Multiple White Matter Research Articles

Neurological deficit following stereotactic radiosurgery for trigeminal neuralgia

We report a unique case of neurological deficit from late onset multiple sclerosis (MS), in a 65-year-old woman, after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). At 3.5months post-SRS for TN, the patient developed ataxia and left leg paraesthesiae and brain MRI showed altered signal and enhancement in the vicinity of the right trigeminal root entry zone (REZ). The symptoms remitted following treatment with intravenous methylprednisolone, however, 10months post-SRS, the patient developed gait ataxia and left lower limb weakness. MRI showed persistent T2 changes at the REZ and multiple new non-enhancing white matter lesions in the cerebrum and spinal cord; and oligoclonal bands were present in the cerebrospinal fluid but not serum. A diagnosis of multiple sclerosis (MS) was made. This report raises the issue of whether the risk of radiation-induced toxicity is increased in patients with MS treated with SRS. We hypothesise that breakdown in the blood brain barrier secondary to the radiosurgery may have triggered a vigorous local inflammatory response.

Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in Rats.

Perinatal infection is a well-identified risk factor for a number of neurodevelopmental disorders, including brain white matter injury (WMI) and Autism Spectrum Disorders (ASD). The underlying mechanisms by which early life inflammatory events cause aberrant neural, cytoarchitectural, and network organization, remain elusive. This study is aimed to investigate how systemic lipopolysaccharide (LPS)-induced neuroinflammation affects microglia phenotypes and early neural developmental events in rats. We show here that LPS exposure at early postnatal day 3 leads to a robust microglia activation which is characterized with mixed microglial proinflammatory (M1) and anti-inflammatory (M2) phenotypes. More specifically, we found that microglial M1 markers iNOS and MHC-II were induced at relatively low levels in a regionally restricted manner, whereas M2 markers CD206 and TGFβ were strongly upregulated in a sub-set of activated microglia in multiple white and gray matter structures. This unique microglial response was associated with a marked decrease in naturally occurring apoptosis, but an increase in cell proliferation in the subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus. LPS exposure also leads to a significant increase in oligodendrocyte lineage population without causing discernible hypermyelination. Moreover, LPS-exposed rats exhibited significant impairments in communicative and cognitive functions. These findings suggest a possible role of M2-like microglial activation in abnormal neural development that may underlie ASD-like behavioral impairments.

Altered whole-brain connectivity in albinism.

Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc.

Socioeconomic status, white matter, and executive function in children.

BackgroundA growing body of evidence links socioeconomic status (SES) to children's brain structure. Few studies, however, have specifically investigated relations of SES to white matter structure. Further, although several studies have demonstrated that family SES is related to development of brain areas that support executive functions (EF), less is known about the role that white matter structure plays in the relation of SES to EF. One possibility is that white matter differences may partially explain SES disparities in EF (i.e., a mediating relationship). Alternatively, SES may differentially shape brain‐behavior relations such that the relation of white matter structure to EF may differ as a function of SES (i.e., a moderating relationship).MethodIn a diverse sample of 1082 children and adolescents aged 3–21 years, we examined socioeconomic disparities in white matter macrostructure and microstructure. We further investigated relations between family SES, children's white matter volume and integrity in tracts supporting EF, and performance on EF tasks.ResultsSocioeconomic status was associated with fractional anisotropy (FA) and volume in multiple white matter tracts. Additionally, family income moderated the relation between white matter structure and cognitive flexibility. Specifically, across multiple tracts of interest, lower FA or lower volume was associated with reduced cognitive flexibility among children from lower income families. In contrast, children from higher income families showed preserved cognitive flexibility in the face of low white matter FA or volume. SES factors did not mediate or moderate links between white matter and either working memory or inhibitory control.ConclusionsThis work adds to a growing body of literature suggesting that the socioeconomic contexts in which children develop not only shape cognitive functioning and its underlying neurobiology, but may also shape the relations between brain and behavior.

Children with Poor Reading Skills at the Word Level Show Reduced Fractional Anisotropy in White Matter Tracts of Both Hemispheres.

