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.     

The ICH guidance in practice: stress degradation studies on ornidazole and development of a validated stability-indicating assay

The present study describes degradation of ornidazole under different ICH prescribed stress conditions (hydrolysis, oxidation and photolysis), and establishment of a stability-indicating reversed-phase HPLC assay. Degradation was found to occur in alkaline medium, under high acidic conditions, under oxidative stress, and also in the presence of light in acid conditions. Previously the drug is only known to decompose under alkaline conditions. Separation of drug and the degradation products under various conditions was successfully achieved on a C-18 column utilising water-acetonitrile in the ratio of 86:14. The detection wavelength was 310 nm. The method was validated with respect to linearity, precision, accuracy, selectivity, specificity and ruggedness. The response was linear in the drug concentration range of 5–500 μg ml⁻¹. The mean values (±RSD) of slope, intercept and correlation coefficient were 45251 (±1.59), 104418 (±2.49) and 0.9996 (±0.03), respectively. The RSD values for intra- and inter-day precision studies were <1 and <2.6%, respectively. The recovery of the drug ranged between 100–103% from a mixture of degradation products. The method was specific to drug and also selective to degradation products.     

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.     

Brain MRI Lesion Load at 1.5T and 3T versus Clinical Status in Multiple Sclerosis

ABSTRACT

BACKGROUND/PURPOSE

To assess correlation between brain lesions and clinical status with 1.5T and 3T magnetic resonance imaging (MRI).

METHODS

Brain MRI fluid‐attenuated inversion‐recovery (FLAIR) sequences were performed in 32 multiple sclerosis (MS) patients. Expanded Disability Status Scale (EDSS) score (mean ± standard deviation) was 2 ± 2.0 (range 0‐8), disease duration 9.3 ± 8.0 (range .8‐29) years.

RESULTS

FLAIR lesion volume (FLLV) at 3T was higher than at 1.5T (P= .01). Correlation between 1.5T FLLV and EDSS score was poor, while 3T FLLV correlated moderately and significantly (r_s= .39, P= .03). When controlling for age and depression, correlations between FLLV and cognitive measures were significant at 1.5T for the Judgment of Line Orientation test (JLO) (r_s=−.44, P= .05), the Symbol Digit Modalities Test (SDMT) (r_s=−.49, P= .02), and the California Verbal Learning Test Delayed Free Recall (CVLT DR) (r_s=−.44, P= .04). Correlations at 3T were also significant for these tests, but of greater magnitude: JLO (r_s=−.70, P= .0005), SDMT (r_s=−.73, P= .0001), CVLT DR (r_s=−.061, P= .003). Additional significant correlations obtained only at 3T included the 2 second‐paced auditory serial addition test (r_s=−.55, P= .01), the Brief Visuospatial Memory Test‐Delayed Free Recall (r_s=−.56, P= .007), and the California Verbal Learning Test Total Recall (r_s=−.42, P= .05).

CONCLUSION

MRI at 3T may boost sensitivity and improve validity in MS brain lesion assessment.

     

Bedside ultrasonography of optic nerve sheath diameter for detection of raised intracranial pressure in nontraumatic neuro-critically ill patients

BACKGROUND Delay in treatment of raised intracranial pressure(ICP) leads to poor clinical outcomes. Optic nerve sheath diameter(ONSD) by ultrasonography(US-ONSD)has shown good accuracy in traumatic brain injury and neurosurgical patients to diagnose raised ICP. However, there is a dearth of data in neuro-medical intensive care unit(ICU) where the spectrum of disease is different.AIM To validate the diagnostic accuracy of ONSD in non-traumatic neuro-critically ill patients.METHODS We prospectivel...     

Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine

Prepulse inhibition (PPI) of the startle reflex provides an operational measure of sensorimotor gating. Deficits in PPI are observed in schizophrenia patients and can be modelled in animals by administration of noncompetitive NMDA antagonists such as phencyclidine (PCP) or dizocilpine (MK-801). Previous studies indicate that the atypical antipsychotic clozapine restores PPI in PCP-treated animals while the typical antipsychotic haloperidol does not. Olanzapine (LY170053) is a novel putative atypical antipsychotic that shares many pharmacological and behavioral properties with clozapine. The present study assessed the ability of olanzapine (0, 1.25, 2.5, 5.0 or 10.0 mg/kg) to antagonize deficits in PPI produced by PCP (1.5 mg/kg) and dizocilpine (0.1 mg/kg). At the two highest doses, olanzapine significantly increased PPI in PCP- and dizocilpine-treated animals without affecting PPI or baseline startle reactivity by itself. These results support the notion that olanzapine is functionally similar to clozapine and may have utility as an atypical antipsychotic agent.     

Unmet Needs in the Pathogenesis and Treatment of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with a prevalence of approximately 1 in 1000. Over the last 30 years, advances in treatment such as use of corticosteroids and immunosuppressants have improved life expectancy and quality of life for patients with lupus and the key unmet needs have therefore changed. With the reduced mortality from disease activity, development of cardiovascular disease (CVD) has become an increasingly important cause of death in patients with SLE. The increased CVD risk in these patients is partly, but not fully explained by standard risk factors, and abnormalities in the immune response to lipids may play a role. Invariant natural killer T cells, which are triggered specifically by lipid antigens, may protect against progression of subclinical atherosclerosis. However, currently our recommendation is that clinicians should focus on optimal management of standard CVD risk factors such as smoking, blood pressure and lipid levels. Fatigue is one of the most common and most limiting symptoms suffered by patients with SLE. The cause of fatigue is multifactorial and disease activity does not explain this symptom. Consequently, therapies directed towards reducing inflammation and disease activity do not reliably reduce fatigue and new approaches are needed. Currently, we recommend asking about sleep pattern, optimising pain relief and excluding other causes of fatigue such as anaemia and metabolic disturbances. For the subgroup of patients whose disease activity is not fully controlled by standard treatment regimes, a range of different biologic agents have been proposed and subjected to clinical trials. Many of these trials have given disappointing results, though belimumab, which targets B lymphocytes, did meet its primary endpoint. New biologics targeting B cells, T cells or cytokines (especially interferon) are still going through trials raising the hope that novel therapies for patients with refractory SLE may be available soon.     

N-methyl-D-aspartate (NMDA) and opioid receptors mediate dynorphin-induced spinal cord injury: behavioral and histological studies.

Both N-methyl-D-aspartate (NMDA) and opioid receptors have been implicated in the pathophysiology of traumatic spinal cord injury and dynorphin-induced paralysis. The present studies compared the effects of the non-competitive NMDA antagonist dextrorphan (Dex) and the kappa-selective opioid antagonist nor-binaltorphimine (nor-BNI) on the acute motor deficits and chronic neuropathological alterations caused by intrathecally administered dynorphin A-(1-17) (Dyn A). Infusion of Dyn A into the rat lower thoracic spinal subarachnoid space produced acute, reversible hindlimb paresis. Histological evaluations of spinal cord sections from these animals at 2 weeks post-infusion revealed ventral grey matter necrosis, neuronal loss and gliosis as well as axonal loss in adjacent white matter; however, there was minimal alteration in serotonin immunocytochemistry caudal to the injury zone. Dex or non-BNI pretreatment each significantly (P less than 0.05) reduced, and to a similar degree, the acute motor deficits and certain histological changes associated with Dyn A administration. These findings further support the hypothesis that dynorphin-induced spinal cord injury involves both NMDA receptors and opioid receptors.