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Background and purpose: Impairment of executive functions (EFs) is a common cognitive symptom post‐stroke and affects independence in daily activities. Previous studies have often relied on brief cognitive tests not fully considering the wide spectrum of EF subdomains. A detailed assessment of EFs was used to examine which of the subdomains and tests have the strongest predictive value on post‐stroke functional outcome and institutionalization in long‐term follow‐up. Methods: A subsample of 62 patients from the Helsinki Stroke Aging Memory Study was evaluated with a battery of seven neuropsychological EF tests 3 months post‐stroke and compared to 39 healthy control subjects. Functional impairment was evaluated with the modified Rankin Scale (mRS) and Instrumental Activities of Daily Living (IADL) scale at 3 months, and with the mRS at 15 months post‐stroke. Institutionalization was reviewed from the national registers of permanent hospital admissions in up to 21‐year follow‐up. Results: The stroke group performed more poorly than the control group in multiple EF tests. Tests of inhibition, set shifting, initiation, strategy formation and processing speed were associated with the mRS and IADL scale in stroke patients. EF subdomain scores of inhibition, set shifting and processing speed were associated with functional outcome. In addition, inhibition was associated with the risk for earlier institutionalization. Conclusions: Executive function was strongly associated with post‐stroke functional impairment. In follow‐up, poor inhibition was related to earlier permanent institutionalization. The results suggest the prognostic value of EF subdomains after stroke. [ABSTRACT FROM AUTHOR]

Background and Purpose: Executive dysfunction and slowed processing speed are central cognitive impairments in cerebral small vessel disease (cSVD). It is unclear whether the subcomponents of executive functions become equally affected and whether computerized tests are more sensitive in detecting early cognitive changes over traditional tests. The associations of specific executive abilities (cognitive flexibility, inhibitory control, working memory) and processing speed with white matter hyperintensities (WMHs) and Instrumental Activities of Daily Living (IADL) were examined., Methods: In the Helsinki Small Vessel Disease Study, 152 older individuals without stroke or dementia were assessed with brain magnetic resonance imaging and comprehensive neuropsychological evaluation. WMH volumes were obtained with automated segmentation. Executive functions and processing speed measures included established paper-and-pencil tests and the computer-based Flexible Attention Test (FAT), Simon task and Sustained Attention to Response Task., Results: White matter hyperintensity volume and IADL were associated with multiple cognitive measures across subdomains independently of demographic factors. The highest effect sizes were observed for FAT numbers and number-letter tasks (tablet modifications from the Trail Making Test), FAT visuospatial span, Simon task and semantic verbal fluency. Some of the widely used tests such as Stroop inhibition, phonemic fluency and digit span were not significantly associated with either WMHs or IADL., Conclusion: Processing speed and executive function subcomponents are broadly related to functional abilities and WMH severity in covert cSVD, but the strength of associations within subdomains is heavily dependent on the assessment method. Digital tests providing precise measures of reaction times and response accuracy seem to outperform many of the conventional paper-and-pencil tests., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Intravenous thrombolysis (IVT) before endovascular treatment (EVT) for acute ischemic stroke might induce intracerebral hemorrhages which could negatively affect patient outcomes. Measuring white matter lesions size using deep learning (DL-WML) might help safely guide IVT administration. We aimed to develop, validate, and evaluate a DL-WML volume on CT compared to the Fazekas scale (WML-Faz) as a risk factor and IVT effect modifier in patients receiving EVT directly after IVT., Methods: We developed a deep-learning model for WML segmentation on CT and validated with internal and external test sets. In a post hoc analysis of the MR CLEAN No-IV trial, we associated DL-WML volume and WML-Faz with symptomatic-intracerebral hemorrhage (sICH) and 90-day functional outcome according to the modified Rankin Scale (mRS). We used multiplicative interaction terms between WML measures and IVT administration to evaluate IVT treatment effect modification. Regression models were used to report unadjusted and adjusted common odds ratios (cOR/acOR)., Results: In total, 516 patients from the MR CLEAN No-IV trial (male/female, 291/225; age median, 71 [IQR, 62-79]) were analyzed. Both DL-WML volume and WML-Faz are associated with sICH (DL-WML volume acOR, 1.78 [95%CI, 1.17; 2.70]; WML-Faz acOR, 1.53 95%CI [1.02; 2.31]) and mRS (DL-WML volume acOR, 0.70 [95%CI, 0.55; 0.87], WML-Faz acOR, 0.73 [95%CI 0.60; 0.88]). Only in the unadjusted IVT effect modification analysis WML-Faz was associated with more sICH if IVT was given (p = 0.046). Neither WML measure was associated with worse mRS if IVT was given., Conclusion: DL-WML volume and WML-Faz had a similar relationship with functional outcome and sICH. Although more sICH might occur in patients with more severe WML-Faz receiving IVT, no worse functional outcome was observed., Clinical Relevance Statement: White matter lesion severity on baseline CT in acute ischemic stroke patients has a similar predictive value if measured with deep learning or the Fazekas scale. Safe administration of intravenous thrombolysis using white matter lesion severity should be further studied., Key Points: White matter damage is a predisposing risk factor for intracranial hemorrhage in patients with acute ischemic stroke but remains difficult to measure on CT. White matter lesion volume on CT measured with deep learning had a similar association with symptomatic intracerebral hemorrhages and worse functional outcome as the Fazekas scale. A patient-level meta-analysis is required to study the benefit of white matter lesion severity-based selection for intravenous thrombolysis before endovascular treatment., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Singing-based treatments of aphasia can improve language outcomes, but the neural benefits of group-based singing in aphasia are unknown. Here, we set out to determine the structural neuroplasticity changes underpinning group-based singing-induced treatment effects in chronic aphasia. Twenty-eight patients with at least mild nonfluent poststroke aphasia were randomized into two groups that received a 4-month multicomponent singing intervention (singing group) or standard care (control group). High-resolution T1 images and multishell diffusion-weighted MRI data were collected in two time points (baseline/5 months). Structural gray matter (GM) and white matter (WM) neuroplasticity changes were assessed using language network region of interest-based voxel-based morphometry (VBM) and quantitative anisotropy-based connectometry, and their associations to improved language outcomes (Western Aphasia Battery Naming and Repetition) were evaluated. Connectometry analyses showed that the singing group enhanced structural WM connectivity in the left arcuate fasciculus (AF) and corpus callosum as well as in the frontal aslant tract (FAT), superior longitudinal fasciculus, and corticostriatal tract bilaterally compared with the control group. Moreover, in VBM, the singing group showed GM volume increase in the left inferior frontal cortex (Brodmann area 44) compared with the control group. The neuroplasticity effects in the left BA44, AF, and FAT correlated with improved naming abilities after the intervention. These findings suggest that in the poststroke aphasia group, singing can bring about structural neuroplasticity changes in left frontal language areas and in bilateral language pathways, which underpin treatment-induced improvement in speech production., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Sihvonen et al.)

