Nadir Abdelrahman

Extent of cerebellum, subcortical and cortical atrophy in patients with MS: A case-control study

Cortical and subcortical atrophy occurs in multiple sclerosis (MS) and relates to clinical outcomes. FreeSurfer, a voxel-based automated software for brain reconstruction was used to investigate the extent of subcortical and cortical atrophy in 71 MS and 17 clinically isolated syndrome (CIS) patients, and 38 normal controls (NC), and to relate group differences to disease type and severity. Segmentation was performed on 3D SPGR T1-weighted MRI 1.5T images. Region-specific subcortical tissue volumes were calculated in mm(3) and cortical thickness in mm. Logistic regression and general linear model analyses, adjusted for age and intracranial volume, examined differences between NC, MS and CIS patients and disease subtypes. The MS group was characterized by significantly lower volumes of thalamus (left and right p<0.0001), left inferior lateral ventricle, third ventricle (p<0.0001), ventral diencephalon, pallidum and putamen bilaterally, as well as of right accumbens and brainstem with corresponding bilateral increase in volumes of lateral ventricles (p<0.01). Focal cortical atrophy areas in the thalamus, inferior parietal lobule of left hemisphere and in right precuneus were also significant in the MS sample. Versus CIS patients, RR or progressive MS patients showed significantly lower volumes of subcortical regions and cortical thinning. Hippocampal atrophy appeared only in advanced disease stages. Cerebellum WM volumes were significantly lower in MS and CIS patients vs. NC. Subcortical and cortical atrophy correlated with higher disability as measured by EDSS. This study confirmed selective deep gray matter atrophy (mostly thalamic), revealed cerebellum WM atrophy from the earliest clinical stages, and showed that cortical thinning advances with disease progression.

Independent contributions of cortical gray matter atrophy and ventricle enlargement for predicting neuropsychological impairment in multiple sclerosis

The primary goal of this study was to investigate associations between regional gray matter (GM) atrophy and neuropsychological function in multiple sclerosis (MS), while accounting for the influence of central brain atrophy (i.e. third ventricle enlargement). Using a cross-sectional design, we studied 59 MS patients with brain MRI and neuropsychological testing. Regional gray matter fractions (rGMFs) were calculated from MRI images for 11 homologous brain areas using the semiautomatic brain region extraction (SABRE) technique. Neuropsychological testing followed consensus panel guidelines and included tests emphasizing episodic memory, working memory and processing speed. The analytic approach was stepwise linear regression, with forward selection and p<0.05 threshold for significance. Consistent with previous research, there were significant correlations between third ventricle width and neuropsychological tests. Stepwise linear regression analyses controlling for third ventricle width retained rGMFs obtained from specific regions within the prefrontal cortex. Left frontal atrophy was associated with tests emphasizing auditory/verbal memory. Right frontal atrophy was associated with impairment in visual episodic and working memory. For the first time, we show an independent relationship between cortical atrophy and cognitive impairment after accounting for the effects of central atrophy.

Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis

Background: Cigarette smoking has been linked to higher susceptibility and increased risk of progressive multiple sclerosis (MS). The effects of smoking on MRI characteristics of patients with MS have not been evaluated. Objectives: To compare the MRI characteristics in cigarette smoker and nonsmoker patients with MS. Methods: We studied 368 consecutive patients with MS (age 44.0 ±SD 10.2 years, disease duration 12.1 ± 9.1 years) comprising 240 never-smokers and 128 (34.8%) ever-smokers (currently active and former smokers). The average number of packs per day smoked (±SD) was 0.95 ± 0.65, and the mean duration of smoking was 18.0 ± 9.5 years. All patients obtained full clinical and quantitative MRI evaluation. MRI measures included T1, T2, and gadolinium contrast-enhancing (CE) lesion volumes (LVs) and measures of central, global, and tissue-specific brain atrophy. The associations between smoking status and MRI measurements were assessed in regression analysis. Results: Smoking was associated with increased Expanded Disability Status Scale (EDSS) scores (p = 0.004). The median EDSS scores (interquartile range) in the ever-smoker group and the active-smoker group were both 3.0 (2.0), compared with 2.5 (2.5) in never-smokers. There were adverse associations between smoking and the lesion measures including increased number of CE lesions (p < 0.001), T2 LV (p = 0.009), and T1 LV (p = 0.003). Smoking was associated with decreased brain parenchymal fraction (p = 0.047) and with increases in the lateral ventricle volume (p = 0.001) and third ventricle width (p = 0.023). Conclusions: Smoking is associated with increased blood–brain barrier disruption, higher lesion volumes, and greater atrophy in multiple sclerosis.

