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ABSTRACT: Discoveries of the mechanisms that underlie the pathogenesis of multiple sclerosis have been acquired at an impressive rate over the last few decades and, as a consequence, a growing number of treatments are becoming available for this disease. This review first analyzes the experience from the early stages of the disease-modifying therapies, then, expanding on the concept of early treatment for improved outcomes, it focuses on natalizumab and its major complication, progressive multifocal leukoencephalopathy. We offer views on the risks associated with the use of natalizumab by underscoring the importance of the JC virus serology and by providing preliminary data on our experience with the extended interval dosing of natalizumab. This approach, which advocates individualized treatment plans, raises the question of the minimum effective natalizumab dose. Extended interval dosing suggests efficacy can be maintained while providing advantages of costs and convenience over regular monthly dosing. More data examining this strategy are necessary.
Therapeutic Advances in Neurological Disorders 03/2012; 5(2):97-104.
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ABSTRACT: Glatiramer acetate (GA) is an immunomodulatory drug approved for the treatment of clinically isolated syndrome (CIS) and relapsing/remitting multiple sclerosis (RRMS). As an antigen-based therapy, GA induces GA-specific antibodies in treated patients and animals. GA-specific antibodies do not neutralize therapeutic effects on relapses and disability. Rather, it has been suggested that GA-specific antibodies may be associated with improved clinical outcomes. We evaluated antibody responses in eight patients with RRMS treated with GA for 15 months and antibody responses in GA-treated C57BL/6 mice before and after induction of experimental autoimmune encephalomyelitis (EAE). There were no significant differences from pretreatment levels of total IgE or GA-specific IgE in patients with RRMS. Total IgG1, IgG3 and GA-specific IgG4 were significantly increased at 15 months of GA treatment. Antibody type and titre were not associated with clinical outcomes, i.e. expanded disability status scale (EDSS) score, disease burden on magnetic resonance images (MRI) or clinical relapses. In contrast, mice with EAE showed a marked increase in GA-specific IgE and GA-specific IgG1 antibody responses. GA-treated mice demonstrated improved clinical symptoms and lower mortality than untreated controls. Our results suggest that antibody responses to GA are heterogeneous among patients with RRMS, with no apparent association between antibody response and clinical outcomes. Clinical improvements in EAE-induced GA-treated mice suggest that GA-specific IgE and IgG1 may contribute to GA treatment effects in EAE.
Scandinavian Journal of Immunology 05/2011; 74(3):219-26. · 2.23 Impact Factor
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ABSTRACT: We describe the case of a 33-year-old woman who presented with a 2-month history of worsening head tremor. The medical evaluation led to the new diagnosis of MS and the MRI of brain demonstrated prominently active disease. Intravenous rituximab was started according to the HERMES trial, and significant improvement was noted. She has received additional rituximab dosing approximately every 6 months, and at the 2-year follow-up the tremor has not recurred. The resolution of head tremor likely resulted from the complete suppression of MS disease activity, which must have allowed restoration of normal neural circuitry. In agreement with a growing body of evidence that supports early control of MS disease activity to prevent accumulation of fixed disability, this case advocates for aggressive immunological therapy at the onset of tremor in MS patients.
Neurological Sciences 05/2011; 32(6):1157-60. · 1.32 Impact Factor
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ABSTRACT: Under the therapeutic point of view, neuromyelitis optica (NMO) poses major challenges. Patients with NMO manifest severe disability from recurrent demyelinating lesions and the therapies are only partially effective. We performed a retrospective analysis of the records of patients followed at our institution and provide suggestions for management of acute relapses and preventive therapy.
We searched the electronic database for patients who met criteria for NMO spectrum between January 2003 and June 2009. Patient characteristics, clinical relapses, treatments, neurological status, and medical complications were recorded.
In the 18 patients who met the criteria for NMO different regimens of chemotherapies seemed to be modestly effective in preventing clinical relapses. After the year 2006, when rituximab began to be used for NMO patients at our institution, a significant reduction of the relapse rate was observed. After the administration of rituximab, we have systematically been monitoring the percentage of the circulating B cells and we suggest that the clinical relapses occurring while on rituximab therapy correlate with the reconstitution of circulating B cells.
The lack of response to therapies approved for multiple sclerosis demands prompt recognition of NMO patients and the NMO-antibody testing can be critically important for that purpose. We have observed remarkable variability of the disease course with long-lasting relapse-free intervals and clusters of severe, disabling attacks. The best effects in preventing and interrupting the high frequency of relapses is achieved with rituximab whose repeated dosing should be guided by monitoring the circulating B-cell counts.
The Neurologist 03/2011; 17(2):98-104. · 1.26 Impact Factor
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Journal of neurology, neurosurgery, and psychiatry 10/2010; 82(11):1296-8. · 4.87 Impact Factor
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Neurology 08/2010; 75(6):568-70. · 8.31 Impact Factor
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Neurology 01/2010; 74(1):91. · 8.31 Impact Factor
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09/2009; , ISBN: 9780470015902
