Multiple Sclerosis Resource Centre
  • Home
  • MSRC Grand Opening 30/05/12
  • About MS
  • MSRC Services
  • Get Involved
  • MS Research News
  • MSRC Groups
  • Useful Resources
  • Advertising
  • MSRC Guest Book
  • Best Bet Diet Group
  • E-Newsletter
  • Contact Us
  • Investor in People
    You are here : Home » MS Research News » Cognition and Cognitive Issues Research

    Cognition and Cognitive Issues Research

    A A A
    [Print this page]

    Share |


    More news can be found in New Pathways Magazine, our bi-monthly publication, and also check daily at MSRC: Latest MS News.

    Hot days worsen cognitive function in MS

    Sunshine, Heat and MSPatients with MS who require high levels of cognitive functioning should consider the effect of warmer weather on their memory and processing speeds, conclude researchers who show for the first time that warm weather might affect cognitive performance as well as lesion activity in MS.

    Researchers from New Jersey in the US found among a group of 45 MS patients who were tested at baseline and after 6 months, cognitive performance declined more in those for whom the weather was warmer at follow-up than at baseline.

    They also conducted a crosssectional investigation, looking at 40 people with MS and 40 matched healthy controls. After controlling for disease variables, there was an association between warmer weather and worse cognitive performance, but only among the patients with MS.

    Writing in Neurology, the authors said their study was “the first to formally investigate the relationship between outdoor temperature and cognition”.

    They said the results have “important implications for treatment,” suggesting that lifestyle decisions by patients with MS might need to take the results into consideration.

    Summer sessions at university might be a bad idea, they said as an example.

    “Clinicians should carefully monitor patients with MS for heat related cognitive exacerbations, which may occur even in the absence of sensorimotor symptomology,” they wrote.

    In an accompanying editorial, two experts from Boston in the US said the study provided some bad news for clinical trials.

    “Now cognitive performance joins the ranks of markers subject to annual fluctuations that potentially bias clinical trials, as do relapse rates and MS lesions.”

    Neurology 2012; doi: WNL.0b013e31824d5834

    Source: Neurology Update (13/03/12)

    Cognitive rehabilitation changes brain function in MS patients

    Cognitive Problems in MSIn a new study published in the March issue of Radiology, functional magnetic resonance imaging (fMRI) shows that cognitive rehabilitation changes brain function and improves cognitive performance in patients with relapsing-remitting multiple sclerosis (MS).

    MS is a nervous system disease affecting the brain and spinal cord. MS damages a material called the myelin sheath that surrounds and protects nerve cells. This damage disrupts messages between the brain and other parts of the body, leading to symptoms such as muscle weakness, coordination and balance difficulties, numbness, problems with vision, memory loss and other cognitive issues. MS affects women more than men and often becomes symptomatic between the ages of 20 and 40.

    In relapsing-remitting MS, the most common type, patients experience a series of attacks followed by partial or complete disappearance of symptoms. The interval between relapses can range from weeks to years.

    For the study, Dr. Massimo Filippi, M.D., professor of neurology at the San Raffaele Vita-Salute University and director of the "BrainMap" interdepartmental research program and the Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute San Raffaele, Milan, Italy and colleagues recruited 20 patients with relapsing-remitting MS.

    Patients were randomized into two groups of 10. The first group received a 12-week program of computer-assisted cognitive rehabilitation of attention and information processing and executive functions, and the second (control) group received no cognitive rehabilitation.

    Aspects of the rehabilitation program included a day-planning task, which employed realistic simulations of a set of scheduled dates and duties to address the patient's ability to organize, plan and develop solution strategies; and an attention task requiring the patient to simulate driving a train, carefully observing the control panel of the train and the countryside while encountering several distractions at increasing levels of difficulty.

    All of the patients underwent neuropsychological assessment and MRI exams at baseline. As compared to their performance at baseline, the patients in the treatment group improved in tests of attention and information processing and executive functions. The fMRI results showed modifications in activity in several brain regions in the rehabilitation group, compared to the non-rehabilitation group. These fMRI modifications were correlated with cognitive improvement.

    Analysis after cognitive rehabilitation found no structural changes in the gray matter or normal-appearing white matter of the brain in the treatment group.

    "The findings demonstrated that computer-assisted cognitive rehabilitation in patients with MS results in an improvement of the trained cognitive functions," Dr. Filippi was quoted as saying.

    "However, the structural integrity of the brain's gray matter and white matter showed no modifications in these patients, suggesting an impairment of structural plasticity."

    Source: Medical Breakthroughs Copyright © 2012 Ivanhoe Broadcast News, Inc (23/02/12)

    Deep-brain stimulation can strengthen memory

    Brain StimulationResearchers at UCLA's David Geffen School of Medicine found a way to stimulate an area of the brain that can strengthen memory and it is not in pill-form interestingly enough.

    “For those of us with MS who are notorious for our memory issues,” says Sierra Blankenship of Lima, “this has got to be the best news ever. Unless you have MS, or know someone with MS, you just would not believe the things that we have done or even said sometimes because of this problem.”

    The area called the entorhinal cortex, the main interface between the hippocampus and neocortex, was the focus and “critically it was the stimulation at the gateway into the hippocampus, and not the hippocampus itself, that proved effective,” said Dr. Fried the school's professor of neurosurgery.

    Researchers followed seven epilepsy patients who had electrodes implanted in their brains, electrodes that were there to pinpoint the area of their seizures, and they were able to monitor their brain activity while memories were being formed by using a game.

    Each patient played a video game that involved the layout of a city and a taxi that would pick up passengers and drop them off at a destination found within the city. Researchers were able to see if deep-brain stimulation of the entorhinal cortex or stimulation of the hippocampus was what changed memory and they found memory was strengthened when stimulation was applied to the entorhinal cortex.

    "When we stimulated the nerve fibers in the patients' entorhinal cortex during learning, they later recognized landmarks and navigated the routes more quickly," said Fried. "They even learned to take shortcuts, reflecting improved spatial memory."

    The findings may see future neuroprothetic devices that would stimulate the brain during specific stages of processing and the greatest part is that strengthening the memory this way doesn't need continuous stimulation; only a “boost” for when learning would be needed.

    The article talks of the millions affected by Alzheimer's and Dr. Fried himself brought up early dementia, but considering researchers at OSU were able to show losing Myelin, the coating around the nerves in the brain, was more than the loss of “just” a coating, help for memory is clearly something needed for those with MS as well.

    Researchers at OSU were able to show cause and affect of demyelination and how it relates to the hippocampus.

    Right now, Fried said their findings “should be interpreted with caution” because of the small number of people who were followed, but it does open a window, albeit small, of opportunity for future studies.

    Either by these researchers, or others, it doesn't matter. Finding ways for millions of people to battle a part of their disease that can create such sadness and frustration is something to look forward to.

    Source: Examiner.com © 2006-2012 Clarity Digital Group LLC (13/02/12)

    Greater brain activation after cognitive rehabilitation for MS

    Brain ActivityNeuroscientists at Kessler Foundation have documented increased cerebral activation in patients with multiple sclerosis (MS) following memory retraining using the modified Story Memory Technique (mSMT). This is the first study to demonstrate that behavioral interventions can have a positive effect on brain function in people with cognitive disability caused by MS, an important step in validating the clinical utility of cognitive rehabilitation.

    According to Nancy Chiaravalloti, PhD, director of Neuropsychology & Neuroscience Research at Kessler Foundation, "This demonstrates that an effective cognitive rehabilitation protocol can lead to changes in the way the brain is actually processing information." Dr. Chiaravalloti is lead author of the article, which was published online by the Journal of Neurology on January 12.

    Cognitive deficits are common in MS, though few studies have examined the efficacy of memory retraining in this population. Previous research conducted at Kessler Foundation demonstrated that mSMT improves new learning and memory in MS.

    The new study utilized functional magnetic resonance imaging (fMRI) to document brain activation patterns before and after memory retraining. In the double-blind, placebo-controlled, randomized clinical trial, 16 individuals were randomly assigned to treatment (n = 8) or placebo (n = 8) groups. Each underwent 10 memory retraining sessions (twice weekly for 5 weeks). After treatment, greater activation was evident on fMRI in the treatment group during performance of a memory task; no change was seen in the placebo group. Increased activation was associated with improved memory performance. These benefits may warrant third-party reimbursement for this intervention in selected patients.

    The article, Increased cerebral activation after behavioral treatment for memory deficits in MS, DOI: 10.1007/s00415-011-6353-x appeared online in the Journal of Neurology on January 12, 2012. Authors are Nancy Chiaravalloti, PhD, Glenn Wylie, DPhil, Victoria Leavitt, PhD, and John DeLuca, PhD, all of Kessler Foundation, West Orange, NJ. The authors also have faculty appointments with UMDNJ-New Jersey Medical School, Newark, NJ.

    Research funded by National Institutes of Health grants RO1 HD045798 & HD45798-S, National MS Society and Kessler Foundation.

    Source: Science Daily Copyright © 1995-2011 ScienceDaily LLC (18/01/12)

    Multiple sclerosis research links brain activity to sharper cognitive decline

    Cognition and MSWhen it comes to communication in the brain, more is usually better. But now scientists have linked increased communication in a network of brain regions to more severe mental impairment in patients with early-stage multiple sclerosis (MS).

    “Measuring how well this network’s connections are working may provide a way to look beyond the wide-ranging symptoms of MS to help us quantify the disorder’s effects on the brain,” says co-author Maurizio Corbetta, MD, the Norman J. Stupp Professor of Neurology at Washington University School of Medicine in St. Louis. “This assessment could be very useful in diagnosing the disease and tracking the effectiveness of new treatments.”

    Scientists at Washington University and the University Medical Center at Hamburg-Eppendorf and the University of Tübingen, both in Germany, published the results in the Proceedings of the National Academy of Sciences.

    MS damages brain cell branches, impairing the cells’ ability to communicate. The disease is highly unpredictable and produces a hodgepodge of symptoms that vary from patient to patient. These include fatigue, numbness, dizziness, pain, bowel and bladder dysfunction, visual impairments, speech disorders, headache, depression and problems with balance, coordination and walking.

    The brain can redirect energy and resources to make it possible for more signals to flow through damaged circuits. But in MS, the researchers speculate, that redirection may lead to a decrease in the brain’s ability to reconfigure itself for different cognitive tasks, such as speaking, processing sensory information, controlling movement, regulating mood and creating and accessing memory.

    The current study focused on whether correlations could be made between the structural damage caused by MS, the cognitive problems experienced by patients and changes in brain networking, which refers to the ability of various regions in the brain to work with each other.

    The study involved 16 patients who had been diagnosed with MS in the previous four years. For comparison, scientists also included 16 healthy individuals. All participants were given an extensive battery of behavioral and cognitive tests, as well as brain scans to look for structural damage. Researchers also evaluated the connectedness of brain regions that often work together in networks.

    The scientists could see damage to brain cell branches on the scans of MS patients. The greater the damage, the more likely patients were to experience difficulties with brain function. These problems affected a range of cognitive domains, including decision-making, memory, attention and other factors. Researchers found that changes in one component of cognitive function that they defined as “cognitive efficiency” correlated with the great majority of symptoms and deficits measured by the battery of cognitive and behavioral tests.

    The scientists also showed that patients with lower cognitive efficiency had enhanced connections in the brain’s default mode network. This network is one of many that supports brain function; it is only active when the brain is not engaged in a particular mental task. Increases in default mode network connectivity gave a direct index of the degree of impairment in cognitive efficiency.

    “This correlation is very surprising because normally we would expect cognitive efficiency to improve with increases in the connectivity of the default mode network,” says lead author David Hawellek, a graduate student at the University Medical Center at Hamburg-Eppendorf. “Prior studies have found that the strength of connections in the default mode network is a direct indicator of how well other networks can interact to support brain function. But that doesn’t seem to be the case here.”

    The observation may result from the fact that the MS patients had only been recently diagnosed. Corbetta speculates that if scientists scan the patients’ brains again in a few years, more extensive damage from MS would likely impair connectivity in the default mode network.

    “Another possibility is that the brain’s response to structural damage from MS may cause the various brain networks to lose their flexibility to interact with each other to support brain function,” says senior author Andreas K. Engel, MD, PhD, professor of physiology at the University Medical Center at Hamburg-Eppendorf. “The networks might thus have become less variable, more often interacting among themselves instead of with other networks.”

    Such a change could register as increased default mode network connectivity on scans, Engel says, but might actually indicate impaired cognitive function in early-stage MS patients.

    MS symptoms tend to flare in intensity episodically. These unpredictable flares, known as relapses, involve worsening of symptoms and the development of new problems. None of the patients in the study was having a relapse. Scientists plan to follow up on their findings by gathering data on the same brain characteristics from individuals who are relapsing.

    “This may give us additional insights into the relationship between changes in brain networks and problems in cognition,” Engel says. “If we can understand the dynamics that lead to these episodes, that may help us find better ways to predict and prevent them.”

    More information: Hawellek DJ, Hipp JF, Lewis CM, Corbetta M, Engel AK. Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis. Proceedings of the National Academy of Sciences, Nov. 22, 2011.

    Source: Medical Xpress © Medical Xpress 2011-2012 (11/01/12)

    Researchers link multiple sclerosis to different area of brain

    MS MRIRadiology researchers at The University of Texas Health Science Center at Houston (UTHealth) have found evidence that multiple sclerosis affects an area of the brain that controls cognitive, sensory and motor functioning apart from the disabling damage caused by the disease's visible lesions.

    The thalamus of the brain was selected as the benchmark for the study conducted by faculty at the UTHealth Medical School. Lead researchers include Khader M. Hasan, Ph.D., associate professor, and Ponnada A. Narayana, Ph.D., professor and director of Magnetic Resonance Imaging (MRI) in the Department of Diagnostic and Interventional Imaging; and Jerry S. Wolinsky, M.D., the Bartels Family and Opal C. Rankin Professor in the Department of Neurology.

    Results of the research were published in a recent edition of The Journal of Neuroscience.

    "The thalamus is a central area that relates to the rest of the brain and acts as the 'post office,' " said Hasan, first author of the paper. "It also is an area that has the least amount of damage from lesions in the brain but we see volume loss, so it appears other brain damage related to the disease is also occurring."

    Researchers have known that the thalamus loses volume in size with typical aging, which accelerates after age 70. The UTHealth multidisciplinary team's purpose was to assess if there was more volume loss in patients with multiple sclerosis, which could explain the dementia-related decline associated with the disease.

    "Multiple sclerosis patients have cognitive deficits and the thalamus plays an important role in cognitive function. The lesions we can see but there is subclinical activity in multiple sclerosis where you can't see the changes," said senior author Narayana. "There are neurodegenerative changes even when the brain looks normal and we saw this damage early in the disease process."

    For the study, researchers used precise imaging by the powerful 3 Tessla MRI scanner to compare the brains of 109 patients with the disease to 255 healthy subjects. The patients were recruited through the Multiple Sclerosis Research Group at UTHealth, directed by Wolinsky, and the healthy controls through the Department of Pediatrics' Children's Learning Institute.

    Adjusting for age-related changes in the thalamus, the patients with multiple sclerosis had less thalamic volume than the controls. The amount of thalamic loss also appeared to be related to the severity of disability.

