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BACKGROUND: Mechanical thrombectomy (MT) is a standard stroke treatment for patients with large vessel occlusions (LVOs). A decisive factor for a successful outcome is, among other things, timely treatment. OBJECTIVE: The objective was to analyze several time points in relation to outcomes and/or surrogate parameters. Furthermore, our data was placed in the context of other clinical trial data. METHODS: We retrospectively evaluated 133 data sets from patients who underwent MT. The correlation of various time periods with parameters, such as the ASPECTS, NIHSS, mRS, and, particularly, the TICI score, was investigated. RESULTS: A correlation was found for both the NIHSS score at discharge and the TICI score with the time periods of arrival and/or start to groin puncture as well as with arrival to the end of the intervention and the duration of the intervention. CONCLUSIONS: This retrospective study is consistent with large randomized clinical trials investigating stroke management and provides data from daily clinical practice.

OBJECTIVE We aimed to estimate the incidence of cerebral sinus and venous thrombosis (CVT) within 1 month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany. METHODS A web-based questionnaire was e-mailed to all departments of neurology. We requested a report of cases of CVT occurring within 1 month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of 9 German states. RESULTS A total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were younger than 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%) vaccination, and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within 1 month from first dose administration was 0.55 (95% confidence interval [CI] = 0.38-0.78) per 100,000 person-months (which corresponds to a risk of CVT within the first 31 days of 0.55 per 100,000 individuals) for all vaccines and 1.52 (95% CI = 1.00-2.21) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (95% CI = 3.46-34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (95% CI = 1.22-10.65) for females compared to non-females. In 26 of 45 patients with CVT (57.8%), VITT was graded highly probable. INTERPRETATION Given an incidence of 0.02 to 0.15 per 100,000 person-months for CVT in the general population, these findings point toward a higher risk for CVT after ChAdOx1 vaccination, especially for women. ANN NEUROL 2021;90:627-639.

Background It is well established that even moderate levels of alcohol affect cognitive functions such as memory, self-related information processing and response inhibition. Nevertheless, the neural mechanisms underlying these alcohol-induced changes are still unclear, especially on the network level. The default mode network (DMN) plays an important role in memory and self-initiated mental activities, hence studying functional interactions of the DMN may provide new insights into the neural mechanisms underlying alcohol-related changes. Methods We investigated resting-state functional connectivity (rsFC) of the DMN in a cohort of 37 heavy drinkers at a breath alcohol concentration of 0.8 g/kg. Alcohol and saline were infused in a single-blind crossover design. Results Intra-network connectivity analyses revealed that participants showed significantly decreased rsFC of the right hippocampus and right middle temporal gyrus under acute alcohol exposure. Moreover, follow-up analyses revealed that these rsFC decreases were more pronounced in participants who reported stronger craving for alcohol. Exploratory inter-network connectivity analyses of the DMN with other resting-state networks showed no significant alcohol-induced changes, but suffered from low statistical power. Conclusions Our results indicate that acute alcohol exposure affects rsFC within the DMN. Functionally, this finding may be associated with impairments in memory encoding and self-referential processes commonly observed during alcohol intoxication. Future resting-state functional magnetic resonance imaging studies might therefore also investigate memory function and test whether DMN-related connectivity changes are associated with alcohol-induced impairments or craving.

RationaleInhibition is a core executive function and refers to the ability to deliberately suppress attention, behavior, thoughts, and/or emotions and instead act in a specific manner. While acute alcohol exposure has been shown to impair response inhibition in the stop-signal and Go/NoGo tasks, reported alcohol effects on attentional inhibition in the Stroop task are inconsistent. Notably, studies have operationalized attentional inhibition variably and there has been intra- and inter-individual variability in alcohol exposure.ObjectiveThis study aimed to examine the acute effects of alcohol on attentional inhibition, considering previous limitations.MethodsIn a single-blind, cross-over design, 40 non-dependent participants with a medium-to-high risk drinking behavior performed a Counting Stroop task (CST) under a baseline and an arterial blood alcohol concentration (aBAC) clamp at 80 mg%. Attentional inhibition was assessed as the alteration of reaction times (RT), error rates (ER), and inverse efficiency scores (IES) between incongruent and congruent trials (interference score). Stroop performance was also assessed regardless of trial-type.ResultsCompared to saline, acute alcohol exposure via an aBAC clamp did not affect CST interference scores but increased RTs and IES in both incongruent and congruent trials.ConclusionsAttentional inhibition (Stroop interference score) was not impaired by clamped moderate alcohol exposure. Acute alcohol impaired Stroop performance evidenced by a general increase in response times. Our findings suggest that response and attentional inhibition do not share the same neurocognitive mechanisms and are affected differently by alcohol. Results could also be explained by automated behaviors known to be relatively unaffected by acute alcohol.

Background and objectives: Bedside sonographic duplex technique (SDT) may be used as an adjunct to cranial computed tomography (CCT) to monitor brain-injured patients after decompressive craniectomy (DC). The present study aimed to assess the value of SDT in repeated measurements of ventricle dimensions in patients after DC by comparing both techniques. Materials and Methods: Retrospective assessment of 20 consecutive patients after DC for refractory intracranial pressure (ICP) increase following subarachnoid hemorrhage (SAH), bleeding and trauma which were examined by SDT and CCT in the context of routine clinical practice. Whenever a repeated CCT was clinically indicated SDT examinations were performed within 24 hours and correlated via measurement of the dimensions of all four cerebral ventricles. Basal cerebral arteries including pathologies such as vasospasms were also evaluated in comparison to selected digital subtraction angiography (DSA). Results: Repeated measurements of all four ventricle diameters showed high correlation between CCT and SDT (right lateral r = 0.997, p &lt, 0.001, left lateral r = 0.997, p &lt, third r = 0.991, p &lt, 0.001, fourth ventricle r = 0.977, p &lt, 0.001). SDT performed well in visualizing basal cerebral arteries including pathologies (e.g., vasospasms) as compared to DSA. Conclusions: Repeated SDT measurements of the dimensions of all four ventricles in patients after DC for refractory ICP increase delivered reproducible results comparable to CCT. SDT may be considered as a valuable bedside monitoring tool in patients after DC.

