White matter changes in young and middle-aged males with chronic prostatitis/chronic pelvic pain syndrome: Tract-based spatial statistics analysis.

The supraspinal mechanism plays a key role in developing and maintaining chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, it is not clear how white matter changes in young and middle-aged males with CP/CPPS. In this cross-sectional study, 23 CP/CPPS patients and 22 healthy controls (HCs) were recruited. Tract-based spatial statistics was applied to investigate the differences in diffusion tensor imaging metrics, including fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD) and axial diffusion (AD), between CP/CPPS patients and HCs. The study also examined the association between white matter alterations and clinical variables in patients using correlation analysis. Compared with HCs, patients showed decreased FA, MD, RD and AD in the body and genu of the corpus callosum and right anterior corona radiata. In addition, they showed increased FA along with decreased MD, RD and AD in the left posterior limb of the internal capsule (PLIC-L), left external capsule and left cerebral peduncle. The FA of PLIC-L was negatively correlated with disease duration (r = -.54, corrected p = .017), while MD and RD were positively correlated (r = .45, corrected p = .042; r = .57, corrected p = .017). These results suggest that CP/CPPS is associated with extensive changes in white matter tracts, which are involved in pain processing. In particular, the FA, MD and RD values in the PLIC-L were correlated with the disease duration, indicating that the long-term course of CP/CPPS may have effects on the white matter microstructure of the pain perception pathways.

Persistent white matter changes in recovered COVID-19 patients at the 1-year follow-up.

There is growing evidence that severe acute respiratory syndrome coronavirus 2 can affect the CNS. However, data on white matter and cognitive sequelae at the 1-year follow-up are lacking. Therefore, we explored these characteristics in this study. We investigated 22 recovered coronavirus disease 2019 (COVID-19) patients and 21 matched healthy controls. Diffusion tensor imaging, diffusion kurtosis imaging and neurite orientation dispersion and density imaging were performed to identify white matter changes, and the subscales of the Wechsler Intelligence scale were used to assess cognitive function. Correlations between diffusion metrics, cognitive function and other clinical characteristics were then examined. We also conducted subgroup analysis based on patient admission to the intensive care unit. The corona radiata, corpus callosum and superior longitudinal fasciculus had a lower volume fraction of intracellular water in the recovered COVID-19 group than in the healthy control group. Patients who had been admitted to the intensive care unit had lower fractional anisotropy in the body of the corpus callosum than those who had not. Compared with the healthy controls, the recovered COVID-19 patients demonstrated no significant decline in cognitive function. White matter tended to present with fewer abnormalities for shorter hospital stays and longer follow-up times. Lower axonal density was detected in clinically recovered COVID-19 patients after 1 year. Patients who had been admitted to the intensive care unit had slightly more white matter abnormalities. No significant decline in cognitive function was found in recovered COVID-19 patients. The duration of hospital stay may be a predictor for white matter changes at the 1-year follow-up.

Clinical utility of brain computed tomography in prediction of post-stroke delirium.

Delirium is a common and serious complication of stroke. Early prediction of delirium is important for preventive strategies and close monitoring of high-risk patients. Pre-existing degenerative and vascular changes in the brain could predispose to delirium. We aimed to determine if computed tomography (CT)-based indices could provide additional information about a risk of stroke-associated delirium beyond easiest-to-access clinical predictors. Using semi-quantitative scales (global cortical atrophy, age-related white matter changes, and Scheltens scale), we assessed global and regional brain atrophy and white matter changes in 88 stroke patients with delirium and 142 patients without delirium matched for age and stroke severity. Patients with delirium had greater global and local brain atrophy (the right temporal region, the left parieto-occipital region, the right frontal and occipital horn, and the right and left temporal horn) than patients without delirium. Scores of white matter changes did not differ between groups with exception of greater white matter damage in the right parieto-occipital area in patients with delirium. The discriminatory properties of studied radiological indices were modest (areas under receiver operator curves: 0.58-0.64). CT-based indices of brain atrophy and white matter changes do not provide additional information about a risk of post-stroke delirium beyond the most important clinical predictors.

White matter changes in primary central nervous system lymphoma patients treated with high-dose methotrexate with or without rituximab.

