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21 results

Page 1 of 2

  • 40 - Statins in multiple sclerosis
  • from Section III - Clinical trials of multiple sclerosis therapies
  • Edited by Jeffrey A. Cohen, Richard A. Rudick
  • Book: Multiple Sclerosis Therapeutics
  • Published online: 05 December 2011
  • Print publication: 20 October 2011, pp 465-471
  • View abstract

    Summary

    Dimethyl fumarate (DMF) is an oral therapy in development for multiple sclerosis (MS). Fumaric acids were first studied in MS in a Phase 1, open-label, baseline-controlled trial using the combination fumaric acid ester preparation Fumaderm. Based upon the encouraging Phase 1 results, Fumapharm partnered with Biogen Idec to conduct a Phase 2 trial of DMF in relapsing-remitting multiple sclerosis (RRMS). The use of DMF in autoimmune diseases arose from a personal view of the immune system, whereby autoimmunity is caused by disruption in the Krebs's cycle. The Phase 2 trial found that 720 mg/d of BG00012 reduced active inflammation. The Phase 3 trials provide pivotal and definitive evidence regarding the safety and efficacy of BG00012 in MS. Ongoing laboratory studies and advanced imaging studies in the Phase 3 trials are evaluating the neuroprotective effects of BG00012. Fumaric acids such as BG00012 are an exciting new class of potential MS treatment.
  • 42 - B-cell-based therapies for multiple sclerosis
  • from Section III - Clinical trials of multiple sclerosis therapies
  • Edited by Jeffrey A. Cohen, Richard A. Rudick
  • Book: Multiple Sclerosis Therapeutics
  • Published online: 05 December 2011
  • Print publication: 20 October 2011, pp 483-497
  • View abstract

    Summary

    In the first of two studies reported by Rose and coworkers, patients with relapsing-remitting multiple sclerosis (RRMS) or secondary-progressive multiple sclerosis (SPMS) were initiated on daclizumab with the same dose. A positive effect on relapses was observed. Safety data coming from daclizumab's regulatory-approved indication in renal transplantation suggest that the drug is overall safe and well tolerated. However, safety data from other of-label indications, such as uveitis, seem to confirm safety concerns regarding a mild increase in infection rate as well as skin reactions. Daclizumab is a novel and promising therapy for MS patients now being tested as monotherapy in a large Phase 3 trial using an active comparator arm. Daclizumab's mechanism of action is not fully understood, but an increase in regulatory immune cells has been related to clinical response and is now thought to play a more important role than direct anti-inflammatory effects derived from IL-2 blockade.
  • Section 4 - ADEM
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 183-222
  • View extract

    Summary

    This chapter focuses on the clinical features of the pathophysiology of acute disseminated encephalomyelitis (ADEM) in children. ADEM can occur at any age, but is more common in pediatric patients than in adults. Few systematic population-based studies have been performed to address the incidence and geographic distribution of ADEM. ADEM was more frequently associated with pediatric exanthematous infections. ADEM is usually a monophasic illness presenting with neurological symptoms and signs within 2 days to 4 weeks after an antecedent event. Neuroimaging studies are useful and essential tools in establishing the diagnosis of ADEM. Fever, encephalopathy, and neurological signs and symptoms are by nature frequent presenting features of ADEM. Many inflammatory and non-inflammatory disorders of the central nervous system (CNS) may have similar clinical and neuroimaging presentation. Patients who do not have encephalopathy are categorized as having a clinical isolated syndrome (CIS).
  • Section 3 - Pediatric MS Biology
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 157-182
  • View extract

    Summary

    This chapter summarizes immune mechanisms and disease biomarkers of pediatric multiple sclerosis (MS) and acute demyelinating syndromes as well as future directions for research. In adult-onset MS, the hallmark of MS pathology has historically been the perivascular inflammatory lesion, associated with demyelination and axonal injury. Cerebrospinal fluid (CSF) profiles including cellular profiles, oligoclonal bands and IgG Index have been used to characterize MS and differentiate it from other diseases. A study of a large cohort of children with inflammatory demyelination and controls, demonstrated that children with inflammatory central nervous system (CNS) demyelination as well as children with autoimmune diabetes, exhibited heightened peripheral T-cell responses to a wide array of self-antigens. Clinically useful biological markers of inflammation are lacking in both adult- and pediatric-onset MS. N-acetylaspartate (NAA) is selectively synthesized in neurons and considered a marker of the functional integrity of neuronal mitochondrial metabolism.
  • Section 7 - Neuromyelitis in Children
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 255-271
  • View extract

