multiple sclerosis (MS) often spans a multidisciplinary care team to adequately manage the disease’s wide spectrum of symptoms and complications—such as the inflammation of the optic nerve, leading to optic neuritis and neuromyelitis optica (NMO).

Literature suggests that approximately half of patients receiving a diagnosis of MS will present with optic neuritis as the first sign of relapsing-remitting MS, whereas those with primary progressive MS are less likely to present with optic neuritis. A key identifier for neuro-ophthalmologists is pain accompanying eye movement, as well as swelling and other evidence of inflammation in the eye and optic nerve.

series titled “Management of Optic Neuritis,” a pair of specialists in neuro-ophthalmology discussed the diagnosis, management, and treatment of these patients, including discussion on therapeutic advances and anti-myelin oligodendrocyte glycoprotein (MOG) disease.

Although physicians treating optic neuritis had previously been quite limited in what they had available to treat the symptom, there are now nearly 2 dozen treatments to utilize. 

, chief of neuro-ophthalmology at Wills Eye Hospital in Philadelphia, Pennsylvania, noted that some patients are still treated with injectable therapy, such as glatiramer acetate or interferon, but many are also treated with oral medications and intravenous infusions.

“While we can prevent a lot of relapses now, where MS therapy needs to move to is how we repair damage,” he said. That area, he added, will be the focus for the next decade in therapeutic development. Advancements in therapy over the past 20 years have shifted what happens in the management of acute optic neuritis—particularly the spectrum of disease with NMO.

“It used to be we would lump all inflammatory optic neuropathy together that looked somewhat like MS,” 

, a neuro-ophthalmologist and associate professor at Baylor College of Medicine in Houston, Texas, said. “We now know that there are some variants and there’s a spectrum of disease. In the early to mid-2000s, a blood test became available for neuromyelitis optica,” Foroozan recalled, noting the discovery of a circulating IgG autoantibody reported in patients with NMO that was absent in those with MS, “which is an antibody to aquaporin 4, and that was a game changer because we could now define—by pathophysiology and identify with a blood test—those patients who were going to be at risk for a more progressive disease.”

Prior to the blood test becoming available, the general belief was that NMO was a variation of MS, despite the fact that the conditions differ greatly both diagnostically and therapeutically. In fact, Foroozan pointed out, some patients treated for NMO will not have an adequate response to traditional therapy for MS. Additionally, physicians were originally taught to only point to NMO if both optic nerves were involved.

Relatively soon after the identification of this antibody to aquaporin 4, physicians began to notice that individuals with more severe optic nerve involvement, poor vision bilaterality, simultaneous involvement, or longer stretches of enhancement of the optic nerve—extending into the optic chiasma, for example— differed immunologically in how inflammation occurred. Sergott noted that patients who do not improve with steroids often lead him to be very suspicious of NMO. In these cases, plasmapheresis can be used and has been with dramatic success.

NMO is a vicious disease. It’s just not a little worse demyelination,” Sergott said. “Beautiful work by Claudia Lucchinetti, MD, from Mayo Clinic has shown that this is a vasculitis that has special preference for the optic nerve, the retina, an area of the brain near the start of the spinal cord called the medulla, the area postrema, and for long segments of the spinal cord.”

Sergott noted that every patient in question should receive an NMO titer and an anti-MOG titer. He pointed to potential identifying symptoms, including uncontrollable hiccups caused by inflammation in the area postrema in the medulla and, rarely, long-lasting itching, which can present prior to vision loss.

As for imaging, Sergott and Foroozan explained that patients with optic neuritis require imaging in the spinal cord—both cervical and thoracic—to find asymptomatic lesions that stretch over several segments of the cord.

“There are patients who will have what’s called seronegative NMO,” Sergott said. “That is, the blood test will be negative, but they’ll have these clinical features or the neuroradiological features, and that’s still NMO.”

Foroozan explained that research on MOG revealed that a group of patients with optic neuritis were very responsive to steroids. These patients were found to be MOG antibody positive. In his experience, about one-third of pediatric patients who develop optic neuritis will have MOG antibodies present.

“Exactly what their role is in the pathogenesis of optic neuritis is not clear, but it is a marker in a group of patients, and that includes pediatric patients who develop optic neuritis,” Foroozan said. “And they can signify in older patients a risk for recurrent optic neuritis or what was previously termed CRION, for chronic relapsing idiopathic optic neuritis. Now we have a spectrum of disease that initially was only considered to be MS and now it has branched into at least 2 other forms, MOG and NMO.”

Sergott noted that a common tip-off for MOG disease is swelling on fundoscopic examination when the patient is unable to see, identifiable as optic nerve swelling and hemorrhages. He and Foroozan agreed that admitting these patients quickly is often best to acquire the proper imaging and see response. The pair explained that after between 3 and 5 days of intravenous steroids, if there is no improvement, it is justifiable to conduct plasmapheresis.

“Especially for the pediatric cases routinely admitted, 1 of the things I’ll look for is an early response to treatment,” Foroozan said. “We talked about a lack of response as being a marker maybe for NMO. One of the things that we’ll see with MOG is a very rapid response. If you’re getting a visual recovery within 24 to 48 hours with IV steroids, I’m very suspicious for MOG.”

Additionally, he added, with MOG there is this tendency for a perineural enhancement pattern to appear on MRI. When there is enhancement of the optic nerve extending into the orbital fat or around the optic nerve sheath, instead of just the nerve itself, that can be a strong indicator of MOG, or at least another type of inflammatory optic neuropathy.

“When I was in medical school, before we had MRI and before we had a lot of things, we thought MS was a rare disease,” Sergott said. “That is not true, and that happened because of MRI. Anytime we get better technology, we become better clinicians and can more precisely treat patients. The teaching, 5 years ago, was that NMO and anti-MOG were rare. I think they’re common.”

Articles

NeurologyLive Peer Exchange

Two experts in neuro-ophthalmology discuss the advances in the identification
and treatment of patients presenting with optic neuritis.

Steps Forward in the Management of Optic Neuritis

Scientific advancement within the field of multiple sclerosis (MS) is moving at a remarkably fast pace. This is demonstrated by the availability of new FDA-approved treatments that expand upon our current therapies, offering enhanced selectivity for key receptors, alternative delivery platforms that enable patients to be treated at home, and lower common adverse effect profiles. The field is also moving toward investigating individuals earlier in the disease course and studying utilization of medical resources prior to the diagnosis of MS, along with identifying the impact of approved treatments in extending the time to a first attack in radiologically isolated syndrome (RIS), new biomarkers that inform on neuronal injury, and enhancements in neuroimaging.

What does the future of MS look like? What are some practical challenges that clinicians are faced with beyond coronavirus disease 2019? Four key themes appear to be important: newly available treatments for MS; incorporating novel and innovative technologies to improve the diagnosis and management of patients; the need to transform how we communicate based on a new generation of patients; and leveraging technology for next-generation care.

