Clemente Roque

Randomized Phase II Trial of Atovaquone with Pyrimethamine or Sulfadiazine for Treatment of Toxoplasmic Encephalitis in Patients with Acquired Immunodeficiency Syndrome: ACTG 237/ANRS 039 Study

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.

Intracarotid chemotherapy with etoposide and cisplatin for malignant brain tumors

Chemotherapy for tumors of the central nervous system has a limited efficacy presumably because of restricted blood‐brain barrier permeability. The advantage of regional intra‐arterial administration of anticancer drugs is an increased uptake during the first passage of the drugs through tumor capillaries. Twenty patients with high‐grade astrocytomas (HGA) and 28 patients with metastatic brain tumors (MBT) received intracarotid/intravertebral infusion of etoposide and cisplatin. Eight patients with HGA who underwent incomplete resection responded to chemotherapy alone. Four additional patients had complete resection of the tumor. Median survival time of the group (responders and nonresponders) has been 14 months. Twelve patients with MBT responded to chemotherapy alone (six had complete response [CR], and six had partial response [PR]) with a median survival time of 7 months. Intra‐arterial chemotherapy (IAC) appears to be effective with acceptable toxicities. Accrual of additional patients is required before a final conclusion can be reached.

Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS

ObjectiveTo assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. DesignA phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine. SettingEight clinical sites in the United States. PatientsForty-two adult HIV-infected patients with confirmed or presumed acute TE. MethodsPatients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy. Main outcome measures Patient response was evaluated clinically and radiologically. ResultsOf the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose. ConclusionThe 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.

Multilevel thoracic disk herniations: CT and MR studies

Thoracic disk herniation is a disorder that can present clinically perplexing problems for physicians. The true incidence of thoracic disk herniation is difficult to assess with various authors reporting an incidence ranging between 0.15 and 1.8% of all disk herniations. Multiple thoracic disk herniations are rare and, to the best of our knowledge, have received little attention in the orthopedic, neurosurgical, and radiological literature. A retrospective review of 680 myelograms performed at our institution was carried out and only three cases of multilevel thoracic disk herniations were found. We analyze these cases, discuss the relative value of the imaging modalities used in their diagnosis, and review the literature dealing with this interesting disorder.

A prospective, multicenter pilot study investigating the utility of flat detector derived parenchymal blood volume maps to estimate cerebral blood volume in stroke patients

Purpose Newer flat panel angiographic detector (FD) systems have the capability to generate parenchymal blood volume (PBV) maps. The ability to generate these maps in the angiographic suite has the potential to markedly expedite the triage and treatment of patients with acute ischemic stroke. The present study compares FP-PBV maps with cerebral blood volume (CBV) maps derived using standard dynamic CT perfusion (CTP) in a population of patients with stroke. Methods 56 patients with cerebrovascular ischemic disease at two participating institutions prospectively underwent both standard dynamic CTP imaging followed by FD-PBV imaging (syngo Neuro PBV IR; Siemens, Erlangen, Germany) under a protocol approved by both institutional review boards. The feasibility of the FD system to generate PBV maps was assessed. The radiation doses for both studies were compared. The sensitivity and specificity of the PBV technique to detect (1) any blood volume deficit and (2) a blood volume deficit greater than one-third of a vascular territory, were defined using standard dynamic CTP CBV maps as the gold standard. Results Of the 56 patients imaged, PBV maps were technically adequate in 42 (75%). The 14 inadequate studies were not interpretable secondary to patient motion/positioning (n=4), an injection issue (n=2), or another reason (n=8). The average dose for FD-PBV was 219 mGy (median 208) versus 204 mGy (median 201) for CT-CBV. On CT-CBV maps 26 of 42 had a CBV deficit (61.9%) and 15 (35.7%) had a deficit that accounted for greater than one-third of a vascular territory. FD-PBV maps were 100% sensitive and 81.3% specific to detect any CBV deficit and 100% sensitive and 62.9% specific to detect any CBV deficit of greater than one-third of a territory. Conclusions PBV maps can be generated using FP systems. The average radiation dose is similar to a standard CTP examination. PBV maps have a high sensitivity for detecting CBV deficits defined by conventional CTP. PBV maps often overestimate the size of CBV deficits. We hypothesize that the FP protocol initiates PBV imaging prior to complete saturation of the blood volume in areas perfused via indirect pathways (ie, leptomeningeal collaterals), resulting in an overestimation of CBV deficits, particularly in the setting of large vessel occlusion.

