Distribution Of White Matter Lesions Research Articles

Vanishing white matter disease: imaging, clinical and molecular correlation in Brazilian families.

To characterize Vanishing White Matter Disease (VWM) cases from a Brazilian University Tertiary hospital, focusing on brain magnetic resonance image (MRI) aspects, clinical and molecular data. Medical records and brain MRI of 13 genetically confirmed VWM patients were reviewed. Epidemiological data such as age at symptom onset, gender and main symptoms were analyzed, along with genetic mutations and MRI characteristics, such as the distribution of white matter lesions and atrophy. The majority of patients were female, with the age of symptom onset ranging from 1year and 6months to 40years. All mutations were identified in the EIF2B5 gene, the most prevalent being c.338G > A (p.Arg113His), and a novel mutation related to the disease was discovered, c.1051G > A (p.Gly351Ser). Trauma or infection were significant triggers. The most frequent symptoms were ataxia and limb spasticity. All MRI scans displayed deep white matter involvement, cystic degeneration, with U-fibers relatively spared and a predilection for the frontoparietal region. Lesions in the corpus callosum and posterior fossa were present in all patients. Follow-up exams revealed the evolution of white matter lesions and cerebral atrophy, which correlated with clinical deterioration. VWM affects various age groups, with a significant clinical and genetic variability. A novel mutation associated with the disease is highlighted. MRI reveals a typical pattern of white matter involvement, characterized by diffuse lesions in the periventricular and deep regions, with subsequent extension to the subcortical areas, accompanied by cystic degeneration, and plays a crucial role in diagnosis and follow-up.

Cerebral lesions sites in neurosarcoidosis: a lesion mapping study.

Sarcoidosis is a granulomatous disease of unknown etiology affecting the central nervous system in up to 15% of the patients. Diagnosis of neurosarcoidosis is very challenging due to the heterogeneity of its clinical manifestation. This study intended to evaluate the distribution of cerebral lesion sites and the potential presence of specific lesion clusters in neurosarcoidosis patients using voxel-based lesion symptom mapping (VLSM). Patients with neurosarcoidosis were retrospectively identified and included between 2011 and 2022. Cerebral lesion sites were correlated voxel-wise with presence and absence of neurosarcoidosis using non-parametric permutation test. Multiple sclerosis patients served as controls for the VLSM-analysis. Thirty-four patients (mean age 52 ± 15years) of whom 13 were diagnosed with possible, 19 with probable and 2 with confirmed neurosarcoidosis were identified. Lesion overlap of neurosarcoidosis patients demonstrated a distribution of white matter lesions in all brain areas, with a periventricular predilection similar to multiple sclerosis. In contrast to multiple sclerosis controls, no propensity for lesions in proximity of the corpus callosum was observed. Neurosarcoidosis lesions appeared smaller and lesion volume was lower in the neurosarcoidosis cohort. The VLSM analysis showed minor associations between neurosarcoidosis and damaged voxels in the bilateral frontobasal cortex. The VLSM analysis yielded significant associations in the bilateral frontal cortex, suggesting that leptomeningeal inflammatory disease with following cortical involvement is a quite specific feature in neurosarcoidosis. Lesion load was lower in neurosarcoidosis than in multiple sclerosis. However, no specific pattern of subcortical white matter lesions in neurosarcoidosis was revealed.

Differential spatial distribution of white matter lesions in Parkinson's and Alzheimer's diseases and cognitive sequelae.