PURPOSE: White matter changes (WMCs) can develop following systemic chemotherapy in patients with primary central nervous system lymphomas (PCNSLs), but the frequency and extent of these changes is not well characterized. This single center retrospective semi-quantitative study was performed to determine the rate, timing and grade of WMC on MRI in adult patients with newly-diagnosed radiotherapy-naïve PCNSL undergoing treatment with high-dose methotrexate (HD-MTX) with or without the addition of rituximab (-R). METHODS: Serial MRI scans of consecutive adult PCNSL patients treated with HD-MTX ± R were assessed for WMC comparing the pre-treatment to post-treatment scans utilizing a 0-to-8-point severity scoring system. RESULTS: Forty-seven PCNSL patients treated with either HD-MTX-R (n = 34; median age 66, 50% male) or HD-MTX (n = 13; median age 53, 54% male) were included in the analysis. WMC were detected in 62% (95% CI 46-76%) overall, in 68% of the HD-MTX-R, and in 46% of the HD-MTX group. Among patients with WMC (n = 29), WMC were first detected at an average of 2.8 months from beginning of therapy in the HD-MTX-R versus at 10.7 months in the HD-MTX group. Average WMC non-zero scores when first detected following the start of treatment were 2.5 (± 1.1) in HD-MTX-R and 1.5 (± 0.6) in HD-MTX. CONCLUSIONS: Development of WMC in PCNSL patients treated with MTX and MTX-R is common. WMC changes appear to be more frequent, occur earlier and are more extensive in patients treated with HD-MTX-R compared to HD-MTX. Prospective studies are required to determine whether WMC correlate with survival or neurocognitive outcomes.

Expanding the clinical and genetic spectra of NKX6-2-related disorder.

Hypomyelinating leukodystrophies (HLDs) affect the white matter of the central nervous system and manifest as neurological disorders. They are genetically heterogeneous. Very recently, biallelic variants in NKX6-2 have been suggested to cause a novel form of autosomal recessive HLD. Using whole-exome or whole-genome sequencing, we identified the previously reported c.196delC and c.487C>G variants in NKX6-2 in 3 and 2 unrelated index cases, respectively; the novel c.608G>A variant was identified in a sixth patient. All variants were homozygous in affected family members only. Our patients share a primary diagnosis of psychomotor delay, and they show spastic quadriparesis, nystagmus and hypotonia. Seizures and dysmorphic features (observed in 2 families each) represent an addition to the phenotype, while developmental regression (observed in 3 families) appears to be a notable and previously underestimated clinical feature. Our findings extend the clinical and mutational spectra associated with this novel form of HLD. Comparative analysis of our 10 patients and the 15 reported previously did, however, not reveal clear evidence for a genotype-phenotype correlation.

Radiotherapy in acromegaly: Long-term brain parenchymal and vascular magnetic resonance changes.

BACKGROUND: Radiation therapy (RT) effectiveness on hormonal reduction is proven in acromegaly; however, collateral long-term effects are still undetermined. This transversal neuroimaging study on a large cohort of acromegalic patients aimed to investigate the rate of parenchymal and vascular changes after RT. MATERIALS AND METHODS: Thirty-six acromegalic patients underwent RT (RT+) after unsuccessful surgery and were compared to RT- acromegalic patients matched for age, gender, adenoma features, clinical and surgical history. All patients underwent magnetic resonance angiography (MRA) to investigate intracranial artery abnormalities and FLAIR sequence to assess white matter changes according to the Wahlund scale. RESULTS: RT+ acromegalic patients had a higher rate of controlled disease (29/36 vs. 12/36, P<0.001). RT+ acromegalic patients had MRI/MRA evaluation 15.3±9.6 years after RT. RT+ acromegalic patients had a significantly higher Wahlund score than RT- acromegalic patients (6.03±6.41 vs. 2.53±3.66, P=0.006) due to increased white matter signal abnormalities at the level of the temporal lobes, the basal ganglia (insula) and the infratentorial regions, bilaterally. Among RT+ patients one died because of temporo-polar anaplastic astrocytoma, one suffered from a stroke due to right internal carotid artery occlusion, one presented with cystic degeneration of the temporal poles. Long-dated RT (>10 years before MR evaluation) was associated with a higher rate of RT-related white matter changes (P=0.0004). CONCLUSIONS: RT seems to have created a cohort of patients with brain parenchymal changes whose clinical and cognitive impact is still unknown. These patients might require a prolonged MRI and MRA follow-up to promptly detect delayed RT-related complications and minimize their clinical consequences.

