"Mind Moments," a podcast from NeurologyLive, brings you an exclusive interview with Bhooma Aravamuthan, MD, DPhil.

Episode 33: Problem Recognition: Cerebral Palsy Diagnosis

The consultant in the department of neurology at Mayo Clinic detailed a number of topics surrounding Parkinson Disease Awareness Month, including the progress made in the last 2 decades.

NeuroVoices: Rodolfo Savica, MD, PhD, on Parkinson Disease Awareness Month

The latest news and research presented in multiple sclerosis and related disorders straight from the virtual conference floor

Coverage of the ACTRIMS Forum 2021 Virtual Meeting

, has been with the team since October 2019. Follow him on Twitter 

Recently published results from an observational study revealed that retinal atrophy is modulated by rituximab (Rituxan; Genentech/Biogen) in patients with relapsing-remitting multiple sclerosis (RRMS), with the greatest attenuation of retinal atrophy occurring after 12 months of treatment.1

Senior author Shiv Saidha, MD, professor of neurology, Johns Hopkins School of Medicine, and colleagues performed serial optical coherence tomography (OCT) scans on patients with RRMS treated with rituximab and compared rates of ganglion cell inner plexiform layer (GCIL) atrophy to patients treated with glatiramer acetate (GA) or natalizumab (Tysabri; Biogen), and healthy cohorts (HCs).

Patients were followed with serial OCT for a median duration of 2.8 years in which rates of GCIPL atrophy were ­­–0.28 µm/year (±0.11) for those treated with rituximab. These results were similar in comparison with those treated with GA (n = 49; –0.33 µm/year [±0.05]; 

 = .69) and natalizumab (n = 88; –0.17 µm/year [±0.10]; 

 = .13), but faster than HCs (n = 78; –0.15 µm/yr [±0.03]; 

During the first 12 months of treatment with rituximab, patients exhibited 0.55 µm/year (±0.23) faster rates of GCIPL atrophy relative to afterwards (n = 25; 

 = .02), during which period GCIPL atrophy rates were ­–0.14 µm/year (±0.13).

What to Expect from the 2021 American Academy of Neurology Annual Meeting

Saidha and colleagues concluded, "our findings raise the possibility that the neuroprotective therapeutic response with rituximab in RRMS may take up to 12 months, though should be confirmed by larger studies.” Participants with uncontrolled hypertension, diabetes mellitus, or glaucoma, and eyes with optic neuritis less than 6 months prior to baseline OCT, or during follow-up, were excluded from the study.

The professor of neurology was recently involved with 2 other studies, the first which found that in the absence of overt metabolic comorbidities, body mass index (BMI) might be associated with 

 in patients with MS. The findings suggested that obesity, a modifiable risk factor, may have an impact on accelerated neurodegeneration in MS.

The second study was presented at MS Virtual 2020, the 8th Joint ECTRIMS-ACTRIMS meeting, and evaluated the evaluated disease-modifying therapies (DMTs) and their effects in slowing retinal atrophy in RRMS.

All told, the data showed that high potency DMTs are associated with slower rates of retinal atrophy compared to low potency DMTs. It also confirmed Lambe’s research by showing that the effect of rituximab on retinal atrophy in MS may take up to 6-12 months.

The results also showed that inner nuclear layer and outer nuclear layer atrophy measures appear to be relatively specific to progressive MS (PMS) and may be novel outcomes for assessing neuroprotection and/or neurorestoration in PMS. Saidha and colleagues concluded that current, conventional, and primarily anti-inflammatory DMTs, both high- and low-potency, have not been shown to significantly reduce retinal atrophy in PMS, unlike RRMS.

1. Lambe J, Risher H, Filippatou AG, et al. Modulation of retinal atrophy with rituximab in multiple sclerosis. 

Published online April 7, 2021. doi: 10.1212/WNL.0000000000011933

2. Filippatou AG, Lambe J, Sotirchos ES, et al. Association of body mass index with longitudinal rates of retinal atrophy in multiple sclerosis. 

. Published online April 16, 2020. doi: 10.1177/1352458519900942

3. Saidha S. Disease modifying therapies and retinal atrophy. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract PS15.01

Articles

Findings suggest that the neuroprotective therapeutic response from rituximab in patients with relapsing-remitting multiple sclerosis may take up to 12 months. 

Rituximab Modulates Retinal Atrophy in Relapsing-Remitting Multiple Sclerosis

Matt Hoffman, Senior Editor for NeurologyLive, has covered medical news for MJH Life Sciences, NeurologyLive’s parent company, since 2017. He hosts the NeurologyLive Mind Moments podcast, as well as Second Opinion on Medical World News. Follow him on Twitter 

2021 American Academy of Neurology (AAN) Annual Meeting

, with a shift to a virtual platform after last year’s meeting, like so many others, was derailed by the COVID-19 pandemic.