    "This is looking at multiple sclerosis in a different way," Hasan said. "The thalami are losing cellular content and we can use this as a marker of what's going on. If we can find a way to detect the disease earlier in a more vulnerable population, we could begin treatment sooner."

    UTHealth co-authors are Indika S. Walimuni, Ph.D., post-doctoral research associate; Humaira Abid, M.D., former post-doctoral research associate; Linda Ewing-Cobbs, Ph.D., professor of pediatrics; and Richard Frye, M.D., former assistant professor of pediatrics and neurology. The research was funded by a grant from the National Institutes of Health. The title of the article is "Multimodal Quantitative Magnetic Resonance Imaging of Thalamic Development and Aging Across the Human Lifespan: Implications to Neurodegeneration in Multiple Sclerosis."

    Source: Eureka Alert! Copyright © 2011 by AAAS, the science society. (23/12/11)

    Potential cognitive decline biomarker identified for earlier disease diagnosis

    MRIResearchers from the Department of Neurology at NYU Langone Medical Center identified for the first time that changes in the tissue located at the junction between the outer and inner layers of the brain, called "blurring", may be an important, non-invasive biomarker for earlier diagnosis and the development of new therapies for degenerative brain conditions, such as multiple sclerosis. The study was published in the Journal of Neuroscience.

    "The findings are significant because this is the first time we have mapped the distinct relationship between blurring of the boundary in the left hemisphere, where verbal language skills are managed, and the impact that changes in this area have on cognitive ability," said Karen Blackmon, PhD, research assistant professor, Department of Neurology and lead author of the study. "The fact that this occurs in healthy brains and appears to be connected with a person's cognitive function has significant implications for our ability to diagnose brain disease earlier and for the potential development of new therapies."

    In the study, 32 healthy adults had an MRI scan of their brain. The images were enhanced to highlight the junction between the area of the brain where neurons control cognitive and motor function, or "grey matter", and the area where longer, myelin-insulated axon cells responsible for efficient transmission of electrical signals, or "white matter", exist. When neurons develop incorrectly among the axons (which can happen in-utero or after a brain injury) they are visible as "blurring" along the edge of this junction on an MRI. Blurring is associated with impaired cognitive conditions, such as epilepsy and Alzheimer's disease, but has never been identified in individuals without these conditions.

    The researchers administered standardized intelligence tests and scored the participants verbal, visual, and spatial cognitive abilities. These abilities are controlled by a distinct area in the brain's left hemisphere and are an established measure of overall cognitive function.

    The researchers found that not only did blurring exist in brains without a degenerative condition, but when the verbal language assessment scores were linked with the MRI data, there was a strong relationship between the amount of blurring and a decreasing level of verbal language skill.

    Source: Medical News Today © MediLexicon International Ltd 2004-2011 (03/11/11)

    Cognitive impairment in MS is expressed in clinical course of the disease in 43-70% of cases

    Cognitive ImpairmentThe leading international experts in the field of neurological research for multiple sclerosis gathered in Florence for the event sponsored by Serono Symposia International Foundation (SSIF) to discuss the correct clinical management of cognitive disorders caused by the disease.

    The event, "Cognition Disorders in MS", was produced with the scientific contribution of Professor Maria Pia Amato from the Department of Neurological and Psychiatric Sciences of the University of Florence, along with Professor Giancarlo Comi from the Experimental Neurology Institute Vita Salute San Raffaele at the University of Milan.

    "It's erroneous and quite simplistic to maintain that multiple sclerosis is debilitating to the physical and motor functions alone," said Professor Amato. "Clinically, cognitive disorders are common and can be highly disabling."

    "It's surprising how, up until now, so little attention has been paid to the range of symptoms and the effects of the drugs used to treat multiple sclerosis," added Professor Comi. "Especially now that we have much more powerful drugs," he concluded, "it becomes increasingly important to assess their impact and identify the most suitable treatment for the specific case."

    "Quite often," said Professor Amato, "patients suffering from the cognitive disorders typical of multiple sclerosis are forced to miss work because of difficulties in completing their tasks, especially when they involve memory impairment - the most frequent symptom - and disturbances in attention or concentration."

    "Cognitive impairment in MS is expressed in clinical course of the disease in 43-70% of cases, it affects 1/3rd of school-aged patients"

    "As a promoter of Continuing Medical Education, SSIF offers its knowledge on an international level," noted Professor Comi, who is also President of the Scientific Committee of SSIF, "and we are very proud to bring together on this level the top experts in neurology and multiple sclerosis research, and to contribute to the debate from the perspective of clinical practices, with the goal of identifying the most appropriate treatments for this disease."

    Serono Symposia International Foundation

    Serono Symposia International Foundation is a non-profit global organization dedicated to the Continuing Medical Education (CME) of healthcare professionals.

    Source: PR Newswire on behalf of Serono Symposia (30/09/11)

    Depression, cognitive impairment often complicate Multiple Sclerosis

    DepressionPatients with multiple sclerosis often also manifest major depression or cognitive impairments, but these associated conditions frequently go undiagnosed or untreated, experts said at the annual congress of the European College of Neuropsychopharmacology.

    "The data are strong now that depression is common" in patients with multiple sclerosis (MS), with a lifetime prevalence in MS patients of about 50%, said Dr. Anthony Feinstein, professor of psychiatry at the University of Toronto. "There must be something particular about MS that predisposes patients to depression.

    "You know that [many MS] patients are going to have major behavioral disturbances. The MS rating scales do not take this into account. They are very oriented to motor symptoms, and ignore to a large degree cognitive and behavioral disturbances," he said in an interview. "The behavioral disturbances can be profound."

    Cognitive impairment occurs in "up to two-thirds of MS patients, relatively independent of physical disability," said John DeLuca, Ph.D., at the same session. "Cognitive impairment can be seen in early stages [of MS], late stages, or never," said Dr. DeLuca, vice president for research at the Kessler Foundation in West Orange, N.J.

    Diagnosing and treating depression in MS patients is important as it can affect quality of life and cognition, and can result in suicidality, said Dr. Feinstein. Suicide among MS patients runs more than sevenfold higher than in the general population, and twice as high compared with patients with other types of neurologic disorders. Study results from other researchers found that MS patients especially at risk for suicide are men, patients younger than 30, and patients during the first 5 years following their initial MS diagnosis.

    Dr. Feinstein reviewed findings from a study he and his associates ran on 140 consecutive patients seen at an MS clinic. The analysis showed a 29% lifetime rate of suicide intention, and a 6% rate of suicide attempts in these patients, which compared with a historical 14% intention rate in the general U.S. population and a historical 4% attempt rate reported in Canada. The study done by Dr. Feinstein identified four predictors of suicide intention in MS patients:

    • A lifetime diagnosis of major depression.

    • More severe major depression with an elevated Hospital Anxiety and Depression Scale score.

    • Living alone.

    • Alcohol abuse.

    These four factors predicted suicidal intent with 70% sensitivity, 95% specificity, and 87% overall predictive ability. One-third of the suicidal patients had received no treatment for their depression, and two-thirds of the patients in this series identified with current major depression were not on antidepressant therapy.

    Treatment for major depression in MS patients should generally follow what’s used to treat major depression in patients without MS. Only two randomized, controlled trials of antidepressant treatment have ever been reported for MS patients, and one of these studies occurred about 50 years ago, Dr. Feinstein noted. "In MS patients you need to be aware of susceptibility to side effects, but still tend to the principals from general psychiatry," he said. "The caveat for dosages is to start low and go slow. You need to be careful, especially with polypharmacy and the [potential] effect on cognition and mood."

    The disease-modifying drugs commonly used today to treat MS "are safe in patients with depression, and do not make patients suicidal. Should a patient develop depression on one of these drugs, treat the depression, which will improve compliance with the disease-modifying drugs. It is not necessary to stop the disease-modifying drugs," he said. MS patients with severe depression who remain unresponsive to antidepressants are potential candidates for electroconvulsive therapy, especially when the risk for suicide is high. But electroconvulsive therapy poses a risk for weakening the blood-brain barrier and worsening MS symptoms, so he recommended first assessing the stability of the blood-brain barrier using gadolinium-contrast MRI.

    MS patients also show a susceptibility to developing other psychiatric disorders, including pseudobulbar affect in up to 10%, bipolar affective disorder, psychosis, and an untreatable form of euphoria caused by a heavy MS-lesion load. Psychosis prevalence in MS patients aged 15-24, when most MS cases first appear, runs 11-fold higher than in the general population, said Dr. Feinstein, who also directs the neuropsychiatry program at Sunnybrook Health Sciences Centre in Toronto.

    Results from studies run by Dr. DeLuca showed that cognitive defects in MS result from slowed information processing speed and impaired learning and memory, and that these deficits can significantly impair everyday life activities. These deficits appear even in MS patients without dementia or physical disability. Risk factors for cognitive impairment include early age of onset for patients with pediatric MS or older age in patients with adult-onset MS; male sex; evidence of grey matter atrophy: evidence of low cognitive reserve: and being in the secondary progressive stage of MS.

    While disease-modifying therapies appear to have little impact on cognitive deficits, a modified approach to learning can make a substantial difference, said Dr. DeLuca, who is also professor of physical medicine and rehabilitation at New Jersey Medical School, Newark. Helpful measures include having patients "slow things down" when attempting to learn something, and asking questions to make sure they understand something correctly. MS patients also find that self-testing on new information helps strengthen their encoding. These patients "learn by slowing down and going over material again and again and testing themselves, which has a huge effect," he said in an interview. "It sounds simplistic, but this is the primary intervention."

    Dr. Feinstein said that he has received honoraria and grant support from Teva, Merck-Serono, and Bayer. Dr. DeLuca said that he has been a consultant to and received grant support from Biogen and Memen Pharmaceuticlas.

    Source: Family Practice News Copyright © 2011 International Medical News Group, LLC. (07/09/11)

    Grey matter damage and overall cognitive impairment in PPMS

    MS MRISummary: This cross-sectional study of patients with primary progressive multiple sclerosis (PPMS) investigates the association between imaging measures and domain specific cognitive impairment.

    In patients, a lower grey matter (GM) peak location magnetization transfer ratio (MTR) - reductions in which are associated with demyelination and axonal loss - was associated with worse overall cognitive performance and GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline. The volume of normal appearing white matter was associated with attention/speed of visual information processing, while T2 lesion load was associated with delayed verbal memory.

    The authors have suggested that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both grey matter and white matter.

    Abstract
    Objectives: To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS).

    Methods: Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported.

    Results: Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55).

    Conclusions: The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

    Tur C, Penny S, Khaleeli Z, Altmann D, Cipolotti L, Ron M, Thompson A, Ciccarelli O.

    Dept. of Brain Repair & Rehab., Inst. Neurology, London, UK/Clinical Neuroimmunology Unit, MS Centre of Catalonia (CEM-Cat), Dept of Med., Barcelona, Spain.

    Source: Pubmed PMID: 21803874 (03/08/11)

    Guided self-help for functional (psychogenic) symptoms

    CBTABSTRACT

    Objectives: Functional (psychogenic or somatoform) symptoms are common in neurology clinics. Cognitive-behavioral therapy (CBT) can be an effective treatment, but there are major obstacles to its provision in practice. We tested the hypothesis that adding CBT-based guided self-help (GSH) to the usual care (UC) received by patients improves outcomes.

    Methods: We conducted a randomized trial in 2 neurology services in the United Kingdom. Outpatients with functional symptoms (rated by the neurologist as “not at all” or only “somewhat” explained by organic disease) were randomly allocated to UC or UC plus GSH. GSH comprised a self-help manual and 4 half-hour guidance sessions. The primary outcome was self-rated health on a 5-point clinical global improvement scale (CGI) at 3 months. Secondary outcomes were measured at 3 and 6 months.

    Results: In this trial, 127 participants were enrolled, and primary outcome data were collected for 125. Participants allocated to GSH reported greater improvement on the primary outcome (adjusted common odds ratio on the CGI 2.36 [95% confidence interval 1.17–4.74; p = 0.016]). The absolute difference in proportion “better” or “much better” was 13% (number needed to treat was 8). At 6 months the treatment effect was no longer statistically significant on the CGI but was apparent in symptom improvement and in physical functioning.

    Conclusions: CBT-based GSH is feasible to implement and efficacious. Further evaluation is indicated.

    Classification of evidence: This study provides Class III evidence that CBT-based GSH therapy improves self-reported general health, as measured by the CGI, in patients with functional neurologic symptoms.

    M. Sharpe, MD, J. Walker, MBChB, C. Williams, MD, J. Stone, PhD, J. Cavanagh, MD, G. Murray, PhD, I. Butcher, PhD, R. Duncan, MD, PhD, S. Smith, PhD and A. Carson, MD

    Full Article

    Source: Neurology Copyright © 2011 by AAN Enterprises, Inc (28/07/11)

    Tools to study the effects of MS on the mind don’t measure up

    Cognitive Problems In MSMultiple sclerosis is known for robbing people of the ability to walk and move as they once did, and for debilitating pain. But beneath these devastating physical effects lies a slow but sometimes serious effect on the mind. Studies have estimated that anywhere from 40% to 70% of patients with the disorder also show signs of cognitive decline such as memory loss.

    Last week, researchers met at the New York Academy of Sciences for a special session on Cognitive Dysfunction in Multiple Sclerosis”. High on the agenda was a group-think about the lack of longitudinal studies and standardization in data collection when it comes to chronicling the effects of the disease on the mind. “Is there a possibility that the neuroscientists could go into a room, close the door, and make up a battery [of tests]?” asked Cleveland Clinic neuroscientist Ranjan Dutta.

    When interviewed at the meeting by Nature Medicine, neuropsychologist Stephen Rao, also of the Cleveland Clinic in Ohio, provided the contrasting example of Alzheimer’s, which can cause relatively precipitous cognitive decline in patients within only a few years, making it easier to measure in the clinic. In comparison, “the rate of decline [in multiple sclerosis] is about 6% of patients per year,” requiring more expensive and longer studies.

    Notably, Alzheimer’s researchers have had more recent success when it comes to agreeing upon what metrics to use. The National Alzheimer’s Coordinating Center (NACC) selected a battery of tests in 2005 to measure cognition including number recall (digit span) and the Weschler scale to judge memory, a mini-mental state exam to assess basic mental function, and the trail-making test for memory and task-switching, among others. “By and large, everyone was familiar with them so we took the path of least resistance,” director Walter Kukull told Nature Medicine.

    After Dutta's suggestion at the meeting of reaching an updated consensus for multiple sclerosis metrics, wisecracks were heard about the survival chances of neuroscientists arguing in a room. But Rao reminded the crowd that researchers in the field have reached an agreement in the past, publishing a consensus paper as far back as 2002 that outlined a battery of tests for cognitive decline. Perhaps it needs updating to 2011 standards, but nonetheless, “it is possible to get consensus,” he proclaimed. Whether it is a true call to action, only time will tell.

    Source: Spoonful Of Medicine (04/07/11)

    Cognitive performance in relapsing remitting multiple sclerosis

    Cognitive ImpairmentAbstract

    Background
    There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS). In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR) battery, we longitudinally assessed cognition in patients with relapsing remitting (RR) MS.

    Methods
    Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST), Paced Auditory Serial Addition Test (PASAT) and five composite scores derived from the CDR computerized cognitive test system (CDR System): Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) measured disability.

