A majority of the time, the diagnosis of progressive multiple sclerosis (MS) is retrospective, despite better drugs to counteract the progression of the disease in patients who are diagnosed early.
In MS and other rare diseases that are not supported by scientific consensus confirming their etiology, physicians have often opted for a “wait-and-see” approach to treatment. It is true that MS in some patients progresses very quickly, while progression is surprisingly slow in others. However, if we want to win the war on this disease, we need to aim to cut off its legs before it even gets off the ground — and that is by early detection, early diagnosis, and early treatment.
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A group of researchers wanted to uncover whether certain observable biomarkers could better help predict the progression of the disease — an ambitious project indeed. To carry out this study, an international team of MS experts met in June 2019 in Italy and discussed the available research on MS, such as its clinical, pathological, biological, and neurological features, according to a study published in Annals of Neurology. With these features clearly identified, they then moved on to target the biomarkers that were associated with MS.
MRI Biomarkers
In this article, we will be summarizing some of their findings, with a focus on the MS biomarkers associated with the central nervous system (CNS).
White Matter
Medical imaging has improved vastly over the years, allowing us to identify lesions more accurately. In patients with a clinically isolated syndrome (CIS), lesion topography at the onset of the disease has a high success rate in determining long-term worsening disability. This is even true in patients who are otherwise asymptomatic but have lesions involving the infratentorial region and the spinal cord.
Researchers have discovered that gadolinium (Gd)-enhancing and spinal cord lesions, as well as new spinal cord lesions occurring in the initial 3 years of a disease, are associated with the development of secondary progressive MS and worsening disability.
Grey Matter Lesions
In MRI scans, researchers observe that in primary MS, cortical lesions are more numerous, which correlates with disability and cognitive impairment. A 7-year follow-up study conducted in relapsing-remitting MS patients shows that having 7 or more cortical lesions can predict conversion to secondary-progressive MS.
Using CNS lesions on MRI scans to predict prognosis in patients with MS is a huge step forward; however, good MRI images can only be obtained by a skilled technician, thus limiting its use, especially if there are more urgent cases ahead of the queue.
Grey Matter Atrophy
Researchers have discovered that grey matter damage can predict worsening prognosis more accurately than white matter damage. Several studies have shown that more severe grey matter damage occurs in patients with primary MS as compared to white matter.
When compared to healthy groups, patients with relapsing-remitting MS and secondary-progressive MS had a much greater rate of grey matter atrophy. Another study showed that patients with primary MS experienced deeper and faster grey matter atrophy compared to other subjects. This is confirmed by another study conducted over a decade that looks into the effects of grey matter atrophy on later disease presentation; results from that study show that grey matter abnormalities and atrophy do indeed eventually lead to worse clinical outcomes.
Spinal Cord
Imaging the spinal cord has always been a challenge due to its small cross-sectional area and the difficulty of getting the patient to stay still in a stiff position throughout the scan. However, recent strategies that limit artifacts, such as cardiac gating and fast imaging sequences, have made obtaining better MRI images of the spinal cord possible.
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From these better-quality images, researchers were able to identify lesions and damages in the spinal cord and determine if any of them were associated with MS. They discovered that spinal cord lesions and damage are associated with worsening outcomes in patients with MS. For example, primary MS patients have large, often confluent, spinal cord lesions that are associated with severe disability.
In addition, primary MS patients also have severe cervical cord atrophy, which is associated with suboptimal locomotor function and clinical disability. When cervical cord atrophy accelerates in a patient, so does the patient’s disability progression.
Looking Ahead
If we are to improve our treatment of MS patients, we need to look ahead. Beyond hoping for breakthroughs in the labs, there are plenty of things we can do now to improve the quality of life of MS patients under our care.
Cognition
MS patients do experience cognitive impairment, such as in processing information and memory. Attending physicians tend to be more concerned with the musculoskeletal effects of MS (and rightly so, since it can place a patient under disability); however, it might be a good idea to ask a few questions about the patient’s cognitive abilities as well. There are many simple cognitive tests that can be done at the clinic, and physicians are advised to perform a cognitive assessment with their MS patients annually.
Patient-Reported Outcomes
Currently, we do not have a standardized survey that MS patients can fill in to report on how they’re coping. This means that physicians only get to receive anecdotes from their patients during clinic visits. Standardized quality of life surveys have been implemented in other diseases, and there is no reason why we should not have one for MS too.
Comorbidities
Although physicians routinely ask about comorbidities whenever seeing a patient for the first time, it might be worth pressing on and learning more about their comorbidities in the case of MS. This is because we know so little about the etiology of the disease. We know that CNS lesions and CNS atrophy can trigger MS, but what, in turn, causes that to occur? Could lifestyle choice play a bigger role than we imagined? If we integrate comorbidity assessment into MS monitoring, we might uncover more clues into the mechanisms that cause MS.
References
Filippi M, Preziosa P, Langdon D. Identifying progression in multiple sclerosis: new perspectives. Annals of Neurology. Published online June 7, 2020. doi:10.1002/ana.25808
Magyari M, Sorensen PS. Comorbidity in multiple sclerosis. Front Neurol. Published online August 21, 2020. doi:10.3389/fneur.2020.00851