The virtual platform will kick off on Saturday, April 17, and run through Thursday, April 22, featuring a vast number of speakers and sessions and thousands of poster presentations. Natalia S. Rost, MD, MPH, FAHA, FAAN, chair, AAN Science Committee; chief, Stroke Division, Massachusetts General Hospital; and professor of neurology, Harvard Medical School, noted that the theme of this year’s meeting will be the celebration of science.

“I'm grateful to have an opportunity to speak to you again after a year of hiatus caused by the COVID-19 pandemic,” Rost said in the opening press conference. “While this has been a trying year for the entire world, specifically, it's been immensely difficult for the medical community and the community of scientists for many of whom their life or being rudely interrupted by the virus. But this also has been the year of tremendous triumph of science, with the extraordinary breakthroughs in diagnosis, vaccine development, and treatments for COVID-19 infection.”

Rost explained that while the format of the meeting is certainly unusual—and one she hopes won't require repeating in the coming years—it offers a solid foundation to build from, and as has been the case for many scientific organizations over the last year, has allowed for the integration of technology advances into the communication of ideas and data.

“Despite all the odds of last year, with over 2000 original abstracts submissions to our virtual annual meeting this year, it's telling me that resilience, remarkable creativity, and academic drive are alive and well among my neuroscience colleagues,” she said.

In the opening press conference, Rost discussed her top 3 selections for the most groundbreaking scientific research being presented at the meeting, importantly noting that all were presented by women, representing the leadership roles and momentum being gained by women in science. This, she said “is another reason for us to celebrate and rejoice.”

Among the long list of highly anticipated presentations of data selected as top science was a presentation regarding the repercussions of the COVID-19 pandemic from Thanh N. Nguyen, MD, of Boston University School of Medicine; data on the investigational agent AMX0035 in amyotrophic lateral sclerosis (ALS), presented by Sabrina Paganoni, MD, PhD, of Massachusetts General Hospital; and findings on the utility of total tau and neurofilament light in neurodegenerative disease, from Michelle M, Mielke, PhD, of Mayo Clinic.

The opening day of the meeting includes a plenary session titled, “Frontiers in Neuroscience,” directed by Paul M. George, MD, PhD, MSE, which highlights some of the basic and translational research into clinical issues of importance. Afterward, George will moderate a live “fireside chat” with the speakers for question-and-answer opportunities. The session, which begins at 10:00 AM ET, includes the following presentations:

Organization and Control of Hippocampal Circuits — presented by Ivan Soltesz, PhD

Decoding Speech Cortex — presented by Edward F. Chang, MD

Microtubules in Health and Disease — presented by Antonina Roll-Mecak, PhD

Stem Cell Therapy for Spinal Cord Injury: Transition to the Clinic — presented by Mark H. Tuszynski, MD, PhD, FAAN

Dissecting the Control of Blood Flow Through Brain Capillaries — presented by Andy Shih, PhD

Additionally, a number of awards for work in research and excellence will be presented over the course of the meeting by the speakers being honored, including the AB Baker Award for Lifetime Achievement in Neurologic Education Keynote Presentation, the Potamkin Prize for Research in Pick’s, Alzheimer’s Disease, and Related Diseases, the Sheila Essey Award for ALS Research, the Norman Geschwind Prize in Behavioral Neurology, and the John Dystel Prize for Multiple Sclerosis Research, among others. As well, the Medical Student Essay Award and Saul R. Korey Presentation will be given at this year’s meeting.

There is also a trio of hot topic-focused sessions scheduled for the course of the conference, with Saturday, April 17, featuring a Neuro-COVID Plenary Session headlined by Rost and George. Then, on Monday, April 19, a midday networking session will offer attendees an opportunity to learn about the AAN’s advocacy work and its Advocacy Committee leadership, facilitated by Nick Johnson, MD, FAAN, and Michael Markowski, DO, FAAN. Following that, a late-day CME session led by Melissa Yu, MD, FAAN, will review concepts of anti-amyloid therapies in Alzheimer disease, as well as the potential indications and considerations for implementation of said therapies in clinical practice.

Also on Monday, beginning at 10:00 AM ET, Holly E. Hinson, MD, MCR, FAAN, and Deborah Hall, MD, PhD, FAAN, will lead a plenary session on current clinical trials conducted over the last year. The session will feature the following presentations:

ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) — presented by Michael Tymianski, MD, PHD, FRCSC

Atogepant Significantly Reduces Mean Monthly Migraine Days in the Phase 3 Trial (ADVANCE) for the Preventive Treatment of Migraine — presented by Jessica Ailani, MD, FAAN

Efficacy and Safety of Lower-Sodium Oxybate in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adult Participants With Idiopathic Hypersomnia — presented by Yves Dauvilliers, MD, PhD

Efficacy, Safety, and Tolerability of Efgartigimod in Patients With Generalized Myasthenia Gravis: Analysis of the Phase 3 ADAPT Study — presented by James F. Howard, Jr., MD, FAAN