The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can promote white matter (WM) microstructure and grey matter (GM) volume while supporting auditory and cognitive functioning and emotional well-being as well as counteracting age-related cognitive decline. Adding a social component to music training, choir singing is a popular leisure activity among older adults, but a systematic account of its potential to support healthy brain structure, especially with regard to ageing, is currently missing. The present study used quantitative anisotropy (QA)-based diffusion MRI connectometry and voxel-based morphometry to explore the relationship of lifetime choir singing experience and brain structure at the whole-brain level. Cross-sectional multiple regression analyses were carried out in a large, balanced sample (N = 95; age range 21-88) of healthy adults with varying levels of choir singing experience across the whole age range and within subgroups defined by age (young, middle-aged, and older adults). Independent of age, choir singing experience was associated with extensive increases in WM QA in commissural, association, and projection tracts across the brain. Corroborating previous work, these overlapped with language and limbic networks. Enhanced corpus callosum microstructure was associated with choir singing experience across all subgroups. In addition, choir singing experience was selectively associated with enhanced QA in the fornix in older participants. No associations between GM volume and choir singing were found. The present study offers the first systematic account of amateur-level choir singing on brain structure. While no evidence for counteracting GM atrophy was found, the present evidence of enhanced structural connectivity coheres well with age-typical structural changes. Corroborating previous behavioural studies, the present results suggest that regular choir singing holds great promise for supporting brain health across the adult life span., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: To examine the associations between recent stressful life events and self-reported fatigue and depressive symptoms in patients with mild traumatic brain injury., Design: Observational cohort study., Participants: Patients (aged 18-68 years) with mild traumatic brain injury (n = 99) or lower extremity orthopaedic injury (n = 34)., Methods: Data on stressful life events and self-reported symptoms were collected 3 months post-injury. Stressful life events in the last 12 months were assessed as part of a structured interview using a checklist of 11 common life events, self-reported fatigue with Barrow Neurological Institute Fatigue Scale, and depressive symptoms with Beck Depression Inventory - Fast Screen., Results: Median number of stressful life events was 1 (range 0-7) in the mild traumatic brain injury group and 1.5 (range 0-6) in the orthopaedic injury group. The groups did not differ significantly in terms of fatigue or depressive symptoms. In the mild traumatic brain injury group, the total number of recent stressful life events correlated significantly with self-reported fatigue (rs = 0.270, p = 0.007) and depressive symptoms (rs = 0.271, p = 0.007)., Conclusion: Stressful life events are associated with self-reported fatigue and depressive symptoms in patients with mild traumatic brain injury. Clinicians should consider stressful life events when managing patients who experience these symptoms, as this may help identifying potential targets for intervention.

Objective: Subjective cognitive complaints are common in patients with cerebral small vessel disease (cSVD), yet their relationship with informant evaluations, objective cognitive functions and severity of brain changes are poorly understood. We studied the associations of subjective and informant reports with findings from comprehensive neuropsychological assessment and brain MRI., Method: In the Helsinki SVD Study, 152 older adults with varying degrees of white matter hyperintensities (WMH) but without stroke or dementia were classified as having normal cognition or mild cognitive impairment (MCI) based on neuropsychological criteria. The measures also included continuous domain scores for memory and executive functions. Cognitive complaints were evaluated with the subjective and informant versions of the Prospective and Retrospective Memory Questionnaire (PRMQ) and Dysexecutive Questionnaire (DEX); functional abilities with the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL); and depressive symptoms with the Geriatric Depression Scale (GDS-15)., Results: Subjective cognitive complaints correlated significantly with informant reports ( r =0.40-0.50, p<0.001). After controlling for demographics, subjective and informant DEX and PRMQ were not related to MCI, memory or executive functions. Instead, subjective DEX and PRMQ significantly associated with GDS-15 and informant DEX and PRMQ with WMH volume and A-IADL., Conclusions: Neither subjective nor informant-reported cognitive complaints associated with objective cognitive performance. Informant-evaluations were related to functional impairment and more severe WMH, whereas subjective complaints only associated with mild depressive symptoms. These findings suggest that awareness of cognitive impairment may be limited in early-stage cSVD and highlight the value of informant assessments in the identification of patients with functional impairment., Competing Interests: MA has received a personal fee for educational event from Merck KGaA. AK has received payment for expert testimony from the Finnish National Insurance Centre, for a neuroradiologist expert testimony on a court of justice, support for travel from Helsinki University Hospital and is the board member of the Finnish Radiological Society. JK and JL are shareholders at Combinostics Ltd. TP is a board member at the Finnish Brain Council, the Finnish Neuropsychological Society, and the Finnish Alzheimer's Disease Research Society. The other authors report no competing of interests., (© 2023 The Authors.)