White Matter Lesions (WML) are a radiological finding common in aged subjects. We explored the impact of WML on underlying neurodegenerative processes. We focused on the impact of WML on two neurodegenerative diseases with different pathology. In this cross-sectional study of 137 subjects (78 female, 59 men, mean age 67.2; 43-87years), we compared WML in healthy controls (HC; n = 55), patients with Alzheimer's disease and amnestic Mild Cognitive Impairment (aMCI), and Parkinson's disease patients with normal cognition and with MCI. Subjects with AD and aMCI were treated as one group (n = 40), subjects with PD and PDMCI were another group (n = 42). MRI T2_FLAIR sequences were analyzed. WML were divided into periventricular (pWML) or subcortical (sWML) depending on their distance from the ventricles. Subjects from the AD + aMCI group, had a significantly greater volume of WML than both HC and the PD + PDMCI group. The volume of WML was greater in the PD + PDMCI than in HC but the difference was not significant. In AD + aMCI subjects, sWML and not pWML were related to a decrease in global cognitive functioning despite greater volume of pWML. In PD + PDMCI, pWML correlate with decline in executive functions and working memory. In HC, pWML correlated with the multidomain decrease corresponding with the aging. This points to a difference between normal aging and pathological aging due to AD and PD brain pathology. The WML location together with underlying disease related neurodegeneration may play a role in determining the effect of WML on cognition. Our results suggest that the impact of WML is not uniform in all patients; rather, their volume, location and cognitive effect may be disease-specific.

The Responses to CGRP in the Territory of the Posterior Cerebral Artery in Migraine.

Calcitonin gene-related peptide (CGRP) is important in trigeminovascular (TMV) sensitization with neurogenic inflammation which might be involved in CGRP-induced headache (CGRP-IH). Distribution of white matter lesions, migraine aura, and functional neuroimaging indicate that posterior circulation is especially exposed to TMV sensitization. The transcranial Doppler (TCD) is able to detect changes in the posterior cerebral artery (PCA) during CGRP stimulation. Thus, we studied CGRP-induced hemodynamic changes in PCA and frequency of CGRP-IH. Twenty healthy subjects and 20 patients with migraine participated in our study. TCD was used to monitor mean arterial velocity in posterior cerebral artery (vmPCA). Simultaneously, end-tidal carbon dioxide (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) were measured. During the experiment, we monitored the frequency of CGRP-IH. We determined the values of vmPCA, Et-CO2, MAP, and HR and calculate the response of vmPCA, Et-CO2, MAP, and HR to CGRP. To test the differences and relationships, statistical methods were applied using SSPS. We found significant decrease in vmPCA in migraine and control groups and found the vmPCA response to be significantly lower in migraine (p = 0.018). Et-CO2 decreases in both groups, and it is significantly lower in migraine (p < 0.001). MAP is significantly higher in migraine (p = 0.001), while HR is not significantly higher in migraine (p = 0.570). CGRP-IH is significantly associated with vmPCA responses (p = 0.003) and migraine (p < 0.001). We concluded that hemodynamic changes in PCA are significantly related to CGRP-IH. The TMV sensitization might be pronounced in posterior circulation explaining clinical and morphologic issues in migraine.

White Matter Lesions May Aid in Differentiating Idiopathic Normal Pressure Hydrocephalus and Alzheimer's Disease.

Idiopathic normal pressure hydrocephalus (iNPH) is often misdiagnosed as Alzheimer's disease (AD) due to overlapping pathophysiology and similar imaging characteristics, including ventricular enlargement and increased white matter lesions (WMLs). To compare the extent and distribution of WMLs directly between iNPH and AD and examine the association with underlying pathophysiology. Twelve patients with iNPH (mean age: 78.08 years; 5 females), 20 with AD (mean age: 75.40 years; 13 females), and 10 normal cognition (NC) participants (mean age: 76.60 years; 7 females) were recruited. The extent and distribution of WMLs and the lateral ventricular volume (LV-V) were evaluated on MRI using voxel-based morphometry analysis. Concentrations of cerebrospinal fluid biomarkers, such as amyloid-β protein (Aβ)42, Aβ40, Aβ38, and tau species, were also measured. Risk factors for small vessel disease (SVD) were assessed by blood examination and medical records. The periventricular WML volume (PWML-V) and deep WML volume (DWML-V) were significantly larger in iNPH than in AD and NC. The DWML-V was dominant in iNPH, while the PWML-V was dominant in AD and NC. GM-V was significantly smaller in AD than in iNPH and NC. The LV-V positively correlated with WML-V in all participants. There was a significant negative correlation between LV-V and Aβ38 in iNPH. Furthermore, there was no significant difference in SVD risk factors between the groups. The differences in the extent and distribution of WMLs between iNPH and AD, especially predominance of DWML-V over PWML-V in iNPH, may reflect decreased fluid and Aβ clearance.