At the time this piece was authored, 22 FDA-approved disease-modifying therapies (DMTs) with indications for clinically isolated syndrome, relapsing forms of MS, active secondary progressive MS, and primary progressive MS were available to patients. In the future, an expansion of whom we are able to treat may occur and approved therapies indicated for subjects with RIS may be defined. In addition, as the definitions of how we diagnose MS in patients evolve to include more biological measures as opposed to clinical and radiological-based metrics, it would not be impossible for us to consider that a treatment or regimen be recommended in individuals or families at high risk for the development of a first central nervous system demyelinating lesion.

Beyond these exciting opportunities for treating individuals much earlier or even before the onset of the disease course, a number of time-relevant issues exist. Do we really need more anti-inflammatory treatments? We currently have a wide-based selection of available therapies with differing mechanisms of action but none with scientific evidence for effective myelin or axonal repair. The field will be further challenged with demonstrating how any positive imaging indices suggestive of reassimilation or improvements in myelin integrity translate to a meaningful improvement in physical function. Also, how generalizable will any reparative trial data be to the spectrum of patients with MS that we care for?

A significant inflection point in the treatment landscape has also occurred recently with the introduction of generic dimethyl fumarate, further crowding the fumarate market given the availability of diroximel fumarate and monomethyl fumarate. As if understanding the vast array of differing treatments for MS was not enough for our patients, we are now challenged with providing additional education regarding the innate differences with therapies that are approved through a different FDA regulatory path, as well as corresponding with medical insurance companies to ensure that patients receive the exact treatment prescribed. The introduction of yet another approved generic treatment—whether another fumarate compound or new branded therapy having a similar mechanism of action to our existing therapies—expands the amount of education needed to fully understand the overt or subtle differences as well as the challenges to the infrastructures in place that work in getting our selected therapies approved for care.

Moving beyond medications that reduce clinical relapses, MRI advancement, and clinical disability, the field is also starving for effective and FDA-approved symptomatic treatments. Our patients continue to commonly struggle with symptoms that greatly impact their quality of life and employment. Fatigue, neuropathic pain, and cognitive difficulties are obstacles for many. Some available DMTs have been shown to reduce negative symptoms related to MS. However, it is not uncommon for patients to use over-the-counter or prescribed off-label agents for targeted relief. Having symptomatic treatments specifically indicated for use in MS will allow for a seamless process from prescription to medication possession.

MRI represents one of the cornerstones in the diagnosis and management of MS. More recent novel imaging approaches have revealed physiological alterations within lesions and in surrounding normal-appearing tissue, reductions in the integrity of cortical and central gray matter structures, along with intra- and perilesional characteristics that correlate with physical disability. Improving our ability to accurately recognize lesions related to inflammatory demyelination as compared to nonspecific white matter features is key. Newly developed imaging tools focused on 3-dimensional conformation, evaluating changes in shape, surface texture, and structure provide new insights into disease stability/advancement, enhancing conventional MRI data and allowing for the analysis of historic MRI data from phase 2/3 trials.

How we communicate the value of the newer generation of treatments or insights related to a personalized management plan may require an adjustment in our approach based not only on the age demographic of those we serve but accessibility of digital information, online platforms, and opinions from those connected in MS support groups. Medical care has evolved substantially over the past decade. Whereas patients would simply follow medical advice provided in the past, a movement beyond “trust but verify” seems to exist— with patients seeking additional opinions through family members or friends who also have MS, online searches, support groups, and social media. Patients also seem to self-diagnose more frequently and, to a greater extent, request a specific regimen for medical management. All in all, strategies used to educate and place patients at ease in the past may not be as effective in our current day-to-day practice.

Technology is expected to play a greater role in nearly every facet of MS care in the future. The hope is that through leveraging a variety of platforms, advancements specific to enhancing our diagnostic, surveillance capabilities, and medical care keep pace with the overall growth of technology outside of medicine. An expansion in the development of prescription digital therapeutics, or software prescribed similar to the prescription of medications at a pharmacy, is expected, and it appears easy to forecast in light of recent events that medical care, in general, is trending more toward visits that are not office based. In addition, artificial intelligence platforms designed by a variety of agencies are also currently evaluating outcomes related to MS by incorporating a wealth of traditional and nontraditional data in large MS datasets to reduce the seemingly randomness of MS.

In this special issue of NeurologyLive®, experts expand upon innovations related to the more accurate identification of MS lesions, how age demographics may play a key role in what and how we communicate, current clinical challenges that health care providers face in clinic as it relates to the wealth of treatment choices, the welcomed/unwelcomed introduction of generic therapies, how technology may change how we practice, and much more. The aim is to highlight key efforts that work toward providing better education and care that our patients with MS expect and deserve.

Letter From the Editor

Guest editor-in-chief Darin T. Okuda, MD, FAAN, FANA, details the fast moving field of multiple sclerosis and the direction the disease is moving towards in 2021. 

The Current and Future Outlook of Multiple Sclerosis

Ever since the approval of interferon beta-1b (Betaseron; Bayer) in 1993, there has been unprecedented growth in the number of disease-modifying therapies (DMTs) for multiple sclerosis (MS). We currently have 22 FDA-approved therapies with several more in the pipeline waiting to enter the market in the next few years. For a disease that has no known cause, no reliable biomarker to measure its activity, and no way of predicting which drug will work the best for a given patient, managing so many drugs for a single disease becomes a daunting task for both general neurologists and MS specialists.

The words of William Osler (1849-1919), the father of modern medicine and one of its greatest icons, have much wisdom: “A young physician starts life with 20 treatments for each disease, while the old physician ends life with 1 treatment for 20 diseases.” This is more relevant now than ever as we try to identify the most appropriate drug for each of our patients with MS, what and when to start, and when to switch. Our challenge is to balance the benefits against the potential adverse effects of high-efficacy drugs vs low- or moderate-efficacy drugs. Understanding the mechanism of action(s) of these drugs with their variable effects on the immune cells is crucial not only when initiating the drug therapy but also when switching the drug. The threshold for each has become quite low as we keep expanding the list of drugs from which to choose.

I cannot overstate the impact of these therapies on functional outcomes in patients with MS. I have been caring for patients with MS since before the first DMT was approved, and I can say with certainty that these drugs have made a huge difference in the way patients now lead their lives. I often tell my patients that MS is not what it used to be. They can now lead productive, healthy lives and achieve their goals. While it was not uncommon to see patients with MS in wheelchairs or using walkers before the first DMT was approved, now, I rarely see such patients. While there has not been a scientific study to prove this point, many senior MS experts I have spoken to agree that all the MS DMTs have improved patients’ quality of life.

