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Rohit Bakshi

Publications and source records attributed to Rohit Bakshi.

At least 19 recordsLinked to original sources

Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis.

BACKGROUND: The relationship of gray and white matter atrophy in multiple sclerosis (MS) to neuropsychological and neuropsychiatric impairment has not been examined. METHODS: In 40 patients with MS and 15 age-/sex-matched normal controls, the authors used SPM99 to obtain whole brain normalized volumes of gray and white matter, as well as measured conventional lesion burden (total T1 hypointense and FLAIR hyperintense lesion volume). The whole brain segmentation was corrected for misclassification related to MS brain lesions. To compare the effects of gray matter, white matter, and lesion volumes with respect to brain-behavior relationships, the MS group (disease duration = 11.2 +/- 8.8 years; EDSS score = 3.3 +/- 1.9) underwent neuropsychological assessment, and was compared to a separate, larger group of age-/sex-matched normal controls (n = 83). RESULTS: The MS group had smaller gray (p = 0.009) and white matter volume (p = 0.018), impaired cognitive performance (verbal memory, visual memory, processing speed, and working memory) (all p < 0.0001), and greater neuropsychiatric symptoms (depression, p < 0.0001; dysphoria, p < 0.0001; irritability, p < 0.0001; anxiety, p < 0.0001; euphoria, p = 0.006; agitation, p = 0.02; apathy, p = 0.02; and disinhibition, p = 0.11) vs controls. Hierarchical stepwise regression analysis revealed that whole gray and white matter volumes accounted for greater variance than lesion burden in explaining cognitive performance and neuropsychiatric symptoms. White matter volume was the best predictor of mental processing speed and working memory, whereas gray matter volume predicted verbal memory, euphoria, and disinhibition. CONCLUSION: Both gray and white brain matter atrophy contribute to neuropsychological deficits in multiple sclerosis.

Atrophy↗

IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event.

BACKGROUND: The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) showed that IM interferon beta-1a (IFNbeta-1a) significantly slows the rate of development of clinically definite multiple sclerosis (CDMS) over 2 years in high-risk patients who experience a first clinical demyelinating event. This report highlights the primary results of a 5-year, open-label extension of CHAMPS (the Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance [CHAMPIONS Study]). OBJECTIVE: To determine if the benefits of IFNbeta-1a observed in CHAMPS are sustained for up to 5 years. METHODS: CHAMPS patients at participating CHAMPIONS sites were enrolled in the study. All patients were offered, but not required to take, IFNbeta-1a 30 microg IM once weekly for up to 5 years (from CHAMPS randomization). Patients who received placebo in CHAMPS were considered the delayed treatment (DT) group, and patients who received IFNbeta-1a in CHAMPS were considered the immediate treatment (IT) group. The primary outcome measure was the rate of development of CDMS. Additional outcomes included disease state classification at 5 years, annualized relapse rates, disability level at 5 years (Expanded Disability Status Scale), and MRI measures at 5 years. RESULTS: Fifty-three percent (203/383) of patients enrolled in CHAMPIONS (n = 100, IT group; n = 103, DT group) and 64% (32/50) of CHAMPS study sites participated in CHAMPIONS. The median time to initiation of IFNbeta-1a therapy in the DT group was 29 months. The cumulative probability of development of CDMS was significantly lower in the IT group compared with the DT group (5-year incidence 36 +/- 9 vs 49 +/- 10%; p = 0.03). Multivariate analysis suggested that the only factors independently associated with an increased rate of development of CDMS were randomization to the DT group and younger age at onset of neurologic symptoms. Few patients in either group developed major disability within 5 years. CONCLUSIONS: These results support the use of IM interferon beta-1a after a first clinical demyelinating event and indicate that there may be modest beneficial effects of immediate treatment compared with delayed initiation of treatment.

Adjuvants, Immunologic↗

Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease).