MRI signs helpful in the differentiation of patients with anterior ischaemic optic neuropathy and optic neuritis

Background/AimsThe aim of this study was to identify specific MRI characteristics of anterior ischaemic optic neuropathy (AION) and optic neuritis (ON) that would aid in the differentiation between these two...

Clinical correlates of white matter lesions in Parkinson's disease using automated multi-modal segmentation measures

BackgroundAge-related white matter lesions (WML) are common, impact neuronal connectivity, and affect motor function and cognition. In addition to pathological nigrostriatal losses, WML are also common co-morbidities in Parkinson's disease (PD) that affect postural stability and gait. Automated brain volume measures are increasingly incorporated into the clinical reporting workflow to facilitate precision in medicine. Recently, multi-modal segmentation algorithms have been developed to overcome challenges with WML quantification based on single-modality input. ObjectiveWe evaluated WML volumes and their distribution in a case-control cohort of PD patients to predict the domain-specific clinical severity using a fully automated multi-modal segmentation algorithm. MethodsFifty-five subjects comprising of twenty PD patients and thirty-five age- and gender-matched control subjects underwent standardized motor/gait and cognitive assessments and brain MRI. Spatially differentiated WML obtained using automated segmentation algorithms on multi-modal MPRAGE and FLAIR images were used to predict domain-specific clinical severity. Preliminary statistical analysis focused on describing the relationship between WML and clinical scores, and the distribution of WML by brain regions. Subsequent stepwise regressions were performed to predict each clinical score using WML volumes in different brain regions, while controlling for age. ResultsWML volume strongly correlates with both motor and cognitive dysfunctions in PD patients (p < 0.05), with differential impact in the frontal lobe and periventricular regions on cognitive domains (p < 0.01) and severity of motor deficits (p < 0.01), respectively. ConclusionAutomated multi-modal segmentation algorithms may facilitate precision medicine through regional WML load quantification, which show potential as imaging biomarkers for predicting domain-specific disease severity in PD.

Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy.

Patients infected with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) can develop a spectrum of neurological disorders, including a leukoencephalopathy of variable severity. Our aim was to characterize imaging, lab, and clinical correlates of severe coronavirus disease 2019 (COVID-19) leukoencephalopathy, which may provide insight into the SARS-CoV-2 pathophysiology. Twenty-seven consecutive patients positive for SARS-CoV-2 who had brain MR imaging following intensive care unit admission were included. Seven (7/27, 26%) developed an unusual pattern of "leukoencephalopathy with reduced diffusivity" on diffusion-weighted MR imaging. The remaining patients did not exhibit this pattern. Clinical and laboratory indices, as well as neuroimaging findings, were compared between groups. The reduced-diffusivity group had a significantly higher body mass index (36 versus 28 kg/m2, P < .01). Patients with reduced diffusivity trended toward more frequent acute renal failure (7/7, 100% versus 9/20, 45%; P = .06) and lower estimated glomerular filtration rate values (49 versus 85 mL/min; P = .06) at the time of MRI. Patients with reduced diffusivity also showed lesser mean values of the lowest hemoglobin levels (8.1 versus 10.2 g/dL, P < .05) and higher serum sodium levels (147 versus 139 mmol/L, P = .04) within 24 hours before MR imaging. The reduced-diffusivity group showed a striking and highly reproducible distribution of confluent, predominantly symmetric, supratentorial, and middle cerebellar peduncular white matter lesions (P < .001). Our findings highlight notable correlations between severe COVID-19 leukoencephalopathy with reduced diffusivity and obesity, acute renal failure, mild hypernatremia, anemia, and an unusual brain MR imaging white matter lesion distribution pattern. Together, these observations may shed light on possible SARS-CoV-2 pathophysiologic mechanisms associated with leukoencephalopathy, including borderzone ischemic changes, electrolyte transport disturbances, and silent hypoxia in the setting of the known cytokine storm syndrome that accompanies severe COVID-19.