Small vessel disease and clinical outcomes after IV rt-PA treatment.

INTRODUCTION: Cerebral small vessel disease (SVD) contributes to dementia and disability in the elderly, and may negatively affect stroke outcomes. We aimed to evaluate to what extent single features and global burden of SVD detected with magnetic resonance (MR) are associated with worse outcomes in patients with ischaemic stroke treated with intravenous thrombolysis. METHODS: We accessed anonymized data and MR images from the Stroke Imaging Repository (STIR) and the Virtual International Stroke Trials Archive (VISTA) Imaging. We described SVD features using validated scales and quantified the global burden of SVD with a combined score. Our mainoutcome was the modified Rankin Scale (mRS) at 90 days after stroke. We used logistic regression and ordinal regression models (adjusted for age, sex, stroke severity, onset to treatment time) to examine the associations between each SVD feature, SVD global burden and clinical outcomes. RESULTS: A total of 259 patients had MR scans available at baseline (mean age±SD=68.7±15.5 years; 131 [49%] males). After adjustment for confounders, severe white matter changes were associated with disability (OR=5.14; 95%CI=2.30-11.48), functional dependency (OR=4.38; 95%CI=2.10-9.13) and worse outcomes in ordinal analysis (OR=2.71; 95%CI=1.25-5.85). SVD score was associated with disability (OR=1.66; 95%CI=1.03-2.66) and functional dependency (OR=1.47; 95%CI=1.00-2.45). Lacunes, enlarged perivascular spaces and brain atrophy showed no association with clinical outcomes. CONCLUSION: Our results suggest that SVD negatively affects stroke outcomes after intravenous thrombolysis. Although white matter changes seem to be the major driver in relation to worse outcomes, global estimation of SVD is feasible and may provide helpful information.

'White matter connectivity and Internet gaming disorder' and broader considerations in the field.

This invited commentary on the paper 'White Matter Connectivity and Internet gaming disorder' by Jeong et al. (unpublished) looks at the implications and importance of the MRI findings in the present study-one of the largest to date-and also considers the broader developments of neuroimaging within the complex, emerging field of 'Internet psychology' and problematic Internet usage.

Pathoconnectomics of cognitive impairment in small vessel disease: A systematic review.

INTRODUCTION: Cerebral small vessel disease (CSVD) is a highly prevalent condition associated with diffuse ischemic damage and cognitive dysfunction particularly in executive function and attention. Functional brain imaging studies can reveal mechanisms of cognitive impairment in CSVD, although findings are mixed. METHODS: A systematic review integrating findings from functional magnetic resonance imaging and electroencephalography in CSVD is involved. RESULTS: CSVD damages long-range white matter tracts connecting nodes within distributed brain networks. It also disrupts frontosubcortical circuits and cholinergic fiber tracts mediating attentional processes. These changes, illustrated within a model of network dynamics, synergistically relate to neurodegenerative pathology contributing to dementia. DISCUSSION: The effects of CSVD on attention and executive functioning are best understood within a network model of cognition as revealed by functional neuroimaging. Analysis of network function in CSVD can improve characterization of disease severity and treatment effects, and it can inform theoretical models of brain function.

White matter changes in familial Alzheimer's disease.

BACKGROUND: Familial Alzheimer's disease (FAD) resulting from gene mutations in PSEN1, PSEN2 and APP is associated with changes in the brain. OBJECTIVE: The aim of this study was to investigate changes in grey matter (GM), white matter (WM) and the cerebrospinal fluid (CSF) in FAD. SUBJECTS: Ten mutation carriers (MCs) with three different mutations in PSEN1 and APP and 20 noncarriers (NCs) were included in the study. Three MCs were symptomatic and seven were presymptomatic (pre-MCs). METHODS: Whole-brain GM volume as well as fractional anisotropy (FA) and mean diffusivity (MD) using voxel-based morphometry and tract-based spatial statistics analyses, respectively, were compared between MCs and NCs. FA and MD maps were obtained from diffusion tensor imaging. RESULTS: A significant increase in MD was found in the left inferior longitudinal fasciculus, cingulum and bilateral superior longitudinal fasciculus in pre-MCs compared with NCs. After inclusion of the three symptomatic MCs in the analysis, the regions became wider. The mean MD of these regions showed significant negative correlation with the CSF level of Aß42, and positive correlations with P-tau181p and T-tau. No differences were observed in GM volume and FA between the groups. CONCLUSIONS: The results of this study suggest that FAD gene mutations affect WM diffusivity before changes in GM volume can be detected. The WM changes observed were related to changes in the CSF, with similar patterns previously observed in sporadic Alzheimer's disease.