Sustained Benefits for 10 kHz Spinal Cord Stimulation Treatment of Painful Diabetic Neuropathy: 6-Month Results from a Multicenter Randomized Controlled Trial — presented by Erika Petersen

Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson’s Disease — presented by Raúl Martinez-Fernandez

Efficacy and Safety Results of the Avalglucosidase alfa Phase 3 COMET Trial in Late-Onset Pompe Disease Patients — presented by Hani Kushlaf, MD, FAAN

Leriglitazone Improved Progression of Myelopathy-related Symptoms, and Reduced Cerebral Lesions in Patients with Adrenomyeloneuropathy in a Phase 2/3 Clinical Study — presented by Reza Seyedsadjadi, MD

FINTEPLA (Fenfluramine) Treatment Improves Everyday Executive Functioning in Patients With Lennox-Gastaut Syndrome: Analysis From a Phase 3 Clinical Trial — presented by Kim I. Bishop, PhD

“I'd like to thank the presenters for doing an exciting science at the times when it's most challenging,” Rost said. “I hope that you all have an opportunity to learn about the entire breadth of the AAN scientific program throughout our upcoming meeting, and we'll see you in the virtual hallways of the annual meeting later this week.”

's coverage of the meeting will begin this week and will extend beyond its conclusion throughout the month of April. It will feature exclusive interviews with a number of experts across the breadth of neurology, as well as in-depth coverage of the top data presentations and addresses that help inform clinical care and decision-making. For more coverage of AAN 2021, 

, and check back regularly to see the latest.

The 2021 AAN Annual Meeting will be held virtually from April 17-24. Follow along with coverage from NeurologyLive, including expert interviews and session recaps.

 joined the MJH Life Sciences team in October 2020. Follow her on Twitter 

Data from a recent study suggest that Asian, Black, and Hispanic patients receive less timely diagnoses of mild cognitive impairment (MCI) and 

Researchers found that patients who identified as Asian (odds ratio [OR], 0.46 [95% CI, 0.38-0.56]; 

 <.001)), Black (OR, 0.73 [95% CI, 0.56-0.94]; 

 <.001), or Hispanic (OR, 0.62 [95% CI, 0.52-0.72]; P <.001)) were less likely to receive a timely diagnosis. Asian patients also received fewer diagnostic evaluation elements such as specialist evaluation, laboratory testing, and neuroimaging (incidence rate ratio [IRR], 0.81 [95% CI, 0.74-0.87]; 

“Little is known about potential racial/ethnic differences with regard to timeliness and comprehensiveness of dementia diagnosis. Addressing this gap is of critical value for informing public health and policy interventions,” wrote first author Elena Tsoy, PhD, postdoctoral fellow, University of California, San Francisco, and colleagues.

Tsoy and colleagues analyzed data from 10,472 Medicare beneficiaries in California with incident diagnoses of dementia or MCI. Beneficiaries had a mean age of 82.9 years (standard deviation [SD], 8) and 6504 (62.1%) were women. Most patients identified as White (n = 7817; 74.6%), 1255 (12.0%) identified as Hispanic, 993 (9.5%) identified as Asian, and 407 (3.9%) identified as Black. A timely diagnosis was defined as diagnosis of MCI rather than dementia. 

Retinal Biomarkers May Serve as Alzheimer Disease Detection Tool

Altogether, only 21.2% of beneficiaries received a timely diagnosis of incident MCI (vs dementia), 34.6% received a specialist evaluation, 16.2% had recommended laboratory testing, and 28.7% had neuroimaging studies.

After adjusting for demographic and geographical factors, the aforementioned associations remained significant, with Asian beneficiaries having the lowest likelihood of an incident MCI diagnosis (OR, 0.45 [95% CI, 0.37-0.55]; 

 <.001), followed by Hispanic (OR, 0.65 [95% CI, 0.55-0.77]; 

 ≤.001) and Black (OR, 0.70 [95% CI, 0.53-0.91]; 

Further analyses revealed that the estimated mean marginal effects of race/ ethnicity on incident diagnosis of MCI were −11.0% (95% CI, −13.2% to −8.8%; 

 < .001) for Asian beneficiaries, −6.6% (95% CI, −8.9% to −4.2%; 

 < .001) for Hispanic beneficiaries, and −5.6% (95% CI, −9.4% to −1.7%; 

In a related editorial, Claudia Kawas, MD, Al and Trish Nichols Chair, clinical neuroscience and professor, neurology and neurobiology & behavior, University of California, Irvine, and colleagues wrote that “given the racial and ethnic diversification of the older population in the US and the higher burden of dementia in some ethnoracial groups, understanding the determinants of dementia as well as barriers to diagnosis in racially and ethnically diverse individuals is ever more crucial.”