    Summary

    This chapter reviews the growing clinical and scientific literature regarding neuromyelitis optica (NMO) and Aquaporin (AQP)-4 autoimmunity, with the emphasis on recent studies in children. Most of the clinical, immunological, and pathological insights into NMO in recent years have emanated from the identification of the disease-specific NMO-IgG antibody and its antigenic target, AQP4. NMO was considered to require absence of clinical disease outside the optic nerve or spinal cord, although clinically silent brain lesions were recognized as common in NMO. Diagnostic criteria published in 1999 proposed negative brain MRI at onset as a supportive criterion to differentiate NMO from multiple sclerosis (MS). McKeon et al. described that the most common cerebrospinal fluid finding in NMO is a lymphocytic or neutrophil predominant leukocytosis and elevated protein. Treatment for NMO must include effective therapies for acute attacks as well as the use of chronic immunosuppressive treatments to prevent attacks and related disability.
  • Chapter 11 - Treatment of breakthrough disease
  • from Section 2 - Pediatric MS Course and Treatment
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 101-111
  • View extract

    Summary

    In adult breakthrough disease, treatment strategies include switching to another first-line agent, adding another agent to the on-going therapy, or switching to a second-line drug such as natalizumab or immunosuppression. Therapeutic strategies such as switch to a second-line agent are typically associated with the possibility of more severe adverse events than those seen with first-line agents, including life-threatening conditions such as progressive multifocal leukoencephalopathy (PML), leukemia, secondary cancers, or infections. The primary goal of breakthrough therapy in pediatric multiple sclerosis (MS) is to prevent disease activity and disability progression in patients who have continued disease activity despite appropriate first-line therapy. Methotrexate (MTX) is a dicarboxylic acid used in the treatment of various cancers and autoimmune diseases. Combination therapy of either first-line drugs or first-line drugs with a second-line agent is sometimes used as an approach to obtain better disease control in breakthrough MS.
  • Section 6 - Acute Complete Transverse Myelitis in Children
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 243-254
  • View extract

    Summary

    Acute transverse myelitis (ATM) is a potentially devastating immune-mediated disorder of the spinal cord that affects all ages. Typical ATM is a monofocal and monophasic inflammatory disorder targeting primarily the spinal cord, resulting in motor, sensory, and autonomic dysfunction. ATM presents with sudden onset of rapidly progressive weakness that most often involves the lower extremities but may include the arms as well. Abnormal findings were reported in four out of six children with ATM who underwent spinal cord MRI. A case series of ATM in childhood reported functional outcomes in a group of 33 individuals using the FIM and WeeFIM tools for measuring performance of daily skills at an average follow-up of eight years following the onset of disease. The initial phase of Guillain-Barré syndrome (GBS) may be confused with ATM because of the similar presentation of muscle weakness, loss of reflexes and meningeal signs.
  • Section 2 - Pediatric MS Course and Treatment
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 75-156
  • View extract

    Summary

    In childhood-onset multiple sclerosis (MS), the cerebrospinal fluid (CSF) profile is not fundamentally different from the adult-onset MS. Magnetic resonance imaging (MRI) is the best imaging technique to detect lesions suggestive of MS in children. The initial clinical course in most patients with childhood-onset MS is relapsing-remitting. In the UCSF cohort, the initial MS event was moderate or severe in 86% of children compared with 56% of adult-onset MS. In the UCSF pediatric-onset cohort, complete recovery was seen in 66%, which was similar to adults seen at the same center, questioning whether children have less irreversible neuronal injury during their first event or/and have a better ability to repair. MS is likely the result of a complex interplay between genes and environment. Potential prognostics factors associated with the assignment of disability milestones have been examined in several cohort studies from adult centers and one cohort from child neurology centers.
  • Section 5 - Optic Neuritis in Children
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 223-242
  • View extract

