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Disclaimer: 'MS Views and News' DOES NOT endorse any products or services found on this blog. It is up to you to seek advice from your healthcare provider. The intent of this blog is to provide information on various medical conditions, medications, treatments, for your personal knowledge and to keep you informed of current health-related issues. It is not a substitute for the advice of your physician. Should you or your family members have any specific medical problem, seek medical care promptly.

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Thursday, July 2, 2020

COVID-19: Preventive Measures in Multiple Sclerosis Patients and Others on Immuno-Modulators

Source: Centers for Disease Control and Prevention       -  Stay Healthy, Stay Home and Wash Your Hands

Disease-modifying therapies used to treat several immune-mediated disorders in neurology may make patients more susceptible to the novel coronavirus... 

Robert Fox, MDRobert Fox, MD
Updated April 7,2020: As the global COVID-19 pandemic continues to roll on, with over 350,000 confirmed cases of the novel coronavirus and over 10,000 deaths in the US, risk of contraction has become especially relevant within the neuroimmunology community. 

As many patients with multiple sclerosis, myasthenia gravis, and other neuroimmune disorders receive disease-modifying therapies (DMTs) that act on the immune system, they may face an increased risk of being infected with the virus and developing more severe symptoms.

With concern growing in the neurology community and beyond, NeurologyLive spoke to Robert Fox, MD, neurologist at the Mellen Center for MS and vice chair for research at the Neurological Institute at Cleveland Clinic, to learn more about what the hospital is doing to counsel patients through this time and provide guidance for staff to help prevent the spread of COVID-19.  

“At this point, the Mellen Center at the Cleveland Clinic is recommending that patients not cancel, interrupt, or delay scheduled doses of their MS medication. We believe that the way the medications work, the duration of action of these medications, and the risks of MS disease activity coming back are all reasons to continue MS therapies without interruption,” Fox said. “Given what we know about the current risks of COVID-19, MS therapy interruptions appear more likely to be harmful than helpful.”

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In response to the heightened concern, the National Multiple Sclerosis Society, with support from the Consortium of Multiple Sclerosis Centers and the Multiple Sclerosis Coalition, has released treatment guidelines regarding DMT use during the COVID-19 pandemic.1

Beyond strongly encouraging patients with MS to adhere to prevention guidelines from the CDC, the organization also recommends that patients continue treatment with their DMTs and discuss any specific risks directly with their MS care provider. In addition, the guidelines state that patients and their providers should strongly consider individual risk-benefit profiles before starting a cell-depleting DMT or a DMT associated with a severe increase in disability after stopping.1

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Severe COVID-19 in Multiple Sclerosis Linked to Disability Status, Age, Obesity

Source: Centers for Disease Control and Prevention       -  Stay Healthy, Stay Home and Wash Your Hands
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Notably, the cohort assessment did not identify a link between exposure to disease-modifying therapies and COVID-19 severity.

By: Matt Hoffman
Published: July 01, 2020


Dr Celine LouapreCéline Louapre, MD, PhD
In a recent attempt to understand the risk factors involved for patients with multiple sclerosis (MS) to possibly develop a severe form of the novel COVID-19 infection, results suggest that neurological disability, age, and obesity were all associated with severe infection. No link was observed between exposure to disease-modifying therapies (DMTs) and COVID-19 severity.1

Conducted by Céline Louapre, MD, PhD, of the Clinical Investigation Center, L'Institut du Cerveau et de la Moelle Épinière, and colleagues, the cohort study included 347 patients with MS. Infection severity was assessed on a 7-point ordinal scale ranging from 1—denoting no hospitalization with no limitations on activities—to 7—denoting death. There was a cutoff at 3 on the scale, which was defined as hospitalized and not requiring supplemental oxygen.