Objectives: Neuropsychiatric symptoms are related to disease progression and cognitive decline over time in cerebral small vessel disease (SVD) but their significance is poorly understood in covert SVD. We investigated neuropsychiatric symptoms and their relationships between cognitive and functional abilities in subjects with varying degrees of white matter hyperintensities (WMH), but without clinical diagnosis of stroke, dementia or significant disability., Methods: The Helsinki Small Vessel Disease Study consisted of 152 subjects, who underwent brain magnetic resonance imaging (MRI) and comprehensive neuropsychological evaluation of global cognition, processing speed, executive functions, and memory. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory Questionnaire (NPI-Q, n = 134) and functional abilities with the Amsterdam Instrumental Activities of Daily Living questionnaire (A-IADL, n = 132), both filled in by a close informant., Results: NPI-Q total score correlated significantly with WMH volume ( r s = 0.20, p = 0.019) and inversely with A-IADL score ( r s  = -0.41, p < 0.001). In total, 38% of the subjects had one or more informant-evaluated neuropsychiatric symptom. Linear regressions adjusted for age, sex, and education revealed no direct associations between neuropsychiatric symptoms and cognitive performance. However, there were significant synergistic interactions between neuropsychiatric symptoms and WMH volume on cognitive outcomes. Neuropsychiatric symptoms were also associated with A-IADL score irrespective of WMH volume., Conclusions: Neuropsychiatric symptoms are associated with an accelerated relationship between WMH and cognitive impairment. Furthermore, the presence of neuropsychiatric symptoms is related to worse functional abilities. Neuropsychiatric symptoms should be routinely assessed in covert SVD as they are related to worse cognitive and functional outcomes.

Background: The usefulness of neurofilament light (NfL) as a biomarker for small vessel disease has not been established. We examined the relationship between NfL, neuroimaging changes, and clinical findings in subjects with varying degrees of white matter hyperintensity (WMH)., Methods: A subgroup of participants (n = 35) in the Helsinki Small Vessel Disease Study underwent an analysis of NfL in cerebrospinal fluid (CSF) as well as brain magnetic resonance imaging (MRI) and neuropsychological and motor performance assessments. WMH and structural brain volumes were obtained with automatic segmentation., Results: CSF NfL did not correlate significantly with total WMH volume (r = 0.278, p = 0.105). However, strong correlations were observed between CSF NfL and volumes of cerebral grey matter (r = -0.569, p < 0.001), cerebral cortex (r = -0.563, p < 0.001), and hippocampi (r = -0.492, p = 0.003). CSF NfL also correlated with composite measures of global cognition (r = -0.403, p = 0.016), executive functions (r = -0.402, p = 0.017), memory (r = -0.463, p = 0.005), and processing speed (r = -0.386, p = 0.022). Regarding motor performance, CSF NfL was correlated with Timed Up and Go (TUG) test (r = 0.531, p = 0.001), and gait speed (r = -0.450, p = 0.007), but not with single-leg stance. After adjusting for age, associations with volumes in MRI, functional mobility (TUG), and gait speed remained significant, whereas associations with cognitive performance attenuated below the significance level despite medium to large effect sizes., Conclusion: NfL was strongly related to global gray matter and hippocampal atrophy, but not to WMH severity. NfL was also associated with motor performance. Our results suggest that NfL is independently associated with brain atrophy and functional mobility, but is not a reliable marker for cerebral small vessel disease., Competing Interests: JKo and JLö are employed by Combinostics Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kartau, Melkas, Kartau, Arola, Laakso, Pitkänen, Lempiäinen, Koikkalainen, Lötjönen, Korvenoja, Ahlström, Herukka, Erkinjuntti and Jokinen.)