Diffusion tensor imaging (DTI) studies showed that microstructural alterations are correlated to reading skills. In this study, we aim to investigate white matter microstructure of a group of Portuguese speakers with poor reading level, using different parameters of DTI. To perform this analysis, we selected children ranging from 8 to 12 years of age, poor readers (n = 17) and good readers (n = 23), evaluated in the word-level ability based on a Latent Class Analysis (LCA) of Academic Performance Test (TDE). Poor readers exhibited significant fractional anisotropy (FA) reductions in many tracts of both hemispheres, but small and restricted clusters of increased radial diffusivity (RD) in the left hemisphere. Spatial coherence of fibers might be the main source of differences, as changes in FA were not similarly accompanied in terms of extension by changes in RD. Widespread structural alterations in the white matter could prevent good reading ability at word level, which is consistent with recent studies demonstrating the involvement of multiple cortical regions and white matter tracts in reading disabilities.

Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response

Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences.

CADASIL RAPIDLY ACCELERATED BY HYPOTENSION POST-TRAUMA: AUTOPSY REVEALS IMPORTANT CONTRIBUTION OF BOTH ARTERIES AND VEINS IN WHITE MATTER PATHOLOGY

Vascular reactivity of subcortical arteries is impaired in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This ‘earthen pipe’ state impairs autoregulation with dependency on blood pressure for brain perfusion. Chronic hypoperfusion can cause ischemic damage but less is known about the effects of acute hypotension. Additionally, the contribution of veins has been overlooked in conditions with leukoaraiosis, in general (including Alzheimer’s disease), and in CADASIL specifically. We describe the imaging and pathological findings of a case in whom CADASIL was dramatically accelerated following acute episodes of hypotension. Interestingly, venous collagenosis was demonstrated in the periventricular white matter regions. Case report with neuroimaging and pathological data. A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture, and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He expired within 5 weeks of the trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy, and multiple cavitations involving deep subcortical grey and white matter. Small arteries had thickened walls, disruption of the muscularis and intimal PAS-positive material (Fig 1A). Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis (Fig 1 B,C). There was no pathological evidence of global hypoxia or diffuse axonal injury. The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. Additionally, collagenosis of veins in the affected white matter regions is a novel finding not yet reported in CADASIL, to our knowledge. A few reports have suggested an integral role of collagenized veins in age-related leukoaraiosis and this may also apply to CADASIL. This case underscores the importance of blood pressure regulation in patients with CADASIL and highlights the potential importance of veins in white matter pathology. Cerebral arterial and venous pathology in white matter hyperintensities in CADASIL A. Arteriole containing PAS positive granular material within the media (arrow). B. Collagenosis of periventricular veins (arrows) highlighted by Masson's trichrome. C. The collagenized veins (arrows) do not contain the PAS positive material within their collagenized walls.

Hyperglycemia Reduces Efficiency of Brain Networks in Subjects with Type 2 Diabetes.

Previous research has shown that the brain is an important target of diabetic complications. Since brain regions are interconnected to form a large-scale neural network, we investigated whether severe hyperglycemia affects the topology of the brain network in people with type 2 diabetes. Twenty middle-aged (average age: 54 years) individuals with poorly controlled diabetes (HbA1c: 8.9−14.6%, 74−136 mmol/mol) and 20 age-, sex-, and education-matched healthy volunteers were recruited. Graph theoretic network analysis was performed with axonal fiber tractography and tract-based spatial statistics (TBSS) using diffusion tensor imaging. Associations between the blood glucose level and white matter network characteristics were investigated. Individuals with diabetes had lower white matter network efficiency (P<0.001) and longer white matter path length (P<0.05) compared to healthy individuals. Higher HbA1c was associated with lower network efficiency (r = −0.53, P = 0.001) and longer network path length (r = 0.40, P<0.05). A disruption in local microstructural integrity was found in the multiple white matter regions and associated with higher HbA1c and fasting plasma glucose levels (corrected P<0.05). Poorer glycemic control is associated with lower efficiency and longer connection paths of the global brain network in individuals with diabetes. Chronic hyperglycemia in people with diabetes may disrupt the brain’s topological integration, and lead to mental slowing and cognitive impairment.

Analysis of head impact exposure and brain microstructure response in a season-long application of a jugular vein compression collar: a prospective, neuroimaging investigation in American football.