Updates in the Management of Relapsing Multiple Sclerosis

For this to quality-of-life improvement to occur, however, physicians need to be proactive. We need to be guided by the patient’s prognostic criteria and then prescribe the most effective therapy as early as possible. Waiting until patients are clinically worse or their MRIs show increased disease burden may be too late. As such, physicians have an increased impetus to act swiftly in initiating a therapy as soon as the diagnosis is made to “save the brain.” Just as in stroke, time is of the essence in the management of MS. Inappropriate or delayed treatment can lead to irreparable harm. Some experts have posited, and I believe with some truth, that “in this day and age, if MS patients do not do well, it is more likely the fault of the treating physicians rather than of the disease’s progression.”

All of this places added stress on an already overworked physician. Physician burnout due to administrative overload is at record high. A recent study published in the 

showed that, for every hour physicians spend with a patient, they spend 2 hours doing administrative work, leaving little time for them to study the latest research updates. It is not unusual for physicians to return home from work late in the evening and spend the little time left in the day logging into the electronic health records system from home to complete clinic work that is still undone. There is hardly any time left to read journals—and even if they do have a little time, what would a general neurologist focus on? Research updates on Parkinson disease, stroke, epilepsy, MS, neuropathies, or headaches? A tremendous amount of progress has been made in all of these areas, as well as in many other diseases, but to grasp all of this information would require considerable time, which these physicians do not have.

Even though we currently have 22 approved therapies for MS, there are no textbooks, published guidelines, or algorithms for when a particular therapy for MS should be initiated or when to switch therapies. General neurologists who may not be well informed about newer drugs may resort to using more familiar drugs that have lower risk management strategies when a newer, more efficacious drug would have been preferable.

Multiple MS drugs means that each insurance company has its favorites based on rebates they receive from pharmaceutical companies, which may well dictate what physicians feel comfortable prescribing. Receiving a diagnosis is stressful in itself to a patient, but made even worse when they learn how much drug therapy may cost them. MS drugs are expensive, and their prices keep increasing each year, nearly tripling over the last 7 years.

 For example, when they were first approved in the 1990s, the cost of 1 year of therapy with interferon beta-1b, interferon beta-1a (Avonex; Biogen), and glatiramer acetate (Copaxone; Teva) ranged from $8000 to $11,000 per year; the same drugs now cost more than $75,000 per year, and the newer drugs cost even more.

All of this puts an added strain on physicians who have to “fight” with insurance companies to get approval for a drug they feel is most appropriate for their patient. While the insurance company’s main objective is to make a profit, the physician is focused on healing the patient. Even 1 millimeter of damage in the brain can destroy 11,000 nerve fibers. A major relapse can easily destroy millions of nerve fibers, leading to a permanent disability.

When this is explained to newly diagnosed patients, they usually understand the rationale for an early and most-effective therapy, rather than taking a chance of finding out later the severity of their disease—whether it be a more mild or a disabling form. It is time-consuming and stressful for a busy physician to convey this concept over and over again to insurance companies in order to get approval for a given drug. Study results show, without any doubt, that the first 5 years of the disease set the tone for the future course the disease may take, so it makes sense to start therapy early, as soon as the diagnosis is made, if not sooner, as in the case of clinically isolated syndrome.

The financial burden of treating this disease is enormous. For a disease that affects about 2.5 million people worldwide, the global MS drug market was valued at $25 billion in 2019 ($14.74 billion of that in North America) and is projected to reach $40.66 billion by 2027.

 As the cost of these drugs continue to skyrocket, the FDA has shown leniency toward getting more generic drugs on the market. However, this has resulted in minimal effects on the prices of medications, which have continued to escalate at about the rate they had before.

Higher prices translate to higher out-of-pocket costs for some patients, especially those with high-deductible health plans, resulting in high-priced therapies becoming inaccessible to some. Results of a recent National Multiple Sclerosis Society survey showed that 40% of respondents had “altered or stopped” DMTs for their MS due to high cost, and more than half were concerned about being able to continue to afford their medication in the coming years.

Generic medicines tend to cost less than their brand-name counterparts because they do not have to repeat animal and clinical studies that were required of the brand-name medicines to demonstrate safety and effectiveness. However, does it always make sense to choose a generic over the brand-name drug? For biological and complex nonbiological medications, this would be difficult to prove without a controlled study. Success in the development of a generic drug depends on the maker’s ability to offer a similar, safe, and effective product at a cost saving. Introduction of a generic version of Copaxone, which is among the most frequently prescribed MS drugs, did very little to lower the cost of that medicine.

An increase in the effective treatment armamentarium for MS is now capable of shutting down disease activity, but it has also propelled us to a threshold of a new frontier to conquer. For a disease that is highly heterogeneous and unpredictable, a personalized treatment is highly desirable. To provide better indicators for prognosis and treatment response, we need biomarkers that are readily available, reliable, and economical, and we need pharmacogenomics to help us navigate to the most appropriate therapy for a given patient. While the current DMTs prevent new lesion formation on MRI, they do not prevent delayed chronic neurodegeneration or bring about regeneration. Indeed, we may have reached a ceiling effect in our current class of drugs and will need to divert our efforts to repair and regeneration, which are the greatest unmet needs in MS therapy.

This is what I foresee as the next frontier to conquer in our fight against MS.

1. Arndt BG, Beasley JW, Watkinson MD, et al. Tethered to the EHR: primary care physician workload assessment using EHR event log data and time-motion observations. 

. 2017;15(5):419-426. doi:10.1370/afm.2121 
2. Hartung DM, Johnston KA, Geddes J, Bourdette DN. Effect of generic glatiramer acetate on spending and use of drugs for multiple sclerosis. 

. 2020;94(13):e1407-e1414. doi:10.1212/WNL.0000000000008936 
3. Multiple sclerosis drugs market size, share & COVID-19 impact analysis, by drug class (immunomodulators, immunosuppressants, interferons, and others), by route of administration (oral and injection (intramuscular, subcutaneous, and intravenous) by distribution channel (hospital pharmacy, retail pharmacy, online pharmacy), and regional forecast, 2020-2027. Fortune Business Insights. Published July 2020. Accessed October 10, 2020. https://www.fortunebusinessinsights.com/industry-reports/multiple-sclerosis-drugs-market-100386 
4. New survey shows 40% of people with MS alter or stop taking medications due to high cost. News release. National Multiple Sclerosis Society; January 13, 2020. Accessed October 10, 2020. https://www.nationalmssociety.org/About-the-Society/News/New-Survey-Shows-40-of-People-with-MS-Alter-or-Sto 

Features

“Is more always better?”: The age-old question is more relevant than ever as clinicians and patients alike navigate an increasingly crowded MS treatment landscape.

Navigating an Expanding Treatment Toolbox for MS

The onset of multiple sclerosis (MS) is commonly seen between age 20 and 40 years, making the millennial generation (aged 24-39 years in 2020) the most likely generation to develop MS in the coming years. As a cohort, millennials manage their health differently from the generations before them and thus will value and expect different things when it comes to their MS care. Furthermore, these differences may create new challenges for the health care team. Current MS practice must adapt to engage this unique generation and create innovative solutions tailored to their specific needs and desires. Doing so could afford this generation better prognostic outcomes as a result of increased engagement and disease management.