BACKGROUND: Neuromyelitis optica is a severe demyelinating disease that selectively involves the optic nerves and the spinal cord but usually spares the brain. It is considered to have a B-cell-induced pathogenesis. Mitoxantrone hydrochloride, a synthetic anthracenedione approved for worsening relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis, has been shown to primarily suppress the humoral response. OBJECTIVE: To evaluate the benefit of mitoxantrone treatment in patients with relapsing neuromyelitis optica. DESIGN: Prospective 2-year study. SETTING: Academic multiple sclerosis center. PATIENTS: Five patients (3 women and 2 men) with an age range of 20 to 51 years and an Expanded Disability Status Scale score of 2.5 to 6.5 (mean +/- SD, 4.40 +/- 1.88). INTERVENTIONS: Monthly intravenous infusions of mitoxantrone hydrochloride, 12 mg/m2, for 6 months followed by 3 additional treatments every 3 months. MAIN OUTCOME MEASURES: Expanded Disability Status Scale score measured every 3 months and during relapses; findings on orbital, brain, and spinal cord magnetic resonance images performed at baseline and at 3, 6, 12, 18, and 24 months; and visual evoked potentials and results of ophthalmologic evaluations performed at baseline and annually. RESULTS: During the 2 years of treatment, 2 patients each had a relapse once within the initial 5 months of treatment (1 severe and 1 moderate). Improvement was seen clinically and on magnetic resonance images in 4 patients. Patients generally tolerated the treatment well, although 1 patient had a reversible decrease in cardiac ejection fraction. CONCLUSION: Our results suggest a beneficial effect of mitoxantrone treatment for relapsing neuromyelitis optica.

Adult↗

The measurement and clinical relevance of brain atrophy in multiple sclerosis.

Brain atrophy has emerged as a clinically relevant component of disease progression in multiple sclerosis. Progressive loss of brain tissue bulk can be detected in vivo in a sensitive and reproducible manner by MRI. Clinical studies have shown that brain atrophy begins early in the disease course. The increasing amount of data linking brain atrophy to clinical impairments suggest that irreversible tissue destruction is an important determinant of disease progression to a greater extent than can be explained by conventional lesion assessments. In this review, we will summarise the proposed mechanisms contributing to brain atrophy in patients with multiple sclerosis. We will critically discuss the wide range of MRI-based methods used to quantify regional and whole-brain-volume loss. Based on a review of current information, we will summarise the rate of atrophy among phenotypes for multiple sclerosis, the clinical relevance of brain atrophy, and the effect of disease-modifying treatments on its progression.

Atrophy↗

A magnetization transfer MRI study of deep gray matter involvement in multiple sclerosis.

BACKGROUND/PURPOSE: Gray matter involvement in multiple sclerosis (MS) is of growing interest with respect to disease pathogenesis. Magnetization transfer imaging (MTI), an advanced MRI technique, is sensitive to disease in normal appearing white matter (NAWM) in patients with MS. DESIGN/METHODS: We tested if MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n= 60) vs. age-matched normal controls (NL, n= 20). Magnetization transfer ratio (MTR) maps were produced from axial proton density, conventional spin-echo, 5 mm gapless slices covering the whole brain. Region-of-interest-derived MTR histograms for the caudate, putamen, globus pallidus, thalamus, and NAWM were obtained. Whole brain MTR was also measured. RESULTS: Mean whole brain MTR and the peak position of the NAWM MTR histogram were lower in patients with MS than NL (P < .001) and mean whole brain MTR was lower in secondary progressive (SP, n= 10) than relapsing-remitting (RR, n= 50, P < .001) patients. However, none of the subcortical gray matter nuclei showed MTR differences in MS vs. NL, RR vs. SP, or SP vs. NL. CONCLUSIONS: The MTI technique used in this cohort was relatively insensitive to disease in the deep gray matter nuclei despite showing sensitivity for whole brain disease in MS. It remains to be determined if other MRI techniques are more sensitive than MTI for detecting pathology in these areas.

Adult↗

Syncope and head CT scans in the emergency department.