Is type 2 diabetes related to leukoaraiosis? an updated review.

A significantly increased interest has been dedicated to the study of the effects of diabetes mellitus (DM) on the brain. DM is associated with an increased risk of stroke and cognitive decline. In patients with DM, neuroimaging discloses with high-frequency structural changes, such as cerebral atrophy, infarcts and white matter lesions, also called leukoaraiosis (LA), an expression of small vessel disease. A previous review showed a relation between DM and both cerebral atrophy and lacunar infarcts, while the question about the relation between DM and LA remained unanswered. In this review, we provide an update on data on this last association. In the reviewed studies, we examined the presence of DM, other disease characteristics, such as duration and complications, and laboratory markers of the disease such as blood glycated hemoglobin (HbA1c), insulin resistance, insulin concentrations and their association with LA. About 40% of the reviewed studies reported a statistically significant association between DM and LA. Long-standing DM and a poor glycemic control were associated with severe LA. Studies using innovative MRI techniques, such as diffusion tensor imaging (DTI), reported a significant association between microstructural white matter alterations and DM. This review highlights more firmly than previously reported the existence of a relation between DM and both presence and severity of LA. These results are possibly due to more sensitive and advanced imaging techniques recently used to study the extent of LA. However, because of the heterogeneous methodology used in the reviewed studies, a definitive conclusion cannot be drawn.

Physical activity in the elderly is associated with improved executive function and processing speed: the LADIS Study.

OBJECTIVES: Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes (ARWMC). METHODS: Data from the Leukoaraiosis And DISability (LADIS) study, a multicenter, European prospective cohort study aimed at examining the role of ARWMC in transition to disability, was used. Subjects in the LADIS study were clinically assessed yearly for 3 years including MRI at baseline and 3-year follow-up. Physical activity was assessed at baseline, and cognitive compound scores at baseline and 3-year assessment were used. RESULTS: Two-hundred-eighty-two subjects (age, y (mean (SD)): 73.1 (± 5.1); gender (f/m): 164/118); MMSE (mean (SD)): 28.3 (± 1.7)) who had not progressed to MCI or dementia, were included. Multiple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3-year follow-up for executive function (baseline: ß: 0.39, 95% CI: 0.13-0.90, p = 0.008; follow-up: ß: 0.24, 95% CI: 0.10-0.38, p = 0.001) and processing speed (baseline: ß: 0.48, 95% CI: 0.14-0.89, p = 0.005; follow-up: ß: 0.15, 95% CI: 0.02-0.29, p = 0.02) but not memory. When including baseline cognitive score as a covariate in the analysis of 3-year follow-up scores, executive function remained significant (ß: 0.11, 95% CI: 0-0.22, p = 0.04). CONCLUSION: Our findings confirm previous findings of a positive effect of physical activity on cognitive functions in elderly subjects, and further extends these by showing that the association is also present in patients with ARWMC.

Concordance of white matter and gray matter abnormalities in autism spectrum disorders: a voxel-based meta-analysis study.