Multimodal Ensemble-Based Segmentation of White Matter Lesions and Analysis of Their Differential Characteristics across Major Brain Regions

White matter lesions (WML) are common in a variety of brain pathologies, including ischemia affecting blood vessels deeper inside the brain’s white matter, and show an abnormal signal in T1-weighted and FLAIR images. The emergence of personalized medicine requires quantification and analysis of differential characteristics of WML across different brain regions. Manual segmentation and analysis of WMLs is laborious and time-consuming; therefore, automated methods providing robust, reproducible, and fast WML segmentation and analysis are highly desirable. In this study, we tackled the segmentation problem as a voxel-based classification problem. We developed an ensemble of different classification models, including six models of support vector machine, trained on handcrafted and transfer learning features, and five models of Residual neural network, trained on varying window sizes. The output of these models was combined through majority-voting. A series of image processing operations was applied to remove false positives in a post-processing step. Moreover, images were mapped to a standard atlas template to quantify the spatial distribution of WMLs, and a radiomic analysis of all the lesions across different brain regions was carried out. The performance of the method on multi-institutional WML Segmentation Challenge dataset (n = 150) comprising T1-weighted and FLAIR images was &gt;90% within data of each institution, multi-institutional data pooled together, and across-institution training–testing. Forty-five percent of lesions were found in the temporal lobe of the brain, and these lesions were easier to segment (95.67%) compared to lesions in other brain regions. Lesions in different brain regions were characterized by their differential characteristics of signal strength, size/shape, heterogeneity, and texture (p &lt; 0.001). The proposed multimodal ensemble-based segmentation of WML showed effective performance across all scanners. Further, the radiomic characteristics of WMLs of different brain regions provide an in vivo portrait of phenotypic heterogeneity in WMLs, which points to the need for precision diagnostics and personalized treatment.

Is there a relationship between white matter lesions associated with migraine and patent foramen ovale? Analysis of a series of patients with chronic migraine

White matter lesions are more prevalent in migraine patients than in the general population, especially those with a high frequency of attacks. A patent foramen ovale has been described as a possible link between migraine and white matter lesions. To determine the existence of a possible relationship between a patent foramen ovale and white matter lesions in a series of patients with chronic migraine. Observational, single-centre, case-control study. Eighty-nine women with chronic migraine were selected. The persistence and characteristics of the patent foramen ovale were assessed by means of a transcranial Doppler study. The patent foramen ovale was classified as small, moderate or massive. Those detected at rest were considered permanent, and the others were classified as latent. The MRI protocol included T1-enhanced sagittal images, FLAIR-T2-enhanced axial images, and a proton density and T2-FSE combined sequence. The white matter lesions were classified as deep, periventricular or both. The prevalence of patent foramen ovale (53.6% versus 48.5%; p = 0.80) and the proportion of massive, permanent patent foramen ovale were similar among patients with and without white matter lesions. Neither was there any difference in the prevalence (55.6% versus 52.6%; p = 1.00) or the characteristics of the patent foramen ovale as a function of the distribution of white matter lesions. The results do not suggest that a patent foramen ovale intervenes in the pathophysiology of the white matter lesions observed in patients with migraine.

Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy.

