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Rohit Bakshi

Publications and source records attributed to Rohit Bakshi.

At least 37 records · Page 2Linked to original sources

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↗

Short-term brain atrophy changes in relapsing-remitting multiple sclerosis.

The objective of this study was to establish whether the time interval of 3 months is sufficient to detect whole-brain atrophy changes in patients with relapsing-remitting (RR) multiple sclerosis (MS). Another aim was to assess the value of monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and of different Gd-enhancement patterns as predictors of brain atrophy. Thirty patients with RRMS (mean disease duration 4.9 years, mean age 34.4 years and mean Expanded Disability Status Scale [EDSS] 1.4) were assessed at baseline and monthly for a period of 3 months with clinical and MRI examinations. Calculations of baseline and monthly absolute and percent changes of MRI measures have been obtained using two semiautomated (Buffalo and Trieste) and one automated (SPM99) segmentation method. Changes of brain parenchymal fraction (BPF) were investigated according to Gd-enhancement patterns. Mean absolute and percent changes of BPF did not significantly differ at any time point in the study for any of the three methods. There was slight but not significant decrease of BPF from baseline to month 3: -0.0004 (0.05%), p=0.093 for Trieste; -0.0006 (0.07%), p=0.078 for Buffalo; and -0.0006 (0.08%), p=0.081 for SPM99 method. In ring-enhancement positive patients, there was a significant difference between baseline and month 3 changes of BPF, EDSS, and number of relapses. Over the study period, we did not demonstrate differences between changes of BPF according to the presence of Gd enhancement. Longitudinally, multiple regression analysis demonstrated that the only clinical or MRI parameter that predicted BPF decrease was the mean absolute change of ring-enhancing lesion load (R=0.62, p=0.003). The noteworthy findings of this study are (1) the observation that a significant brain atrophy progression cannot be detected over a 3-month period in RRMS; (2) the demonstration that the ring-enhancement pattern may contribute to more severe brain tissue loss in the short term; and (3) the lack of relationship between the presence and duration of Gd-enhancement activity and brain volume changes in the short term.

Adult↗

Functional imaging during covert auditory attention in multiple sclerosis.

Recent literature suggests that the brain in multiple sclerosis (MS) undergoes reorganization that subserves the performance of visual and motor tasks. We identified sites of cerebral activity in 16 MS patients while performing a covert attention (CA) task, presented in the auditory modality. Positron emission tomography (PET) revealed activation of rostral/dorsal anterior cingulate cortex (ACC) in normal subjects studied previously. Activity in this region was not significant in MS patients, but there was a large region of activity in superior temporal cortex. Decreased activation of frontal attentional networks and greater activity in sensory/perceptual cortical areas (auditory association cortex) suggests a reduction of transmission along white matter tracts connecting these regions. This study demonstrates cingulate hypoactivity and cerebral reorganization during auditory attention in MS.

Acoustic Stimulation↗

Role of MRI in multiple sclerosis I: inflammation and lesions.

Conventional magnetic resonance imaging (MRI) can improve accuracy in the diagnosis of multiple sclerosis (MS). Metrics derived from conventional MRI are now routinely used to detect therapeutic effects and extend clinical observations. Hyperintense lesions on T2-weighted MRI scans are related primarily to increased water content and thus cannot distinguish between inflammation, edema, demyelination, Wallerian degeneration, and axonal loss. In addition, T2-weighted and post-contrast images are not sufficiently sensitive to detect occult disease affecting normal appearing gray and white matter. They do not show a reliable correlation with clinical measures of disability and do not provide a complete assessment of therapeutic outcomes. In the past few years a host of advanced MRI techniques and analysis methods have been introduced for the assessment of MS. These MRI techniques appear to have better reliability as surrogate markers for monitoring the pathologic processes that most likely are related to disease activity and clinical progression. They are able to reveal a range of tissue changes that include edema, inflammation, demyelination, axonal loss, and neurodegeneration. Therefore, in a disease with a high degree of longitudinal variability of clinical signs and symptoms within and between patients, and with no current adequate biological markers of disease progression, non-conventional MRI techniques provide a powerful tool to non-invasively study pathological substrates of overt lesions and normal appearing brain tissue. In particular, the use of these techniques is promising in elucidating mechanisms underlying the accumulation of tissue damage, repair and functional reorganization of neural pathways in patients with MS.

Humans↗

Neuroimaging of HIV and AIDS related illnesses: a review.