BackgroundHistorical approaches to protect the brain from outside the skull (eg, helmets and mouthpieces) have been ineffective in reducing internal injury to the brain that arises from energy absorption during sports-related collisions. We aimed to evaluate the effects of a neck collar, which applies gentle bilateral jugular vein compression, resulting in cerebral venous engorgement to reduce head impact energy absorption during collision. Specifically, we investigated the effect of collar wearing during head impact exposure on brain microstructure integrity following a competitive high school American football season.MethodsA prospective longitudinal controlled trial was employed to evaluate the effects of collar wearing (n=32) relative to controls (CTRL; n=30) during one competitive football season (age: 17.04±0.67 years). Impact exposure was collected using helmet sensors and white matter (WM) integrity was quantified based on diffusion tensor imaging (DTI) serving as the primary outcome.ResultsWith similar overall g-forces and total head impact exposure experienced in the two study groups during the season (p>0.05), significant preseason to postseason changes in mean diffusivity, axial diffusivity and radial diffusivity in the WM integrity were noted in the CTRL group (corrected p<0.05) but not in the collar group (p>0.05). The CTRL group demonstrated significantly larger preseason to postseason DTI change in multiple WM regions compared with the collar group (corrected p<0.05).DiscussionReduced WM diffusivity alteration was noted in participants wearing a neck collar after a season of competitive football. Collar wearing may have provided a protective effect against brain microstructural changes after repetitive head impacts.Trial registration numberNCT02696200.

56. Intracerebroventricular and Intravenous AAV Gene Therapy in Canine Globoid Cell Leukodystrophy

Globoid cell leukodystrophy (GLD), or Krabbe disease, results from a deficiency in the hydrolytic enzyme galactosylceramidase (GALC), which is responsible for degrading the central and peripheral nervous system (CNS, PNS) myelin lipids galactosylceramide and galactosylsphingosine (psychosine). Symptoms in infants include irritability and stiffness with disease progressing rapidly to a vegetative state and death typically resulting by 2 years of age. GLD is naturally occurring in dogs and signs include ataxia, tremors, pelvic limb paralysis, loss of hearing, and blindness, with disease progression warranting euthanasia at 15.9 ± 4.6 weeks. In GLD dogs, GALC concentrations are decreased in leukocytes, CSF, and tissues and psychosine concentrations are elevated in serum and CSF. Conduction velocities in peripheral nerves of GLD dogs are < 50% of normal and G-ratios of the sciatic nerve are significantly higher than normal. Brain stem auditory evoked response testing exhibits a loss of waveform integrity and increased central conduction time consistent with auditory system demyelination. MRI of the brain shows T2-weighted hyperintensity of the white matter, widened sulci, and enlarged ventricles and MRS identified decreases in N-acetylaspartate and increases in choline. Diffusion tensor imaging established decreased fractional anisotropy and increased radial diffusivity in multiple white matter tracts including the corpus callosum and posterior internal capsule. Histologically, GLD dogs revealed severe loss of myelin, a decrease in oligodendrocytes, astrogliosis, and microgliosis. Combination gene therapy has been evaluated in GLD affected dogs using AAVrh10 encoding canine GALC (AAVrh10-cGALC). Two GLD dogs received a low dose of AAVrh10-cGALC, 1.2E12, by combination intravenous (IV) and intracerebroventricular (ICV) injection routes and displayed a modest increase in survival to 17.9 and 22.1 weeks of age. Two additional GLD dogs were treated with an increased dose of AAVrh10-cGALC, 1.9E13, and survival was further increased to 30.3 and 43.1 weeks of age. Both low and high dose combination IV and ICV therapy delayed the onset of neurological signs and prevented the onset of tremors, one of the debilitating neurologic signs in untreated GLD dogs. High dose AAVrh10-cGALC, but not low dose, resulted in complete normalization of pelvic and thoracic limb NCV and near normal sensory NCV. Combination therapy of either dose had negligible effect on the auditory system, as treated animals showed little to no improvement in distance between waveform peaks or hearing threshold over untreated animals. After high dose treatment with AAVrh10-cGALC, GALC activity reached near normal levels in the cerebellum and sciatic nerve, with levels decreasing in more distal brain regions. GALC levels in the liver and heart were intermediate between affected untreated GLD and normal control dogs. Interestingly, the highest GALC activity was found in the quadriceps muscle. GLD dogs treated with high dose AAV had CSF psychosine concentrations lower than untreated and low dose AAV-treated GLD dogs, despite being substantially older. Efficacy of hematopoietic stem cell transplant (HSCT) alone and in combination with IV AAVrh10-cGALC is currently being evaluated in GLD dogs. Ongoing studies suggest that addition of IV infusion of AAVrh10-cGALC substantially increases survival as compared to HSCT alone.

