Social cognition may exert a central role in the daily lives of MS patients

An international team of multiple sclerosis (MS) researchers showed that longitudinal changes in social cognition are associated with psychological outcomes of daily living, suggesting that x. The article, "Social Cognition in Multiple Sclerosis: A 3-Year Follow-Up MRI and Behavioral Study" (doi: 10.3390/diagnostics11030484) was published on March 9, 2021, in Diagnostics. It is available open access at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001246/.

The authors are Helen M. Genova, PhD, of Kessler Foundation's Center for Neuropsychology and Neuroscience Research, and Stefano Ziccardi, PhD, Marco Pitteri, PhD, and Massimiliano Calabrese, MD, of the University of Verona. Dr. Genova also has an academic appointment at Rutgers University.

Some recent MS research, including work led by Dr. Genova, has shown that social cognition deficits may affect people with MS who otherwise have no other cognitive impairments. Social cognition, which is required to understand and process the emotions of others, is an extremely important skill set for forming successful relationships with others, and deficits in this area can significantly affect a person's quality of life.

Previous studies investigating the prevalence of social cognition impairment among people with MS suggested that impairment tracked with symptoms such as cognitive fatigue. More research was needed to clarify these results and determine whether changes to the area of the brain called the amygdala–known to be associated with emotions–correlated with social cognition. Moreover, no study had investigated the social cognition performance in people with MS with a longitudinal perspective, meaning that no data existed on the evolution of social cognition deficits over time.

In this three-year follow-up study, MS researchers conducted a longitudinal investigation of the evolution of social cognition deficits and amygdala damage in a group of 26 cognitively-normal people with relapsing-remitting MS. They analyzed the association between social cognition and several domains related to psychological well-being. Concurrently, they investigated the evolution of amygdala lesion burden and atrophy and their association with social cognition performance.

To gather data, the team used a battery of neuropsychological tests; social cognition tasks to assess theory of mind, facial emotion recognition, and empathy; and 3T-MRI to analyze structural amygdala damage. They then compared these findings to baseline data collected from participants three years prior.

The results confirmed that, despite being classified as cognitively normal, people with relapsing-remitting MS showed a significantly lower performance in several social cognition domains as compared to a matched group of healthy controls. These domains include facial emotion recognition, in particular fear and anger, as well as empathy. Longitudinal changes in the social cognition domain were also found to be associated with psychological outcomes of daily living, such as depression, anxiety, fatigue, and social functioning quality of life.

We confirmed the longitudinal stability of social cognition deficits in cognitively-normal people with relapsing-remitting MS, mirroring the amygdala structural damage and psychological well-being. These results confirm that social cognition exerts a key role in MS, affecting individuals' everyday lives. Our research highlights the need to identify treatments to improve social cognition in this population."

Dr. Helen M. Genova, PhD, of Kessler Foundation's Center for Neuropsychology and Neuroscience Research

Source:

Kessler Foundation

Journal reference:

Ziccardi, S., et al. (2021) Social Cognition in Multiple Sclerosis: A 3-Year Follow-Up MRI and Behavioral Study. Diagnostics. doi.org/10.3390/diagnostics11030484.

Posted in: Medical Research News | Medical Condition News

Tags: Amygdala, Anxiety, Biogen, Brain, Depression, Diagnostics, Disability, Evolution, Eye, Fatigue, Imaging, Laboratory, Medical School, Medicine, Multiple Sclerosis, Neuroimaging, Neuroscience, Research, Sclerosis, Traumatic Brain Injury, Virtual Reality

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Disease Progression and Therapy Response Vary in MS by Ethnicity

Multiple sclerosis (MS) affects Whites, African Americans, and Hispanics differently, a new study finds, and there are big gaps in how they respond to disease-modifying therapies (DMTs).

“Hispanics and African Americans develop a more severe disease course and accumulate more MS-related disability over time despite similar sociodemographic backgrounds and similar patterns of DMT use throughout their disease, suggesting that socioeconomic status and access to health care may not be the main determinants of health,” said neurologist Carlos Pérez, MD, of the University of Texas Health Science Center, Houston. He spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and in a follow-up interview.

“In addition,” Pérez said, “therapeutic responses to individual DMTs, as well as tolerance and side-effect profiles, are also variable among racial/ethnic groups.”

The researchers tracked 150 patients with MS at the University of Texas Health Science Center – 50 Whites, 50 African American, and 50 Hispanic – who were age and gender matched. The average age of the subjects was 45, and 74% of those in each group were women.

While educational levels between the groups were similar, African Americans had a much higher rate of lost employment because of disability (38%) than Hispanics (19%) and Whites (15%, P = .02). Fifty-seven patients (38%) needed escalation of therapy, and 63% were African American.