All told, 21% (n = 73) of patients had a severity score of ≥3, and 3.5% (n = 12) died from COVID-19. A higher proportion of those with a severity score of ≥3 had no DMT exposure (46%) compared to those with DMT exposure (15.5%; P <.001). As mentioned, age was independently associated with a higher risk of an infection severity ≥3 (odds ratio [OR] per 10 years: 1.9; 95% CI, 1.4–2.5), as was Expanded Disability Status Scale (EDSS) score ≥6 (OR, 6.3; 95% CI. 2.8-–4.4), and obesity (OR, 3.0; 95% CI, 1.0–8.7).

Notably, EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06), and then obesity (R2, 0.01). The median EDSS score was 2.0 (range, 0–9.5), and 81.8% (n = 284) of the population were receiving a DMT.

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“The identification of these risk factors could provide a rationale for an individual strategy of clinical management in patients with MS during the COVID-19 pandemic,” Louapre and colleagues wrote. “Risk factors associated with the severity of COVID-19 in patients with MS are unknown. DMTs may modify the risk of developing a severe COVID-19 infection, besides identified risk factors such as age and comorbidities.”

This registry, dubbed Covisep, is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. Those included were patients presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020.

“COVID-19 has significantly changed medical practice for several weeks, and it is likely to remain an issue for months,” the authors concluded. “Our data do not support an increased risk of a severe outcome associated with DMTs, which should reinforce the recommendation of not stopping current DMTs and not delaying treatment initiation in patients who have higher disease inflammatory activity, the risk for relapses, or subsequent disability.”

These results echo the previous understanding of MS specialists as well as add to the literature that has been collected thus far from other assessments. A number of neurologic complications have been observed in patients with COVID-19 infection, and the infection has shown links to conditions such as stroke.

In a recent NeurologyLive News Network series, Jiwon Oh, MD, PhD, assistant professor of medicine, Division of Neurology, University of Toronto, commented on the potential risk factors that may increase a patient with MS’s risk of acquiring coronavirus or complications of COVID-19. Watch below as she discusses what is being done in clinical practice to reduce a patient’s risk during the pandemic.

click here to read more and watch a video


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High-Contrast Visual Acuity Test and Optic Neuritis

Source: Centers for Disease Control and Prevention  -  Stay Healthy, Stay Home and Wash Your Hands
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Key opinion leaders discuss the importance of the high-contrast visual acuity tests to monitor for cognitive impairment in patients with optic neuritis subtypes. 

Robert Sergott, MD; Rod Foroozan, MD
PUBLISHED June 30, 2020




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CLICK here to read the discussion


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Targeting Bruton Tyrosine Kinase for Multiple Sclerosis Treatment

An in-depth look into the expanding landscape of multiple sclerosis treatments that target bruton tyrosine kinase. 

By: Jennifer S. Sun, PhD - June 30, 2020

Bruton Tyrosine Kinase (BTK), a Tec family nonreceptor tyrosine kinase1 critical for the development of B cells and several other hematopoietic lineages2 (except for T cells, plasma cells, and natural killer cells3), is a recent focus of therapeutics.4 BTK informs immune responses by acting as an early downstream amplification enzyme of the B-cell antigen receptor (BCR)5-8 and cytokine receptor pathways.8,9 BTK signaling influences antigen presentation on B cells10 and is essential to the production of antibodies, proinflammatory cytokines and chemokines, and cell adhesion molecules.11,12 Through these mechanisms, BTK helps transmit the signals that allow immune cells to respond to foreign antigens by targeting the cells presenting them for destruction.13-15

Harmful consequences arise when the immune system mistakes self-proteins as foreign antigens, with BTK promoting autoantibody secretion by autoreactive B cells.8,14,15 Autoimmune diseases such as multiple sclerosis (MS)16 result from this dysregulated production of autoantibodies, which leads to destruction of normal tissue.17 Malfunctioning BTK mutants have been linked to increased disease susceptibility, correlating with diminished numbers of mature B cells and immunoglobulin isotypes.18,19 BTK therefore serves as an important target for therapeutic agents that modulate innate immunity.

