Abstract
In community-acquired bacterial meningitis (CABM) intracranial vascular alterations are devastating complications which are triggered by neuroinflammation and result in worse clinical ...outcome. The Neutrophil-to-Lymphocyte ratio (NLR) represents a reliable parameter of the inflammatory response. In this study we analyzed the association between NLR and elevated cerebral blood flow velocity (CBFv) in CABM-patients. This study included all (CABM)-patients admitted to a German tertiary center between 2006 and 2016. Patients’ demographics, in-hospital measures, neuroradiological data and clinical outcome were retrieved from institutional databases. CBFv was assessed by transcranial doppler (TCD). Patients’, radiological and laboratory characteristics were compared between patients with/without elevated CBFv. Multivariate-analysis investigated parameters independently associated with elevated CBFv. Receiver operating characteristic(ROC-)curve analysis was undertaken to identify the best cut-off for NLR to discriminate between increased CBFv. 108 patients with CABM were identified. 27.8% (30/108) showed elevated CBFv. Patients with elevated CBFv and normal CBFv, respectively had a worse clinical status on admission (Glasgow Coma Scale: 12 9–14 vs. 14 11–15;
p
= 0.005) and required more often intensive care (30/30 100.0% vs. 63/78 80.8%;
p
= 0.01).The causative pathogen was
S. pneumoniae
in 70%. Patients with elevated CBFv developed more often cerebrovascular complications with delayed cerebral ischemia (DCI) within hospital stay (
p
= 0.031). A significantly higher admission-NLR was observed in patients with elevated CBFv (median IQR: elevated CBFv:24.0 20.4–30.2 vs. normal CBFv:13.5 8.4–19.5;
p
< 0.001). Multivariate analysis, revealed NLR to be significantly associated with increased CBFv (Odds ratio 95%CI 1.042 1.003–1.084;
p
= 0.036). ROC-analysis identified a NLR of 20.9 as best cut-off value to discriminate between elevated CBFv (AUC = 0.713,
p
< 0.0001, Youden's Index = 0.441;elevated CBFv: NLR ≥ 20.9 19/3063.5% vs. normal CBFv: NLR > 20.9 15/7819.2%;
p
< 0.001). Intracranial vascular complications are common among CABM-patients and are a risk factor for unfavorable outcome at discharge. Elevated NLR is independently associated with high CBFv and may be useful in predicting patients’ prognosis.
Altered gut microbiota may trigger or accelerate alpha-synuclein aggregation in the enteric nervous system in Parkinson's disease (PD). While several previous studies observed gut microbiota ...alterations in PD, findings like diversity indices, and altered bacterial taxa itself show a considerable heterogeneity across studies. We recruited 179 participants, of whom 101 fulfilled stringent inclusion criteria. Subsequently, the composition of the gut microbiota in 71 PD patients and 30 healthy controls was analyzed, sequencing V3–V4 regions of the bacterial 16S ribosomal RNA gene in fecal samples. Our goal was (1) to evaluate whether gut microbiota are altered in a southern German PD cohort, (2) to delineate the influence of disease duration, stage, and motor impairment, and (3) to investigate the influence of PD associated covariates like constipation and coffee consumption. Aiming to control for a large variety of covariates, strict inclusion criteria were applied. Finally, propensity score matching was performed to correct for, and to delineate the effect of remaining covariates (non-motor symptom (NMS) burden, constipation, and coffee consumption) on microbiota composition. Prior to matching altered abundances of distinct bacterial classes, orders, families, and genera were observed. Both, disease duration, and stage influenced microbiome composition. Interestingly, levodopa equivalent dose influenced the correlation of taxa with disease duration, while motor impairment did not. Applying different statistical tests, and after propensity score matching to control for NMS burden, constipation and coffee consumption,
Faecalibacterium
and
Ruminococcus
were most consistently reduced in PD compared to controls. Taken together, similar to previous studies, alterations of several taxa were observed in PD. Yet, further controlling for PD associated covariates such as constipation and coffee consumption revealed a pivotal role of these covariates. Our data highlight the impact of these PD associated covariates on microbiota composition in PD. This suggests that altered microbiota may mediate the protective effect of i.e., coffee consumption and the negative effect of constipation in PD.
