Factors associated with emotional and behavioral outcomes in adolescents with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) onset during adolescence has the potential to disrupt a key period of psychosocial maturation. OBJECTIVE: We aimed to examine the prevalence and risk factors associated with emotional and behavioral outcomes in adolescents with MS. METHODS: The Behavioral Assessment System for Children-2nd Edition (BASC-2) was completed by 31 adolescents with MS (mean age = 16.1 years), 31 age-matched controls, and parents of all participants. BASC-2 outcomes were compared between groups. Base rates were examined for scores falling at least one or two standard deviations below norm. Associations between BASC-2 outcomes and features of disease severity and IQ were examined. RESULTS: Youth with MS were reported by their parents to have more symptoms of depression and somatization and lower adaptive skills compared with reports by parents of controls. On the self-report, patients endorsed more problems of inattention/hyperactivity and lower self-reliance relative to controls. Behavioral concerns and reduced adaptive functioning in the MS group were associated with fatigue, poor relations with parents, and perceived social stress. Psychosocial outcomes did not associate with number of relapses, Expanded Disability Status Scale score, disease duration, brain lesion volume or IQ. CONCLUSION: Youth with MS are at risk of difficulties in behavioral and emotional health. Relations with parents emerged as a key factor influencing the emotional well-being of youth with MS, suggesting an important role for family-centered care in this population.

Diffusion tensor imaging and cognitive speed in children with multiple sclerosis.

OBJECTIVES: To compare white matter (WM) integrity in children with MS and healthy children using diffusion tensor imaging (DTI), and correlate DTI findings with disease activity, lesion burden, and cognitive processing speed. METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) in normal-appearing white matter (NAWM) were measured in four corpus callosum (CC), eight hemispheric regions, and the normal-appearing thalamus of 33 children and adolescents with MS and 30 age-matched healthy controls. Images were acquired on a GE LX 1.5T scanner. DTI parameters used were 25 directions, b = 1000 s/mm(2), and 5mm slice thickness. MS patients had T2 lesion volumes and Expanded Disability Status Scale (EDSS) scores were measured; all participants underwent two speeded cognitive tasks (Visual Matching and Symbol Digit Modalities Test (SDMT)). RESULTS: MS participants displayed lower FA values in the genu (p<0.005), splenium (p<0.001) and in NAWM of bilateral parietal, temporal, and occipital lobes (p<0.001) versus controls. FA and MD in the thalamus did not differ between groups. Higher lesion volumes correlated with reduced FA in CC and hemispheric NAWM. DTI metrics did not correlate with EDSS. FA values in CC regions correlated with Visual Matching (p<0.001) and SDMT (p<0.005) in MS participants only. INTERPRETATION: DTI analyses indicate widespread NAWM disruption in children with MS-with the degree of abnormality correlating with impaired cognitive processing speed. These findings support an early onset tissue pathology in MS and illustrate its functional consequence.

MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.

OBJECTIVE: Brain MRI measures were correlated with neuropsychological function in 35 pediatric-onset multiple sclerosis (MS) patients and 33 age- and sex-matched healthy controls. METHOD: Mean age of MS patients was 16.3 ± 2.3 years with average disease duration of 4.3 ± 3.1 years. Cortical gray matter, thalamic, and global brain volumes were calculated for all participants using a scaling factor computed using normalization of atrophy method to normalize total and regional brain volumes for head size. T1- and T2-weighted lesion volumes were calculated for MS patients. RESULTS: Cognitive impairment (CI) was identified in 29% of the MS cohort. Cognitive deficits predominantly involved attention and processing speed, expressive language, and visuomotor integration. Relative to controls, the MS group showed significantly lower thalamic volume (p < .001), total brain volume (p < .008), and gray matter volume (p < .015). Corpus callosum area and thalamic volume differentiated patients identified as having CI from those without CI (p < .05). Regression models controlling for disease duration and age indicated that thalamic volume accounted for significant incremental variance in predicting global IQ, processing speed, and expressive vocabulary (ΔR2 ranging from .43 to .60) and was the most robust MRI predictor of cognition relative to other MRI metrics. CONCLUSIONS: The robust association between cognitive function and reduced size of thalamus and global brain volume in pediatric-onset MS patients implicate neurodegenerative processes early in the disease course, and suggest that plasticity of an immature central nervous system is not sufficient to protect patients from the deleterious consequences of MS on cognitive neural networks. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Regional brain atrophy in children with multiple sclerosis.

We used cross-sectional tensor-based morphometry to visualize reduced volume in the whole brains of pediatric patients with multiple sclerosis, relative to healthy controls. As a marker of local volume difference, we used the Jacobian determinant of the deformation field that maps each subject to a standard space. To properly assess abnormal differences in volume in this age group, it is necessary to account for the normal, age-related differences in brain volume. This was accomplished by computing normalized z-score Jacobian determinant values at each voxel to represent the local volume difference (in standard deviations) between an individual subject and an age- and sex-matched healthy normal population. Compared with healthy controls, pediatric patients with multiple sclerosis exhibited significantly reduced volumes within the thalamus and the splenium of the corpus callosum and significant expansions in the ventricles. While T2-weighted lesion volume was correlated with reduced splenium volume, no correlation was found between T2-weighted lesion volume and reduced thalamic volume. Reduced volumes of the optic pathways, including that of the optic tracts and optic radiations, correlated with disease duration. Our results suggest that focal inflammatory lesions may play an important role in tract degeneration, including transsynaptic degeneration.

Treatment of cutaneous leishmaniasis with aminosidine (paromomycin) ointment: double-blind, randomized trial in the Islamic Republic of Iran.

