Clinical and electrophysiological improvement of adrenomyeloneuropathy with steroid treatment.
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Biomedical subjects
Publications and source records attributed to R Bakshi.
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INTRODUCTION: The Beck Depression Inventory-Fast Screen (BDI-FS) is a brief self-report inventory designed to evaluate depression in patients with medical illness. As depressive disorder is especially prominent in multiple sclerosis (MS), a cost-effective procedure for identifying depressive disorder in MS is sorely needed. The BDI-FS may be useful in this regard although, to date, its validity in MS patients has not been assessed. METHODS: Fifty-four consecutive MS patients were studied. All underwent psychological assessment, which included the BDI-FS and other self-report measures of depression. Forty-eight caregiver/informants were interviewed using the Neuorpsychiatric Inventory (NPI). Retrospective chart reviews were conducted by a single trained research assistant, blind to the results of psychological testing and interviews, to determine if antidepressant medications had been prescribed. RESULTS: The BDI-FS was significantly correlated with other self-report measures of depression (P < 0.001) and with informant reported dysphoria (P < 0.01), In addition, BDI-FS scores discriminated MS patients undergoing treatment for depressive disorder from untreated MS patients (P = 0.01). CONCLUSION: These data support the concurrent and discriminative validity of the BDI-FS in MS. As the test is brief and not confounded with neurological symptoms, it is recommended for depression screening in this population.
The objective of this study was to determine the clinical characteristics of multiple sclerosis (MS) in African American (AA) patients in the New York State Multiple Sclerosis Consortium (NYSMSC) patient registry. The NYSMSC is a group of 18 MS centers throughout New York State organized to prospectively assess clinical characteristics of MS patients. AAs comprise 6% (329) of the total NYSMSC registrants (5602). Demographics, disease course, therapy, and socioeconomic status were compared in AA registrants versus nonAfrican Americans (NAA). There was an increased female preponderance and a significantly younger age at diagnosis in the AA group. AA patients were more likely to have greater disability with increased disease duration. No differences were seen in types of MS and use of disease modifying therapies. Our findings suggest a racial influence in MS. Further genetic studies that consider race differences are warranted to elucidate mechanisms of disease susceptibility.
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Cortical and subcortical gray matter hypointensities on T2-weighted MR images (T2WI) occur commonly in MS brains and have been related to disease duration, clinical course, and the level of neurologic disability. These hypointensities have been reported to occur in the thalamus, basal ganglia, and rolandic cortex. We assessed whether T2 hypointensity is associated with the severity of white matter plaques and atrophy of MS brains. In 114 MS patients, hypointensity of the thalamus, putamen, caudate, and sensorimotor cortex was ordinally rated against age- and gender-matched normal controls on 1.5-T MRI fast spin-echo axial T2WI. Regional and global T2 hyperintense and T1 hypointense parenchymal lesion loads were ordinally rated. Enlargement of subarachnoid and ventricular spaces (atrophy) was ordinally rated vs. age- and gender-matched normal controls. T2 hypointensity was highly, positively correlated with many other MRI variables. Regression modeling showed that T2 hypointensity was related to total atrophy, total T2 lesion load, third ventricular enlargement, parietal atrophy, and to a lesser extent, frontal T1 lesions and cerebellar T2 lesions, but not related to gadolinium enhancement. Ordinal ratings of T2 lesions and central atrophy showed high correlations with quantitative computerized assessments. We conclude that gray matter hypointensity on T2WI may reflect pathologic iron deposition and brain degeneration in MS. This T2 hypointensity is associated with brain atrophy and other MR markers of tissue damage. Further study is warranted to determine if T2 hypointensity is predictive of disease course in MS and is a useful surrogate outcome measure in therapeutic trials.
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BACKGROUND: Autopsy studies showed cortical and juxtacortical multiple sclerosis (MS) plaques. Fluid-attenuated inversion recovery (FLAIR) is an advanced magnetic resonance imaging sequence that reveals tissue T2 prolongation with cerebrospinal fluid suppression, allowing detection of superficial brain lesions. OBJECTIVES: To assess FLAIR, T1-weighted, and T2-weighted images for detecting lesions in or near the cerebral cortex in patients with MS and to explore the relation between cortical lesions and cortical atrophy. DESIGN, SETTING, AND PATIENTS: Cross-sectional study in a university MS clinic of 84 patients with MS and 66 age-matched healthy controls receiving 1.5-T fast FLAIR, T2-weighted, and T1-weighted images. MAIN OUTCOME MEASURES: Regional cortical atrophy was rated vs controls. Cortical and juxtacortical lesions were ovoid hyperintensities involving the cortex and/or gray-white junction. RESULTS: A total of 810 cortical and juxtacortical lesions were seen by FLAIR in patients (mean, 9.6 per patient), most commonly in the superior frontal lobe. Cortical and juxtacortical lesions were identified in 72 patients and 6 controls. Fourteen percent of cortical and juxtacortical lesions were seen on T1-weighted images and 26% were seen on T2-weighted images. More cortical and juxtacortical lesions were present in secondary progressive disease than relapsing-remitting disease. The total number of cortical and juxtacortical lesions correlated significantly with disease duration and the regional number correlated with the degree of regional atrophy. After taking into account noncortical (white matter) lesions, only the cortical and juxtacortical lesion count predicted atrophy in that region. CONCLUSIONS: FLAIR can detect many cortical and juxtacortical lesions in MS, which were appreciated previously in autopsy studies but usually missed by magnetic resonance imaging during life. Cortical and juxtacortical plaque formation may contribute to cortical atrophy in MS.
