T2 hypointensity in the deep gray matter of patients with benign multiple sclerosis.

BACKGROUND: Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, commonly occurs in multiple sclerosis (MS). However, GM T2 hypointensity in benign MS (BMS) has not yet been characterized. OBJECTIVE: To determine the presence of deep GM T2 hypointensity in BMS, compare it to secondary progressive (SP) MS and assess its association with clinical and diffusion tensor (DT) MRI measures. METHODS: Thirty-five cognitively unimpaired BMS, 26 SPMS patients, and 25 healthy controls were analyzed for normalized T2-intensity in the basal ganglia and thalamus, global T2 hyperintense lesion volume, global atrophy, and white matter and GM DT metrics. RESULTS: BMS and SPMS patients showed deep GM T2 hypointensity compared with controls. T2 hypointensity was similar in both MS subgroups and moderately correlated (r = -0.45 to 0.42) with DT MRI metrics. GM T2 hypointensity in BMS showed a weak to moderate correlation (r = -0.44 to -0.35) with disability. CONCLUSIONS: GM in BMS is not spared from structural change including iron deposition. However, while T2 hypointensity is related to global tissue disruption reflected in DT MRI, the expression of benign versus non-benign MS is likely related to other factors.

Quantitative imaging and sigmoidoscopy to assess distribution of rectal microbicide surrogates.

Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose-based microbicide surrogate or viscosity-matched semen surrogate, labeled with gadolinium-DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium-sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29-102%; P<0.001), as far as the splenic flexure (approximately 60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV-sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.

Thalamic atrophy and cognition in multiple sclerosis.

OBJECTIVES: Recent studies have indicated that brain atrophy is more closely associated with cognitive impairment in multiple sclerosis (MS) than are conventional MRI lesion measures. Enlargement of the third ventricle shows a particularly strong correlation with cognitive impairment, suggesting clinical relevance of damage to surrounding structures, such as the thalamus. Previous imaging and pathology studies have demonstrated thalamic involvement in MS. In this study, we tested the hypothesis that thalamic volume is lower in MS than in normal subjects, and that thalamic atrophy in MS correlates with cognitive function. METHODS: We studied 79 patients with MS and 16 normal subjects. A subgroup of 31 MS subjects underwent cognitive testing. The thalamus was segmented in whole from three-dimensional MRI scans. We also determined whole brain atrophy (brain parenchymal fraction), third ventricular width, and whole brain T2-weighted (fluid-attenuated inversion recovery) hyperintense, T1 hypointense, and gadolinium-enhanced lesion volumes. RESULTS: Normalized thalamic volume was 16.8% lower in the MS group (p < 0.0001) vs controls. Cognitive performance in all domains was moderately to strongly related to thalamic volume in the MS group (r = 0.506 to 0.724, p < 0.005), and thalamic volume entered and remained in all regression models predicting cognitive performance. Thalamic volume showed a weak relationship to physical disability score (r = -0.316, p = 0.005). CONCLUSION: These findings suggest that thalamic atrophy is a clinically relevant biomarker of the neurodegenerative disease process in multiple sclerosis.

MRI findings in Susac's syndrome.

BACKGROUND: Susac syndrome (SS) is a self-limited syndrome, presumably autoimmune, consisting of a clinical triad of encephalopathy, branch retinal artery occlusions, and hearing loss. All three elements of the triad may not be present or recognized, and MR imaging is often necessary to establish the diagnosis. OBJECTIVE: To determine the spectrum of abnormalities on MRI in SS. METHODS: The authors reviewed the MR images of 27 previously unreported patients with the clinical SS triad, and 51 patients from published articles in which the MR images were depicted or reported. RESULTS: All 27 patients had multifocal supratentorial white matter lesions including the corpus callosum. The deep gray nuclei (basal ganglia and thalamus) were involved in 19 (70%). Nineteen (70%) also had parenchymal enhancement and 9 (33%) had leptomeningeal enhancement. Of the 51 cases from the literature, at least 32 had callosal lesions. The authors could not determine the presence of callosal lesions in 18 of these patients, and only one was reported to have a normal MRI at the onset of encephalopathy. CONCLUSIONS: The MR scans in SS show a rather distinctive pattern of supratentorial white matter lesions that always involve the corpus callosum. There is often deep gray matter, posterior fossa involvement, and frequent parenchymal with occasional leptomeningeal enhancement. The central callosal lesions differ from those in demyelinating disease, and should support the diagnosis of SS in patients with at least two of the three features of the clinical triad.

A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.

The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem/Riamet; Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (> or = 12 years old) with acute, uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] = 91.7, 97.9%) for artemether-lumefantrine and 100% (90% CI = 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse events were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups showed QTc prolongations but without any cardiac complication, and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen, and were higher, particularly for lumefantrine, than those previously observed with the four-dose regimen, explaining the greater efficacy of the six-dose regimen in a drug-resistant setting. These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria.

Acute transverse myelitis after influenza vaccination: magnetic resonance imaging findings.

Descriptions in the literature of magnetic resonance imaging (MRI) findings in post-vaccination myelitis are scarce. Described here is a case of acute transverse myelitis that occurred after administration of an influenza vaccination. T1-weighted MRIs showed diffuse, fusiform spinal cord enlargement, extending from C-3 to rostral thoracic levels. Intramedullary lesions containing increased T2 signal were found in the areas of cord enlargement. The involvement on MRI was profound, extending far rostral to the level of the discrete clinical myelopathy. The lesions did not enhance after contrast administration. The patient had a complete long-term recovery of neurological function. This represents the first report of MRI findings in acute transverse myelitis after influenza vaccination.