CONTEXT: Patients presenting with syncope to the emergency department (ED) of a community hospital were evaluated. AIM: The objective of this study is to examine the use and results of head computerized tomography (CT) scans in patients presenting with syncope to the ED of a community hospital. SETTINGS AND DESIGN: A retrospective chart review of patients presenting with syncope to the emergency room was conducted. METHODS AND MATERIALS: We reviewed the charts of patients who presented to the ED over a 6-month period with syncope. When performed, head CT scan findings were noted, and their relationship to the clinical presentation was examined. RESULTS: One hundred twenty-eight patients were identified. Forty-four patients had their head CT scans performed. In 1 patient, the CT scan showed evidence of infarction in the posterior circulation. In 19 patients, the head CT scan was normal. Twenty-four patients had abnormal findings unrelated to the ED presentation. CONCLUSIONS: Head CT scans were commonly used in our series of syncope patients. Abnormal findings pertinent to the syncope were observed in only 1 patient. A prospective study examining yield in a larger series of patients may help define the utility of this neuroimaging modality in syncope.

Adult↗

The relationship between whole brain volume and disability in multiple sclerosis: a comparison of normalized gray vs. white matter with misclassification correction.

We used SPM99 to obtain normalized whole brain volumes of gray matter, white matter, and total parenchyma in patients with multiple sclerosis (MS) (n = 41) and age-/sex-matched normal controls (n = 18). As SPM99's automated gray/white matter volumes were significantly influenced by tissue compartment misclassification due to the effect of MS-related brain lesions, we corrected these automated volumes for misclassification before performing our primary analyses. For MS patients (disease duration = 9.5 +/- 6.3 years; EDSS score = 3.2 +/- 1.8; 25FTW = 6.6 +/- 3.1 s), we also measured lesion load (total T1 hypointense [T1LV] and FLAIR hyperintense lesion volume [FLLV]), central brain atrophy (third ventricular width [TVW] and bicaudate ratio [BCR]), and clinical status (Expanded Disability Status Scale [EDSS] and 25-ft timed walk [25FTW]). Patients with MS had lower gray matter (707 +/- 33 cm(3) [-3.9%], P = 0.003) and total parenchymal volume (1088 +/- 48 cm(3) [-3.8%], P = 0.003), but only a trend for lower white matter volume (381 +/- 25 cm(3) [-3.7%], P = 0.052) relative to normal controls (gray matter: 736 +/- 33 cm(3); total parenchyma: 1132 +/- 49 cm(3); white matter: 396 +/- 26 cm(3)). Gray matter atrophy was related to clinical status (EDSS, 25FTW, and disease duration), lesion load (T1LV and FLLV), and central brain atrophy (TVW and BCR), whereas white matter atrophy was related to only central brain atrophy. These findings suggest that gray matter loss is related to other aspects of brain pathology and has more clinical relevance than white matter atrophy in MS.

Adult↗

Predicting quality of life in multiple sclerosis: accounting for physical disability, fatigue, cognition, mood disorder, personality, and behavior change.

Health-related quality of life (HQOL) is poor in multiple sclerosis (MS) but the clinical precipitants of the problem are not well understood. Previous correlative studies demonstrated relationships between various clinical parameters and diminished HQOL in MS. Unfortunately, these studies failed to account for multiple predictors in the same analysis. We endeavored to determine what clinical parameters account for most variance in predicting HQOL, and employability, while accounting for disease course, physical disability, fatigue, cognition, mood disorder, personality, and behavior disorder. In 120 MS patients, we measured HQOL (MS Quality of Life-54) and vocational status (employed vs. disabled) and then conducted detailed clinical testing. Data were analyzed by linear and logistic regression methods. MS patients reported lower HQOL (p<0.001) and were more likely to be disabled (45% of patients vs. 0 controls). Physical HQOL was predicted by fatigue, depression, and physical disability. Mental HQOL was associated with only depression and fatigue. In contrast, vocational status was predicted by three cognitive tests, conscientiousness, and disease duration (p<0.05). Thus, for the first time, we predicted HQOL in MS while accounting for measures from these many clinical domains. We conclude that self-report HQOL indices are most strongly predicted by measures of depression, whereas vocational status is predicted primarily by objective measures of cognitive function. The findings highlight core clinical problems that merit early identification and further research regarding the development of effective treatment.