About 30% of subjects switched DMTs because of intolerance/adverse events, and 47% of those were African American. Interferons most commonly caused adverse effects in African Americans (61%), and Whites were the most likely to not tolerate glatiramer acetate (39%) than Hispanics (8%) and African Americans (13%).

What might be behind the disparities? “It is possible that genetic factors may play a greater role than previously thought. A recent study reported that Hispanic and African American patients with MS have higher levels of peripheral blood plasmablasts, which may provide indirect evidence for potential biological mechanisms underlying racial and clinical disparities in MS,” Pérez said. “These mechanisms appear to involve higher degrees of inflammation in the central nervous system. This may explain why African Americans may respond better to higher-efficacy therapies initially, when inflammatory processes predominate MS-related pathology, rather than at later stages of the disease when inflammation plays a less prominent role. Neurologists should consider higher-efficacy DMT as first line. We have begun to do this in our practice.”

Pérez said the findings offer other lessons. “Neurologists should consider that Caucasian patients tolerate glatiramer acetate less frequently, compared with other racial groups, and potentially consider using alternative DMTs unless the benefits outweigh the risks, such as during pregnancy.”

He also noted that African Americans treated with oral DMTs at baseline were more likely to develop worsening disability over time. “This argues in favor of infusion therapies as first-line treatment,” he said, adding that more Hispanics with MS were not on treatment – or discontinued treatment – compared with Whites and African Americans.

Close Patient Monitoring Is Key

Atlanta-area neurologist Mitzi Joi Williams, MD, who was asked to comment on the study findings, said in an interview that it “adds to the body of real-world evidence to assist understanding of MS in minority populations.”

She noted that African American patients who started on infusions appeared to be more stable. “There are a great deal of questions surrounding starting patients on injectables versus higher-efficacy therapy initially to prevent disability and this may lend credence to the need for closer examination of initial therapy for these patients. It is important to closely monitor patients and consider a switch in DMT if there is any clinical or radiologic progression, especially for African American and Hispanic patients since there is a great deal of data to suggest they may have more aggressive disease.”

Moving forward, more research like this is needed, she said. “Patients did all have insurance and were largely educated, but there could be other social determinants of health – i.e., transportation, lapses in insurance, or technology barriers – that may have led to worse outcomes.”

No study funding was reported, and Pérez reported no disclosures. Williams disclosed research support from EMD Serono, Genentech, and Novartis and advisory committee/consultant relationships with AbbVie, Biogen Idec, Bristol-Myers Squibb, EMD Serono, Genentech, Novartis, and Sanofi Genzyme.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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Infections — Especially Urinary and Kidney — Are Higher in MS

Each year, roughly 1 in 60 adult patients with multiple sclerosis (MS) aged 65 years and under is hospitalized with urinary or kidney infections, a new study suggests. That’s more than quadruple the rate in a control cohort. Other types of infections affected patients with MS at a higher rate too.

Dr Riley Bove

“The relative risk of all types of inpatient infections and most types of outpatient infections was significantly elevated among the patients with MS. While we expected there to be increased relative risk of urinary or kidney and respiratory infections, we also found higher relative risk of viral, fungal, skin, and opportunistic infections,” said study lead author Riley Bove, MD, an assistant professor at the Weill Institute for Neurosciences at the University of California, San Francisco, who presented the findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. She answered follow-up questions in an interview.

The researchers analyzed U.S. commercial insurer claim data from 2010 to 2019. They matched patients with MS (aged 18-64 years who had 2 or more diagnoses of MS at least 30 days apart and met other criteria) to controls who had diagnoses for any other condition at least 30 days apart and met other criteria.

A total of 87,755 patients were included in the study (mean age, 47.3 years; 75.7% female). In outpatient claims, urinary and kidney infections were the most common infections by far in patients with MS. They were also much more common than in the control cohort (14.23% vs. 7.82%; relative risk, 1.82; 95% confidence interval, 1.77-1.87; P < .0001).

Other results for outpatient claims — patients with MS versus controls — were: pneumonia/influenza (3.20% vs. 2.76%; RR, 1.16; 95% CI, 1.10-1.23; P < .0001), other respiratory/throat (30.31% vs. 30.05%; RR, 1.01; 95% CI, 0.99-1.02; P = .24), viral (6.83% vs. 5.74%; RR, 1.19; 95% CI, 1.15-1.23; P < .0001), skin (5.99% vs. 4.73%; RR, 1.26; 95% CI, 1.22-1.32; P < .0001), fungal (6.30% vs. 4.88%; RR, 1.29; 95% CI, 1.24-1.34; P < .0001), and opportunistic infections (1.02% vs. 0.68%; RR, 1.50; 95% CI, 1.35-1.66; P < .0001).