The ability to produce words through singing can be preserved in severe aphasia, but the benefits of group-based singing rehabilitation in aphasia are largely unknown. Our aim was to determine the efficacy of a multicomponent singing intervention on communication and speech production, emotional-social functioning and caregiver well-being in aphasia. Fifty-four patients with acquired brain injury and chronic aphasia and their family caregivers ( n = 43) were recruited. Using a crossover randomized controlled trial design, participants were randomized to two groups who received a 4-month singing intervention either during the first or second half of the study in addition to standard care. The intervention comprised weekly group-based training (including choir singing and group-level melodic intonation therapy) and tablet-assisted singing training at home. At baseline, 5- and 9-month stages, patients were assessed with tests and questionnaires on communication and speech production, mood, social functioning, and quality of life and family caregivers with questionnaires on caregiver burden. All participants who participated in the baseline measurement ( n = 50) were included in linear mixed model analyses. Compared with standard care, the singing intervention improved everyday communication and responsive speech production from baseline to 5-month stage, and these changes were sustained also longitudinally (baseline to 9-month stage). Additionally, the intervention enhanced patients' social participation and reduced caregiver burden. This study provides novel evidence that group-based multicomponent singing training can enhance communication and spoken language production in chronic aphasia as well as improve psychosocial wellbeing in patients and caregivers. https://www.clinicaltrials.gov, Unique identifier: NCT03501797., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Traumatic brain injury (TBI) causes deficits in executive function (EF), as well as problems in behavioural and emotional self-regulation. Neurological music therapy may aid these aspects of recovery. We performed a cross-over randomized controlled trial where 40 persons with moderate-severe TBI received a 3-month neurological music therapy intervention (2 times/week, 60 min/session), either during the first (AB, n  = 20) or second (BA, n  = 20) half of a 6-month follow-up period. The evidence from this RCT previously demonstrated that music therapy enhanced general EF and set shifting. In the current study, outcome was assessed with self-report and caregiver-report questionnaires performed at baseline, 3-month, 6-month, and 18-month stages. The results showed that the self-reported Behavioural Regulation Index of the Behaviour Rating Inventory of Executive Function (BRIEF-A) improved more in the AB than BA group from baseline to 3-month stage and the effect was maintained in the 6-month follow-up. No changes in mood or quality of life questionnaires were observed. However, a qualitative content analysis of the feedback revealed that many participants experienced the intervention as helpful in terms of emotional well-being and activity. Our results suggest that music therapy has a positive effect on everyday behavioural regulation skills after TBI.

Background: Return to work (RTW) might be delayed in patients with complicated mild traumatic brain injury (MTBI), i.e., MTBI patients with associated traumatic intracranial lesions. However, the effect of different types of lesions on RTW has not studied before. We investigated whether traumatic intracranial lesions detected by CT and MRI are associated with return to work and post-concussion symptoms in patients with MTBI., Methods: We prospectively followed up 113 adult patients with MTBI that underwent a brain MRI within 3-17 days after injury. Return to work was assessed with one-day accuracy up to one year after injury. Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and Glasgow Outcome Scale Extended (GOS-E) were conducted one month after injury. A Kaplan-Meier log-rank analysis was performed to analyze the differences in RTW., Results: Full RTW-% one year after injury was 98%. There were 38 patients with complicated MTBI, who had delayed median RTW compared to uncomplicated MTBI group (17 vs. 6 days), and more post-concussion symptoms (median RPQ 12.0 vs. 6.5). Further, RTW was more delayed in patients with multiple types of traumatic intracranial lesions visible in MRI (31 days, n = 19) and when lesions were detected in the primary CT (31 days, n = 24). There were no significant differences in GOS-E., Conclusions: The imaging results that were most clearly associated with delayed RTW were positive primary CT and multiple types of lesions in MRI. RTW-% of patients with MTBI was excellent and a single intracranial lesion does not seem to be a predictive factor of disability to work., (© 2022. The Author(s).)

Objective: To examine perceived injustice and its associations with self-reported symptoms and return to work at 3 months after injury in a prospectively recruited sample of patients with mild traumatic brain injury (mTBI)., Design: Observational study., Setting: TBI outpatient unit., Participants: Adult patients aged 18 to 68 years with mTBI (n = 100) or orthopedic injury ([OI]; n = 34)., Main Measures: The Injustice Experience Questionnaire (IEQ) and its associations with the Rivermead Post Concussion Questionnaire (RPQ), Beck Depression Inventory-Second Edition (BDI-II), PTSD Checklist-Civilian Version (PCL-C), and Pain Visual Analog Scale (PVAS). Information on injury-related characteristics, compensation seeking and litigation, and return-to-work status was also collected., Results: Median IEQ total score was 3 (range, 0-23) in the mTBI group and 2.5 (range, 0-25) in the OI group. In the mTBI group, IEQ was significantly correlated with RPQ (rs = 0.638, P < .01), BDI-II (rs = 0.612, P < .01), PCL-C (rs = 0.679, P < .01), and PVAS (rs = 0.232, P < .05). The association between IEQ and PCL-C (rs =0.797, P < .01) and BDI-II (rs = 0.395, P < .05) was also found in the OI group. In both groups, patients who were still on sick leave at 3 months after injury tended to report higher perceived injustice (IEQ total score) than patients who had returned to work or studies. However, this difference did not reach statistical significance., Conclusions: Perceived injustice is associated with self-reported symptoms in patients with mTBI. Our results suggest that perceived injustice could be a relevant construct to consider in clinical management of patients with mTBI. Also, perceived injustice could be a potential target for psychological interventions promoting recovery after mTBI., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Post-traumatic headache (PTH) is a common symptom following mild traumatic brain injury (mTBI). Patients at risk to develop acute PTH (aPTH) and further persistent PTH (pPTH) need to be recognized., Methods: This is a one-year follow-up of 127 patients with mTBI, aged 18 to 68, referred to outpatient clinic in the Helsinki University Hospital. Symptoms were assessed at the emergency department (ED), with structured interview at outpatient clinic visit and with Rivermead post-concussion symptom questionnaire at one, three, and 12 months after injury. Psychiatric disorders were assessed with Structured Clinical Interview for DSM-IV Axis I disorders at 3-4 months and return to work (RTW) from patient records., Results: At one month, 77/127 patients (61%) had aPTH. According to multiple logistic regression analysis, risk factors for aPTH were headache at the emergency department (ED) (OR 5.43), other pain (OR 3.19), insomnia (OR 3.23), and vertigo (OR 5.98). At three months, 17 patients (22% of aPTH patients) had developed pPTH, and at one year, 4 patients (24% of pPTH patients) still presented with pPTH. Risk factors for pPTH at three months were older age (OR 1.06) and current insomnia (OR 12.3). The frequency of psychiatric disorders did not differ between the groups. pPTH patients performed worse on their RTW., Conclusions: Risk factors for aPTH were insomnia, headache at ED, other pain, and vertigo and for pPTH, insomnia and older age. RTW rate was lower among pPTH patients., (© 2022. The Author(s).)