BackgroundBased on clinical, immunological and histopathological evidence, MOG-IgG-associated encephalomyelitis (MOG-EM) has emerged as a distinct disease entity different from multiple sclerosis (MS) and aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder (NMOSD). MOG-EM is associated with a broader clinical phenotype including optic neuritis, myelitis, brainstem lesions and acute disseminated encephalomyelitis with a substantial clinical and radiological overlap to other demyelinating CNS disorders.ObjectiveTo evaluate common clinical, MRI and CSF findings, as well as therapy responses in patients with longitudinal extensive transverse myelitis (LETM) as initial clinical presentation of MOG-EM.MethodsAfter excluding patients with a known diagnosis of MS, we identified 153 patients with myelitis of which 7 fulfilled the inclusion criteria and were investigated for MRI, CSF and clinical parameters.ResultsPatients with LETM as first clinical presentation of MOG-EM display similar characteristics, namely a lack of gadolinium-enhancement in spinal cord MRI, marked pleocytosis, negative oligoclonal bands, a previous history of infections/vaccinations and response to antibody-depleting treatments for acute attacks and long-term treatment.ConclusionsWe identify common pathological findings in patients with LETM as first clinical presentation of MOG-EM which distinguishes it from other forms of LETM and should lead to testing for MOG-IgG in these cases.

The objective of this study was to assess and compare ventricle diameters in patients after decompressive craniectomy by using cranial computed tomography (CCT) versus sonographic duplex technique (SDT). A total of 102 consecutive patients after decompressive craniectomy following brain infarct, bleeding and trauma were examined by CCT and SDT. SDT was performed within 24 h after repeated postinterventional control CCT and the correlation between both methods was assessed via measurement of dimensions of all four ventricles. In addition, midline shifts and overall cerebral anatomy was evaluated. A high correlation was found between CCT and SDT in measuring the diameters of all four ventricles (right lateral r = 0.978, p

Background Endovascular treatment has become standard of care for the treatment of acute ischemic stroke with large vessel occlusion. However, patients treated in clinical practice differ from the selected populations randomized in clinical trials. Aims The German Stroke Registry Endovascular Treatment (GSR-ET) aims at a systematic evaluation of outcome, safety, and process parameters of endovascular stroke treatment in standard of care in Germany. Methods The GSR-ET is an academic, independent, prospective, multicenter, observational registry study. Participating stroke centers from all over of Germany consecutively enroll patients transferred to the angiography suite with an intention to be treated with endovascular stroke treatment. Patients receive regular care. Data are collected as part of clinical routine. Baseline clinical and procedural information and clinical follow-up information after 90 days are recorded. Here, we present an analysis of baseline data of the first 1662 patients included in the GSR-ET. Results The registry was established in June 2015. By 31 December 2017, 1662 patients were enrolled in 23 active sites. Mean age was 72 ± 13 years, 50% were female, and median National Institutes of Health Stroke Scale on admission was 15 (IQR 10–19), 88% had anterior circulation occlusion. Median ASPECT score was 8 (IQR 7–10) prior to intervention. Fifty-nine percent of patients received intravenous thrombolysis prior to thrombectomy. Mean “onset-to-groin” time was 224 ± 176 min. Conclusions Baseline characteristics of stroke patients undergoing thrombectomy in clinical practice differ from those in the randomized trials. The GSR-ET will provide valuable insights into practices of endovascular treatment in routine care of acute ischemic stroke. (GSR-ET ClinicalTrials.gov Identifier: NCT03356392.)

Peripheral facial nerve palsy (FP) is the most common single nerve affection. Most cases are idiopathic, but a relevant fraction is caused by potentially treatable aetiologies including infections. Not all current diagnosis and treatment guidelines recommend routine cerebrospinal fluid (CSF) analysis in the diagnostic workup of this symptom. In this study, we evaluated frequency of aetiologies and relevance of CSF analysis in an interdisciplinary cohort. We retrospectively analysed all cases of newly diagnosed FP treated at a German university medical centre in a 3-year period. Diagnostic certainty was classified for infectious aetiologies according to clinical and CSF parameters. 380 patients with FP were identified, 63 children and 317 adults. Idiopathic Bell´s palsy was predominant in 61 %. 25 % of FP was attributed to infections, and other causes were identified in 14 %. Clinical presentation alone was not conclusive for infectious aetiology, in almost half of patients with infection-attributed FP the reported symptoms or clinical signs did not differ from common symptoms of idiopathic Bell`s palsy. Determination of C-reactive protein or white blood cell count was not helpful in the identification of infectious causes, and radiological imaging was performed in a high proportion of adult patients without conclusive results. Nuchal rigidity was found only in 7 % of patients with CSF pleocytosis. The predominant infectious agents were Borrelia burgdorferi, VZV and HSV, and in most of these cases diagnosis relied on the findings of CSF analysis. This study outlines the importance of careful differential diagnosis to identify infectious causes of facial nerve palsy. The high incidence and frequent unspecific clinical presentation of infectious FP underlines the importance of including CSF analysis in the diagnostic routine workup of FP.