Comparison of Three Different Methods for Measurement of Cervical Cord Atrophy in Multiple Sclerosis

BACKGROUND AND PURPOSE: Evidence is mounting that spinal cord atrophy significantly correlates with disability in patients with multiple sclerosis (MS). The purpose of this work was to validate 3 different measures for the measurement of cervical cord atrophy on high-resolution MR imaging in patients with MS and in normal control subjects (NCs). We also wanted to evaluate the relationship between cervical cord atrophy and clinical disability in the presence of other conventional and nonconventional brain MR imaging metrics by using a unique additive variance regression model. MATERIALS AND METHODS: We studied 66 MS patients (age, 41.2 ± 12.4 years; disease duration, 11.8 ± 10.7 years; Expanded Disability Status Scale, 3.1 ± 2.1) and 19 NCs (age, 30.4 ± 12.0 years). Disease course was relapsing-remitting (34), secondary-progressive (14), primary-progressive (7), and clinically isolated syndrome (11). The cervical cord absolute volume (CCAV) in cubic millimeters and 2 normalized cervical cord measures were calculated as follows: cervical cord fraction (CCF) = CCAV/thecal sac absolute volume, and cervical cord to intracranial volume (ICV) fraction (CCAV/ICV). Cervical and brain lesion volume measures, brain parenchyma fraction (BPF), and mean diffusivity were also calculated. RESULTS: CCAV (P < .0001) and CCF (P = .007) showed the largest differences between NCs and MS patients and between different disease subtypes. In regression analysis predicting disability, CCAV was retained first (R2 = 0.498; P < .0001) followed by BPF (R2 = 0.08; P = .08). Only 8% of the variance in disability was explained by brain MR imaging measures when coadjusted for the amount of cervical cord atrophy. CONCLUSIONS: 3D CCAV measurement showed the largest differences between NCs and MS patients and between different disease subtypes. Cervical cord atrophy measurement provides valuable additional information related to disability that is not obtainable from brain MR imaging metrics.

Gender-related differences in MS: a study of conventional and nonconventional MRI measures

Background Studies showed gender-associated differences in multiple sclerosis (MS) disease evolution and in the evolution of conventional magnetic resonance imaging (MRI) findings. Objective The aim of this study was to investigate gender differences according to a number of conventional and nonconventional MRI measures in patients with MS. Methods We examined 763 consecutive patients with MS [499 (19.2% men) relapsing-remitting (RR), 230 (24.8% men) secondary-progressive, and 34 (44.1% men) primary-progressive], 32 (21.9% men) patients with clinically isolated syndrome (CIS), and 101 (30.7% men) normal controls (NC). Patients were assessed using conventional and nonconventional MRI measures. Gender-related MRI differences were investigated using general linear model analysis, corrected for MS disease type. Results In the total MS group, male patients showed lower normalized peripheral gray matter (GM) (P < 0.001) and normalized GM (P = 0.011) volumes than female patients. Female patients presented lower normalized white matter (WM) volumes (P = 0.011). These gender effects were not observed in NC. Male patients also showed more advanced central atrophy (P = 0.022). In RRMS male patients, there was also a higher lateral ventricle volume (P = 0.001). The GM-WM normalized ratio was lower for male patients with MS compared with male NC (0.97 vs. 1.09, P < 0.001) but not in patients with CIS compared with NC. Conclusions There were no significant gender-related differences regarding nonconventional MRI measures. GM and central atrophy are more advanced in male patients, whereas WM atrophy is more advanced in female patients. These gender-related MRI differences may be explained by the effect of sex hormones on brain damage and repair mechanisms.

Cortical atrophy and personality in multiple sclerosis.

