Ceftriaxone therapy in patients with PLS with severe fatigue was associated with an improvement in fatigue but not with cognitive function or an experimental laboratory measure of infection in this study. Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with PLS.

Eighty-seven patients with definite multiple sclerosis (MS) were examined neurologically and administered the Mini-mental State examination (MMS) to assess cognitive disability at the beginning and end of a one-year study. A CT scan was performed in 37. A group of 16 patients with stable spinal cord injuries (SCI) were studied in a similar manner. Of the MS patients, 47% had a mean General Health Questionnaire (GHQ) score in the abnormal range. This was a higher rate than in SCI patients (P = 0.004). Mean depression scores were similar in MS and SCI patients, but MS patients with brain involvement were more depressed than those with cord lesions only (P = 0.05). Depression score was unrelated to functional disability but was correlated with the degree of neurological impairment (P = 0.03). Euphoric patients were more likely to have brain involvement (P = 0.006), to have progressive MS (P less than 0.0001), and to have enlarged ventricles (P = 0.04) and were more impaired cognitively (P = 0.04) than noneuphoric patients. These results suggest that depression in MS patients is partly determined by the presence of brain involvement, but that it is also an emotional reaction to the disorder. Euphoria and cognitive disorder are reflections of brain involvement.

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Abstract-Mitoxantrone is the first drug approved for the treatment of secondary progressive multiple sclerosis (SPMS) in the United States. This assessment considers use of mitoxantrone in the treatment of MS. Mitoxantrone probably reduces the clinical attack rate and reduces attack-related MRI outcomes in patients with relapsing MS (Type B recommendation). Also, mitoxantrone may have a beneficial effect on disease progression in patients with MS whose clinical condition is worsening (Type B recommendation). The potential for serious toxicity of mitoxantrone, however, must be taken into account when considering this therapy in individual patients. Moreover, because the potential clinical benefits on disease progression appear to be only modest, the results of the single phase III trial should be replicated in another (and hopefully much larger) clinical study before this agent is widely recommended for the treatment of patients with MS. NEUROLOGY 2003;61:1332-1338 Mitoxantrone hydrochloride (Novantrone) is an anthracenedione that has been used as an antineoplastic agent to treat hormone-refractory prostate cancer and acute nonlymphocytic leukemia in adults. It exerts its antineoplastic action by intercalating into DNA and producing both DNA strand-breaks and interstrand cross-links; it also interferes with RNA synthesis and markedly inhibits the enzyme topoisomerase II, which aids in the DNA repair process. [1][2][3][4] In the treatment of MS, mitoxantrone represents the latest in a long line of general immunosuppressive agents studied in this disease. Previously, most such agents have not shown clear-cut benefits in this condition. [5][6][7][8][9][10] On the basis of a phase III clinical trial in Europe, 11,12 and an earlier phase II study, 13 mitoxantrone recently received an expanded indication from the Food and Drug Administration (FDA) for use in secondary progressive MS (SPMS), in progressiverelapsing MS, and for patients with worsening relapsing-remitting (RR) MS. This last category is defined as patients whose neurologic status remains significantly abnormal between MS attacks.Mitoxantrone is the first drug approved for these indications in the United States, and it is the purpose of this assessment to consider both the evidence leading to the recent FDA approval as well as the appropriate clinical role of this agent in the management of patients with MS.Description of the analytic process. Articles for this review were searched in Medline under the keywords mitoxantrone and MS. Forty-one articles were identified by this search. The abstracts of these articles were reviewed and the original articles were selected for inclusion in the analysis only if they were either controlled trials or case series using mitoxantrone in the treatment of MS. Five such articles were identified, in addition to the phase III trial. 11,12 In addition, the reference lists of the articles found in this manner were also reviewed to identify articles or abstracts not found by the computer search.Analysis of the evidence. Followi...

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