Structural brain abnormalities in patients with vestibular migraine

New advances in understanding the pathophysiology of vestibular migraine (VM) have suggested a large overlap between migraine and vestibular pathways. We explored the regional distribution of gray (GM) and white matter (WM) abnormalities in VM patients in comparison to migraine patients with (MWA) and without aura (MWoA) and their correlations with patients’ clinical manifestations. Using a 3.0 Tesla scanner, brain T2-weighted and 3D T1-weighted MRI scans were acquired from 19 VM, 19 MWA, 19 MWoA and 20 age-matched controls. GM and WM volumetric abnormalities were estimated using voxel-based morphometry (SPM12). Compared to controls, migraine patients had decreased GM volume of the left cerebellum and an increased GM volume of the left temporal lobe. VM patients had a selective GM volume increase of frontal and occipital regions compared to controls and the other two groups of migraineurs and no regions with decreased GM volume. Compared to MWoA and MWA, VM had increased GM volume of the left thalamus. Regional GM abnormalities did not correlate with disease duration and attack frequency. No WM volumetric differences were detected between migraine patients and controls. These results show that GM volume abnormalities of nociceptive and multisensory vestibular brain areas occur in VM patients. Overall, our findings suggest that an abnormal brain sensitization might lead to a dismodulation of multimodal sensory integration and processing cortical areas in VM patients.     

Differentiating shunt-responsive normal pressure hydrocephalus from Alzheimer disease and normal aging: pilot study using automated MRI brain tissue segmentation

Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 ± 8.0 years-old), 17 AD patients (10 men, 72.1 ± 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 ± 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33 % relative to HC characterized AD (P < 0.005). High preoperative ventricular and near normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3 % accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.     

Patterns of white matter atrophy in frontotemporal lobar degeneration

BACKGROUND: Structural magnetic resonance imaging (MRI) has been used to investigate the in vivo pathology of frontotemporal lobar degeneration. However, few neuroimaging studies have focused on white matter (WM) alterations in this disease. OBJECTIVES: To use volumetric MRI techniques to identify the patterns of WM atrophy in vivo in 2 clinical variants of frontotemporal lobar degeneration-frontotemporal dementia (FTD) and semantic dementia-and to compare the patterns of WM atrophy with those of gray matter (GM) atrophy in these diseases. DESIGN: Structural MRIs were obtained from patients with FTD (n = 12) and semantic dementia (n = 13) and in cognitively healthy age-matched controls (n = 24). Regional GM and WM were classified automatically from high-resolution T1-, T2-, and proton density-weighted MRIs with Expectation-Maximization Segmentation and compared between the groups using a multivariate analysis of covariance model that included age and WM lesion volumes as covariates. RESULTS: Patients with FTD had frontal WM atrophy and frontal, parietal, and temporal GM atrophy compared with controls, who had none. Patients with semantic dementia had temporal WM and GM atrophy and patients with FTD had frontal GM atrophy. Adding temporal WM volume to temporal GM volume significantly improved the discrimination between semantic dementia and FTD. CONCLUSIONS: These results show that patients with frontotemporal lobar degeneration who are in relatively early stages of the disease (Clinical Dementia Rating score, 1.0-1.2) have WM atrophy that largely parallels the pattern of GM atrophy typically associated with these disorders.     

Diffuse axonal injury in mild traumatic brain injury: a 3D multivoxel proton MR spectroscopy study

Since mild traumatic brain injury (mTBI) often leads to neurological symptoms even without clinical MRI findings, our goal was to test whether diffuse axonal injury is quantifiable with multivoxel proton MR spectroscopic imaging (¹H-MRSI). T1- and T2-weighted MRI images and three-dimensional ¹H-MRSI (480 voxels over 360 cm³, about 30 % of the brain) were acquired at 3 T from 26 mTBI patients (mean Glasgow Coma Scale score 14.7, 18–56 years old, 3–55 days after injury) and 13 healthy matched contemporaries as controls. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-matter/white-matter (GM/WM) and cerebrospinal fluid fractions were obtained in each voxel. Global GM and WM absolute metabolic concentrations were estimated using linear regression, and patients were compared with controls using two-way analysis of variance. In patients, mean NAA, Cr, Cho and mI concentrations in GM (8.4 ± 0.7, 6.9 ± 0.6, 1.3 ± 0.2, 5.5 ± 0.6 mM) and Cr, Cho and mI in WM (4.8 ± 0.5, 1.4 ± 0.2, 4.6 ± 0.7 mM) were not different from the values in controls. The NAA concentrations in WM, however, were significantly lower in patients than in controls (7.2 ± 0.8 vs. 7.7 ± 0.6 mM, p = 0.0125). The Cho and Cr levels in WM of patients were positively correlated with time since mTBI. This ¹H-MRSI approach allowed us to ascertain that early mTBI sequelae are (1) diffuse (not merely local), (2) neuronal (not glial), and (3) in the global WM (not GM). These findings support the hypothesis that, similar to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction rather than cell death dominates shortly after injury.     