Neuroimaging technology continues to unfold in a very exciting way, providing almost limitless information about the structural and functional integrity of the nervous system. In patients with an immunocompromised state such as those infected with human immunodeficiency virus (HIV) and subsequently developing acquired immunodeficiency syndrome (AIDS), neurologic complications represent an important manifestation requiring vigilance. Many of the central nervous system (CNS) disorders related to HIV and AIDS are treatable and without prompt diagnosis and treatment, will lead to significant morbidity or death. Neuroimaging plays an increasingly pivotal role in the early diagnosis and longitudinal monitoring of these conditions. The author intends to provide an overview of neuroimaging technology and its applications including various magnetic resonance imaging (MRI) and functional imaging techniques in the evaluation of patients with HIV and AIDS related CNS disorders. The role of neuroimaging in this population includes early detection of direct HIV infection, opportunistic infections, neoplasia, or cerebrovascular diseases. In addition, through a wide breadth of imaging techniques, the pathology, neurochemistry and metabolism of lesions can be studied to clarify the differential diagnosis, such as discriminating infection vs. neoplasia.

AIDS Dementia Complex↗

Role of MRI in multiple sclerosis II: brain and spinal cord atrophy.

A growing body of evidence indicates that irreversible tissue destruction including axonal and neuronal degeneration is a key component of the multiple sclerosis (MS) disease process. Magnetic resonance imaging (MRI) is a powerful technique that can be combined with semiautomated or automated computer assisted analysis approaches to detect progressive atrophy of the brain and spinal cord with high sensitivity and reproducibility. The pathophysiology of central nervous system (CNS) atrophy in MS is unknown but likely represents an epiphenomenon related to the effects of inflammation including chronic demyelination, axonal injury, neuronal loss and Wallerian degeneration. Other factors that may contribute to tissue atrophy include injury to the normal appearing gray and white matter by mechanisms such as loss of growth factors, altered electrical conduction and pathologic iron deposition. Prospective studies have suggested that atrophy in MS is predicted by previous inflammatory activity as measured by overt MRI lesions. Gadolinium (Gd)-enhancing lesions have shown a particularly strong predictive value in some but not all longitudinal studies of brain atrophy. Brain atrophy has also been related in cross-sectional and longitudinal studies to T2-hypointense lesions in deep grey matter, suggesting a link between tissue iron deposition and atrophy. The measurement of brain atrophy seems to be of growing clinical relevance as a biomarker of the MS disease process. Atrophy should now be included as a secondary endpoint in trials of therapies aimed at limiting disease progression. Currently available anti-inflammatory immunomodulatory agents and immunosuppressive treatments, while effective at preventing clinical deterioration, have shown at best partial effects in preventing CNS atrophy. Thus, there is a need to further validate atrophy as an outcome measure and ultimately develop treatment strategies that will protect against the destructive aspects of the disease process. This should in turn lead to better long term neurologic functioning and a better quality of life for patients with MS.

Atrophy↗

Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden.

BACKGROUND: Cognition and magnetic resonance imaging correlations are well established in patients with multiple sclerosis (MS), but it is unclear whether lesion burden or atrophy accounts for most of the predictive variance. These indices have been directly compared in only a few studies. No such study included measurement of the third ventricle, which was strongly predictive of neuropsychological competence in the early literature. Furthermore, few studies accounted for the influence of age, premorbid intelligence, or depression. OBJECTIVE: To determine if conventional measures of lesion burden or atrophy predict cognitive dysfunction in MS while accounting for age, premorbid intelligence, and depression. METHODS: We studied 37 patients with MS and 27 controls matched according to demographic variables. Correlations between neuropsychological tests and the following magnetic resonance imaging indices were considered: T1 hypointense lesion volume, fluid-attenuated inversion recovery hyperintense lesion volume, third ventricle width, bicaudate ratio, and brain parenchymal fraction. Regression models predicting neuropsychological performance controlled for the effects of age, premorbid intelligence, and depression. We included only those tests discriminating patients with MS from controls. RESULTS: In each regression model, third ventricle width was the sole magnetic resonance imaging measure retained. When this variable was removed from consideration, brain parenchymal fraction was retained in all analyses. CONCLUSIONS: Brain atrophy accounts for more variance than lesion burden in predicting cognitive impairment in MS, and central atrophy in particular is strongly associated with neuropsychological morbidity. This finding may be explained in part by atrophy of the thalamus, a deep gray matter structure that mediates cognitive function via cortical and subcortical pathways. Enthusiasm for the clinical utility of third ventricle width is tempered by modest intraobserver and interobserver reliability.

Adult↗

Special populations: the management of seizures in HIV-positive patients.

An increasing percentage of patients with new-onset seizures are HIV positive. The evaluation and management is distinctly different from managing the non-HIV-infected patient. Clinicians must be familiar with comorbid infectious etiologies and the relative value of electroencephalogram, imaging, and serum and cerebrospinal fluid laboratory tests. Traditional antiepileptic drug (AED) therapies are contraindicated and may lead to increased HIV viral replication through either directed cellular mechanisms or interference with antiretroviral therapies. Newer AEDs have pharmacokinetic properties that make them reasonable choices, although none have been specifically studied for efficacy or safety in HIV. Lastly, optimal choice of an AED should reflect commonly encountered neurologic and psychiatric comorbidities.