Peripheral sphingolipids are associated with variation in white matter microstructure in older adults

Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging.

The selective anatomical vulnerability of ALS: ‘disease-defining’ and ‘disease-defying’ brain regions

A large multiparametric MRI study has been undertaken to evaluate anatomical patterns of basal ganglia, white matter and cortical grey matter involvement in ALS. Unaffected brain regions are mapped in patients with significant disability. Multiple white matter diffusivity measures, cortical grey matter density alterations, basal ganglia volumes and subcortical grey matter atrophy patterns are evaluated. Results demonstrated a strikingly selective anatomical vulnerability pattern in ALS that preferentially affects specific grey matter structures, commissural white matter tracts and basal ganglia regions, suggestive of networkwise neurodegeneration in ALS. In conclusion, ALS pathology exhibits predilection for selective and inter-connected anatomical sites that can be comprehensively characterized in vivo by multiparametric neuroimaging. The systematic characterization of unaffected brain regions in ALS has implications for the development of classifier analyses and elucidation of disease biology. The involvement and sparing of contiguous brain regions raises important pathophysiological, phylogenetic and ontogenetic questions regarding ALS pathogenesis and disease spread.

White matter microstructural changes are associated with alcohol use in patients with panic disorder

BackgroundA close relationship between panic disorder (PD) and alcohol use disorder (AUD) has been suggested. We aimed to investigate alterations in white matter (WM) volume or integrity in patients with PD comorbid with AUD. MethodsForty-nine patients with PD, free of comorbid AUD (PD−AUD), and 20 patients with PD comorbid with AUD (PD+AUD) were investigated. All subjects were assessed using the Panic Disorder Severity Scale, Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Depression Inventory, and CAGE questionnaire. Voxel-based morphometry and tract-based spatial statistics were used for imaging analysis. ResultsIncreased fractional anisotropy (FA), as well as decreased mean diffusivity and radial diffusivity were observed in multiple WM tracts, including the body and splenium of the corpus callosum and the retrolenticular part of the internal capsule, in the PD+AUD group compared to the PD–AUD group. CAGE scores in the PD+AUD group and ASI-R scores in the PD−AUD group were significantly correlated with FA values for the corpus callosum. No WM volume differences were found. LimitationsThe present study should be considered preliminary due to relatively small sample size. ConclusionsOur findings revealed microstructural changes in multiple WM tracts, including the corpus callosum and internal capsule, suggesting they could be significant neural correlates of AUD in patients with PD.

Elevated Expression of the Cerebrospinal Fluid Disease Markers Chromogranin A and Clusterin in Astrocytes of Multiple Sclerosis White Matter Lesions.

Using proteomics, we previously identified chromogranin A (CgA) and clusterin (CLU) as disease-related proteins in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). CgA and CLU are involved in cell survival and are implicated in neurodegenerative disorders and may also have roles in MS pathophysiology. We investigated CgA and CLU expression in lesions and nonlesional regions in postmortem brains of MS patients and controls and in the brains of marmosets with experimental autoimmune encephalomyelitis. By quantitative PCR, mRNA levels of CgA and CLU were elevated in white matter but not in grey matter of MS patients. In situ analyses showed greater expression of CgA and CLU in white matter lesions than in normal-appearing regions in MS patients and in the marmosets, primarily in or adjacent to perivascular spaces and inflammatory infiltrates. Both proteins were expressed by glial fibrillary acidic protein-positive astrocytes. CgA was more localized in astrocytic processes and endfeet surrounding blood vessels and was abundant in the superficial glia limitans and ependyma, 2 CSF-brain borders. Increased expression of CgA and CLU in reactive astrocytes in MS white matter lesions supports a role for these molecules as neuro-inflammatory mediators and their potential as CSF markers of active pathological processes in MS patients.

Atypical age-dependent effects of autism on white matter microstructure in children of 2-7 years.