Prevalence of cardiac right left shunts in migraine: a population-based case–control study

We aimed to investigate the prevalence of cardiac right left shunts (RLS) in population-based samples of subjects with migraine with aura (n = 42), migraine without aura (n = 44) and controls without headache (n = 41). Cardiac RLS was assessed with transcranial Doppler sonography with intravenous injection of saline. Prevalence of RLS was highest in migraineurs with aura (45.2%) compared to migraineurs without aura (34.1%) and controls (41.5%). Permanent as opposed to latent RLS was more common among patients with migraine with aura (40.5%) than in patients with migraine without aura (23.3%) or controls (24.4%). Differences did not reach statistical significance between the three groups (p = 0.564 for RLS prevalence, p = 0.349 for prevalence of permanent shunts). Our data implicate a trend towards higher prevalence of RLS with larger shunts in subjects with migraine with aura.     

Mild cognitive impairment in Parkinson's disease is associated with a distributed pattern of brain white matter damage

This study assesses the patterns of gray matter (GM) and white matter (WM) damage in patients with Parkinson's disease and mild cognitive impairment (PD‐MCI) compared with healthy controls and cognitively unimpaired PD patients (PD‐Cu). Three‐dimensional T1‐weighted and diffusion tensor (DT) magnetic resonance imaging (MRI) scans were obtained from 43 PD patients and 33 healthy controls. Cognition was assessed using a neuropsychological battery. Tract‐based spatial statistics was applied to compare DT MRI indices between groups on a voxel‐by‐voxel basis. Voxel‐based morphometry was performed to assess GM atrophy. Thirty PD patients were classified as MCI. Compared with healthy controls, PD‐Cu and PD‐MCI patients did not have GM atrophy. No region of WM damage was found in PD‐Cu patients when compared with healthy controls. Relative to healthy controls and PD‐Cu patients, PD‐MCI patients showed a distributed pattern of WM abnormalities in the anterior and superior corona radiata, genu, and body of the corpus callosum, and anterior inferior fronto‐occipital, uncinate, and superior longitudinal fasciculi, bilaterally. Subtle cognitive decline in PD is associated with abnormalities of frontal and interhemispheric WM connections, and not with GM atrophy. DT MRI might contribute to the identification of structural changes in PD‐MCI patients prior to the development of dementia. Hum Brain Mapp 35:1921–1929, 2014. © 2013 Wiley Periodicals, Inc.     

Voxel-based morphometry and intellectual assessment in patients with congenital bilateral perisylvian syndrome

Congenital bilateral perisylvian syndrome (CBPS) presents with heterogeneous clinical manifestations such as pseudobulbar palsy, language disorder, variable cognitive deficits, epilepsy, and perisylvian abnormalities (most frequently polymicrogyria) on imaging studies. We investigated the relationship between seizures and extent of gray matter (GM) and white matter (WM) abnormalities using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI) as well the association between seizures, structural abnormalities and cognitive ability. In this cross-sectional study, we evaluated 51 healthy volunteers and 18 patients with CBPS with epilepsy (seizure group, n = 7) and without (non-seizure group, n = 11). We used VBM (SPM8/DARTEL) to investigate areas with excess and atrophy of both gray and white matter, comparing groups of patients with controls. Intellectual ability of patients was assessed by the WISC-III or WAIS-III. Both groups with CBPS and the control group were homogeneous with respect to gender (p = 0.07) and age (p = 0.065). Besides perisylvian polymicrogyria, the seizure group exhibited areas with GM and WM reduction including temporal, frontal, parietal and occipital lobes. In contrast, we identified fewer areas with GM and WM reduction in the non-seizure group. The seizure group presented worse intellectual performance (performance IQ and global IQ) than the non-seizure group. The seizure group presented with a more widespread pattern of cortical and sub-cortical abnormalities, as well as worse cognition. Our results suggest that patients with CBPS and epilepsy appear to have widespread neuronal damage that goes beyond the areas with MRI-visible perisylvian polymicrogyria.     

