Cocoa, neurovascular coupling, and neurodegeneration: The good, the bad, and the ugly
Neurology September 3, 2013 81:863-864; published ahead of print August 7, 2013
Though the human brain is only ∼2% of body mass, it represents more than 20% of total body oxygen and energy consumption,1,2 and the supply of blood to the active neurons must match their metabolic demand. Fortunately, the tight coupling between capillary endothelial cells, astrocytes, pericytes, and neurons—dubbed the neurovascular unit—ensures precise modulation of regional blood flow in response to local metabolic demand. This integration of
supply and demand, termed neurovascular coupling (NVC), is critical to neurophysiologic health. Indeed, accumulating evidence shows an important role for cerebral vascular insufficiency in neurodegenerative diseases ranging from vascular cognitive impairment3 to Alzheimer disease.4 Therefore, targeting cerebral vascular pathology is a promising option for primary and secondary prevention of neurodegenerative diseases and subsequent cognitive impairments.
TYSABRI: The improvement of cognitive functions is associated with a decrease of plasma Osteopontin levels in Natalizumab treated Relapsing Multiple Sclerosis.
Risk factors for rare diseases can be risky to define: PML and Tysabri (natalizumab)
Neurology September 3, 2013 81:858-859
When rare neurologic diseases become topics of editorials in journals such as Nature Neuroscience,1 the New England Journal of Medicine,2 and Neurology®,3 there is usually something more of general interest than the rare disease itself. Such is the case for progressive multifocal leukoencephalopathy (PML), the JC virus–induced demyelinating disease that was once relegated for discussion to the back of the textbook, whether in microbiology or neurology. Not any longer. Incidence and publication of cases of PML have risen more than 50-fold within the last decade. Renewed recognition of PML started in the mid-1980s, when it was recognized as an AIDS-defining illness in 1%–3% of all HIV-1–infected persons, still true in the era of combined antiretroviral therapy.4 PML is reported in patients with underlying neoplastic diseases, organ transplants, and rheumatic diseases, but by 2004, PML dramatically entered the mainstream as a serious adverse event associated with a promising monoclonal antibody therapy, natalizumab, for treatment of relapsing-remitting multiple sclerosis (MS). Nature itself showed that demyelinating diseases of substantially different etiologies and pathologies can occur in the same brain, and remarkably enough in some cases, not with a fatal outcome. In 2006, the estimated occurrence of PML in natalizumab-treated patients with MS, with an average treatment of 17 months, was 1 per 1,000.5 With more than 115,000 patients globally treated with natalizumab for longer periods of time, that estimate is 1 per 330.6 In patients who test positive for antibodies to JCV, have a clinical history of immune suppressive treatment before natalizumab, and have received more than 24 doses, the number of PML cases is 1 per 90.
AUBAGIO (Teriflunomide) in relapsing multiple sclerosis: therapeutic utility.
Teriflunomide is an oral, once-daily disease-modifying therapy (DMT) approved in the USA, Australia, and Argentina for the treatment of relapsing forms of multiple sclerosis (RMS). Teriflunomide reversibly limits the expansion of activated T and B cells associated with the inflammatory process purportedly involved in multiple sclerosis pathogenesis, while preserving lymphocytes for routine immune surveillance. In an extensive clinical development program, teriflunomide demonstrated consistent benefits on both clinical and magnetic resonance imaging outcomes. In long-term studies, teriflunomide treatment was associated with low rates of relapse and disability progression for up to 8 years. The safety profile of teriflunomide has been well characterized, with adverse events generally mild to moderate in nature and infrequently leading to permanent treatment discontinuation. The evidence reviewed here indicates that teriflunomide is an effective addition to the current DMTs used to treat RMS....
Laquinimod for multiple sclerosis.
We found low-level evidence for the use of laquinimod as a disease-modifying therapy for MS because only one study with limited quality (high risk of attrition bias) was included. The published study suggests that laquinimod at a dose of 0.6 mg orally administered once daily may be safe and have potential benefits for most patients with RRMS in the short term. We are waiting for the publication of ongoing trials....
Therapeutic Decisions in Multiple Sclerosis-Moving Beyond Efficacy
In this article, we focus primarily on the safety of DMTs in the context of understanding their pharmacological characteristics, including molecular targets, mechanism of action, chemical structure, and metabolism. Recognizing the individual classes of DMTs described here may be valuable when considering use of such agents sequentially or possibly in combination....
L-Selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients
Objective: To find biomarkers identifying patients at risk for the development of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment.
Conclusions: The cell-based assessment of the percentage of L-selectin-expressing CD4 T cells could provide an urgently needed biomarker for individual PML risk assessment....
Mesenchymal Stem Cells (MSC) derived from mice with Experimental Autoimmune Encephalomyelitis (EAE) suppress EAE and have similar biological properties with MSC from healthy donors.
A Long-Term Follow-Up Study Using IPMSSG Criteria in Children With CNS Demyelination.
Comparison of BLADE and conventional T2-TSE sequences for the sagittal visualization of the cervical spinal cord in multiple sclerosis patients - A case report.
Inhibition of Endogenous Activated Protein C Attenuates Experimental Autoimmune Encephalomyelitis by Inducing Myeloid-Derived Suppressor Cells.
Autoantigens and Autoantibodies in Multiple Sclerosis.
Gene expression changes underlying cortical pathology: clues to understanding neurological disability in multiple sclerosis.
Chromosomal radiosensitivity in patients with multiple sclerosis.
Magnetic resonance monitoring of lesion evolution in multiple sclerosis.
Targeting ion channels for the treatment of autoimmune neuroinflammation.
Assessing humoral immunocompetence after alemtuzumab treatment in MS
Immune competence after alemtuzumab treatment of multiple sclerosis
Neurology September 3, 2013 81:872-876; published ahead of print August 7, 2013
Retinal periphlebitis is associated with multiple sclerosis severity
Neurology September 3, 2013 81:877-881; published ahead of print July 31,2013