Our objective was to evaluate tumor hemodynamics of paragangliomas of the head and neck. A 2D magnetic resonance projection angiography (MRPA) protocol was developed. Six patients with histologically proven paragangliomas were included in the study. The sequence protocol and data post-processing procedure were optimized in view of a high temporal resolution and maximum contrast-to-noise ratio. Image-time series of two freely orientated slabs could be obtained. Correlation analysis was performed to generate selective arterial and venous weighted angiographic images. Glomus tumors showed a rapid and intense homogeneous enhancement following the intravenous administration of contrast material. The smallest tumors investigated measured 10mm and could be visualized clearly. Time-resolved analysis of the tumor enhancement revealed an early bolus arrival within the vascular bed of the tumor and prolonged incomplete washout indicating blood pooling. The dynamic contrast enhancement of glomus tumors can be evaluated non-invasively with MRPA providing a high temporal resolution and high image quality. The characteristic contrast enhancement of glomus tumors can be helpful in the diagnostic workup of lesions that may mimic glomus tumors

Background: Varicella zoster virus (VZV) reactivation is a common infectious disease in neurology and VZV the second most frequent virus detected in encephalitis. This study investigated characteristics of clinical and laboratory features in patients with VZV infection. Methods: Two hundred eighty two patients with VZV reactivation that were hospitalized in the department of neurology in the time from 2005 to 2013 were retrospectively evaluated. Results from cerebrospinal fluid (CSF) analysis were available from 85 patients. Results: Trigeminal rash was the most common clinical manifestation, followed by segmental rash, CNS infection, facial nerve palsy, postherpetic neuralgia, and radiculitis. MRI of the brain performed in 25/33 patients with encephalitis/meningitis did not show any signs of infection in the brain parenchyma. Only one patient showed contrast enhancement in the hypoglossal nerve. General signs of infection such as fever or elevated CRP values were found in only half of the patients. Furthermore, rash was absent in a quarter of patients with CNS infection and facial nerve palsy, and thus, infection could only be proven by CSF analysis. Although slight inflammatory CSF changes occurred in few patients with isolated rash, the frequency was clearly higher in patients with CNS infection and facial nerve palsy. Conclusion: Monosegmental herpes zoster is often uncomplicated and a diagnostic lumbar puncture is not essential. In contrast, CSF analysis is an essential diagnostic tool in patients with skin lesions and cranial nerve or CNS affection. In patients with neuro-psychiatric symptoms and inflammatory CSF changes analysis for VZV should be performed even in the absence of skin lesions. CA extern

We performed a genome-wide association study in 1,194 controls and 150 patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR, n = 96) or anti-leucine-rich glioma-inactivated1 (anti-LGI1, n = 54) autoimmune encephalitis. Anti-LGI1 encephalitis was highly associated with 27 single-nucleotide polymorphisms (SNPs) in the HLA-II region (leading SNP rs2858870 p = 1.22 × 10

The outcome of bacterial meningitis critically depends on the rapid initiation of bactericidal antibiotic therapy and adequate management of septic shock. In community-acquired meningitis, the choice of an optimum initial empirical antibiotic regimen depends on the regional resistance patterns. Pathogens resistant to antibacterials prevail in nosocomial bacterial meningitis. Dexamethasone is recommended as adjunctive therapy for community-acquired meningitis in developed countries. In comatose patients, aggressive measures to lower intracranial pressure

While the utility of experimental free-access alcohol self-administration paradigms is well established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self-administration studies.Timeline Follow-back drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing 1 of 2 similar alcohol self-administration paradigms. In study 1, 18 social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self-infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D-LAYA), who participated in 2 sessions of alcohol self-infusion up to a maximum BAC of 120 mg%, and a nonexposed age-matched control group of 42 (28 females, mean age 18.4 years) subjects.In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to prestudy levels (p 0.05, respectively). In study 2, alcohol-exposed participants reported 7.1% and non-alcohol-exposed controls 6.5% fewer drinking days at poststudy measurement (p 0.001), while percent heavy drinking days and drinks per drinking day did not differ.These data suggest that participation in intravenous alcohol self-administration experiments does not increase subsequent real-life drinking of young adults.

Background Meningeosis neoplastica is a diffuse metastatic spread of tumor cells in the subarachnoid space. Although first recognized in 1870, systematic investigations regarding cerebrospinal fluid (CSF) constituents in this condition are scarce. Methods Routine CSF samples analyzed from 2001 to 2012 at the Laboratory of Clinical Neurochemistry, University of Göttingen, were re-evaluated. Patients, whose CSF contained malignant cells were included in this study. Results Patients (n = 132, age 59.1 ± 29.1, 58% women) were identified, whose CSF contained malignant cells. The most frequent primary tumor was breast cancer (32.6%), followed by lung cancer (25.0%) and hematologic malignancies (21.2%). The most frequent clinical symptoms were affections of cranial nerves (41.7%), psychiatric abmormalities (32.6%) and radicular lesions of the lower extremities (20.5%). CSF cell counts ranged from 0 to 4692 cells/μl (median 4 cells/μl) and were elevated in 50%. The CSF-to-serum albumin ratio was abnormal in 69.4%. It ranged from 1.8 to 330 x 10-3 (median 17.5 x 10-3). Total CSF protein ranged from 166 to 15,840 mg/l (median 1012 mg/l). CSF lactate was elevated (>2.4 mmol/l) in 65.2% [3.6 mmol/l (1.3/15.6 mmol/l); median (minimum/maximum)]. In 50% of all patients CSF lactate was ≥3.5 mmol/l. The CSF cell counts correlated significantly with the CSF lactate levels and the CSF protein contents. In 56 of 118 CSF samples (47.5%) ferritin was elevated, and in 25 of 65 carcinoma patients (38.5%) an intrathecal production of carcinoembryonic antigen (CEA) was detected. Granulocytes were found in 52.7% of the CSF samples. The percentages of granulocytes and lymphocytes were higher in samples with an elevated cell count. Conclusion In approximately 50% of CSF samples with meningeosis neoplastica the CSF cell count is not elevated. Diagnosis may be missed when only CSF samples with elevated cell counts are subjected to cytological analysis. CSF lactate and protein and the CSF-to-serum albumin ratio are frequently increased in meningeosis neoplastica. The differential diagnosis between meningeosis neoplastica and central nervous infections, in particular tuberculous or fungal meningitis, can be difficult. peerReviewed

Lyme borreliosis is the most frequent tick-borne infection in Europe. It is a multisystemic disease affecting the skin, joints, heart, in rare cases the eyes and regularly the nervous system. Taking current clinical and microbiological guidelines into account, neuroborreliosis can in general be diagnosed and treated successfully. An appropriate guideline-conform antibiotic treatment is effective and in most cases recovery from acute neuroborreliosis is complete. Nevertheless, the evidence base regarding pharmacological treatment needs reform and improvement. Contrary to this scientifically based medical opinion, divergent opinions presented in the media cause uncertainty and confusion among patients and also some physicians. The currently available scientific data on epidemiology, treatment and performance of microbiological testing reveals gaps and therefore a large scope for interpretation. In clinical practice, diagnostics and therapeutic methods that do not fulfill the criteria of evidence-based medicine are widely used due to the uncertain data situation. The Clinical Network Neuroborreliosis (KNN) is a publicly funded network of clinicians and clinical laboratory physicians with the goal to improve knowledge for disease-oriented evaluation of diagnostic and therapeutic methods. In addition, the Robert Koch Institute (RKI) and the KNN are performing an epidemiological study for collation and estimation of the number of neuroborreliosis cases in Germany (aNBorD study).

