Chandra M. Pandey

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.)

Modulation of autoimmune diseases by nitric oxide.

Nitric oxide (NO) is an intercellular messenger that performs a number of functions, including neurotransmission, vasodilatation, inhibition of platelet aggregation, and modulation of leukocyte adhesion. NO has recently been shown to act as a potent cytotoxic effector molecule as well as to play an important role in the pathogenesis of organ-specific autoimmunity. NO may also modulate the immune response by interfering with Th1/Th2 balance in autoimmune diseases. This review will discuss the role of NO and nitric oxide synthase (NOS) in pathophysiologic and therapeutic implications in various autoimmune diseases with particular reference to T helper-1 (Th1) and T helper-2 (Th2) cytokines.

Biological correlates of diffusivity in brain abscess

Restricted diffusion in brain abscess is assumed to be due to a combination of inflammatory cells, necrotic debris, viscosity, and macromolecules present in the pus. We performed diffusion‐weighted imaging (DWI) on 41 patients with proven brain abscesses (36 pyogenic and five tuberculous), and correlated the apparent diffusion coefficient (ADC) from the abscess cavity with viable cell density, viscosity, and extracellular‐protein content quantified from the pus. On the basis of the correlation between cell density and ADC in animal tumor models and human tumors in the literature, we assumed that the restricted ADC represents the cellular portion in the abscess cavity. We calculated restricted and unrestricted lesion volumes, and modeled cell density over the restricted area with viable cell density per mm3 obtained from the pus. The mean restricted ADC in the cavity (0.65 ± 0.01 × 10–3 mm2/s) correlated inversely with restricted cell density in both the pyogenic (r = −0.90, P = <0.05) and tuberculous (0.60 ± 0.04 × 10–3 mm2/s, r = −0.94, P = <0.05) abscesses. We conclude that viable cell density is the main biological parameter responsible for restricted diffusion in brain abscess, and it is not influenced by the etiological agents responsible for its causation. Magn Reson Med, 2005.

Discriminant analysis to classify glioma grading using dynamic contrast-enhanced MRI and immunohistochemical markers.

IntroductionThe purpose of the present study was to look for the possible predictors which might discriminate between high- and low-grade gliomas by pooling dynamic contrast-enhanced (DCE)-perfusion derived indices and immunohistochemical markers.MethodsDCE-MRI was performed in 76 patients with different grades of gliomas. Perfusion indices, i.e., relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), permeability (ktrans and kep), and leakage (ve) were quantified. MMP-9-, PRL-3-, HIF-1α-, and VEGF-expressing cells were quantified from the excised tumor tissues. Discriminant function analysis using these markers was used to identify discriminatory variables using a stepwise procedure. To look for correlations between immunohistochemical parameters and DCE metrics, Pearsons correlation coefficient was also used.ResultsA discriminant function for differentiating between high- and low-grade tumors was constructed using DCE-MRI-derived rCBV, kep, and ve. The form of the functions estimated are “D1 = 0.642 × rCBV + 0.591 × kep − 1.501 × ve − 1.550” and “D2 = 1.608 × rCBV + 3.033 × kep + 5.508 × ve − 8.784” for low- and high-grade tumors, respectively. This function classified overall 92.1% of the cases correctly (89.1% high-grade tumors and 100% low-grade tumors). In addition, VEGF expression correlated with rCBV and rCBF, whereas MMP-9 expression correlated with kep. A significant positive correlation of HIF-1α with rCBV and VEGF expression was also found.ConclusionDCE-MRI may be used to differentiate between high-grade and low-grade brain tumors non-invasively, which may be helpful in appropriate treatment planning and management of these patients. The correlation of its indices with immunohistochemical markers suggests that this imaging technique is useful in tissue characterization of gliomas.

Reduction in oxidative stress and cell death explains hypothyroidism induced neuroprotection subsequent to ischemia/reperfusion insult.

Hypometabolic state following hypothermia is known to protect tissues from ischemic injury. Hypothyroidism produces a hypometabolic state. The present study was undertaken to investigate the protective effects of hypothyroidism following cerebral ischemia and to ascertain the underlying mechanism. Euthyroid (E) and hypothyroid (H) animals were exposed to a 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion (I/R). Specific enzymatic methods and flowcytometry were used to assess the quantitative changes of molecules involved in neuronal damage as well as in protection. As compared to euthyroid ischemic reperfused (E + I/R) rats, H + I/R rats had insignificant neurological deficit, and smaller area of infarct. H + I/R rats had significantly lower markers of oxidative stress, and lactate dehydrogenase (LDH) activity (a marker for necrosis). Natural antioxidant activity (particularly superoxide dismutase) and integrity of mitochondria (membrane potential) were maintained in H + I/R group but not in E + I/R group. The number of neurons undergoing apoptosis significantly lower in hypothyroid ischemic rats as compared to euthyroid ones. These results suggest that hypothyroid animals face ischemia and reperfusion much better compared to euthyroid animals. A possible explanation could be the decreased oxidative stress and maintained antioxidant activity that finally leads to a decrease in necrosis and apoptosis. These observations may suggest strategies to induce brain-specific downregulation of metabolism that may have implications in the management of strokes in human beings.

