Early changes in MS


PLoS One. 2018 Jul 6;13(7):e0200254. doi: 10.1371/journal.pone.0200254. eCollection 2018.

Health-related quality of life, neuropsychiatric symptoms and structural brain changes in clinically isolated syndrome.

Hyncicova E, Kalina A, Vyhnalek M, Nikolai T, Martinkovic L, Lisy J, Hort J, Meluzinova E, Laczó J.



Neuropsychiatric symptoms and reduced health-related quality of life (HRQoL) are frequent in multiple sclerosis, where are associated with structural brain changes, but have been less studied in clinically isolated syndrome (CIS).


To characterize HRQoL, neuropsychiatric symptoms (depressive symptoms, anxiety, apathy and fatigue), their interrelations and associations with structural brain changes in CIS.


Patients with CIS (n = 67) and demographically matched healthy controls (n = 46) underwent neurological and psychological examinations including assessment of HRQoL, neuropsychiatric symptoms and cognitive functioning, and MRI brain scan with global, regional and lesion load volume measurement.


The CIS group had more, mostly mild, depressive symptoms and anxiety, and lower HRQoL physical and social subscores (p≤0.037). Neuropsychiatric symptoms were associated with most HRQoL subscores (β≤-0.34, p≤0.005). Cognitive functioning unlike clinical disability was associated with depressive symptoms and lower HRQoL emotional subscores (β≤-0.29, p≤0.019). Depressive symptoms and apathy were associated with right temporal, left insular and right occipital lesion load (ß≥0.29, p≤0.032). Anxiety was associated with lower white matter volume (ß = -0.25, p = 0.045).


Mild depressive symptoms and anxiety with decreased HRQoL are present in patients with CIS. Neuropsychiatric symptoms contributing to decreased HRQoL are the result of structural brain changes and require complex therapeutic approach in patients with CIS.

Ever felt you’ve been dealt a band hand in life, that your credits and debits simply do not square up? The question I’ve often asked myself is why even in the face of adversity do we strive on? It’s not fear of failure that keeps us going, nor is it that death has suddenly become unpalatable. It is because our brains have been programmed to believe in success in all shapes and sizes. A colleague once told me that human beings speak from their hearts and sing from their brains.

Last week at the NHS70 celebrations, a clinical neuropsychologist came to my stand to ask my opinion on whether our personalities are hard wired into our brains (our mind), i.e. is it nurture or is it in our genes (evolution)? My reply was that I suspected it was a bit of both. I pointed out that neurochemical and synaptic changes have been documented in schizophrenia and bipolar disorders, however, negative life events in a person’s life probably also had a significant role to play.

A number of studies in MS have found an association between cognitive dysfunction (brain processing e.g. memory, language, intelligence), depression, anxiety, apathy and a negative impact on quality of life. Structural changes in brain areas have also be related to the severity of neuropsychiatric symptoms – for example, brain volume loss has been associated with increased depression, as have a high lesion load in the frontal and temporal regions. The question is how early are these changes taking place?

In this study the investigators evaluated 67 CIS (clinically isolated syndrome – first symptom of MS), compared to control cases without MS. They found even at the CIS stage more depressive symptoms and anxiety were reported, but were mostly mild and mild-moderate, respectively. Although, the level depression did not affect overall quality of life, CIS cases did report more limitation in “physical functioning”, “social functioning”, “bodily pain” and “general health”. The latter was found to be more likely to be linked to slower cognitive processing speed and self-perceived lower cognitive performance. Unlike studies before, they did not find significant link with fatigue levels (generally speaking fatigue is related to disease duration). Equally, as the disability level is often low at this stage, the investigators did not find a relationship between EDSS scores and neuropsychiatric symptoms. On a structural level, greater anxiety scores were related to lower white matter brain volume, while greater depression scores correlated with higher lesion load in the right temporal lobe.

En face, this type of research comes across as wishy-washy. However, it is important to realize its strengths. As neuroscientists were can bee too focused in what we perceive as organic brain disorders. It is good to see research that challenges this percept. The psyche forms a part of the organic brain, and any dysfunction in this is as real as any physical disability. It is therefore not surprising that around 30% of those who experience depression and anxiety at the CIS stage also have a greater risk of progressing clinically.

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Neuro Doc Gnanapavan

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