Atypical age-dependent changes of white matter (WM) microstructure play a central role in abnormal brain maturation of the children with autism spectrum disorder (ASD), but their early manifestations have not been systematically characterized. The entire brain core WM voxels were surveyed to detect differences in WM microstructural development between 31 children with ASD of 2-7 years and 19 age-matched children with typical development (TD), using measurements of fractional anisotropy (FA) and radial diffusivity (RD) from diffusion tensor imaging (DTI). The anatomical locations, distribution, and extent of the core WM voxels with atypical age-dependent changes in a specific tract or tract group were delineated and evaluated by integrating the skeletonized WM with a digital atlas. Exclusively, unidirectional FA increases and RD decreases in widespread WM tracts were revealed in children with ASD before 4 years, with bi-directional changes found for children with ASD of 2-7 years. Compared to progressive development that raised FA and lowered RD during 2-7 years in the TD group, flattened curves of WM maturation were found in multiple major WM tracts of all five tract groups, particularly associational and limbic tracts, in the ASD group with trend lines of ASD and TD crossed around 4 years. We found atypical age-dependent changes of FA and RD widely and heterogeneously distributed in WM tracts of children with ASD. The early higher WM microstructural integrity before 4 years reflects abnormal neural patterning, connectivity, and pruning that may contribute to aberrant behavioral and cognitive development in ASD. Hum Brain Mapp 37:819-832, 2016. © 2015 Wiley Periodicals, Inc.

How to make an oligodendrocyte.

Oligodendrocytes produce myelin, an insulating sheath required for the saltatory conduction of electrical impulses along axons. Oligodendrocyte loss results in demyelination, which leads to impaired neurological function in a broad array of diseases ranging from pediatric leukodystrophies and cerebral palsy, to multiple sclerosis and white matter stroke. Accordingly, replacing lost oligodendrocytes, whether by transplanting oligodendrocyte progenitor cells (OPCs) or by mobilizing endogenous progenitors, holds great promise as a therapeutic strategy for the diseases of central white matter. In this Primer, we describe the molecular events regulating oligodendrocyte development and how our understanding of this process has led to the establishment of methods for producing OPCs and oligodendrocytes from embryonic stem cells and induced pluripotent stem cells, as well as directly from somatic cells. In addition, we will discuss the safety of engrafted stem cell-derived OPCs, as well as approaches by which to modulate their differentiation and myelinogenesis in vivo following transplantation.

Exploratory screening for Fabry's disease in young adults with cerebrovascular disorders in northern Sardinia.

BackgroundThe etiologic determinants of stroke in young adults remain a diagnostic challenge in up to one-fourth of cases. Increasing evidences led to consider Fabry’s disease (FD) as a possible cause to check up. We aimed at evaluating the prevalence of unrecognized FD in a cohort of patients with juvenile stroke in northern Sardinia.MethodsFor this study, we enrolled 178 patients consecutively admitted to our Neurological Ward for ischemic stroke, transient ischemic attack, intracerebral haemorrhage, neuroradiological evidence of silent infarcts, or white matter lesions possibly related to cerebral vasculopathy at brain MRI, and cerebral venous thrombosis. The qualifying events have to occur between 18 and 55 years of age.ResultsWe identified two patients with an α-galactosidase A gene variant, with a prevalence of 0.9 %. According to recent diagnostic criteria, one patient, included for the occurrence of multiple white matter lesions at brain MRI, had a diagnosis of definite FD, the other, included for ischemic stroke, had a diagnosis of uncertain FD.ConclusionsOur study places in a middle position among studies that found a prevalence of FD up to 4 % and others that did not find any FD patients. Our findings confirm that FD should be considered in the differential diagnosis of patients with juvenile stroke, particularly those with a personal or familial history positive for cerebrovascular events, or evidence of combined cardiologic and/or renal impairment. All types of cerebrovascular disorders should be screened for FD, including patients with white matter lesions possibly related to cerebral vasculopathy at brain MRI.

Magnetic resonance brain imaging in patients with visual vertigo.

Patients with visual vertigo (VV) report dizziness provoked by moving visual surroundings. It has been suggested that these subjects develop a compensation strategy for a vestibulo-proprioceptive deficit and rely excessively on visual input. We have postulated that patients with VV might have brain abnormalities that interfere with appropriate processing of visual stimulation and performed a brain MRI study to verify this hypothesis. Patients with VV of more than 3 months duration were included. They were asked to complete the Situational Characteristic Questionnaire (SCQ) that scores for the symptoms of VV. Dizzy patients without VV served as controls. A brain MRI was performed with a Siemens 1.5 Tesla scanner in patients and controls. Twenty-four patients with VV were included. Their mean SCQ score was 1.45 ± 0.9 (normal 0.16 ± 0.28). In 50% of patients, abnormalities in MRI imaging were found. Thirty-three percent of 27 controls demonstrated an abnormal brain MRI. The two groups were similar in respect to the prevalence of a localized hemispheric or posterior fossa lesion (P = 0.13), but VV patients had more unspecific white matter brain changes than controls (P = 0.009). Patients and controls did not differ in age and gender distribution (P = 0.9) or the history of a neurotological event preceding their symptoms (P = 0.3). Our study suggests that multiple white matter lesions might contribute to occurrence of the phenomenon of VV. Future prospective large-scale studies by specific MR techniques are indicated to validate our preliminary findings and elucidate the pathological mechanism of VV.