    Results
    The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT) and were also strongly related to disability (EDSS and MSFC). Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention]), and a moderate impairment both to sustained attention (Continuity of Attention d 0.6) and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic memory]), when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory) and episodic memory (Quality of Episodic Memory) were unimpaired.

    Conclusions
    Preliminary validation of the CDR System indicated that for most, but not all measures psychometric properties were adequate and the measures were related to disability (EDSS and MSFC) and other measures of cognition.

    Chris Edgar , Peter J Jongen , Evert Sanders , Christian Sindic , Sophie Goffette , Michel Dupuis , Philippe Jacquerye , Daniel Guillaume , Regine Reznik and Keith Wesnes

    Full article

    Source: BMC Neurology © 1999-2011 BioMed Central Ltd (14/06/11)

    Donepezil no help for memory deficits in MS

    AriceptThe acetylcholinesterase inhibitor donepezil (Aricept) failed to improve multiple sclerosis patients' memory impairments in a placebo-controlled, multicenter trial, researchers said.

    Neither patients' impressions of memory function nor their scores on an objective test of verbal memory -- the two primary outcome measures in the 120-person trial -- were better after 24 weeks of treatment with 10 mg/day of donepezil, reported Lauren Krupp, MD, of the State University of New York at Stony Brook.

    The treatment also had no statistically significant benefits on secondary endpoints, although there was a trend favoring improvement in clinicians' impressions of change, she and her colleagues wrote in the April 26 issue of Neurology.

    The findings, although disappointing, were not entirely unexpected, the researchers indicated.

    "Cognitive impairment affects 40% to 60% of individuals with MS, and no medication has been consistently shown to be effective for this problem," they wrote.

    On the other hand, an earlier randomized trial with donepezil conducted in 2004 by several of the same researchers had found a modest benefit.

    In the new report, Krupp and colleagues argued that the drug may still be beneficial in MS-related cognitive impairment -- just not strongly enough to be reliably detected in a 120-patient trial.

    "The power estimation for the present sample was derived from [the earlier trial] and it is possible that those results represent an unusually large effect for MS," the researchers conceded.

    They noted that some prior studies had pointed to decreased cholinergic activity in MS patients, which would suggest that a cholinesterase inhibitor such as donepezil should be helpful.

    That, along with the effect seen in the clinicians' impressions of change in the new trial, is an indication that it would be premature to give up on this approach, Krupp and colleagues contended.

    Patients in the trial were a mean of about 47 years old with about 62% having the relapsing-remitting form of MS while the others had primary or secondary progressive disease. Mean time since onset of symptoms was about 13 years.

    Mean baseline score on the Selective Reminding Test (part of the Brief Reportable Battery), the trial's primary objective endpoint, was 37 points.

    Increases of 1.7 and 1.6 points were seen in the placebo and donepezil groups, respectively, following the 24-week treatment period.

    There were no significant differences between the groups in performance on other objective neuropsychological tests, including other portions of the Brief Repeatable Battery, Judgment of Line Orientation, the Delis-Kaplan Executive Functions Systems Sorting Test, and two measures taken from the Minimal Assessment of Cognitive Function in MS.

    The other primary endpoint in the trial, patients' impressions of memory change, also showed essentially no difference between treatments (36.1 points for donepezil versus 35.6 points for placebo). A similar result was seen for patients' impressions of cognitive change.

    But clinicians in the double-blind trial did report more improvement in memory and cognition, albeit not reaching the P=0.05 standard for statistical significance.

    Mean scores for the clinicians' impression of memory change were 37.7 points in the donepezil group versus 23.7 points with placebo (P=0.10).

    For cognitive change, the mean was 34.4 points in the donepezil group and 25.4 points in the placebo group (P not reported).

    These ratings were given by patients' treating neurologists who, like participants and study investigators, were unaware of the treatment assignments.

    Weaker trends toward more improvement with donepezil in memory and cognition were seen in ratings given by participants' spouses or other family members, when available.

    Donepezil was also associated with more side effects, including higher rates of diarrhea and other gastrointestinal problems and more frequent urination.

    The study was funded by the National Institutes of Health and the National Center for Research Resources.

    Study authors reported consulting, advisory board, and/or speaking fees for a large number of commercial entities including Acorda, Genentech, Pfizer, Novartis, sanofi-aventis, Teva, Biogen Idec, Bayer Schering, and EMD Serono.

    Source: MedPage Today © 2011 Everyday Health, Inc. (03/05/11)

    Warm weather linked to worse cognition in MS

    Cognitive Problems In MSWarmer weather is associated with worse cognitive functioning among individuals with multiple sclerosis (MS), according to research released Feb. 17 to be presented at the annual meeting of the American Academy of Neurology, which will be held from April 9 to 16 in Honolulu.

    Victoria M. Leavitt, Ph.D., of the Kessler Foundation in West Orange, N.J., and colleagues evaluated cognitive functioning among 40 individuals with MS and 40 matched healthy controls using neuropsychological tests and high resolution magnetic resonance imaging. Daily temperatures were recorded on the days testing was performed.

    The investigators found that individuals with MS scored 70 percent better on cognitive testing on cooler days as compared to warmer days. But they found no link between cognitive test scores and temperature for individuals without MS.

    "These findings have implications for clinical treatment, as fluctuations in cognitive status may herald otherwise quiescent exacerbations. Also, patient awareness of heat-related cognitive decline may guide life decisions, and researchers must consider the cognitive impact of temperature when planning clinical trials," the authors write.

    Source: Doctor's Lounge Copyright © 2001-2011 Doctors Lounge. (22/02/11)

    Reorganization in cognitive networks with progression of MS

    Cognitive Problems In MSAbstract

    Objectives: Cognitive dysfunction (CD) is frequent in multiple sclerosis (MS) and can occur at early stages. Whereas functional reorganization with disease progression has been described for the motor system in MS using fMRI, no such studies exist for cognition. We attempted to assess the concept of functional reorganization concerning cognition using a simple “Go/No-go” fMRI paradigm.

    Methods: Patients with a clinically isolated syndrome (CIS, n = 10), relapsing-remitting MS (RRMS) (n = 10), or secondary progressive MS (SPMS) (n = 10), and 28 healthy controls (HC), underwent a comprehensive neuropsychological test battery, clinical examination, structural imaging, and an fMRI Go/No-go discrimination task at 3 T.

    Results: Patients performed worse than HC regarding memory, sustained attention and concentration, and information processing. These differences were driven by patients with SPMS. The fMRI task elicited activation in a widespread network including bilateral mesial and dorsolateral frontal, parietal, insular, basal ganglia, and cerebellar regions. Task performance was similar between phenotypes, but deviation from the activation pattern observed in HC and patients with CIS increased with disease progression. Patients with RRMS showed increased brain activation in the precuneus, both superior parietal lobes, and the right fusiform gyrus, and recruited the hippocampus with increasing demands. Patients with SPMS demonstrated the most abnormal network function, including recruitment of pre-SMA, bilateral superior and inferior parietal, dorsolateral prefrontal, right precentral, bilateral postcentral, and right temporal brain areas.

    Conclusion: Using a cognitive fMRI paradigm, we were able to confirm adaptive changes of neuronal activation with progressing MS and to provide strong evidence for their compensatory nature, at least partially.

    M. Loitfelder, MSc, F. Fazekas, MD, K. Petrovic, MSc, S. Fuchs, MD, S. Ropele, PhD, M. Wallner-Blazek, MD, M. Jehna, MSc, E. Aspeck, MD, M. Khalil, MD, R. Schmidt, MD, C. Neuper, PhD and C. Enzinger, MD

    Author Affiliations

    From the Department of Neurology (M.L., F.F., K.P., S.F., S.R., M.W.-B., M.J., E.A., M.K., R.S., C.E.) and Section of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz; and Institute of Psychology (M.L., M.J., C.N.), Karl-Franzens-University Graz, Austria.

    Source: Neurology Copyright © 2011 by AAN Enterprises, Inc. (14/02/11)

    Relevance of cognitive deterioration in early relapsing-remitting MS
    Cognitive Problems in MSAbstract
    Objective: To assess longitudinally cognitive functioning in relapsing-remitting multiple sclerosis (RRMS) patients and its relationship with clinical and MRI variables.

    Methods: Early RRMS patients and matched healthy controls were assessed in parallel in three testing sessions over 3 years, using the Rao's Brief Repeatable Battery of Neuropsychological Tests.

    Patients also underwent an MRI analysis of T2-weighted lesion volume (T2LV), number of gadolinium-enhanced lesions and whole brain atrophy. Forty-nine RRMS patients (mean age 36.9 +/- 8.9 years; mean disease duration 2.9 +/- 1.7 years, mean Expanded Disability Status Scale, 1.7 +/- 0.7) and 56 healthy controls were recruited.

    Results: At baseline, cognitive impairment was detected in 15 patients (30.6%). After 3 years, cognitive functioning worsened in the 29.3% of patients, whereas Expanded Disability Status Scale progression was observed in only three patients. The most sensitive test to detect cognitive deterioration over time was the Symbol Digit Modalities Test (SDMT). Only the presence of moderate cognitive impairment at baseline predicted further cognitive deterioration (p = 0.03). Among MRI variables, T2LV showed a weak to moderate relationship with some cognitive tasks.

    Conclusions: Over a 3-year period cognitive deterioration can be expected in approximately one-third of MS patients with relatively short disease duration. The SDMT is particularly suitable for longitudinal assessment of MS-related cognitive changes.

    Amato MP, Portaccio E, Goretti B, Zipoli V, Iudice A, Della Pina D, Malentacchi G, Sabatini S, Annunziata P, Falcini M, Mazzoni M, Mortilla M, Fonda C, De Stefano N.

    Department of Neurology, University of Florence, Italy.

    Source: Pubmed PMID: 20729256 (06/09/10)

    Can mental activity protect against memory problems in MS?

    A new study shows that a mentally active lifestyle may protect against the memory and learning problems that often occur in multiple sclerosis (MS). The study is published in the June 15, 2010, print issue of Neurology®, the medical journal of the American Academy of Neurology.

    “Many people with MS struggle with learning and memory problems. This study shows that a mentally active lifestyle might reduce the harmful effects of brain damage on learning and memory. That is, learning and memory ability remained quite good in people with enriching lifestyles, even if they had a lot of brain damage (brain atrophy on brain scans). In contrast, persons with lesser mentally active lifestyles were more likely to suffer learning and memory problems, even at milder levels of brain damage,” said study author James Sumowski, PhD, with the Kessler Foundation Research Center in West Orange, New Jersey.

    The study involved 44 people around the age of 45 who had MS for an average of 11 years. The study authors measured lifetime enrichment with word knowledge, typically acquired through activities that involve reading and education.

    The study found that those with a mentally active lifestyle had good scores on the tests of learning and memory even if they had higher amounts of brain damage. For example, on a test of verbal learning and memory, participants were given up to 15 tries to learn a list of 10 words, and were then asked to recall the list after 30 minutes. Among people with mentally active lifestyles, learning and recall was similar in those with lower and higher amounts of brain damage (recall decline of about one percent: 9.6 words to 9.5 words).

    In contrast, among persons with less intellectually enriching lifestyles, learning was slower and recall was lower after 30 minutes among those with higher amounts of brain damage compared to those with lower amounts of damage (recall decline of about 16 percent: 9.6 words to 8.0 words).

    “The findings suggest that enriching activities may build a person’s ‘cognitive reserve,’ which can be thought of as a buffer against disease-related memory impairment. Differences in cognitive reserve among persons with MS may explain why some persons suffer memory problems early in the disease, while others do not develop memory problems until much later, if at all,” said Sumowski. “These results open up a whole new area of inquiry in MS that could have a significant impact,” said Peter A. Arnett, PhD, of Penn State University in University Park, Pa., who wrote an editorial accompanying the study. “There’s the potential that people could improve their cognitive reserve to reduce or prevent cognitive problems later.”

    Arnett said the possibility is particularly appealing because people typically live with MS for many years, and cognitive problems are common. “More research is needed before any firm recommendations can be made, but it seems reasonable to encourage people with MS to get involved in activities that might improve their cognitive reserve, such as mentally stimulating activities like crossword puzzles and word games, regular exercise, and social relationships.”

    “These findings are similar to research on cognitive reserve in aging and Alzheimer’s disease,” Sumowski said. “Studies on aging have also shown that engagement in specific cognitive leisure activities, such as reading books or playing games, also protects against the effects of Alzheimer’s disease. More research is needed to investigate the contribution of specific leisure activities to cognitive reserve in people with MS.”

    The study was supported by the National Multiple Sclerosis Society and the National Institutes of Health.

    Source: American Academy of Neurology ©2010 American Academy of Neurology (15/06/10)

    Memantine trial for cognitive impairment in multiple sclerosis

    Cognitive Impairment In MSAbstract

    Background: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimer's disease.

    Objective: Determine whether memantine improves cognitive performance (CP) among subjects with multiple sclerosis (MS) and cognitive impairment (CI).

    Methods: This double-blind, randomized, placebo-controlled trial (Clinicaltrials.gov NCT00300716) compared memantine 10 mg twice a day (4 week titration followed by 12 weeks on the highest tolerated dose) with placebo. The primary outcome was the change from baseline to exit on the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test-II (CVLT-II) Long Delay Free Recall (LDFR). Secondary outcomes included additional neuropsychological tests; self-report measures of quality of life, fatigue, and depression; and family/caregiver reports of subjects' CI and neuropsychiatric symptoms.

    Results: The differences between the groups on the change on the PASAT (placebo-memantine = 0.0 correct responses, 95% CI 3.4, 3.4; p = 0.9) and on CVLT-II LDFR (placebo-memantine = -0.6 words, 95% CI -2.1, 0.8; p = 0.4) as well as on the other cognitive tests were not significant. Subjects on memantine had no serious adverse events (AEs) but had more fatigue and neurological AEs as well as, per family members' reports, less cognitive improvement and greater neuropsychiatric symptoms than subjects on placebo.

    Conclusion: Memantine 10 mg twice a day does not improve CP in subjects with MS, ages 18-65, without major depression, who have subjective cognitive complaints and perform worse than one SD below the mean on the PASAT or on the California Verbal Learning Test-II (total recall or delayed free recall).

    Lovera J, Frohman E, Brown T, Bandari D, Nguyen L, Yadav V, Stuve O, Karman J, Bogardus K, Heimburger G, Cua L, Remingon G, Fowler J, Monahan T, Kilcup S, Courtney Y, McAleenan J, Butler K, Wild K, Whitham R, Bourdette D.

    Louisiana State University Health Sciences Center, Dept Neurology, New Orleans, LA, 70003, USA.

    Source: Pubmed PMID: 20483885 (28/05/10)

    Resveratrol, can it actually improve your brain function?

    GrapesCan Resveratrol, the so-called miracle molecule found in red wine, peanuts and an obnoxious plant called Chinese Giant Knotweed, actually improve your brain function?

    Scientists at Northumbria University in the UK have just published a double-blind, peer-reviewed study in the journal, American Journal of Clinical Nutrition, which concludes that a relatively modest dose of this compound in the form of one or two capsules may just do that. In their study, 24 subjects were given one capsule of a supplement called Biotivia Bioforte Resveratrol containing 250 mg of the trans-Resveratrol isomer in each dose.

