Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis
ABSTRACT We report a randomized, double-blind, placebo-controlled pilot trial of systemic high-dose recombinant interferon alfa-2a (rIFNA) in 20 patients with relapsing-remitting (RR) multiple sclerosis (MS). Patients received 9 million IU rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions on serial MRI occurred in two of 12 rIFNA-treated and in seven of eight placebo-treated patients (p < 0.005). There was only one enlarging MRI lesion in the rIFNA group, whereas 27 new or enlarging lesions were present in the placebo group (p < 0.01). Baseline lymphocyte interferon gamma production of 19.10 +/- 7.12 IU/ml significantly decreased to 3.03 +/- 0.66 IU/ml (p < 0.04) in the rIFNA group, whereas production was unchanged in the placebo group. The rIFNA was tolerated without dropouts or serious side effects, but fever, malaise, fatigue (interfering with daily activities in two patients), and leukopenia occurred frequently. Neuropsychological tests excluded neurotoxicity. High-dose systemic rIFNA might reduce clinical and MRI signs of disease activity in RR MS and should be investigated in larger trials.
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ABSTRACT: e review studies that have examined the relationship between magnetic reso- nance imaging findings and clinical disability, postmortem observations, and cog- nitive dysfunction in patients with multiple sclerosis. We also review the use of magnetic resonance imaging findings as an outcome measure in clinical trials assessing the efficacy of new therapeutic agents for the treatment of multiple sclerosis. More ad- vanced applications of magnetic resonance imaging and their use in multiple sclerosis is ad- dressed later in the article. Arch Intern Med. 1998;158:565-573Archives of Internal Medicine 158(6):565-573. · 17.33 Impact Factor
- Annals of Neurology 01/1995; 37(1):7-15. DOI:10.1002/ana.410370105 · 9.98 Impact Factor
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ABSTRACT: Immunological therapy with cytokines can cause acute, subacute, delayed and, occasionally, irreversible toxicity to the CNS. Neurotoxic adverse effects are manifested by changes in cognitive, motor and emotional functioning. Although these changes are sometimes global in nature, most subacute neurotoxic symptoms attributable to interferon-α, interleukin-2 and tumour necrosis factor are specific to frontal-subcortical dysfunction and involve specific neuroanatomical and neurochemical systems. The symptoms observed typically include memory deficits, difficulties with motivation and flexible thinking (frontal lobe executive function) and motor coordination. Reasoning, language functions and visual perception are generally not affected. Depression and other psychiatric presentations are common and appear to be due to the biochemical changes induced by cytokines rather than psychological reactions to the illness for which the agents are administered. The mechanism of action of cytokines on brain function may include alterations in neurotransmitter function (mostly involving opioid and dopaminergic systems), induction of the release of neuroendocrine hormones and of other cytokines. Improved understanding of the mechanism of cytokine action in the brain is guiding the development of treatment interventions to reduce or eliminate CNS toxicity without sacrificing therapeutic efficacy. In addition, studies of cytokine neurotoxicity have advanced our knowledge of the normal role of these agents in the CNS.CNS Drugs 01/1995; 3(1):56-68. DOI:10.2165/00023210-199503010-00006 · 5.11 Impact Factor