Review: SPECT, MRI and Cognitive Dysfunction in Multiple Sclerosis

The featured article is ‘SPECT, MRI and cognitive functions in multiple sclerosis’ by Pozzilli and colleagues and freely available here. The aim in this study was to clarify the distribution of 99mTc HMPAO (used as a marker of cerebral blood flow) in the brains of people with relapsing-remitting multiple sclerosis with ‘mild physical and cognitive disturbance’. The authors selected 17 people with Multiple Sclerosis from a Multiple Sclerosis outpatient clinic. However the selection criteria aren’t clear – there is no mention of consecutive patients being considered or random assignment otherwise.  The exclusion criteria are clearly stated as those with chronic progressive illness and MMSE scores less than 23 or a score greater than 4 on the Kurtzke Expanded Disability Status Scale. There is some information on the sample demographics/scores with an average MMSE of 28.5. I wasn’t able to identify power calculations for estimating sample size.

A neuropsychological test battery was administered including verbal memory digit span component of the WAIS and measures of auditory and visual memory amongst others. 17 people with Multiple Sclerosis but without cognitive impairment were selected matching for basic demographics. Patients underwent an MRI scan using a 1.5 Tesla scanner and a neuroradiologist who was blinded to the diagnosis rated the white matter lesions. The lesions were classed as single or confluent. The area of the corpus callosum was identified by what sounds like manual demarcation on the imaging software. I wasn’t clear on how the ‘graphic table’ worked but presumed that the software had a function for calculating areas that had been demarcated. SPECT scans were also obtained and rated by investigators blind to the diagnosis. The researchers chose several regions of interest and ‘normalised’ the data. This involved dividing the activity in voxels by the average whole brain voxel activity.

Here’s a link to an Open University video on SPECT being performed on the heart which shows the general principles of SPECT.

On the neuropsychology tests the MS group performed significantly worse than controls on language tests, short term verbal memory, rey auditory verbal learning and figure memory. However a number of the cognitively impaired patients were unable to complete some of the tests.

The Mann-Whitney U test was used to analyse the lobar asymmetry values presumably because the data was ranked after being normalised. The Mann-Whitney U test is being used for comparison of ordinal unpaired data to see if they come from the same distribution. Here’s a video on YouTube that covers the Mann-Whitney U test (albeit at the end) and also with some focus on the software being used.

For the SPECT and MRI data, there were only a few significant differences between the groups. Thus there was a significantly larger third ventricle index value in the cognitively impaired group, and significantly larger asymmetric cerebral blood flow values in the control group in the parietal and temporal lobes compared to people with cognitive dysfunction. The authors concluded that the auditory test was one of the most sensitive at picking up memory impairment. It wasn’t clear if this was related to the significant differences they found in the cerebral blood flow in the temporal lobe in the two groups. They also commented on the most sensitive associations with cognitive dysfunction being the corpus callosal area and third ventricle width which itself might reflect atrophy of related areas. The sample size is relatively small and it would be interesting to see if these findings were replicated on larger sample sizes. The corpus callosal fibres obviously interconnect the hemispheres but does this reduction simply mean that there are less connections and that this results from the disease process. As this is a cross-sectional study we don’t know if these findings are independent of the disease process itself.

This is a small study which generates testable hypotheses for use in further studies.

STT4 (larger replication study with confirmation of findings, construction of appropriate rehabilitation strategy, intervention with appropriate rehabilitation strategy in further trial and if successful, incorporation of treatment strategy into policy)

Steps To Treatment (STT)

STT = Steps To Treatment. An estimate of the number of steps between the results and translation into treatment. This is an opinion.


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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.


  1. In 2006, Laura Lawes was diagnosed with Multiple Scelrosis and given a life expectancy of one year. Three years later, she was not only living strong, but she gave birth to her first son. It was called “a miracle birth”. These miracles are possible today, because of the work organizations, such as yourself, have done. Here, at (a website dedicated to disease preventions and treatments) we are inspired by stories such as this, and would like to join you in fighting this cause. If you could, please list us as a resource or host our social book mark button, it would be much appreciated. Lets create more of these miracles; together.If you want more information on that please email me back with the subject line as your URL.


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