Interactions between T cells, B cells, and myeloid cells promote MS pathology,16 and BTK is a component of signaling events with a critical role in regulating hematopoietic cell circulation.20 MS is a chronic, inflammatory, demyelinating disease of the central nervous system21 and is the most common, nontraumatic, disabling neurological autoimmune disease, with approximately 2.3 million cases diagnosed worldwide.22 B cells contribute to MS pathogenesis as a result of being skewed toward a proinflammatory profile involving antibody production, antigen presentation, T-cell stimulation, production of proinflammatory cytokines, formation of ectopic meningeal germinal centers, and deposition of oligoclonal bands of immunoglobulin in areas of active demyelination.23-25 Briefly, the body’s immune system begins to attack myelin, a protective sheath covering nerve fibers. The nervous system is consequently “short-circuited,” potentially permanently.26

Treatments for MS aim to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability.27 The most well-studied type of therapy targeting B cells consists of monoclonal antibodies (mAbs) that deplete B cells through mechanisms of antibody-dependent cellular cytotoxicity and apoptosis.23 Rituximab, for example, a mAb targeting the B-cell antigen CD20, depletes B cells and reduces T cells in the cerebrospinal fluid. However, rituximab is incapable of penetrating the blood-brain barrier (BBB) or lymphoid organs and is unsuccessful in slowing disease progression.23,28 To overcome the limitations of mAbs,28 MS treatment efforts have turned to BTK inhibitors (FIGURE).29


The ideal BTK inhibitor would be a rapidly reversible, BBB-penetrant, highly selective, modulatory approach to target B-cell activation without widespread depletion of B cells.8,9,23,30,31 Rather, the B-cell response to BCR stimuli is lowered, tolerogenic B cells are maintained, and antigen-mediated proinflammatory activation is neutralized.8,12,15,31 BTK is already a target in treatment of lymphoma, leukemia, and rheumatoid arthritis via the prominent BTK inhibitor ibrutinib. However, ibrutinib exhibits off-target kinase-inhibitory effects and is associated with immunosuppression and bleeding complications.32-34 BTK inhibitors in development for chronic administration thus have more refined pharmacologic profiles, including high BTK selectivity and moderate clearance.29,35





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Ocrelizumab Compared to Glatiramer Acetate and Dimethyl Fumarate for MS

Jul 02, 2020 — Mark Freedman, MD, outlines a retrospective trial presented at the Consortium of Multiple Sclerosis Centers (CMSC) 2020 Meeting reviewing first-line ocrelizumab compared to glatiramer acetate and dimethyl fumarate for treatment of relapsing-remitting multiple sclerosis.

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Short-Commitment Dosing Regimen Gives Cladribine An Advantage in MS

The professor of clinical neurology, and director of the MS Division and Multiple Sclerosis Center of Excellence at University of Miami discussed the EMD Serono agent’s history and advantages for the patient community.


Dr Kottil RammohanKottil Rammohan, MD
In mid-2019, cladribine (Mavenclad; EMD Serono) was approved as an oral therapy for the treatment of relapsing multiple sclerosis (MS), as well as active secondary progressive MS. The synthetic agent targets lymphocytes and selectively suppresses the immune system, with the goal of depleting those lymphocytes in order to “reset” the system.

It was approved based on the data from a trial including more than 1300 patients with relapsing forms of MS, ultimately showing a significant decrease in the number of relapses experienced by patients who had ≥1 relapse in the previous year, compared to placebo. Its unique dosing regimen has offered patients a more convenient method of medication administration, and up to 10 years of data from its clinical development program, consisting of the CLARITY (NCT00213135), CLARITY-EXT (NCT00641537), ORACLE-MS (NCT00725985), and PREMIERE (NCT01013350) studies.

To find out more about how cladribine got to this point and what it offers the MS patient community, NeurologyLive spoke with Kottil Rammohan, MD, professor of clinical neurology, and director, MS Division and Multiple Sclerosis Center of Excellence, University of Miami.

NeurologyLive: Could you provide a brief overview of how cladribine got to this point through its development?