Relevance of early cervical cord volume loss in the disease evolution of clinically isolated syndrome and early multiple sclerosis: a 2-year follow-up study

Upper cervical cord area (UCCA) atrophy is a prognostic marker for clinical progression in longstanding multiple sclerosis (MS). The objectives of the study were to quantify UCCA atrophy and evaluate its impact in clinically isolated syndrome (CIS) and relapsing–remitting MS (RRMS); to compare converting CIS patients with stable CIS, and to study changes of UCCA and brain white matter (WM) and grey matter (GM) at 2-year follow-up. 110 therapy-naive patients including 53 CIS [6 ± 6 months after symptom onset (SO)] and 57 early RRMS (SO: 12 ± 9 months) underwent sagittal 3D-T1w brain MR (3T). Mean UCCA (C1–C3 level), WM and GM, disability status (EDSS), pyramidal and sensory functional scores, motoric fatigue were assessed at baseline (BL), 12 and 24 months. Volumes were compared with 34 age- and gender-matched healthy controls to assess atrophy. RRMS (78.1 ± 8.7 mm², p = 0.011) and converting CIS (77.3 ± 8.0 mm², p = 0.046) presented with baseline UCCA atrophy, when compared with controls (82.7 ± 5.2 mm²), but not stable CIS (82.6 ± 7.4 mm², p = 0.998). Baseline WM was reduced in RRMS (509.3 ± 25.7 ml vs. controls: 528.4 ± 24.1 ml, p = 0.032). Baseline UCCA correlated negative with muscular weakness and fatigability in all patients and RRMS. EDSS exceeding 3 was associated with lower baseline UCCA. Longitudinal atrophy rates were higher in UCCA than in brain volumes. Early cervical cord atrophy in CIS and RRMS was confirmed and may represent a potential new risk marker for conversion from CIS to MS. Baseline atrophy and atrophy change rates were higher in UCCA compared to WM and GM, suggesting that cervical cord volumetry might become an additional MRI marker relevant in future clinical studies in CIS and early MS.     

Comparison of diffusion tensor imaging and voxel-based morphometry to detect white matter damage in Alzheimer's disease

Regional atrophy of gray matter (GM) in Alzheimer's disease (AD) is well known; however, the relationship between macroscopic and microscopic changes of cerebral white matter (WM) is uncertain. The aim of this study was to investigate the pattern of GM, WM atrophy, and microscopic WM changes in the same individuals with AD. All subjects (10AD and 15 healthy controls [HC]) underwent a MRI scanning at 1.5 T, including a 3-dimensional volumetric scan and diffusion tensor imaging (DTI). We performed statistical parametric mapping (SPM) with DTI to evaluate the patterns of the microscopic WM changes, as well as voxel-based morphometry (VBM) for GM and WM volume changes between patients with AD and HC. GM atrophy was detected, mainly in posterior regions, and WM atrophy was similarly distributed, but less involved on VBM analysis. Unlike WM atrophy on VBM analysis, microscopic WM changes were shown in the medial frontal, orbitofrontal, splenium of the corpus callosum, and cingulum on DTI analysis with SPM. We demonstrated that the pattern of macroscopic WM atrophy was similar to GM atrophy, while microscopic WM changes had a different pattern and distribution. Our findings suggest that WM atrophy may preferentially reflect the secondary changes of GM atrophy, while microscopic WM changes start earlier in frontal areas before GM and WM atrophy can be detected macroscopically.     