Bacterial meningitis remains a disease with high mortality and long-term morbidity. Outcome critically depends on the rapid initiation of effective antibiotic therapy. Since a further increase of the incidence of pathogens resistant to antibacterials can be expected both in community-acquired and nosocomial bacterial meningitis, the choice of an optimum initial empirical antibiotic regimen will gain significance. In this context, the use of antibiotics which are bactericidal but do not lyse bacteria, may emerge as a therapeutic option. Conversely, the role of corticosteroids, which decrease the entry of hydrophilic antibacterials into the cerebrospinal fluid, as adjunctive therapy will probably decline as a consequence of the increasing antibiotic resistance of bacteria causing meningitis. Consequent vaccination of all children at present is the most efficient manner to reduce disease burden.

Zusammenfassung Für die Differenzialdiagnose und die Behandlung einer Infektion des Zentralnervensystems kommt dem Liquorbefund eine zentrale Bedeutung zu. Zusammen mit den klinischen und mikrobiologischen Befunden sollte die Art der Infektion rasch erkannt und daraus eine spezifische Behandlung abgeleitet werden. Bereits durch die Konstellation weniger Parameter der Liquorgrundanalytik (Zellzahl, Laktat, Gesamtproteingehalt), die innerhalb kurzer Zeit auch von nicht spezialisierten Zentrallabors geliefert werden, stehen meist die wesentlichen und für die weitere Diagnostik und Therapie entscheidenden Informationen zur Verfügung. Allerdings können die definitiven Diagnosen auch nach Erhalt weiterer Liquorparameter (Zellbilder, Erregerdirektfärbungen, Blut-Liquor-Schrankenfunktion, intrathekale Immunglobulinsynthese, oligoklonale IgG-Banden) ungeklärt bleiben. Daher ist der enge Informationsaustausch zwischen dem Labor und den Klinikern eine wichtige Voraussetzung zur Gestaltung der erweiterten erregerbasierten Spezialdiagnostik und somit erfolgreichen Diagnosestellung.

BackgroundWhether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years).MethodRisk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment.ResultsAn increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ⩾70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41–12.46, p ConclusionsDepression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.

Presence of BB-specific antibodies in the cerebrospinal fluid (CSF) with evidence of their intrathecal production in conjunction with the white cell count in the CSF and typical clinical symptoms is the traditional diagnostic gold standard of Lyme neuroborreliosis (LNB). Few data are available on the CSF lactate concentration in European adults with the diagnosis of acute LNB. The objective of the study was to investigate the CSF changes during acute LNB. Routine CSF parameters [leukocyte count, protein, lactate and albumin concentrations, CSF/serum quotients of albumin (QAlb), IgG, IgA and IgM, and oligoclonal IgG bands] and the Borrelia burgdorferi (BB)-specific antibody index were retrospectively studied in relation to the clinical presentation in patients diagnosed with acute LNB. A total of 118 patients with LNB were categorized into the following groups according to their symptoms at presentation; group 1: polyradiculoneuritis (Bannwarth’s syndrome), group 2: isolated facial palsy and group 3: predominantly meningitic course of the disease. In addition to the CSF of patients with acute LNB, CSF of 19 patients with viral meningitis (VM) and 3 with neurolues (NL) were analyzed. There were 97 patients classified with definite LNB, and 21 as probable LNB. Neck stiffness and fever were reported by 15.3% of patients. Most of these patients were younger than 50 years. Polyradiculoneuritis was frequently found in patients older than 50 years. Lymphopleocytosis was found in all patients. Only 5 patients had a CSF lactate ≥3.5 mmol/l, and the mean CSF lactate level was not elevated (2.1 ± 0.6 mmol/l). The patients with definite LNB had significantly higher lactate levels than patients with probable LNB. Elevated lactate levels were accompanied by fever and headache. In the Reiber nomograms, intrathecal immunoglobulin synthesis was found for IgM in 70.2% followed by IgG in 19.5%. Isoelectric focussing detected an intrathecal IgG synthesis in 83 patients (70.3%). Elevated BB AIs in the CSF were found in 97 patients (82.2%). Patients with VM showed lower CSF protein concentration and CSF/serum quotients of albumin than LNB patients. In acute LNB, all patients had elevated cerebrospinal fluid (CSF) leukocyte counts. In contrast to infections by other bacteria, CSF lactate was lower than 3.5 mmol/l in all but 5 patients. The CSF findings did not differ between polyradiculoneuritis, facial palsy, and meningitis. The CSF in LNB patients strongly differed from CSF in VM patients with respect to protein concentration and the CSF/serum albumin quotient. peerReviewed

Background: Patients with meningitis are often difficult to classify into bacterial (BM) or benign viral (VM) meningitis. To facilitate the differential diagnosis, S100B and Tau protein in the cerebrospinal fluid (CSF) were measured and compared with standard laboratory parameters. Methods: S100BCSF, TauCSF, and routine parameters (CSF leukocyte count, proteinCSF, lactateCSF, serum C-reactive protein, blood leukocyte count and body temperature) were analyzed in 33 patients with microbiologically confirmed BM and in 19 with VM. Their classification accuracy, sensitivity and specificity were studied by receiver operating characteristic (ROC) curves. Results: S100BCSF concentrations were higher in BM than in VM patients (p = 0.03) and showed a promising accuracy (90%) for the differential diagnosis of BM versus VM. Its discriminative properties were comparable to routine parameters. Of all parameters, S100BCSF showed the highest specificity (100%) with an optimal cut-off of 3.1 ng/ml. TauCSF concentrations were useless for the discrimination (p = 0.64). Conclusions: In contrast to TauCSF, S100BCSF concentrations ≧3.1 ng/ml are promising to discriminate bacterial from viral meningitis.