Tsoy and colleagues found that increasing age (OR for every additional 5 years, 0.80 [95% CI, 0.77-0.82]; 

 <.001), residence in a highly disadvantaged neighborhood (OR, 0.73 [95% CI, 0.63-0.84]; 

 <.001), and greater comorbidity burden (OR for every additional comorbid condition, 0.96 [95% CI, 0.94- 0.98]; 

 <.001) were also associated with a lower likelihood of an incident MCI diagnosis rather than dementia.

They also found that individuals who identified as Asian were less likely to receive recommended diagnostic workup services (IRR, 0.81 [95% CI, 0.74-0.87]; 

 <.001). This remained significant in fully adjusted models.

Marginal effects analyses showed a mean effect of −15.7% (95% CI, −21.2% to −10.2%; 

 <.001) of receiving recommended diagnostic services for Asian beneficiaries. Other variables associated with lower likelihood of diagnostic workup services were older age (IRR for every additional 5 years, 0.98 [95% CI, 0.98-0.99]; 

 <.001) and greater neighborhood disadvantage (IRR, 0.91 [95% CI, 0.86-0.96]; 

Tsoy and colleagues also found that Black beneficiaries residing in highly disadvantaged neighborhoods had a lower likelihood of receiving a diagnosis of MCI (B = 0.713; standard error [SE], 0.318; 

 = .02). A similar interaction was seen between Hispanic ethnicity and greater neighborhood disadvantage ((B = 0.133; SE, 0.050; 

 = .03) in association with the number of recommended diagnostic services.

 <.001) and Hispanic (OR, 0.60 [95% CI, 0.46-0.78]; 

 <.001) beneficiaries that received a specialist evaluation were also less likely to receive a diagnosis of incident MCI than White beneficiaries.

“Recruiting diverse populations into research requires directed resources to cultivate trust and engage with different communities. Importantly, physicians must be made aware of the disproportionate effect of dementia in underrepresented and diverse communities and fully recognize the biases of the medical establishment in the diagnosis and care of these underserved individuals. It is a challenge we all must address,” Kawas and colleagues concluded.

1. Tsoy E, Kiekhofer RE, Guterman EL, et al. Assessment of racial/ethnic disparities in timeliness and comprehensiveness of dementia diagnosis in California. 

 Published online March 29, 2021. doi:10.1001/jamaneurol.2021.0399
2. Kawas CH, Corrada MM, Whitmer RA. Diversity and disparities in dementia diagnosis and care: A challenge for all of us. 

 Published online March 29, 2021. doi:10.1001/jamaneurol.2021.0285

Researchers analyzed data from the 10,472 Medicare beneficiaries diagnosed with mild cognitive impairment or dementia in California. 

Minorites May Receive Less Timely MCI Diagnoses Than White Individuals

This is a 2-part interview. To view part 1, 

At the American Stroke Association’s (ASA) 

, March 17–19, a number of abstracts highlighted the inequalities in stroke care across different racial and ethnic groups, as well as the reasons behind why these inequalities exist. In 1 study, researchers found significant race-ethnic and geographical disparities in the delivery of endovascular therapy, calling for the need to improve access for all eligible patients with stroke.

Another abstract included findings from the Transitions of Care Stroke Disparities Study, which rooted similar issues and explored how social determinants of health can play a role in stroke incidence and disparities in care.

 Researchers concluded that mechanisms by which education, economic conditions, and psychosocial factors all may influence these outcomes, but that additional research is needed.

Stroke expert Ralph Sacco, MD, MS, FAHA, FAAN, was a part of each of these studies and claims that it’s time to start turning statistics into action. Sacco, chair of neurology and Olemberg Family Chair of Neurological Disorders at the University of Miami Miller School of Medicine, sat down as part of our NeuroVoices series to provide perspective on what communities can begin to do to improve these disparities.

How can we start to improve the disparities within different racial groups? Who needs to come to the table for this change to come about?

A lot of our mantra is to turn these measurements into action. We always remind both the public and our physicians that before you can make a change, you have to know there’s a problem. Much of our data first begins to show a disparity and then we try to delve into what is driving that disparity and how can we correct it.

Some of those things are educational campaigns. We need to get the word out still, particularly in underserved populations, about calling 9-1-1 and getting urgent attention for stroke. We need to continue to emphasize that.

High blood pressure is the “silent killer,” and many people don’t know their blood pressure is elevated. Getting more access to individuals to have their blood pressure checked and then being able to know their numbers and get them on the right medications is important. A lot of what the American Heart Association focuses on is understanding about lifestyle modification. We focus on weight reduction, physical activity, not smoking, dieting. All of that to help reduce the risk of stroke.

The other thing that we’ve worked on in the Florida Stroke Registry was to educate our systems and learn from each other. Some people can give TPA and endovascular therapy very rapidly and they have all the systems set up to do that. In the early phases of our Florida Stroke Registry, we created these modules where we instructed people about giving TPA in the CT scanner, having the TPA ready to go, calling when the EMS person gets there, having the EMS person call the emergency room personnel to let them know a stroke patient is coming. All of these things are done to try to reduce delays in care.