Although the cognitive disorder of multiple sclerosis (MS) is well characterized, little is known about personality changes that may occur in this disease. There are reliable personality tests available for research in neurological disease, based on the well-known Five Factor Model. Preliminary research suggests that cognitively impaired MS patients exhibit elevation in Neuroticism, and diminution in Extraversion, Agreeableness, and Conscientiousness, as do patients with Alzheimers disease. We predicted that these characteristics would be associated with lower neocortical volume. We studied 44 patients using brain MRI and the NEO Five-Factor Inventory. Regression models controlling for T2 lesion volume, depression, and cognitive dysfunction revealed significant correlation between cortical atrophy and reduction in Extraversion and Conscientiousness. Discrepancies between patient- and informant-reports were found, and overreporting of high Openness and Conscientiousness among patients was associated with lower neocortical volume. A final regression model accounting for depression, cognitive function, and personality accounted for 38% of the variance in neocortical volume. These findings suggest that cortical atrophy in MS is associated with adverse impact on personality, although longitudinal research is needed to test this hypothesis.

Increased tissue damage and lesion volumes in African Americans with multiple sclerosis

Background: African American (AA) patients with multiple sclerosis (MS) have more rapid disease progression and poorer responses to disease-modifying therapies than white American (WA) patients with MS. Objectives: To investigate brain MRI characteristics in AA compared to WA in a cohort of consecutive patients with MS. Methods: We studied 567 patients with MS (age: 45.1 ± SD 9.8 years, disease duration: 13.4 ± 8.6 years), comprised of 488 WA and 79 AA. All patients obtained clinical and quantitative MRI evaluation. The majority of patients, 96% of AA and 94% of WA, were on disease-modifying therapies. The MRI measures included T1-, T2-, and gadolinium contrast-enhancing (CE) lesion volumes (LV) and CE number, global and tissue-specific brain atrophy, and magnetization transfer ratio (MTR) in lesions and normal-appearing gray matter (NAGM) and white matter (NAWM). The associations between race and clinical and MRI measurements were assessed in regression analysis. Results: The MTR values in lesions and in NAGM and NAWM were significantly lower in AA compared to WA. The AA group had 31% greater T2-LV and 101% greater T1-LV compared to WA. The MS Severity Score for AA (mean ± SD = 4.3 ± 2.9) was greater than for WA (3.8 ± 2.5), despite a shorter disease duration in AA, indicating more aggressive clinical disease. Conclusions: African American patients showed increased tissue damage, as measured by magnetization transfer ratio, and presented higher lesion volumes compared to white Americans. The greater tissue damage and faster lesion volume accumulation may explain the rapid clinical progression in African American patients.

Use of perfusion- and diffusion-weighted imaging in differential diagnosis of acute and chronic ischemic stroke and multiple sclerosis

Abstract Objective: To investigate differences in lesions and surrounding normal appearing white matter (NAWM) by perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in patients with acute and chronic ischemic stroke and multiple sclerosis (MS). Methods: Study subjects included 45 MS patients, 22 patients with acute ischemic stroke and 20 patients with chronic ischemic stroke. All subjects underwent T2-weighted imaging (WI), flair attenuated inversion recovery (FLAIR), DWI and dynamic contrast enhanced PWI. Apparent diffusion coefficient (ADC) and mean transit time (MTT) maps were generated and values were calculated in the acute and chronic ischemic and demyelinating lesions, and in NAWM for distances of 5, 10 and 15 mm. Fifty-three acute ischemic and 33 acute demyelinating lesions, and 775 chronic ischemic and 998 chronic demyelinating lesions, were examined. Univariate, multivariate and data mining analyses were used to examine the feasibility of a prediction model between different lesion types. Correctly and incorrectly classified lesions, true positive (TP), false positive (FP) and precision rates were calculated. Results: Patients with acute ischemic lesions presented more prolonged mean MTT values in lesions (p=0.002) and surrounding NAWM for distances of 5, 10 and 15 mm (all p<0.0001) than those with acute demyelinating lesions. In multinomial logistic regression analysis, 65 of 86 acute lesions were correctly classified (75.6%). The TP rates were 81.1% for acute ischemic lesions and 66.7% for acute demyelinating lesions. The FP rates were 33.3% for acute ischemic and 18.9% for acute demyelinating lesions. The precision was 79.6% for classification of acute ischemic lesions and 68.8% for prediction of acute demyelinating lesions. The logistic model tree decision algorithm revealed that prolonged MTT of surrounding NAWM for a distance of 15 mm (≥7459.2 ms) was the best classifier of acute ischemic versus acute demyelinating lesions. Patients with chronic ischemic lesions presented higher mean ADC (p<0.0001) and prolonged MTT (p=0.013) in lesions, and in surrounding NAWM for distances of 5, 10 and 15 mm (all p<0.0001), compared to the patients with chronic demyelinating lesions. Data mining analyses did not show reliable predictability for correctly discerning between chronic ischemic and chronic demyelinating lesions. The precision was 56.7% for classification of chronic ischemic and 58.9% for prediction of chronic demyelinating lesions. Discussion: We found prolonged MTT values in lesions and surrounding NAWM of patients with acute and chronic ischemic stroke when compared to MS patients. The use of PWI is a promising tool for differential diagnosis between acute ischemic and acute demyelinating lesions. The results of this study contribute to a better understanding of the extent of hemodynamic abnormalities in lesions and surrounding NAWM in patients with MS.