The defining quality of the millennial generation is their use of technology, although some may describe it as a dependence. Millennials are digital natives, meaning they are the first generation to grow up with the internet, and they integrate technology throughout multiple aspects of their everyday lives. Ninety-three percent of millennials own a smartphone, and nearly 100% use the internet.

 Furthermore, the millennial generation is the most educated generation yet, with 36% of millennial women and 29% of millennial men holding at least a bachelor’s degree as of 2017.

Their education and tech savviness enable millennials to leverage technology to better manage their health. In fact, 55% of millennials said they believed health-related information on the internet is as reliable as information from medical professionals, more than any other generation.

 Providers should value this personal motivation to seek out health information and continue to encourage patients’ self-learning. The advantages of easily accessing a multitude of information from a wide variety of sources on the internet, however, must be balanced with an understanding of the differing degrees of validity between sources. Less than half of millennials were concerned with finding false or misleading health data on the internet, the lowest percentage among all generations.

 Pointing patients toward trusted sources of information is an important first step to help encourage a credible knowledge source for these patients and to create a shared knowledge base between patient and provider. Equipping millennial patients in this way will emphasize their autonomy and facilitate shared decision-making between the patient and provider.

Building Trust to Enhance Patient Counseling

Current trends demonstrate an overall lack of trust in medical doctors by millennials; less than half of millennials were very satisfied with information from their doctor.

 Additionally, millennials were the least likely generation to respond, “I always listen to my doctor(s)” compared with other generations. Medical providers can build trust by understanding the communication strategies that millennials prefer.

As digital natives, millennials expect easy accessibility, rapid turn-around, and direct communication.

 Easy online appointment scheduling, short wait times, and online patient portals where patients can access their results and communicate directly with providers are examples of baseline logistics that health care providers can implement to start off on the right foot with their millennial patients. Millennials also value medical information directly from their peers: 4 out of 10 millennials trust their peers more than they trust medical professionals when it comes to their health.

 Providers can build off this heightened trust in social circles by utilizing young adult patient support groups to allow millennial patients with MS to share their experiences and learn from their peers. Highly versed in social media platforms, this generation could transform patient advocacy both locally and globally.

Using social media as a way to engage millennial patients with MS can be effective if done correctly. Millennials do, however, have a healthy dose of skepticism when it comes to health information on social media specifically. While 67% of Americans reported seeing health information on social media, only 35% said the information was even “mostly accurate.”

 Curated social media content from providers and clinics should emphasize the validity of the content by referencing studies, citing a trusted school or research organization, or including explanations directly from a medical professional. Consistency in communication style and content is key to bridging the gap between millennial patients and health care providers.

It would be a disservice to all patients not to note the complex impact of race on mistrust in the medical profession specifically.

 Ramifications from historic unjust medical practices continue to influence current medical practice, exemplified by the decreased participation in clinical trials by minorities due to the influence of the US Public Health Service Syphilis Study at Tuskegee (commonly known as the Tuskegee Syphilis Study).

 Because the millennial generation is the most diverse population in America, with minorities making up almost half of the population

 mistrust in medical providers and medical institutions may be heightened within the millennial cohort. It is imperative for providers to understand the history of racism in American medicine and the complex ways in which it influences patients today. Establishing a shared understanding of these health injustices with millennial patients can help rebuild trust one patient at a time.

Millennials are the most cost-conscious generation yet, and understandably so; millennials have higher levels of student loan debt, poverty, and unemployment rates than the 2 previous generations— Generation X and baby boomers—had at the same stage of their life cycles.

 This economic strain leads millennials to often cut corners when it comes to their health care, a dangerous trend when diagnosed with a chronic, progressive disease like MS. More than half of millennials admit to delaying or avoiding medical treatment due to cost.

 It is well known that the cost of MS care is substantial, and MS-specific health care costs have been shown to increase with disease severity. Those with mild to moderate disease severity spent an average of $30,000 on health care costs per year compared with $100,000 per year for those with severe disability.

 Therefore, a key strategy to decreasing overall costs for millennial patients is emphasizing disease prevention. For example, although disease-modifying therapies (DMTs) often account for the majority of MS-related health care costs due to their high price tags, an effective DMT is a patient’s best resource for preventing the frequency and severity of relapses and for slowing disease progression. Emphasizing the cost-saving strategy of disease prevention from the day of diagnosis is important to encourage millennials with MS to invest in their health care. As
new DMTs continue to be developed, often with greater efficacy at the expense of higher costs, it is imperative for providers to navigate costs with millennial patients when making treatment decisions. Treatment plans need to be individualized and align with each patient’s unique values and goals, as well as financial feasibility. These cost conversations should be initiated by providers to demonstrate a common understanding of the immense financial burden that an MS diagnosis entails. There is also a clear, increased need for financial advisers within MS practices to help millennial patients financially plan for lifelong MS health care costs.

Millennials report the worst mental and behavioral health outcomes compared to any prior generation.

 Compounding these trends is the increased prevalence of mental health disorders among the MS population in general. Patients with MS are 3 times more likely to experience anxiety or depression compared with the general population.

 Furthermore, inequity in mental and behavioral health prevalence has been seen among different demographics. In a survey of 1500 individuals, people who identify as LGBTQ+ were 3 times more likely to experience a mental health condition. Black and Hispanic respondents were more likely to experience every mental and behavior symptom assessed in the study compared with the study population as a whole.

Because millennials are the most diverse generation to date, MS providers should understand the increased burden of mental health on this generation as well as the unique experience of specific millennial demographics. Increased collaboration with mental health providers is imperative to providing quality MS care to millennial patients. Incorporating standardized depression and anxiety assessments into clinic workflow can equip providers to track mental health outcomes in their patient populations over time and serve as a launching point for provider-initiated conversations about mental health. Quality MS care must not only treat this unpredictable disease, but also adequately address the multiple disease sequelae experienced by patients, including mental and behavioral health.

Millennials are a technologically savvy, cost-conscious, diverse, and educated population who experience unique financial and mental health burdens compared with previous generations. Their distinctive characteristics drive change across multiple different sectors, including health care, and these changes create ripple effects across all generations. For example, millennial demand for technology has led Generation X and baby boomers to increasingly adopt technological platforms in their own lives.

 Early analysis of the youngest generation, Generation Z (those born after 1996), signal similar preferences to millennials, only heightened.

MS care not only needs to adapt to better serve millennial patients with MS, but to adequately serve
all generations past, present, and future. Innovative solutions geared specifically toward millennials will allow for increased patient engagement now and in the years to come.