ObjectiveTo characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 (LMNB1).MethodsNinety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of LMNB1 and its upstream genes. We examined LMNB1 expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed.ResultsWe identified 4 patients from 3 families with LMNB1 duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of LMNB1 in patients with duplication was significantly increased. The clinical features of our patients with LMNB1 duplication were similar to those reported previously, except for the high frequency of cognitive impairment in our patients. We found 2 patients from 1 family carrying a 249-kb genomic deletion upstream of LMNB1. Patients with the deletion exhibited relatively earlier onset, more prominent cognitive impairment, and fewer autonomic symptoms than patients with duplication. The presence of cerebellar symptoms and lesions may be characteristic in our patients with the deletion compared with the previously reported family with the deletion. Magnetic resonance images of patients with the deletion exhibited a widespread distribution of white matter lesions including the anterior temporal region.ConclusionsWe identified 4 Japanese families with ADLD carrying duplication or deletion upstream of LMNB1. There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of LMNB1.

Perivenular Distribution of White Matter Lesions Evaluated by MRI Can Differentiate MS Lesions from Inflammatory Small Vessel Diseases (P6.121)

Perivenular Distribution of White Matter Lesions Evaluated by MRI Can Differentiate MS Lesions from Inflammatory Small Vessel Diseases (P6.121)

Regional Distribution of Cerebral White Matter Lesions Years After Preeclampsia and Eclampsia

To assess the distribution of cerebral white matter lesions in women who had eclampsia, preeclampsia, or normotensive pregnancies. The pathophysiology of these lesions, more often seen in formerly eclamptic and preeclamptic women, is unclear but may be related to a predisposition for vascular disease, the occurrence of the posterior reversible encephalopathy syndrome, or both while pregnant. Assessing the distribution of such lesions may give insight into their pathophysiology and possible consequences. This retrospective cohort study determined the presence, severity, and location of white matter lesions on cerebral magnetic resonance imaging scans of 64 formerly eclamptic, 74 formerly preeclamptic, and 75 parous control women. Formerly preeclamptic and eclamptic women have white matter lesions more often (34.4% [n=47] compared with 21.3% [n=16]; P<.05) and more severely (0.07 compared with 0.02 mL; P<.05) than parous women in a control group. In all women, the majority of lesions was located in the frontal lobes followed by the parietal, insular, and temporal lobes. White matter lesions are more common in women with prior pregnancies complicated by preeclampsia or eclampsia compared with parous women in a control group. In no group does regional white matter lesion distribution correspond to the occipitoparietal edema distribution seen in posterior reversible encephalopathy syndrome.

A genome-wide association study of brain lesion distribution in multiple sclerosis

Brain magnetic resonance imaging is widely used as a diagnostic and monitoring tool in multiple sclerosis and provides a non-invasive, sensitive and reproducible way to track the disease. Topological characteristics relating to the distribution and shape of lesions are recognized as important neuroradiological markers in the diagnosis of multiple sclerosis, although these have been much less well characterized quantitatively than have traditional measures such as T2 hyperintense or T1 hypointense lesion volumes. Here, we used voxel-level 3 T magnetic resonance imaging T1-weighted scans to reconstruct the 3D topology of lesions in 284 subjects with multiple sclerosis and tested whether this is a heritable phenotype. To this end, we extracted the genotypes from a published genome-wide association study on these same individuals and searched for genetic associations with lesion load, shape and topological distribution. Lesion probability maps were created to identify frequently affected areas and to assess the overall distribution of T1 lesions in the subject population as a whole. We then developed an original algorithm to cluster adjacent lesional voxels (cluxels) in each subject and tested whether cluxel topology was significantly associated with any single-nucleotide polymorphism in our data set. To focus on patterns of lesion distribution, we computed the first 10 principal components. Although principal component 1 correlated with lesion load, none of the remaining orthogonal components correlated with any other known variable. We then conducted genome-wide association studies on each of these and found 31 significant associations (false discovery rate <0.01) with principal component 8, which represents a mode of variation of lesion topology in the population. The majority of the loci can be linked to genes related to immune cell function and to myelin and neural growth; some (SYK, MYT1L, TRAPPC9, SLITKR6 and RIC3) have been previously associated with the distribution of white matter lesions in multiple sclerosis. Finally, we used a bioinformatics approach to identify a network of 48 interacting proteins showing genetic associations (P < 0.01) with cluxel topology in multiple sclerosis. This network also contains proteins expressed in immune cells and is enriched in molecules expressed in the central nervous system that contribute to neural development and regeneration. Our results show how quantitative traits derived from brain magnetic resonance images of patients with multiple sclerosis can be used as dependent variables in a genome-wide association study. With the widespread availability of powerful computing and the availability of genotyped populations, integration of imaging and genetic data sets is likely to become a mainstream tool for understanding the complex biological processes of multiple sclerosis and other brain disorders.