Working with EMS, there have been transport policies that have been established. EMS has a big program now where they’re trying to get dispatchers to be better trained in recognizing stroke with certain symptoms over the phone so they can dispatch appropriately and get them quickly to an acute stroke hospital. A lot of it is educational awareness, giving people the right tools to more rapidly recognize and treat acute stroke.

A big area of focus for us right now is transitions of care. People come into the hospital, they receive this great care, but we’re worried that when they leave the hospital, there is a gap in care. When they go back to the community, is everything communicated? Do they remain taking their medicines? Is your blood pressure well controlled? Do they take anti-platelets as needed? There’s this concern that there’s not a good transition of care, and therefore, there’ll be a higher risk of recurrent stroke, or possibly a readmission for complications from stroke. We’re beginning to focus a lot more on models, systems, and interventions to improve the transition of care.

Why has there been limited research on the relationship of social determinants of health on severity and disability? What advantages does this type of research bring to the stroke community?

There has been an interest in social determinants of health. The problem sometimes is collecting the data. For example, in our Florida Stroke Registry, we don’t have a lot of social determinants of health collected. We didn’t even have education or occupation. We have their zip code, but we don’t have their full address. There’s certain things that are not well coded in acute stroke registries for social determinants of health. This analysis used their zip code and then we worked with a company to give us other social determinants of health. How many parks, how much access to fruits and vegetables, socioeconomic status based on income in the area, crime status, access to physical activities and gyms. These are all environmental determinants that describe the community in which you live in.

We wanted to connect that with the actual acute stroke performance and then the transitions of care. Why is that important? It’s not just about changing your blood pressure medication or taking an aspirin. There are other things that we have to be advocates for. We can tell everybody about the right diet, but if they can’t get to the right places to buy the right food, that’s an issue. Access to healthy food delivery areas are important. We can tell people to exercise but if I live in an urban area where there are no safe places to walk or a park, that’s a problem.

These are important findings, but we then have to advocate to government and other non-government entities about policies to improve access to healthy food, make fruits and vegetables more affordable for people who can’t afford them, make sure parks or facilities for physical activity are opened for others to utilize. Other ways to rethink in a different way to provide access to some of these other environmental determinants that we lose sight of that are important for determining stroke risk as well as stroke outcomes.

Did you have any takeaways from any specific data presented at ISC 2021 regarding COVID-19 and stroke?

There have been many presentations about COVID throughout the year that have been published and we’re still learning quite a bit about the virus in stroke. Early on, we saw in the Florida Stroke Registry and in other places that the number of people coming in with stroke was dropping and we were worried that people were having symptoms and staying home. That’s 1 perception. It’s not clear why the amount of stroke cases dropped off.

We quickly educated all of our hospitals on how to provide acute stroke care, using PPE, and all the precautions someone must take regarding COVID-19. Our stroke centers came up to speed quickly to continue to provide acute care. Then working with the American Heart Association, we tried to tell the public to not delay, don’t be fearful to call 9-1-1.

There was also a lot of concern about young people with stroke and COVID-19 hypercoagulability. It is shown that patients with severe cases of COVID-19 have this market inflammatory and thrombotic storm that could occur with the inflammation that their body responds to with the virus. There was some concern back and forth. It’s still not clear whether stroke is increased or not. Some say it is, some say it’s not clear. Obviously, if you have severe COVID-19, the risk of major complications, including thrombotic and clotting complications which include stroke, go up. But it’s not severely increased like we originally thought in the beginning.

The other interesting area that we’re still learning about is post-acute COVID. Some of that may be more cognitive, not necessarily stroke, but there’s this concern of brain fog and other neurological sequelae. Numerous people are beginning to look at that. Will people who survive COVID have increased risk of stroke? Will they have increased risk of cognitive decline? There’s still a lot more that we need to understand about COVID-19 and those who had been infected, even the mild infections, and what their repercussions are. That’s what’s being looked at. Right now, the good thing is that obviously more people are getting vaccinated, and the cases are going down. We didn’t see, which we were worried about, a huge surge in strokes with COVID-19.

1. Wang K, Gutierrez CM, Mueller NH, et al. Disparities in delivery of endovascular therapy: data from the Florida Stroke Registry. Presented at International Stroke Conference; March 17–19. Abstract P875

2. Gardener H, Wang K, Rodriguez A, et al. A multi-level exploration of the social determinants of health in Florida: initial findings from the Transitions of Care Stroke Disparities study. Presented at International Stroke Conference; March 17–19. Abstract P882

The chair of neurology and Olemberg Family Chair of Neurological Disorders at the University of Miami Miller School of Medicine discussed solutions to improve disparities in stroke care and the need for future research on social determinants of health. 