Hematoma expansion (HE) is the most important therapeutic target during acute care of patients with intracerebral hemorrhage (ICH). Imaging biomarkers such as non-contrast CT (NCCT) markers have been ...associated with increasing risk for HE. The aim of the present study was to evaluate the influence of NCCT markers with functional long-term outcome and with HE in patients with deep (basal ganglia and thalamus) ICH who represent an important subgroup of patients at the highest risk for functional deterioration with HE due to the eloquence of the affected brain region.
From our prospective institutional database, all patients maximally treated with deep ICH were included and retrospectively analyzed. NCCT markers were recorded at diagnostic imaging, ICH volume characteristics were volumetrically evaluated, and all patients received follow-up imaging within 0-48 h. We explored associations of NCCT makers with unfavorable functional outcome, defined as modified Rankin scale 4-6, after 12 months and with HE. Bias and confounding were addressed by multivariable regression modeling.
In 322 patients with deep ICH, NCCT markers were distributed as follows: irregular shape: 69.6%, heterogenous density: 55.9%, hypodensities: 52.5%, island sign: 19.3%, black hole sign: 11.5%, and blend sign: 4.7%. Upon multivariable regression analyses, independent associations were documented with the functional outcome for irregular shape (aOR: 2.73, 95%CI: 1.42-5.22,
= 0.002), heterogenous density (aOR: 2.62, 95%CI: 1.40-4.90,
= 0.003) and island sign (aOR: 2.54, 95%CI: 1.05-6.14,
= 0.038), and with HE for heterogenous density (aOR: 5.01, 95%CI: 1.93-13.05,
= 0.001) and hypodensities (aOR: 3.75, 95%CI: 1.63-8.62,
= 0.002).
NCCT markers are frequent in deep ICH patients and provide important clinical implications. Specifically, markers defined by diverging intra-hematomal densities provided associations with a 5-times higher risk for HE and a 2.5-times higher likelihood for unfavorable functional long-term outcome. Hence, these markers allow the identification of patients with deep ICH at high risk for clinical deterioration due to HE.
Based on artificial intelligence (AI), 3D angiography (3DA) is a novel postprocessing algorithm for "DSA-like" 3D imaging of cerebral vasculature. Because 3DA requires neither mask runs nor digital ...subtraction as the current standard 3D-DSA does, it has the potential to cut the patient dose by 50%. The object was to evaluate 3DA's diagnostic value for visualization of intracranial artery stenoses (IAS) compared to 3D-DSA.
3D-DSA datasets of IAS (n
= 10) were postprocessed using conventional and prototype software (Siemens Healthineers AG, Erlangen, Germany). Matching reconstructions were assessed by two experienced neuroradiologists in consensus reading, considering image quality (IQ), vessel diameters (VD
), vessel-geometry index (VGI = VD
/VD
), and specific qualitative/quantitative parameters of IAS (e.g., location, visual IAS grading low-/medium-/high-grade and intra-/poststenotic diameters d
in mm). Using the NASCET criteria, the percentual degree of luminal restriction was calculated.
In total, 20 angiographic 3D volumes (n
= 10; n
= 10) were successfully reconstructed with equivalent IQ. Assessment of the vessel geometry in 3DA datasets did not differ significantly from 3D-DSA (VD
:
= 0.994,
= 0.0001; VD
:
= 0.994,
= 0.0001; VGI:
= 0.899,
= 0.0001). Qualitative analysis of IAS location (3DA/3D-DSA:n
= 1, n
= 1, n
= 4, n
= 2, n
= 2) and the visual IAS grading (3DA/3D-DSA:n
= 3, n
= 5, n
= 2) revealed identical results for 3DA and 3D-DSA, respectively. Quantitative IAS assessment showed a strong correlation regarding intra-/poststenotic diameters (r
= 0.995, p
= 0.0001; r
= 0.995, p
= 0.0001) and the percentual degree of luminal restriction (r
= 0.981; p
= 0.0001).
