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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.
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Biomarcadores , Enfermedad de Parkinson , Proteómica , Humanos , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/diagnóstico , Biomarcadores/sangre , Masculino , Proteómica/métodos , Femenino , Anciano , Persona de Mediana Edad , Aprendizaje Automático , Trastorno de la Conducta del Sueño REM/sangre , Trastorno de la Conducta del Sueño REM/diagnóstico , Estudios de Casos y Controles , Espectrometría de MasasRESUMEN
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.
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Lysosomal and synaptic dysfunctions are hallmarks in neurodegeneration and potentially relevant as biomarkers, but data on early Parkinson's disease (PD) is lacking. We performed targeted mass spectrometry with an established protein panel, assessing autophagy and synaptic function in cerebrospinal fluid (CSF) of drug-naïve de novo PD, and sex-/age-matched healthy controls (HC) cross-sectionally (88 PD, 46 HC) and longitudinally (104 PD, 58 HC) over 10 years. Multiple markers of autophagy, synaptic plasticity, and secretory pathways were reduced in PD. We added samples from prodromal subjects (9 cross-sectional, 12 longitudinal) with isolated REM sleep behavior disorder, revealing secretogranin-2 already decreased compared to controls. Machine learning identified neuronal pentraxin receptor and neurosecretory protein VGF as most relevant for discriminating between groups. CSF levels of LAMP2, neuronal pentraxins, and syntaxins in PD correlated with clinical progression, showing predictive potential for motor- and non-motor symptoms as a valid basis for future drug trials.
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BACKGROUND AND OBJECTIVES: Whether MRI or CT is preferable for the evaluation of patients with suspected stroke remains a matter of debate, given that the imaging modality acquired at baseline may be a relevant determinant of workflow delays and outcomes with it, in patients with stroke undergoing acute reperfusion therapies. METHODS: In this post hoc analysis of the SWIFT-DIRECT trial that investigated noninferiority of thrombectomy alone vs IV thrombolysis (IVT) + thrombectomy in patients with an acute ischemic anterior circulation large vessel occlusive stroke eligible to receive IVT within 4.5 hours after last seen well, we tested for a potential interaction between baseline imaging modality (MRI/MR-angiography [MRA] vs CT/CT-angiography [CTA]) and the effect of acute treatment (thrombectomy vs IVT + thrombectomy) on clinical and safety outcomes and procedural metrics (primary analysis). Moreover, we examined the association between baseline imaging modality and these outcomes using regression models adjusted for age, sex, baseline NIH Stroke Scale (NIHSS), occlusion location, and Alberta Stroke Program Early CT Score (ASPECTS) (secondary analysis). Endpoints included workflow times, the modified Rankin scale (mRS) score at 90 days, the rate of successful reperfusion, the odds for early neurologic deterioration within 24 hours, and the risk of symptomatic intracranial hemorrhage. The imaging modality acquired was chosen at the discretion of the treating physicians and commonly reflects center-specific standard procedures. RESULTS: Four hundred five of 408 patients enrolled in the SWIFT-DIRECT trial were included in this substudy. Two hundred (49.4%) patients underwent MRI/MRA, and 205 (50.6%) underwent CT/CTA. Patients with MRI/MRA had lower NIHSS scores (16 [interquartile range (IQR) 12-20] vs 18 [IQR 14-20], p = 0.012) and lower ASPECTS (8 [IQR 6-9] vs 8 [IQR 7-9], p = 0.021) compared with those with CT/CTA. In terms of the primary analysis, we found no evidence for an interaction between baseline imaging modality and the effect of IVT + thrombectomy vs thrombectomy alone. Regarding the secondary analysis, MRI/MRA acquisition was associated with workflow delays of approximately 20 minutes, higher odds of functional independence at 90 days (adjusted odds ratio [aOR] 1.65, 95% CI 1.07-2.56), and similar mortality rates (aOR 0.73, 95% CI 0.36-1.47) compared with CT/CTA. DISCUSSION: This post hoc analysis does not suggest treatment effect heterogeneity of IVT + thrombectomy vs thrombectomy alone in large artery stroke patients with different imaging modalities. There was no evidence that functional outcome at 90 days was less favorable following MRI/MRA at baseline compared with CT/CTA, despite significant workflow delays. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03192332.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Arterias , Angiografía por Tomografía Computarizada , Imagen por Resonancia Magnética , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugíaRESUMEN
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética , Neoplasias Encefálicas/patología , Imagen de Difusión por Resonancia Magnética/métodos , EdemaRESUMEN