Adult↗

Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity.

BACKGROUND: Gray matter magnetic resonance imaging T2 hypointensity, a marker of iron deposition, is associated with clinical impairment and brain atrophy in cross-sectional studies of multiple sclerosis. Treatment with intramuscular interferon beta-1a limits brain atrophy in the second year of treatment. OBJECTIVE: To test whether T2 hypointensity predicts brain atrophy and whether interferon affects this relationship. DESIGN: Post hoc analysis. SETTING: A multicenter treatment trial conducted at tertiary care comprehensive multiple sclerosis centers. Patients Patients with multiple sclerosis who took part in a 2-year clinical trial in which they received intramuscular interferon beta-1a (30 mug/wk) or placebo. MAIN OUTCOME MEASURES: Deep gray matter T2 hypointensity, brain parenchymal fraction (BPF), and total T2, gadolinium-enhancing, and T1 lesion volumes. RESULTS: T2 hypointensity in various gray matter areas correlated with baseline BPF (r = 0.19-0.39; P = .001-.03). In placebo-treated patients (n = 68), baseline T2 hypointensity predicted the change in BPF in the first year and throughout 2 years (r = 0.26-0.42; P<.001-.03). T2 hypointensity was chosen in regression modeling as the best predictor of BPF change at the 1-year (R(2) = 0.23; P = .002) and 2-year (R(2) = 0.33; P<.001) time points after accounting for all magnetic resonance imaging variables. In the interferon group (n = 65), no relationship existed between baseline T2 hypointensity and BPF change. CONCLUSIONS: Gray matter T2 hypointensity predicts the progression of brain atrophy in placebo- but not interferon beta-1a-treated patients. This predictive effect is seen as early as the first year. We hypothesize that interferon beta may exert its effect on brain atrophy in part by reducing a cascade of events that involve iron deposition as a mediator of neurotoxicity or as a disease epiphenomenon.

Adult↗

Multiple sclerosis medical image analysis and information management.

Magnetic resonance imaging (MRI) has become a central tool for patient management, as well as research, in multiple sclerosis (MS). Measurements of disease burden and activity derived from MRI through quantitative image analysis techniques are increasingly being used. There are many complexities and challenges in building computerized processing pipelines to ensure efficiency, reproducibility, and quality control for MRI scans from MS patients. Such paradigms require advanced image processing and analysis technologies, as well as integrated database management systems to ensure the most utility for clinical and research purposes. This article reviews pipelines available for quantitative clinical MRI research in MS, including image segmentation, registration, time-series analysis, performance validation, visualization techniques, and advanced medical imaging software packages. To address the complex demands of the sequential processes, the authors developed a workflow management system that uses a centralized database and distributed computing system for image processing and analysis. The implementation of their system includes a web-form-based Oracle database application for information management and event dispatching, and multiple modules for image processing and analysis. The seamless integration of processing pipelines with the database makes it more efficient for users to navigate complex, multistep analysis protocols, reduces the user's learning curve, reduces the time needed for combining and activating different computing modules, and allows for close monitoring for quality-control purposes. The authors' system can be extended to general applications in clinical trials and to routine processing for image-based clinical research.

Humans↗

Magnetic resonance imaging advances in multiple sclerosis.