OBJECTIVE: To compare the parasitological and clinical efficacy of four weeks versus two weeks of treatment with aminosidine (paromomycin) ointment in patients with cutaneous leishmaniasis caused by Leishmania major in the Islamic Republic of Iran. METHODS: Double-blind, randomized trial of four weeks of aminosidine ointment (n = 108) vs two weeks of aminosidine ointment and two weeks of placebo (n = 108). Patients were assessed on days 15, 29, 45, and 105 for clinical cures and clinical and parasitological cures. FINDINGS: Four weeks' treatment gave significantly better cure rates than two weeks' treatment: on day 29, there were 80/108 (74%) vs 64/108 (59%) clinical cures (P = 0.05) and 47 (44%) vs 26 (24%) clinical and parasitological cures (P = 0.005). By day 45, fewer patients who received four weeks' treatment had required rescue treatment with antimonials than those who received two weeks' treatment: 20 (19%) vs 36 (33%) (P = 0.02). On day 105, the results still favoured those who had been allocated four weeks of active treatment, but the differences were no longer as clearly significant. No side-effects were observed or reported. CONCLUSION: Approximately two-thirds of patients given ointment for four weeks were cured clinically. Although about half of those cured might have recovered spontaneously even without treatment, four weeks of aminosidine ointment could become the first-line treatment for uncomplicated cutaneous leishmaniasis due to L. major, with antimonials needed in only the one-third of patients not cured by the end of treatment with aminosidine. This would considerably reduce the costs and side-effects associated with antimonial drugs.

Treatment of cutaneous leishmaniasis with aminosidine (paromomycin) oitment: double-blind, randomized trial in the Islamic Republic of Iran

Objective: To compare the parasitological and clinical efficacy of four weeks versus two weeks of treatment with aminosidine (paromomycin) oitment in patients with cutaneous leishmaniais caused by Leishmania Major in the Islamic Republic of Iran. Methods: Double-blind, randomized trial of four weeks of aminosidine oitment (n=108) vs two weeks of aminosidine oitment and two weeks of placebo (n=108). Patients were assessed on days 15, 29, 45, and 105 for clinical cures and clinical and parasitological cures. Findings: Four weeks' treatment gave significantly better cure rates than two weeks' treatment: on day 29, there were 80/108 (74 cent) vs 64/108 (59 cent) clinical cures (P=0.05) AND 47 (44 cent) vs 26 (24 cent) clinical and parasitological cures (P=0.005). By day 45, fewer patients who received four weeks' treatment had required rescue treatment with antimonials than those who received two weeks' treatment, but the differences were no longer as clarly sigificant. No side-effects were observed or reported. Conclusion: Aproximately twi-thirds of patients given oitment for four weeks were cured clinically. Although about half of those cured might have recoverde stontaneouly even without treatment, four weeks of aminosidine ointment could become the first-line treatment for uncomplicated cutaneous leishmaniasis due to L. major, with antimonials needed in only the one-third of patients not cured by the end of treatment with aminosidine. This would considerably reduce the costs and side-effects associated with antimonial drugs

Use of stents to treat kinks causing obstruction in a left internal mammary artery graft.

Left internal mammary arteries (LIMA) are used routinely as grafts to the left anterior descending coronary artery (LAD) in selected patients undergoing coronary artery bypass graft (CABG) surgery because of better long-term patency rates. Pathology other than fibrointimal hyperplasia, accelerated atherosclerosis, or thrombus can sometimes cause obstructive lesions in such grafts. This report illustrates a kink in a LIMA graft to the LAD causing an obstructive lesion shortly after surgery and describes the subsequent management of this lesion with intracoronary stents.

A randomised, double-blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran.

Safety and efficacy of killed (autoclaved) L. major promastigotes, ALM, mixed with BCG against zoonotic cutaneous leishmaniasis was tested in healthy volunteers (n = 2453) in a randomized double blind trial vs. BCG as control. Side-effects were similar in both groups but tended to be slightly more frequent and prolonged in the ALM + BCG group. Leishmanin skin test conversion (induration > or =5 mm) was significantly greater in the ALM + BCG than in the BCG group (36.2% vs. 7.9% on day-80 and 33% vs. 19%, after 1 year, respectively). Cumulative incidence rates for 2 years, were similar in both groups (18.0% vs. 18.5%). However, LST responders on day 80 (> or =5 mm) had a significantly lower incidence (35%) of CL during the first year than non-responders. A single dose of ALM + BCG is not sufficiently immunogenic to provide a measurable response when compared to BCG alone. A single dose of this vaccine has been shown to be safe with no evidence of an exacerbating response following natural infection; hence, multiple doses or other adjuvants should be considered to increase its immunogenicity.

Treatment of cutaneous leishmaniasis with itraconazole. Randomized double-blind study.

OBJECTIVE: To compare the efficacy of itraconazole with placebo in the treatment of cutaneous leishmaniasis caused by Leishmania major. DESIGN: Double-blind placebo-controlled study. SETTING: Patients were selected from volunteers wit cutaneous leishmaniasis who lived in a hyperendemic area. PATIENTS: One hundred forty patients were randomly selected for this double-blind study. Exclusion criteria were pregnancy, gestation, age younger than 12 years, and duration of disease of more than 4 months. INTERVENTION: Each patient received itraconazole (7 mg/kg per day) or placebo for a 3-week period. The patients were kept under observation for an additional 30-day period. OUTCOME. The study was completed as planned in 131 patients. RESULTS: Complete healing occurred in 59% of the itraconazole group in comparison with 44.3% of the patients who were treated with placebo capsules. No difference was found between the 2 groups with respect to adverse effects. CONCLUSIONS: Although itraconazole has the advantage of being an oral agent that is used in the treatment of cutaneous leishmaniasis, the low response rate in patients receiving itraconazole indicates that itraconazole cannot be used as the single agent in the treatment of patients with cutaneous leishmaniasis caused by L. major.