Title:
MANAGEMENT OF PATIENTS WITH MULTIPLE SCLEROSIS: THE NATALIZUMAB THERAPY
Summary:
Multiple sclerosis is an inflammatory disease of the central nervous system characterized by multifocal demyelinating lesions and inflammatory and degenerative damage. The clinical course is highly variable, with alternating remissions and relapses, and subsequent progressive course. Motor, sensory, cerebellar, mental and visual functions are the systems involved. In addition, about half of patients develop variable cognitive impairments: the casualness of times, the course of the disease, its severity and the site of injury outbreak contribute to the onset of significant variability of the patient’s mental state. Natalizumab is a monoclonal antibody indicated in relapsing remitting multiple sclerosis with high activity.
The aims of this study were to assess efficacy, tolerability and impact on the quality of life in a cohort of 23 patients and to analyze cognitive performances and mood disorder in a subgroup of 10 patients, after one year’s therapy. The drug has shown to significantly reduce the clinical relapse rate, the development of T2 and the gadolinium-enhancing lesions and it has also proved to have excellent tolerability and safety.
The cognitive assessment showed an improvement in test scores for frontal functions, attention, working memory and mood. In our analysis, Natalizumab was effective in reducing neurologic disability and disease activity. It has also shown to have a positive effect on quality of life and mental status: improving depressive symptoms and cognitive performances. The data obtained are consistent with those of pivotal studies and literature, but beed further confirmation.
Key words:
Multiple Sclerosis, Natalizumab, Cognitive Impairment
Index
Summary pag 2
Multiple Sclerosis (MS)
Pathological description pag 3
Therapeutic description pag 11
Immunological mechanisms pag 16
MS and cognitive impairment pag 18
Neuroimaging in MS cognitive impairments pag 22
Neurobiological patterns of MS cognitive impairment pag 25 Natalizumab
Biochemical characteristics and action mechanism pag 28
Pre-clinical and clinical development: references to main studies pag 31
Immunogenicity, safety and tolerability pag 34
Progressive Multifocal Leucoencephalopathy pag 35
Indications and treatment procedures pag 37
Natalizumab and cognitive impairment pag 39
Study aims pag 41
Patients pag 41
Method pag 42
Clinical and neuroradiological assessment pag 42
Quality of life assessment pag 44
Fatigue Severity Scale pag 44
Beck Depression Inventory pag 45
Neuropsychological assessment pag 46
Statistical Analysis pag 52
Results pag 53
Clinical and neuroradiological assessment pag 53
Quality of life assessment pag 54
Neuropsychological assessment pag 55
Discussion and conclusions pag 57
Tables and graphics pag 66
Addenda pag 71
Bibliography pag 79
