Ponnada A. Narayana

Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double-blind, placebo-controlled trial

To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis.

Reduced Anterior Corpus Callosum White Matter Integrity is Related to Increased Impulsivity and Reduced Discriminability in Cocaine-Dependent Subjects: Diffusion Tensor Imaging

Brain imaging studies find evidence of prefrontal cortical dysfunction in cocaine-dependent subjects. Similarly, cocaine-dependent subjects have problems with behaviors related to executive function and impulsivity. Since prefrontal cortical axonal tracts cross between hemispheres in the corpus callosum, it is possible that white matter integrity in the corpus callosum could also be diminished in cocaine-dependent subjects. The purpose of this study was to compare corpus callosum white matter integrity as measured by the fractional anisotropy (FA) on diffusion tensor imaging (DTI) between 18 cocaine-dependent subjects and 18 healthy controls. The Barratt Impulsiveness Scale (BIS-11) and a continuous performance test: the Immediate and Delayed Memory Task (IMT/DMT) were also collected. Results of the DTI showed significantly reduced FA in the genu and rostral body of the anterior corpus callosum in cocaine-dependent subjects compared to controls. Cocaine-dependent subjects also had significantly higher BIS-11 scores, greater impulsive (commission) errors, and reduced ability to discriminate target from catch stimuli (discriminability) on the IMT/DMT. Within cocaine dependent subjects there was a significant negative correlation between FA in the anterior corpus callosum and behavioral laboratory measured impulsivity, and there was a positive correlation between FA and discriminability. The finding that reduced integrity of anterior corpus callosum white matter in cocaine users is related to impaired impulse control and reduced ability to discriminate between target and catch stimuli is consistent with prior theories regarding frontal cortical involvement in impaired inhibitory control in cocaine-dependent subjects.

Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy

Brain water may increase in hepatic encephalopathy (HE). Diffusion tensor imaging was performed in patients with cirrhosis with or without HE to quantify the changes in brain water diffusivity and to correlate it with neuropsychological (NP) tests. Thirty‐nine patients with cirrhosis, with minimal (MHE) or overt HE, were studied and compared to 18 controls. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in corpus callosum, internal capsule, deep gray matter nuclei, periventricular frontal, and occipital white matter regions in both cerebral hemispheres. The MD and FA values from different regions in different groups were compared using analysis of variance and Spearmans rank correlation test. In 10 patients with MHE, repeat studies were performed after 3 weeks of lactulose therapy to look for any change in MD, FA, and NP scores. Significantly increased MD was found with insignificant changes in FA in various regions of brain in patients with MHE or HE compared with controls, indicating an increase in interstitial water in the brain parenchyma without any microstructural changes. A significant correlation was found between MD values from corpus callosum, internal capsule, and NP test scores. After therapy, MD values decreased significantly and there was a corresponding improvement in NP test scores. Further analysis showed that MD values were different for different grades of minimal or overt HE. In conclusion, the increase in MD with no concomitant changes in FA in cirrhosis with minimal or early HE indicates the presence of reversible interstitial brain edema. (HEPATOLOGY 2006;43:698–706.)

Serial changes in the white matter diffusion tensor imaging metrics in moderate traumatic brain injury and correlation with neuro-cognitive function.

Diffuse axonal injury (DAI) that follows traumatic brain injury (TBI) is thought to be a major contributor to neurocognitive dysfunction that sometimes follows TBI. Conventional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and neuropsychological tests (NPT) were performed on 38 TBI patients [hemorrhagic DAI (H-DAI, n=8), non-hemorrhagic (Nh-DAI, n=7), with no apparent DAI on conventional MRI (NA-DAI, n=23)] with a Glasgow Coma Scale score ranging between 9 and 13. The fractional anisotropy (FA) and mean diffusivity (MD) were quantified from different regions of the corpus callosum (CC), and peri-ventricular white matter (PWM) within 5-14 days and 6 months following TBI. Patients in all three groups showed decreased FA in the anterior limb of the internal capsule (ALIC) and the posterior limb of the internal capsule (PLIC), while the genu of the CC showed a decrease in the H-DAI group during the early period following TBI that persisted 6 months later, which appeared to be consistent with axonopathy. In patients without abnormalities on conventional MRI and DTI in the initial phase, a significant decrease in FA and increase in MD were observed in a few regions of the CC at 6 months, which was suggestive of demyelination/gliosis. The changes in FA and MD in the CC and PWM at 6 months follow-up showed significant correlation with some of the NPT performed in the three groups. DTI demonstrates axonopathy in the acute stage, as well as at secondary stages, at 6 months post-injury in the CC and PWM in regions of normal-appearing white matter on conventional MRI.

Cell death in experimental intracerebral hemorrhage: The “black hole” model of hemorrhagic damage

