Publications by authors named "Christian Enzinger"

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

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Background And Objectives: Data from randomized trials on the treatment effect of pure thrombolysis in patients with vessel occlusion are lacking. We examined data from a corresponding subsample of patients from the multicenter, randomized, placebo-controlled WAKE-UP trial to determine whether MRI-guided IV thrombolysis with alteplase in unknown-onset ischemic stroke benefits patients presenting with vessel occlusion.

Methods: Patients with an acute ischemic lesion visible on MRI diffusion-weighted imaging but no marked parenchymal hyperintensity on fluid-attenuated inversion recovery images were randomized to treatment with IV alteplase or placebo.

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MRI has considerably increased our pathophysiological knowledge of age-related brain abnormalities. Brain abnormalities regularly seen on MRI of older adults are atrophy, and changes related to small vessel disease (SVD). SVD-related changes include white matter hyperintensities (WMH), lacunes, microbleeds, microinfarcts and perivascular spaces.

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Article Synopsis
  • White matter hyperintensities (WMH) increase with age and vary significantly between individuals, prompting the need for age- and sex-specific data for better assessment.
  • This study pooled data from nearly 15,000 healthy individuals aged 18-97 to analyze WMH volumes using MRI and established centile curves based on age and sex.
  • Findings reveal that WMH volumes increase significantly with age, with females having larger volumes, and these changes follow different patterns based on specific white matter locations, providing valuable normative data for clinical interpretations.
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Background And Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS.

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  • A significant portion of spontaneous intracerebral hemorrhages (ICH) arise from macrovascular causes, necessitating a swift diagnosis, often through invasive procedures like digital subtraction angiography (DSA), which aren't suitable for all patients.
  • This study aimed to develop a new risk stratification score, the MACRO score, incorporating MRI findings to improve the identification of macrovascular causes of ICH.
  • The MACRO score successfully incorporates various patient factors and MRI markers, demonstrating better predictive capabilities than current CT-based scores, validating its effectiveness in a diverse patient population.
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  • Cerebral small vessel disease (SVD) can lead to various cerebrovascular issues, but research on sex differences in SVD is limited.
  • This study analyzed data from over 20,000 patients with acute ischemic stroke to examine whether the presence and severity of cerebral microbleeds (CMB) and other SVD markers differ between males and females.
  • Results showed that males had more frequent CMB while females had fewer lacunes but higher severe white matter hyperintensities, indicating distinct SVD characteristics based on sex.
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  • White matter hyperintensities (WMH) are linked to cognitive impairment but solely measuring their volume doesn't fully explain the cognitive deficits.
  • Lesion network mapping (LNM) offers a new way to assess how WMH connects with brain networks, potentially improving our understanding of their impact on cognition.
  • In a study of 3,485 patients, LNM scores outperformed WMH volumes in predicting cognitive performance, especially in attention, processing speed, and verbal memory, but not for language functions.
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In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function.

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Delirium is a common complication in acute stroke patients, occurring in 15-35% of all stroke unit admissions and is associated with prolonged hospital stay and a poor post-stroke prognosis. Managing delirium in acute stroke patients necessitates an intensive and multiprofessional therapeutic approach, placing a significant burden on healthcare staff. However, dedicated practical recommendations for delirium management developed for the population of acute stroke patients are lacking.

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Objectives: Cerebral amyloid angiopathy (CAA)-associated lobar intracerebral hemorrhage (ICH) has a high risk of recurrence, but the underlying mechanisms remain uncertain. We, therefore, aimed to characterize patterns of recurrent ICH.

Methods: We investigated early recurrent ICH (≥1 recurrent ICH event within 90 days of the index event) and ICH clusters (≥2 ICH events within 90 days at any time point) in 2 large cohorts of consecutive patients with first-ever ICH and available MRI.

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Hippocampal atrophy (tissue loss) has become a fundamental outcome parameter in clinical trials on Alzheimer's disease. To accurately estimate hippocampus volume and track its volume loss, a robust and reliable segmentation is essential. Manual hippocampus segmentation is considered the gold standard but is extensive, time-consuming, and prone to rater bias.

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The optic nerve is frequently involved in multiple sclerosis (MS). However, MRI of the optic nerve is considered optional in the differential diagnosis of optic neuropathy symptoms either at presentation or in established MS. In addition, unlike spinal cord imaging in comparable scenarios, no role is currently recommended for optic nerve MRI in patients presenting with optic neuritis for its confirmation, to plan therapeutic strategy, within the MS diagnostic framework, nor for the detection of subclinical activity in established MS.