    In previous studies of Resveratrol the compound has been shown to have potent anti-aging properties in animals, as well as the ability to protect cells against a remarkable range of diseases. Resveratrol seems to perform much the same function in animals the same way it does in plants; that is, act as the organism's immune and defense system. The supplement's ability to activate certain genes called sirtuins was discovered by Dr. David Sinclair at Harvard about three years ago and since that time has been the subject of hundreds of studies and trials. Albert Einstein Medical School, for example, has applied to present the results of its trial on diabetes patients to the American Diabetes Association Science Meeting in June.

    In the Northumbria study, Bioforte resveratrol increased the brain blood flow in the human subjects while they were performing mental tasks by a substantial amount. The effect seemed to be turned on by the increased demand caused by the cognitive tasks being performed by the student subjects. This implies that the effect of Resveratrol on cerebral blood flow is activated on demand when the brain is called upon to perform a challenging mental task. Could this mean that the compound can be taken in the morning before taking an exam, for example, and spring into action when needed to boost the brain's ability to cope with the exam? Possibly; however, much more study is needed to determine the proper dosage and timing for this application.

    James Betz PhD, the managing director of Biotivia, the company whose supplement was purchased on the open market for use in the Northumbria trial, stated in response to this question, "This study is extremely important because it is a peer-reviewed human clinical trial, not an animal study or a study of cells in a culture. What this study tells us is that Resveratrol clearly does improve one of the key parameters of brain performance. Whether this translates into improved cognition over the short or long term is still to be determined. In the meantime, there are heaps of other reasons to take Resveratrol and given that it has not been found to be in any way toxic, it may be worth considering as a primary daily addition to your supplement regimen."

    About Biotivia

    Biotivia established 1992 in Vienna and currently has US offices in New York, Los Angeles, Kansas City and international offices in the UK, Spain, Austria, Denmark, Italy, the Netherlands, Germany, Singapore, Xi'an China and Mumbai India.

    Biotivia pioneered the science of natural health supplement design and development based upon evidence of efficacy and safety drawn from the company's own studies and trials and in collaboration with world renowned research organizations.

    Biotivia presently supplies researchers, physicians and scientists employed at Harvard, Stanford, Yale, Georgetown, The Albert Einstein Medical Center, University of Texas, M.D. Anderson Cancer Center, the University of California, and many others.

    Biotivia is the first supplement manufacturer in the world to apply advanced "Active Packaging" technologies to its products to insure the highest level of freshness and potency even after the container is opened.

    Source: Medical News Today © 2010 MediLexicon International Ltd (04/05/10)

    CogniFit coaches MS patients to improve memory & cognition

    Cognifit LogoCogniFit™, Inc., a leading maker of Brain Fitness Software, announced a new, independent study that shows CogniFit Personal Coach brain training software improves the cognitive function and skills of Multiple Sclerosis (MS) patients.

    Many people with MS suffer some cognitive impairment as a result of disease. Patients who trained with the program showed significant improvement in 10 fundamental cognitive skills. Results of this study are published in the current issue of NeuroRehabilitation.

    During this study, one group of MS patients used CogniFit Personal Coach software for 20-30 minutes, three times a week for 12 weeks, and a control group did not participate in any training. For those individuals who used CogniFit Personal Coach, memory skills showed the greatest improvement. The training group exhibited a general memory increase of 21%, a visual working memory increase of 20% and a verbal-auditory working memory increase of 20% over and beyond that of the control group.

    Post-hoc, finer-grained analyses of the data showed that linguistic short-term and working memory had improved by 14% and 16% respectively in the cognitive training group over and beyond improvements in the control group. The post-hoc analyses also revealed that participants in the cognitive training group were exhibiting significant improvements, over those in the control group, in naming speed (9%), speed of object recall (10%), focused attention (8%), visuo-motor attention (10%) and visual spatial working memory (8%).

    The study also examined the unprompted and voluntary adherence rate of MS patients to cognitive training and results show that despite fatigue, a common characteristic side-effect of MS, the majority of the patients (71%) adhered to the training program. Patients who did not adhere were younger than patients who adhered, and in those patients severity of the disease was lower.

    MS is a chronic inflammatory disease that causes lesions in the nervous system. As part of the nervous system, the brain often sustains some of this damage, leading to cognitive impairment. Although attention/concentration and processing speed, as well as executive functions such as verbal fluency, concept formation, abstract reasoning, planning and monitoring are commonly affected by MS, memory is one of the areas that is most compromised. Researchers believe that CogniFit Personal Coach's ability to target the areas that need training most led to the dramatic improvements seen particularly across the different types of memory.

    "While patients in the cognitive training group were significantly improving vital cognitive functions using an enjoyable cognitive intervention at home, in the control group cognitive growth was often non-existent," said Dr. Evelyn Shatil, article author and Head of Cognitive Science at CogniFit. "We also observed high real-life adherence rates for patients with neurological disorders who trained - unprompted and voluntarily - in the privacy of their homes. Together, the findings offer great hope for comprehensive home-based personalized medicine which combines cognitive training interventions with medication therapy."

    CogniFit Personal Coach provides scientifically validated cognitive training that is tailored to meet the specific needs of individuals. Following a baseline assessment, users engage in exercises designed to train their brain which continually adjust to the level of the user. As a result, people using CogniFit software are challenged enough to improve their abilities, but not frustrated by the software's difficulty level. As users' skills improve, the training also evolves.

    Previous studies using the CogniFit Personal Coach software have shown its ability to improve cognitive skills in elderly people with satisfactory and lower cognitive function.

    Source: Medical News Today © 2010 MediLexicon International Ltd (19/03/10)

    Efficacy and specificity of intensive cognitive rehabilitation of attention and executive functions in multiple sclerosis

    Cognitive Problems in MS

    Summary
    Intensive neuropsychological rehabilitation of attention, information processing and executive functions is effective in patients with relapsing-remitting MS and low levels of disability, and also leads to improvement in depression. J Neurol Sci. 2009 Oct 12. (Epub ahead of print)

    Details
    In this double-blind, placebo controlled, clinical trial the authors investigated the efficacy of intensive cognitive treatment given to people with MS with a degree of cognitive dysfunction.

    The 20 people in this study were divided into two groups. One group received intensive neuropsychological treatment consisting of one hour sessions of computer-assisted training of attention, information processing and planning exercises for executive functions. The other group received no training.

    The sessions took place three times a week over a three month period.

    The authors found that the people who received intensive cognitive rehabilitation scored significantly higher in all cognitive tests than people who did not receive any rehabilitation treatment. They also found that cognitive rehabilitation improved depression scale scores. Despite the small number of participants, this study highlights the importance of cognitive rehabilitation for people with MS and cognitive dysfunction.

    Source MS Society of Canada (28/10/09)

    Increasing cognition in MS by playing computer games

    Neural Cognition

    Is it really possible to improve some, MS related, cognition issues by playing computer games?

    Doctors from Baylor College of Medicine in Houston seem to think so. According to their poster presentation at the World Congress on Treatment and Research in Multiple Sclerosis (ACTRIMS + ECTRIMS + LACTRIMS) Montreal, Quebec, Canada (Sept. 17-20, 2008) they conclude that trends toward improvement in information processing accuracy, memory, and attention occur with the use of online cognitive rehabilitation programs.

    It’s estimated that at least 65% of Multiple Sclerosis patients endure cognition problems on a day to day basis. Challenges with multi-tasking, memory attention, executive functioning, information processing, learning, and visuospatial abilities are common and can negatively impact quality of life and stress levels.

    The BCM doctors set out to understand whether using computer-assisted cognitive rehabilitation (CACR) would help patients with mild to moderate cognitive impairment. After 18 weeks of using computer assisted rehabilitation, the twelve individuals enrolled in the trial, showed improvement between 19-38 percentile points in the various cognitive areas. That’s exciting news when you are struggling to learn a new task, follow a recipe, remember your own family’s names, or how to do simple math in your head.

    Finding sites that offer free brain fitness exercises online isn’t too difficult and here are a few to help get you started. Happy Neuron, Fit Brains, and Lumosity. So, go ahead and start exercising your brain today. You have everything to gain.

    For more info: BCM's Poster Presentation

    Source: examiner.com © 2009 Clarity Digital Group LLC (02/09/09)

    Cognitive deficits in multiple sclerosis patients with cerebellar symptoms

    MS Cognitive Problems

    Background:
    Cerebellar dysfunction is common in patients with multiple sclerosis (MS). However, neuropsychological studies of this clinical feature are lacking.

    Objective:
    We investigate the neuropsychological features in relapsing-remitting MS (RR-MS) patients with and without cerebellar dysfunction.

    Methods:
    Twenty-one RR-MS patients with cerebellar dysfunction (RR-MSc), characterised by prevalent ataxic gait and nystagmus, and 21 RR-MS patients without any cerebellar manifestation (RR-MSnc) pair-matched for demographical and clinical variables were studied. All patients from each group underwent an extensive battery of neuropsychological tests. Magnetic resonance imaging analysis included hyperintense fast fluid-attenuated inversion-recovery lesion load in the whole brain as well as in the four lobes separately.

    Results:
    Any significant differences were detected in total and regional lesion load measurements between the two groups. RR-MSc group performed equally as well as the RR-MSnc group on many of the cognitive exploration measures. Nevertheless, the RR-MSc group performed more poorly than the RR-MSnc group on attention tests (Symbol Digit Modalities Test) and verbal fluency tests (Controlled Oral Word Association Test); neither of the test results proved to be affected by regional lesion loads.

    Conclusion:
    These results highlight the importance of considering cognitive deficits associated with the presence of cerebellar symptoms in RR-MS.

    Valentino P, Cerasa A, Chiriaco C, Nisticò R, Pirritano D, Gioia M, Lanza P, Canino M, Del Giudice F, Gallo O, Condino F, Torchia G, Quattrone A.

    Institute of Neurology, University Magna Graecia, Catanzaro, Italy

    Source: PubMed PMID: 19542264 (08/07/09)

    New website for people with Multiple Sclerosis

    MS Invigor8, a website developed by researchers at the University of Southampton, to treat fatigue in people with Multiple Sclerosis (MS) using Cognitive Behaviour Therapy (CBT) will be completed on Friday (12 December) and is ready to be trialled.

    The research team led by Professor Rona Moss-Morris at the School of Psychology, with the technological side led by Dr Gary Wills at the School of Electronics and Computer Science, now seeks 40 people in the UK who experience MS fatigue to take part in the web-based trial which will begin on 12th January.

    The team adopted an approach which used eight sessions of manualised CBT to treat fatigue in MS effectively, and developed an Internet based version of the package.

    'We know this works because six months after the manual treatment, not only had fatigue substantially reduced, but people with MS reported levels of fatigue that were significantly lower than those of a matched healthy, non-fatigued group,' said Professor Moss-Morris.

    The researchers found that a limitation of the manual package is that skilled CBT therapists are not available to many people with MS due to the lack of available resources and difficulty of access. The new web-based package will enable effective treatment for more people with minimal therapist time.

    The team used expert services users to work with them to develop eight sessions to assess users’ levels of fatigue, their patterns of activity and rest and then to enable them to manage issues such as sleep patterns and stress. The programme is interactive and personalised allowing people to set goals for managing their fatigue and work towards developing and maintaining a healthier lifestyle.

    Lawrence Gilbert, an expert service user who has been very involved in the process from the outset, said:

    'MS can be like a Duracell battery, you could be going along fine and then suddenly the energy drains out of you. My concern has always been that the fatigue, which is a part of the condition, could be wrongly attributed to being just "all in the mind". The approach taken by the Southampton team is not like that at all.'

    To access more information about the programme and the development team, please visit: http://octopussy.ecs.soton.ac.uk/MSInvigor8/Intro/index.php

    People interested in knowing more about the trials which begin next month, should contact: Louise Bell on [email protected]

    Source: AlphaGalileo © AlphaGalileo Foundation 2008 (11/12/08)

    Cognitive impairment and structural brain damage in benign multiple sclerosis

    MRI

    OBJECTIVE: Although in benign multiple sclerosis (BMS) locomotor disability is absent or only minimal, subclinical cognitive impairment seems to occur in many cases. Diffusion tensor (DT) MRI enables us to quantify the extent of "actual" tissue damage, which goes undetected when using conventional MRI. Against this background, we investigated the extent of structural brain damage underlying cognitive dysfunction in BMS, with the ultimate aim to move a first step toward a more reliable definition of this disease phenotype.

    METHODS: Conventional and DT MRI scans of the brain were acquired from 62 BMS patients. Thirty-six secondary progressive multiple sclerosis (SPMS) patients and 19 healthy subjects served as controls. In BMS patients, neuropsychological tests exploring memory, attention, and frontal lobe functions were administered. Normalized brain volume (NBV), mean diffusivity (MD), and fractional anisotropy (FA) of the normal-appearing white matter (NAWM) and MD of the gray matter (GM) were computed.

    RESULTS: Twelve BMS patients (19%) fulfilled predefined criteria for cognitive impairment. BMS patients had abnormal MD and FA values from both NAWM and GM. Whereas BMS patients without cognitive impairment had lower T2 LV (p = 0.03), higher NBV (p = 0.006), and lower average GM MD (p = 0.03) than SPMS patients, BMS patients with cognitive impairment did not significantly differ from SPMS patients for any MRI-derived metric.

    CONCLUSIONS: In benign multiple sclerosis (BMS), cognitive dysfunction is associated with severe structural brain damage, which resembles that of patients with a much more disabling disease course. A reliable definition of BMS should, therefore, include the preservation of cognitive functioning as an additional requisite.

    From the Neuroimaging Research Unit (M.R., G.R., M. Filippi) and Department of Neurology (M.R., E.J., F.P., M. Falautano, V.M., G.C., M. Filippi), Scientific Institute and University Ospedale San Raffaele, Milan; Department of Neurology (D.C.), Scientific Institute Don Gnocchi, Milan; Multiple Sclerosis Center (A.G.), Ospedale di Gallarate, Gallarate; Multiple Sclerosis Center (A.B.), Ospedale di Orbassano, Orbassano; and Multiple Sclerosis Center (R.C., F.M.), Spedali Civili, Brescia, Italy.


    Source: Pubmed PMID: 18815387 (09/10/08)

    EPO may prove useful in the treatment Multiple Sclerosis memory problems

    EPO

    A drug used to increase blood production in both medical treatments and athletic doping scandals seems to also improve memory in those using it.

    New research published in BMC Biology says that the memory enhancing effects of erythropoietin (EPO) are not related to its effects on blood production but are due to direct influences on neurons in the brain. The findings may prove useful in the treatment of diseases affecting brain function, such as schizophrenia, multiple sclerosis, and Alzheimer’s.

    Patients given EPO to treat chronic kidney failure had been observed to have improved cognition after starting the drug. “These effects of EPO were thought to result from the blood-boosting effects of the drug,” explains Hannelore Ehrenreich at the Max Planck Institute, “but the finding of receptors for EPO on nerve cells in the brain suggests that some other mechanism might be involved.”

    To investigate the mechanisms of EPO-enhanced cognition, the researchers injected mice with EPO every other day for three weeks (11 doses) to test the effects of long-term exposure. After the treatment period, mice given EPO had better memory in some situations than did mice that had been given a placebo instead. The improvement in memory lasted up to three weeks from the last EPO dose and outlasted increased blood-cell production, but had disappeared by four weeks. Mice given three doses saw no benefit with respect to memory improvement.