Magnetic resonance imaging (MRI) has become a core component of clinical management and scientific research in multiple sclerosis (MS), providing essential information about tissue structure and function. MRI is now the most important laboratory diagnostic and longitudinal monitoring technology. A number of conventional MRI techniques, which include T2-weighted, T1-weighted, and gadolinium-enhanced imaging, are used to identify overt lesions and quantify tissue atrophy. MRI is highly sensitive in detecting brain and spinal cord involvement in MS and can visualize multifocal lesions, occult disease, and macroscopic atrophy. Advanced MRI techniques, such as magnetization transfer imaging, spectroscopy, diffusion-weighted imaging, and functional MRI, have added to our understanding of the pathogenesis of the disease. The precise role of these newer imaging approaches continues to be defined. In this supplement to the Journal of Neuroimaging, the authors review the role of conventional and advanced MRI techniques in detecting tissue changes in MS, diagnosing and monitoring patients, and charting the progression of disease in new and established patients.

Atrophy↗

Measurement of brain and spinal cord atrophy by magnetic resonance imaging as a tool to monitor multiple sclerosis.

Evaluation of brain and spinal cord atrophy by magnetic resonance imaging (MRI) has become an increasingly important component of understanding the multiple sclerosis (MS) disease process. These destructive aspects of the disease develop early in the disease course. A growing body of data links brain and spinal cord atrophy to clinical impairment more closely than can be linked with conventional measures of overt lesions. Thus, irreversible tissue damage may be a key factor leading to disease progression. In this review, the authors present the proposed mechanisms leading to central nervous system (CNS) atrophy. They describe the available MRI-based techniques to measure regional and global atrophy of the brain and spinal cord. They compare the rate of atrophy among MS phenotypes and summarize the emerging data linking atrophy to neurological and neuropsychological impairment. Finally, they discuss the effect of disease-modifying immunotherapies on the rate of CNS atrophy in patients with MS. Future research to clarify the etiology and pathophysiology of brain and spinal cord atrophy should provide new targets for therapeutic development.

Atrophy↗

Imaging of multiple sclerosis: role in neurotherapeutics.

Magnetic resonance imaging (MRI) plays an ever-expanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normal-appearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1- or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

Animals↗

Interhemispheric asymmetry of brain diffusivity in normal individuals: a diffusion-weighted MR imaging study.

BACKGROUND AND PURPOSE: Previous neuroimaging studies have suggested asymmetries in brain diffusivity may exist. The purpose of this study was to assess whether water diffusivity in deep gray matter structures shown by diffusion-weighted (DW) imaging differs between the right and left cerebral hemispheres in normal individuals. METHODS: Brain MR imaging was obtained in 23 healthy volunteers. A multisection image without diffusion weighting, and images with weighting applied in the read, phase, and section directions with a b-factor of 1000 s/mm(2) were collected. Diffusivity was computed separately in each direction, and the results were averaged to form mean diffusivity maps. Quantitative diffusivity values were obtained from the globus pallidus, putamen, caudate, thalamus, white matter, and CSF by using a standardized region of interest template. Interhemispheric differences were assessed by using a paired sample t test. RESULTS: Mean diffusivity was higher in the: left (mean +/- SD: 0.689 x 10(-3)+/- 0.069 x 10(-3)mm(2)/s) versus right (0.642 x 10(-3)+/- 0.071 x 10(-3)mm(2)/s) caudate (% difference, P value: 7.0%, P = .001); right (0.745 x 10(-3)+/- 0.053 x 10(-3)mm(2)/s) versus left (0.706 x 10(-3)+/- 0.050 x 10(-3)mm(2)/s) globus pallidus (5.2%, P < .001); left (0.720 x 10(-3)+/- 0.059 x 10(-3)mm(2)/s) versus right (0.674 x 10(-3)+/- 0.052 x 10(-3)mm(2)/s) putamen (6.4%, P < .001); right (0.750 x 10(-3)+/- 0.040 x 10(-3)mm(2)/s) versus left (0.716 x 10(-3)+/- 0.031 x 10(-3)mm(2)/s) thalamus (4.5%, P < .001). No significant right versus left difference was seen in the CSF (P = .291), anterior frontal white matter (P = .834), or centrum semiovale (P = .320). CONCLUSION: Gray matter diffusivity may differ between hemispheres of the brain in healthy individuals. Analysis of deep gray matter lesions requires caution, as statistically significant interhemispheric differences may not always be indicative of disease.

