Comment on the article entitled 'Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis' by Reuter F, Zaaraoui W, Crespy L, Faivre A, Rico A, Malikova I, Soulier E, Viout P, Ranjeva JP, Pelletier J, Audo

Fahmy Aboul-Enein, MD,
January 12, 2011

Dear Sir, We have read with great interest the article by Reuter et al. entitled 'Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis' 1 , which seems related to another recent published article. 1,2

Whether steadily ongoing, but clinically silent axonal changes occur in all MS patients and MS subtypes, and if so, progressive axonal changes occur already at the earliest disease stages is still under intense discussion, and of most importance to MS patients, neurologists and researchers. 3-8

The demographics, clinical and MRI data were very similar in both papers. 1,2

For example, the baseline T2 lesion load (T2LL) reported here, was 2.825 (mean, n=24) 1 vs. 2.9 (mean, n=23) reported elsewhere 2

etc., all suggestive that at least 23 of the included MS patients were the same in both studies(?). The used neuropsychological assessment (NpA) was identically described in both publications. 2

However, the numbers of the included MS patients (n=23 vs. n=24) and controls (n=13 vs. n=24) and the numbers of 'cognitive impaired' MS patients differed (baseline, 29% [7 out of 24] of the patients vs. 22% [5 out of 23] of the patients and at year 5, 54% of the patients [13 out of 24] vs. 39% of the patients [9 out of 23]). 1,2 How can these differences be explained? Additionally, NpA consisted of a plenty of exertive and time consuming tests and was described as 'exhaustive'. Were the tests performed in one or multiple sessions? Had disease modifying drugs or their side effects an influence on NpA testing? Figure 1 might be misleading. Bar charts with 'the % of the patients with cognitive impairment' can never replace the detailed information of scatter plots providing single values of patients and controls. Moreover, a regression plot with T2LL (as independent variable?) and cognitive impairment index (CII) would have been preferred by some reviewer and the readers to avoid any confusion or over- interpretation. The T2LL was found increased from 3cm? (mean) at baseline to 4.5cm? (mean) 5 years later. Were the T2LL and the CII correlated weakly or moderately?

Competing Interest: None declared.


1. Reuter F, Zaaraoui W, Crespy L, et al. Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis. J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2010.213744

2. Zaaraoui W, Reuter F, Rico A, et al. Occurrence of neuronal dysfunction during the first 5 years of multiple sclerosis is associated with cognitive deterioration. Journal of Neurology doi: 10.1007/s00415-010-5845-4

3. Kirov II, Patil V, Babb JS, et al. MR spectroscopy indicates diffuse multiple sclerosis activity during remission. J Neurol Neurosurg Psychiatry 2009;80:1330-6.

4. Aboul-Enein F, Krss?k M, H?ftberger R, et al. Reduced NAA-levels in the NAWM of patients with MS is a feature of progression. A study with quantitative magnetic resonance spectroscopy at 3 Tesla. PLoS One 2010;5(7):e11625.

5. Aboul-Enein F, Krss?k M, H?ftberger R, et al. Diffuse white matter damage is absent in neuromyelitis optica. AJNR Am J Neuroradiol 2010;31:76-9.

6. Serbecic N, Aboul-Enein F, Beutelspacher SC, et al. Heterogeneous pattern of retinal nerve fiber layer in multiple sclerosis. High resolution optical coherence tomography: potential and limitations. PLoS One. 2010;5(11):e13877.

7. Serbecic N, Beutelspacher SC, Aboul-Enein FC, et al. Reproducibility of highresolution optical coherence tomography measurements of the nerve fibre layer with the new Heidelberg Spectralis optical coherence tomography. Br J Ophthalmol doi:10.1136/bjo.2010.186221

8. Gilmore CP, Cottrell DA, Scolding NJ, et al. A window of opportunity for no treatment in early multiple sclerosis? Mult Scler 2010;16:756-9.

Conflict of Interest:

None declared

Conflict of Interest

None declared