In the healthy human brain the hippocampus is known to work in concert with a variety of cortical brain regions. It has recently been linked to the default network of the brain, with the precuneus being its core hub. Here we studied the remote effects of damage to the hippocampus on functional connectivity patterns of the precuneus. From 14 epilepsy patients with selective, unilateral hippocampal sclerosis and 8 healthy control subjects, we acquired functional MRI data during performance of an object-location memory task. We assessed functional connectivity of a functionally defined region in the precuneus, which showed the typical properties of the default network: significant task-related deactivation, which was reduced in patients compared to control subjects. In control subjects, a largely symmetrical pattern of functional coherence to the precuneus emerged, including canonical default network areas such as ventral medial prefrontal cortex, inferior parietal cortex, and the hippocampi. Assessment of group differences within the default network areas revealed reduced connectivity to the precuneus in ipsilesional middle temporal gyrus and hippocampus in left hippocampal sclerosis patients compared to controls. Furthermore, left hippocampal sclerosis patients showed lower connectivity than right hippocampal sclerosis patients in left middle temporal gyrus, ventral medial prefrontal cortex, and left amygdala. We report remote effects of unilateral hippocampal damage on functional connectivity between distant brain regions associated with the default network of the human brain. These preliminary results underline the impact of circumscribed pathology on functionally connected brain regions.

In order to investigate the factors influencing interhemispheric hippocampal connectivity we used fMRI to assess the time course of hippocampal activity during a spatial memory task. Data were obtained from 14 patients with unilateral hippocampal sclerosis and focal unilateral medial temporal lobe epilepsy. Correlation coefficients between left and right hippocampal BOLD signal fluctuations were determined in each patient as a measure for interhemispheric hippocampal coupling. On the group level a non-parametric Spearman correlation analysis was performed to assess relations of hippocampal connectivity to age, age at epilepsy onset, disease duration, and task performance.In all except for one patient correlation coefficients between left and right hippocampal time courses reached significance. Interhippocampal connectivity exhibited the strongest correlation to age at onset, i.e. patients with later onset showed greater connectivity. It was negatively correlated with disease duration, but not with age.Our findings underline the malicious effect of epileptic seizures on brain structures inevitably engaged with core cognitive functions. The results suggest that a measure of interhemispheric interplay – even at a coarse time-scale – might reflect the functional status of brain structures.

Background: Gelastic epilepsy due to hypothalamic hamartomas is usually a severe condition encompassing both epileptic seizures and an epileptic encephalopathy associated with behavioral and cognitive impairments. Here we report the effects of interstitial radiosurgery in the treatment of this generally pharmacoresistant epilepsy syndrome. Methods: Twenty-four consecutive patients (3–46 years of age, 7 women, mean age 21.9 years, mean duration of epilepsy 17.6 years) with gelastic epilepsy due to MR-ascertained hypothalamic hamartoma and a minimum follow-up period of 1 year were included in this evaluation. Treatment was performed by interstitial radiosurgery using stereotactically implanted 125 I seeds. Effects of treatment on seizure frequency and possible side effects were assessed prospectively. Factors influencing outcome and side effects were analyzed statistically. Results: After a mean 24-month follow-up period following the last radiosurgical treatment, 11/24 patients were seizure free or had seizure reduction of at least 90% (Engel class I and II), in some cases only after repeated treatment. The duration of epilepsy prior to radiosurgery negatively influenced outcome. Treatment was well tolerated in most patients. Headache, fatigue, and lethargy were transient side effects associated with the development of brain edema extending from the implantation site in five patients. Four patients had a weight gain of more than 5 kg which was severe in two patients. The majority of those patients whose cognitive functions initially deteriorated showed subsequent recovery of cognitive functions, but episodic memory in two patients showed persistent decline at 1 year follow-up. Longer disease duration increased the risk for cognitive side effects, and larger hamartoma size and eccentric seed positioning increased the risk for radiogenic brain edema. Neither perioperative mortality nor neurologic impairments, visual field defects, or endocrinologic disturbances were encountered following treatment. Conclusion: Interstitial radiosurgery was efficacious in significantly improving gelastic epilepsy in about half of the patients treated in this series. Weight gain may occur as a side effect, whereas other severe side effects reported following microsurgical removal of the hamartoma were absent. The study results strongly suggest early causal treatment, as chances for seizure control are higher and the risk for cognitive side effects is lower in patients with shorter disease duration.

The encoding of verbal stimuli elicits left-lateralized activation patterns within the medial temporal lobes in healthy adults. In our study, patients with left- and right-sided temporal lobe epilepsy (LTLE, RTLE) were investigated during the encoding and retrieval of word-pair associates using functional magnetic resonance imaging. Functional asymmetry of activation patterns in hippocampal, inferior frontal, and temporolateral neocortical areas associated with language functions was analyzed. Hippocampal activation patterns in patients with LTLE were more right-lateralized than those in patients with RTLE (P

Prior to cochlear implant (CI) surgery in children, the integrity of the auditory pathway is sometimes assessed by electrical ear canal stimulation (ECS). However, the evaluation of reactions as auditory is subjective. To test the prognostic value of ECS, functional magnetic resonance imaging (fMRI) was performed during ECS vicariously in 18 adult CI candidates. Activation of the primary auditory cortex was detected in 9 of 16 cases when auditory sensations during ECS occurred, and tended to be more bilaterally distributed in CI candidates than in normal-hearing controls. ECS sensations only tended to correlate with fMRI activations. However, solely frequency discrimination during electrical stimulation predicted CI outcome, but neither other auditory sensations nor fMRI activations did so satisfactorily, which limits the diagnostic value of these measures. Instead, preoperative residual hearing (nonamplified and amplified) was a robust predictor for CI benefit.