BACKGROUND: Numerous questions regarding procedural details of distal stroke thrombectomy remain unanswered. This study assesses the effect of anesthetic strategies on procedural, clinical and safety outcomes following thrombectomy for distal medium vessel occlusions (DMVOs). METHODS: Patients with isolated DMVO stroke from the TOPMOST registry were analyzed with regard to anesthetic strategies (ie, conscious sedation (CS), local (LA) or general anesthesia (GA)). Occlusions were in the P2/P3 or A2-A4 segments of the posterior and anterior cerebral arteries (PCA and ACA), respectively. The primary endpoint was the rate of complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3) and the secondary endpoint was the rate of modified Rankin Scale score 0-1. Safety endpoints were the occurrence of symptomatic intracranial hemorrhage and mortality. RESULTS: Overall, 233 patients were included. The median age was 75 years (range 64-82), 50.6% (n=118) were female, and the baseline National Institutes of Health Stroke Scale score was 8 (IQR 4-12). DMVOs were in the PCA in 59.7% (n=139) and in the ACA in 40.3% (n=94). Thrombectomy was performed under LA±CS (51.1%, n=119) and GA (48.9%, n=114). Complete reperfusion was reached in 73.9% (n=88) and 71.9% (n=82) in the LA±CS and GA groups, respectively (P=0.729). In subgroup analysis, thrombectomy for ACA DMVO favored GA over LA±CS (aOR 3.07, 95% CI 1.24 to 7.57, P=0.015). Rates of secondary and safety outcomes were similar in the LA±CS and GA groups. CONCLUSION: LA±CS compared with GA resulted in similar reperfusion rates after thrombectomy for DMVO stroke of the ACA and PCA. GA may facilitate achieving complete reperfusion in DMVO stroke of the ACA. Safety and functional long-term outcomes were comparable in both groups.
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Anestésicos , Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Arteria Cerebral Posterior , Resultado del Tratamiento , Accidente Cerebrovascular/cirugía , Trombectomía/efectos adversos , Trombectomía/métodos , Estudios Retrospectivos , Procedimientos Endovasculares/métodosRESUMEN
Introduction: Multi-professional interdisciplinary tumor boards (ITB) are essential institutions to discuss all newly diagnosed, relapsed or complex cancer patients in a team of specialists to find an optimal cancer care plan for each individual patient with regard to national and international clinical practice guidelines, patient´s preference and comorbidities. In a high-volume cancer center, entity-specific ITBs take place at least once a week discussing a large number of patients. To a high level of expertise and dedication, this also requires an enormous amount of time for physicians, cancer specialists and administrative support colleagues, especially for radiologists, pathologists, medical oncologists and radiation oncologists, who must attend all cancer-specific boards according to certification requirements. Methods: In this 15-month prospective German single-center analysis, we examined the established structures of 12 different cancer-specific ITBs at the certified Oncology Center and demonstrate tools helping to optimize processes before, during and after the boards for optimal, time-saving procedures. Results: By changing pathways, introducing revised registration protocols and new digital supports we could show that the workload of preparation by radiologists and pathologists could be reduced significantly by 22.9% (p=<0.0001) and 52.7% (p=<0.0001), respectively. Furthermore, two questions were added to all registration forms about the patient´s need for specialized palliative care support that should lead to more awareness and early integration of specialized help. Discussion: There are several ways to reduce the workload of all ITB team members while maintaining high quality recommendations and adherence to national and international guidelines.
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PURPOSE: Our article is dedicated to describing the state-of-the-art in imaging techniques for assessing prodromal dementia with Lewy bodies (pro-DLB) with a psychiatric-onset. MATERIALS AND METHODS: Imaging biomarker techniques are discussed. RESULTS: (123)-I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography (123I-FP-CIT SPECT) seems to be a promising method as it reveals abnormalities in pro-DLB with a psychiatric-onset. New potential biomarkers can be revealed via novel techniques, such as manual segmentation in magnetic resonance imaging (MRI), which helps detect atrophy of the substantia innominata in pro-DLB with a psychiatric-onset as opposed to an onset with mild cognitive impairment (MCI). FDG-PET can also help us distinguish patients with mixed pro-DLB from those pro-DLB patients with a psychiatric-onset or MCI-onset. Changes in large-scale networks in the posterior standard mode and in attentional networks could be early signs in resting-state functional MRI to characterise pro-DLB. CONCLUSIONS: In conclusion, there is a wide range of techniques that need to be explored in large-scale studies and are of promising value in understanding pro-DLB with a psychiatric-onset.
