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Updated: May 5, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Asymptomatic MS
1MS Clinic and Department of Neurology, Cerrahpaşa School of Medicine, Istanbul University, Istanbul, Turkey.
Abstract:
"Asymptomatic multiple sclerosis (MS)" or "subclinical MS" describes "a clinically silent disease state of MS" discovered by chance either by imaging or at autopsy, or with incidental findings shown by other diagnostic tools that are consistent or suggestive of MS, and that cannot be explained by any other disease or condition. Since the early 1960s there have been a number of autopsy studies reporting cases, in which histopathological brain changes consistent with MS were found, despite that none had any clinical symptom or sign of the disease during their lifetime. Several reports have also shown that asymptomatic first-degree relatives of MS patients may have oligoclonal bands in their cerebrospinal fluids or may turn out to have abnormal evoked potential studies. With the extensive availability of MRI lately, the incidence of individuals having these studies performed for indications other than suspicion of inflammatory demyelinating disease of the central nervous system (CNS) such as primary headaches or trauma, revealing unsuspected brain and/or spinal cord lesions compatible with MS had raised. A number of such case-series reported recently had resulted in increased awareness of this finding and to its relationship to clinical multiple sclerosis. This situation is now referred as "radiologically isolated syndrome (RIS)" and is the most common type of "asymptomatic MS". Since it is well known that MS has an asymptomatic period of unknown duration in many individuals preceding its initial presentation, either as a clinically isolated syndrome or in rare instances as primary progressive-MS, it is likely that a number of MS patients will be diagnosed by chance as RIS at an early stage before converting to clinical disease. Currently this issue has gained a wide interest as there are no established protocols regarding how to study and follow these individuals or whether they should be treated or not! However, not all patients with RIS are predestined to develop clinical disease and it was recently shown that the rate of conversion to clinical MS is about one-third of RIS cases at five years. Although that there may be some risk factors suggestive of a higher or earlier conversion to clinical disease, none are definite and the current evidence is not supportive of initiating treatment in patients diagnosed as RIS.
Insights
Asymptomatic multiple sclerosis (MS), or subclinical MS, is a silent disease state discovered incidentally. Radiologically isolated syndrome (RIS) is the most common form, with about one-third of cases progressing to clinical MS within five years.
Area of Science:
- Neurology
- Neuroimmunology
- Radiology
Background:
- Asymptomatic multiple sclerosis (MS) refers to a clinically silent disease state discovered incidentally through imaging, autopsy, or other diagnostic tools.
- Historically, autopsy studies identified MS-like brain changes in individuals without clinical symptoms.
- The advent of MRI has increased the detection of unsuspected central nervous system (CNS) lesions compatible with MS, leading to the recognition of Radiologically Isolated Syndrome (RIS).
Purpose of the Study:
- To define and discuss the concept of asymptomatic multiple sclerosis (MS) and its most common presentation, Radiologically Isolated Syndrome (RIS).
- To highlight the diagnostic challenges and the lack of established protocols for managing individuals with RIS.
- To review the current understanding of RIS conversion to clinical MS and treatment implications.
Main Methods:
- Review of historical autopsy studies reporting subclinical MS.
- Analysis of recent case series and literature on Radiologically Isolated Syndrome (RIS).
- Discussion of diagnostic findings including MRI, cerebrospinal fluid (CSF) oligoclonal bands, and evoked potential studies.
Main Results:
- Radiologically Isolated Syndrome (RIS) is the most frequent form of asymptomatic MS.
- Approximately one-third of individuals with RIS progress to clinically diagnosed MS within five years.
- Current evidence does not support initiating treatment for all RIS patients due to uncertain conversion risk and lack of definitive risk factors.
Conclusions:
- Asymptomatic MS, particularly RIS, represents an early, often incidentally detected, stage of the disease.
- Further research is needed to establish clear guidelines for the monitoring and management of RIS.
- The decision to treat RIS should be individualized, considering the current lack of definitive evidence for early intervention.
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