1. Vogels EA. Millennials stand out for their technology use, but older generations also embrace digital life. Pew Research Center. September 9, 2019. Accessed October 12, 2020. 

https://www.pewresearch.org/fact-tank/2019/09/09/us-generations-technology-use/

2. Fry R, Igielnik R, Patten E. How millennials today compare with their grandparents 50 years ago. Pew Research Center. March 16, 2018. Accessed October 13, 2020. 

https://www.pewresearch.org/fact-tank/2018/03/16/how-millennials-compare-with-their-grandparents

3. Weber Shandwick and KRC Research. The great American search for healthcare information. November 13, 2018. Accessed October 12, 2020. 

https://www.webershandwick.com/wp-content/uploads/2018/11/Healthcare-Info-Search-Report.pdf

4. Waljee JF, Chopra V, Saint S. Mentoring millennials. JAMA. 2020;323(17):1716-1717. doi:10.1001/jama.2020.3085

5. Sullivan LS. Trust, risk, and race in American medicine. Hastings Cent Rep. 2020;50(1):18-26. doi:10.1002/hast.1080

6. Scharff DP, Mathews KJ, Jackson P, Hoffsuemmer J, Martin E, Edwards D. More than Tuskegee: understanding mistrust about research participation. J Health Care Poor Underserved. 2010;21(3):879-897. doi:10.1353/hpu.0.0323

7. Millennials in adulthood. Pew Research Center. March 7, 2014. Accessed October 13, 2020. 

https://www.pewsocialtrends.org/2014/03/07/millennials-in-adulthood

8. Five ways tech-savvy millennials alter health care landscapes. News release. PNC Healthcare. March 23, 2015. Accessed October 13, 2020. 

https://www.prnewswire.com/news-releases/five-ways-tech-savvy-millennials-alter-health-care-landscape-300054028.html

9. Owens GM. Economic burden of multiple sclerosis and the role of managed care organizations in multiple sclerosis management. Am J Manag Care. 2016;22(suppl 6):s151-s158.

10. APA Stress in America survey: Generation Z stressed about issues in the news but least likely to vote. News release. American Psychological Association. October 30, 2018. Accessed October 13, 2020. 

https://www.apa.org/news/press/releases/2018/10/generation-z-stressed

11. Beier ML. Multiple sclerosis and mental health: 3 common challenges. Johns Hopkins Medicine. Accessed October 13, 2020. 

https://www.hopkinsmedicine.org/health/conditions-and-diseases/multiple-sclerosis-ms/multiple-sclerosis-and-mental-health-3-common-challenges

12. Mind Share Partners. Mental Health at Work 2019 Report. Accessed October 13, 2020. 

https://www.mindsharepartners.org/mentalhealthatworkreport

13. Parker K, Igielnik R. On the cusp of adulthood and facing an uncertain future: what we know about Gen Z so far. Pew Research Center. May 14, 2020. Accessed October 13, 2020. 

https://www.pewsocialtrends.org/essay/on-the-cusp-of-adulthood-and-facing-an-uncertain-future-what-we-know-about-gen-z-so-far/

Effectively navigating the nuances of this unique patient population will ultimately help drive innovative solutions for this generation and those to come.

Managing MS in Millennials

that has occurred over the course of the coronavirus disease 2019 (COVID-19) pandemic has shined an even brighter light on the already recognized care access challenges faced by patients with chronic, debilitating diseases such as multiple sclerosis (MS)—one that often requires repeat clinic visits and consults with a large team of health care professionals. With many of those visits now taking place virtually out of necessity, it has added support to the argument that there is a “clear and tremendous” need for more digital and telehealth-based interventions in MS.

This has long been the focus of clinical neuropsychologist Leigh Charvet, PhD, of the division of MS at NYU Langone Health in New York, who told 

that when these digital interventions are brought home to patients, clinicians reach a much broader spectrum of people living with MS—a highly important facet for research. Access to these resources, she said, underscores the demand for symptomatic management and rehabilitation, areas of treatment that often fall second to relapse prevention despite their immense impact on patient quality of life. To learn more about the digital therapeutic landscape and telemedicine’s place in the future treatment of MS, 

: Can you describe the evolution of your research into digital, home-based interventions for patients with MS?

: My entry into this world was with cognitive remediation, which we know that we need a lot of training to do. That’s probably one of the early therapies that has very well designed and accessible computer-based or online-based training. That was really our first entry into this, to send people computers to their home and supervise them remotely to complete our first trial. They did 60 sessions over 12 weeks, so you could just imagine that that wouldn’t have been able to be done if they were coming to clinic. In general, with cognition, we also think of what a lot of times we call the “invisible symptoms” that have such a burden on day-to-day living for so many people. That definitely includes fatigue, and things like pain, and emotional distress is another huge component for many of us. Our approach has been to evaluate computer-based or app-based interventions targeting these symptoms remotely, and we do that because we can reach many more people and provide the adequate number of treatment sessions.

Our particular focus moved from that cognitive rehabilitation trial to evaluating the use of noninvasive brain stimulation, in particular, something called transcranial direct current stimulation (tDCS). That’s in the world of noninvasive brain stimulation therapies, but it can be portable and wearable. We knew that we could reach people in their homes, so we developed a whole protocol where we do live video visits to help people self-administer, with supervision, tDCS. The idea with tDCS is it may be therapeutic on its own. For instance, it is approved in many countries for the treatment of depression, but we’re particularly interested in its ability to boost rehabilitative outcomes. The idea is that pairing the stimulation while you’re doing a training activity may boost the benefit of the training activity. We took our cognitive remediation that we had established and then added tDCS to that.

That also brought us into the world of some motor rehabilitation. For instance, there is an established at-home hand exercise program to strengthen and recover hand function, where we’re actually adding tDCS to that right now in the clinical trial. We’re also very interested in types of exercise, physical therapy, and aerobic exercise at home paired with the brain stimulation to see if we can boost the benefit of that training activity.

We’re interested in its benefits for fatigue, in general. There are a lot of parameters on how to use it, and in our research program, we’re sending it home. And with our absolutely amazing patient participants who are true collaborators, we’ve designed a platform where we can reach people in their homes and have the high volume of sessions and sample sizes needed to really evaluate these emerging therapeutics. In that work, what we’ve seen is that people are able to do what would seem on paper to be very complicated procedures in their homes with supervision. We’ve learned how to take on the technical burden on our side, and then guide people to be able to do these therapies very successfully in their homes.

How easily could these interventions be incorporated into standard care that patients with MS receive?

I think we’re pretty close to that, but there are a lot of these emerging therapeutics—and this is not specific to MS, especially as these things are computer-based—where there’s a disconnect between a provider or therapist telling a patient, “Here’s something that you can access that will help you,” and then the patient actually doing that. We all know that you should go to the gym every day, but if I don’t have a personal trainer or somebody watching me, I’m not going to do it. It’s hard to change the behavior. Because of the brain stimulation part with tDCS, we are live with patients through video visits every time. That’s really helped to have that behavioral adoption of the daily treatments, and I think that is a critical ingredient, that there is this supervised, connected onboarding of these daily therapies. There are all these wonderful tools out there, and many of them need more research, but the uptake is not there yet, and I think that connection is necessary for wider-scale adoption and people truly benefiting from these therapies.

