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) testing. FP‐CIT SPECT visualized the density of presynaptic dopamine transporters in both striata, each subdivided into a limbic, executive and sensorimotor subregion according to the atlas of Tziortzi et al (Cereb Cortex 24, 2014, 1165). CERAD testing quantified cognitive function. Results In the CERAD testing, PD patients exhibited deficits in the domains of semantic memory, attention, visuospatial function, non‐verbal memory and executive function. After correction for multiple testing, the performance of the subtests Figure Recall and Trail‐Making Test A correlated significantly with FP‐CIT uptake into the ipsilateral executive subregion. The performance of the subtest Figure Saving correlated significantly with FP‐CIT uptake into the contralateral executive subregion. Conclusions The significant correlation between cognitive function and density of nigrostriatal dopamine transporters, as assessed by FP‐CIT SPECT, indicate that striatal dopaminergic pathways—primarily the executive striatal subregion—are relevant to cognitive processing in PD

Acute stroke treatment and outcome in the oldest old (90 years and older) at a tertiary care medical centre in Germany-a retrospective study showing safety and efficacy in this particular patient population

Background Stroke is among the most common causes of death and disability worldwide. Despite the relevance of stroke-related disease burden, which is constantly increasing due to the demographic change in industrialized countries with an ageing population and consecutively an increase in age-associated diseases, there is sparse evidence concerning acute stroke treatment and treatment-related outcome in the elderly patient group. This retrospective study aimed at analysing patient characteristics, therapy-related complications and functional outcome in stroke patients aged 90 years or older who underwent acute stroke treatment (i.e. intravenous thrombolysis, mechanical thrombectomy, or both). Methods We identified files of all inpatient stays at the Department of Neurology at Saarland University Medical Center (tertiary care level with a comprehensive stroke unit) between June 2011 and December 2018 and filtered for subjects aged 90 years or older at the time of admission. We reviewed patient files for demographic data, symptoms upon admission, (main) diagnoses, comorbidities, and administered therapies. For patients admitted due to acute stroke we reviewed files for therapy-related complications and functional outcome. We compared the modified Rankin scale (mRS) scores upon admission and at discharge for these patients. Results We identified 566 inpatient stays of subjects aged 90 years or older. Three hundred sixty-seven of the 566 patients (64.8%) were admitted and discharged due to symptoms indicative of stroke. Two hundred eleven patients received a diagnosis of ischaemic stroke. These 211 patients were analysed subsequently. Sixty-four patients qualified for acute stroke treatment (intravenous thrombolysis n = 22, mechanical thrombectomy n = 26, intravenous thrombolysis followed by mechanical thrombectomy n = 16) and showed a significant improvement in their functional status as measured by change in mRS score (admission vs. discharge, p 0.001) with 7 (10.9%) observed potentially therapy-related complications (relevant drop in haemoglobin n = 2, subarachnoidal haemorrhage n = 1, cerebral haemorrhage n = 3, extracranial bleeding n = 1). One intravenous thrombolysis was stopped because of an uncontrollable hypertensive crisis. Patients who did not qualify for these treatments (including those declining acute treatment) did not show a change of their functional status between admission and discharge (p 0.064). Conclusion Our data indicate that acute stroke treatment is effective and safe in the oldest old. Age alone is no criterion to withhold an acute intervention even in oldest old stroke patients

Red-Sequence Galaxies at High Redshift by the COMBO-17+4 Survey

We investigate the evolution of the galaxy population since redshift 2 with a focus on the colour bimodality and mass density of the red sequence. We obtain precise and reliable photometric redshifts up to z=2 by supplementing the optical survey COMBO-17 with observations in four near-infrared bands on 0.2 square degrees of the COMBO-17 A901-field. Our results are based on an H-band-selected catalogue of 10692 galaxies complete to H=21.7. We measure the rest-frame colour (U_280-V) of each galaxy, which across the redshift range of our interest requires no extrapolation and is robust against moderate redshift errors by staying clear of the 4000A-break. We measure the colour-magnitude relation of the red sequence as a function of lookback time from the peak in a colour error-weighted histogram, and thus trace the galaxy bimodality out to z~1.65. The (U_280-V) of the red sequence is found to evolve almost linearly with lookback time. At high redshift, we find massive galaxies in both the red and the blue population. Red-sequence galaxies with log M_*/M_sun>11 increase in mass density by a factor of ~4 from z~2 to 1 and remain nearly constant at z<1. However, some galaxies as massive as log M_*/M_sun=11.5 are already in place at z~2.Comment: 18 pages, 11 figures, accepted for publication in Ap

Short-chain fatty acids and intestinal inflammation in multiple sclerosis: modulation of female susceptibility by microbial products?

