Abstract Parkinson’s disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to the disabling motor stage. ...We need objective biomarkers for early/pre-motor disease stages to be able to intervene and slow the underlying neurodegenerative process. Here, we validate a targeted multiplexed mass spectrometry assay for blood samples from recently diagnosed motor Parkinson’s patients ( n = 99), pre-motor individuals with isolated REM sleep behaviour disorder (two cohorts: n = 18 and n = 54 longitudinally), and healthy controls ( n = 36). Our machine-learning model accurately identifies all Parkinson patients and classifies 79% of the pre-motor individuals up to 7 years before motor onset by analysing the expression of eight proteins—Granulin precursor, Mannan-binding-lectin-serine-peptidase-2, Endoplasmatic-reticulum-chaperone-BiP, Prostaglaindin-H2-D-isomaerase, Interceullular-adhesion-molecule-1, Complement C3, Dickkopf-WNT-signalling pathway-inhibitor-3, and Plasma-protease-C1-inhibitor. Many of these biomarkers correlate with symptom severity. This specific blood panel indicates molecular events in early stages and could help identify at-risk participants for clinical trials aimed at slowing/preventing motor Parkinson’s disease.
Flow disruption achieved by braided intrasaccular implants is a novel treatment strategy for cerebrovascular aneurysms. We hypothesized that the degree of intra-aneurysmal flow disruption can be ...quantified in vitro and is influenced by device position across the aneurysm neck. We tested this hypothesis using the Medina® Embolization Device (MED).
Ten different patient-specific elastic vascular models were manufactured. Models were connected to a pulsatile flow circuit, filled with a blood-mimicking fluid and treated by two operators using a single MED. Intra-aneurysmal flow velocity was measured using conventional and high-frequency digital subtraction angiography (HF-DSA) before and after each deployment. Aneurysm neck coverage by the implanted devices was assessed with flat detector computed tomography on a three-point Likert scale.
A total of 80 individual MED deployments were performed by the two operators. The mean intra-aneurysmal flow velocity reduction after MED implantation was 33.6% (27.5-39.7%). No significant differences in neck coverage (p = 0.99) or flow disruption (p = 0.84) were observed between operators. The degree of flow disruption significantly correlated with neck coverage (ρ = 0.42, 95% CI: 0.21-0.59, p = 0.002) as well as with neck area (ρ = -0,35, 95% CI: -0.54 --0.13, p = 0.024). On multiple regression analysis, both neck coverage and total neck area were independent predictors of flow disruption.
The degree of intra-aneurysmal flow disruption after MED implantation can be quantified in vitro and varies considerably between different aneurysms and different device configurations. Optimal device coverage across the aneurysm neck improves flow disruption and may thus contribute to aneurysm occlusion.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most false negative findings in DWI of ischemic stroke are in patients with minor deficits clinically localized to the brainstem. Our goal was to evaluate the benefit of a thin-sliced sagittal DWI in ...addition to conventional axial DWI at 1.5T for the detection of brainstem infarctions.
Data of patients with symptoms consistent with acute and subacute brainstem infarction and an MRI examination including standard axial DWI and thin-sliced sagittal DWI were retrospectively analyzed. Patients with the later diagnosis of a TIA, an inflammation or a tumor of the brainstem were excluded from analysis. Diffusion restrictions were identified by two independent raters blinded for the final clinical diagnosis in three separate reading steps: First, only axial DWI, secondly only sagittal DWI, and lastly both DWIs together. Presence and size of DWI-lesions were documented for each plane. Differences between the observers were settled in consensus in a separate joint reading.
Of 73 included patients, 46 patients were clinically diagnosed with brainstem infarction. Inter-observer agreement was excellent for the detection of brainstem lesions in axial and sagittal DWI (kappa = 0.94 and 0.97). In 28/46 patients (60.9%) lesions were detected in the axial plane alone, whereas in 6 more patients (73.9%) lesions were detected in the review of both sequences together. All lesions undetectable in the axial plane were smaller than 5 mm in cranio-caudal direction.