What kind of barriers to adoption of these therapies have you experienced from both patients and the clinical community?

There are 2 types of pushback; 1 is awareness. Raising awareness for your patients of this tool does not mean that they’ll use it and benefit from it. That’s a common experience for a provider. Maybe [the provider] is aware of the tool, they refer their patients who then have the tool, but they hear, “Oh, I looked at it twice, and I didn’t do it.” There’s that critical period of structured onboarding, how to use it, in order to have an adequate evaluation. I think that causes premature dismissal of some things that are actually of great therapeutic benefit. Second, despite moving the dial on the acceptability of telehealth at a lightning rate because of COVID-19, there’s always been the pushback of “people can’t do that.” [Excuses like] my patient isn’t computer or tech savvy, or my patient has too much cognitive involvement or too many motor impairments to be able to do that. However, if you take care of designing the intervention, those are all easily overcome, and that’s what we found in our journey with our program.

Do you anticipate that more MS centers will adopt these interventions for at least some patients as they are validated?

Well, the short answer is absolutely. But I think what you raised is the critical piece, in terms of validation. What happens is, you have a glut of apps and online programs, and some are very science based. They take what we know from in-person therapy and make it into a digital therapeutic for access. Others are very different, and it’s hard for the consumer—it’s hard for the researcher—to tell the difference sometimes between what is what. We need carefully controlled clinical trials to guide our use because nobody wants to tell anybody to use something, to put the time into something, that hasn’t been demonstrated to be worth their time. I don’t think it would replace anything that we do now. We have our provider care, our nursing support, our social worker support, our therapists—physical, occupational, all kinds of therapists that we work with. That’s already comprehensive care on-site, but this would supplement it because we know that so many people in between these visits still have significant burden of disease, primarily with these symptoms for which there aren’t any tools to readily manage them. Therefore, access to these digital therapeutics might fill that need.

How might these digital and telehealth approaches influence data collection for the study of the MS population?

It will absolutely have a positive effect in getting therapies evaluated for what we call pragmatic practical use, so very downstream. For very good reasons, clinical trials have that rigorous enrollment eligibility criteria because it’s a different set of questions. We’re on the total opposite end of the spectrum in that we want to reach as many people living with MS as possible, to have these tools evaluated. Then we can see that maybe there’s a segment or something that wouldn’t benefit from them, but let us find out by including everybody. We’re much more focused on inclusion, and in that, we’ve been able to demonstrate that it’s very important for evaluation of these types of therapies—any kind of tele- or digital therapeutics—to include the broadest spectrum of people living with MS as possible. That’s important for so many reasons. There’s a segment of people living with MS who are left out of a lot of clinical trials right now, and they face even more burden to get to a clinic visit to receive some type of therapy for a trial. We’ve been encouraged by being able to reach so many more people than are typically reached in a clinical trial to evaluate these therapies.

Clinical Viewpoint

As the adoption of telemedicine rises, the ability to incorporate digital and telehealth-based therapies offers clinicians a unique opportunity to supplement the comprehensive care model.

The Future Is Digital: Telemedicine Is Helping Open Doors to More Comprehensive Care in MS

Brain imaging research in multiple sclerosis (MS) is experiencing an acceleration of technological progress. Fueled by the relentless pace of innovation in magnetic resonance imaging (MRI) and the recent outburst of artificial intelligence (AI), these advances are the crest of a new wave of scientific tools for the MS clinic.

Since its introduction nearly 3 decades ago, 2-dimensional (2D) multislice brain MRI sequences—such as proton-density, T2, fluid-attenuated inversion recovery (FLAIR), and T1 scans—have become the workhorses of any diagnostic or follow-up brain MRI exams for MS. The longevity of these scans, often referred to as conventional MRI, is explained by their high sensitivity in the detection of white matter lesions (WMLs) of the brain (represented as hyper- or hypointense focal areas) and their robust imaging on any 1.5-T and 3-T clinical scanners. However, recent advances in ultra-fast MRI sequences are about to completely transform the way these conventional brain scans are routinely acquired in hospitals and medical imaging centers.

Advances in Image Acquisition and Analysis

One of these new MRI sequences is simultaneous multislice (SMS), which collects multiple imaging slices concurrently.

 SMS can cut the scan time of conventional 2D multislice scans by a factor of 2 without degradation of image quality.

 Another technique, compressed sensing, collects and utilizes heavily undersampled data; this can reduce the scan time of any 2D or 3D anatomical scans by 20% to 50% while maintaining virtually equivalent image quality.

 Wave–controlled aliasing in parallel imaging is another technical breakthrough that combines an undersampling strategy with an efficient 3D encoding; this technique can massively accelerate any 3D T2, FLAIR, and T1 brain scan to reduce scan times to 1 to 2 minutes.

 Finally, AI-based image reconstruction techniques can improve the image quality of undersampled data, thus enabling shorter scans.

 This significant reduction in scan time will provide crucial benefits. First and foremost, patients will experience less discomfort as a result of a much shorter MRI exam, possibly as short as 10 minutes or even less. Second, a scan will be quickly repeated if motion affects image quality, enabling radiologists and neurologists to evaluate their patients’ images more consistently. Last, high-resolution 3D brain scans will replace conventional 2D brain scans, which produce thick-slice images, often containing large gaps between each slice. These important innovations will pave the way for widespread adoption of automated image analysis tools that provide invaluable information about MS disease activity.

Over the past decade, a multitude of image analysis techniques have been developed to automatically segment brain tissues and lesions using high-resolution 3D anatomical scans. These techniques rely on various approaches, including statistical methods (Method for Inter-Modal Segmentation Analysis

), machine-learning classifiers (Classification using DErivative-based Features

), and deep- learning algorithms (3D U-Net

). Currently, fully automated image analysis solutions powered by AI, including those from CorTechs Labs,

 Icometrix, and Quantib, are even offered as products that are approved for clinical use. Therefore, a flurry of imaging-based measures could be factored into the routine evaluation of patients with MS, including longitudinal volume changes of brain tissues, total/regional lesion load, and individual lesions.

Brain volume changes—which include whole-brain atrophy and regional brain atrophy (eg, cortical atrophy, thalamic atrophy)—are particularly useful as a measurement of brain tissue loss and have become widely accepted measures of neurodegeneration

; they are among the best predictors of physical and cognitive disability. Clinical trials evaluating new disease-modifying therapies (DMTs) for MS already incorporate brain atrophy measures as critical end points in their cohort studies. Further, ongoing efforts to improve the accuracy and reliability of these measures and build large normative reference data sets using cloud computing platforms will allow the ability to track brain atrophy routinely in individual patients. Tracking individual lesions, particularly the formation of new WMLs, is also useful to assess the biological response of a patient to DMTs targeting MS inflammatory activity. By automatically comparing a baseline 3D scan to a follow-up 3D scan, reliable detection of new lesions is now possible without using T1-enhancing lesions,

 thus preventing the repetitive use of macrocyclic and linear gadolinium-based contrast agents, a clinical practice that is being intensively debated because of possible safety concerns.