MRI characteristics and scoring in HDLS due to CSF1R gene mutations

To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5. We reviewed 20 brain MRI scans of 15 patients with autopsy- or biopsy-verified HDLS and CSF1R mutations. We assessed sagittal T1-, axial T1-, T2-, proton density-weighted and axial fluid-attenuated inversion recovery images for distribution of white matter lesions (WMLs), gray matter involvement, and atrophy. We calculated a severity score based on a point system (0-57) for each MRI scan. Of the patients, 93% (14 of 15) demonstrated localized WMLs with deep and subcortical involvement, whereas one patient revealed generalized WMLs. All WMLs were bilateral but asymmetric and predominantly frontal. Fourteen patients had a rapidly progressive clinical course with an initial MRI mean total severity score of 16.7 points (range 10-33.5). Gray matter pathology and brainstem atrophy were absent, and the corticospinal tracts were involved late in the disease course. There was no enhancement, and there was minimal cerebellar pathology. Recognition of the typical MRI patterns of HDLS and the use of an MRI severity score might help during the diagnostic evaluation to characterize the natural history and to monitor potential future treatments. Indicators of rapid disease progression were symptomatic disease onset before 45 years, female sex, WMLs extending beyond the frontal regions, a MRI severity score greater than 15 points, and mutation type of deletion.

Observational Study for MRI Characteristics in HDLS with a Known Gene Mutation on Chromosome 5 (P06.180)