Attention and processing speed performance in multiple sclerosis is mostly related to thalamic volume

Cognitive impairment (CI), mainly involving attention and processing speed (A-PS), is a common and disabling symptom in multiple sclerosis (MS). Symbol Digit Modalities Test (SDMT) is one of the more sensitive and reliable tests to assess A-PS deficits in MS. Structural MRI correlates of A-PS in MS still need to be clarified. This study aimed to investigate, in a large group of MS patients, the relationship between regional gray matter (GM) atrophy and SDMT performance. 125 relapsing remitting MS patients and 52 healthy controls (HC) underwent a 3 T–MRI protocol including high-resolution 3D–T1 imaging. All subjects underwent a neurological evaluation and SDMT. A Voxel Based Morphometry analysis was performed to assess: 1) correlations between regional GM volume and SDMT performance in MS patients; 2) regional differences in GM volume between MS patients and HC. Thalamic, putamen and cerebellar volumes were also calculated using FIRST tool from the FMRIB Software Library. A linear regression analysis was performed to assess the contribution of each one of these structures to A-PS performance. A significant negative correlation was found between regional GM volume and SDMT score at the level of the thalamus, cerebellum, putamen, and occipital cortex in MS patients. Thalamus, cerebellum and putamen also showed significant GM atrophy in MS patients compared to HC. Thalamic atrophy is also an independent and additional contributor to A-PS deficits in MS patients. These findings support the role of thalamus as the most relevant GM structure subtending A-PS performance in MS, as measured by SDMT.     

Patterns of regional gray matter and white matter atrophy in cortical multiple sclerosis

We investigated the patterns of regional distribution of focal lesions, white matter (WM) and gray matter (GM) atrophy in patients with cortical (cort) MS in comparison to classical (c) MS patients. Nine cort-MS, nine c-MS and nine age-matched healthy controls (HC) underwent a brain MRI exam, including FLAIR and high-resolution T1-weighted scans. MS patients underwent neurological and neuropsychological assessment. Between-group differences of GM and WM volumes and their correlations with neuropsychological performances were assessed with voxel-based morphometry. FLAIR and T1 lesion probability maps (LPMs) were also obtained. Performance at neuropsychological tests was worse in cort-MS than in c-MS patients. Compared to HC, MS patients had a distributed pattern of GM and WM atrophy. No GM/WM area was more atrophic in c-MS vs cort-MS patients. Compared to c-MS, cort-MS patients experienced GM atrophy of frontal–temporal–parietal areas and cingulate cortex and WM atrophy of the cingulum bundle, bilateral cerebral peduncles, right inferior longitudinal fasciculus and left superior longitudinal fasciculus. FLAIR and T1 LPMs did not differ between c-MS vs cort-MS patients. A higher susceptibility to neurodegenerative processes in key brain regions known to be related to cognitive functions is likely to underlie the clinical manifestations of cort-MS.     

Migraine with aura and brain magnetic resonance imaging abnormalities in patients with CADASIL

BACKGROUND: Migraine with aura (MA) is one of the clinical hallmarks of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease of the brain caused by mutations in the NOTCH3 gene, but its exact mechanisms are unknown. OBJECTIVES: To describe the patterns of MA in CADASIL and to compare brain magnetic resonance signal abnormalities between CADASIL patients with and without MA. DESIGN: Comparison of brain magnetic resonance signal abnormalities between cases and controls. SETTING: Patients with CADASIL seen at Lariboisière Hospital. PATIENTS: Forty-one CADASIL patients with MA and 31 age-matched CADASIL controls without MA. RESULTS: The mean age at onset of MA was significantly younger in women compared with men and occurred a mean of 15 years prior to stroke onset. A majority of patients (56%) reported at least 1 migraine attack with atypical aura. All CADASIL patients either with or without MA had white matter signal abnormalities on T2-weighted imaging. There was no difference in the frequency and distribution of brain signal abnormalities between CADASIL patients with and without MA. CONCLUSIONS: In CADASIL, MA is characterized by an unusually high frequency of attacks of migraine with atypical aura. The distribution and extent of magnetic resonance signal abnormalities did not differ according to migraine phenotype.     

Voxel-based morphometric study of brain volume changes in patients with Alzheimer’s disease assessed according to the Clinical Dementia Rating score

We evaluated the volume reduction of gray matter (GM) and white matter (WM) in patients with an Alzheimer’s disease (AD) assessment based on the Clinical Dementia Rating (CDR) score. Patients with AD (n = 61), with no subcortical WM ischemia, and healthy control patients (n = 33) underwent T1-weighted spoiled gradient echo sequences, which were analyzed using voxel-based morphometry. Global GM volume reduction was observed in patients with a CDR score of 1 or a CDR score of 2, and WM volume reduction was observed in patients with a CDR score of 2. Regional GM volume reduction was found in the right inferior frontal gyrus, bilateral dorso-lateral and medial temporal lobes; WM volume reduction was found in the bilateral temporal subcortex (family-wise error, p < 0.01). A CDR score of 0.5 was associated with volume reduction in the left olfactory gyrus. The peak z-score and spatial extent of volume reduction increased with increasing CDR score and were higher on the left side. GM volume reduction increased with increasing CDR scores and suggests a possible pathomechanism of AD.     