There are at least two fundamental unanswered questions in the literature on autism spectrum disorders (ASD): Are abnormalities in white (WM) and gray matter (GM) consistent with one another? Are WM morphometric alterations consistent with alterations in the GM of regions connected by these abnormal WM bundles and vice versa? The aim of this work is to bridge this gap. After selecting voxel-based morphometry and diffusion tensor imaging studies comparing autistic and normally developing groups of subjects, we conducted an activation likelihood estimation (ALE) meta-analysis to estimate consistent brain alterations in ASD. Multidimensional scaling was used to test the similarity of the results. The ALE results were then analyzed to identify the regions of concordance between GM and WM areas. We found statistically significant topological relationships between GM and WM abnormalities in ASD. The most numerous were negative concordances, found bilaterally but with a higher prevalence in the right hemisphere. Positive concordances were found in the left hemisphere. Discordances reflected the spatial distribution of negative concordances. Thus, a different hemispheric contribution emerged, possibly related to pathogenetic factors affecting the right hemisphere during early developmental stages. Besides, WM fiber tracts linking the brain structures involved in social cognition showed abnormalities, and most of them had a negative concordance with the connected GM regions. We interpreted the results in terms of altered brain networks and their role in the pervasive symptoms dramatically impairing communication and social skills in ASD patients.

White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

BACKGROUND: Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM. METHODS: We used post-mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro-caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles. RESULTS: The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P<0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P<0.01), with most prominent axonal abnormalities observed in the frontal WM (P<0.05). The SIs of arterioles in CADASIL were increased by 25-45% throughout the regions assessed, with the highest change in the mid-frontal region (P=0.000). CONCLUSIONS: Our results suggest disruption of either cortico-cortical or subcortical-cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures.

Cerebral Small Vessel Disease and Infarct Growth in Acute Ischemic Stroke Treated with Intravenous Thrombolysis.

We investigated relations between cerebral small vessel disease (cSVD) markers and evolution of the ischemic tissue from ischemic core to final infarct in people with acute ischemic stroke treated with intravenous thrombolysis. Data from the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) were used. Any pre-existing lacunar infarcts and white matter hyperintensities (WMH) were assessed on magnetic resonance (MR) before thrombolytic therapy. Acute ischemic core and final infarct volume were then assessed by two independent radiologists. The relationship among baseline markers of cSVD, acute ischemic core volume, final infarct volume, infarct growth (IG = final infarct - ischemic core), and infarct growth ratio (IGR = final infarct/ischemic core) was then assessed using linear and ordinal regression adjusted for age, sex, onset-to-treatment time, and stroke severity. We included 165 patients, mean (± SD) age 69.5 (± 15.7) years, 74 (45%) males, mean (± SD) ischemic core volume 25.48 (± 42.22) ml, final infarct volume 52.06 (± 72.88) ml, IG 26.58 (± 51.02) ml, IGR 8.23 (± 38.12). Seventy (42%) patients had large vessel occlusion, 20 (12%) acute small subcortical infarct. WMHs were present in 131 (79%) and lacunar infarcts in 61 (37%) patients. Final infarct volumes were 53.8 ml and 45.2 ml (WMHs/no WMHs), p = 0.139, and 24.6 ml and 25.9 ml (lacunar infarcts/no lacunar infarcts), p = 0.842. In linear and ordinal regression analyses, presence of lacunar infarcts was associated with smaller IG (ß = - 0.17; p = 0.024; cOR = 0.52; 95%CI = 0.28-0.96, respectively) and WMHs were associated with smaller IGR (ß = - 0.30; p = 0.004; cOR = 0.27; 95%CI = 0.11-0.69, respectively). In people with acute ischemic stroke treated with intravenous thrombolysis, cSVD features were associated with smaller growth of the acute ischemic area, suggesting less salvageable tissue at time of reperfusion therapy.

Population-based case-control study of white matter changes on brain imaging in transient ischemic attack and ischemic stroke.