Intracerebral hemorrhage (ICH) has a poor prognosis that may be the consequence of the hematomas effect on adjacent and remote brain regions. Little is known about the mechanism, location, and severity of such effects. In this study, rats subjected to intracerebral blood injection were examined at 100 days. Stereology (neuronal count and density) and volume measures in the perihematoma rim, the adjacent and overlying brain, and the substantia nigra pars reticulata (SNr) were compared with contralateral brain regions at 100 days and the perihemorrhage region at 24 hours and 7 days. In addition, cytochrome c release was investigated at 24 hours, 3 days, and 7 days. At 100 days, post‐ICH rats showed no difference in neuronal density in the perihemorrhagic scar region or regions of the striatum immediately surrounding and distal to the perihemorrhage scar. The cell density index in the ipsilateral field was 16.2 ± 3.8 versus the contralateral control field of 15.6 ± 3.2 (not significant). Volume measurements of the ipsilateral striatum revealed a 20% decrease that was compensated by an increase in ipsilateral ventricular size. The area of the initial ICH as measured by magnetic resonance imaging correlated with the degree of atrophy. In the region immediately surrounding the hematoma, cytochrome c immunoreactivity increased at 24 hours and 3 days, and returned toward baseline by day 7. At 24 hours, stereology in the peri‐ICH region showed decreased density in the region where cytochrome c immunoreactivity was the highest. Neuronal density of the ipsilateral SNr was significantly less than the contralateral side (9.6 ± 1.9 vs 11.6 ± 2.3). Histologic damage from ICH occurred mainly in the immediate perihemorrhage region. Except for SNr, we found no evidence of neuronal loss in distal regions. We have termed this continued destruction of neurons, which occurs over at least 3 days as the neurons come into proximity to the hematoma, the “black hole” model of hemorrhagic damage.

Improved Identification of Intracortical Lesions in Multiple Sclerosis with Phase-Sensitive Inversion Recovery in Combination with Fast Double Inversion Recovery MR Imaging

BACKGROUND AND PURPOSE: Accurate detection and classification of purely intracortical lesions in multiple sclerosis (MS) are important in understanding their role in disease progression and impact on the clinical manifestations of the disease. However, detection of these lesions with conventional MR imaging remains a challenge. Although double inversion recovery (DIR) has been shown to improve the sensitivity of the detection of cortical lesions, this sequence has low signal-to-noise ratio (SNR), poor delineation of lesion borders, and is prone to image artifacts. We demonstrate that intracortical lesions can be identified and classified with greater confidence by the combination of DIR with phase-sensitive inversion recovery (PSIR) images. MATERIALS AND METHODS: A total of 16 subjects with MS were included in this study. DIR, PSIR, and fluid-attenuated inversion recovery (FLAIR) images were acquired and inspected by 3 experts, with identification of lesions by consensus. PSIR and DIR images were jointly used to classify lesions as purely intracortical, mixed gray-white matter, and juxtacortical. The difference in the number of lesions detected in each category was compared between combined PSIR and DIR and conventional FLAIR. RESULTS: PSIR consistently allowed a clearer classification and delineation of lesions. Combined PSIR and DIR images showed a 337% improvement in the total number of lesions detected compared with FLAIR alone. Detection of intracortical lesions was improved by 417% compared with FLAIR. Detection of mixed gray-white matter and juxtacortical lesions was improved by 396% and 130%, respectively, compared with FLAIR. CONCLUSION: Reliable detection and classification of intracortical lesions in MS are greatly improved by combined use of PSIR and DIR.

Diffusion tensor fractional anisotropy of the normal-appearing seven segments of the corpus callosum in healthy adults and relapsing-remitting multiple sclerosis patients.

To investigate the utility of whole‐brain diffusion tensor imaging (DTI) in elucidating the pathogenesis of multiple sclerosis (MS) using the normal‐appearing white matter (NAWM) of the corpus callosum (CC) as a marker of occult disease activity.

Magnetic Resonance Spectroscopy in the Monitoring of Multiple Sclerosis

In addition to providing information on tissue structure, magnetic resonance (MR) technology offers the potential to investigate tissue metabolism and function. MR spectroscopy (MRS) offers a wealth of data on the biochemistry of a selected brain tissue volume, which represent potential surrogate markers for the pathology underlying multiple sclerosis (MS). In particular, the N‐acetylaspartate peak in an MR spectrum is a putative marker of neuronal and axonal integrity, and the choline peak appears to reflect cell‐membrane metabolism. On this basis, a diminished N‐acetylaspartate peak is interpreted to represent neuronal/axonal dysfunction or loss, and an elevated choline peak represents heightened cell‐membrane turnover, as seen in demyelination, remyelination, inflammation, or gliosis. Therefore, MRS may provide a unique tool to evaluate the severity of MS, establish a prognosis, follow disease evolution, understand its pathogenesis, and evaluate the efficacy of therapeutic interventions, which complements the information obtained from the various forms of assessment made by conventional MR imaging.

Randomized study combining interferon and glatiramer acetate in multiple sclerosis

A double‐blind, randomized, controlled study was undertaken to determine whether combined use of interferon β‐1a (IFN) 30μg intramuscularly weekly and glatiramer acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing–remitting multiple sclerosis.

In vivo serial diffusion tensor imaging of experimental spinal cord injury

In vivo longitudinal diffusion tensor imaging (DTI) of rodent spinal cord injury (SCI) was carried out over a period of eight weeks post‐injury. A balanced, rotationally invariant, alternating gradient polarity icosahedral diffusion encoding scheme was used for an unbiased estimation of the DTI metrics. The fractional anisotropy (FA), diffusivities along (longitudinal), and perpendicular (transverse) to the fiber tracts, were estimated for the ventral, dorsal, and lateral white matter. In all the three regions, the DTI metrics were observed to be significantly different in injured cords relative to the uninjured controls close to the epicenter of the injury. However, these differences gradually disappeared away from the epicenter. The spatio‐temporal changes in the DTI metrics showed a recovery pattern that is region specific. Although the temporal trends in the tissue recovery in rostral and caudal sections seem to be similar, overall the DTI metrics were observed to be closer to the normal tissue values in the caudal relative to the rostral sections (rostral–caudal asymmetry).