Lymphocyte subsets in pediatric migraine

Aseptic inflammation due to activated immune cells has been implicated in the pathomechanism of migraine. We measured the prevalence of regulatory T cells (Tregs), along with that of CD4⁺/CD8⁺ lymphocytes and their Th1/Th2 commitment in pediatric migraine. Children and adolescents suffering from migraine without aura, migraine with aura and hemiplegic migraine ictally (n = 53, 27, and 20, respectively), also interictally (n = 33) were recruited and compared to 24 healthy children. Our results indicated comparable prevalence of Tregs, CD4⁺ and Th1/Th2 committed cells. CD8⁺ prevalence was lower, and CD4⁺/CD8⁺ ratio was higher in ictal phase irrespective of the subtype of migraine. No association between CD8⁺ prevalence and gender, body weight, disease onset and attack duration in migraine subtypes was found. CD8⁺ prevalence was normal in patients in interictal phase. These results suggest the absence of major systemic alteration of adaptive immunity in children and adolescents suffering from migraine; however, a transient decrease of CD8⁺ prevalence during the ictal phase was detected irrespective of the subtype of migraine.     

Increased orbital frontal gray matter volume after cognitive behavioural therapy in paediatric obsessive compulsive disorder

Abstract

Objectives. Identify differences in regional brain volume between medication-free pediatric OCD patients and controls and examine changes after cognitive behavioural therapy. Methods. We assessed 29 medication-free paediatric OCD patients (Age: M =?13.78 years; SD =?2.58; range 8.2–19.0) and 29 controls, matched on age and gender, with T1-weighted MR scans in a repeated measures, pre-post treatment design. Voxel based morphometry (VBM) following diffeomorphic anatomical registration through exponential lie algebra (DARTEL) was used to test voxel-wise for the effects of diagnosis and treatment on regional gray matter (GM) and white matter (WM) volumes. Results. After cognitive behavioural therapy, orbitofrontal GM and capsula externa WM increased in paediatric OCD relative to controls. In patients, changes in symptom severity (delta CY-BOCS) correlated positively with GM volume in the orbitofrontal cortex after treatment. Furthermore, before treatment, paediatric OCD patients, compared to the controls, showed larger GM volume in left frontal pole and left parietal cortex and larger WM volume in cingulum and corpus callosum. Conclusions. Our findings underscore the involvement of the ventral frontal-striatal circuit in paediatric OCD and the plasticity of this circuit in response to the modulatory effects of CBT. The possible relation to brain development is discussed.     

Patients with migraine do not have MRI-visible cortical lesions

Migraine patients with multiple brain white matter hyperintensities (WMHs) may represent a diagnostic challenge. Using double inversion recovery (DIR) imaging, we studied whether cortical lesions (CLs) could be seen in these patients. Approval of the institutional review boards and written informed consent were obtained from each participant. CLs and WM lesions were assessed on brain scans from 32 migraine patients with WMHs (17 patients with and 15 without aura), and in two control groups, consisting of 15 relapsing-remitting multiple sclerosis (RRMS) patients and 20 healthy controls, matched for age and gender. By definition, brain WM lesions were detected in all migraine and RRMS patients. The number and volume of WM lesions were lower in migraine versus RRMS patients (p?<?0.0001). No CLs were identified in migraine patients and healthy controls, whereas 20 CLs were seen in 9 (60?%) RRMS patients. The application of DIR imaging to assess focal cortical involvement seems to be useful in the diagnostic workup of patients with WMHs of unknown etiology, including those with migraine.     