    “Young mice systematically treated with EPO for three weeks have improved memory, similar to the dramatic improvements observed in endurance and muscular performance athletes who use EPO to boost performance”, says Ehrenreich. The specific memory improvements were associated with the hippocampus, a structure in the brain involved in learning and memory, among other functions.

    The researchers did a series of experiments on hippocampal tissue taken from the mice and found that EPO directly affected the neurons in this structure. “EPO had pronounced effects on short-term and long-term plasticity in the hippocampus as well as on synaptic transmission”, the researchers report. “Treatment with EPO seems to increase the number of inhibitory circuits, which actually increases the efficiency of transmission of excitatory nerve impulses in specific neurons, resulting in greater short-term and long-term plasticity in memory pathways in the hippocampus.”

    These findings begin to shed light on the mechanisms of improvements in cognition seen in patients with schizophrenia and multiple sclerosis as a result of treatment with this drug. As well as working to refine these findings, further studies might also investigate the effects of EPO on other brain regions that might be associated with improvements in motor functions in multiple sclerosis, and investigate the potential of using EPO or targeting the networks involved in EPO-generated neuronal plasticity in the treatment of neurodegenerative diseases.

    Source: Scientific Blogging (09/09/08)

    Prevalence and Patterns of Cognitive Dysfunction in Benign MS
    The combination of neuropsychological profiling and quantitative magnetic resonance imaging (MRI) for patients with benign multiple sclerosis (benign MS) provides a more reliable and comprehensive definition of their disease, and thus of their prognostic factors for the subsequent evolution of their disease, according to a study presented at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

    Benign MS is generally defined as absence of locomotor disability after 15 years or more of disease onset. However, as Monica Falautano, PhD, Co-Investigator and Psychologist, Functional Unit of Psychology, San Raffaele Scientific Institute, University Vita-Salute, Milan, Italy, said, "We feel that in patients with benign multiple sclerosis, their cognition and dysfunction in cognitive performance are underestimated… as in a recent review where they detected mild [cognitive] impairment with a patient with benign multiple sclerosis."

    Dr. Falautano and colleagues therefore conducted a study with the aim of investigating the prevalence and patterns of cognitive dysfunction in a large sample of patients with benign MS, and to explore conventional and diffusion tensor (DT) MRI patterns underlying this cognitive dysfunction. This should allow potential markers to be defined for identification of patients with benign MS who have a more severe "occult" disease burden, she said.

    They enrolled patients with a confirmed diagnosis of benign MS, defined as absence of locomotor disability through a disease duration of 15 years or more and accompanied by an expanded disability status scale (EDSS) no more than 3.0.

    The 61 patients enrolled had a mean age of 46 years and 38% were male. They underwent extensive neurological and neuropsychological (NPS) evaluation, and conventional and DT MRI brain scans. Their mean EDSS was 1.5 at a mean disease duration of 22 years, and with a mean education level of 12 years.

    Performances in the NPS evaluation tests exploring the main cognitive domains were compared between these patients and demographically and educationally matched healthy controls. These domains and tests were for: language (Token test; Phonemic fluency [VPF]; Semantic fluency), memory (Digit span; Corsi span [CS]; Short tale [ST]; Acquisition of pairs of words [APW]; Rey-Osterrieth recall), executive functions (Raven matrices; Wisconsin card sorting test), construction (Rey-Osterrieth copy [copy ROCF]; Ten-point clock test), and attention (Attentive matrices; Trail-making test [TMT]; Paced auditory serial attention test [PASAT]; Stroop test).

    Following the MRI acquisition and analysis, two sets of comparisons were analysed within the benign MS patient group, based on definitions of cognitive impairment (patient test score 2 standard deviations below normal control mean = test failed) and cognitive normality (all patient test scores at or above the normal control mean).

    This identified paired groups of patients who were cognitively impaired (n = 11; failure in three tests) versus cognitively unimpaired (n = 50) and cognitively normal (n = 21) versus not cognitively normal (n = 40).

    The performances in individual tests across the cognitively unimpaired versus cognitively impaired comparison demonstrated significant group differences for attentive-executive functioning, verbal learning, long-term memory and visual-spatial cognition: TMT (P =.008), PASAT (P =.013), CS (P =.006), ST (P =.010), APW (P =.003), VPF (P =.016) and copy ROCF (P =.002).

    Similar differences were seen for cognitively normal versus not cognitively normal, with better performances for exploring attentive-executive functioning and verbal long-term memory: TMT (P =.013), ST (P =.001 and CS (P =.032).

    When related to conventional and DT MRI findings, these different patient subgroups again showed some significant differences. For cognitively unimpaired versus cognitively impaired significant differences were seen for normal-appearing white matter (NAWM) mean diffusivity (P =.010) and its peak height (P =.001), NAWM fractional anisotropy (P =.008) and its peak height (P =.001), and grey matter mean diffusivity (P =.018).

    For cognitively normal versus not cognitively normal, the only significant difference across the MRI data was for peak height of NAWM fractional anisotropy (P =.028).

    These analyses indicate that despite absence of locomotor disability in patients with benign MS, the prevalence of cognitive impairment is similar to that of the general population of patients with MS (40%-65%). This finding thus confirms that criteria for identifying benign MS are misleading as it actually represents a clinical category where a significant proportion can have clinically undetected cognitive problems, according to the researchers.

    Overall, these MRI findings are consistent with more severe "occult" brain tissue damage in the cognitively impaired and not cognitively normal patients with benign MS than in their respective comparative groups, suggesting that these subgroups of patients with benign MS might also differ in their medium to long-term clinical evolution.

    Dr. Falautano noted, "It is also important for patients with benign multiple sclerosis to undergo neuropsychological evaluation because even if they do not present physical impairment, we can find mild or also moderate cognitive impairment, which will be important for their treatment."

    Source: Presentation title: Prevalence and Patterns of Cognitive Dysfunction in Benign MS: A Psycholetric and MRI Study. Abstract P747 (23/10/07)

    Cognitive impairment in multiple sclerosis: Evidence-based analysis and recommendations
    Abstract

    Cognitive impairment is common in multiple sclerosis (MS), occurring at all stages of the disease, and can be a major source of vocational disability, social impairment, and impoverished quality of life.

    Dysfunction in free recall from long-term memory, speed of information processing, working memory, and abstract reasoning are frequently observed in MS. Despite weak correlation with disease duration and physical disability status, the degree of cognitive impairment in MS has been related to the extent of topographically specific neuronal tissue damage and loss.

    Additional clinical factors including disease course, fatigue, affective disturbance, and medication can impact on the degree of MS-related cognitive impairment.

    We suggest that the symbol digits modalities test, paced auditory serial addition task, the clock drawing test and the MS neuropsychological screening questionnaire be considered as valid and relevant screening tests for cognitive impairment in MS.

    Jeffrey M. Rogersa and Peter K. PanegyresabaNeurosciences Unit, Health Department of Western Australia, Perth, Western Australia, Australia bNeurodegenerative Disorders Research, The Mount Medical Centre, Perth, Western Australia, Australia

    Source: Journal of Clinical Neuroscience Volume 14, Issue 10, October 2007, Pages 919-927 (02/10/07)

    Internet-based cognitive testing in multiple sclerosis
    Cognitive impairment in multiple sclerosis is difficult to study because of the heterogeneity and variability of this disease. The gold standard for measurement of cognitive function in multiple sclerosis is a full battery of neurocognitive tests, which is time consuming and expensive. Some cognitive tests like the PASAT, a measure of working verbal memory and processing speed, have been proposed for screening and follow-up of cognitive function in clinical trials. We studied whether we could measure cognitive function in multiple sclerosis over the Internet.

    For this we used the Cognitive Stability Index (CSI)TM, developed for persons with known or suspected primary central nervous system illness. The CSI was compared with formal neurocognitive testing (NPsych) and the PASAT in a cross-sectional study of 40 consecutive multiple sclerosis patients with subjective cognitive complaints. NPsych revealed that only 18 of the 40 patients (46%) were cognitively impaired. Although both the CSI and the PASAT were equalivalent in their specificity (86%), the CSI was significantly more sensitive than the PASAT (83% versus 28%).

    We conclude that the CSI, because of its availability over the Internet, has great potential as a tool for screening and follow up of cognitive function in multiple sclerosis.

    Source: Multiple Sclerosis 2007; 13: 1011—1019 (26/09/07)

    Thalamic atrophy and cognition in multiple sclerosis
    Objectives: Recent studies have indicated that brain atrophy is more closely associated with cognitive impairment in multiple sclerosis (MS) than are conventional MRI lesion measures. Enlargement of the third ventricle shows a particularly strong correlation with cognitive impairment, suggesting clinical relevance of damage to surrounding structures, such as the thalamus. Previous imaging and pathology studies have demonstrated thalamic involvement in MS. In this study, we tested the hypothesis that thalamic volume is lower in MS than in normal subjects, and that thalamic atrophy in MS correlates with cognitive function.

    Methods: We studied 79 patients with MS and 16 normal subjects. A subgroup of 31 MS subjects underwent cognitive testing. The thalamus was segmented in whole from three-dimensional MRI scans. We also determined whole brain atrophy (brain parenchymal fraction), third ventricular width, and whole brain T2-weighted (fluid-attenuated inversion recovery) hyperintense, T1 hypointense, and gadolinium-enhanced lesion volumes.

    Results: Normalised thalamic volume was 16.8% lower in the MS group (p < 0.0001) vs controls. Cognitive performance in all domains was moderately to strongly related to thalamic volume in the MS group (r = 0.506 to 0.724, p < 0.005), and thalamic volume entered and remained in all regression models predicting cognitive performance. Thalamic volume showed a weak relationship to physical disability score (r = –0.316, p = 0.005).

    Conclusion: These findings suggest that thalamic atrophy is a clinically relevant biomarker of the neurodegenerative disease process in multiple sclerosis.

    Source: Neurology Copyright © 2007 by AAN Enterprises, Inc. (18/09/07)

    Computer-Based Cognitive Rehab Improves Attentional Functions in Multiple Sclerosis Patients
    Computer-based drill and practice cognitive rehabilitation can be used to help improve attentional functions in patients with multiple sclerosis, researchers reported at the 22nd Congress of the European Committee for Treatment and research in Multiple Sclerosis (ECTRIMS).

    "Speech information processing in attentional tasks gets better with a cognitive rehabilitation program that is computerised and tailor made," said lead investigator Marta Renom, BA, speech and language therapist, Multiple Sclerosis Foundation - Day Hospital, Barcelona, Spain.

    The investigators recruited 50 patients from the hospital and stratified 23 to the control group and 27 to the rehabilitation group.

    During the study, the investigators used an assessment protocol that included neuropsychological, psychosocial and medical parameters. It was given 4 times at 6-monthly intervals. Between the second and the third assessment, the rehabilitation cohort participated in a 6-month cognitive rehabilitation program.

    At baseline, control subjects were younger than the treatment group (41.5 vs 47.8, respectively; P = .017). They were similar in terms of years of schooling (11.4 vs 10.8, respectively) and gender (female/male: 16/7 vs 16/11, respectively).

    Statistically significant improvements were observed in the treatment group that received computer-based rehabilitation. Reaction times in tonic alertness (P = .035), phasic alertness (P = .017) and divided attention (P = .017) all improved significantly.

    Treated patients also achieved a significant decrease in standard deviation in tonic alertness (P = .048). For the control group, there was significant worsening in reaction times in tonic alertness (P = .021). There were no significant changes in other remaining attentional functions.

    "Less consistent changes were found for executive functions subtests, memory and language domains, as well as emotional and quality of life indicators," the authors wrote.

    The investigators concluded that a computer-based drill and practice cognitive rehabilitation program could be useful for improving attentional functions in patients with MS.

    "The most basic attentional function (tonic alertness) seems to be the most sensitive. Its effect on other cognitive domains such as executive functions, language and memory is less well defined, as well as its generalisation to quality of life and emotional aspects," they added.

    [Presentation title: Effects of Cognitive Rehabilitation in Multiple Sclerosis. Abstract P428]

    Source: Doctor's Guide Channels Copyright (c) 1995-2006 Doctor's Guide Publishing Limited. All rights reserved. (05/10/06)

    Differential cognitive impairment for diverse forms of multiple sclerosis
    Abstract (provisional)

    Background

    Cognitive impairment is a common feature in multiple sclerosis (MS) patients and occurs in 60% of all cases. Unfortunately, neurological examination does not always agree with the neuropsychological evaluation in determining the cognitive profile of the patient. On the other hand, psychophysiological techniques such as event-related potentials (ERPs) can help in evaluating cognitive impairment in different pathologies. Behavioural responses and EEG signals were recorded during the experiment in three experimental groups: 1) a relapsing-remitting group (RRMS), 2) a benign multiple sclerosis group (BMS) and 3) a Control group. The paradigm employed was a spatial attention task with central cues (Posner experiment). The main aim was to observe the differences in the performance (behavioural variables) and in the latency and amplitude of the ERP components among these groups.

    Results

    Our data indicate that both MS groups showed poorer task performance (longer reaction times and lower percentage of correct responses), a latency delay for the N1 and P300 component, and a different amplitude for the frontal N1. Moreover, the deficit in the BMS group, indexed by behavioural and pyschophysiological variables, was more pronounced compared to the RRMS group.

    Conclusions

    The present results suggest a cognitive impairment in the information processing in all of these patients. Comparing both pathological groups, cognitive impairment was more accentuated in the BMS group compared to the RMSS group. This suggests a silent deterioration of cognitive skills for the BMS that is not usually treated with pharmacological or neuropsychological therapy.

    Javier J JJ Gonzalez-Rosa , Manuel M Vazquez-Marrufo , Encarnacion E Vaquero , Pablo P Duque , Monica M Borges , Miguel A MA Gamero , Carlos C Gomez and Guillermo G Izquierdo

    Source: BMC Neuroscience 2006 (19/05/06)

    OHSU study finds ginkgo beneficial for MS symptoms

    When it comes to her health, Janice Winfield of Portland, Ore., does her research. That's why the stay-at-home mom, who was diagnosed with multiple sclerosis in July 2000, was willing to turn to popular, over-the-counter herbal supplements like ginkgo biloba to deal with memory problems, fatigue and occasional muscle pain. "I'm definitely interested in alternative medicine," said Winfield, 49, whose form of the neurological disease – relapsing-remitting MS – is characterised by frequent symptom flare-ups. Ginkgo "is not only given to someone like me with MS. There's benefit to anyone taking it."

    Findings by scientists in the Oregon Health & Science University School of Medicine's Department of Neurology and the OHSU MS Center of Oregon appear to back up that claim. A study presented this month at the American Academy of Neurology's 57th Annual Meeting in Miami Beach, Fla., suggests that ginkgo may be effective in improving attention in MS patients with cognitive impairment. Side effects also were minimal.

    The study's lead author, Jesus Lovera, M.D., a research fellow and instructor in neurology, OHSU School of Medicine, said those receiving ginkgo "performed better on a test that measures a person's ability to pay attention and to sort conflicting information." Of 39 patients completing the study, 20 received ginkgo biloba and 19 received placebo.