A classical observation in neurology is that aphasic stroke patients with impairments in speech production can nonetheless sing the same utterances. This preserved ability suggests a distinctive neural architecture for singing that could contribute to speech recovery. However, to date, these structural correlates remain unknown. Here, we combined a multivariate lesion-symptom mapping and voxel-based morphometry approach to analyse the relationship between lesion patterns and grey matter volume and production rate in speech and singing tasks. Lesion patterns for spontaneous speech and cued repetition extended into frontal, temporal and parietal areas typically reported within the speech production network. Impairment in spontaneous singing was associated with damage to the left anterior-posterior superior and middle temporal gyri. Preservation of grey matter volume in the same regions where damage led to poor speech and singing production supported better performance in these tasks. When dividing the patients into fluent and dysfluent singers based on the singing performance from demographically matched controls, we found that the preservation of the left middle temporal gyrus was related to better spontaneous singing. These findings provide insights into the structural correlates of singing in chronic aphasia and may serve as biomarkers to predict treatment response in clinical trials using singing-based interventions for speech rehabilitation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH)., Methods: Participants of the Helsinki Small Vessel Disease Study (n = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation., Results: Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single-leg stance, timed up-and-go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant-evaluated IADL, but not on self-evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up-and-go performance., Conclusion: The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Post-stroke cognitive impairment is a common and well-known consequence of supra-tentorial infarct, but its prevalence and severity after infra-tentorial infarct is unclear. We compared the frequencies and prognostic value of domain-specific cognitive deficits after supra-tentorial and infra-tentorial infarct., Methods: In a consecutive cohort of patients with first-ever stroke (N = 244) admitted to Helsinki University Hospital, 37 patients had an infra-tentorial infarct. Patients were assessed with a comprehensive neuropsychological examination 3 months post-stroke covering 9 cognitive domains and functional disability was assessed at 15 months with the modified Rankin Scale., Results: There were no statistically significant differences between the frequencies of cognitive deficits in patients with infra-tentorial vs supra-tentorial infarct. Altogether 73% of patients with infra-tentorial infarct and 82% of patients with supra-tentorial infarct had impairment in at least one cognitive domain. Further 42% of patients with infra-tentorial infarct and 47% of those with supra-tentorial infarct had deficits in 3 or more cognitive domains. In patients with infra-tentorial infarct, visuo-constructional deficits were significantly associated with functional disability at 15 months (OR 9.0, 95%CI 1.3-62.5, p = 0.027). In patients with supratentorial infarct, executive deficits (OR 2.9, 95%CI 1.5-5.8, p = 0.002) and visuo-constructional deficits (OR 2.9, 95%CI 1.5-5.7, p = 0.001) showed associations with functional disability at 15 months., Conclusion: Cognitive deficits are as common in patients with infra-tentorial infarct as in those with supra-tentorial infarct, and it is important to recognize them to meet the needs of rehabilitation., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Automated analysis of neuroimaging data is commonly based on magnetic resonance imaging (MRI), but sometimes the availability is limited or a patient might have contradictions to MRI. Therefore, automated analyses of computed tomography (CT) images would be beneficial., Methods: We developed an automated method to evaluate medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and the severity of white matter lesions (WMLs) from a CT scan and compared the results to those obtained from MRI in a cohort of 214 subjects gathered from Kuopio and Helsinki University Hospital registers from 2005 - 2016., Results: The correlation coefficients of computational measures between CT and MRI were 0.9 (MTA), 0.82 (GCA), and 0.86 (Fazekas). CT-based measures were identical to MRI-based measures in 60% (MTA), 62% (GCA) and 60% (Fazekas) of cases when the measures were rounded to the nearest full grade variable. However, the difference in measures was 1 or less in 97-98% of cases. Similar results were obtained for cortical atrophy ratings, especially in the frontal and temporal lobes, when assessing the brain lobes separately. Bland-Altman plots and weighted kappa values demonstrated high agreement regarding measures based on CT and MRI., Conclusions: MTA, GCA, and Fazekas grades can also be assessed reliably from a CT scan with our method. Even though the measures obtained with the different imaging modalities were not identical in a relatively extensive cohort, the differences were minor. This expands the possibility of using this automated analysis method when MRI is inaccessible or contraindicated., (© 2021. The Author(s).)