Thin-sliced sagittal DWI in addition to axial DWI improves the detection rate of brainstem infarction with little additional expenditure of time.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim was to evaluate a novel method of threshold-free prediction of brain infarct from computed tomography perfusion (CTP) imaging in comparison to conventional ischemic thresholds. In a ...multicenter cohort of 161 patients with acute large vessel occlusion who received endovascular therapy, brain infarction was predicted by CTP using (1) optimized parameter cut-off values determined by ROC curve analysis and (2) probabilistic logistic regression threshold-free analysis. Predicted infarct volumes and prediction errors based on four perfusion parameter maps were compared against observed infarcts. In 93 patients with successful recanalization, the mean observed infarct volume was 35.7 ± 61.9 ml (the reference for core infarct not savable by reperfusion). Optimal parameter thresholds predicted mean infarct volumes between 53.2 ± 44.4 and 125.0 ± 95.4 ml whereas threshold-free analysis predicted mean volumes between 35.9 ± 28.5 and 36.1 ± 29.0 ml. In 68 patients with persistent occlusion, the mean observed infarct volume was 113.4 ± 138.3 ml (the reference to define penumbral infarct savable by reperfusion). Predicted mean infarct volumes by parameter thresholds ranged from 91.4 ± 81.5 to 163.8 ± 135.7 ml, by threshold-free analysis from 113.2 ± 89.9 to 113.5 ± 89.0 ml. Threshold-free prediction of infarct volumes had a higher precision and lower patient-specific prediction error than conventional thresholding. Penumbra to core lesion mismatch estimate may therefore benefit from threshold-free CTP analysis.
Glioblastoma with multiple foci (mGBM) and multiple brain metastases share several common features on magnetic resonance imaging (MRI). A reliable preoperative diagnosis would be of clinical ...relevance. The aim of this study was to explore the differences and similarities between mGBM and multiple brain metastases on MRI.
We performed a retrospective analysis of 50 patients with mGBM and compared them with a cohort of 50 patients with multiple brain metastases (2-10 lesions) histologically confirmed and treated at our department between 2015 and 2020. The following imaging characteristics were analyzed: lesion location, distribution, morphology, (T2-/FLAIR-weighted) connections between the lesions, patterns of contrast agent uptake, apparent diffusion coefficient (ADC)-values within the lesion, the surrounding T2-hyperintensity, and edema distribution.
A total of 210 brain metastases and 181 mGBM lesions were analyzed. An infratentorial localization was found significantly more often in patients with multiple brain metastases compared to mGBM patients (28 vs. 1.5%, p < 0.001). A T2-connection between the lesions was detected in 63% of mGBM lesions compared to 1% of brain metastases. Cortical edema was only present in mGBM. Perifocal edema with larger areas of diffusion restriction was detected in 31% of mGBM patients, but not in patients with metastases.
We identified a set of imaging features which improve preoperative diagnosis. The presence of T2-weighted imaging hyperintensity connection between the lesions and cortical edema with varying ADC-values was typical for mGBM.
Although Dementia with Lewy bodies (DLB) is the second most common form of dementia in elderly patients, it remains underdiagnosed compared with Alzheimer's (AD) and Parkinson's diseases (PD). This ...may be explained by overlapping clinical symptoms, e.g. Parkinsonism. While current MRI research focuses primarily on atrophy patterns of the frontal and temporal lobes, we focus on brainstem characteristics of DLB. In particular, we focused on brainstem atrophy patterns distinguishing DLB from Progressive Supranuclear Palsy (PSP) and PD based as the most common differential diagnoses.
We identified patients diagnosed with DLB, PD, PSP, and a control group (CTRL) in our psychiatric and neurological archives. All patients with competing diagnoses and without a high-quality T1 MPRAGE 3D dataset were excluded. We assessed atrophy patterns in all patients (1) manually and (2) using FastSurfer's segmentation algorithm in combination with FreeSurfer's brainstem volumetric calculations. We compared classical measurement methods and ratios with automated volumetric approaches.