    Researchers found there were no differences in results between the two groups in the areas of gender, education, type of MS, years since onset, or baseline performance on a battery of neuropsychological tests. But the ginkgo group was four seconds – about 13 percent – faster than the placebo group on a timed color and word test that measures attention and such "executive functions" as planning, decision making, and controlling goal-directed behaviour and execution of deliberate actions. During the test, called a "Stroop," patients are shown coloured boxes and asked to name the colors. They are then shown the names of colours printed with different-coloured inks, such as the word "green" printed in red, and asked to read the word. Finally, patients are asked to describe the ink used for each word. Lovera said the differences in the Stroop result would be comparable to differences in scores between healthy people ages 30 to 39 and those ages 50 to 59.

    Ginkgo appeared to be more beneficial for MS patients having specific problems in the Stroop, so "we would like to do another study in which we choose patients that are impaired in this particular test," Lovera said. "We would also like to test it at higher doses."

    Ginko biloba is among several complementary and alternative medicine therapies being investigated by OHSU's Department of Neurology for their effects on symptoms of neurological disease. Studies have ranged from clinical trials of lactoferrin for treating Alzheimer's disease to the use of yoga as a therapy for MS fatigue.

    Ginkgo is derived from the leaves of the ginkgo tree, one of the oldest species of trees, and has been used for thousands of years by the Chinese as an herbal remedy for a variety of ailments. It contains potent antioxidants called flavoglycosides that have been shown to have neuroprotective effects in animal models of spinal cord injury. It also has terpene-lactones that block a substance known as platelet activitating factor, which is important in regulating blood vessel function as well as the mediating inflammation and the sticking of inflammatory cells to blood vessels.

    Many MS patients have long suspected that ginkgo improves disease symptoms. In a recent survey of 1,913 patients in Oregon, 20 percent reported using the supplement and 39 percent found it to be beneficial. However, until now, there was no evidence the supplement had any effect on memory. "It has been shown to be of benefit in Alzheimer's, but we did not know if it would work for MS," Lovera said. "We wanted to see if there was any suggestion that it could help patients with MS that are having cognitive problems."

    Lovera said the study results demonstrate that ginkgo shouldn't be discounted for treating MS, but its safety and efficacy must be tested in much larger clinical trials before doctors should recommend it to their patients.

     "The study suggests that for cognitive problems, it may only help a certain group of patients," he said. "We need to study this further." And for MS sufferers like Winfield, who participated in the ginkgo study, the herbal supplement will remain one of the many weapons in her arsenal for fighting the disease. "I would do it again," she said of taking ginkgo. "It could have a benefit for me that I didn't have before." But she emphasizes that "every MS is different, so what might work for me may not work for anybody else. But when it comes to alternative medicine, I'm all for that."

    Source: Oregon Health & Science University School of Medicine (30/10/05)

    Effects of a Cognitive-Behavioral Program for Women With Multiple Sclerosis
    Journal of Neuroscience Nursing)
    Updated: Oct 28th 2005

    By Sinclair, Vaughn G; Scroggie, Jennifer

    Abstract: The purpose of this quasi-experimental study was to evaluate the effectiveness of a cognitive-behavioral intervention for women with multiple sclerosis (MS). Thirty-seven adult women with MS participated in a group-based intervention program titled "Beyond MS," which was led by master's-prepared psychiatric nurses.

    For participants, the program involved reading a manual and meeting for five weekly group sessions. Perceived health competence, coping behaviours, psychological well-being, quality of life, and fatigue were measured at four time periods: 5 weeks before the beginning of the intenvention, immediately before the intervention, at the end of the 5-week intervention, and at a 6-month follow-up. There were significant improvements in the participants' perceived health competence (p < .01), indices of adaptive and maladaptive coping (p < .04), and most measures of psychological well-being (p < .05) from pre- to postintervention. The positive changes brought about by this relatively brief intervention program were maintained during the 6- month follow-up period. This cognitive-behavioral intervention has also been used effectively in the rheumatoid arthritis population and may be adaptable to benefit individuals with other chronic conditions.

    Multiple sclerosis (MS) is a chronic, progressive, demyelinating disease of the central nervous system. The current prevalence in the United States is approximately 350,000 (Holland, 2004), with an annual incidence of about 12,000 and initial onset typically occurring between the ages of 18 and 45 years (Frohman, 2003). Given the progressive nature of MS, individuals living with this condition must cope with substantial disease-related stress and the uncertainty of their future disease course.

    Although the role of stress in triggering MS exacerbations has been debated for years, recent studies have established links between stressful life events and exacerbations (Ackerman et al., 2002; Buljevac et al., 2003; Mohr, Goodkin, Nelson, Cox, & Weiner, 2002; Mohr, Hart, Julian, Cox, & Pelletier, 2004). On a daily basis, persons with MS deal with significant stressors related to uncertainty about the future, functional and cognitive impairments, and general loss of control in their lives (Mindcn, 1992). After diagnosis, their greatest stressors include fatigue, uncertainty about the future, and difficulties in maintaining a job (Buelow, 1991). Researchers have also documented the experience of chronic sorrow, encompassing sadness, anger, frustration, fear, and helplessness, that surfaces when persons with MS feel out of control (Hainsworth, 1994; Minden, 1992). High levels of uncertainty about the future course of the illness and perceived stress have been correlated with mood disturbances in persons with MS (Kroencke, Denney, & Lynch, 2001; Wineman, Schwetz, Goodkin, & Rudick, 1996).

     Many individuals with MS become depressed, with point prevalence rates reported in the literature between 25% and 54% (Beatty, 1993; Chwastiak et al.; Murray, 1995; Schiffer, 1990). The depression may be partially caused by MS-specific processes, but a variety of psychosocial factors also can contribute to depression in this population (Mohr & Cox, 2001). The emotional component of this disease experience, therefore, presents complex and difficult challenges. There is a need for effective psychosocial interventions to help individuals with MS cope with the emotional challenges associated with living with the condition.

    This article presents findings of a cognitive-behavioral intervention program for women with MS. The program was designed to enhance perceived control and thereby affect coping skills as well as psychological and physical outcomes.

    Review of the Literature

    The manner in which individuals handle their emotional challenges may affect the course of their disease. Perceptions of disease-related stressors, particularly uncertainty, affect coping behaviours that can, in turn, affect psychological outcomes (Brassington & Marsh, 1998; Wineman, Durand, & Steiner, 1994). Learned helplessness, the antithesis of perceived control, has been significantly correlated with both social and functional disability in persons with MS (McGuinness, 1996). Perceptions of helplessness have been associated with both neurological impairment and emotional instability and mediated the relationship between impairment and fatigue severity (Van der Werf, Evers, Jongen, & Bleijenberg, 2003).

    Because MS entails daily uncertainty, confidence in one's ability to rise to the challenge (i.e., self-efficacy) should help neutralise the stressor of unpredictability. A high level of perceived control, whether measured as internal locus of control, self-efficacy, mastery, or perceived health competence, has surfaced in the MS literature as a construct affecting psychological and physical outcomes. For persons with MS, an effective internal locus of control has been linked with positive psychosocial adjustment, less depression, an active personal life (Murray, 1995), and a more benign course of MS (Wassem, 1991). Self-efficacy represents a form of perceived control applied to specific challenges and has been a significant predictor of adjustment to MS (Wassem, 1992). After adjusting for sociodemographic and medical factors in their regression analyses, Schwartz, Coulthard-Morris, and Zeng (1996) reported that a low sense of mastery was the best psychosocial predictor of both global fatigue and fatigue-related distress. More severe fatigue was correlated with higher levels of depression in their sample. Self-efficacy has emerged as a significant predictor of health-promoting behaviors in individuals with MS (Stuifbergen & Becker, 1994), with subsequent impacts on quality of life, as demonstrated in a structural equation model of health promotion and quality of life derived from a sample of 786 individuals with MS (Stuifbergen, Seraphine, & Roberts, 2000). Gulick (2001) found that certain personal attributes (Le., positive attitude, a sense of humour, perceived control over stress) mediated the effects of emotional distress on functionality in a large sample of 686 persons with MS. The psychosocial literature on MS therefore implies that psychosocial interventions for this population should focus on improving perceptions of control or selfefficacy.

    Various approaches to psychosocial intervention have been attempted in this population. Support groups (Spiegelberg, 1980), medical discussion groups (Pavlou, Hartings, & Davis, 1978), extensive group psychotherapy (Crawford & Mdvor, 1985; Hartings, Pavlou, & Davis, 1976), cognitive-behavioral therapy (CBT) groups (Foley & Bedell, 1987; Larcombe & Wilson, 1984), CBT delivered via reading a manual or conducting a telephone interview (Mohr et al., 2000), and coping-skills interventions (Schwartz, 1999; Schwartz & Rogers, 1994). Among these researchers, those who used some form of cognitive-behavioral intervention found them to be effective at significantly reducing depression levels (Crawford & Mdvor; Foley & Bedell; Larcombe & Wilson; Mohr et al.), symptoms of depression (Mohr et al.), and anxiety and distress levels (Crawford & Mclvor). Most of the samples were small (i.e., fewer than 30 participants per treatment group).

    More recent interventions partially based on the behavioural principles of social cognitive theory (Bandura, 1986, 1998) have reported positive psychological and physical changes. Mathiowetz, Matuska, and Murphy (2001) used a 6-week energy conservation course in a quasi-experimental study in which 54 subjects served as their own controls. The researchers' intervention resulted in significant improvements in fatigue impact, self-efficacy, and several aspects of quality of life (i.e., vitality, social functioning, mental health). Stuifbergen, Becker, Blozis, TTimmerman, and Kullberg (2003) used a randomised controlled trial to assess the effectiveness of a wellness intervention program for women with MS. This program used an eight-session format to deliver health-promotion information and practice techniques, incorporate individualised goal setting and monitoring, and attempt to enhance self-efficacy for health behaviours. The intervention resulted in significant improvements in self-efficacy, health behaviors, and aspects of quality of life, including pain and mental health. In general, the interventions for persons with MS that have been based on cognitive-behavioural or behavioral principles have been most effective.

    This article discusses findings of a pilot program of a cognitive-behavioral intervention titled "Beyond MS." This intervention program was modeled after "Rising Above Arthritis" (subsequently renamed "Beyond Arthritis"), a program developed with funding from the Arthritis Foundation to help women with rheumatoid arthritis (RA) develop a sense of competence in dealing with both arthritis- related problems and other life stressors (Sinclair, Wallston, Dwyer, Blackburn, & Fuchs, 1998). In a sample of 90 women with RA, analysis of changes between pre- and postintervention averaged scores revealed significant improvement on all measures of personal coping resources (e.g., helplessness and perceived control \p < .001], adaptive and maladaptive pain coping behaviour indices \p < .05], and all measures of psychological well-being [p < .05]). Furthermore, the positive changes brought about by the program were maintained during a 3-month follow-up period.

    Both RA and MS are progressive, highly unpredictable autoimmune conditions. Both patient populations deal with stress related to uncertainty, disability, fatigue, pain, and dependence on others for assistance. The researchers therefore believed that a psychosocial program that had promising effects in a sample of women with RA merited investigation with a sample of women with MS.

    The pilot study to modify the initial RA intervention and test its effects with women with MS was funded by the National Multiple Sclerosis Society, with initial program evaluation funding from the Middle Tennessee Chapter of the Multiple Sclerosis Society.

    Conceptual Model

    The Lazarus and Folkman Stress and Coping Model (Lazarus & Folkman, 1984) underscores the pivotal role perception plays in adaptation to stress. According to the model, individuals respond to stressors by appraising the potency of the stressor (the primary appraisal) and appraising their resources for meeting the challenge (the secondary appraisal). These two types of appraisal influence coping behaviors that affect psychological well-being and perceptions of quality of life. This model (Fig 1) indicates that an intervention designed to enhance a sense of perceived control or competence would positively affect appraisal mechanisms and thereby affect coping patterns and psychological outcomes. The "Beyond MS" program teaches cognitive means of making stressors seem less threatening and augments resources for meeting challenges by affecting appraisal mechanisms through a variety of strategies.

    Fig 1. Lazarus and Folkman's Stress and Coping Model (source: Lazurus & Folkman, 1984)

    Hypotheses

    Two hypotheses guided this research: (a) compared to preintervention scores, postintervention scores will reflect a positive impact on patients' perceptions of competence, coping behaviours, psychological well-being, and healthrelated quality of life, and fatigue; and (b) compared to initial postintervention scores, 6-month follow-up scores indicating perceived health competence, coping behaviours, psychological well-being, health- related quality of life, and fatigue will reflect stabilisation or improvement.

    Methods

    Sample

    Following institutional review board approval of the protocol, the researchers recruited, with the help of local neurologists and the Middle Tennessee Multiple Sclerosis Society, a convenience sample of 47 women diagnosed by a neurologist with definite or probable MS. This pilot study sample size was small, so gender, stage of the disease, and degree of disability were controlled to limit variability caused by these potentially confounding variables. The inclusion criteria included female gender; relapsing remitting MS; and ambulatory Expanded Disability Status Scale (Kurtze, 1983) scores (less than 6). The women in this convenience sample voluntarily contacted the researchers. Six women withdrew from the study before the first session because of work conflicts, children requiring surgery, care of critically ill parents, or disease exacerbations. Four women withdrew after attending only one session. One of them had a debilitating back injury, one experienced an extreme exacerbation, and two found they were too fatigued to come to the weekly sessions. Thirty-seven women completed the program and provided postintervention data.

    Because of limited funding for this pilot project, the investigators could recruit only a small sample and were primarily looking for postintervention improvement trends. Despite the sample size, the findings indicated that the effect size of the intervention was sufficient to contribute to significant improvements on a variety of measures.

    A cohort of 18 women completed "Beyond MS" during 1996-1997 as part of an initial program evaluation funded by the Middle Tennessee Multiple Sclerosis Society. A second cohort of 19 women completed the same program in 2002-2003 as part of a pilot research project funded by the National Multiple Sclerosis Society. The two programs were led by the same group leader and the same coleader with MS, who served as both cofacilitator and role model. Both leaders were master's-prepared psychiatric-mental health nurses with experience in group facilitation and group-based interventions. The group meetings were held from 6-8 pm on five consecutive Tuesdays. The 37 women all were high school graduates, as is not unusual among convenience samples of volunteers for educational interventions. Nineteen (51%) had college degrees, and 10 others had graduate degrees (27%). Twenty-five (68%) were married, eight were single, and four were divorced. Most were employed outside the home; 22 (60%) worked full time, and seven (19%) worked part time. Four (11%) were unemployed and on disability. Most listed their occupation as professional (51%), managerial (16%), or clerical (14%). One woman was African American; all of the others were White. The age range was 22-59 years (average and median age = 38 years). Thirteen (35%) had been diagnosed within the past year. The time since diagnosis ranged from a few weeks to 20 years; the average time was 5 years.

    Procedure

    This pilot study used a quasi-experimental design in which subjects acted as their own controls. Two preintervention measures were collected on each individual during a 5-week period. After meeting the entry criteria and giving written informed consent, participants completed and returned the first survey approximately 5 weeks before beginning the program (Tl). Participants completed the same measures during the week before beginning the program (T2), immediately after completing the program (T3), and at a 6-month follow-up (T4). The Tl and T4 data were collected by mail. The T2 assessment was mailed to the participants before the program, completed at home before the participants reviewed any program material, and collected by the researchers at the first group session. The T3 assessment was completed at the end of the fifth group session to ensure timely postsession data collection. The two preintervention assessments (Tl, T2) provided baseline data during a time period when there was no intervention, and the 6-month follow- up data (T4) allowed us to assess improvement, stabilisation, or dissipation in the changes observed immediately after the intervention.

