Cognitive impairment, fatigue and depression in multiple sclerosis: Is there a difference between benign and non-benign MS?
Related Experiment Video
Updated: Aug 5, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Hans Bogaardt1, Daniel Golan2, Marissa A Barrera3
1School of Allied Health Science and Practice, University of Adelaide, Adelaide, Australia.
Introduction:
Multiple Sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). The severity of disability in people with MS (PwMS) is generally measured with the Expanded Disability Status Scale (EDSS). A variant of MS known as 'benign MS' (BMS) has been defined as an EDSS score of 3 or lower, combined with a disease duration of 10 years or longer; however, there is disagreement in the field about whether BMS really exists. Given that the EDSS does not capture cognitive issues, communication dysfunction, fatigue, depression, or anxiety properly, its ability to accurately represent disability in all PwMS, including BMS, remains questionable.
Methods:
In this study, 141 persons with BMS (PwBMS) were included, consisting of 115 females (82%) and 26 males (18%) with a mean age of 50.8 (±8.68). A computerized test battery (NeuroTrax®) was used to assess cognition, covering seven cognitive domains (memory, executive function, visual-spatial processing, verbal function, attention, information processing, and motor skills). Fatigue was measured using the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was used to assess symptoms of depression. Cognitive impairment was defined for this study as when someone has a score lower than 85 in at least two subdomains of the cognitive test battery. Rates of impairment were compared to 158 persons with non-benign MS (PwNBMS; with a disease duration of 10 years and longer and an EDSS score higher than 3) and 487 PwMS with a disease duration of fewer than 10 years.
Results:
Cognitive impairment was found in 38% of PwBMS and in 66% of PwNBMS (p<0.001). In PwBMS, the lowest rate of impairment was found in the verbal function domain (18%) and the highest rate of impairment in the domain of information processing (32%). Fatigue and depression were found in 78% and 55% of all PwBMS, with no difference in these rates between PwBMS and PwNBMS (p = 0.787 and p = 0.316 resp.) CONCLUSION: Cognitive impairment, fatigue and depression are common among people with an EDSS-based definition of benign MS. These aspects should be incorporated into a new and better definition of truly benign MS.
Insights
Cognitive impairment, fatigue, and depression are common in benign multiple sclerosis (MS) despite low Expanded Disability Status Scale (EDSS) scores. Current definitions of benign MS may not fully capture the patient experience.
Area of Science:
- Neurology
- Neuroscience
- Clinical Medicine
Background:
- Multiple Sclerosis (MS) is a chronic CNS disease impacting disability, often measured by the Expanded Disability Status Scale (EDSS).
- Benign MS (BMS) is defined by low EDSS scores (≤3) and long disease duration (≥10 years), but its existence and definition are debated.
- The EDSS may not adequately assess cognitive function, fatigue, depression, or anxiety in people with MS (PwMS).
Purpose of the Study:
- To investigate the prevalence of cognitive impairment, fatigue, and depression in individuals meeting the EDSS-based definition of benign MS (BMS).
- To compare these outcomes in PwBMS with those in PwMS with non-benign MS (PwNBMS) and shorter disease duration.
- To evaluate the adequacy of the current EDSS-based definition of BMS.
Main Methods:
- 141 individuals with BMS (PwBMS) and 158 with non-benign MS (PwNBMS) (≥10 years duration, EDSS >3) were assessed.
- Cognitive function was evaluated using the NeuroTrax® computerized test battery across seven domains.
- Fatigue was measured by the Fatigue Severity Scale (FSS), and depression by the Beck Depression Inventory (BDI).
Main Results:
- Cognitive impairment affected 38% of PwBMS compared to 66% of PwNBMS (p<0.001).
- Information processing (32%) and verbal function (18%) were the most and least affected cognitive domains in PwBMS, respectively.
- Fatigue (78%) and depression (55%) were highly prevalent in PwBMS, with no significant difference compared to PwNBMS.
Conclusions:
- Cognitive impairment, fatigue, and depression are prevalent in individuals classified with benign MS based on EDSS.
- The current EDSS-based definition of benign MS may be insufficient to capture the full spectrum of disability.
- A revised definition of benign MS should incorporate cognitive, fatigue, and mood assessments for a more accurate representation.
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