One hundred two patients were enrolled and evaluated in this study. Patients with DLB (n = 37) showed on average less atrophy of the brainstem than patients with PSP (n = 21), but a significantly more pronounced atrophy than patients with PD (n = 36) and the control group (CTRL, n = 8). The mean measured sagittal diameters of the midbrain were 8.17 ± 1.06 mm (mean ± standard deviation) for PSP, 9.45 ± 0.95 mm for DLB, 10.37 ± 0.99 mm for PD and 10.74 ± 0.70 for CTRL. The mean measured areas of the midbrain were 81 ± 18 mm
for PSP, 105 ± 17 mm
for DLB, 130 ± 26 mm
for PD and 135 ± 23 mm
for CTRL. The mean segmented volumes of the midbrain were 5595 ± 680 mm
for PSP, 6051 ± 566 mm
for DLB, 6646 ± 802 mm
for PD and 6882 ± 844 mm
for CTRL. The calculated midbrain pons ratios did not show superiority over the absolute measurements of the midbrain for distinguishing PSP from DLB. Because of the relatively uniform atrophy throughout the brainstem, the ratios were not suitable for distinguishing DLB from PD.
DLB patients exhibit homogenous atrophy of the brainstem and can be distinguished from patients with PSP and PD by both manual measurement methods and automated volume segmentation using absolute values or ratios.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background The best strategy to identify patients with suspected acute ischemic stroke and unknown vessel status (large vessel occlusion) for direct transport to a comprehensive stroke center instead ...of a nearer primary stroke center is unknown. Methods and Results We used mathematical modeling to estimate the impact of 10 increasingly complex prehospital triage strategy paradigms on the reduction of population-wide stroke-related disability. The model was applied to suspected acute ischemic stroke patients in (1) abstract geographies, and (2) 3 real-world urban and rural geographies in Germany. Transport times were estimated based on stroke center location and road infrastructure; spatial distribution of emergency medical services calls was derived from census data with high spatial granularity. Parameter uncertainty was quantified in sensitivity analyses. The mothership strategy was associated with a statistically significant population-wide gain of 8 to 18 disability-adjusted life years in the 3 real-world geographies and in most simulated abstract geographies (net gain -4 to 66 disability-adjusted life years). Of the more complex paradigms, transportation of patients with clinically suspected large vessel occlusion based on a dichotomous large vessel occlusion detection scale to the nearest comprehensive stroke center yielded an additional clinical benefit of up to 12 disability-adjusted life years in some rural but not in urban geographies. Triage strategy paradigms based on probabilistic conditional modeling added an additional benefit of 0 to 4 disability-adjusted life years over less complex strategies if based on variable cutoff scores. Conclusions Variable stroke severity cutoff scores were associated with the highest reduction in stroke-related disability. The mothership strategy yielded better clinical outcome than the drip-'n'-ship strategy in most geographies.
Background and aims Postinterventional hypothermia is a frequent complication in patients with large-vessel occlusion strokes (LVOS) after mechanical thrombectomy (MT). This inadvertent hypothermia ...might potentially have neuroprotective but also adverse effects on patients’ outcomes. The aim of the study was to determine the rate of hypothermia in patients with LVOS receiving MT and its influence on functional outcome. Methods We performed a monocentric, retrospective study using a prospectively derived databank, including all LVOS patients receiving MT between 2015 and 2021. Predictive values of postinterventional body temperature and body temperature categories (hyperthermia (≥38°C), normothermia (35°C–37.9°C), and hypothermia (<35°C)) on functional outcome were analyzed using multivariable Bayesian logistic regression models. Favorable outcome was defined as modified Rankin Scale (mRS) ≤3. Results Of the 480 included LVOS patients with MT (46.0% men; mean ± SD age 73 ± 12.9 years), 5 (1.0%) were hyperthermic, 382 (79.6%) normothermic, and 93 (19.4%) hypothermic. Postinterventional hypothermia was significantly associated with unfavorable functional outcome (mRS > 3) after 90 days (OR 2.06, 95% CI 1.01–4.18, p = 0.045). For short-term functional outcome, patients with hypothermia had a higher discharge NIHSS (OR 1.38, 95% CI 1.06 to 1.79, p = 0.015) and a higher change of NIHSS from admission to discharge (OR 1.35, 95% CI 1.03 to 1.76, p = 0.029). Conclusion Approximately a fifth of LVOS patients in this cohort were hypothermic after MT. Hypothermia was an independent predictor of unfavorable functional outcomes. Our findings warrant a prospective trial investigating active warming during MT.