Objective: To describe the MRI characteristics of HDLS patients with a known gene mutation on chromosome 5. Background Adult-onset leukoencephalopathies are a heterogeneous group of rare disorders, with natural histories ranging from being asymptomatic to inexorably progressive and fatal. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was first described in 1984, and is an autosomal dominant disorder. Currently, 23 HDLS reports have been published. The pathological hallmark of HDLS is cerebral white matter lesions (WML) with axonal spheroids.Recently, a chromosome 5 mutation, CSF1R , was identified. Design/Methods: Twenty brain MRIs of 15 patients with autopsy/biopsy verified HDLS and chromosome 5 mutations were reviewed. Sagittal T1-, axial T1-, T2- weighted, and FLAIR images were assessed for distribution of WML, grey matter involvement, and atrophy. Results: In this study, the mean age of onset was 44 years (range, 19-71); mean disease duration was 5 years (range, 3-11); and the mean age at death was 50 years (30-75). 80 % (12/15) demonstrated focal WML, whereas in two the lesions were patchy. One patient had generalized WMLs. All patients had bilateral, though slightly asymmetric lesions. WMLs with frontal predominance, involving deep and subcortical regions, were found in all cases. 93 % (14/15) had periventricular involvement, while 73% (11/15) had involvement of the corpus callosum. Of the latter, seven had more than one callosal segment affected and five had involvement of the entire corpus callosum. Typically, brain atrophy was present in the same region as the WMLs; however, in three cases isolated atrophy of the parietal, occipital and temporal cortices were found, respectively. Central atrophy was invariably present. Corticospinal tract involvement occurred late in the disease course. The grey matter, brain stem and cerebellum were spared, and enhancement was absent. Conclusions: MRI is valuable in helping to define the natural history of HDLS and will be useful in assessing future treatment responses. The MRI patterns of HDLS are sufficiently typical to aid in diagnosis. Supported by: ZKW is partially supported by the NIH/NINDS 1RC2NS070276, NS057567, P50NS072187, Mayo Clinic Florida (MCF) Research Committee CR program (MCF #90052030), Dystonia Medical Research Foundation, and a gift from Carl Edward Bolch, Jr., and Susan Bass Bolch (MCF #90052031/PAU #90052). SF is partially supported by MCF Research Committee CR program ( MCF #90052030). CS was partially supported by Anna-Lisa och Bror Bjornssons-, Sven and Dagmar Salens-, Signe och Olof Wallenius- and Gamla Tjanarinnor Foundations, Sweden. The Swedish Society of Medicine Gothenburg (GLS), Sweden, The Swedish Society of Medicine Sweden, The Swedish and Gothenburg Societies for the Neurologically Disabled and The Gothenburg Foundation for Neurological Research. Disclosure: Dr. Sundal has nothing to disclose. Dr. Fujioka has nothing to disclose. Dr. Van Gerpen has nothing to disclose. Dr. Wider has nothing to disclose. Dr. Aasly has nothing to disclose. Dr. Shuster has nothing to disclose. Dr. Ghetti has received personal compensation for activities with Bayer Pharmaceuticals Corporation. Dr. Ghetti has received research support from the National Institute of Health. Dr. Garbern has received personal compensation for activities with Genzyme Corporation, Lundbeck Research USA, Inc., StemCells, Inc, and Serono, Inc. as a consultant and/or speaker. Dr. Garbern has received personal compensation in an editorial capacity for Medlink Neurology. Dr. Garbern has received research support from Genzyme Corporation. Dr. Tselis has received research support from Teva Neuroscience and Biogen Idec. Dr. Swerdlow has received personal compensation for activities with Eisai, Inc. as a consultant. Dr. Miller has nothing to disclose. Dr. Rademakers has nothing to disclose. Dr. Dickson has nothing to disclose. Dr. Broderick has nothing to disclose. Dr. Wszolek has received personal compensation in an editorial capacity for Parkinsonism and Realted Disorders and European Journal of Neurology. Dr. Roeber has nothing to disclose.

Spatiotemporal distribution of white matter lesions in relapsing–remitting and secondary progressive multiple sclerosis

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. MS lesions show a typical distribution pattern and primarily affect the white matter (WM) in the periventricular zone and in the centrum semiovale. Objective: To track lesion development during disease progression, we compared the spatiotemporal distribution patterns of lesions in relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS). Methods: We used T1 and T2 weighted MR images of 209 RRMS and 62 SPMS patients acquired on two different 1.5 Tesla MR scanners in two clinical centers followed up for 25 (± 1.7) months. Both cross-sectional and longitudinal differences in lesion distribution between RRMS and SPMS patients were analyzed with lesion probability maps (LPMs) and permutation-based inference. Results: MS lesions clustered around the lateral ventricles and in the centrum semiovale. Cross-sectionally, compared to RRMS patients, the SPMS patients showed a significantly higher regional probability of T1 hypointense lesions (p≤0.03) in the callosal body, the corticospinal tract, and other tracts adjacent to the lateral ventricles, but not of T2 lesions (peak probabilities were RRMS: T1 9%, T2 18%; SPMS: T1 21%, T2 27%). No longitudinal changes of regional T1 and T2 lesion volumes between baseline and follow-up scan were found. Conclusion: The results suggest a particular vulnerability to neurodegeneration during disease progression in a number of WM tracts.