Background: Multiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Experi mental data suggest a role of intestinal microbiota and microbial products such as short-chain fatty acids (SCFAs) in the pathogenesis of MS. A recent clinical study reported benefcial efects (mediated by immunomodulatory mecha nisms) after oral administration of the SCFA propionate in MS patients. Based on available evidence, we investigated whether SCFAs and the fecal infammation marker calprotectin are altered in MS. Methods: 76 subjects (41 patients with relapsing–remitting MS and 35 age-matched controls) were investigated in this case–control study. All subjects underwent clinical assessment with established clinical scales and provided fecal samples for a quantitative analysis of fecal SCFA and fecal calprotectin concentrations. Fecal markers were com pared between MS patients and controls, and were analyzed for an association with demographic as well as clinical parameters. Results: Median fecal calprotectin concentrations were within normal range in both groups without any group-spe cifc diferences. Fecal SCFA concentrations showed a non-signifcant reduction in MS patients compared to healthy subjects. Female subjects showed signifcantly reduced SCFA concentrations compared to male subjects. Conclusions: In our cohort of MS patients, we found no evidence of an active intestinal infammation. Yet, the vast majority of the investigated MS patients was under immunotherapy which might have afected the outcome meas ures. The sex-associated diference in fecal SCFA concentrations might at least partially explain female predominance in MS. Large-scale longitudinal studies including drug-naïve MS patients are required to determine the role of SCFAs in MS and to distinguish between disease-immanent efects and those caused by the therapeutic regime

Consecutive Eyeball Pressure Tests Reflect Clinically Relevant Vagal Dysfunction and Recovery in a Patient With Guillain-Barré-Syndrome With Tenacious Cardiac Dysautonomia

Cardiac dysautonomia is a potentially life-threatening complication of Guillain-Barré syndrome (GBS). Proper and prompt recognition of patients at risk and subsequent intensive care unit (ICU) monitoring are mandatory to prevent fatal outcome. Eyeball pressure testing (EP) has been suggested as an easy applicable bedside test for vagal overreactivity in GBS and thus identifying patients at risk. Yet, there is only sparse follow-up data concerning the course of EP findings in GBS. We report a 25 years-old male patient with GBS who underwent consecutive EP (n = 11) during his ICU stay over a period of 11 weeks. The series of tests performed in this patient (and corresponding clinical events) show that EP data might represent an approximation of vagal dysfunction and vagal recovery in GBS. Interestingly, we observed a much longer duration of pathological EP compared to a previous report. The tenacious cardiac dysautonomia in this patient necessitated long-term application of a transvenous temporary pacemaker

Why we fail: mechanisms and co-factors of unsuccessful thrombectomy in acute ischemic stroke

Purpose Mechanical thrombectomy (MT) is an effective treatment for patients suffering from acute ischemic stroke. However, recanalization fails in about 16.5% of interventions. We report our experience with unsuccessful MT and analyze technical reasons plus patient-related parameters for failure. Methods Five hundred ninety-six patients with acute ischemic stroke in the anterior circulation and intention to perform MT with an aspiration catheter and/or stent retriever were analyzed. Failure was defined as 0, 1, or 2a on the mTICI scale. Patients with failing MT were analyzed for interventional progress and compared to patients with successful intervention, whereby parameters included demographics, medical history, stroke presentation, and treatment. Results One hundred of the 596 (16.8%) interventions failed. In 20 cases, thrombus could not be accessed or passed with the device. Peripheral arterial occlusive disease is common in those patients. In 80 patients, true stent retriever failure occurred. In this group, coagulation disorders are associated with poor results, whereas atrial fibrillation is associated with success. The administration of intravenous thrombolysis and intake of nitric oxide donors are associated with recanalization success. Intervention duration was significantly longer in the failing group. Conclusion In 20% of failing MT, thrombus cannot be reached/passed. Direct carotid puncture or surgical arterial access could be considered in these cases. In 80% of failing interventions, thrombus can be passed with the device, but the occluded vessel cannot be recanalized. Rescue techniques can be an option. Development of new devices and techniques is necessary to improve recanalization rates. Assessment of pre-existing illness could sensitize for occurring complications

Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin

Background Peripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens, autoimmunity, trauma, tumors, cholesteatoma or further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difcult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specifc T cells change during active infections, we hypothesized that such changes may also help to identify the causative pathogen in PFPs of unknown origin. Methods In this observational study, pathogen-specifc T cells were quantifed in blood samples of 55 patients with PFP and 23 healthy controls after stimulation with antigens from varicella-zoster virus (VZV), herpes-simplex viruses (HSV) or borrelia. T cells were further characterized by expression of the inhibitory surface molecule CTLA-4, as well as markers for diferentiation (CD27) and proliferation (Ki67). Pathogen-specifc antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics. Results Patients with PFP were more often HSV-seropositive than controls (p=0.0003), whereas VZV- and borreliaspecifc antibodies did not difer between groups. Although the quantity and general phenotypical characteristics of antigen-specifc T cells did not difer either, expression of CTLA-4 and Ki67 was highly increased in VZV-specifc T cells of 9 PFP patients, of which 5 showed typical signs of cutaneous zoster. In the remaining 4 patients, a causal relationship with VZV was possible but remained unclear by clinical standard diagnostics. A similar CTLA-4- and Ki67- expression profle of borrelia-specifc T cells was also found in a patient with acute neuroborreliosis. Discussion In conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specifc T cell characteristics seem insufcient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specifc T cell phenotype and function may allow identifcation of VZV- and borrelia-triggered PFPs. If confrmed in larger studies, antigen-specifc immune-phenotyping may have the potential to improve specifcity of the clinical diagnosis

Pre- and in-hospital delays in the use of thrombolytic therapy for patients with acute ischemic stroke in rural and urban Egypt

BackgroundReducing pre- and in-hospital delays plays an important role in increasing the rate of intravenous thrombolysis (IVT) in patients with acute ischemic stroke. In Egypt, the IVT rate has increased steadily but is still far away from an ideal rate.AimThe study aimed to investigate the factors associated with pre- and in-hospital delays of IVT among patients with acute ischemic stroke coming from urban and rural communities.MethodsThis prospective, multicenter, observational cohort study was conducted from January 2018 to January 2019. Patients with acute ischemic stroke, who did not receive IVT, were included in the study. Patients were recruited from three large university stroke centers in Egypt, Assiut (south of Egypt), Tanta (north of Egypt), both serving urban and rural patients, and the University Hospital in Cairo (capital city), only serving an urban community. All participants underwent the National Institutes of Health Stroke Scale and full neurological assessment, urgent laboratory investigations, and computed tomography or magnetic resonance imaging to confirm the stroke diagnosis. The patients were subjected to a structured questionnaire that was designed to determine the parameters and time metrics for the pre- and in-hospital delays among patients from rural and urban regions.ResultsA total of 618 patients were included in the study, of which 364 patients (58.9%) lived in rural regions and 254 (41.1%) in urban regions. General demographic characteristics were similar between both groups. Approximately 73.3% of patients who arrived within the therapeutic time window were urban patients. The time from symptom onset till hospital arrival (onset to door time, ODT) was significantly longer among rural patients (738 ± 690 min) than urban patients (360 ± 342 min). Delayed onset to alarm time (OAT), initial misdiagnosis, and presentation to non-stroke-ready hospitals were the most common causes of pre-hospital delay and were significantly higher in rural patients. For patients arriving within the time window, the most common causes of in-hospital delays were prolonged laboratory investigations and imaging duration.ConclusionThe limited availability of stroke-ready hospitals in rural Egypt leads to delays in stroke management, with subsequent treatment inequality of rural patients with acute stroke

Die Stiftung

Die Stiftung : Vermögen verwalten, Zukunft gestalten. - 1994. - XXIX, 177 S. - Augsburg, Univ., Diss., 199

Sphingolipids: Important Players in Multiple Sclerosis

Multiple Sclerosis (MS) is the most common cause for permanent disability in young adults. Current pathophysiological understanding has identified an autoaggressive immune reaction with infiltration of immune cells into the central nervous system and local inflammatory and demyelinating reactions. The current therapy focuses on a modulation or suppression of immune functions. Sphingolipids, main components of nervous tissue, have been linked to MS already 60 years ago with the description of an unusual myelin lipid distribution in diseased patients. There is tremendous information developing on the role of different sphingolipids in MS. Antibodies against sphingomyelin, sulfatide or galacosylceramide have been detected in serum or CSF of MS patients, although up to now, this knowledge did not find its way into clinical use. Ceramide and the enzymes linked to its production have been described to play a pivotal role in oligendrocyte damage and demyelination. Nowadays, especially sphingosine-1-phosphate (S1P) is in the focus of pathophysiological research and therapy development. A S1P analogue, FTY720, is a widely distributed therapy against relapsing-remitting MS, attenuating the emigration of activated, autoreactive lymphocytes from lymph nodes, thereby preventing new inflammatory infiltration into the central nervous system. Beside, there is more and more evidence, that especially S1P receptors on oligodendrocytes and astrocytes are involved in demyelination processes and subsequent axonal degeneration, important features of chonic progressive MS disease course. Further information and research on the manifold role of sphingolipids are needed to prepare the ground for further clinical trials. This review focuses on the current knowledge of the role of sphingolipids in MS and describes the current therapeutical implications