Anticonvulsants↗

Correction for intracranial volume in analysis of whole brain atrophy in multiple sclerosis: the proportion vs. residual method.

Two techniques that correct (normalize) regional and whole brain volumes according to head size-the proportion method (tissue-to-intracranial volume ratio) and the residual method (regression-based predicted brain tissue volumes)-are used pervasively in neuroimaging research, but have received little critical evaluation or direct comparison. Using a quantitatively derived MRI data set of patients with multiple sclerosis (n = 18) and age-/sex-matched normal controls (n = 18), we introduced various types of error into estimates of intracranial volume (ICV) and absolute parenchymal volume (APV) to observe how this error affected the final outcome of normalized brain measures and their ability to detect group differences, as computed by a proportion (brain parenchymal fraction [BPF]) and residual method (predicted parenchymal volume [PPV]). The results indicated that systemic error in ICV and APV values considerably affected BPF means based on the proportion method, except with dependent-related systematic APV error, but essentially did not change statistical power associated with group differences in BPF. Random error altered BPF means to a much smaller extent, but was associated with moderate reductions in statistical power. On the other hand, PPV estimates based on the residual method were unaffected by these same ICV and APV errors, except with dependent-related systematic APV error, and were not associated with reductions in statistical power. Our findings suggest that head size correction of brain regions with the residual method generally may provide advantages over the proportion method.

Adult↗

Construct validity and frequency of euphoria sclerotica in multiple sclerosis.

Using the Neuropsychiatric Inventory (NPI), we studied euphoria and other behavioral changes in 75 consecutive, unselected multiple sclerosis (MS) patients and 25 healthy controls. We also assessed disease duration, clinical course, physical disability, personality, depression, insight, cognition, and caregiver distress. Factor analysis identified a cluster of symptoms--labeled euphoria/disinhibition--similar to the euphoria sclerotica syndrome originally described by Charcot and others. The euphoria/disinhibition factor score was elevated in 9% of patients and associated with secondary-progressive course, low agreeableness, poor insight, impaired cognition, and high caregiver distress. Thus, we used the NPI to validate the euphoria syndrome in multiple sclerosis (MS) and determined its frequency, and its neurological and psychological correlates.

Adolescent↗

Central nervous system atrophy and clinical status in multiple sclerosis.

In this review, the authors focus on clinical aspects of central nervous system (CNS) atrophy in multiple sclerosis (MS), including the relationship between atrophy and disability, disease course, disease duration, quality of life, and fatigue. Cross-sectional studies have demonstrated a moderate but significant correlation between brain or spinal cord atrophy and physical disability in patients with MS. Longitudinal studies (>/= 5 years) have shown that CNS atrophy is a significant predictor of subsequent long-term neurologic deterioration. The clinical relevance of CNS atrophy is reinforced by studies showing that atrophy accounts for more variance than conventional lesion measures in predicting disability. Impaired quality of life and both urodynamic and sexual dysfunction, but not fatigue, are associated with brain atrophy. It is likely that once the level of CNS atrophy reaches a critical threshold, patients begin to suffer clinical impairment and disease progression. Longitudinal studies suggest that CNS atrophy may occur in patients with clinically isolated demyelinating syndromes who are at high risk for developing clinically definite MS. Longitudinal natural history studies in relapsing-remitting, secondary progressive, and primary progressive MS have suggested that patients develop CNS atrophy at a faster rate in the first few years of disease than later in the disease course. Similarly, long-term follow-up studies have shown a poor relationship between disease duration and the rate of brain atrophy. The authors conclude that measurement of atrophy of the CNS is emerging as a clinically relevant biomarker of the MS disease process.

Atrophy↗

Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis.

Neuropsychological impairment is a common feature of multiple sclerosis. Affected patients often have deficits in information-processing speed and memory and exhibit psychopathological states such as depression. A minority of patients have rarer affect/mood disorders such as euphoria sclerotica and pathological laughter/crying. Neuropsychological impairment is a major predictor of low quality of life, unemployment, and caregiver distress. Studies evaluating correlations between neuropsychological impairment and findings on magnetic resonance imaging show that neuropsychological dysfunction is associated with lesion burden and diffuse disease in normal-appearing brain tissue. However, measures of tissue atrophy including whole-brain and central atrophy are especially well correlated with and predictive of cognitive impairment. Moreover, recent studies have shown that conventional measures of brain atrophy explain more variance in neuropsychological dysfunction than do measures of lesion burden. In particular, neuropsychological outcomes correspond highly with linear measures of subcortical atrophy such as ventricle enlargement. Within the domain of emotional dysfunction, both lesion burden and atrophy are related to major depressive disorder. Brain atrophy also predicts euphoria and disinhibition. The preliminary data suggest that although lesion burden primarily predicts depressive disorder, both lesion burden and atrophy predict the presence of euphoria. Euphoria and disinhibition likely represent personality change associated with worsening cognition as the disease progresses. Taken together, this growing body of data on magnetic resonance imaging to neuropsychological correlations supports the clinical relevance and validity of brain atrophy as a measure of disease progression in multiple sclerosis. Continuing research focuses on the possible relationship between measures of regional brain atrophy and cognitive and emotional impairment.