Cerebrospinal fluid analysis is of prime importance to establish an early diagnosis of central nervous system infections. Beside the basic diagnostics containing CSF white cell count, lactate concentration and protein analysis, the targeted search for agents of bacterial, viral or fungal CNS infectious diseases is essential. Decisive methods are bacterial and fungal staining techniques, microbiological culture methods, nucleic acid amplification and antigen detection methods or indirect identification of pathogens by serologic testings including the determination of pathogen-specific intrathecal immunoglobulin synthesis. Besides imparting basic principles of cerebrospinal fluid analysis, this article focuses on special aspects of detection of infectious agents. Well-directed questions and a close communication between clinician and laboratory allow optimal diagnostic analysis for successful confirmation of the diagnosis and for optimal treatment of the patient.

Situationally adaptive behavior relies on the identification of relevant target stimuli, the evaluation of these with respect to the current context and the selection of an appropriate action. We used functional magnetic resonance imaging (fMRI) to disentangle the neural networks underlying these processes within a single task. Our results show that activation of mid-ventrolateral prefrontal cortex (PFC) reflects the perceived presence of a target stimulus regardless of context, whereas context-appropriate evaluation is subserved by mid-dorsolateral PFC. Enhancing demands on response selection by means of response conflict activated a network of regions, all of which are directly connected to motor areas. On the midline, rostral anterior paracingulate cortex was found to link target detection and response selection by monitoring for the presence of behaviorally significant conditions. In summary, we provide new evidence for process-specific functional dissociations in the frontal lobes. In target-centered processing, target detection in the VLPFC is separable from contextual evaluation in the DLPFC. Response-centered processing in motor-associated regions occurs partly in parallel to these processes, which may enhance behavioral efficiency, but it may also lead to reaction time increases when an irrelevant response tendency is elicited.

Gender-related differences in brain activation patterns and their lateralization associated with cognitive functions have been reported in the field of language, emotion, and working memory. Differences have been hypothesized to be due to different cognitive strategies. The aim of the present study was to test whether lateralization of brain activation in the hippocampi during memory processing differs between the sexes. We acquired functional magnetic resonance imaging data from healthy female and male study participants performing a spatial memory task and quantitatively assessed the lateralization of hippocampal activation in each participant. Hippocampal activation was significantly more left lateralized in women, and more right lateralized in men. Correspondingly, women rated their strategy as being more verbal than men did.

INTRODUCTION The growing mastery of motor tasks is one of the most visible changes in the developing child. The cortex is known to play a central role in learning, planning, and performance of motor tasks. We investigated the age dependency of motor cortex activation using functional magnetic resonance imaging (fMRI). METHODS Thirty-two right-handed subjects were studied: 11 children (median age 9 years, range 6 - 10 years), 10 adolescents (median age 13 years, range 11 - 15 years), and 11 adults (median age 27 years, range 23 - 42 years). The subjects performed a simple, paced unilateral motor task (repetitive squeezing of a ball with the right hand). Also, we set up a control experiment (visual stimulation using an alternating checkerboard pattern) in which no age-related differences were expected. RESULTS Compared to children, adults showed significantly increased activation of the bilateral sensorimotor cortex, parietal areas, the supplementary motor area, and the cerebellum. In the visual stimulation experiment there were no age-related differences. CONCLUSION Children show a significant difference in the degree of cortical activation compared to adults when performing a simple motor task. The change in fMRI activation patterns may reflect a maturation process of primary and secondary motor areas.

Several studies have attempted to identify the neuronal basis of sex differences in cognition. However, group differences in cognitive ability rather than genuine neurocognitive differences between the sexes may account for their results. Here, we compare with functional magnetic resonance imaging the relation between gender, individual task performance, and planning-related brain activation. Men and women preselected to display identical performance scores showed a strong relation between individual task performance and activation of the right dorsolateral prefrontal and right inferior parietal cortex activation during a visuospatial planning task. No gender-specific activations were found. However, a different pattern emerged when subjects had to execute the motor responses to the problems. Better performance was associated with right dorsolateral prefrontal and right parahippocampal activations, and females exhibited a stronger right hippocampal activation than males. These findings underline that an individual's performance level rather than his or her sex largely determines the neuronal activation patterns during higher-level cognition.

Production and release of the pneumococcal virulence factors pneumolysin and lipoteichoic and teichoic acid in 75 clinical isolates were investigated. No difference was found between strains causing systemic infection or localized respiratory infection and isolates from asymptomatic carriers. This suggests that the presence of pneumolysin and lipoteichoic and teichoic acid is a necessary but not a sufficient condition for pneumococcal infection and development of invasive disease.

Survivors of prolonged cerebral anoxia often remain in the persistent vegetative state (PVS). In this study, long-term PVS patients were investigated by 15O-H(2)O PET to analyze their central processing of pain. The study was approved by the local Ethics Committee, the experiments were performed in accordance with the Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin for a mean of 1.6 years (range 0.25-4 years) were investigated. We performed functional PET of the brain using 15O-labelled water during electrical nociceptive stimulation. Additionally, a brain metabolism study using 18F-fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set) were acquired in all patients. PET data were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to a study-specific brain template. MRI and FDG PET showed severe cortical impairment at the structural and the functional level, that is, general atrophy of various degrees and a widespread significant hypometabolism, respectively. Pain-induced activation (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate cortex contralateral to the stimulus and in the posterior insula ipsilateral to the stimulus (P

Pneumolysin, a virulence factor of Streptococcus pneumoniae with cytotoxic and proinflammatory activities, occurs at concentrations from 0.85 to 180 ng/ml in cerebrospinal fluid (CSF) of meningitis patients. In pneumococcal cultures and in a rabbit meningitis model, the concentrations of pneumolysin in supernatant and CSF were lower after addition of nonbacteriolytic bactericidal antibiotics (rifampin and clindamycin) than after incubation with ceftriaxone.