    The researchers also collected open-ended feedback for program evaluation purposes. The participants completed a questionnaire about the program during the last group session and again at the 6- month follow-up.

    Description of the Intervention Program

    The format of the RA program was three group sessions accompanied by three videotapes and a manual. Because developing and using videotapes was not financially feasible in the MS study, the "Beyond MS" program was delivered in five group sessions and used only a manual. The manual contained readings and exercises designed to promote application of the content discussed in the group sessions. The topics covered in the sessions reflected the input of a focus group of women with MS who had evaluated the content of the original RA intervention program. In response to the focus group feedback, content was added related to coping with losses, uncertainty, depression, fatigue, and communication with health professionals.

    Session 1. The first session addressed the mind-body connection and ways to set reasonable boundaries on the demands and expectations of others (e.g., supervisors, coworkers, family, friends). Women with MS deal with disease-related fatigue on a daily basis, and must learn to balance the needs of others with their own needs and limitations. Common reasons for difficulties with boundary setting were addressed. Women with MS must set effective boundaries to avoid undue stress and energy loss resulting from controlling or manipulative relationships or from failure to recognize their own boundaries with respect to others. Many individuals exert a great deal of energy trying to control people whom they cannot control.

    Session 2. The discussion focused on the role of expectations, particularly negative or unrealistic expectations (e.g., perfectionism), in raising stress levels and how attributions about stressful events reflect a style of interpreting setbacks that can affect psychological distress and levels of optimism about the future. Common cognitive distortions also were discussed; these negative mental habits magnify stress by promoting anxious, pessimistic thought processes. The cognitive model for analyzing stressful situations was presented and applied (when requested) to specific situations presented to participants throughout the program.

    Session 3. The topic was managing fears. Fatigue and pain management techniques were reviewed to enhance participants' sense of control and self-efficacy. Cognitive refraining, a general stress management technique, was discussed and practiced.

    Session 4. Constructive methods of anger and depression management were discussed, as were flexible problem solving and creative approaches to stressful circumstances.

    Session 5. The discussion centered on ways to enhance social support, beginning with effective communication. Open, direct communication about boundaries, feelings, and the need for assistance and understanding can minimize stress in relationships. Common barriers to effective communication with healthcare providers were discussed. Finally, the facilitators provided practical information about dealing with insomnia.

    At each session, the women were encouraged to identify content that could be applied to their lives and to set goals and practice changes in behavior related to the issues they identified. Although the "Beyond MS" program is broad in scope, a central theme is reinforced throughout the reading material, manual exercises, and group sessions: Individuals have s\ome control over their response to an upsetting event or problem. This principle can be applied to any stressful situation. Altering one's attitudes, expectations, and thought processes to be more positive, confident, relaxed, and realistic can alter the response to a situation. By letting go of the aspects of the problem beyond their control and aggressively dealing with their mental approach and the more malleable aspects of the problem, individuals can lessen their stress levels. Although the relationship between stress and MS exacerbation is still under investigation, more effective stress management skills should improve psychological outcomes, regardless of whether exacerbations can be prevented. Facilitators encouraged the participants to examine whether changes in attitudes, expectations, thought processes, or communication patterns could affect their stress levels and promote more adaptive coping behavior. The emphasis was on aggressively addressing malleable stressors and reactions to stress in general. The program's positive tone is epitomised by the slogan "I have MS; it doesn't have me."

    Measures

    Data related to demographic and background variables (e.g., age, education, marital status, employment, race, length of time diagnosed with MS, medications) were collected at baseline. All of the following measures were completed by both cohorts at four different times, with the exception of the quality-of-life instrument, which was only used with the second cohort. All of these instruments have established validity and reliability, with extensive use in patient populations with chronic illness. The alpha reliability in this sample for all measures used in both cohorts is reported in Table 1.

    Personal coping resources. The Perceived Health Competence Scale (Smith, Wallston, & Smith, 1995) is an 8 item measure of the extent to which individuals perceive control over their health status in general. Scores range from 1 to 5; higher scores indicate greater perceived control over health conditions.

    Coping behaviour. The 28-item brief COPE (Carver, 1997) was used to assess situational coping patterns. The participants were instructed to select the frequency with which they used coping strategies to deal with problems in their lives, particularly fatigue and MS-related problems. Scores range from 1 to 4, with higher scores indicating that participants use the coping strategies more frequently. The 13 subscales in this instrument that were derived from the original COPE instrument measure self-distraction, active coping, denial, substance use, use of emotional support, use of instrumental support, behavioral disengagement, venting, positive refraining, planning, humour, religion, and acceptance.

    Psychological well-being. The 5-item Satisfaction with Life Scale (Diener, Emmons, Larsen, & Griffin, 1985) was administered, along with the 20-item version of the Positive and Negative Affect Schedule (PANAS; Watson, Clark, & TeUegen, 1988). Scores on the Satisfaction with Life Scale range from 1 to 6, with higher scores indicating greater life satisfaction. The PANAS contains two statistically independent, 10-item subscales assessing positive and negative affect. Participants were asked to record their feelings from the past week using the PANAS. Scores range from 1 to 5, with higher scores indicating greater frequency of a particular feeling noted within the past week. The negative-affect score from this instrument correlates highly with measures of depression (Smith, Wallston, & Dwver, 1995).

    Table 1. Scale Reliabilities Using Averaged Preintervention Scores

    Health-related quality of life. For the second cohort only, health-related quality of life was measured with an abbreviated version of the Multiple Sclerosis Quality of Life Instrument (MSQOL; Vickrey, Hays, Harooni, Myers, & Ellison, 1995). The MSQOL contains the SF36 (Ware & Sherbourne, 1992) and adds 18 items to cover the domains of energy, health distress, pain, social function, sexual function and satisfaction, and overall quality of life. We substituted the SF-12 (Ware, Kosinski, & Keller, 1996) for the SF- 36 to shorten the survey and lessen the burden on participants. The SF-12 provides reliable summary scores for both the Physical Component Summary and Mental Component Summary scales, reproducing at least 90% of the variance in the same summary scales using the SF- 36. Score ranges vary by item on the SF-12, but higher scores indicate greater functionality on the measure. Each of the summary scales is composed of weighted-item contributions associated with eight subscales designed to measure functional health and well- being. These eight subscales assess general health, bodily pain, physical functioning, role limitations caused by physical problems, role limitations caused by emotional problems, social functioning, mental health, and vitality. As a construct, health-related quality of life incorporates outcomes for both physical well-being (reflected in the Physical Component Summary scale of the SF-12 and several subscales of the MSQOL), and psychological well-being (reflected in the Mental Component Summary scale of the SF-12 and several subscales of the MSQOL).

    Physical well-being. All participants completed the 9-item Fatigue Severity Scale (Krupp, LaRocca, Muir-Nash, & Steinberg, 1989) to assess perceptions of fatigue intensity and its impact on their lives. Scores range between 1 and 7, with higher scores indicating greater fatigue levels.

    Results

    To test the first hypothesis (Le., the postintervention scores will reflect a positive effect on patients' perceptions of competence, coping behaviors, psychological well-being, healthrelated quality of life, and fatigue when compared to preintervention scores), the investigators used either t tests or multivariate analysis of variance (MANO VA) to compare pre- and postintervention mean scores. Multiple subscales or measures used with both cohorts were combined into appropriate indices for adaptive coping, maladaptive coping, and psychological well-being and used in within-subjects MANOVAs over four points in time, with subsequent univariate analyses of individual measures used when indicated.

    Table 2. Univariate Analysis of Measures of Maladaptive Coping

    An index of personal coping resources could not be constructed, because only one measure for this construct was used in both cohorts- perceived health competence. Comparison of averaged preintervention scores with averaged postintervention scores revealed that the perceived health competence mean of 3.41 (SD = 0.62) rose to 3.67 (SD = 0.69). This change indicated a significant improvement in perceived competence (t [33] = 3.16; p < .01). The effect size for this variable was 0.23.

    The Brief COPE contains 13 subscales that were derived from a longer version of the COPE, which was used with the earlier cohort. From a theoretical perspective, four of these subscales could be classified as maladaptive in this patient population-venting, denial, self-distraction, and behavioral disengagement. The other candidate for consideration in this index was substance abuse, but the wording of the items did not differentiate between use of alcohol and the use of prescription medications, which is useful and adaptive in this patient population. Therefore, the substance abuse subscale was not included in the Maladaptive Coping Index. The MANOVA results for the Maladaptive Coping Index were significant (F [3,29] = 3.85; p = .02), justifying exploration of univariate measures used in this index. Planned comparisons of averaged preintervention with averaged postintervention scores revealed significant decreases in two maladaptive subscales: self- distraction (t [34] = -2.40; p < .03) and venting (t [34] = -2.26; p < .04). Table 2 displays the preand postintervention means of the Maladaptive Coping subscales and the results of univariate analysis of these subscales.

    A separate Adaptive Coping Index was constructed from five theoretically adaptive subscales-active coping, positive refraining, planning, use of religion, and use of humour. Other subscale candidates for this index could be viewed as either adaptive or maladaptive and therefore were omitted. These subscales included acceptance, which could be adaptive or associated with passivity, as well as use of emotional support and use of instrumental support, which could be adaptive or associated with excessive dependence. The MANOVA results for the Adaptive Coping Index were significant (F [3,32] = 4.08; p < .02), justifying exploration of univariate measures used in this index. The subscale related to use of humor reflected significant improvement (t [34] = 2.3; p < .03). Table 3 displays the pre- and postintervention means of the adaptive coping subscales and the results of univariate analysis of these subscales.

    To measure psychological well-being outcomes, a Psychological Well-Being Index was created from the Satisfaction with Life Scale positive and negative subscales of the PANAS. These three measures of psychological well-being were combined into a Psychological WellBeing Index for the purposes of multivariate analysis. The MANOVA was significant (F [9, 222] = 2.30; p < .02). Univariate analysis of the individual measures of psychological well-being could therefore be explored. Using planned comparisons of averaged preintervention scores with averaged post intervention scores, the negative affect subscale of the PANAS reflected significant improvement (f [33] = -3.12; p < .01). The effect size for this variable was 0.24. Improvements in the positive affect subscale of the PANAS were nearly significant (f [33] = 1.97; p < .06). There were no significant changes in life satisfaction scores, although there was a trend toward greater life satisfaction. Table 4 displays the preand postintervention means for the three measures of psychological well-being and the results of univariate analysi\s of these measures.

    The MSQOL instrument was completed only by the second cohort (n = 19). Significant improvements were evident in this small sample. Averaged preintervention scores were compared with averaged postintervention scores, and the standard SF-12 algorithm was then used to compute the 8 subscales and 2 summary scales. There were no significant changes in the Physical Component Summary scale, but the Mental Component Summary scale (MCS-12) was significantly improved from a preintervention mean of 42 to a postintervention mean of 47 (t [17] = 2.32; p = .03). Although the SF-12 does not provide for reliable interpretation of changes in the 8 individual subscales, the summary scale interpretations are highly reliable and the MCS- 12 summary scale is highly correlated with three subscales-mental health, social functioning, and role limitations stemming from emotional problems (Ware, Kosinski, & Keller, 1996).

    Table 3. Univariate Analysis of Measures of Adaptive Coping

    Table 4. Univariate Analysis of Measures of Psychological Well- Being

    The MSQOL provides additional items related to health-related quality of life. Some of these scales also demonstrated significant improvement, despite the small sample size. Scores on the health- distress subscale reflected significant improvement (t [17] = - 5.09; p < .001), as did the satisfaction with sexual function subscale (t [16] = 2.14; p <.05).

    Other than the Physical Component Summary score from the SF-12, the only measure of physical outcomes used was the Fatigue Severity Scale. There were no significant improvements in fatigue severity scores, although the trend was in a positive direction, with the preintervention mean of 5.67 decreasing to a post intervention mean of 5.59.

    With respect to the first hypothesis, significant postintervention improvements were noted in perceived competence, adaptive and maladaptive coping indices, psychological well-being, and health-related quality-of life scores. There were no significant improvements in physical outcomes. The first hypothesis was basically supported in this pilot sample.

    With respect to the second hypothesis (i.e., compared to initial postintervention scores, 6-month follow-up scores will reflect stabilization or improvement), comparisons between initial postintervention scores and 6-month follow-up scores on perceived health competence, coping behaviors, psychological well-being, health-related quality of life, and fatigue did stabilize or improve. The second hypothesis was therefore supported. The one significant change, in the Maladaptive Coping Index, reflected continued improvement over the follow-up period (t [33] = -2.44; p = .02), primarily because of a continuation of decreases in scores on the venting and behavioral disengagement coping subscales.

    Preliminary Qualitative Analysis

    To help us collect open-ended feedback for program evaluation purposes, the participants filled out a questionnaire about the program during the last group session and at 6-month follow-up. There were four questions.

    "Which aspects of the program were most helpful to you?" There were four major categories of responses. The women stated that they (a) enjoyed being with other women who snared their concerns, fears, and frustrations and who could relate to their feelings; (b) enjoyed the type of social interaction the group promoted, particularly camaraderie and laughter; (c) learned a great deal from the program material and one another about managing stress and symptoms (because of the sharing of ideas and experience); and (d) gained hope for living a more normal life with MS.

    "Have you made any changes in your approach to challenges because of anything learned in the program?" Participants offered a wider spectrum of responses, as well as more specific responses. Their replies reflected nine types of changes: (a) they noted a more realistic acknowledgement and acceptance of their limitations; (b) they challenged unrealistic, perfectionistic expectations of themselves and thus were able to be more tolerant of themselves; (c) they set healthy boundaries on others who had unrealistic expectations of them; (d) they became more assertive in asking for help; (e) they tried to challenge negative, self-destructive thinking patterns; (f) they absorbed new tools for managing challenges (specifically, reframing); (g) they began to face their challenges with a more positive, optimistic attitude; (h) they noted more creativity in their approach to problem solving; and (i) they noted positive changes in friendships because of heightened tolerance and interpersonal sensitivity. One participant offered a concise summary of her new attitude toward her unpredictable disease: "I have MS. I can't really do anything about that. I am still a person who can contribute to society, and I just need to seek out my role and carry through with it. When the MS prevents me from doing what I want, so what? I may have to rest more during certain times, but that is OK, too."

    "Do you have any suggestions for changes in the program (either content or format)?" Several women would have preferred a longer program (i.e., more sessions). Some suggested that the manual and questionnaires be made available online for greater convenience. Some suggested that more time be devoted to discussion of homework questions. Comments regarding the manual were universally positive. The group members agreed that the 2-hour session time was appropriate. (Longer sessions would have been too tiring, particularly because they took place after many participants' work day.)

    "How satisfied were you with the program?" No one indicated dissatisfaction with the program in any way.