In regard to inpatient hospitalizations, the results for patients with MS versus controls were: urinary/kidney infections (1.60% vs. 0.36%; RR, 4.49; 95% CI, 3.98-5.08; P < .0001), pneumonia/influenza (0.77% vs. 0.35%; RR, 2.22; 95% CI, 1.94-2.54; P < .0001), other respiratory/throat (0.43% vs. 0.18%; RR, 2.37; 95% CI, 1.97-2.85; P < .0001), viral (0.23% vs. 0.09%; RR, 2.5; 95% CI, 1.99-3.36; P < .0001), skin (0.57% vs. 0.29%; RR, 1.95; 95% CI, 1.68-2.27; P < .0001), fungal (0.32% vs. 0.09%; RR, 3.69; 95% CI, 2.86-4.77; P < .0001), and opportunistic infections (0.07% vs. 0.04%; RR, 1.94; 95% CI, 1.26-2.97; P = .0024).

A Common and Treatable Condition

“Bladder dysfunction may be present in over 80% of persons in MS and can be a significant source of decreased function and quality of life in addition to increased health care costs and morbidity,” neurologist Barbara Giesser, MD, of the University of California, Los Angeles, said in an interview. “It is common among persons with MS to have bladders that do not empty urine completely. This can predispose them to bladder and kidney infections. Also, some patients may try to self-manage bladder symptoms by restricting fluids, and this can predispose them to infection as well.”

Giesser, who was asked to comment on the present research, advised neurologists to bring up urinary disorders themselves instead of waiting for patients to mention them. “Patients are often embarrassed to start a discussion about genitourinary dysfunction with their neurologists but will be very appreciative of the opportunity for it to be investigated and treated,” she said. “Neurologists should make sure that this area of neurologic function is addressed in the routine management of their patients with MS because bladder dysfunction, morbidity, and complications associated with it are treatable and preventable.”

For her part, Bove recommended “early and effective identification of risk, appropriate referral to first-line interventions such as pelvic floor physical therapy and patient education, and early referral to urologists skilled in treating neurogenic bladder. Further, it is important to monitor side effects of medications to ensure there are no unrecognized immune deficits.”

She also cautioned that “common symptoms of [urinary tract infections] in people with MS include symptoms that are also prevalent in neurogenic bladder: urgency, incontinence, and frequency. It is possible that having baseline lower urinary tract symptoms could mask the recognition of a urinary infection, resulting in delayed recognition and treatment of the infections.”

EMD Serono funded the study. Bove is funded by the National MS Society’s Harry Weaver Award. She has received research support from Biogen and Roche Genentech and consulting/advisory board fees from Alexion, Biogen, EMD Serono, Roche Genentech, Sanofi Genzyme, and Novartis. Giesser reported no disclosures.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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How is RRMS Different from PPMS and SPMS?

Multiple sclerosis is a neurodegenerative disorder that damages the nerves in the brain and spinal cord, leading to problems with muscle movement, balance and vision. The illness is an example of a demyelinating disease, where the protective coating called myelin that surrounds nerve fibres becomes damaged.

Multiple sclerosis follows a different course in every individual but there are three main ways in which the disease can progress depending on which form of the illness a patient has.

Relapsing remitting multiple sclerosis

Around 80% of all individuals with multiple sclerosis have the relapsing remitting form of the disease. These individuals have periods where their symptoms are mild or absent (remission), followed by periods of symptom relapse. Symptoms may occur suddenly and in acute bouts or exacerbations.

During these periods of relapse, symptoms may become worse each time and the relapsing remitting form of this condition may eventually progress to secondary progressive multiple sclerosis, where there are few or no periods of remission. Relapsing remitting multiple sclerosis may be diagnosed when two episodes of relapse are separated by more than 30 days or there has only been one relapse but there is MRI evidence of newly scarred or damaged myelin three months later.

Secondary-progressive multiple sclerosis

Patients with this form of multiple sclerosis often experience phases of relapse followed by remission at first, but this later gives way to progressive disease, characterized by worsening symptoms and few or no periods of remission.

Primary-progressive multiple sclerosis

The least common form of multiple sclerosis is the primary progressive form which occurs in about 10% to 15% of all cases and usually in people aged over 40 years. In this form of the condition, symptoms get worse over time rather than occurring in bouts or as sudden attacks.

Primary progressive multiple sclerosis may be diagnosed if there have been no previous symptoms of relapse but the patient has become increasingly disabled over a period of at least one year.