Dementia with Lewy bodies (DLB) is the second most common dementia type in patients older than 65 years. Its atrophy patterns remain unknown. Its similarities to Parkinson's disease and differences ...from Alzheimer's disease are subjects of current research.
The aim of our study was (i) to form a group of patients with DLB (and a control group) and create a 3D MRI data set (ii) to volumetrically analyze the entire brain in these groups, (iii) to evaluate visual and manual metric measurements of the innominate substance for real-time diagnosis, and (iv) to compare our groups and results with the latest literature. We identified 102 patients with diagnosed DLB in our psychiatric and neurophysiological archives. After exclusion, 63 patients with valid 3D data sets remained. We compared them with a control group of 25 patients of equal age and sex distribution. We evaluated the atrophy patterns in both (1) manually and (2) via Fast Surfers segmentation and volumetric calculations. Subgroup analyses were done of the CSF data and quality of 3D T1 data sets.
Concordant with the literature, we detected moderate, symmetric atrophy of the hippocampus, entorhinal cortex and amygdala, as well as asymmetric atrophy of the right parahippocampal gyrus in DLB. The caudate nucleus was unaffected in patients with DLB, while all the other measured territories were slightly too moderately atrophied. The area under the curve analysis of the left hippocampus volume ratio (< 3646mm
) revealed optimal 76% sensitivity and 100% specificity (followed by the right hippocampus and left amygdala). The substantia innominata's visual score attained a 51% optimal sensitivity and 84% specificity, and the measured distance 51% optimal sensitivity and 68% specificity in differentiating DLB from our control group.
In contrast to other studies, we observed a caudate nucleus sparing atrophy of the whole brain in patients with DLB. As the caudate nucleus is known to be the last survivor in dopamine-uptake, this could be the result of an overstimulation or compensation mechanism deserving further investigation. Its relative hypertrophy compared to all other brain regions could enable an imaging based identification of patients with DLB via automated segmentation and combined volumetric analysis of the hippocampus and amygdala.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Dementia with Lewy bodies (DLB) is a type of dementia often diagnosed in older patients. Since its initial symptoms range from delirium to psychiatric and cognitive symptoms, the diagnosis ...is often delayed.
Objectives
In our study, we evaluated the magnetic resonance imaging (MRI) of patients suffering from DLB in correlation with their initial symptoms taking a new pragmatic approach entailing manual measurements in addition to an automated volumetric analysis of MRI.
Methods
A total of 63 patients with diagnosed DLB and valid 3D data sets were retrospectively and blinded evaluated. We assessed atrophy patterns (1) manually for the substantia innominata and (2)
via
FastSurfer for the most common supratentorial regions. Initial symptoms were categorized by (1) mild cognitive impairment (MCI), (2) psychiatric episodes, and (3) delirium.
Results
Manual metric MRI measurements revealed moderate, but significant substantia-innominata (SI) atrophy in patients with a psychiatric onset. FastSurfer analysis revealed no regional volumetric differences between groups.
Conclusion
The SI in patients with DLB and a psychiatric-onset is more atrophied than that in patients with initial MCI. Our results suggest potential differences in SI between DLB subtypes at the prodromal stage, which are useful when taking a differential-diagnostic approach. This finding should be confirmed in larger patient cohorts.
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