Hierarchical cluster analysis of multimodal imaging data identifies brain atrophy and cognitive patterns in Parkinson’s disease

BackgroundParkinson's disease (PD) is a heterogeneous condition. Cluster analysis based on cortical thickness has been used to define distinct patterns of brain atrophy in PD. However, the potential of other neuroimaging modalities, such as white matter (WM) fractional anisotropy (FA), which has also been demonstrated to be altered in PD, has not been investigated.ObjectiveWe aim to characterize PD subtypes using a multimodal clustering approach based on cortical and subcortical gray matter (GM) volumes and FA measures.MethodsWe included T1-weighted and diffusion-weighted MRI data from 62 PD patients and 33 healthy controls. We extracted mean GM volumes from 48 cortical and 17 subcortical regions using FSL-VBM, and the mean FA from 20 WM tracts using Tract-Based Spatial Statistics (TBSS). Hierarchical cluster analysis was performed with the PD sample using Ward's linkage method. Whole-brain voxel-wise intergroup comparisons of VBM and TBSS data were also performed using FSL. Neuropsychological and demographic statistical analyses were conducted using IBM SPSS Statistics 25.0.ResultsWe identified three PD subtypes, with prominent differences in GM patterns and little WM involvement. One group (n = 15) with widespread cortical and subcortical GM volume and WM FA reductions and pronounced cognitive deficits; a second group (n = 21) with only cortical atrophy limited to frontal and temporal regions and more specific neuropsychological impairment, and a third group (n = 26) without detectable atrophy or cognition impairment.ConclusionMultimodal MRI data allows classifying PD patients into groups according to GM and WM patterns, which in turn are associated with the cognitive profile.     

Progression of regional atrophy in the left hemisphere contributes to clinical and cognitive deterioration in multiple sclerosis: A 5‐year study

In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five‐year follow‐up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual‐echo and 3D T1‐weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse‐onset and primary progressive MS) and 16 matched controls. Lesion probability maps were obtained. Longitudinal changes of GM and WM volumes and their association with clinical and cognitive deterioration were assessed using tensor‐based morphometry and SPM12. At FU, 36/66 (54.5%) MS patients showed a significant disability worsening, 14/66 (21.2%) evolved to a worse clinical phenotype, and 18/63 (28.6%) developed cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM atrophy, involving cortex, deep GM and cerebellum, and atrophy of the majority of WM tracts, which further progressed at FU (P < 0.001, uncorrected). Compared to stable patients, those with clinical and cognitive worsening showed a left‐lateralized pattern of GM and WM atrophy, involving deep GM, fronto‐temporo‐parieto‐occipital regions, cerebellum, and several WM tracts (P < 0.001, uncorrected).GM and WM atrophy of relevant brain regions occur in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage may be among the factors contributing to clinical and cognitive worsening in these patients. Hum Brain Mapp 38:5648–5665, 2017. © 2017 Wiley Periodicals, Inc.     

Gray matter atrophy and white matter lesions burden in delayed cognitive decline following carbon monoxide poisoning

Gray matter (GM) atrophy and white matter (WM) lesions may contribute to cognitive decline in patients with delayed neurological sequelae (DNS) after carbon monoxide (CO) poisoning. However, there is currently a lack of evidence supporting this relationship. This study aimed to investigate the volume of GM, cortical thickness, and burden of WM lesions in 33 DNS patients with dementia, 24 DNS patients with mild cognitive impairment, and 51 healthy controls. Various methods, including voxel-based, deformation-based, surface-based, and atlas-based analyses, were used to examine GM structures. Furthermore, we explored the connection between GM volume changes, WM lesions burden, and cognitive decline. Compared to the healthy controls, both patient groups exhibited widespread GM atrophy in the cerebral cortices (for volume and cortical thickness), subcortical nuclei (for volume), and cerebellum (for volume) (p < .05 corrected for false discovery rate [FDR]). The total volume of GM atrophy in 31 subregions, which included the default mode network (DMN), visual network (VN), and cerebellar network (CN) (p < .05, FDR-corrected), independently contributed to the severity of cognitive impairment (p < .05). Additionally, WM lesions impacted cognitive decline through both direct and indirect effects, with the latter mediated by volume reduction in 16 subregions of cognitive networks (p < .05). These preliminary findings suggested that both GM atrophy and WM lesions were involved in cognitive decline in DNS patients following CO poisoning. Moreover, the reduction in the volume of DMN, VN, and posterior CN nodes mediated the WM lesions-induced cognitive decline.