autonomic imbalance
Archives of Neurology recent issues
Archives of Neurology publishes peer-reviewed original contributions of interest to clinicians. It provides practicing physicians with access to the latest information from leading centers of neurological research. It is published monthly.
- ORIGINAL CONTRIBUTION: Heterogeneity in Response to Interferon Beta in Patients With Multiple Sclerosis: A 3-Year Monthly Imaging Study
Objectives To investigate the heterogeneity in magnetic resonance image (MRI) patterns of response to interferon beta across patients with multiple sclerosis or within an individual patient over time.
Design, Setting, and Patients Fifteen patients with relapsing-remitting multiple sclerosis underwent monthly MRIs and clinical examinations (6-month pretherapy phase and 36-month therapy phase) and bimonthly neutralizing antibody tests. On each MRI, the total number of contrast-enhancing lesions was noted. Therapy MRI responders were defined as those with a reduction of 60% or more in the total number of contrast-enhancing lesions during each semester of therapy.
Intervention Subcutaneous administration of interferon beta-1b, 250 µg, every other day for 3 years.
Main Outcome Measure Reduction in the number of contrast-enhancing lesions.
Results Eight patients (53.3%) were MRI responders and 7 (46.7%) were nonresponders. Of those 7, 3 (20.0%) had only an initial optimal reduction of the total number of contrast-enhancing lesions, 2 (13.3%) never reached an optimal response, and 2 (13.3%) had a delayed optimal response. No clear association between neutralizing antibody profile and MRI response was evident.
Conclusions Multiple MRI evaluations disclose that approximately only half of the patients treated with interferon beta achieve and maintain a full response to the drug over time, although an additional small number of individuals may still restore an optimal response to the drug after an initial failure.
Published online November 10, 2008 (doi:10.1001/archneur.66.1.noc80047).
- ORIGINAL CONTRIBUTION: Decrease in the Numbers of Dendritic Cells and CD4+ T Cells in Cerebral Perivascular Spaces Due to Natalizumab
Objective To extend our studies on the prolonged and differential effect of natalizumab on T lymphocyte numbers in the cerebrospinal fluid, we investigated the number and phenotypes of leukocytes and the expression of major histocompatibility complex (MHC) classes I and II in cerebral perivascular spaces (CPVS). We hypothesized that natalizumab reduces the number of antigen presenting cells in CPVS.
Design A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining.
Subjects A patient with multiple sclerosis (MS) who developed progressive multifocal leukoencephalopathy (PML) during natalizumab therapy. Controls included location-matched cerebral autopsy material of patients without disease of the central nervous system, patients with MS not treated with natalizumab, and patients with PML not associated with natalizumab therapy.
Results The absolute number of CPVS in the patient with MS treated with natalizumab was significantly lower than in the control groups owing to extensive destruction of the tissue architecture. The expression of MHC class II molecules and the number of CD209+ dendritic cells were significantly decreased in the CPVS of the patient with MS treated with natalizumab. No CD4+ T cells were detectable.
Conclusions Our observations may explain the differential and prolonged effects of natalizumab therapy on leukocyte numbers in the cerebrospinal fluid.
Published online October 13, 2008 (doi:10.1001/archneur.65.12.noc80051).
- ABOUT THIS JOURNAL: About This Journal
- THIS MONTH IN ARCHIVES OF NEUROLOGY: This Month in Archives of Neurology
- EDITORIAL: Fine-tuning the Homeostasis of Regulatory T Cells: New Mechanism of Immunomodulatory Therapy in Multiple Sclerosis
- ANNOUNCEMENT: E-mail a Friend
- NEUROLOGICAL REVIEW: Management of and Prognosis With Medulloblastoma: Therapy at a Crossroads
Medulloblastoma is the most common malignant childhood brain tumor and, although relatively uncommon in older patients, poses a therapeutic challenge in adults. With current means of therapy, children with nondisseminated medulloblastoma have a high likelihood of long-term survival; 80% or more will be alive 5 years after diagnosis and treatment, with many free of the disease. Even in children with disseminated disease, intensified therapy has been associated with improved survival rates, although some of this improvement may be more apparent than real. The quality of life in long-term survivors is a major issue, and most children who survive have substantial neurologic and cognitive sequelae. The outcome in infants and younger children with medulloblastoma is suboptimal, although there is some evidence to suggest that intensification of therapy has improved the likelihood of disease control. A better understanding of the biological characteristics of medulloblastoma including the cell or cells of origin and the aberrant cellular signaling pathways involved has the promise of dramatically changing tumor stratification and treatment in the near future. However, these biological advances have yet to be integrated into the treatment of medulloblastoma in children or adults.
- ANNOUNCEMENT: Topic Collections
- NEUROLOGICAL REVIEW: Review of Tissue Plasminogen Activator, Ischemic Stroke, and Potential Legal Issues
The use of tissue plasminogen activator in ischemic stroke is controversial. Many practicing physicians believe that its usefulness is established, while others, including professional specialty societies, are less sanguine. A review of the literature appears to show that the use of tissue plasminogen activator is efficacious and can result in highly improved outcomes for a majority of eligible patients. These findings may implicate important potential legal issues. Informed consent concerns and, potentially, medical malpractice claims may result, particularly in the context of evidence-based practice, pay for performance, and the currently limited use of tissue plasminogen activator for eligible patients.
- ORIGINAL CONTRIBUTION: Interferon Beta-Induced Restoration of Regulatory T-Cell Function in Multiple Sclerosis Is Prompted by an Increase in Newly Generated Naive Regulatory T Cells
Background Naturally occurring regulatory T (Treg) cells are functionally impaired in patients with relapsing-remitting multiple sclerosis. We recently showed that prevalences of newly generated CD31-coexpressing naive Treg cells (recent thymic emigrant–Treg cells) are critical for suppressive function of circulating Treg cells, and a shift in the homeostatic composition of Treg-cell subsets related to a reduced de novo generation of recent thymic emigrant–Treg cells may contribute to the multiple sclerosis (MS)–related Treg-cell dysfunction. Interferon beta, an immunomodulatory agent with established efficacy in MS, lowers relapse rates and slows disease progression. Emerging evidence suggests that Treg-cell suppressive capacity may increase in patients with MS undergoing treatment with interferon beta, although the mechanisms mediating this effect are uncertain.
Objective To evaluate the effect of interferon beta treatment on the suppressive activity and the homeostasis of circulating Treg cells in patients with MS.
Participants Twenty patients with relapsing-remitting MS and 18 healthy control subjects.
Interventions Administration of interferon beta.
Main Outcome Measures Effect of interferon beta on Treg-cell homeostasis and suppressive capacity.
Results Suppressive capacities of Treg cells were consistently upregulated at 3 and 6 months after treatment with interferon beta. The restoration of Treg-cell function was paralleled by increased naive recent thymic emigrant–Treg cells and a coincidental reduction in memory Treg cells.
Conclusion The increase in Treg-cell inhibitory capacity mediated by interferon beta treatment can be explained by its effect on the homeostatic balance within the Treg cell compartment.