DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.

Multiple sclerosis (MS) is an immune-mediated neurologic disease in which acute inflammatory events early in the disease course contribute to subsequent neurologic disability. The early relapsing inflammatory phase is followed by a progressive degenerative phase in which the frequency of acute inflammatory attacks diminishes but progressive loss of neurologic function continues. Current immune therapies are most effective in suppressing the acute inflammatory events that characterize the earlier stages of disease. Optimal suppression of these inflammatory events is likely to have the best potential for delaying or preventing loss of axons and decline in neurologic function. In view of these considerations, and because MS is a heterogeneous disease and response to disease-modifying agents (DMA) varies across individuals, it is important to identify suboptimal responders as early as possible to allow therapeutic modification while the opportunity to avert future loss of function remains. At present, no criteria for identifying suboptimal responders have been validated. In January 2004, a group of neurologists from 16 MS centers in the United States met to develop a consensus on criteria for defining suboptimal response for use in compelling clinical situations and to prompt clinical studies to validate the efficacy of these criteria. Consensus criteria included relapse rates of either 1/year or unchanged from pretreatment rates, incomplete recovery from multiple attacks, evolution of polyregional neurologic involvement, recurrent brainstem or spinal cord lesions, and cumulative loss of neurologic function sufficient to disrupt daily activities. The panel then considered the use of mitoxantrone for patients with worsening MS and a suboptimal response to DMA therapy.

The clinical presentation, risk factors, laboratory data, and neuroimaging and neuropathological findings in 26 patients with autopsy proved central nervous system (CNS) aspergillosis are reviewed. Eleven patients had hematological malignancies (8 underwent bone marrow transplantation), 8 patients underwent liver transplantation, and 3 patients had acquired immunodeficiency syndrome. Four had illnesses resulting in immunosuppression (systemic lupus erythematosus, infected aortic graft, neuroblastoma, and fulminant hepatic failure). The most common presenting clinical symptoms of CNS aspergillosis were fever and a strokelike syndrome. Risk factors for developing CNS aspergillosis included neutropenia, immunosuppressive therapy, low CD4 counts, and retransplantation. Spinal fluid findings were nondiagnostic. Computed tomograms and magnetic resonance scans of the head showed low-density lesions or hemorrhagic infarctions. Most aspergillosis cases occurred in the setting of widely disseminated disease commonly arising from the lung. Pathologically, multiple areas of necrosis throughout the brain were seen. Aspergillus invasion of blood vessel walls was seen microscopically. Amphotericin B with or without flucytosine was not effective treatment.

Cerebrospinal fluid from 582 persons was analyzed by a double-antibody radioimmunoassay for the presence of material cross-reactive with peptide 43-88 of human myelin basic protein (BP). In a group of 104 patients with multiple sclerosis (MS), 23 of 33 individuals clinically judged to have had an exacereation within two weeks prior to the time CSF was obtained had detectable material ranging from 2 to 200 ng/ml. In the remaining 71 MS patients who either were stable or had had an exacerbation more than two weeks before, only 1 patient had a marginally elevated level of immunoreactive material. CSF from 53 persons with cerebrovascular disease was studied, and 13 of 29 with recent infarctions had values of 2 to 540 ng/ml. The degree of elevation in strokes generally paralleled the predicted volume of the lesion, but the amounts detected did not correlate quite so closely temporally with onset as they did with the periods of active disease in MS. Of the remaining 425 patients, 29 had immunoreactive material of 2 to 400 ng/ml in their CSF. Most of these patients with detectable material had acute diseases known to affect the myelin sheath. Eight of 10 persons with acute disseminated encephalomyelitis had no detectable material. The presence in CSF of material cross-reactive with BP peptide 43-88 does not have diagnostic specificity for MS but can be used as a means for determining recent myelin injury. The type of BP peptide formed and mechanisms for clearance of BP and BP peptides may be important in determining the biological consequences following release of this potentially immunogenic material from the central nervous system.