Atrophy↗

Combination therapy for multiple sclerosis: the treatment strategy of the future?

Multiple sclerosis (MS) is an inflammatory autoimmune disease characterised by demyelination and axonal loss in the CNS. Although new immunomodulatory therapies including interferon-beta and glatiramer acetate became available during the last decade, these therapies are only partially effective. There is a continuing need to develop more effective treatment strategies to combat the chronic and progressive aspects of the disease. In view of the complex pathophysiology underlying the MS disease process, combination therapy offers a rational therapeutic approach. Combining immunomodulatory agents with different mechanisms of action that promote synergistic or additive effects represents an important objective in MS therapeutic research. Ultimately, the optimal therapies will likely include strategies that promote repair and limit tissue destruction in combination with anti-inflammatory interventions.

Adjuvants, Immunologic↗

MR imaging in toxoplasmosis encephalitis after bone marrow transplantation: paucity of enhancement despite fulminant disease.

We present a patient who underwent bone marrow transplantation (BMT) after developing chronic myelocytic leukemia. Four months after BMT, he became comatose and died. MR imaging revealed multifocal brain lesions that were progressive but produced no edema. Postcontrast studies revealed that most of the lesions were nonenhancing. There was only discrete, irregular leptomeningeal enhancement with possible minimal enhancement of the cortex and subcortical white matter. Autopsy showed overwhelming toxoplasmosis encephalitis. This case illustrates that toxoplasmosis lesions may lack obvious contrast enhancement in the brain of the immunocompromised patients, despite severe involvement. Recognition of this unusual MR imaging manifestation of toxoplasmosis should lead to earlier diagnosis and treatment.

Adult↗

A semiautomated measure of whole-brain atrophy in multiple sclerosis.

Brain atrophy is a proposed MRI marker of irreversible pathologic damage in multiple sclerosis (MS). The brain parenchymal fraction (BPF) is the ratio of brain parenchymal volume to the total volume within the surface contour. We developed a semiautomated measure of BPF using commercially available edge-finding and thresholding software (30-min analysis time per patient). We measured BPF in 78 patients with MS and 17 healthy controls. BPF was lower in a cohort of patients with MS (n=50) (0.843+/-0.042, range 0.743-0.906) age-matched to controls (0.877+/-0.020, range 0.835-0.901) (p<0.001). BPF correlated inversely with third ventricular width (r=-0.785, p<0.001), and total T1 hypointense lesion volume (r=-0.347, p=0.011), but not with total T2 hyperintense lesion volume (r=-0.213, p=0.13). BPF correlated negatively with expanded disability status scale (EDSS) score (r=-0.391, p=0.0006) and disease duration (r=-0.281, p=0.01). Stepwise regression compared the relative abilities of MRI variables to predict clinical data. By regression of age, BPF, third ventricular width, T2 lesions, and T1 lesions, BPF was the best predictor of disability score (R(2)=0.204, p<0.001). Third ventricular width was the best predictor of disease duration (R(2)=0.316, p<0.001). None of the MRI variables differed between relapsing-remitting (RR) (n=60) and secondary progressive (SP) (n=18) disease course (p>0.05). The intrarater, interrater, and scan-rescan BPF variability (COV) was 0.31%, 0.34%, and 0.41% and the accuracy against a phantom was 99.1%. We conclude that whole-brain atrophy in MS can be reliably and readily quantified by a semiautomated approach. Longitudinal studies are warranted to determine if this method provides a sensitive biologic marker of the MS disease process.

Adult↗

Selective caudate atrophy in multiple sclerosis: a 3D MRI parcellation study.

Deep gray matter damage may be an important component of the multiple sclerosis (MS) disease process. We tested whether caudate atrophy occurs in MS, and whether it correlates with conventional MRI or clinical markers of disease progression. Caudate nuclei of 24 MS patients and 10 age-matched healthy controls were traced, normalized, reconstructed and visualized from MRI scans. Normalized bicaudate volume was 19% lower in MS controls ( p< 0.001), an effect that persisted after adjusting for whole-brain atrophy ( p< 0.008). Caudate volume did not correlate with disease duration, physical disability score, whole-brain atrophy, or total T2 hyperintense or T1 hypointense lesion load (all p > 0.05). We conclude that selective caudate atrophy is associated with MS and may occur through direct mechanisms.

Adult↗