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Topoisomerase II (topo II) is a dyadic enzyme found in all eukaryotic cells. Topo II is involved in a number of cellular processes related to DNA metabolism, including DNA replication, recombination and the maintenance of genomic stability. We discovered a correlation between the development of postnatal testis and increased binding of topo IIalpha to the chromatin fraction. We used this observation to characterize DNA-binding specificity and catalytic properties of purified testis topo IIalpha. The results indicate that topo IIalpha binds a substrate containing the preferred site with greater affinity and, consequently, catalyzes the conversion of form I to form IV DNA more efficiently in contrast to substrates lacking such a site. Interestingly, topo IIalpha displayed high-affinity and cooperativity in binding to the scaffold associated region. In contrast to the preferred site, however, high-affinity binding of topo IIalpha to the scaffold-associated region failed to result in enhanced catalytic activity. Intriguingly, competition assays involving scaffold-associated region revealed an additional DNA-binding site within the dyadic topo IIalpha. These results implicate a dual role for topo IIalpha in vivo consistent with the notion that its sequestration to the chromatin might play a role in chromosome condensation and decondensation during spermatogenesis.
OBJECTIVE: Brain atrophy may occur early in the course of multiple sclerosis (MS) and may be associated with disability. Brain magnetic resonance imaging (MRI) of 114 MS patients (group A) were analyzed for regional atrophy (vs age-/gender-matched controls) and T1 and T2 lesions using 4-point rating systems. Thirty-five separate patients (group B) were analyzed for cortical atrophy (ordinal scale), third ventricular width, and total T2 hyperintense lesion volume (computer assisted). In group A, regression modeling indicated that inferior frontal atrophy (P = .0003) and T2 lesions in the pons (P = .02) predicted physical disability (Expanded Disability Status Scale [EDSS] score). Secondary progressive (SP) versus relapsing patients were predicted by inferior parietal (P = .002), superior parietal (P = .006), temporal (P = .008), inferior frontal (P = .01), superior frontal (P = .01), cerebellum (P = .01), occipital (P = .01), and midbrain (P = .02) atrophy. SP patients were also predicted by total atrophy (P = .01) and third ventricular enlargement (P = .03) but not T1 or T2 lesions. In group B, the regression model predicting EDSS score included only superior frontal atrophy (r = 0.515, P = .002). Mean kappa coefficients of ordinal ratings were 0.9 (intraobserver) and 0.8 (interobserver). Ordinal ratings correlated well with quantitative assessments. The authors conclude that brain atrophy is closely associated with physical disability and clinical course in MS patients and can be appreciated using a semiquantitative MRI regional rating system.
Parenchymal hypodensity is a proposed risk factor for hemorrhage after recombinant tissue plasminogen activator (TPA) thrombolysis for ischemic stroke. In Buffalo, NY, and Houston, TX, the authors reviewed 70 patients who were treated with intravenous TPA for acute middle cerebral artery (MCA) stroke. Two observers blinded to clinical outcome analyzed initial noncontrast head computed tomography (CT) scans. Basal ganglia CT hypodensity was quantitated in Hounsfield units (HUs). Contralateral-ipsilateral difference in density was calculated using the asymptomatic side as a control. Ictus time to TPA averaged 2.5 hours. Six patients developed symptomatic intraparenchymal hematomas (2 fatal). The hemorrhage group had more severe basal ganglia hypodensity (mean 7.5 +/- 1.4, range 6-10 HU) than the nonhemorrhage group (2.2 +/- 1.4, range 0-9 HU) (P < .0001). The hemorrhage group had hypodensity of > 5 HU; the nonhemorrhage group had hypodensity of < or = 4 HU, except 1 patient with hypodensity of 9 HU. In predicting hemorrhage, the positive predictive value of hypodensity > 5 HU was 86%; the negative predictive value was 100%. Prethrombolysis NIH Stroke Scale (NIHSS) deficit (P = .0007) and blood glucose (P = .005) were also higher in the hemorrhage group. Age, gender, smoking, hypertension, and ictus time to TPA infusion did not differ between the 2 groups. Logistic regression indicated that basal ganglia hypodensity was the best single predictor of hemorrhage. Hypodensity and NIHSS score together predicted all cases of hemorrhage. The authors conclude that basal ganglia hypodensity quantified by CT may be a useful method of risk stratification to select acute MCA stroke patients for thrombolytic therapy.