NeuroVoices: Ralph Sacco, MD, MS, on Improving Disparities and Expanding Research in Stroke Care

The effects of anakinra (NCT04025554) and tolebrutinib on paramagnetic rim lesions (PRL) as seen on 7-Tesla magnetic resonance imaging (MRI) are being evaluated in 2 studies as part of a new phase 2a clinical trial paradigm for multiple sclerosis (MS).

Americas Committee for Treatment and Research

, February 25-27, by first author Jemima Akinsanya, DO, neuroimmunology clinical fellow, National Institutes of Health (NIH).

Anakinra is a recombinant human interleukin-1 receptor antagonist and was approved by the FDA for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease in 2001.

 Tolebrutinib, meanwhile, is an investigational, orally available, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor. 

 spoke with Akinsanya to learn more about how the 2 medications could improve patient care in MS. She also discussed further research she would like to see conducted with the treatments.

 Can you provide an overview of these 2 studies you’re working on?

 Yes. We are currently enrolling for the trial for the BTK inhibitor tolebrutinib. For anakinra, we've already started administering anakinra to patients in that trial.

So, anakinra is an injectable medication that the patients give to themselves daily, and we're doing MRIs to look and see if there's any modulation of the PRL, which you know, is the lesion that has both chronic and active inflammation components to it. And for the BTK inhibitor trial, with tolebrutinib, patients will take an oral medication daily. And, same thing, we're also going to be looking at MRI to see if there's any modulation of that PRL. So, both trials are looking to see if there's modulation of the PRL.

How could these medications help improve MS patient care?

The biggest thing that we are hoping for is to help with progression of disease. There are a lot of patients who have stable MRIs, but they have a progressive disease course clinically. And we really don't have good treatment options for these patients that don’t have enhancing lesions on their MRI for us to treat and like an acute flare that we can objectively identify. If there were new treatment options for these patients who are clinically worsening by, maybe progressively having difficulty walking, or progressive weakness, even though they're not having acute flares on their MRI, that would be a huge breakthrough for MS patients.

These medications are not yet approved for MS, I have to add. But, in terms of the mechanism, the fact that these medications are acting on microglia, is different than some of the other disease modifying therapies that are on the market right now.

What further research would you like to see in this area? 

I would love to see more research specifically looking at progressive MS it’s something very common when patients come in, and it's very disheartening as a clinician to not be able to provide more options for these patients. So, I'm excited to see what, down the line, could help. It's such a huge quality of life hindrance for patients, so to be able to provide them with treatments that can help slow the neuro degeneration and not just the acute inflammation would make a huge impact on them.

Transcript has been edited for clarity. For more coverage of ACTRIMS Forum 2021, click 

1. Akinsanya J, Absinta M, Dargah-zade N, et al. Toward the use of paramagnetic rim lesions in proof-of-concept clinical trials for treating chronic inflammation in multiple sclerosis. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P126.
2. Kineret® (anakinra) for injection, for subcutaneous use. FDA label. Updated December 2012. Accessed March 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103950s5136lbl.pdf

Jemima Akinsanya, DO, Neuroimmunology Clinical Fellow at the National Institutes of Health, discussed new studies of anakinra and tolebrutinib in MS. 

Treating Paramagnetic Rim Lesions in Multiple Sclerosis

In an effort to assess the timing and impact of psychiatric, cognitive, and motor abnormalities in patients with Huntington disease (HD), researchers concluded that the initial manifestation of HD is increasingly likely to be motor, and less likely to be psychiatric, as age at presentation increases, and is independent of pathogenic CAG repeat length.

Lead author Branduff McAllister, BSc, PhD, research associate, Cardiff University, and colleagues evaluated the clinical features of 6316 individuals with HD from the European REGISTRY study. Patients completed Clinical Characteristics Questionnaire (CCQ) that assessed 8 symptoms: motor, cognitive, apathy, depression, preservative/obsessive behavior, irritability, violent/aggressive behavior, and psychosis.

They found that as age at first manifestation increased, motor presentations became more likely (odds ratio [OR] per 10-year increase in onset age, 1.06 [95% CI, 1.04-1.07]; 

 = 7.4 x 10-22) but psychiatric presentations became less likely (OR per 10-year increase in onset age, 0.96 [95% CI, 0.95-0.97]; 

Among patients over the age of 60 years old, 68.6% had initial motor abnormalities with far fewer having psychiatric (11.5%) or cognitive (6.7%) presentations. “The presence of psychiatric and cognitive symptoms in HD gene carriers is associated with significantly reduced functional capacity, emphasizing the importance of early recognition and management of these symptoms,” McAllister et al wrote.