BACKGROUND AND PURPOSE: White matter changes (WMC) are a common finding on brain imaging and are associated with an increased risk of ischemic stroke. They are most frequent in small vessel stroke; however, in the absence of comparisons with normal controls, it is uncertain whether WMC are also more frequent than expected in other stroke subtypes. Therefore, we compared WMC in pathogenic subtypes of ischemic stroke versus controls in a population-based study. METHODS: We evaluated the presence and severity of WMC on computed tomography and on magnetic resonance brain imaging using modified Blennow/Fazekas scale and age-related white matter changes scale, respectively, in a population-based study of patients with incident transient ischemic attack or ischemic stroke (Oxford Vascular Study) and in a study of local controls (Oxford Project to Investigate Memory and Ageing) without history of transient ischemic attack or ischemic stroke, with stratification by stroke pathogenesis (Trial of Org10172 in Acute Stroke Treatment classification). RESULTS: Among 1601 consecutive eligible patients with first-ever ischemic events, 1453 patients had computed tomography brain imaging, 562 had magnetic resonance imaging, and 414 patients had both. Compared with 313 controls (all with computed tomography and 131 with magnetic resonance imaging) and after adjustment for age, sex, diabetes mellitus, and hypertension, moderate/severe WMC (age-related white matter changes scale) were more frequent in patients with small vessel events (odds ratio, 3.51 [95% confidence interval, 2.13-5.76]; P<0.0001) but not in large artery (odds ratio, 1.03 [95% confidence interval, 0.64-1.67]), cardioembolic (odds ratio, 0.87 [95% confidence interval, 0.56-1.34]), or undetermined (odds ratio, 0.90 [95% confidence interval, 0.62-1.30]) subtypes. Results were consistent for ischemic stroke and transient ischemic attack, for other scales, and for magnetic resonance imaging and computed tomography separately. CONCLUSIONS: In contrast to small vessel ischemic events, WMC were not independently associated with other pathogenic subtypes, suggesting that WMC are unlikely to be an independent risk factor for nonsmall vessel events.

White matter changes on magnetic resonance imaging: a risk factor for stroke in an African population?

BACKGROUND: White matter changes are frequently observed incidental findings in elderly individuals. Many studies in Europe and the United States have assessed the association of white matter changes with stroke and other diseases. No similar study has been conducted in sub-Saharan Africa, where risk factors for stroke differ. Our objective was to explore the association between severity of white matter changes (based on visual rating scales) and stroke in a Nigerian population. METHODS: Magnetic resonance imaging (MRI) scans of 50 patients were retrospectively assessed and scored using 3 different visual rating scales (by Fazekas et al, Scheltens et al, and Manolio et al). The scores were classified as either mild or severe. Clinical indications and MRI scan results were classified into vascular (stroke) and nonvascular groups. The association between severity of white matter changes and stroke on MRI was explored using the Student t test, the Chi-square test, and multiple regression analysis at an alpha level of .05. RESULTS: White matter changes were consistently and significantly more severe in patients with stroke than in patients without stroke (.01 ≤ P < .001; odds ratios 4.58 and 13.3, respectively) using the 3 visual rating scales. This finding was independent of age and gender as confirmed by regression analysis (adjusted odds ratios 4.8 and 9.2; .015 ≤ P ≤ .003). CONCLUSIONS: Our findings suggest that severity of white matter changes in Nigerians may be a significant risk factor for stroke independent of age and gender. Prospective larger studies will be required to confirm its role in predicting stroke and stroke recurrence independent of other vascular risk factors, such as hypertension, diabetes, and cardiac diseases.

Leukoaraiosis is associated with short- and long-term mortality in patients with intracerebral hemorrhage.

BACKGROUND: There are few recent European studies of mortality after intracerebral hemorrhage (ICH), particularly long-term follow-up studies. No previous European studies have included information on leukoaraiosis. METHODS: We studied all consecutive patients hospitalized with a first-ever intracerebral hemorrhage between 2005 and 2009 in a well-defined area and assessed the prognostic value of various baseline clinical and radiologic factors. Leukoaraiosis was scored on the baseline computed tomographic (CT) scan as described by van Swieten et al, with an overall score from 0 to 4. RESULTS: One hundred thirty-four patients were followed up for a median of 4.7 years (interquartile range 2.5-6.6). Overall mortality was 23% at 2 days, 30% at 7 days, 37% at 30 days, 46% at 1 year, and 53% at 2 years. Factors independently associated with increased 30-day mortality were warfarin use, leukoaraiosis score, intraventricular hemorrhage, and Glasgow Coma Scale (GCS) score. Factors independently associated with long-term mortality in the 85 patients who survived the first 30 days were leukoaraiosis score, coronary heart disease, and initial GCS score. Recurrent ICH occurred in 4.5% and was significantly more frequent after lobar ICH than after ICH in other locations (11.1% v 0%; P = .025). CONCLUSIONS: In unselected patients in Southern Norway with first-ever ICH, severe leukoaraiosis is independently associated with both 30-day and long-term mortality in 30-day survivors. Warfarin is independently associated with 30-day mortality and coronary heart disease with long-term mortality in 30-day survivors. Recurrent ICH is more frequent after lobar ICH than after ICH in other locations.