Summary: The anticonvulsant agent valproate (VPA) may cause hyperammonemic encephalopathy. Magnetic resonance imaging (MRI) and proton MR spectroscopic (MRS) findings in a patient with VPA-induced hyperammonemic encephalopathy are described. MRI showed a metabolic–toxic lesion pattern with bilateral T2-hyperintense lesions in the cerebellar white matter and in the globus pallidus. MR spectroscopic findings were indistinguishable from hepatic encephalopathy with severe depletion of myoinositol and choline and with glutamine excess. N-Acetylaspartate levels were moderately decreased. Quantitative MRS gave detailed insight into alterations of brain metabolism in VPA-induced encephalopathy.

In three patients with acute occlusion of the basilar artery intra-arterial fibrinolysis resulted in only partial recanalization and revealed severe stenosis as the underlying cause. Application of micro-stents without previous dilatation resulted in vessel re-opening. Two patients had an excellent clinical outcome. One patient died 10 days after the stroke due to brainstem infarction. Emergency primary stent application may improve the outcome in acute basilar artery occlusion, if intra-arterial thrombolysis fails to re-establish a sufficient flow.

Object. Postoperative cerebellar hemorrhage as a complication of supratentorial surgery is an increasingly recognized clinical entity. So far, it has remained unclear whether this complication constitutes an intraoperative or postoperative event. The observation of such cases prompted the authors to analyze retrospectively their series of supratentorial craniotomies. The aim of this study was to determine the incidence of cerebellar hemorrhage and its temporal relationship to supratentorial surgery. Methods. The authors reviewed discharge notes and reports on postoperative computerized tomography (CT) scans for 1650 patients who had undergone supratentorial craniotomy between January 1998 and February 2001. The retrospective study led to the identification of 10 patients who had sustained cerebellar hemorrhage as a complication of supratentorial surgery. Because it was routine to perform CT scanning following craniotomy, an early CT scan obtained within the 1st postoperative hour (mean 24 minutes after wound closure) was available in eight of the 10 patients. In seven of these patients no hemorrhage was found immediately after surgery, and in only one patient was there the suspicion of cerebellar hemorrhage. In the whole series of 10 patients, cerebellar hemorrhage was detected during the later postoperative course, after a mean interval of 7 hours and 35 minutes (range 1 hour and 49 minutes–144 hours) following surgery. The incidence of cerebellar hemorrhage was 0.6% of all patients who underwent supratentorial surgery. Among patients suffering from epilepsy the incidence was 4.6%, and in those patients who underwent temporal lobe resection it was 12.9%. Conclusions. The authors have demonstrated that cerebellar hemorrhage as a complication of supratentorial surgery arises not as an intraoperative event, but as a postoperative event. Resective nontumorous temporal lobe procedures place patients at particular risk for this complication. Evidence suggests that the complication might be precipitated by postoperative suction drainage.

Objective To compare the costs of care for community-dwelling dementia patients with the costs of care for dementia patients living in nursing homes from the societal perspective. Design Cross-sectional bottom-up cost of illness study nested within the multicenter German AgeCoDe-cohort. Setting Community and nursing homes. Participants One hundred twenty-eight community-dwelling dementia patients and 48 dementia patients living in nursing homes. Intervention None. Measurements Utilization and costs of medical care and long term care, including formal and informal social and nursing care based on proxy interviews. Informal care was valued using the replacement cost method. Results Unadjusted mean annual total costs including informal care were €29,930 ($43,997) for community-dwelling patients and €33,482 ($49,218) for patients living in nursing homes. However, multiple regression analysis controlling for age, sex, deficits in basic and instrumental activities of daily living and comorbidity showed that living in the community significantly increased total costs by €11,344 ($16,676; P P Conclusion From the societal perspective care for dementia patients living in the community tends to cost more than care in nursing homes when functional impairment is controlled for.

Tremorogenesis in Parkinson's disease (PD) is assumed to involve a cerebral network including the thalamus. An imaging study was performed on eight PD patients with strictly unilateral resting tremor using fluorodeoxyglucose positron emission tomography coregistered to 3-dimensional magnetic resonance imaging. Increased metabolic activity of high statistical significance (P

A 21-year-old man presented with headache, hypotonia, hypothermia, and somnolence, deteriorating to a Glasgow Coma Scale score of 3 within days. Hormonal testing revealed panhypopituitarism. His cerebral MRI showed a gadolinium-enhancing lesion in the pituitary gland with adjacent changes to the hypothalamus, midbrain, and basal ganglia (figures 1 and 2). Therapy with prednisolone resulted in rapid improvement. Ma2 antibodies were found in the patient’s serum and CSF. FDG-PET demonstrated a tumor mass in the superior mediastinum and histology revealed a mediastinal seminoma. Ma2 antibody–mediated paraneoplastic disease has to be considered as a rare differential diagnosis in patients presenting with acute panhypopituitarism.1 MRI data on admission were provided by the Department of Radiology, Bruderkrankenhaus St. Josef, Paderborn.

We report an intramedullary angiolipoma with spinal cord compression studied by MRI, angiography and CT. Angiolipomas of the spine are rare benign tumours containing vascular and mature adipose elements. They are epidural in more than 90 % of the cases; only three cases of intramedullary angiolipoma are described. The clinical picture is nonspecific, but MRI and CT suggest the diagnosis.

We present the rare case of a 31-year-old man who developed a germinoma 22 years after resection of a mature teratoma of the pineal region. The initial stereotactic biopsy showed a granulomatous inflammation, but no malignant cells. The correct diagnosis could only be confirmed in a second cerebral biopsy, allowing for proper treatment with radiation therapy. The need to consider metachronous germinoma in this setting is discussed.

In the case reported, neurological complaints were pain and dysaesthesiae in the lower back and thigh, as well as paresis of the ileopsoas muscle. MRI of the lumbar spine showed an intradural-extramedullary mass at the level of L1 homogeneously enhancing with gadolinium. This mass was situated at the tip of an intrathecal catheter implanted 11 years before for a morphine trial infusion as therapy for phantom pain after amputation of the right arm. Now, removal of the catheter was performed. Cultures of lumbar CSF and the catheter tip demonstrated coagulase negative staphylococcus. Antibiotic medication with cephalosporines was given for 6 weeks. After removal of the catheter, the patient was free of pain and he progressively regained full neurological function. Although most catheter-associated granulomas reported so far were sterile in nature, bacterial infection should still be considered even years after catheter placement.