VASCULITIS OWING TO INFECTION

Infections are a recognized cause of secondary vasculitis. A variety of pathogens have a propensity to involve blood vessels. Vasculitis, non-vasculitic vasculopathy, and mycotic aneurysms lead to infarction and hemorrhage of nervous system tissue. Treatment of infection-related vasculitis should include appropriate antimicrobial therapy directed against the offending pathogen, and appropriate management of cerebrovascular complications.

Glucose metabolic changes in nontumoral brain tissue of patients with brain tumor following radiotherapy : A preliminary study

PURPOSE Our goal was to measure the effect of radiotherapy on the brain glucose metabolism of tumoral and nontumoral tissue of patients with brain malignancies. METHOD Fifteen patients with primary or metastatic brain tumors were studied with 2-deoxy-2-[18F]fluoro-D-glucose and PET prior to radiotherapy, and nine of them were rescanned 1 week after completing radiotherapy. RESULTS Brain metabolism in patients (all brain regions except for tumoral and edematous tissue) was lower than that of matched controls (34.0 +/- 8.3 vs. 46.5 +/- 6.4 mumol/100 g/min; p < or = 0.0001). Five of the nine patients retested after radiotherapy showed decrements in tumor metabolism (47 +/- 10%; p < or = 0.05) and increases in brain metabolism (10 +/- 4%; p < or = 0.004), and the other four showed no changes in tumor or in brain metabolism. Radiotherapy-induced changes in tumor metabolism were negatively correlated with changes in brain metabolism (r = 0.85, p < or = 0.004), but not with changes in tumor volume (assessed with MR images). CONCLUSION The study indicates that radiotherapy-induced increases in metabolism of nontumoral tissue are secondary to decreased tumor metabolic activity and not just due to volume reduction.

Feasibility studies of virtual laryngoscopy by CT and MRI-from data acquisition, image segmentation, to interactive visualization

Virtual endoscopy concept has been applied to study the larynx, as well as other hollow organs in recent years, assuming a clean lumen. In this work, we investigated the feasibility of virtual laryngoscopy by (1) studying currently available imaging protocols, (2) developing a suitable image segmentation method, and (3) constructing art efficient visualization system. By utilizing helical computed tomography (CT), the images for laryngeal volume can be obtained during a breath hold with 0.3 mm resolution. A fast pulse sequence using 1.5 T magnetic resonance (MR) imager can achieve 1 mm resolution within few minutes. The gain in tissue contrast on MR images is at the cost of resolution, and motion artifacts must be considered during image segmentation. A first-order Lagrange interpolation was applied to mitigate the reduced resolution, as well as partial volume effect and noise on the MR images. An automatic segmentation algorithm was adapted to extract the wall volume of the larynx. The algorithm considers local voxel property and classifies voxels based on the local property in the KL (Karhunen-Loeve) space. A visualization system was constructed for examining the mucosa and wall geometry with anatomical references in three dimensions. It navigates inside the lumen, as well as outside the larynx interactively with capability of inspecting and zooming into the regions of interest. It can also cut the larynx in any orientation to open the whole volume for viewing the entire inner surface. The procedure was tested on 2 volunteers and 2 patients. The segmentation performed consistently for all the studies and showed to be relatively insensitive to mild respiratory motion artifacts in the MR images. Image processing was accomplished within a few minutes on PC and low-end SGI platforms. These studies demonstrated the feasibility of virtual laryngoscopy for diagnosis of laryngeal abnormalities.