New expert guidance on discussing the sensitive topic of brain atrophy in multiple sclerosis (MS) has been released.
Robert Zivadinov, MD, PhD
On the basis of data from surveys, workshops, and other sources, a team of providers, patients and researchers has developed 13 recommendations to help improve treatment adherence and underline the importance of a healthy lifestyle, guideline author Robert Zivadinov, MD, PhD, professor of neurology, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, told Medscape Medical News.
“It’s very important to explain to patients that they can’t just rely on disease-modifying treatments and the work is done; there are so many different lifestyle choices they need to undertake in order to grapple with this problem,” he stated
The paper was published online November 14, 2022, in the Journal of Neurology.
Clinicians rely on MRI to investigate a patient’s MS disease status. Scans reveal the number of contrast-enhancing lesions, new or enlarging T2 lesions, and T1 hypointense “black holes” (white matter lesions) and can be used as biomarkers for diagnosis, monitoring, and treatment response.
But increasingly, brain atrophy is used as a prognostic biomarker for development of cognitive dysfunction and physical disability in patients.
“For many years, MS was mostly about the appearance of lesions and relapses, but now with the effectiveness of therapies, the lesions are less of a problem and continuous loss of tissue over time is much more important and what leads to disability and disease progression,” said Zivadinov.
However, discussing brain atrophy with patients should be handled with tact, sensitivity, and in context, he added.
Over the course of 2 years, the authors conducted workshops and surveys to gather relevant data on provider practices for discussing MRI findings, as well as patient perceptions about such findings.
Thirteen MS specialists from six US MS centers participated in the survey, along with 26 randomly selected patients with MS. At the end of this process, participants developed 13 recommendations.
The recommendations stress the need for providers to explain to patients what brain anatomy is and how it’s measured. Providers should impress on patients the need for standardized MRI exams and discuss background on volumetric changes.
The authors stressed the need to communicate how an individual patient’s atrophy measurements compare with normal aging. “Each one of us loses a percentage of our brain volume every year from age 18 years onwards, but this is accelerated by up to fivefold in MS patients,” said Zivadinov.
To prevent alarming patients who might think their brain is shrinking rapidly, clinicians should consider referring to “changes in brain volume” rather than “brain atrophy” or “neurodegeneration,” the authors note.
Timing and Language
The timing and language used to convey information pertaining to brain atrophy should tailored to individual patients on the basis of their background and disease status, the authors note.
But interpreting brain volume changes at the individual patient level is challenging. Technical issues such as the type of scanner used may affect brain volume measures, as can individual fluctuations based on such things as the menstrual cycle and intake of coffee and alcohol, said Zivadinov.
Clinicians should also explain to patients that although MS therapies are quite effective in preventing new lesions and relapses, loss of tissue or brain atrophy may still lead to disease progression, said Zivadinov. “Patients should understand they need to take therapies that can help this phenomenon.”
In general, sphingosine-1-phosphate (S1P) receptor inhibitors may slow brain atrophy by about 30%. This compares with MS therapies that tend to slow lesion progression by more than 90%.
“S1P receptor inhibitors are probably one of the best drugs to slow down brain atrophy”, said Zivadinov, adding monoclonal antibodies may also curb atrophy.
Researchers are developing another class of drugs, Bruton tyrosine kinase (BTK) inhibitors, that may have a better effect on neurodegeneration, said Zivadinov. BTK regulates the functions of B cells and myeloid cells implicated in the pathogenesis of MS.
Clinicians should also communicate to patients with MS the benefits of physical and mental exercises such as games that can slow or reverse neurodegeneration that leads to brain atrophy, said Zivadinov.
Providers should allot additional time during clinical visits to discuss these topics. A discussion guide may be a helpful resource to support these discussions, said the authors.
Zivadinov said that he and his co-authors would like to develop a “pocket brochure” with the recommendations that clinicians can keep on their desk for handy referral.
The process used to develop these recommendations could be used as a model for other diseases, said Zivadinov.
Commenting for Medscape Medical News, Torge Rempe, MD, assistant professor in the Department of Neurology, College of Medicine, University of Florida, said he appreciated that the authors developed the new guidance based on data from multiple stakeholders.
“Based on the collective agreements of patients, providers, and researchers, the authors propose helpful recommendations on how to best communicate the relevance of brain atrophy to persons with multiple sclerosis,” he stated.
Rempe noted that brain atrophy and accelerated brain volume loss are important biomarkers for long-term disability and cognitive impairment in MS.
“While still limited by significant noise and a high degree of variability across scanners, clinical utility has become more relevant with emergence of commercially available volumetric segmentation tools,” he said.
He noted that absence of accelerated brain volume loss has even been proposed as a fourth criterion of “no evidence of disease activity” (NEDA). “However, interpretation of annualized brain volume loss on an individual patient level remains difficult, making good education and explanation to patients important as well as challenging.”
Zivadinov reports that he has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Keystone Heart, Protembis, and Novartis for speaking and consultant fees. He received financial support for research activities from Sanofi, Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Keystone Heart, Protembis, and V-WAVE Medical. Rempe reports no relevant conflicts of interest.
J Neurol. Published November 14, 2022. Abstract
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