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Objectives: To explore the experiences and acceptability of music-cued motor imagery (MCMI), music-cued gait training (MCGT), and combined MCMI and MCGT (MCMI-MCGT) in people with multiple sclerosis (pwMS). We also aimed to explore participants' self-rated health status postintervention and gather recommendations for further programme development.

Design: Qualitative study alongside the double-blind randomised controlled real and imagined gait training with music-cueing (RIGMUC) multicentre trial of MCMI, MCGT and MCMI-MCGT.

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Background And Objectives: Chronic kidney disease (CKD) may be associated with the pathogenesis and phenotype of cerebral small vessel disease (SVD), which is the commonest cause of intracerebral hemorrhage (ICH). The purpose of this study was to investigate the associations of CKD with ICH neuroimaging phenotype, volume, and location, total burden of small vessel disease, and its individual components.

Methods: In 2 cohorts of consecutive patients with ICH evaluated with MRI, we investigated the frequency and severity of CKD based on established Kidney Disease Improving Global Outcomes criteria, requiring estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.

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Background: Actual and imagined cued gait trainings have not been compared in people with multiple sclerosis (MS).

Objective: To analyze the effects of cued motor imagery (CMI), cued gait training (CGT), and combined CMI and cued gait training (CMI-CGT) on motor, cognitive, and emotional functioning, and health-related quality of life in people with MS.

Methods: In this double-blind randomized parallel-group multicenter trial, people with MS were randomized (1:1:1) to CMI, CMI-CGT, or CGT for 30 minutes, 4×/week for 4 weeks.

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Background: Walking impairment is one of the most prevalent symptoms in people with multiple sclerosis (pwMS). In this study, we aimed to explore the usefulness of a simple walking test, the Timed 25 Foot Walk (T25FW), in detecting subtle differences in "fully ambulatory" pwMS compared to HC.

Methods: We therefore investigated retrospective data from a clinical real-life cohort of 650 pwMS.

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Background: Knowledge about factors that are associated with post-stroke cognitive outcome is important to identify patients with high risk for impairment. We therefore investigated the associations of white matter integrity and functional connectivity (FC) within the brain's default-mode network (DMN) in acute stroke patients with cognitive outcome three months post-stroke.

Methods: Patients aged between 18 and 85 years with an acute symptomatic MRI-proven unilateral ischemic middle cerebral artery infarction, who had received reperfusion therapy, were invited to participate in this longitudinal study.

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Background: Recent small subcortical infarcts (RSSI) are the neuroimaging hallmark feature of small vessel disease (SVD)-related acute lacunar stroke. Long-term data on recurrent cerebrovascular events including their aetiology after RSSI are scarce.

Patients And Methods: This retrospective study included all consecutive ischaemic stroke patients with an MRI-confirmed RSSI (in the supply area of a small single brain artery) at University Hospital Graz between 2008 and 2013.

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Purpose: QSM provides insight into healthy brain aging and neuropathologies such as multiple sclerosis (MS), traumatic brain injuries, brain tumors, and neurodegenerative diseases. Phase data for QSM are usually acquired from 3D gradient-echo (3D GRE) scans with long acquisition times that are detrimental to patient comfort and susceptible to patient motion. This is particularly true for scans requiring whole-brain coverage and submillimeter resolutions.

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Introduction: Brain viscoelasticity as assessed by magnetic resonance elastography (MRE) has been discussed as a promising surrogate of microstructural alterations due to neurodegenerative processes. Existing studies indicate that multiple sclerosis (MS) is associated with a global reduction in brain stiffness. However, no study to date systematically investigated the MS-related characteristics of brain viscoelasticity separately in normal-appearing white matter (NAWM), deep gray matter (DGM) and T2-hyperintense white matter (WM) lesions.

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Introduction: White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating cognitive health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. We propose that lesion network mapping (LNM), enables to infer if brain networks are connected to lesions, and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders.

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Article Synopsis
  • White matter hyperintensities (WMH) correlate with major dementia causes, particularly arteriolosclerosis and amyloid pathology; the study aimed to pinpoint specific WMH locations linked to vascular risk and amyloid-β (Aβ42) status.* -
  • Data from 3,132 patients were analyzed, revealing that vascular risk was associated with WMH in the anterior/superior corona radiata and middle cerebellar peduncle, while Aβ42 positivity linked to WMH in the posterior thalamic radiation and splenium.* -
  • The findings suggest WMH patterns differ between vascular risk factors and Aβ42 pathology, indicating the need for further research on how these factors impact white matter
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Background: Individual disease-modifying treatment (DMT) decisions might differ between female and male people with MS (pwMS).

Objective: To identify sex-related differences in DMT strategies over the past decades in a real-world setting.

Methods: In this cohort study, data from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), a nationwide prospectively collected registry mandatory for reimbursement, were retrospectively analyzed.

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