The main objective of this prospective cohort study was to evaluate whether traumatic microbleeds (TMBs) are a significant prognostic factor of return to work (RTW), post-traumatic symptoms, and overall recovery in patients with mild traumatic brain injury (mTBI). One hundred and thirteen patients with mTBI were recruited from the Helsinki University Hospital emergency units. All patients underwent multi-contrast 3T magnetic resonance imaging (MRI) 3-17 days after mTBI. Patients were evaluated in the Traumatic Brain Injury Outpatient Clinic of Helsinki University Hospital 1 month after injury. Post-concussion symptoms were assessed with the Post-Concussion Symptom Questionnaire (RPQ) and overall recovery was assessed with the Glasgow Outcome Scale Extended (GOS-E). Their time to RTW was continuously measured up to 1 year after TBI. Median RTW was 9 days (interquartile range [IQR] 4-30) after mTBI and full RTW rate after 1 year was 98%. Patients with TMBs ( n  = 22) did not have more post-concussion symptoms (median RPQ 10.0 vs. 7.0, p  = 0.217) or worse overall recovery (58% vs. 56% with GOS-E = 8, p  = 0.853) than patients without TMBs ( n  = 91). There was no significant difference in time to RTW (13.5 vs. 7.0 days, p  = 0.063). In this study, patients with TMBs did not have delayed RTW or more post-concussion symptoms than other patients with mTBI. TMBs in mTBI do not seem to be a significant prognostic factor of RTW.

Background and Purpose: Cerebral small vessel disease is characterized by progressive white matter hyperintensities (WMH) and cognitive decline. However, variability exists in how individuals maintain cognitive capabilities despite significant neuropathology. The relationships between individual cognitive reserve, psychological resilience and cognitive functioning were examined in subjects with varying degrees of WMH., Methods: In the Helsinki Small Vessel Disease Study, 152 subjects (aged 65-75 years) underwent a comprehensive neuropsychological assessment, evaluation of subjective cognitive complaints and brain magnetic resonance imaging with volumetric WMH evaluation. Cognitive reserve was determined by education (years) and the modified Cognitive Reserve Scale (mCRS). Psychological resilience was evaluated with the Resilience Scale 14., Results: The mCRS total score correlated significantly with years of education (r = 0.23, p < 0.01), but it was not related to age, sex or WMH volume. Together, mCRS score and education were associated with performance in a wide range of cognitive domains including processing speed, executive functions, working memory, verbal memory, visuospatial perception and verbal reasoning. Independently of education, the mCRS score had incremental predictive value on delayed verbal recall and subjective cognitive complaints. Psychological resilience was not significantly related to age, education, sex, WMH severity or cognitive test scores, but it was associated with subjective cognitive complaints., Conclusions: Cognitive reserve has strong and consistent associations with cognitive functioning in subjects with WMH. Education is widely associated with objective cognitive functioning, whereas lifetime engagement in cognitively stimulating leisure activities (mCRS) has independent predictive value on memory performance and subjective cognitive complaints. Psychological resilience is strongly associated with subjective, but not objective, cognitive functioning., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Traumatic brain injury (TBI) is characterized by a complex pattern of abnormalities in resting-state functional connectivity (rsFC) and network dysfunction, which can potentially be ameliorated by rehabilitation. In our previous randomized controlled trial, we found that a 3-month neurological music therapy intervention enhanced executive function (EF) and increased grey matter volume in the right inferior frontal gyrus (IFG) in patients with moderate-to-severe TBI ( N = 40). Extending this study, we performed longitudinal rsFC analyses of resting-state fMRI data using a ROI-to-ROI approach assessing within-network and between-network rsFC in the frontoparietal (FPN), dorsal attention (DAN), default mode (DMN), and salience (SAL) networks, which all have been associated with cognitive impairment after TBI. We also performed a seed-based connectivity analysis between the right IFG and whole-brain rsFC. The results showed that neurological music therapy increased the coupling between the FPN and DAN as well as between these networks and primary sensory networks. By contrast, the DMN was less connected with sensory networks after the intervention. Similarly, there was a shift towards a less connected state within the FPN and SAL networks, which are typically hyperconnected following TBI. Improvements in EF were correlated with rsFC within the FPN and between the DMN and sensorimotor networks. Finally, in the seed-based connectivity analysis, the right IFG showed increased rsFC with the right inferior parietal and left frontoparietal (Rolandic operculum) regions. Together, these results indicate that the rehabilitative effects of neurological music therapy after TBI are underpinned by a pattern of within- and between-network connectivity changes in cognitive networks as well as increased connectivity between frontal and parietal regions associated with music processing., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Noelia Martínez-Molina et al.)