BACKGROUND AND PURPOSE: We sought to compare the safety and efficacy of direct urokinase thrombolysis with systemic heparin anticoagulation for superior sagittal sinus thrombosis (SSST). METHODS: At University at Buffalo (NY) and University of Texas (Dallas, Houston), we reviewed 40 consecutive patients with SSST, treated with local urokinase (thrombolysis group) or systemic heparin anticoagulation (heparin group). The thrombolysis group (n=20) received local urokinase into the SSS followed by systemic heparin anticoagulation. The heparin group (n=20) received systemic heparin anticoagulation only. Neurological dysfunction was rated as follows: 0, normal; 1, mild (but able to ambulate and communicate); 2, moderate (unable to ambulate, normal mentation); and 3, severe (unable to ambulate, altered mentation). RESULTS: Age (P=0.49), sex (P=0.20), baseline venous infarction (P=0.73), and predisposing illnesses (P=0.52) were similar between the thrombolysis and heparin groups. Pretreatment neurological function was worse in the thrombolysis group (normal, n=5; mild, n=8; moderate, n=4; severe, n=3) than in the heparin group (normal, n=8; mild, n=8; moderate, n=3; severe, n=1) (P=NS). Discharge neurological function was better in the thrombolysis group (normal, n=16; mild, n=3; moderate, n=1; severe, n=0) than in the heparin group (normal, n=9; mild, n=6; moderate, n=5; severe, n=0) (P=0.019, Mann-Whitney U test). Hemorrhagic complications were 10% (n=2) in the thrombolysis group (subdural hematoma, retroperitoneal hemorrhage) and none in the heparin group (P=0.49). Three of the heparin group patients developed complications of the underlying disease (status epilepticus, hydrocephalus, refractory papilledema). No deaths occurred. Length of hospital stay was similar between the groups (P=0.79). CONCLUSIONS: Local thrombolysis with urokinase is fairly well tolerated and may be more effective than systemic heparin anticoagulation alone in treating SSST. A randomized, prospective study comparing these 2 treatments for SSST is warranted.
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OBJECTIVE: To describe hyperintense vessels sign (HVS) in patients with acute stroke on fluid-attenuated inversion recovery (FLAIR) MRI and determine its clinical significance and utility. BACKGROUND: Enhancement of vessels on postcontrast MRI in patients with acute stroke is considered an indicator of early brain ischemia. Recently, the FLAIR technique has shown promise in earlier and better detection of ischemic brain parenchymal lesions. METHODS: Two observers retrospectively reviewed 304 MRI of patients with stroke and identified 30 patients with acute middle cerebral artery stroke and HVS on FLAIR obtained within 24 hours of symptom onset. These patients were evaluated with contrast-enhanced MRI (n = 9), MR angiography of carotid and intracranial circulation (n = 30), cerebral angiography (n = 8), transcranial Doppler (n = 17), and SPECT (n = 16). The extent of HVS was compared with final infarct size and NIH Stroke Scale score. RESULTS: HVS on FLAIR was seen in 10% of the patients with acute stroke. HVS was associated with large vessel occlusion or severe stenosis (>90%). Intravascular enhancement on contrast MRI was observed in vessels that were hyperintense on FLAIR. Both cortical and subcortical infarcts demonstrated HVS. MR angiographic and cerebral angiographic findings of large vessel occlusion or severe stenosis (>90%), slow flow, low velocities by transcranial Doppler, and hypoperfusion on SPECT correlated with HVS. HVS was the earliest ischemic change in three patients scanned within 3 hours of ictus. Final infarct size was smaller than the area showing HVS in all patients. CONCLUSION: HVS on FLAIR MRI is an indicator of slow flow and early ischemia as a result of large vessel occlusion or stenosis and inadequacy of collateral circulation. HVS does not mean that infarction has occurred but indicates brain tissue at risk of infarction. It should prompt consideration of revascularization and flow augmentation strategies.
It is unclear whether brain MRI lesions are associated with depression in multiple sclerosis (MS). Neurological dysfunction in depressed (n= 19) and non-depressed (n = 29) MS patients was rated by expanded disability status scale (EDSS). EDSS was weakly predictive of the presence of (p = 0.03) and severity of (p = 0.01) depression. After correcting for EDSS, the presence of depression was predicted by superior frontal and superior parietal hypointense TI lesions (p<0.01); the severity of depression was predicted by superior frontal, superior parietal and temporal TI lesions, lateral and third ventricular enlargement, and frontal atrophy (p<0.01). Depression was not related to bright T2 lesions or enhancement. We conclude that atrophy and cortical-subcortical disconnection due to frontal and parietal white matter destructive lesions may contribute to depression in MS.
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