    Summary

    This chapter reviews the presentation of children with optic neuritis (ON) and compares these children to the 457 adults enrolled across the 15 institutions who participated in the ON treatment trial (ONTT). ON is part of a broader category of disorders, collectively referred to as the optic neuropathies, causing dysfunction of the optic nerve. Acute demyelinating ON may occur as a clinically isolated syndrome as in adults, or it may be concurrent with widespread demyelination as in acute disseminated encephalomyelitis. Visual recovery is usually good in children with ON. The ONTT has a tremendous impact on the use of multiple sclerosis (MS) therapies in adults with ON and other clinically isolated syndromes. Treatment is based on adult studies and includes short-term and long-term therapies, which may hasten some aspects of visual recovery and decrease the disease burden and risk of MS, respectively.
Demyelinating Disorders of the Central Nervous System in Childhood
  • Demyelinating Disorders of the Central Nervous System in Childhood
  • Edited by Dorothée Chabas, Emmanuelle L. Waubant
  • Published online: 11 April 2011
  • Print publication: 17 March 2011
  • View description
    Although multiple sclerosis and other disorders of myelin formation and repair are most commonly associated with adults, they can also occur in infants, children and adolescents. Up to 5 percent of those with MS experience symptoms before the age of 18, and the number of cases diagnosed is rising. There is a lack of awareness about these diseases in childhood, however, even amongst pediatric neurologists and MS specialists. Demyelinating Disorders of the Central Nervous System in Childhood provides comprehensive coverage of these diseases, highlighting throughout the differences between management in childhood and in adults. With sections dedicated to the diagnosis, course, treatment and biology of pediatric MS, detailed chapters on other childhood demyelinating diseases, including acute disseminated encephomyelitis, optic neuritis, acute complete transverse myelitis and neuromyelitis optica, are also provided. Essential reading for pediatric neurologists and MS specialists, this book will also be valuable reading for adult neurologists and pediatricians.
  • Chapter 7 - Pediatric multiple sclerosis course and predictive factors
  • from Section 2 - Pediatric MS Course and Treatment
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 75-86
  • View extract

    Summary

    In childhood-onset multiple sclerosis (MS), the cerebrospinal fluid (CSF) profile is not fundamentally different from the adult-onset MS. Magnetic resonance imaging (MRI) is the best imaging technique to detect lesions suggestive of MS in children. The initial clinical course in most patients with childhood-onset MS is relapsing-remitting. In the UCSF cohort, the initial MS event was moderate or severe in 86% of children compared with 56% of adult-onset MS. In the UCSF pediatric-onset cohort, complete recovery was seen in 66%, which was similar to adults seen at the same center, questioning whether children have less irreversible neuronal injury during their first event or/and have a better ability to repair. MS is likely the result of a complex interplay between genes and environment. Potential prognostics factors associated with the assignment of disability milestones have been examined in several cohort studies from adult centers and one cohort from child neurology centers.
  • Section 1 - Pediatric MS Diagnosis
  • Edited by Dorothée Chabas, University of California, San Francisco, Emmanuelle L. Waubant, University of California, San Francisco
  • Book: Demyelinating Disorders of the Central Nervous System in Childhood
  • Published online: 11 April 2011
  • Print publication: 17 March 2011, pp 19-74
  • View extract

    Summary

    Pediatric multiple sclerosis (MS), once considered a rare childhood illness, has been increasingly recognized as a disabling acquired pediatric neurological disease requiring early recognition and intervention. Males get affected with before puberty while females are more often hit around or after puberty. Race, ethnicity, and ancestry may also influence disease susceptibility and course differently. Epidemiological data clearly indicate that adult MS is a geographically related disease, with disease rates rising with an increased distance from the equator in both northern and southern hemispheres. A few candidates have been identified as associated with pediatric MS in a few epidemiological studies (neurotropic viruses, Chlamydia pneumonia, passive smoking). Seroepidemiologic and pathologic evidences have strongly suggested that prior infection with members of the Herpesviridae family may be associated with the development of MS in adulthood. The most studied member of the Herpesviridae family in MS patients has been Epstein-Barr virus (EBV).

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