The sensitivity of contrast enhanced magnetic resonance imaging (MRI) in the detection of connective tissue reactions accompanying the maturation of subdural haematomas (SDH) was studied. An outer enhancing layer between the SDH and the tabula interna of the vault was shown in 16 out of 17 cases. In early SDH this outer enhancing layer presumably is due to vascular congestion and/or increased vascular permeability. A thickening of the outer enhancing layer and/or an inner enhancing layer between the haematoma and the subarachnoid space was visible in 9 patients and represented a haematoma capsule formed by proliferating granulation tissue. In 5 SDH septations were found, 3 SDH consisted almost completely of enhancing granulation tissue. Thus, contrast enhanced MRI delivers additional information about the structure of SDH, which are useful for determining the extent of surgical treatment especially in chronic SDH.

Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods: Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Molndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. Results: A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). Conclusions: The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians. (C) 2013 The Alzheimer's Association. All rights reserved.

Patients with ventricular drainage may develop lesions of the corpus callosum. In order to study frequency, pathogenesis and clinical relevance of callosal lesions, 301 routine CT investigations of 79 patients with ventricular drainage were reviewed. Hypodense lesions in the anterior part of the corpus callosum were observed in 7 patients with longstanding hydrocephalus of variable origin, in 2 cases the corpus callosum was slightly swollen. All 7 patients showed signs of forced ventricular drainage. The callosal alterations were clinically inapparent and potentially reversible. Knowledge of these lesions is important to avoid misinterpretation.

Objective : Our goal was to optimize the efficiency of contrast material (CM) application in routine examinations of the neck by the use of spiral CT and slow power injection. Materials and Methods : Dynamic studies were performed in 14 patients to establish a set protocol for spiral CT examinations of the neck. Prospectively, 100 patients were examined either by use of the spiral technique with 100 ml CM (30 g iodine) injected in two phases or in conventional CT with 150 ml CM (45 g iodine). Vascular and parenchymal enhancement was evaluated at three distinct levels of the neck. Results : Despite the reduced CM volume in spiral CT, vascular enhancement was significantly higher at all three levels. Parenchymal enhancement was comparable in both groups. CM exploitation in vascular opacification (ratio of mean enhancement to applied CM volume) was 0.87 in spiral CT compared with 0.43 in conventional CT. Conclusion : Spiral CT significantly increases the efficiency of CM application and is well suited for routine examinations of the neck.

Background Social support has been suggested to positively influence cognition and mortality in old age. However, this suggestion has been questioned due to inconsistent operationalisations of social support among studies and the small number of longitudinal studies available. This study aims to investigate the influence of perceived social support, understood as the emotional component of social support, on cognition and mortality in old age as part of a prospective longitudinal multicentre study in Germany. Methods A national subsample of 2,367 primary care patients was assessed twice over an observation period of 18 months regarding the influence of social support on cognitive function and mortality. Perceived social support was assessed using the 14-item version of the FSozU, which is a standardised and validated questionnaire of social support. Cognition was tested by the neuropsychological test battery of the Structured Interview for the Diagnosis of Dementia (SIDAM). The influence of perceived support on cognitive change was analysed by multivariate ANCOVA; mortality was analysed by multivariate logistic and cox regression. Results Sample cognitive change (N = 1,869): Mean age was 82.4 years (SD 3.3) at the beginning of the observation period, 65.9% were female, mean cognition was 49 (SD 4.4) in the SIDAM. Over the observation period cognitive function declined in 47.2% by a mean of 3.4 points. Sample mortality (N = 2,367): Mean age was 82.5 years (SD 3.4), 65.7% were female and 185 patients died during the observation period. Perceived social support showed no longitudinal association with cognitive change (F = 2.235; p = 0.135) and mortality (p = 0.332; CI 0.829-1.743). Conclusions Perceived social support did not influence cognition and mortality over an 18 months observation period. However, previous studies using different operationalisations of social support and longer observation periods indicate that such an influence may exist. This influence is rather small and the result of complex interaction mechanisms between different components of social support; the emotional component seems to have no or only a limited effect. Further research is needed to describe the complex interactions between components of social support. Longer observation periods are necessary and standardised operationalisations of social support should be applied.

The source of Parkinson disease-linked α-synuclein (aSyn) in human cerebrospinal fluid (CSF) remains unknown. We decided to measure the concentration of aSyn and its gradient in human CSF specimens and compared it with serum to explore its origin. We correlated aSyn concentrations in CSF versus serum (QaSyn) to the albumin quotient (Qalbumin) to evaluate its relation to blood–CSF barrier function. We also compared aSyn with several other CSF constituents of either central or peripheral sources (or both) including albumin, neuron-specific enolase, β-trace protein and total protein content. Finally, we examined whether aSyn is present within the structures of the choroid plexus (CP). We observed that QaSyn did not rise or fall with Qalbumin values, a relative measure of blood–CSF barrier integrity. In our CSF gradient analyses, aSyn levels decreased slightly from rostral to caudal fractions, in parallel to the recorded changes for neuron-specific enolase; the opposite trend was recorded for total protein, albumin and β-trace protein. The latter showed higher concentrations in caudal CSF fractions due to the diffusion-mediated transfer of proteins from blood and leptomeninges into CSF in the lower regions of the spine. In postmortem sections of human brain, we detected highly variable aSyn reactivity within the epithelial cell layer of CP in patients diagnosed with a range of neurological diseases; however, in sections of mice that express only human SNCA alleles (and in those without any Snca gene expression), we detected no aSyn signal in the epithelial cells of the CP. We conclude from these complementary results that despite its higher levels in peripheral blood products, neurons of the brain and spinal cord represent the principal source of aSyn in human CSF. peerReviewed