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Enfermedad de Alzheimer , Enfermedad por Cuerpos de Lewy , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad de Alzheimer/diagnóstico , Tomografía Computarizada de Emisión de Fotón Único/métodos , Neuroimagen , Imagen por Resonancia Magnética , Síntomas ProdrómicosRESUMEN
BACKGROUND: 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. METHODS: 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. RESULTS: 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 mm2 for PSP, 105 ± 17 mm2 for DLB, 130 ± 26 mm2 for PD and 135 ± 23 mm2 for CTRL. The mean segmented volumes of the midbrain were 5595 ± 680 mm3 for PSP, 6051 ± 566 mm3 for DLB, 6646 ± 802 mm3 for PD and 6882 ± 844 mm3 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. CONCLUSIONS: 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.
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Enfermedad por Cuerpos de Lewy , Enfermedad de Parkinson , Parálisis Supranuclear Progresiva , Humanos , Anciano , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Parálisis Supranuclear Progresiva/patología , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/patología , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Imagen por Resonancia Magnética/métodos , Atrofia/patología , Diagnóstico DiferencialRESUMEN
BACKGROUND: Prodromal dementia with Lewy bodies (DLB) can emerge with the onset of mild cognitive impairment (MCI). Standard biomarkers can help identify such patients to improve therapy and treatment strategies. Our review aims to describe the latest evidence on promising biomarkers in prodromal DLB with MCI onset (MCI-LB). METHODS: We selected articles on different biomarkers in MCI-LB from PubMed and conducted a narrative review. RESULTS: We identified potentially promising clinical biomarkers, e.g., (1) assessing autonomic symptoms specifically, (2) describing the cognitive profile in several subdomains including executive and visual functions, and (3) measuring the speed of speech. In addition, we describe the measurement of seeding amplification assays of alpha-synuclein in cerebrospinal fluid as a relevant biomarker for MCI-LB. Electroencephalographic markers, as in calculating the theta/beta ratio or intermittent delta activity, or analyzing peak frequency in electroencephalography-methods also potentially useful once they have been validated in large patient cohorts. The 18F fluorodesoxyglucose positron emission tomography (FDG-PET) technique is also discussed to investigate metabolic signatures, as well as a specific magnetic resonance imaging (MRI) technique such as for the volumetric region of interest analysis. CONCLUSIONS: These biomarker results suggest that MCI-LB is a promising field for the use of biomarkers other than established ones to diagnose early prodromal DLB. Further large-scale studies are needed to better evaluate and subsequently use these promising biomarkers in prodromal DLB.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infection which can affect the central nervous system. In this study, we sought to investigate associations between neuroimaging findings with clinical, demographic, blood and cerebrospinal fluid (CSF) parameters, pre-existing conditions and the severity of acute COVID-19. MATERIALS AND METHODS: Retrospective multicenter data retrieval from 10 university medical centers in Germany, Switzerland and Austria between February 2020 and September 2021. We included patients with COVID-19, acute neurological symptoms and cranial imaging. We collected demographics, neurological symptoms, COVID-19 severity, results of cranial imaging, blood and CSF parameters during the hospital stay. RESULTS: 442 patients could be included. COVID-19 severity was mild in 124 (28.1%) patients (moderate n = 134/30.3%, severe n = 43/9.7%, critical n = 141/31.9%). 220 patients (49.8%) presented with respiratory symptoms, 167 (37.8%) presented with neurological symptoms first. Acute ischemic stroke (AIS) was detected in 70 (15.8%), intracranial hemorrhage (IH) in 48 (10.9%) patients. Typical risk factors were associated with AIS; extracorporeal membrane oxygenation therapy and invasive ventilation with IH. No association was found between the severity of COVID-19 or blood/CSF parameters and the occurrence of AIS or IH. DISCUSSION: AIS was the most common finding on cranial imaging. IH was more prevalent than expected but a less common finding than AIS. Patients with IH had a distinct clinical profile compared to patients with AIS. There was no association between AIS or IH and the severity of COVID-19. A considerable proportion of patients presented with neurological symptoms first. Laboratory parameters have limited value as a screening tool.