Adult↗

Regional lobar atrophy predicts memory impairment in multiple sclerosis.

BACKGROUND AND PURPOSE: In recent studies, measures of whole brain atrophy were strongly correlated with neuropsychological testing, explaining more variance than measures of lesion burden in patients with multiple sclerosis. The relationship between regional lobar atrophy and cognitive impairment is yet to be examined. We endeavored to assess the clinical significance of regional lobar atrophy in multiple sclerosis. METHODS: In a cross-sectional study, we evaluated 31 patients with multiple sclerosis with brain MR imaging and neuropsychological testing. Impairment was determined by comparison with demographically matched healthy controls. MR imaging generated measures of lesion burden (fluid-attenuated inversion recovery hyperintense volume), general atrophy (brain parenchymal fraction), central atrophy (lateral ventricle volume), and lobar atrophy (regional brain parenchymal fraction of frontal, temporal, parietal, and occipital lobes in each hemisphere). Neuropsychological testing emphasized measures of processing speed and memory, because these are commonly affected in multiple sclerosis. RESULTS: Patients with multiple sclerosis showed significant atrophy and impairment on all neuropsychological tests. Regional atrophy accounted for the most variance in all regression models predicting memory performance. Left temporal atrophy was the primary predictor of auditory/verbal memory (partial r's = 0.55-0.61), and both left and right temporal atrophy predicted visual/spatial memory performance (partial r's = 0.51-0.67). Models predicting learning consistency retained frontal lobe atrophy measures (partial r's = 0.44-0.68). Central and general atrophy measures were the primary predictors in modeling processing speed (partial r's = 0.42-0.64). CONCLUSION: Regional atrophy accounts for more variance than lesion burden, whole brain atrophy, or lateral ventricle volume in predicting multiple sclerosis-associated memory dysfunction.

Adult↗

Magnetic resonance imaging in multiple sclerosis.

Magnetic resonance imaging (MRI) has played a central role in the clinical management and scientific investigation of multiple sclerosis (MS) and has become the most important ancillary tool for diagnosing and monitoring the disease. Conventional MRI techniques are used to assess overt lesions and atrophy in the central nervous system and include spin-echo T2-weighted, pre- and post-gadolinium-enhanced spin-echo T1-weighted, and fluid-attenuated inversion-recovery images. Advanced MRI techniques such as diffusion-weighted imaging, magnetization transfer imaging, magnetic resonance spectroscopy, and functional MRI have increased our understanding of the pathogenesis of MS. The role of these newer techniques in clinical practice remains under investigation. In this review, we will focus on the role of MRI in the diagnosis and management of MS. We will also review how advanced MRI techniques contribute to our understanding of MS.

Atrophy↗

The use of magnetic resonance imaging in the diagnosis and long-term management of multiple sclerosis.

Magnetic resonance imaging (MRI) continues to evolve, providing almost boundless information about tissue structure and function that can be obtained noninvasively in vivo. MRI is a key tool in the diagnosis and longitudinal monitoring of patients with multiple sclerosis (MS). The technique is highly sensitive for the definition of brain and spinal cord involvement in MS, including the ability to detect multifocal lesions, diffuse (occult) disease, and macroscopic atrophy. Conventional MRI techniques, which include T2-weighted, T1-weighted, and gadolinium-enhanced imaging, are used primarily to detect overt lesions but can also be used to quantify tissue atrophy. Variations of these techniques also are important, and refinements are under way. The ability to demonstrate lesion dissemination in space and time has led to the common use of MRI as a paraclinical measure to support a diagnosis of MS, including in patients with clinically isolated demyelinating syndromes. In addition, MRI is used to monitor the progress of disease in patients with clinically definite MS, including assessment of lesions and atrophy. The use of conventional MRI in the diagnosis and longitudinal management of patients with MS is the focus of this review.

Atrophy↗