Kottil Rammohan, MD: It was after the discovery of the cause for the bubble babies who are born immunodeficient. And when those children were studied, what was found was they were perfectly normal in every way, except they had no lymphocytes. The lymphocytes were severely, severely depleted. Then the enzyme that was the basis of that abnormality was discovered to be adenosine deaminase—ADA—and adenosine deaminase deficiency led to the severe lymphopenia that was seen in these patients.

That gave the idea for Ernie Bueller and his colleagues at Scripps to potentially utilize this as a mechanism to deplete lymphocytes—they were looking mainly for hematological and oncological reasons to do it—and what they did was to put a chlorine molecule on deoxyadenosine and that literally recreated the ADA deficiency that was seen in these children. The molecule had the ability to be toxic to lymphocytes, and the beauty of it was that you could adjust the dose and control the lymphopenia. That was the beginning of cladribine, and cladribine became the drug of choice for hairy cell leukemia, a type of leukemia in which it was extremely effective, and then people started looking at the lymphocyte as a target for a variety of autoimmune disorders, including multiple sclerosis. The story goes that Ernie Bueller’s sister, who had multiple sclerosis, was treated by Jack Sipe from Scripps. It was an IV formulation—nobody knew the dose to use at the time—so a very large dose was used. But it clearly was effective in controlling progression of MS, and that led to a whole series of trials of the IV formulation until the tablet was discovered.

The tablet is about 40% efficient compared to the IV formulation. The dose is 60% more, so the comparable dose tablet will achieve the same thing as the IV formulation. So, it was very convenient.  The drug has a very short half-life, but in the time that is it is in the body, it goes after the lymphocytes, so the effect of the drug is long-lasting. Even though the half-life is only a few hours, the drug has a lasting effect on producing lymphocyte depletion.

Could you provide a brief overview of the CLARITY study and its extension?




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EEG Abnormalities in Acutely Ill Patients With COVID-19

COVID-19 alert
If you think you have been exposed to COVID‑19 and develop a fever and symptoms, such as cough or difficulty breathing, call your healthcare provider for medical advice. 
Source: Centers for Disease Control and Prevention       -  Stay Healthy, Stay Home and Wash Your Hands
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Preliminary findings from a retrospective sample series in the Bronx, New York.




Daniel J. Correa, MD, MScDaniel J. Correa, MD, MSc
Since the first reports of COVID-19 emerged, it became clear that beyond the respiratory and multi-system organ failure, with resultant mortality, SARS-CoV-2/ COVID-19 infection often involved brain and nerves.1-6 In a report of 214 patients from  Wuhan, China published in JAMA Neurology, neurological involvement was more common in severely affected patients with COVID-19 (45.5%) than those with less severe illness (30.2%), and included acute stroke, impaired consciousness, muscle injury, and rarely seizures (1 patient), or peripheral neuropathies.1 A retrospective comparison of patients who either had recovered and were discharged or were deceased showed more prevalent impairment of consciousness among those who were eventually deceased (22%) compared with those who recovered (1%).2 Altered mental status has been recognized as a neurological manifestation of acutely ill patients admitted with COVID-19; the multiple metabolic or cardiorespiratory disturbances, the progressing viral infection, cytokine storm, or coagulopathies contribute to the abnormal mental status. Awareness and recognition of neurological involvement is essential to guide treatment decisions as the pandemic unfolds.
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While there were several case reports of seizures (new onset or re-emergent) in patients with COVID-19,7 a report published in Epilepsia on a larger group of 304 patients from Hubei, China concluded that “there was no evidence suggesting an additional risk of acute symptomatic seizures in people with COVID-19.”8 Our experience has been somewhat different. In our hospital network in New York, which was at the epicenter of the COVID-19 pandemic in the United States, we encountered numerous patients with neurological manifestations, including patients with seizures. Whether direct transmission of the virus to the central nervous system (CNS) also plays a role in the CNS manifestations or seizures is unclear.