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COVID-19 , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , COVID-19/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/etiología , Neuroimagen , Factores de Riesgo , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiologíaRESUMEN
Background Evidence supporting a potential benefit of thrombectomy for distal medium vessel occlusions (DMVOs) of the anterior cerebral artery (ACA) is, to the knowledge of the authors, unknown. Purpose To compare the clinical and safety outcomes between mechanical thrombectomy (MT) and best medical treatment (BMT) with or without intravenous thrombolysis for primary isolated ACA DMVOs. Materials and Methods Treatment for Primary Medium Vessel Occlusion Stroke, or TOPMOST, is an international, retrospective, multicenter, observational registry of patients treated for DMVO in daily practice. Patients treated with thrombectomy or BMT alone for primary ACA DMVO distal to the A1 segment between January 2013 and October 2021 were analyzed and compared by one-to-one propensity score matching (PSM). Early outcome was measured by the median improvement of National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours. Favorable functional outcome was defined as modified Rankin scale scores of 0-2 at 90 days. Safety was assessed by the occurrence of symptomatic intracerebral hemorrhage and mortality. Results Of 154 patients (median age, 77 years; quartile 1 [Q1] to quartile 3 [Q3], 66-84 years; 80 men; 94 patients with MT; 60 patients with BMT) who met the inclusion criteria, 110 patients (median age, 76 years; Q1-Q3, 67-83 years; 50 men; 55 patients with MT; 55 patients with BMT) were matched. DMVOs were in A2 (82 patients; 53%), A3 (69 patients; 45%), and A3 (three patients; 2%). After PSM, the median 24-hour NIHSS point decrease was -2 (Q1-Q3, -4 to 0) in the thrombectomy and -1 (Q1-Q3, -4 to 1.25) in the BMT cohort (P = .52). Favorable functional outcome (MT vs BMT, 18 of 37 [49%] vs 19 of 39 [49%], respectively; P = .99) and mortality (MT vs BMT, eight of 37 [22%] vs 12 of 39 [31%], respectively; P = .36) were similar in both groups. Symptomatic intracranial hemorrhage occurred in three (2%) of 154 patients. Conclusion Thrombectomy appears to be a safe and technically feasible treatment option for primary isolated anterior cerebral artery occlusions in the A2 and A3 segment with clinical outcomes similar to best medical treatment with and without intravenous thrombolysis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zhu and Wang in this issue.
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Isquemia Encefálica , Infarto de la Arteria Cerebral Anterior , Accidente Cerebrovascular , Masculino , Humanos , Anciano , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Isquemia Encefálica/etiología , Estudios Retrospectivos , Infarto de la Arteria Cerebral Anterior/etiología , Resultado del Tratamiento , Trombectomía/métodosRESUMEN
PURPOSE: Diffusion-weighted imaging (DWI) is important for differentiating residual tumor and subacute infarctions in early postoperative magnetic resonance imaging (MRI) of central nervous system (CNS) tumors. In cases of pneumocephalus and especially in the presence of intraventricular trapped air, conventional echo-planar imaging (EPI) DWI is distorted by susceptibility artifacts. The performance and robustness of a newly developed DWI sequence using the stimulated echo acquisition mode (STEAM) was evaluated in patients after neurosurgical operations with early postoperative MRI. METHODS: We compared EPI and STEAM DWI of 43 patients who received 3Tesla MRI within 72â¯h after a neurosurgical operation between 1 October 2019 and 30 September 2021. We analyzed susceptibility artifacts originating from air and blood and whether these artifacts compromised the detection of ischemic changes after surgery. The DWI sequences were (i) visually rated and (ii) volumetrically analyzed. RESULTS: In 28 of 43 patients, we found severe and diagnostically relevant artifacts in EPI DWI, but none in STEAM DWI. In these cases, in which artifacts were caused by intracranial air, they led to a worse detection of ischemic lesions and thus to a possible failed diagnosis or lack of judgment using EPI DWI. Additionally, volumetric analysis demonstrated a 14% smaller infarct volume detected with EPI DWI. No significant differences in visual rating and volumetric analysis were detected among the patients without severe artifacts. CONCLUSION: The newly developed version of STEAM DWI with highly undersampled radial encodings is superior to EPI DWI in patients with postoperative pneumocephalus.