Additionally, monitoring persistent WMLs will become clinically relevant as some of the chronic lesions slowly expand over time. These slowly expanding lesions are in the spot- light of MS investigators, as they are believed to reflect the demyelination and axonal loss as a result of a smoldering inflammation behind an intact blood-brain barrier.

 Investigators suspect that this chronic inflammation drives the disease worsening observed in patients with progressive MS.

 For this reason, an ongoing race exists in the MS pharmaceutical industry to deliver the first brain-penetrant therapy that could stop this smoldering inflammation.

Other features of MS lesions may also have clinical significance. Specific lesion morphological characteristics, such as shape and surface features extracted from high-resolution 3D brain MRI scans, could help differentiate MS lesions from nonspecific WMLs.

 Additionally, lesion phenotyping based on 3D morphology may open new avenues for developing outcome measures, which would reflect the biological activity of MS lesions such as myelin repair.

Another feature, lesion intensity, is now assessed qualitatively in the clinic. As an example, chronic black holes that are known to be areas of permanent tissue destruction are defined as severely hypointense lesions on T1-weighted scans; however, depending on the type of MRI sequence and parameters of the T1 scan, the level of hypointensity can significantly change, thus hampering the proper identification of these black holes. A quantitative measure of the
T1 signal, referred to as T1 relaxation time, would provide a standardized metric of black holes, enabling their robust discrimination in the clinic.

 Initially dedicated to research, quantitative MRI techniques measuring T1 and T2 relaxation times have been significantly improved in terms of accuracy, reproducibility, and overall workflow. Some of these techniques, such as MAGnetic resonance image Compilation (MAGiC),

 2 inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE),

 are moving into the realm of clinical imaging. These techniques may even become the future workhorses of clinical MS brain protocols thanks in part to their additional capability of synthesizing multiple image contrasts simultaneously.

The advances discussed so far rely on MRI techniques that produce conventional image contrasts (eg, proton-density, T1, T2, and FLAIR). Unfortunately, these types of contrasts lack specificity regarding the underlying pathological mechanisms involved in the development of MS lesions. This poor specificity frequently complicates the evaluation of patients suffering from radiological mimics of MS, putting these patients at risk of receiving a misdiagnosis when there is an overreliance on MRI findings. Brain lesions related to comorbidities in patients with MS could be falsely interpreted as MS lesions and mislead treatment decisions. Therefore, a crucial need exists for MRI techniques to deliver biomarkers specific to MS pathology; currently, 2 extremely promising imaging biomarkers are in the research pipe- line to help address this issue of specificity (

The first and most mature biomarker is the central vein sign (CVS),

 which corresponds to the presence of a small vein running centrally through a focal lesion. The perivenular formation of MS lesions is a well-known biological phenomenon initiated by the breakdown of the blood-brain barrier, which releases inflammatory cells that radially diffuse from the inflamed vein into the surrounding brain tissue leading to focal demyelination. Advanced MRI techniques sensitive
to the magnetic properties of the brain can image these small veins thanks to the difference in magnetic susceptibility between venous blood and parenchymal tissue. One such technique is susceptibility-weighted imaging (SWI), which was initially developed to perform cerebral venograms. However, SWI scans acquire thick-slice images that do not allow adequate visualization of central veins running in a multitude of directions. For a more sensitive and robust detection of the CVS, optimized susceptibility-based techniques can be used instead. Indeed, T2*-weighted 3D echo-planar imaging (or T2*-3DEPI) and FLAIR* (a combination of FLAIR and T2*) produce high-isotropic-resolution 3D images that facilitate the identification of brain lesions with central veins.

 From a clinical perspective, CVS will be helpful for the differential diagnosis of MS. Multiple clinical studies have recently demonstrated that patients with MS have a significantly higher proportion of brain lesions with CVS than patients with migraine,

 Encouraged by these results, an ongoing multicenter study is investigating the diagnostic potential of CVS in undiagnosed patients with typical or atypical onset. By comparing the current diagnostic criteria against the prediction based on CVS detection, this large-scale prospective study could demonstrate a significant gain in speed and accuracy of MS diagnosis.

 Another potential benefit of CVS could be the detection of the disease even before its clinical manifestation. Indeed, patients with radiological findings but without any history of clinical symptoms can have a significant proportion of their brain lesions with CVS, suggestive of subclinical MS disease.

The second biomarker is the so-called paramagnetic rim lesions (PRLs). Using the susceptibility-based MRI techniques introduced above, along with advanced quantitative susceptibility mapping post-processing techniques, investigators very recently demonstrated that some MS lesions possess a paramagnetic rim located at their edges.

 This rim appears to correspond to the accumulation of iron-laden macrophages or microglia, which are thought to be the generation of the smoldering inflammation discussed previously. Although not all patients with MS have PRLs, those with PRLs clearly experience a more aggressive disease.

 These findings point to the potential value of PRLs as a prognostic biomarker. In addition, PRLs appear to be very specific to MS lesions

 and may be a complementary biomarker for MS diagnosis. To prepare for future clinical use of these biomarkers, automated solutions for the detection of CVS and PRLs are already in development using probabilistic methods,

 as well as deep-learning algorithms (CVSnet

Although imaging WMLs is the bread and butter of clinical MRI, cortical lesions are seen with increasing clinical importance and will become important radiological findings for predicting disease progression as well as evaluating new therapies for neuroprotection. Because of their specificity regarding MS pathology, cortical lesions are now part of the MRI diagnostic criteria for MS. However, in practice, these lesions remain difficult to detect reliably using conventional MRI scans. Newer techniques such as phase-sensitive inversion recovery

 and the very recent inversion-recovery susceptibility-weighted imaging with enhanced T2 weighting

 can improve the visualization of cortical lesions on 3T scanners, especially the detection of subpial lesions associated with cognitive decline and disease progression. Meanwhile, another powerful strategy for imaging cortical lesions with high sensitivity utilizes scanners with a stronger magnetic field, such as the 7-T scanner.

Seven-tesla MRI produces exquisite images of the human brain by achieving very high spatial resolution—on the order of hundreds of micrometers. This high-end imaging device has been intensively used in clinical research over the past 10 years to noninvasively investigate MS pathology developing in patients’ brains.

 This sustained research effort has brought new insights into the understanding of cortical and white matter MS lesions

 and sparked the discoveries of the CVS and PRLs. The recent FDA approval of the first 7-T MRI for clinical use is another major step forward for MS imaging, as it will enrich the clinician’s toolbox for diagnosing MS43 and speed up the clinical translation of future imaging biomarkers yet to be discovered with this cutting-edge imaging technology.