Differentiation of infective from neoplastic brain lesions by dynamic contrast-enhanced MRI

IntroductionIt is not always possible to differentiate infective from neoplastic brain lesions with conventional MR imaging. In this study, we assessed the utility of various perfusion indices in the differentiation of infective from neoplastic brain lesions.Methods A total of 103 patients with infective brain lesions (group I, n=26) and neoplastic brain lesions (high-grade glioma, HGG, group II, n=52; low-grade glioma, LGG, group III, n=25) underwent dynamic contrast-enhanced MR imaging. The perfusion indices, including relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), transfer coefficient (ktrans) and leakage (ve), were calculated and their degree of correlation with immunohistologically obtained microvessel density (MVD) and vascular endothelial growth factor (VEGF) determined. The rCBV was corrected for the leakage effect. Discriminant analysis for rCBV, rCBF, ktrans and ve was performed to predict the group membership of each case and post hoc analysis was performed to look for group differences.ResultsThe rCBV, rCBF, ktrans, ve, MVD and VEGF were significantly different (P<0.001) between the three groups. Discriminant analysis showed that rCBV predicted 73.1% of the infective lesions, 84.6% of the HGG and 72.0% of the LGG. The rCBF classified 86.5% of the HGG, 80.0% of the LGG and 65.4% of the infective lesions. The ktrans discriminated 98.1% of the HGG, 76.0% of the LGG and 88.5% of the infective lesions correctly. The ve classified 98.1% of the HGG, 76.0% of the LGG and 84.6% the infective lesions. The rCBV was correlated significantly with MVD and VEGF, while the correlation between ktrans and MVD was not significant.ConclusionPhysiological perfusion indices such as ktrans and ve appear to be useful in differentiating infective from neoplastic brain lesions. Adding these indices to the current imaging protocol is likely to improve tissue characterization of these focal brain mass lesions.

Treatment-Induced Plasticity in Cerebral Palsy: A Diffusion Tensor Imaging Study

Diffusion tensor imaging is used as a measure of white-matter organization to probe mechanisms underlying clinical responses. Diffusion tensor imaging and clinical assessment in 8 patients with spastic quadriparesis (mean age, 6.13 years) was performed before and 6 months after therapy (botulinum injection, followed by physiotherapy). All patients were graded on the basis of gross motor function. Serial diffusion tensor imaging was also performed on 10 age/sex-matched controls at baseline and after 6 months. Regions of interests were placed on corticospinal tracts at different levels (i.e., corona radiata, posterior limb of internal capsule, midbrain, pons, and upper medulla) and on other major white-matter tracts, in both patients and controls. A significant increase in fractional anisotropy was evident in corticospinal tracts at the level of the posterior limb of the internal capsule and periventricular white matter of the temporal lobe, relative to baseline values in the patient group. Gross motor function classification system grades improved in all patients during follow-up relative to baseline values. The increase in fractional anisotropy in corticospinal tracts, along with improved clinical motor scores, suggests plasticity of the central motor pathway after combined therapy.

Predictors of long-term survival in patients with gallbladder cancer

The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer. A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival <24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status (P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival.

Toll-Like Receptor 4 Polymorphism and Its Association with Symptomatic Neurocysticercosis

BACKGROUND Symptoms and signs of neurocysticercosis (NCC) are nonspecific and depend upon several factors, including the host immune response to the parasite. Toll-like receptors (TLRs) play an important role in innate immunity. Susceptibility of humans to NCC in relation to TLR polymorphism is unknown. The present study examines TLR4 polymorphism in human NCC and its role in symptomatic disease. METHODS A total of 140 patients with NCC (82 symptomatic [ie, with active epilepsy] and 58 asymptomatic) and 150 healthy control subjects were examined for TLR4 Asp299Gly and Thr399Ile polymorphisms by means of polymerase chain reaction and restriction fragment-length polymorphism. RESULTS TLR4 Asp299Gly and Thr399Ile were significantly associated with the occurrence of NCC (P < .001 for Asp299Gly; P = .003 for Thr399Ile) and progression to symptomatic NCC, compared with control subjects (P < .001 for Asp299Gly; P < .001 for Thr399Ile) or asymptomatic NCC (P < .001 for Asp299Gly; P = .002 for Thr399Ile). Frequency of haplotype Gly/Thr (P <.001) was observed to be a risk factor for susceptibility to NCC. Gly and Ile carriers had a statistically significant association with NCC (P < .001 for Gly; P = .003 for Ile) and symptomatic NCC (P < .001 for Gly; P <or= .001 for Ile), compared with control subjects. Both carriers were also associated with symptomatic NCC (P < .001 for Gly; P < .004 for Ile), when compared with asymptomatic NCC.

Quantification of age- and gender-related changes in diffusion tensor imaging indices in deep grey matter of the normal human brain

This study aimed to demonstrate age-related and gender-related changes in diffusion tensor imaging (DTI) indices of deep grey matter (GM) nuclei of the normal human brain. DTI was performed on 142 subjects (age: 10-52 years). Regions of interest were placed on the caudate nucleus (CN), putamen, globus pallidus, frontal white matter (WM), occipital WM, anterior and posterior limb of internal capsule, genu of the corpus callosum and splenium in all participants. The quadratic regression model was used to describe age-related and gender-related changes in DTI indices for GM and WM. We observed increased fractional anisotropy (FA) values with age up to adulthood in GM, and a rise up to the third decade of life followed by a decrease in FA for WM. We observed higher FA values in males compared to females in CN and all WM regions. Decreased mean diffusivity with age was observed in GM and WM irrespective of gender. This normative data may be valuable in the diagnosis of neurodegenerative diseases.