Offering quality care for patients with seizures and epilepsy during the COVID-19 pandemic has been the preoccupation of many physicians treating these patients and consensus recommendations have been made.9 The electroencephalogram (EEG) is one of the main tools used in the evaluation of patients with seizures and epilepsy. Limiting the risk of infection to the EEG technologists, while also offering adequate EEG studies for patients with seizures is important, and using simplified EEG montages has been proposed.10


CONTINUE Reading 


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Wednesday, July 1, 2020

Boosting Cellular Energy at Sites of Myelin Loss May Stop MS Progression

COVID-19 alert
If you think you have been exposed to COVID‑19 and develop a fever and symptoms, such as cough or difficulty breathing, call your healthcare provider for medical advice. 
Source: Centers for Disease Control and Prevention       -  Stay Healthy, Stay Home and Wash Your Hands
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Loss of myelin in nerve cell fibers — the hallmark of multiple sclerosis (MS) — leads to a shortage of mitochondria, a cell’s powerhouse, denying these damaged fibers the energy they need to work as intended, a new study shows.
Boosting the migration of mitochondria to affected nerve fibers, supplying them with needed energy, may help to protect nerves from degeneration and halt disease progression. Indeed, it may offer a new way of treating progressive MS.
MS is caused by the destruction of myelin, the fat-rich substance that wraps around and insulates nerve cell fibers (axons). Axons are projections of nerve cells that conduct the electric impulses that allow these cells to communicate.
To work as intended, damaged axons require large amounts of energy, which is provided by mitochondria. To compensate for the resulting energy imbalance, neurons respond by increasing their mitochondrial content. Mitochondria are small cellular organelles that work as the cell’s power plant: they produce energy molecules such as ATP, the most common cellular energy source.
However, in nerve cells of MS patients, mitochondria function is often affected. Evidence suggests people with progressive MS have genetic alterations that impair energy production.
A team led by researchers at the University of Edinburgh investigated whether targeting mitochondria in neurons could help mitigate the loss of myelin (demyelination). The study was supported by the National MS Society.
Researchers hypothesized that neurons would respond to demyelination by moving mitochondria from the neuron’s body to the damaged axon.
Real-time imaging of fluorescent mitochondria showed that in healthy neurons in mice — namely, in Purkinje neurons (found in the cerebellum, the center for motor coordination) and sensory dorsal root ganglia (DGR) neurons — mitochondria migrated into the region of the axon where demyelination was present. They named this process “axonal response of mitochondria to demyelination” or ARMD.
ARMD peaked at five days post-demyelination in the cerebellum neurons, and by day seven in the DGR neurons, showing that axons are vulnerable for a few days after myelin is destroyed, and the therapeutic window to target this response process is short.
Next, researchers evaluated several ways of enhancing mitochondrial numbers and migration. One was by boosting the levels of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-alpha), a key protein involved in mitochondria production. This boost led to an increase in the content and transport of mitochondria to axons, mimicking the ARMD process.
Based on this result, researchers tested pioglitazone, a type 2 diabetes medicine (sold as Actos, among other brand names) known to boost the PGC1-alpha pathway. The treatment was seen to recreate previous findings, with the therapy enhancing mitochondria transport to the axons.
“Taken together, these findings indicate the potential of targeting mitochondrial dynamics and biogenesis in neurons to enhance ARMD,” researchers wrote.
Since mitochondria function is deficient in progressive MS, namely in the complex IV (a key component for the production of energy), researchers evaluated whether ARMD could still be neuroprotective for neurons lacking sufficient complex IV.
They observed that in six out of 18 progressive MS cases analyzed, a positive correlation existed between complex IV deficient neurons and mitochondria content, area, and number. This supported the idea that, despite complex IV deficiency, neurons affected by MS still respond to demyelination by mobilizing mitochondria to their axons.
Researchers then developed a mouse model deficient for the complex IV (called COX10Adv mutant mice), and tested pioglitazone.
The treatment was given in the animal’s diet for six weeks. Results showed that mitochondrial content in axons increased significantly, and protected neurons from demyelinating lesions.