The AI-based 3DA is a resilient algorithm for the visualization of IAS and shows comparable results to 3D-DSA. Hence, 3DA is a promising new method that allows a considerable patient-dose reduction, and its clinical implementation would be highly desirable.
BackgroundSpinocerebellar ataxia type 17 (SCA17) is a rare, autosomal-dominantly inherited neurodegenerative disease caused by a CAG/CAA repeat expansion in the TATA-box-binding protein (TBP) gene. ...Clinically, SCA17 is quite variable and includes cerebellar and hypokinetic-rigid symptoms, chorea as well as cognitive impairment. Thus, the disease is also called a Huntington disease phenocopy (HDL-4).Case HistoryA 39-year-old female patient presented with cognitive impairment and behavioural symptoms with affect lability and impulsivity that had been present since the age of 35 and had progressed rapidly over time. Clinical findings included stance and gait ataxia, saccadic gaze, chanting speech and generalized chorea. The family history was unremarkable. Brain imaging showed isolated cerebellar atrophy with normal visualisation of the basal ganglia. The molecular-genetic diagnostics for Huntington’s disease was unremarkable. In the extended human genetic examination, a homozygous expanded allele with 44 CAG/CAA repeats in the TBP gene was detected, thus confirming the diagnosis of SCA17. Within 2 years, the patient showed a clear increase in cognitive changes and behavioural disturbance.ConclusionsIn the present case, a homozygous expanded allele with 44 CAG/CAA repeats in the TBP gene leads to an early age of manifestation, in contrast to SCA17 patients with comparable heterozygous intermediate repeat expansions with reduced penetrance. Furthermore, the index patient showed faster progression of symptoms, suggesting that SCA17 homozygous trinucleotide expansions are associated with a more severe disease course even with intermediate repeat expansions.
Background and purpose
Sarcoidosis is a granulomatous disease of unknown etiology affecting the central nervous system in up to 15% of the patients. Diagnosis of neurosarcoidosis is very challenging ...due to the heterogeneity of its clinical manifestation. This study intended to evaluate the distribution of cerebral lesion sites and the potential presence of specific lesion clusters in neurosarcoidosis patients using voxel-based lesion symptom mapping (VLSM).
Methods
Patients with neurosarcoidosis were retrospectively identified and included between 2011 and 2022. Cerebral lesion sites were correlated voxel-wise with presence and absence of neurosarcoidosis using non-parametric permutation test. Multiple sclerosis patients served as controls for the VLSM-analysis.
Results
Thirty-four patients (mean age 52 ± 15 years) of whom 13 were diagnosed with possible, 19 with probable and 2 with confirmed neurosarcoidosis were identified. Lesion overlap of neurosarcoidosis patients demonstrated a distribution of white matter lesions in all brain areas, with a periventricular predilection similar to multiple sclerosis. In contrast to multiple sclerosis controls, no propensity for lesions in proximity of the corpus callosum was observed. Neurosarcoidosis lesions appeared smaller and lesion volume was lower in the neurosarcoidosis cohort. The VLSM analysis showed minor associations between neurosarcoidosis and damaged voxels in the bilateral frontobasal cortex.
Conclusions
The VLSM analysis yielded significant associations in the bilateral frontal cortex, suggesting that leptomeningeal inflammatory disease with following cortical involvement is a quite specific feature in neurosarcoidosis. Lesion load was lower in neurosarcoidosis than in multiple sclerosis. However, no specific pattern of subcortical white matter lesions in neurosarcoidosis was revealed.
The role of neuroinflammation in the pathophysiology of seizures is increasingly recognized, and the evaluation of potential biochemical markers of inflammatory processes in seizures and status ...epilepticus (SE), such as C‐reactive protein (CRP), has gained attention. The present study assessed the first CRP level obtained in an SE episode regarding its value for SE outcome prediction. Among 362 admissions for SE during the study period, 231 episodes satisfied the inclusion criteria. Higher initial CRP concentrations were independently associated with in‐hospital mortality and poor functional outcome at discharge in logistic regression models adjusting for SE severity, severity of SE etiology, and development of treatment refractoriness. Therefore, initial CRP levels may add to the prediction of SE prognosis. The pathomechanisms through which CRP is linked with the prognosis of SE, however, remain to be established.