Effect of Simulated Microgravity on Human Brain Gray Matter and White Matter--Evidence from MRI.

BackgroundThere is limited and inconclusive evidence that space environment, especially microgravity condition, may affect microstructure of human brain. This experiment hypothesized that there would be modifications in gray matter (GM) and white matter (WM) of the brain due to microgravity.MethodEighteen male volunteers were recruited and fourteen volunteers underwent -6° head-down bed rest (HDBR) for 30 days simulated microgravity. High-resolution brain anatomical imaging data and diffusion tensor imaging images were collected on a 3T MR system before and after HDBR. We applied voxel-based morphometry and tract-based spatial statistics analysis to investigate the structural changes in GM and WM of brain.ResultsWe observed significant decreases of GM volume in the bilateral frontal lobes, temporal poles, parahippocampal gyrus, insula and right hippocampus, and increases of GM volume in the vermis, bilateral paracentral lobule, right precuneus gyrus, left precentral gyrus and left postcentral gyrus after HDBR. Fractional anisotropy (FA) changes were also observed in multiple WM tracts.ConclusionThese regions showing GM changes are closely associated with the functional domains of performance, locomotion, learning, memory and coordination. Regional WM alterations may be related to brain function decline and adaption. Our findings provide the neuroanatomical evidence of brain dysfunction or plasticity in microgravity condition and a deeper insight into the cerebral mechanisms in microgravity condition.

Quantitative assessments of traumatic axonal injury in human brain: concordance of microdialysis and advanced MRI.

Axonal injury is a major contributor to adverse outcomes following brain trauma. However, the extent of axonal injury cannot currently be assessed reliably in living humans. Here, we used two experimental methods with distinct noise sources and limitations in the same cohort of 15 patients with severe traumatic brain injury to assess axonal injury. One hundred kilodalton cut-off microdialysis catheters were implanted at a median time of 17 h (13-29 h) after injury in normal appearing (on computed tomography scan) frontal white matter in all patients, and samples were collected for at least 72 h. Multiple analytes, such as the metabolic markers glucose, lactate, pyruvate, glutamate and tau and amyloid-β proteins, were measured every 1-2 h in the microdialysis samples. Diffusion tensor magnetic resonance imaging scans at 3 T were performed 2-9 weeks after injury in 11 patients. Stability of diffusion tensor imaging findings was verified by repeat scans 1-3 years later in seven patients. An additional four patients were scanned only at 1-3 years after injury. Imaging abnormalities were assessed based on comparisons with five healthy control subjects for each patient, matched by age and sex (32 controls in total). No safety concerns arose during either microdialysis or scanning. We found that acute microdialysis measurements of the axonal cytoskeletal protein tau in the brain extracellular space correlated well with diffusion tensor magnetic resonance imaging-based measurements of reduced brain white matter integrity in the 1-cm radius white matter-masked region near the microdialysis catheter insertion sites. Specifically, we found a significant inverse correlation between microdialysis measured levels of tau 13-36 h after injury and anisotropy reductions in comparison with healthy controls (Spearman's r = -0.64, P = 0.006). Anisotropy reductions near microdialysis catheter insertion sites were highly correlated with reductions in multiple additional white matter regions. We interpret this result to mean that both microdialysis and diffusion tensor magnetic resonance imaging accurately reflect the same pathophysiological process: traumatic axonal injury. This cross-validation increases confidence in both methods for the clinical assessment of axonal injury. However, neither microdialysis nor diffusion tensor magnetic resonance imaging have been validated versus post-mortem histology in humans. Furthermore, future work will be required to determine the prognostic significance of these assessments of traumatic axonal injury when combined with other clinical and radiological measures.