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Neoplasias , Neumocéfalo , Humanos , Imagen Eco-Planar/métodos , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética , Imagen de Difusión por Resonancia Magnética/métodos , Sistema Nervioso Central , ArtefactosRESUMEN
OBJECTIVE: To validate the ERC-recommended facial landmark-distance for oropharyngeal airway sizing in children. METHODS: We conducted a prospective observational study in anaesthetised, spontaneously breathing children ≤12 years undergoing cranial MRI. Oropharyngeal airways were inserted following the distance from the maxillary incisors to the mandibular angle. Primary outcome was the rate of properly sized oropharyngeal airways on MRI, defined as the distal end positioned within 10 mm from the epiglottis without contacting it. Secondary outcomes were the occurrence of tongue protrusion, oropharyngeal airways clinical efficacy, and related adverse events. Furthermore, we calculated probabilities for the estimation of proper size when considering five facial landmark-distances and optimal rules based on biometric parameters. RESULTS: In 94 children with a mean (SD) age of 4.7 (±3) years, 47.9% [95%-CI 38%-57.9%] oropharyngeal airways were properly sized, while 23.4% [95%-CI 15.9%-33%] were undersized, and 28.7% [95%-CI 20.5%-38.7%] oversized. Tongue protrusion occurred in 59.1% [95%-CI 38.2%-77.2%] of undersized and 15.6% [95%-CI 7.6%-29.2%] of properly sized oropharyngeal airways. No oropharyngeal airway required replacement. Comparing probabilities for five landmark-distances, "maxillary incisors to the angle of the mandible" proved superior for proper sizing at 41.2% [95%-CI 32%-51.7%]. The best-fit formula was "22.43 + 17.54 × log(weight[kg])" with a probability of 61.7% [95%-CI 51.5%-70.9%]. CONCLUSION: Although the facial landmark-distance "maxillary incisors to the angle of the mandible" does not reliably predict oropharyngeal airway size, no clinical problems have been encountered. Since it can be considered the least inaccurate facial landmark-distance, it can serve as an approximation, but the efficacy of oropharyngeal airways should be evaluated clinically. REGISTERED CLINICAL TRIAL: German Clinical Trials Register; DRKS00025918.
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Cara , Orofaringe , Humanos , Niño , Lactante , Preescolar , Orofaringe/diagnóstico por imagen , Respiración , Imagen por Resonancia Magnética , Estudios ProspectivosRESUMEN
BACKGROUND: A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS: SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS: Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION: Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT03192332.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Trombolisis Mecánica , Accidente Cerebrovascular , Humanos , Fibrinolíticos/uso terapéutico , Terapia Trombolítica/métodos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/cirugía , Accidente Cerebrovascular Isquémico/etiología , Resultado del Tratamiento , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Reperfusión , Trombolisis Mecánica/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.
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Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Masculino , Activador de Tejido Plasminógeno , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Tiempo de Tratamiento , Terapia Trombolítica , Trombectomía , Isquemia Encefálica/terapia , Resultado del Tratamiento , FibrinolíticosRESUMEN
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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Background: Benefits and challenges resulting from advances in genetic diagnostics are two sides of the same coin. Facilitation of a correct and timely diagnosis is paralleled by challenges in interpretation of variants of unknown significance (VUS). Focusing on an individual VUS-re-classification pipeline, this study offers a diagnostic approach for clinically suspected hereditary muscular dystrophy by combining the expertise of an interdisciplinary team. Methods: In a multi-step approach, a thorough phenotype assessment including clinical examination, laboratory work, muscle MRI and histopathological evaluation of muscle was performed in combination with advanced Next Generation Sequencing (NGS). Different in-silico tools and prediction programs like Alamut, SIFT, Polyphen, MutationTaster and M-Cap as well as 3D- modeling of protein structure and RNA-sequencing were employed to determine clinical significance of the LAMA2 variants. Results: Two previously unknown sequence alterations in LAMA2 were detected, a missense variant was classified initially according to ACMG guidelines as a VUS (class 3) whereas a second splice site variant was deemed as likely pathogenic (class 4). Pathogenicity of the splice site variant was confirmed by mRNA sequencing and nonsense mediated decay (NMD) was detected. Combination of the detected variants could be associated to the LGMDR23-phenotype based on the MRI matching and literature research. Discussion: Two novel variants in LAMA2 associated with LGMDR23-phenotype are described. This study illustrates challenges of the genetic findings due to their VUS classification and elucidates how individualized diagnostic procedure has contributed to the accurate diagnosis in the spectrum of LGMD.
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BACKGROUND: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. METHODS: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. FINDINGS: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047). INTERPRETATION: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. FUNDING: Medtronic and University Hospital Bern.