Without a doubt, MS imaging is set to undergo an exciting technological transformation. The next-generation MRI techniques discussed here will provide clinicians with an unprecedented wealth of information about this complex and multifaceted disease. By fully embracing these technological and scientific shifts on the horizon, neurologists will enhance their ability to diagnose earlier and more accurately, identify and anticipate the trajectory of the disease, and adapt treatment strategies to keep the irreversible progression of the disease at bay. Lastly, integrating rapidly innovative imaging biomarkers into the clinical trials of emerging drugs—especially those promoting neuroprotection and neurorepair—will help finally turn the tables on this debilitating disease. All in all, the future of MS imaging is very bright.

1. Feinberg DA, Setsompop K. Ultra-fast MRI of the human brain with simultaneous multi-slice imaging. J Magn Reson. 2013;229:90-100. doi:10.1016/j.jmr.2013.02.002

2. Kean M, Coleman L, Josan S, Schmitt B. Epilepsy imaging with simultaneous multi-slice turbo spin echo. MAGNETOM Flash. 2015(63):96-99. https://cdn0.scrvt.com/39b415fb07de4d9656c7b516d8e2d907/1800000002474939/798edf786b9b/Epilepsy_Imaging_with_SMS_TSE_1800000002474939.pdf 

3. Mönch S, Sollmann N, Hock A, Zimmer C, Kirschke JS, Hedderich DM. Magnetic resonance imaging of the brain using compressed sensing - quality assessment in daily clinical routine. Clin Neuroradiol. 2020;30(2):279-286. doi:10.1007/s00062-019-00789-x

4. Polak D, Cauley S, Huang SY, et al. Highly-accelerated volumetric brain examination using optimized wave-CAIPI encoding. J Magn Reson Imaging. 2019;50(3):961-974. doi:10.1002/jmri.26678

5. Werth K, Ledbetter L. Artificial intelligence in head and neck imaging: a glimpse into the future. Neuroimaging Clin N Am. 2020;30(3):359-368. doi:10.1016/j.nic.2020.04.004

6. Valcarcel AM, Linn KA, Vandekar SN, et al. MIMoSA: an automated method for intermodal segmentation analysis of multiple sclerosis brain lesions. J Neuroimaging. 2018;28(4):389-398. doi:10.1111/jon.12506

7. Selvaganesan K, Whitehead E, DeAlwis PM, et al. Robust, atlas-free, automatic segmentation of brain MRI in health and disease. Heliyon. 2019;5(2):e01226. doi:10.1016/j.heliyon.2019.e01226

8. La Rosa F, Abdulkadir A, Fartaria MJ, et al. Multiple sclerosis cortical and WM lesion segmentation at 3T MRI: a deep learning method based on FLAIR and MP2RAGE. Neuroimage Clin. 2020;27:102335. doi:10.1016/j.nicl.2020.102335

9. CorTechs Labs receives US FDA clearance for quantitative brain image analysis. News release. CorTechs Labs. September 19, 2017. Accessed October 12, 2020. https://www.cortechslabs.com/company/news/fda-510k-clearance-2017/

10. Rocca MA, Battaglini M, Benedict RH, et al. Brain MRI atrophy quantification in MS: from methods to clinical application. Neurology. 2017;88(4):403-413. doi:10.1212/WNL.0000000000003542

11. Schmidt P, Pongratz V, Küster P, et al. Automated segmentation of changes in FLAIR-hyperintense white matter lesions in multiple sclerosis on serial magnetic resonance imaging. Neuroimage Clin. 2019;23:101849. doi:10.1016/j.nicl.2019.101849

12. McDonald JS, McDonald RJ. MR imaging safety considerations of gadolinium-based contrast agents: gadolinium retention and nephrogenic systemic fibrosis. Magn Reson Imaging Clin N Am. 2020;28(4):497-507. doi:10.1016/j.mric.2020.06.001

13. Elliott C, Arnold DL, Chen H, et al. Patterning chronic active demyelination in slowly expanding/evolving white matter MS lesions. AJNR Am J Neuroradiol. 2020;41(9):1584-1591. doi:10.3174/ajnr.A6742

14. Elliott C, Belachew S, Wolinsky JS, et al. Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis. Brain. 2019;142(9):2787-2799. doi:10.1093/brain/awz212

15. Newton BD, Wright K, Winkler MD, et al. Three-dimensional shape and surface features distinguish multiple sclerosis lesions from nonspecific white matter disease. J Neuroimaging. 2017;27(6):613-619. doi:10.1111/jon.12449

16. Sivakolundu DK, Hansen MR, West KL, et al. Three-dimensional lesion phenotyping and physiologic characterization inform remyelination ability in multiple sclerosis. J Neuroimaging. 2019;29(5):605-614. doi:10.1111/jon.12633

17. Thaler C, Faizy T, Sedlacik J, et al. T1- thresholds in black holes increase clinical-radiological correlation in multiple sclerosis patients. PLoS One. 2015;10(12):e0144693. doi:10.1371/journal.pone.0144693

18. Tanenbaum LN, Tsiouris AJ, Johnson AN, et al. Synthetic MRI for clinical neuroimaging: results of the Magnetic resonance image Compilation (MAGiC) prospective, multicenter, multireader trial. AJNR Am J Neuroradiol. 2017;38(6):1103-1110. doi:10.3174/ajnr.A5227

19. Kober T, Granziera C, Ribes D, et al. MP2RAGE multiple sclerosis magnetic resonance imaging at 3T. Invest Radiol. 2012;47(6):346-352. doi:10.1097/RLI.0b013e31824600e9

20. Hsieh JJL, Svalbe I. Magnetic resonance fingerprinting: from evolution to clinical applications. J Med Radiat Sci. Published online June 28, 2020. doi:10.1002/jmrs.413

21. Hagiwara A, Warntjes M, Hori M, et al. SyMRI of the brain: rapid quantification of relaxation rates and proton density, with synthetic MRI, automatic brain segmentation, and myelin measurement. Invest Radiol. 2017;52(10):647-657. doi:10.1097/RLI.0000000000000365

22. Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12(12):714-722. doi:10.1038/nrneurol.2016.166

23. Sati P, Thomasson DM, Li N, et al. Rapid, high-resolution, whole-brain, susceptibility-based MRI of multiple sclerosis. Mult Scler. 2014;20(11):1464-1470. doi:10.1177/1352458514525868

24. Sati P, George IC, Shea CD, Gaitán MI, Reich DS. FLAIR*: a combined MR contrast technique for visualizing white matter lesions and parenchymal veins. Radiology. 2012;265(3):926-932. doi:10.1148/radiol.12120208

Advanced imaging technology collides with artificial intelligence in what is shaping up to be a revolutionary period for the diagnosis and management of MS.

November 2020

Steps Forward in the Management of Optic Neuritis

The Current and Future Outlook of Multiple Sclerosis

Navigating an Expanding Treatment Toolbox for MS

Managing MS in Millennials

The Future Is Digital: Telemedicine Is Helping Open Doors to More Comprehensive Care in MS

The Future of Multiple Sclerosis Imaging