Amantadine Doubles Daily ON Time Without Dyskinesia in Parkinson Disease

Cognitive impairment was the most significantly associated symptom with reduced total functional capacity (TFC; OR per unit decrease in TFC, 1.28 [95% CI, 1.23-1.35]; 

 = 1.6 x 10-25). Depression was significantly associated with total lower scores on CCQ, aligning with its prevalence early in the disease course. Significant associations were observed between depression and female sex (OR, 1.77 [95% CI, 1.44-2.17]; 

 = 7.0 x 10-8), as well as tobacco use and irritability (OR per extra cigarette per day, 1.02 [95% CI, 1.01-1.03]; 

McAllister and colleagues also found no significance in the relationship between CAG repeat length and the relative proportions of motor, cognitive, and psychiatric onset cases. Cases of repeat lengths of more than 59 CAG were shown to have a more balanced distribution of motor, cognitive, and psychiatric presentations, mirroring the trends seen for juvenile HD cases.

In those cases, individuals with an onset before the age of 20 were equally likely to present with motor (24.5%), cognitive (21.8%) or psychiatric features (28.2%), contrasting to patients with adult-onset HD, which had higher likely of manifestation with motor than psychiatric.

Among a subpopulation of 5609 individuals with HD, more than 99% had experienced motor symptoms compatible with HD, indicating why motor abnormalities remain the diagnostic standard for clinical onset of HD. Despite motor symptoms not explicitly defined in the CCQ, contemporaneous data from Unified Huntington’s Disease Rating Scale showed that 96.8% of the study population had chorea, alongside variable amounts of incoordination, dystonia, and rigidity.

There was a strong inverse correlation between pathogenic GAC repeat length (40-55 CAG inclusive) and mean age at symptom onset for all symptoms analyzed. Pathogenic CAG length explained 66.3% of the variance in age at onset of motor symptoms, in line with previous estimates, according to the study authors.

The timing of motor and psychiatric symptoms in HD gene carriers was shown to vary with symptom type and CAG length. Overall, 42.4% of patients with HD (2140 of 5042) reported at least 1 psychiatric or cognitive symptom in advance of motor symptoms, with a further 22.3% (1126 of 5042) reporting at least 1 of these symptoms at the same time as motor abnormalities.

McAllister B, Gusella JF, Landwehrmeyer GB, et al. Timing and impact of psychiatric, cognitive, and motor abnormalities in Huntington disease. 

. Published online March 25, 2021. doi: 10.1212/WNL.0000000000011893

Overall, 42.4% of patients with Huntington disease reported at least 1 psychiatric or cognitive symptom before motor symptoms, with depression being the most common. 

Psychiatric, Cognitive Symptoms Common in Huntington Disease Gene Carriers

 on ContagionLive, a sister publication of NeurologyLive. 

 have been reported in women aged 18 to 48 who received Johnson & Johnson's Janssen COVID-19 vaccine, causing the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) to pause administration at federal sites pending a larger investigation. 

Reports of the rare blood clotting disorder were recorded 6 to 16 days following administration of the one-shot adenovirus Ad26.COV2.S vaccine. As of Tuesday morning, 1 woman with the condition has died and a second woman in Nebraska is hospitalized and in critical condition.

Based on this, the federal agencies have advised that states distributing the vaccine also pause their operations.

"We are aware of an extremely rare disorder involving people with blood clots in combination with low platelets in a small number of individuals who have received our COVID-19 vaccine. The United States Centers for Disease Control (CDC) and Food and Drug Administration (FDA) are reviewing data involving six reported U.S. cases out of more than 6.8 million doses administered," Johnson & Johnson said in a statement. "In addition, we have been reviewing these cases with European health authorities. We have made the decision to proactively delay the rollout of our vaccine in Europe."

The pharmaceutical company went on to say that "people who have received our COVID-19 vaccine and develop severe headache, abdominal pain, leg pain, or shortness of breath within three weeks after vaccination should contact their health care provider."

The FDA and CDC investigators intend to collaborate on assessment of possible links between the Janssen vaccine and cerebral venous thrombosis in order to discern whether the company’s Emergency Use Authorization (EUA) should continue as-is or become limited.

The FDA reiterated the importance of an indefinite pause during this investigation in a statement shared on Twitter Tuesday morning.

"This is important to ensure that the health care provider community is aware of the potential for these adverse events and can plan due to the unique treatment required with this type of blood clot," 

The CDC’s Advisory Committee on Immunization Practices (ACIP) will hold an emergency meeting on the matter this Wednesday, according to 

Per the CDC, more than 6 million people in the US have received Janssen’s vaccine thus far, and another 9 million doses have been shipped to different states.

Comparatively, Pfizer-BioNTech and Moderna have delivered 23 million-plus doses weekly of their two-dose mRNA vaccines to the US, comprising a significant majority of the US’ vaccine distribution. No significant safety concerns have emerged from either product.

Just last month, the Biden administration 

announced the acquisition of another 100 million doses of Ad26.COV2.S from Janssen

, to be delivered in the latter half of 2021.

 in manufacturing at its Baltimore plant due to the inadvertent mixing of vaccine ingredients. The error resulted in the loss of up to 15 million doses.

