Constantinescu_EU Neurology 09/03/2010 13:33 Page 72
Multiple Sclerosis
Ninety-two newly diagnosed MS and CIS patients were studied by Camp et al.
29
studied a group of 99 PP MS patients over two years.
Glanz et al.
22
The BRB of neuropsychological tests was performed, Patients were assessed at 12-month intervals using the BRB of
and conventional T
2
-weighted images acquired. Lesion volumes and neuropsychological tests. Also, at each assessment the T
1
and T
2
tissue volumes were computed. Patients were classified as lesion volumes and partial brain volume were estimated. At baseline,
cognitively intact or impaired by comparison with cognitive scores there was moderate correlation between T
1
and T
2
lesion volumes
achieved by 27 healthy volunteers. There was no statistical difference and cognitive function. Overall cognitive function did not change over
between the intact and impaired groups in any MRI measure, the study period, although results on individual tests showed some
suggesting that cognitive impairment may pre-date the appearance of decline. There was no correlation between the changes seen on MRI
gross structural abnormalities on MRI. and cognitive function.
Longitudinal Studies Quantitative Magnetic Resonance Imaging
Several longitudinal studies investigating cognitive decline using Studies of Cognitive Impairment in
MRI have now been performed, with follow-up from three Multiple Sclerosis
months to 8.5 years. Mariani et al.
23
investigated 19 moderately Most conventional MRI studies have used LV as a measure of disease
impaired RR (initially) MS patients over an average of two years. burden, but excluded contribution from MRI-normal-appearing brain
Neuropsychological tests indicated a very mild overall impairment, tissue (NABT). Studies that estimate tissue loss include NABT, but not
which did not decline over the study period. There was also no exclusively. Quantitative MRI modalities such as magnetisation transfer
evidence of change on MRI. Mattioli et al.
24
investigated nine mildly imaging have been shown to be sensitive to changes even within the
disabled RR MS patients over three months using gadolinium- NABT, and can therefore be used to assess its contribution directly.
enhanced MRI and neuropsychological evaluation. Again, there was
no overall decline in cognitive performance, and in patients whose Filippi
30
assessed NABT change using MTR in 19 patients with MS.
scores reduced in absolute terms there was no correlation with Neuropsychological testing was performed and patients classified as
the changes on MRI. impaired (n=12) or intact (n=7). Lesions were identified and brain
volume estimated. MTR summary statistics were computed within
Hohol et al.
25
studied 44 MS patients with various disease courses lesions and in the whole NABT by excluding the lesions. In the
over a period of one year. Frequent scanning with conventional MRI impaired group the LV was higher, brain volume smaller, lesion MTR
was performed and two MRI measures, total lesion volume (LV) and lower and NABT MTR lower. A multivariate regression model revealed
brain-to-intracranial cavity volume ratio were estimated automatically. that MTR of the NABT was the only significant predictor of cognitive
Significant correlations were found between neuropsychological test function in the impaired group. A similar study methodology was
scores and the MRI measures at both baseline and follow-up. followed by Zivadinov,
31
but focusing on early RR MS. The study
However, cognitive performance did not worsen on average over the involved 63 MS patients and 30 healthy controls. An extensive BNT
study period. Nevertheless, change in information processing speed was administered and 15 patients were found to be impaired. NABT
and attention was found to correlate with change in total LV. MTR was significantly lower in the patient group, and was lowest in
the impaired group. However, lesion volumes did not differ between
Zivadinov et al.
26
studied a homogeneous group of 53 early-phase RR impaired and intact patients, although there was a trend for reduced
MS patients with a two-year follow-up period to investigate whether MTR in the lesions of the impaired group. Brain volume was also
cognitive decline depends on progression in lesion burden or on the smaller in the impaired group than the intact group. Overall cognitive
loss of brain tissue. A BNT was used, and MRI measures were T
1
and impairment correlated with both brain volume and NABT MTR, even
T
2
lesion volumes and brain parenchymal volume (BPV). Patients were though these predictors did not correlate with each other.
categorised as cognitively improved, stable or worsened at follow-up.
At baseline, cognitive function did not correlate with any MRI Recently, diffusion-weighted MRI (DWI) has become a popular research
measure. However, BPV reduced significantly more in patients who tool in MS. Using an appropriate protocol, diffusion tensor imaging (DTI)
were cognitively worsened at follow-up. Furthermore, decline in can be performed and quantitative metrics that detail the diffusivity in
cognitive function over the two-year study period correlated with vivo computed; these metrics are thought to reflect demyelination.
reduction in BPV but not LV. Several studies have now employed this to measure changes in the
NABT. Rovaris et al.
32
studied 34 RR MS patients using DTI metrics as
Sperling et al.
27
studied 28 patients over a period of four years with well as conventional MRI measures. Patients also underwent an
assessment at baseline, one year and four years. Initially, 15 patients extensive BNT. No significant difference on MRI was detected between
were RR and 13 chronic progressive. The BRB tests were performed. cognitively intact and impaired patient groups. However, mean
Lesion volumes were automatically estimated in four regions in diffusivity of brain tissue and NABT moderately correlated with some
the brain. Lesion volumes correlated significantly with cognitive cognitive test scores. Benedict et al.
33
performed a similar study on 40
performance at baseline and at each follow-up. No cognitive decline RR MS and 20 SP MS patients. Again, there were moderate correlations
or change on MRI was detected over the study period. between cognitive function and MRI measures. Intact and impaired
patients differed in conventional MRI measures, but not in metrics
Piras et al.
28
studied 12 RR MS patients at baseline and at 8.5 years. derived from diffusion data.
Patients underwent neuropsychological testing and MRI. LV and
cortical and subcortical atrophy were estimated. There was mild Sophisticated analysis techniques have been developed that use DWI
cognitive impairment at baseline, and significant worsening at to estimate orientation of the white-matter fibres. Tractography can
follow-up. There were also apparent changes on MRI; however, these then produce stream lines that approximate the path of the fibres
did not correlate with the cognitive decline. through the brain.
34
This scheme has been developed into a method
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