One of the most mysterious things about multiple sclerosis (MS) is the wide variety of symptoms and lack of uniformity in disability progression. Although some symptoms can be traced to lesions in specific areas of the central nervous system, including the brain, spine, and optic nerves, there is often a disconnect between relapses, lesions, and disability. Little about MS follows predictable patterns.
In the MS community, I’ve heard lots of questions regarding this apparent disconnect. People with MS are sincerely trying to make sense of the disease and find an explanation for their unpredictable experiences. Here are some common questions and potential explanations.
“I had a relapse, but my annual MRI didn’t show any active lesions. Why not?”
Magnetic resonance imaging (MRI) is helpful in the diagnosis of MS because it can detect inflammation and demyelination that primarily affects white matter in the brain or spinal cord. Active inflammation and new demyelination show up in MRI as gadolinium-enhancing lesions. As inflammation resolves and the body works to repair itself, lesions will no longer enhance. Researchers have indicated that it could take monthly MRI scans to catch these lesions as they come and go.
“Why am I still having lots of symptoms if I don’t have any new lesions?” Or the apparent opposite: “I have lots of lesions, but honestly my MS isn’t so bad. How come?”
The disconnect between symptoms and lesions is called the clinico-radiological paradox of MS. It basically means that clinical symptoms and radiological changes detected by standard MRIs do not correlate. This dissociation is multifaceted and may be explained by the presence of lesions in clinically silent regions, the degree and nature of neuroplasticity, and diagnostic shortcomings such as a lack of spinal MRI or underestimation of damage to normal-appearing brain tissue (both white and gray matter).
“Why do I have more cognitive problems and disability when my MRI doesn’t show much disease activity?”
Even in early stages of MS, changes in normal-appearing white and gray matter can lead to brain atrophy (loss of brain volume). Atrophy is more difficult to measure using standard MRI sequences than gadolinium-enhancing lesions. Research shows that brain atrophy correlates with disability progression and cognitive decline in people with MS and the association becomes even stronger in primary progressive MS. Cognitive impairment in MS can affect information processing speed, attention, recent and long-term memory, executive functions, and visuospatial abilities. General intelligence, language, and certain aspects of memory, such as short-term capacity and implicit memory, are spared. Dementia is rare in MS.
“Are there any studies that show how common it is to have a relapse or disability progression without new lesions?”
A Norwegian study that examined disease activity in 72 people with relapsing-remitting MS showed that the most patients with disease activity during one year of follow-up had relapses without MRI progression (21.2 percent), disability progression without MRI progression (27.3 percent), or MRI progression alone (36.4 percent). Only 6.1 percent experience both MRI progression and relapse, and only 9.1 percent experienced both MRI progression and disability progression.
See more helpful articles:
Horakova D, Kalincik T, et al. Clinical correlates of grey matter pathology in multiple sclerosis. BMC Neurol. 2012 Mar 7;12:10. doi: 10.1186/1471-2377-12-10.
Lavery AM, Verhey LH, Waldman AT. Outcome measures in relapsing-remitting multiple sclerosis: capturing disability and disease progression in clinical trials. Mult Scler Int. 2014;2014:262350. doi: 10.1155/2014/262350. Epub 2014 May 4.
Lipp I, Tomassini V. Neuroplasticity and Motor Rehabilitation in Multiple Sclerosis. Front Neurol. 2015;6:59. doi:10.3389/fneur.2015.00059.
Nygaard GO, Celius EG, et al. A Longitudinal Study of Disability, Cognition and Gray Matter Atrophy in Early Multiple Sclerosis Patients According to Evidence of Disease Activity. PLoS One. 2015 Aug 17;10(8):e0135974. doi: 10.1371/journal.pone.0135974. eCollection 2015.
Watties MP, Steenwiik MD, Stangel M. MRI in the Diagnosis and Monitoring of Multiple Sclerosis: An Update. Clin Neuroradiol. 2015 Oct;25 Suppl 2:157-65. doi: 10.1007/s00062-015-0430-y. Epub 2015 Jul 23.
Zapata-Arriaza E, Díaz-Sánchez M. Clinico-radiological dissociation in multiple sclerosis: Future prospects. World J Neurosci. 2013;3:147-153. doi: 10.4236/wjns.2013.33019.