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Monday, June 29, 2020

Considerations for Wearing Cloth Face Coverings

If you think you have been exposed to COVID‑19 and develop a fever and symptoms, such as cough or difficulty breathing, call your healthcare provider for medical advice. 
Source: Centers for Disease Control and Prevention       -  Stay Healthy, Stay Home and Wash Your Hands
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Updated June 28, 2020


  • CDC recommends that people wear cloth face coverings in public settings when around people outside of their household, especially when other social distancing measures are difficult to maintain.
  • Cloth face coverings may help prevent people who have COVID-19 from spreading the virus to others.
  • Cloth face coverings are most likely to reduce the spread of COVID-19 when they are widely used by people in public settings.
  • Cloth face coverings should NOT be worn by children under the age of 2 or anyone who has trouble breathing, is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.





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Spiritual Well-being

  Stay Healthy, Stay Home and Wash Your Hands
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Spirituality may be thought of as that which gives meaning and a feeling of vitality to one’s life. When people connect with their spirituality, they feel centered, calm and energized. Spirituality is a powerful aspect of the human experience that can help fuel one’s efforts to achieve wellness in the face of life’s challenges and obstacles, including a diagnosis of MS.

Religious beliefs may or may not be central to a person’s spirituality. For some, religion is the driving force or organizing principle of their spirituality. For others, spirituality is reflected in their connection to nature, other people, art forms, or anything else that gives their lives particular meaning.

Many times in life people become aware of being on a spiritual journey, most often when confronted by a major shift or crisis. The Chinese character for crisis consists of two characters, one being for danger and the other for opportunity. Each crisis brings fears about the uncertain future but also opportunities for growth, including:
  • Becoming more self-aware
  • Discovering inner strengths and resources
  • Finding meaning in the challenge
  • Discovering greater balance, harmony and purpose
  • Changing feelings of powerlessness into feelings of creative strength
  • Finding opportunities for personal growth and increased resilience
  • Deepened, more meaningful relationships with others
If you imagine life as a path – and crises or challenges as detours along the way – the following resources can help you navigate the journey.

Recognizing the emotional impact

Grief is a natural reaction to loss. Whether it’s the loss of a loved one, a diagnosis of MS, a change in one’s ability function or any other disruption in one’s life path, healthy grieving is the first step toward healing. The grieving process sets the stage for goal-setting, creative problem-solving and personal growth. 

Identifying what drains you and sustains you

Dealing with changes and challenges takes energy. Given that fatigue is one of the most common and challenging MS symptoms, it is helpful to identify the things in your life that drain you physically and emotionally, as well as the things in your life that stimulate, fuel and replenish you.

Getting your priorities in order

When energy is limited and life’s challenges seem to create endless hurdles, it is helpful to prioritize the ways you spend your energy – both physical and emotional – and time. Focusing your energies on the things that are most important to you, and most in line with your goals and personal values, is part of staying on your spiritual path.

Connecting with your true self

Part of a spiritual journey is connecting with one’s true self – the self that recognizes and trust its own motives, emotions and ideas, recognizes its strengths and weaknesses, acts in ways that reflect personal values and needs, and allows true intimacy with others.

Building spirituality into your life

Daily life often feels too pressured to allow time for inner reflection, awareness of feelings – our own and others’ – and personal growth. Finding and maintaining one’s spiritual self involves carving out time and space to explore, nurture and refuel one’s inner self, to focus with intention on opportunities for change and growth and to remain open to new ideas, feelings and ways of interacting with the world.

Maintaining balance in your relationships

A person’s life challenges, including the unpredictable symptoms of MS, also affect close family and friends – at times altering the roles and responsibilities in a relationship, impacting shared activities, challenging intimacy, requiring a redefinition of shared plans and goals. Working to maintain balance and connection in valued relationships is part of one’s spiritual path.

Additional resources

Apps
  • Headspace: Guided Meditation and Mindfulness
  • Calm: Meditation to Relax, Focus and Sleep Better
Websites

Article produced by:   National MS Society


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