Background: Dementia is among the most frequent causes of institutionalization. To serve the purpose of preventive strategies, there are no follow-up studies that have evaluated the actual impact of post-stroke dementia on institutionalization. We therefore compared the institutionalization rate and length of stay in an institutional care facility of patients with post-stroke dementia with stroke patients without dementia., Methods: We included 410 consecutive patients aged 55 to 85 years with ischemic stroke who were admitted to Helsinki University Hospital (The SAM cohort). Hospitalization and nursing home admissions were reviewed from national registries. Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders 3rd edition (DSM-III) criteria using extensive clinical assessments performed 3 months post-stroke. The cohort had a follow-up 21 years later., Results: Compared to patients without dementia, post-stroke dementia was associated with shorter survival time (6.60 vs 10.10 years, p < 0.001), shorter time spent not institutionalized (5.40 vs 9.37 years, p < 0.001), but not with time spent permanently institutionalized (0.73 vs 1.10 years, p = 0.08). Post-stroke dementia was associated with higher rates and earlier permanent institutionalization compared to absence of post-stroke dementia (HR 1.53, 95% CI 1.07-2.18) in a Cox regression model adjusting for age, status of living alone at baseline, modified Rankin Scale at baseline, history of atrial fibrillation, and cardiac failure., Conclusions: Post-stroke dementia is associated with earlier permanent institutionalization. Due to significantly shorter survival, the time spent in nursing homes was not significantly longer in patients with post-stroke dementia compared with patients without post-stroke dementia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: We evaluated the prevalence of psychiatric disorders in mild traumatic brain injury (MTBI) patients and investigated psychiatric comorbidity in relation to subjective symptoms and return to work (RTW)., Methods: We recruited 103 MTBI patients (mean age 40.8 years, SD 3.1) prospectively from University Hospital. The patients were followed up for one year. The Rivermead Post-Concussion Symptom Questionnaire (RPQ) and Extended Glasgow Outcome Scale (GOSE) were administered one month after MTBI. Three months after MTBI, any psychiatric disorders were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders., Results: Psychiatric disorders were diagnosed in 26 patients (25.2%). The most common disorders were previous/current depression. At three months, there was no difference between patients with psychiatric disorders versus those without them in RTW (95.7% vs. 87.3%, p = 0.260) or at least in part-time work (100% vs. 94.4%, p = 0.245). In Kaplan-Meier analysis, the median time to RTW was 10 days for both groups. The median RPQ score was 13.0 (Interquartile range (IQR) 6.5-19.0) in patients with a psychiatric disorder compared to 8.5 (IQR 2.3-14.0) in those without one ( p = 0.021); respectively, the median GOSE was 7.0 (IQR 7.0-8.0) compared to 8.0 (IQR 7.0-8.0, p = 0.003)., Conclusions: Approximately every fourth patient with MTBI had a psychiatric disorder. These patients reported more symptoms, and their functional outcome measured with GOSE at one month after MTBI was worse. However, presence of any psychiatric disorder did not affect RTW. Early contact and adequate follow-up are important when supporting the patient's return to work.

Purpose: Severity of white matter lesion (WML) is typically evaluated on magnetic resonance images (MRI), yet the more accessible, faster, and less expensive method is computed tomography (CT). Our objective was to study whether WML can be automatically segmented from CT images using a convolutional neural network (CNN). The second aim was to compare CT segmentation with MRI segmentation., Methods: The brain images from the Helsinki University Hospital clinical image archive were systematically screened to make CT-MRI image pairs. Selection criteria for the study were that both CT and MRI images were acquired within 6 weeks. In total, 147 image pairs were included. We used CNN to segment WML from CT images. Training and testing of CNN for CT was performed using 10-fold cross-validation, and the segmentation results were compared with the corresponding segmentations from MRI., Results: A Pearson correlation of 0.94 was obtained between the automatic WML volumes of MRI and CT segmentations. The average Dice similarity index validating the overlap between CT and FLAIR segmentations was 0.68 for the Fazekas 3 group., Conclusion: CNN-based segmentation of CT images may provide a means to evaluate the severity of WML and establish a link between CT WML patterns and the current standard MRI-based visual rating scale.

Traumatic brain injury (TBI) causes lifelong cognitive deficits, particularly impairments of executive functioning (EF). Musical training and music-based rehabilitation have been shown to enhance cognitive functioning and neuroplasticity, but the potential rehabilitative effects of music in TBI are still largely unknown. The aim of the present crossover randomized controlled trial (RCT) was to determine the clinical efficacy of music therapy on cognitive functioning in TBI and to explore its neural basis. Using an AB/BA design, 40 patients with moderate or severe TBI were randomized to receive a 3-month neurological music therapy intervention either during the first (AB, n  = 20) or second (BA, n  = 20) half of a 6-month follow-up period. Neuropsychological and motor testing and magnetic resonance imaging (MRI) were performed at baseline and at the 3-month and 6-month stage. Thirty-nine subjects who participated in baseline measurement were included in an intention-to-treat analysis using multiple imputation. Results showed that general EF (as indicated by the Frontal Assessment Battery [FAB]) and set shifting improved more in the AB group than in the BA group over the first 3-month period and the effect on general EF was maintained in the 6-month follow-up. Voxel-based morphometry (VBM) analysis of the structural MRI data indicated that gray matter volume (GMV) in the right inferior frontal gyrus (IFG) increased significantly in both groups during the intervention versus control period, which also correlated with cognitive improvement in set shifting. These findings suggest that neurological music therapy enhances EF and induces fine-grained neuroanatomical changes in prefrontal areas.

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi ( P <0.001 for global cognitive function, processing speed, executive functions, and memory and P <0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes ( P <0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases-a sub study of Health 2000 Survey ( n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers ( n = 46), 52.5% of Hp1-2 carriers ( n = 141) and 51.2% of Hp2-2 carriers ( n = 129) had severe WML ( p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers ( p = 0.201). In addition, 68.9% of Hp1-1 carriers ( n = 45), 58.5% of Hp1-2 carriers ( n = 135), and 61.8% of Hp2-2 carriers ( n = 126) had one or more lacunar lesions ( p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups ( p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort.

