Cognitive decline in Multiple Sclerosis patients.

Cognitive impairment is a common phenomenon in multiple sclerosis (MS), occurring at all stages of the disease, even at the earliest, and can be a major source of disability, social impairment, and impoverished quality of life. Cognitive dysfunction is mainly focused on working memory, conceptual reasoning, verbal fluency, speed of information processing, attention and executive function. Additional clinical factors, including disease course, fatigue and affective disturbance, can impact the degree of MS-related cognitive impairment. We present the results from the two-phases of our prospective study on cognitive decline in MS patients using the data collected from the A' Neurologic clinic at AHEPA hospital, Thessaloniki, Greece. Most of the patients of the present study revealed mild cognitive impairment with mild influence on the everyday function. We found weak correlation between cognitive deficit and the duration of MS, as well as the physical disability status and moderate correlation between cognitive impairment and the type of the disease as well as MRI findings (atrophy and lesion load). Our results also indicate that the currently available battery of neuropsychological tests: California Verbal Learning test (CVLT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test and Paced Auditory Serial Addition Test (PASAT) can be used as a reliable tool in the diagnosis of cognitive deficits of MS patients, as related to their degree of disability and to the type of their disease. Evaluation of cognitive functions should be incorporated in the regular assessment and monitoring of MS patients since they seem to be well correlated with the progression of the disease.

Late-life Depression and Alzheimer Disease: A Potential Synergy of the Underlying Mechanisms.

A number of biological and clinical characteristics typical of late life depression (LLD) have been suggested by recent research findings. The close association of LLD with cognitive impairment is now well documented and evidenced. However, it is still not clear whether it is depression that leads to cognitive decline, and in more severe cases, to dementia. The work presented in this review article suggests that depression and dementia frequently and strongly copresent, even if the causality remains largely opaque.

Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System.

Chronic inflammation is characterized by longstanding microglial activation followed by sustained release of inflammatory mediators, which aid in enhanced nitrosative and oxidative stress. The sustained release of inflammatory mediators propels the inflammatory cycle by increased microglial activation, promoting their proliferation and thus stimulating enhanced release of inflammatory factors. Elevated levels of several cytokines and chronic neuroinflammation have been associated with many neurodegenerative disorders of central nervous system like age-related macular degeneration, Alzheimer disease, multiple sclerosis, Parkinson's disease, Huntington' disease, and tauopathies. This review highlights the basic mechanisms of neuroinflammation, the characteristics of neurodegenerative diseases, and the main immunologic responses in CNS neurodegenerative disorders. A comprehensive outline for the crucial role of microglia in neuroinflammation and neurodegeneration and the role of Toll-like receptor signalling in coexistence of inflammatory mechanisms and oxidative stress as major factors responsible for progression of neurodegeneration have also been presented.

The probable auto-antigenic role of lipids (anti-ganglioside antibodies) in the pathogenesis of Alzheimer's disease.

We examined the sera of 103 demented patients of a mean age of 75 years and 60 age-matched healthy individuals, using ELISA, to investigate the levels of IgM antibodies against GM1, GD1b, and GQ1b gangliosides and their possible correlation with clinical parameters (age, severity, and type of dementia). All the individuals that demonstrated positive titers of anti-ganglioside antibodies were demented patients whereas normal controls showed borderline or negative values. Significant correlation was revealed between IgM anti-GM1 and both the age of the patients and the severity of dementia. Most of the patients with increased IgM anti-GD1b titers suffered from AD.

Vascular oxidative stress and mitochondrial failure in the pathobiology of Alzheimer's disease: a new approach to therapy.

Vascular and metabolic dysfunctions and mitochondrial failure are now believed to be contributors to Alzheimer's disease (AD) pathogenesis. Vascular dysfunction includes reduced cerebral blood flow (CBF), blood-brain barrier (BBB) disturbances and cerebral amyloid angiopathy (CAA). Mitochondrial failure results in deregulation of Ca(2+) homeostasis and elevated reactive oxygen species (ROS) generation, both of which are linked to neurotoxicity. Increased levels of ROS stimulate proinflammatory gene transcription and release of cytokines, such as IL-1, IL-6, and TNF-α, and chemokines, thereby inducing neuroinflammation. Conversely, inflammatory reactions activate microglia and astrocytes to generate large amounts of ROS, so neuroinflammation could be perceived as a cause and a consequence of chronic oxidative stress. The interaction between oxidative stress and neuroinflammation leads to amyloid-ß (Aß) generation. The deposition of Aß peptide in the brain generates a cascade of pathological events, including the formation of neurofibrillary tangles (NFTs), inflammatory reactions, increased oxidative stress and mitochondrial dysfunction, which are causative factors of cell death and dementia. The purpose of this paper is to provide current evidence on vascular dysfunction and mitochondrial failure, both in neurons and glia and in brain vascular wall cells in the context of potential application for treatment of AD and other neurodegenerations.

Anti-MuSK- and anti-AChR-positive myasthenia gravis induced by d-penicillamine.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction usually caused by antibodies to the nicotinic acetylcholine receptor (AChR) and occasionally to muscle-specific kinase (MuSK). D-penicillamine is a therapeutic agent for several diseases, but can also induce a number of immune-mediated disorders, including MG, as a side-effect. In most patients with D-penicillamine-induced MG, anti-AChR antibodies are detected, but the presence of anti-MuSK antibodies has not been reported previously. CASE: The case reported was a female patient who presented with myasthenic symptoms after D-penicillamine administration for scleroderma. RESULTS: Both anti-AChR and anti-MuSK antibodies were identified in the patient's serum. The anti-MuSK antibodies were of the IgG4 subclass, as in idiopathic MG. Both types of antibody gradually disappeared after discontinuation of D-penicillamine. A significant improvement in symptoms was observed and the patient gradually became free of MG symptoms, without requiring any treatment for MG. Another four double-positive (anti-AChR and anti-MuSK antibodies) patients were identified during a retrospective study, but none had been treated with D-penicillamine. CONCLUSION: D-penicillamine can cause anti-AChR and anti-MuSK antibody-positive MG, a rare phenomenon which is reversed after discontinuation of D-penicillamine treatment.

Increase in interleukin-6 levels is related to depressive phenomena in the acute (relapsing) phase of multiple sclerosis.

The aim of the present study was to investigate the possible connection between interleukin-6, the acute phase (relapse) of multiple sclerosis (MS), and depression. The authors determined and statistically evaluated the levels of interleukin-6 and its soluble receptor in the serum of 28 MS patients in relapsing, 14 MS patients in remission, and 20 control subjects, as well as the presence of depression among these individuals. The results of our study indicate that depression is not only very common during relapses of MS, but also that the levels of IL-6 increase during the acute phase of the disease, especially when depression is detected.