The FDA and CDC made the call after 6 reports of the serious blood clot event, which has so far been linked to 1 patient death. 

Johnson & Johnson COVID-19 Vaccine Paused After Reports of Cerebral Venous Thrombosis

According to a recent announcement, the National Institutes of Aging (NIA) will be conducting a new innovative study to determine whether medicines currently FDA-approved to treat conditions other than dementia can help prevent or treat Alzheimer disease (AD).

Neurologist Madhav Thambisetty, MD, DPhil, will lead the project in collaboration with researchers at Harvard Medical School, Rutgers University, and Johns Hopkins University School of Medicine, to design a new approach that would be an alternative to traditional drug discovery.

The study, titled Drug Repurposing for Effective Alzheimer’s Medicines (DREAM), will focus on drugs that have already been shown safe and effective for other conditions. The investigators will forego observing data from animal testing models and will instead look at data from large numbers of people who have already been treated with these compounds for other disorders.

"The DREAM study represents a one-of-a-kind initiative to integrate ‘omics’-based drug discovery approaches with analyses of patient-level data from large longitudinal health-care databases using state-of-the-art pharmacoepidemiologic methods to facilitate identification of drug repurposing candidates for ADRD,” Thambisetty et al wrote in a peer-reviewed journal.

Complexities With Conducting Real-World Dementia Trials

Plans for the DREAM study were recently published in 

Alzheimer’s and Dementia: Translational and Clinical Interventions

 Based on abnormal glycolysis as a primary progenitor pathway, researchers hypothesized that there may be greater than 20 related and distinct biochemical pathways that are dysregulated in the AD-related dementia (ADRD) brain. These abnormalities may precede or influence the brain changes that lead to dementia.

To further test this hypothesis, the investigators generated a list of 250 genes that are known to regulate individual reactions within the component pathways of the Alzheimer Disease Aberrant Metabolism (ADAM) network. Using these genetic regulators within the aforementioned dysregulated pathways, 35 FDA-approved drugs were identified as potential repurposing candidates. Of these 35, the team selected 15 drugs as the best candidates for further analysis.

The DREAM study leverages 2 large population-based data sources for pharmacoepidemiologic analyses, the first being the insurance claims data from the Medicare program, and the second is the Clinical Practice Research Datalink (CPRD) GOLD, which is a large United Kingdom primary care database containing de-identified data on nearly 15 million people. Results from the DREAM study could help guide future research, especially if an identified drug appears to reduce the risk or severity of AD and ADRDs.

The hypothesis of repurposing drugs for AD has become increasingly popular in recent years. Cleveland Clinic recently announced that it will conduct a 

, an FDA-approved anti-cancer drug, in early-stage AD or mild cognitive impairment (MCI). That project is comprised of 2 dual studies and is led by Marwan Sabbagh, MD, and Boris Decourt, PhD.

Sabbagh, along with colleagues including Jeffrey Cummings, MD, ScD, who serves as the director emeritus of the Lou Ruvo Center for Brain Health at Cleveland Clinic, and vice chair of the Department of Brian Health at the University of Nevada – Las Vegas, recently published a yearly report on the 

, in which the group noted there was an increase in the number of repurposed agents in the pipeline from 2019 to 2020.

 This datapoint drew Cummings’ attention as a potential area to prioritize.

One [thing that stuck out] was the great increase in the number of repurposed compounds that are in the pipeline. One of the things that alarmed me though was the relatively small number of agents coming into phase 1. We really have to get those drugs out of the lab, out of the animals, and into humans more successfully.”

1. NIA study identifies FDA-approved drugs that may also be helpful for dementia. News release. NIH. April 8, 2021. Accessed April 12, 2021. 

https://www.nia.nih.gov/news/nia-study-identifies-fda-approved-drugs-may-also-be-helpful-dementia

2. Desai RJ, Varma VR, Gerhard T, et al. Targeting abnormal metabolism in Alzheimer disease: The Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study. 

Published online November 26, 2020. doi: 10.1002/trc2.12095

3. Cleveland Clinic Lou Ruvo Center for Brain Health receives NIH and ADDF grants, totaling $4.6 million to study FDA-approved cancer drug lenalidomide in Alzhimer’s disease. News release. Cleveland Clinic. January 27, 2021. Accessed April 12, 2021. 

https://newsroom.clevelandclinic.org/2021/01/27/cleveland-clinic-lou-ruvo-center-for-brain-health-receives-nih-and-addf-grants-totaling-4-6-million-to-study-fda-approved-cancer-drug-lenalidomide-in-alzheimers-disease/

4. Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer’s disease drug development pipeline: 2020. 

. Published online July 16, 2020. doi: 10.1002/trc2.12050

A group of 15 repurposed agents were identified as the best candidates for activity against the network of 20 related and distinct biochemical pathways that are dysregulated in AD-related dementia. 

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