Objective: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium., Methods: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis., Results: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition., Conclusions: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Aim and Scope: A Gradient Echo Plural Contrast Imaging technique (GEPCI) is a post-processing method, which can be used to obtain quantitative T2* values and generate multiple synthetic contrasts from a single acquisition. However, scan duration and image reconstruction from k-space data present challenges in a clinical workflow. This study aimed at optimizing image reconstruction and acquisition duration to facilitate a post-processing method for synthetic image contrast creation in clinical settings., Materials and Methods: This study consists of tests using the American College of Radiology (ACR) image quality phantom, two healthy volunteers, four mild traumatic brain injury patients and four small vessel disease patients. The measurements were carried out on a 3.0 T scanner with multiple echo times. Reconstruction from k-space data and DICOM data with two different coil-channel combination modes were investigated. Partial Fourier techniques were tested to optimize the scanning time., Conclusions: Sum of squares coil-channel combination produced artifacts in phase images, but images created with adaptive combination were artifact-free. The voxel-wise median signed difference of T2* between the vendor's adaptive channel combination and k-space reconstruction modes was 2.9 ± 0.7 ms for white matter and 4.5 ± 0.6 ms for gray matter. Relative white matter/gray matter contrast of all synthetic images and contrast-to-noise ratio of synthetic T1-weighted images were almost equal between reconstruction modes. Our results indicate that synthetic contrasts can be generated from the vendor's DICOM data with the adaptive combination mode without affecting the quantitative T2* values or white matter/gray matter contrast.

Background and Purpose: Haptoglobin (Hp) is an acute phase plasma protein protecting tissues from oxidative damage. It exists in 2 variant alleles ( hp1/hp2 ) giving rise to 3 protein isoforms with different biochemical properties and efficiency to limit oxidative stress. We previously found that hp2 variant is associated with stroke risk in the patients with carotid stenosis and the risk of ischemic cardiovascular events in a general population cohort. This study examined the hypothesis that Hp genotype is associated with general cardiovascular risk in patients with stroke., Methods: Hp was genotyped in SAM study (Helsinki Stroke Aging Memory, n=378). A total of 1426 individuals ascertained from a nationally representative cross-sectional health survey served as population controls., Results: Hp genotype frequencies were 15.6% ( hp1-1 ), 44.2% ( hp1-2 ), and 40.2% ( hp2-2 ) in patients with stroke. During a mean of 7.5-year follow-up after first-ever stroke, hp2 carriers had a substantially higher rate of cardiac deaths (24.5% versus 8.5%; P =0.006) and a trend toward more fatal strokes (23.5% versus 13.6%; P =0.122). The combined risk of ischemic cardiovascular deaths was 2.4-fold higher among hp2 carriers (95% confidence interval, 1.28-4.43) after adjustment for major cardiovascular risk factors., Conclusions: Hp2 allele is associated with premature ischemic cardiovascular deaths after first-ever ischemic stroke., (© 2017 American Heart Association, Inc.)

Background: Cerebral small vessel disease (SVD) is characterised by progressive white matter hyperintensities (WMH), cognitive decline and loss of functional independence. The correspondence between neuroimaging findings and the severity of clinical symptoms has been modest, however, and thus the outcome may be affected by various host factors. We investigated the predictive value of educational and occupational attainments as proxy measures of cognitive reserve on long-term cognitive and functional outcome in patients with different degrees of WMH., Methods: In the Leukoaraiosis and Disability (LADIS) study, 615 older individuals with WMH were evaluated with brain MRI and detailed clinical and neuropsychological assessments at 3-year follow-up. A prolonged follow-up of functional and cognitive status was administered with a structured telephone interview after up to 7 years., Results: Higher levels of educational and occupational attainment were strongly related to baseline cognitive scores and predicted a slower rate of decline at 3-year follow-up in measures of processing speed, executive functions and memory independently of WMH volume and other confounders. The deleterious effect of WMH on processing speed and memory was moderated by education and occupation. Education mitigated the relation of WMH volume on 7-year cognitive status. Moreover, higher education and occupational attainments were related to favourable outcome at 7-year follow-up as defined by sustained functional independence and lower mortality., Conclusions: The results support the presumption that cognitive reserve plays a significant role as a buffer against the clinical manifestations of SVD and may in part explain high individual variability in outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD)., Methods: Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia., Results: Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years., Discussion: Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.

Objective: Parenchymal hematoma (PH) following intravenous thrombolysis (IVT) in ischemic stroke can occur either within the ischemic area (iPH) or as a remote PH (rPH). The latter could be, at least partly, related to cerebral amyloid angiopathy, which belongs to the continuum of cerebral small vessel disease. We hypothesized that cerebral white matter lesions (WMLs)-an imaging surrogate of small vessel disease-are associated with a higher rate of rPH., Methods: We analyzed 2,485 consecutive patients treated with IVT at the Helsinki University Hospital. Blennow rating scale of 5 to 6 points on baseline computed tomographic head scans was considered as severe WMLs. An rPH was defined as hemorrhage that-contrary to iPH-appears in brain regions without visible ischemic damage and is clinically not related to the symptomatic acute lesion site. The associations between severe WMLs and pure rPH versus no PH, pure iPH versus no PH, and pure rPH versus pure iPH were studied in multivariate logistic regression models., Results: rPHs were mostly (74%) located in lobar regions. After adjustments, the presence of severe WMLs was associated with pure rPH (odds ratio [OR] = 6.79, 95% confidence interval [CI] = 2.57-17.94) but not with pure iPH (OR = 1.45, 95% CI = 0.83-2.53) when compared to patients with no PH. In direct comparison of pure rPH with pure iPH, severe cerebral WMLs were further associated with higher iPH rates (OR = 3.60, 95% CI = 1.06-12.19)., Interpretation: Severe cerebral WMLs were associated with post-thrombolytic rPH but not with iPH within the ischemic area. Ann Neurol 2016;80:593-599., (© 2016 American Neurological Association.)