In this international, noncomparative, randomized phase II trial, we evaluated the effectiveness and tolerance of atovaquone suspension (1500 mg orally twice daily) plus either pyrimethamine (75 mg per day after a 200-mg loading dose) or sulfadiazine (1500 mg 4 times daily) as treatment for acute disease (for 6 weeks) and as maintenance therapy (for 42 weeks) for toxoplasmic encephalitis (TE) in patients infected with human immunodeficiency virus. Twenty-one (75%) of 28 patients receiving pyrimethamine (95% lower confidence interval [CI], 58%) and 9 (82%) of 11 patients receiving sulfadiazine (95% lower CI, 53%) responded to treatment for acute disease. Of 20 patients in the maintenance phase, only 1 experienced relapse. Eleven (28%) of 40 eligible patients discontinued treatment as a result of adverse events, 9 because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. Although gastrointestinal side effects were frequent, atovaquone-containing regimens are otherwise well tolerated and safe and may be useful for patients intolerant of standard regimens for toxoplasmic encephalitis.

Background and Purpose-Diffusion-weighted MRI (DWI) is highly sensitive to early cerebral ischemia, but its dependence on lesion location, acuity, and etiology remains unknown. Furthermore, although a marked perfusionweighted MRI (PWI)-DWI mismatch may exist in a subset of acute strokes, the frequency and distribution of these mismatches have never been methodically characterized in an unselected population. To address these 2 issues, we evaluated echo-planar imaging in 117 consecutive patients with signs and symptoms of acute stroke. Methods-Clinical diagnoses were determined by chart review. Fluid-attenuated inversion recovery (FLAIR), DWI, and PWI sequences were scored for lesion acuity, neuroanatomy, and vascular territory. Lesion and PWI-DWI mismatch volumes were determined by image analysis. Results-DWI was more sensitive than was FLAIR for the detection of stroke for all subtypes in all anatomic distributions and at all tested time intervals. Although DWI exhibited its greatest benefit over FLAIR during the first 6 hours, it was still superior to FLAIR even after 24 hours. PWI abnormalities were detected in 49% of patients with DWI abnormalities. In the majority of these cases, the PWI-DWI mismatch was substantially larger than the DWI lesion itself. Both the largest DWI lesion volumes and the largest mismatch volumes occurred in patients with carotid disease. Conclusions-DWI nearly doubles the likelihood of detecting acute ischemic stroke lesions compared with FLAIR for all etiologies and in all anatomic locations. In the hyperacute period (0 to 6 hours), DWI more than triples the likelihood of acute-stroke detection over FLAIR. PWI reveals a measurable mismatch compared with DWI nearly 50% of the time; and in more than half of these patients, the ratio of the volume of the PWI lesion to the DWI lesion is several times larger than the core ischemic lesion itself. In the final analysis, approximately one fourth of all stroke patients present with a large volume of potentially salvageable tissue at risk for infarction. (Stroke. 2001;32:2774-2781.)

The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.

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