The Relationship between Normal Cerebral Perfusion Patterns and White Matter Lesion Distribution in 1,249 Patients with Multiple Sclerosis

The pathological differences underlying the clinical disease phases in multiple sclerosis (MS) are poorly characterized. We sought to explore the relationship between the distribution of white matter (WM) lesions in relapsing-remitting (RR) and secondary progressive (SP) MS and the normal regional variability of cerebral perfusion. WM lesions were identified and quantified on a single magnetic resonance imaging scan from 1,249 patients with MS. The spatial distribution of lesions was compared between early RR, late RR, and SP MS in the context of normal cerebral perfusion patterns provided by a single-photon emission-computed tomography atlas of healthy individuals. Patients with SP MS had more distinct and larger lesions than patients with RR MS. Across all subjects, lesions were present in regions of relatively lower normal perfusion than normal appearing WM. Further, lesions in SP MS were more common in areas of lower perfusion as compared to the lesion distribution in early and late RR MS. Chronic plaques were more prevalent in WM regions with lower relative perfusion. Lesions in more highly perfused regions were more commonly observed in early RR MS and therefore, may be more likely to successfully remyelinate and resolve.

Cerebral distribution of white matter lesions in migraine with aura patients

The objective of the study was to compare the cerebral distribution of white matter lesions (WMLs) between migraine patients with different aura symptoms. Migraine with aura (MA) patients were consecutively enrolled as part of the Shunt-Associated Migraine (SAM) study. According to clinical symptoms, aura was classified as motor, aphasic, sensory, visual or vertebrobasilar. Standard and FLAIR (fluid attenuated inversion recovery) T(2)-weighted MRI sequences were inspected for WMLs by three independent raters blinded to clinical data. WMLs were assessed in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Schelten's scale. Interobserver agreement was good to excellent (k = 0.64 to 0.96, p < .0001). One hundred and eighty-five patients (77% women) were included. Aura symptoms were classified as visual in 172 (99%) patients, sensory in 76 (42%), aphasic in 54 (30%), motor in 39 (21%) and vertebrobasilar in 17 (9%) patients. One hundred and four patients (57%) exhibited more than one type of aura. D-WMLs were mainly detected in the frontal lobes (86%). There was no association between type of aura and the presence of WMLs in any cerebral location. Aura symptoms do not influence the cerebral distribution of WMLs associated with migraine disease.

Cerebral white matter lesions in patients with dementia – from MCI to severe Alzheimer's disease

Background Brain images of patients with Alzheimer's disease (AD) on magnetic resonance imaging (MRI) show white matter lesions (WML), which are attributed to degenerative changes of small vessels. These lesions are supposed to be among the factors supporting the diagnosis of probable AD; however their correlation with the severity of dementia requires further studies. Methods We examined four groups of patients with cognitive impairment: Ten patients with amnestic-MCI (Mild Cognitive Impairment), 11 with mild AD (21–24 points in MMSE), 17 with moderate AD (11–20 points in MMSE) and 15 with severe AD (3–10 points in MMSE). The T2 and FLAIR MRI sequences of the brain of each patient were assessed using the White Matter Lesions Semiquantitive Rating Scale, taking into consideration the amount, size and distribution of WML. Results WML of the brain were seen in almost all patients with AD and MCI on T2 and FLAIR sequences. The positive correlation between the patients' age and the amount and size of WML, in subcortical (T2: p < 0.01, r = 0.39; FLAIR: p < 0.05, r = 0.31) and in the periventricular region (T2: p < 0.05, r = 0.28; FLAIR: p < 0.05, r = 0.35) has been shown on both sequences. There was no correlation between the size or distribution of lesions and either hypertension or homocysteine blood level. The analysis revealed also that in both sequences, the severity of lesions in the periventricular region increased with the progression of the disease (T2: p = 0.038; FLAIR: p = 0.02). Conclusions A significant factor correlating with the location of WML in patients with MCI and AD is the age of patient. The amount and size of WML in the periventricular and subcortical regions of the brain correlates with the severity of dementia. Hypertension and hyperhomocysteinemia have no influence on the presence of described lesions.