Sources

  1. http://www.nhs.uk/Conditions/Multiple-sclerosis/Pages/Causes.aspx
  2. www.nlm.nih.gov/medlineplus/tutorials/multiplesclerosis/nr229105.pdf
  3. http://www.who.int/mental_health/neurology/Atlas_MS_WEB.pdf
  4. http://mssociety.ca/en/pdf/ms-effects.pdf
  5. http://www.nice.org.uk/nicemedia/live/10930/29202/29202.pdf

Further Reading

  • All Multiple Sclerosis Content
  • Multiple sclerosis (MS)
  • Multiple Sclerosis Symptoms
  • Multiple Sclerosis Diagnosis
  • Multiple Sclerosis Causes
More…

Last Updated: Aug 23, 2018

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

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Functions of MHC in the Immune System

The major histocompatibility complex (MHC) is a group of genes that encode proteins on the cell surface that have an important role in immune response.

Credit: Juan Gaertner/Shutterstock.com

Their main role is in antigen presentation where MHC molecules display peptide fragments for recognition by appropriate T-cells. This is an important process in the immune system response for destroying invading pathogens.

The MHC complex on the cell surface is necessary for cell self-recognition and the prevention of the immune system targeting its own cells. Certain MHC alleles are associated with an increased risk of autoimmune disease such as Hodgkin’s lymphoma and multiple sclerosis.

Another function of the major histocompatibility complex is tissue allorecognition, an important factor in the prevention of successful organ transplantation.

MHC and antigen presentation

The MHC controls how the immune system detects and responds to specific antigens. Antigen specificity of T-cell recognition is controlled by MHC molecules with different antigen presentation between MHC class I and class II molecules.  

The two classes of MHC molecule have a similar function involving the delivery of short peptides to the cell surface for recognition by CD8+ and CD4+ T-cells respectively. MHC class I molecules present antigens that are intracellular or endogenous, whilst MHC class II molecules present antigens that are extracellular or exogenous. The MHC class I complex at the surface of the cell disconnects over time, leading to internalization into the endosome and entrance into the MHC class II pathway.

Cross presentation also occurs where MHC class I molecules present extracellular antigens to CD8+ T-cells. Degradation through autophagy can cause endogenous antigens to be presented by MHC class II molecules. Many viruses have evolved proteins that prevent antigen presentation by MHC molecules through the degradation or mislocalization of MHC molecules. Cross presentation is particularly important for responding to viruses that do not readily infect antigen-presenting cells.

MHC and autoimmunity

Certain MHC molecules are associated with an increased risk of autoimmune and inflammatory diseases. The MHC HLA-B antigens were first found to have increased frequency in patients with Hodgkin’s lymphoma in 1967. Other conditions associated with specific MHC molecules include multiple sclerosis, Crohn’s disease and rheumatoid arthritis.

A pooled analysis of MHC disease associations found that there is shared disease susceptibility to alleles that arise from HLA-DR4 haplotypes, indicating that there is both common and disease-specific associations between MHC and autoimmunity.

The mechanism behind the association between MHC and autoimmune disease has not been fully defined but is potentially reflecting a breakdown in tolerance to self-antigens in abnormal MHC class II molecule antigen presentation. Specific MHC class II alleles are therefore likely determinates of autoantigen targeting, resulting in disease association.

MHC and tissue allorecognition

Allorecognition is the ability of an organism to distinguish its tissues from those of another organism within the same species and has important implications for transplantation. A risk of organ transplantation is the alloresponse, where the histoincompatible antigen is recognized, producing an adaptive immune response via the employment of allospecific T-cells.

This can lead to rejection of the transplanted tissue. The MHC is involved in the direct mechanism of allorecognition where T-cells recognize determinants on the donor MHC molecule-peptide complex displayed at the cell surface. This is because the MHC molecules display an antigenic determinant called an epitope that is either self or non-self, with antigens from the transplanted cells recognized as non-self.  

To prevent an alloresponse in non-tolerant recipients, immunosuppressive drugs are provided but are known to cause long-term adverse effects. Increased understanding of the MHC role in tissue allorecognition may produce future targets for immunomodulation, reducing the requirement for long-term immunosuppression in transplant patients.

 

Sources:

  • The major histocompatibility complex and its functions.
  • British Society for Immunology: Antigen Processing and Presentation.
  • Towards a systems understanding of MHC class I and MHC class II antigen presentation.
  • Defining the Role of the MHC in Autoimmunity: A Review and Pooled Analysis.
  • Pathways of major histocompatibility complex allorecognition.

Further Reading

  • All Immunology Content
  • What is Immunology?
  • Classical Immunology
  • Clinical Immunology
  • Developmental Immunology
More…

Last Updated: Aug 23, 2018

Written by

Shelley Farrar Stoakes

Shelley has a Master's degree in Human Evolution from the University of Liverpool and is currently working on her Ph.D, researching comparative primate and human skeletal anatomy. She is passionate about science communication with a particular focus on reporting the latest science news and discoveries to a broad audience. Outside of her research and science writing, Shelley enjoys reading, discovering new bands in her home city and going on long dog walks.

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