    Discussion

    The intervention was based on the Lazarus and Folkman Stress and Coping Model (1984), which underscores the pivotal role of perceptions in adaptation to stress. This model suggests that an intervention designed to enhance a sense of competence would positively affect appraisals of stressors, thereby affecting coping patterns and psychological outcomes. Consistent with the Lazarus and Folkman theory, our intervention apparently affected perceived health competence, coping behaviours, and subsequent psychological outcomes. A larger sample would enable exploration of path analysis to determine whether the direction of impact among the variables was also consistent with the theory.

    The intervention affected psychological outcomes in a positive manner. The improvement in the health distress subscale scores of the MSQOL was consistent with the change noted in the negative affect subscale of the PANAS. In addition, the positive affect subscale of the PANAS registered nearly significant improvement (p < .06). These findings were consistent with the significant improvements related to the Mental Component Summary scale of the SF-12, which reflects psychological well-being. This summary scale correlates highly with the three subscales related to mental health, social functioning, and role limitations stemming from emotional problems (Ware et al., 1996). The findings related to our measures of psychological well- being, including subscales from the health-related quality-of-life measure, were therefore consistent and theoretically predictable. The Satisfaction with Life Scale was the only measure related to psychological well-being that did not reflect improved scores, although there was a trend in a positive direction. The Satisfaction with Life Scale contains 5 items, including In most ways my life is ideal; IfI could live my life over, I would change almost nothing; and The conditions of my life are excellent. It is hard to imagine that a woman with MS would endorse these items in an extremely positive way. It is therefore not surprising that no changes were noted in the scores from this instrument.

    It is very difficult to positively affect physical outcomes when dealing with a progressive disease such as MS, so changes in reported fatigue severity were not expected. For the same reason, we were not surprised by the lack of improvement in the Physical Component Summary scale of the SF-12, which is focused on physical functionality. (Additional factors are that the intervention may have been too brief to elicit positive changes in fatigue levels and that it did not have an exercise component.)

    This pilot study had limitations related to the small sample size and relative homogeneity of the sample. The program needs further testing among both women and men who are in different stages of MS, as well as among members of different demographic groups, specifically less well-educated and more ethnically diverse participants. Circumstances did not allow us to use randomized wait- list control groups in this study. On a positive note, the intervention is theoretically based, it elicited a similar pattern of significant improvements in a sample of women with RA, and it demonstrated significant improvements despite the small sample size.

    The "Beyond MS" program resulted in significant improvements in perceived health competence, coping behaviors, and a variety of psychological outcomes in a relatively small sample. Furthermore, the program was cost effective, using a manual and five group sessions to deliver its outcomes. The "Beyond MS" program is positive in tone; it encourages aggressive action when change is possible and acceptance of the unchangeable. The group dynamic was positive. Participants felt free to express feelings, embracing the type of sharing and empathy mat can readily develop among individuals who face similar challenges. There is a great need for a positive program to promote adaptive coping in the MS population, and we believe "Beyond MS" has demonstrated its potential for effective use. The optimal psychosocial intervention program for individuals with MS, in terms of effectiveness and efficiency of delivery, might include features from several interventions dis\cussed in the literature. Future studies are needed to explore aspects of effective psychosocial interventions and their effect on various types of participants, so that interventions can be matched to the individuals most likely to benefit from them. The "Beyond MS" program was well received by our participants, and the findings warrant further investigation into its usefulness.

    Acknowledgments

    The authors gratefully acknowledge their funding sources. The initial program evaluation was supported by the Middle Tennessee Multiple Sclerosis Society and the Iota Chapter of Sigma Theta Tau Honorary Nursing Society. The pilot research study was funded by the National Multiple Sclerosis Society. The authors gratefully acknowledge Joseph Hepworth, PhD, for his statistical consultation on this project.

    Both RA and MS are progressive, highly unpredictable autoimmune conditions.

    Women with MS must set effective boundaries to avoid undue stress and energy loss resulting from controlling or manipulative relationships or from failure to recognize their own boundaries with respect to others.

    I Have MS. I can't really do anything about that I am still a person who can contribute to society, and I just need to seek out my role and carry through with it.

    References

    Ackerman, K. D., Heyman, R., Rabin, B. S.,Anderson, B. P., Houck, P. R., Frank, I., et al. (2002). Stressful life events precede exacerbations of multiple sclerosis. Psychosomatic Medicine. 64. 916- 920.

    Bandura.A. (1986). Social foundations of thought and action: A social cognitive theory. Englewood Cliffs, NJ: Prentice Hall.

    Bandura.A. (1998). Health promotion from the perspective of social cognitive theory, KycbolaRy and Health, 13, 623-649.

    Beatty, W. W. (1993). Cognitive and emotional disturbances in multiple sclerosis. Nennilogic Clinics, 77, 189-204.

    Brassington, J. C., & Marsh, N.V. (1998). Neuropsychological aspects of multiple sclerosis. Neumpsychalogy Rei'leie. 8. 43-77.

    Buelow.J. M. (1991). A correlational study of disabilities, stressors and coping methods in victims of multiple sclerosis.Journal of Neuroscience Nursing, 23, 247-251.

    Buljevac, D., Hop, W. C., Reedekcr.W., Janssens.A. C., van der Meche, F. G., va Doom, P. A., et al. (2003). Self-reported stressful life events and exacerbations in multiple sclerosis: Prospective study. Iirttisb Medical Journal. 327. 646.

    Carver, C. S. (1997). You want to measure coping but your protocol's too long: Consider the Brief COPE, / nlerneilioiieiljoiirnetl of Behavioral Medicine. 4(1), 92-100.

    Chwastiak, L., Ehclc, D. M., Gibbons, L. E., Sullivan, M., Bowen, J. D., & Kraft, G. H. (2002). Depressive symptoms and severity of illness in multiple sclerosis: Epidemiologic study of a large community sample. American Journal of Psycblaliy. 159. 1862-1868.

    Cohen, J. (1988). Statistical power-analysis for the behavioral sciences. Hillsdale, NJ: Erlbaum.

    Crawford,J. D., & Mclvor, G. P. (1985). Group psychotherapy: Benefits in multiple sclerosis. Archill's of Physical Medicine and Rehabilitation. 66, 810-813.

    Diener, E., Emmons, R.A., Larsen, R.J., & Griffin, S. (1985). The satisfaction with life scale. Journal of Personality Assessment. 49. 71-75.

    Foley, F. W., & Bedell, J. R. (1987). Efficacy of stress- inoculation training in coping with multiple sclerosis.Journal of Consulting and Clinical toychohgy. 6. 919-922.

    Frohman, E. M. (2003). Multiple sclerosis. Medical Clinics of North America. 87. 867-897.

    Gulick, E. E. (2001). Emotional distress and activities of daily living functioning in persons with multiple sclerosis. Nursing Research, 50, 147-154.

    Hainsworth, M. A. (1994). Living with multiple sclerosis: The experience of chronic sorrow. Journal of Nuuroscteiice Nursing, 26, 237-240.

    Hartings, M. F., Pavlou, M. M., & Davis, EA. (1976). Group counseling of MS patients in a program of comprehensive care. Journal of Chronic Diseases, 2V, 65-73.

    Holland, N. J. (2004). Clinical bulletin: Information fur health professionals. New York: National Multiple Sclerosis Society.

    Kroencke, D. C., Denney, D. K., & Lynch, S. G. (2001). Depression during exacerbations in multiple sclerosis:The importance of uncertainty. Multiple Sclerosis, 7. 237-242.

    Krupp, L. B., LaRocca, N. G., Muir-Nash, J., & Stcinberg.A. D. (1989). The fatigue severity scale: Application to patients with multiple sclerosis and systemic lupus erythematosus. Archives of Neurology, 46, 1121-1123.

    Kurtzke, J. F. (1983). Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Nenrolog), .13, 1444-1452.

    Larcombe, N. A., & Wilson, P. H. (1984). An evaluation of cognitive behavior therapy for depression in patients with multiple sclerosis. British Journal of Psychiatry. 145. 366-371.

    Lazarus, R. S., & Folkman, S. (1984). Stress, appraisal and coping. New York: Springer.

    Mathiowetz,V, Matuska, K. M., & Murphy, M. E. (2001). Efficacy of an energy conservation course for persons with multiple sclerosis. Archives of Physical Medicine anil Rehabilitation, 82, 449-456.

    McGuinness, S. (1996). Learned helplessness in the multiple sclerosis population. Journal of Nenroscience Nursing. 28. 163-170.

    Mindcn, S. L. (1992). Psychotherapy for people with multiple sclerosis. Journal of Nettropsycbiatry and Clinical Neurosciences. 4(2), 198-213.

    Mohr, D. C., & Cox, D. (2001). Multiple sclerosis: Empirical literature for the clinical health psychologist. Journal of Clinical Psychology, 57, 479-499.

    Mohr, D. C., Goodkin, D. E., Nelson, S., Cox, D., & Weiner, M. (2002). Moderating effects of coping on the relationship between stress and the development of new brain lesions in multiple sclerosis. Psychosomatic Medicine, 64. 803-809.

    Mohr, D. C., Hart, S. L., Julian. L., Cox, D., & Pelletier, D. (2004). Association between stressful life events and exacerbation in multiple sclerosis: A mcta-analysis. lirilish Medical Journal. 328, 731-741.

    Mohr, D. C., Likosky.W., Bcrtagnolli.A., Goodkin, D. E.,Wende, J. V, Dwycr, E, et al. (2000). Telephone-administered cognitive- behavioral therapy for the treatment of depressive symptoms in multiple sclerosis. Journal of Consulting and Clinical Psychology. 68, 356-361.

    Murray,T. J. (1995).The psychosocial aspects of multiple sclerosis. M?Hmlogic Clinics, 13. 197-221.

    Pavlou, M., Hartings, M., & Davis, EA. (1978). Discussion groups for medical patients. Psychotherapy and I'sycbosomalics. 30. 105- 115.

    Schiffcr, R. B. (1990). Disturbances of affect. In S.M. Rao (Ed.), Neiimbehavitmil aspects of multiple sclerosis. New York: Oxford University Press.

    Schwartz, C. E. (1999). Teaching coping skills enhances quality of life more than peer support: Results of a randomized trial with multiple sclerosis patients. Health Psychology. IH. 211-220.

    Schwartz, C. E., Coulthard-Morris, L.,& Zeng, Q. (1996). Psychosocial correlates of fatigue in multiple sclerosis. Archives of Physical Medicine and Rehabilitation. 77(2), 165-170.

    Schwartz, C. E., & Rogers, M. (1994). Designing a psychosocial intervention to teach coping flexibility. Rehabilitation Psycbology. 39, 61-76.

    Sinclair, V. G., Wallston, K. A., Dwyer, K. A., Blackburn, D. S., & Fuchs, H. (1998). Effects of a cognitive-behavioral intervention for women with rheumatoid arthritis. Research in Nursing & Health. 21. 315-326.

    Smith, C.A.,Wallston, K.A., & Dwyer, K.A. (1995). On babies and bathwater: Disease impact and negative affoctivity In the self- reports of persons with rheumatoid arthritis. Health Psycbolofy: 14. 64-7.1.

    Smith, M. S., Wallston, K. A., & Smith, C. A. (1995). The development and validation of the Perceived Health Competence Scale. Health Educalion Research: Theory and Practice. 10. 51-64.

    Spiegelberg, N. (1980). Support group improves quality of life. Rehabilitation Nursing, 5, 9-11.

    Stuifbergen, A. K., & Becker, H. (1994). Predictors of health promoting lifestyles in persons with disabilities. Research in Nursing and Health, 17, 3-13.

    Stuifbergen, A. K., Becker, H., Blozis, S., Timmerman, G., & Kullberg, V. (2003). A randomized clinical trial of a wellness intervention for women with multiple sclerosis. Archives of Physical Medicine and Rehabilitation, 84, 467-476.

    Stuifbergen, A. K., Scraphine, A., & Roberts, G. (2000). An explanatory model of health promotion and quality of life in chronic disabling conditions. Nursing Research. 49(3), 122-129.

    Van derWerf, S. P., Evers, A., Jongen, P.J., & Bleijenberg, G. (2003). The role of helplessness as mediator between neurological disability, emotional instability, experienced fatigue and depression in patients with multiple sclerosis. Multiple Sclerosis. 9(1), 89-94.

    Vickrey, B. G., Hays, R. D., Harooni, R., Myers, L. W., & Ellison, G. W. (1995). A health-related quality of life measure for multiple sclerosis. Quality of Life Research, 4, 187-206.

    Ware, J. E., Kosinski, M., & Keller, S. D. (1996). A 12-item short-form health survey: Construction of scales and preliminary test of reliability and validity. Medical Care, 34, 220-233.

    Ware, J. E., & Sherbourne, C. D. (1992). A 36-item short-form health survey (SF-36): Conceptual framework and item selection. Medical Care, 30, 473-483.

    Wassem, R. (1991). A test of the relationship between health locus of control and the course of multiple sclerosis. Rehabilitation Nursing, 16, 189-193.

    Wassem, R. (1992). Self-efficacy as a predictor of adjustment to multiple sclerosis. Journal of Neuroscience Nursing, 24, 224-229.

    Watson, D., Clark, L. A., & Tellegen, A. (1988). Development and validation of brief measures of positive and negative affect: The PANAS scales. Journal of Personality and Social Psychology, 54, 1063- 1070.

    Wineman, N. M., Durand, E. J., & Steiner, R. P. (1994). A comparative analysis of coping behaviors in persons with multiple sclerosis or a spinal cord injury. Research in Nursing & Health, 17, 185-194.

    Wineman, N. M., Schwetz, K. M., Goodkin, D. E., & Rudick, R.A. (1996). Relationships among illness uncertainty, stress, coping, and emotional well-being at entry into a clinical drug trial. Applied Nursing Research, 9(2), 53-60.

    Questions or comments about this article may be directed to Vaughn G. Sinclair, PhD APRN BC, Professor of Nursing, Vanderbilt University School of Nursing, 461 21st Avenue South, Nashville, TN 37240-0008 or via e-mail at [email protected]. She is a professor of nursing at Vanderbilt University School of Nursing, Nashville, TN.

    Jennifer Scroggie, MSN APRN BC, is an assistant professor of nursing at Vanderbilt University School of Nursing, Nashville, TN.

    Copyright 2005 American Association of Neuroscience Nurses 0047- 2606/05/3705/0000249$5.00(30/10/05)

    Related Items
    Bone Marrow Transplant Research
    Botox Research And News
    Complementary Therapies
    Diet
    Drugs
    Endo-parasites & 'Helpful' Organisms
    Environmental Factors And MS Research
    Ethnic Groups and MS Research
    Exercise
    Familial Risk of Multiple Sclerosis Research
    General Health
    General Research Articles
    General Research News
    Hyperbaric Oxygen Therapy Research
    Lightning Process® And Multiple Sclerosis Research
    Mercury Amalgam Fillings Research
    MS and Genetics Research
    MS Knowledge
    Myelin Research
    Neuropsychiatric and Psychological Research
    New Discoveries
    Optical Assessments and MS Research
    Other Conditions Research
    Paediatric Multiple Sclerosis Research
    Pain Research
    Pregnancy And MS Research
    Quality Of Life Research
    Sex
    Stem Cell Research & Treatment
    Vaccinations & MS Research
    Vitamin B12 Research
    Vitamin D Research & News


    Did you find this information useful? Would you like to comment on this page? Let us know what you think! We welcome all comments and feedback on any aspect of our website - please click here to contact us.