Glatiramer acetate recovers microscopic tissue damage in patients with multiple sclerosis. A case-control diffusion imaging study.

Traditional magnetic resonance imaging (MRI) techniques have contributed to the management of multiple sclerosis (MS) but are limited in their ability to detect neuronal damage. Advanced MRI metrics provide assessment of microscopic neuronal changes; however, few studies have examined the effects of MS therapies on these measures. This prospective, open-label, observational study evaluated the effect of subcutaneous glatiramer acetate (GA) 20mg/day on the 1- and 2-year changes in diffusion-weighted imaging (DWI) measures in patients with relapsing-remitting (RR) MS and in age- and sex-matched healthy controls (HC). Inclusion criteria were age 18-65, RR disease course, expanded disability status scale (EDSS) score ≤5.5 and disease duration<20 years. MS patients and HC underwent 1.5T MRI scans and clinical examinations at baseline and at 1- and 2-year follow-up. Nineteen RRMS patients and 16 HC completed the 1-year follow-up and 16 MS patients and 13 HC the 2-year follow-up of the study. In MS patients, treatment with GA promoted recovery of DWI mean parenchymal diffusivity (MPD) at year 1 (-7.1%, p=0.007) and at year 2 (-10.1%, p=0.028). The recovery of DWI MPD was significantly higher in MS patients compared to HC at year 1 (p=0.01) and year 2 (p<0.001). GA promoted recovery of DWI entropy at 2 years (-1.2%, p=0.018). No significant DWI MPD and entropy changes were observed in HC over the follow-up. No significant deterioration in magnetization transfer ratio occurred over the follow-up in MS patients and HC. Patients on GA and HC did not develop significant global or regional atrophy over 2 years. GA significantly improved microscopic tissue damage in the brain, as measured by DWI over the 1- and 2-year follow-up.

MRI characteristics of familial and sporadic multiple sclerosis patients

Purpose: To investigate the MRI characteristics in a large cohort of multiple sclerosis (MS) patients with and without a family history of MS. Methods: Enrolled in this prospective study were 758 consecutive MS patients (mean age 46.2 ± 10.1 years, disease duration 13.6 ± 9.2 years and EDSS 3.4 ± 2.1), of whom 477 had relapsing–remitting, 222 secondary-progressive, and 30 primary-progressive disease courses and 29 had clinically isolated syndrome. One hundred and ninety-six patients (25.9%) had a positive family history of MS. Patients were assessed using measurements of lesions, brain atrophy, magnetization transfer ratio (MTR) and diffusion-weighted imaging. Results: The familial MS group had greater T1-lesion volume (p=0.009) and a trend for lower MTR of T1-lesion volume (p=0.047) than the sporadic MS group. No clinical differences were found between familial versus sporadic group, or by a degree of affected relative subgroups. Conclusions: While familial MS was associated with more severe T1-lesion volume and its MTR characteristics, there were no clinical status differences between familial and sporadic MS patients. Therefore, a better understanding of the genetic and/or epigenetic influences causing these differences can advance the understanding and management of MS.