In patients with lobar intracerebral hemorrhage (ICH), etiologic characterization represents a tradeoff between feasibility, resource allocation, and diagnostic certainty. This study investigated the ...accuracy and clinical utility of the simplified Edinburgh CT criteria to identify underlying cerebral amyloid angiopathy (CAA).
This external validation analyzed 210 consecutive patients with lobar ICH and available CT and MRI studies from a prospective single-center observational cohort study (2006-2015, Longitudinal Cohort Study on ICH Care UKER-ICH, NCT03183167). We investigated the interrater variability and diagnostic accuracy of the simplified Edinburgh CT-based criteria for identification of ICH associated with probable CAA according to MRI-based modified Boston criteria as a reference standard. We evaluated the utility of the simplified Edinburgh criteria by decision curve analysis, comparing the theoretical clinical net benefit (weighted benefit-harm at varying threshold probabilities) of the high-risk category (finger-like projections and subarachnoid hemorrhage) for ruling in and the low-risk category (neither finger-like projections nor subarachnoid hemorrhage) for ruling out with the assumptions of no or all patients having CAA (default strategies).
Of 210 patients, 70 (33.3%) had high risk, 67 (31.9%) had medium risk, and 73 (34.8%) had low risk for CAA-associated ICH according to simplified Edinburgh CT criteria, showing moderate interrater variability. Discrimination was good (area under the receiver operating characteristics curve 0.74, 95% CI 0.67-0.81) without evidence of poor calibration (Hosmer-Lemeshow,
= 0.54) for validation of MRI-based diagnosis of probable CAA (n = 94 of 210, 44.8%). The rule-in criteria (high risk), had 87.1% (79.3%-92.3%) specificity, and the rule-out criteria (low risk), had 80.9% (71.1%-88.0%) sensitivity. Decision curve analysis suggested a theoretical clinical net benefit for ruling in but not for ruling out probable CAA compared to default strategies.
Applying the simplified Edinburgh CT criteria during diagnostic workup seems clinically useful and may accurately identify CAA in patients with lobar ICH.
ClinicalTrials.gov Identifier: NCT03183167.
This study provides Class II evidence that in patients with lobar hemorrhages, the simplified Edinburgh criteria accurately identify those at high risk of CAA.
Background and Purpose
The relationship between ischemic stroke site and occurrence of poststroke epilepsy (PSE) is incompletely understood. This study intended to evaluate incidence and temporal ...profiles of seizures and to correlate ischemic lesion sites with PSE using voxel‐based lesion symptom mapping (VLSM).
Methods
Patients with imaging‐confirmed first‐ever ischemic stroke without prior history of epilepsy were prospectively included. Demographic data, cardiovascular risk factors, and National Institute of Health Stroke Scale (NIHSS) scores were assessed. Data on seizures and modified Rankin scale scores were determined within a 90‐day period after stroke onset. Ischemic lesion sites were correlated voxel wise with occurrence of PSE using nonparametric permutation test. Age‐ and sex‐matched patients with first‐ever ischemic strokes without PSE after 90 days served as controls for the VLSM analysis.
Results
The stroke database contained 809 patients (mean age: 68.4 ± 14.2 years) with first‐ever imaging‐confirmed ischemic strokes without history of epilep. Incidence of PSE after 90‐day follow‐up was 2.8%. Five additional patients were admitted to the emergency department with a seizure after 90‐day follow‐up. Fifty percent of the seizures occurred in the acute phase after stroke. PSE patients had higher NIHSS scores and infarct volumes compared to controls without PSE (p < .05). PSE patients had infarcts predominantly involving the cerebral cortex. The hemisphere‐specific VLSM analysis shows associations between PSE and damaged voxels in the left‐hemispheric temporo‐occipital transition zone.
Conclusions
The data indicate that PSE occurs in a small proportion of patients with rather large ischemic strokes predominantly involving the cerebral cortex. Especially patients with ischemic lesions in the temporo‐occipital cortex are vulnerable to develop PSE.
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