Increased risk for ex-vacuo ventriculomegaly with leukoencephalopathy (EVL) in whole brain radiation therapy and repeat radiosurgery treated brain metastasis patients.

INTRODUCTION: Cerebral atrophy with leukoencephalopathy is a known morbidity after whole brain radiation therapy (WBRT), resulting in ex-vacuo ventriculomegaly with leukoencephalopathy (EVL). Here we studied the correlation between WBRT, stereotactic radiosurgery (SRS), and risk for EVL in brain metastases patients. METHODS: In a retrospective study, we identified 195 patients (with 1,018 BM) who underwent SRS for BM (2007-2017) and had > 3 months of MRI follow-up. All patients who underwent ventriculoperitoneal shunting were excluded. Cerebral atrophy was measured by ex-vacuo-ventriculomegaly, defined based on Evans' criteria. Demographic and clinical variables were analyzed using logistic regression models. RESULTS: Ex-vacuo ventriculomegaly was observed on pre-radiosurgery imaging in 29.7% (58/195) of the study cohort. On multivariate analysis, older age was the only variable associated with pre-radiosurgery ventriculomegaly. Of the 137 patients with normal ventricular size before radiosurgery, 27 (19.7 %) developed ex-vacuo ventriculomegaly and leukoencephalopathy (EVL) post-SRS. In univariate analysis, previous whole brain radiation therapy was the main factor associated with increased risk for developing EVL (OR = 5.08, p < 0.001). In bivariate models that included prior receipt of WBRT, both the number of SRS treatments (OR = 1.499, p = 0.025) and WBRT (OR = 11.321, p = 0.003 were independently associated with increased EVL risk. CONCLUSIONS: While repeat radiosurgery contributes to the risk of EVL in BM patients, this risk is ∼20-fold lower than that associated with WBRT.

Spatial and Temporal Gait Characteristics in Patients Admitted to a Neuro-Rehabilitation Department with Age-Related White Matter Changes: A Gait Analysis and Clinical Study.

BACKGROUND: Patients with age-related white matter changes (ARWMC) frequently present a gait disorder, depression and cognitive impairment. Our aims are to define which alterations in the gait parameters are associated with motor or neuro-psychological impairment and to assess the role of motor, mood or cognitive dysfunction in explaining the variance of the gait parameters. METHODS: Patients with gait disorders admitted to a Neuro-rehabilitation Department, affected by vascular leukoencephalopathy who had ARWMC confirmed by a brain MRI, were consecutively enrolled, classified by a neuroradiological scale (Fazekas 1987) and compared to healthy controls. We excluded subjects unable to walk independently, subjects with hydrocephalus or severe aphasia, with orthopaedic and other neurological pathologies conditioning the walking pattern. Patients and controls were assessed by clinical and functional scales (Mini Mental State Examination, Geriatric Depression Scale, Nevitt Motor Performance Scale, Berg Balance Scale, Functional Independence Measure), and computerised gait analysis was performed to assess the spatial and temporal gait parameters in a cross-sectional study. RESULTS: We recruited 76 patients (48 males, aged 78.3 ± 6.2 years) and 14 controls (6 males, aged 75.8 ± 5 years). In the multiple regression analysis, the gait parameter with overall best model summary values, associated with the ARWMC severity, was the stride length even after correction for age, sex, weight and height (R2 = 0.327). The motor performances justified at least in part of the gait disorder (R2 change = 0.220), but the mood state accounted independently for gait alterations (R2 change = 0.039). The increase in ARWMC severity, the reduction of motor performance and a depressed mood state were associated with a reduction of stride length (R = 0.766, R2 = 0.587), reduction of gait speed (R2 = 0.573) and an increase in double support time (R2 = 0.421). CONCLUSION: The gait disorders in patients with ARWMC are related to motor impairment, but the presence of depression is an independent factor for determining gait alterations and functional status. These data pave the way for longitudinal studies, including gait parameters, to quantitatively assess gait changes after treatment or to monitor the natural progression of the gait disorders.