Disability Assessment In Multiple Sclerosis

The relative rarity of Primary/Progressive (PP) and Transitional/Progressive (TP) Multiple Sclerosis has meant that little documentation of Cognitive function in such patients is currently available.

The aim of this study was to investigate the Cognitive skills of patients with PP and TP Multiple Sclerosis relative to matched healthy controls, and to examine the relationship of this impairment to MRI parameters.

Sixty-three patients (43 PP, 20 TP) were individually matched with healthy controls, who undertook the same Cognitive tasks as the patient group.

The NeuroPsychological assessment comprised Rao's brief repeatable battery, a reasoning test, and a measure of Depression. Patients also underwent T₁- and T₂-weighted Brain MRI.

These patients were taken from a larger cohort (158 PP, 33 TP).

In whom it had been demonstrated that there were no significant differences between the mean scores of the PP and TP groups on any of the Cognitive variables.

The 63 patients were therefore taken as one group for comparison with the healthy controls.

These patients performed significantly worse than the controls in tests of Verbal Memory, Attention, Verbal Fluency and Spatial Reasoning. An impairment index was constructed and applied to the patient data.

This correlated modestly with T₂-lesion load (r = 0.45, P = 0.01), T₁-HypoIntensity load (r = 0.45, P = 0.01) and Cerebral volume (r = -0.35, P = 0.01).

Thus, PP and TP Multiple Sclerosis patients demonstrate significant Cognitive Dysfunction when compared with matched healthy controls.

The relationship between this Impairment and MRI parameters is moderate.

Suggesting that Cognitive Dysfunction in PP and TP Multiple Sclerosis has a complex and multifactorial Etiology, which is not adequately explained by pathology as demonstrated on conventional MRI.

It is generally believed that most T₂-weighted (T₂) lesions in the Central White Matter of patients with Multiple Sclerosis begin with a variable period of T₁-weighted (T₁) Gadolinium (Gd) enhancement.

And that T₁ Gd-enhancing and T₂ lesions represent stages of a single pathological process.

Lesion probability maps can be used to test this hypothesis by providing a quantitative description of the spatial distribution of these two types of lesions across a patient population.

The simplest prediction of this hypothesis would be that the spatial distributions of T₁ Gd-enhancing and T₂ lesions are identical.

We generated T₁ Gd-enhancing and T₂ lesion probability maps from 19 patients with Relapsing/Remitting Multiple Sclerosis.

There was a significantly higher probability (P = 0.001) for T₂ lesions to be found in the Central relative to the Peripheral White Matter (risk ratio 4.5).

Although the relative distribution of T₁ Gd-enhancing lesions was not significantly different (P = 0.7) between Central and Peripheral White Matter regions (risk ratio 0.6).

Longitudinal data on the same population were used to demonstrate a similar distribution asymmetry.

Between new T₁ Gd-enhancing and new T₂ lesions that developed over the course of 1 year. Alternative hypotheses to explain this observation were tested.

1. We found no spatial difference in the likelihood of development of persistent T₂ lesions following T₁ Gd enhancement.

2. The relative distribution of T₁ Gd-enhancing lesions was shown to be independent of the dose of Gd contrast agent and the frequency of scanning.

Our findings suggest that a proportion of the PeriVentricular T₂ lesion volume may arise from mechanisms other than those associated with early breakdown of the Blood-Brain Barrier leading to T₁ Gd enhancement.

The purpose of this study was to relate abnormalities of Motor Conduction time to the presence of Spinal Cord MRI lesions in Progressive Multiple Sclerosis.

And to investigate the relationship between changes in Motor Conduction over time and clinical and MRI changes.

Central Motor Conduction Time (CMCT), serial MRI of the Brain and Spinal Cord, and clinical evaluations were carried out in 20 patients with Primary and Secondary/Progressive Multiple Sclerosis.

CMCT was carried out at the beginning and end of the study while the clinical and MRI examinations occurred at monthly intervals for 12 months. Median CMCT to abductor Pollicis Brevis was 14.8 ms (range 8.8-27.4 ms).

The response latency to Tibialis Anterior correlated with Disability measured on the Expanded Disability Status Scale.

Latencies to upper limb muscles correlated with Cervical MRI lesion load and the presence of Atrophy of the Cervical Cord.

Over the 12-month study period, 15 of 19 patients deteriorated clinically.

However, an increase in Motor Response Latencies occurred only in the four patients who had developed new Cord lesions.

The results suggest that prolonged CMCT is related to Spinal Cord lesion load and that, over time, changes in the CMCT occur only when Spinal Cord Lesion Load increases.

Clinical change in Progressive Multiple Sclerosis may therefore occur without either the development of new Lesions on MRI scans or an increase in Motor Conduction time.

This suggests that clinical deterioration in these patients may occur by a mechanism other than increasing DeMyelination. This may be Progressive Axonal Degeneration.

We performed fast Fluid-Attenuated Inversion Recovery (fFLAIR) and Conventional Spin Echo (CSE) Brain MRI in 32 Multiple Sclerosis (MS) patients (eight each Benign, Relapsing/Remitting, Primary/Progressive, and Secondary/Progressive).

We compared number and site of Lesions detected on each sequence. With initial separate assessment, we identified a total of 3,668 lesions - 2,892 by CSE and 2,943 by fFLAIR.

Following simultaneous review of the sequences, we identified an additional 217 lesions on fFLAIR and 229 on CSE.

1. fFLAIR detected fewer lesions in the Posterior Fossa (66 versus 138, p = 0.001)
2. fewer small (< 5 mm) discrete Cerebral White Matter lesions (671 versus 829, p = 0.0002)
3. more SubCortical lesions (542 versus 306, p < 0.0001)
4. and more large discrete lesions (419 versus 385, p = 0.0006).

Its relatively poor detection of Posterior Fossa lesions makes it premature for fFLAIR to replace CSE as the primary sequence for detecting MS lesions in clinical trials.

In this study we evaluated the relationships between clinical variables and lesion volumes measured from Magnetic Resonance Imaging (MRI) scans in a large cohort of Multiple Sclerosis (MS) patients.

One hundred and thirty MS patients studied:
• 36 Relapsing/Remitting (RR)
• 39 Benign (B)
• 42 Secondary/Progressive (SP)
• 13 Primary/Progressive (PP) courses

There was a significant correlation (r = 0.3; p = 0.0006) between the total lesion load and the EDSS score when the whole cohort of patients was considered.

This correlation increased (r = 0.5) when only patients with RRMS and SPMS were considered.

Our data indicate that a correlation between Disability and MRI lesion volume in MS exists, but its strength is moderate.

Objective
To assess the usefulness of serial Cord MRI in patients with Progressive Multiple Sclerosis.

Methods
Monthly MRI of the Brain and Spinal Cord with and without Gadolinium enhancement was carried out in 19 patients with Progressive Multiple Sclerosis (10 Primary/Progressive, nine Secondary/Progressive) over the course of one year.

Results
During this period there were 132 active lesions in the Brain and only six in the Cord.

One hundred and twelve (85%) active Brain lesions occurred in the Secondary/Progressive group; three new Cord Lesions occurred in each group.

In the Secondary/Progressive group MRI activity was high in patients who had superimposed relapses.

Whereas in those who progressed without relapse and in the Primary/Progressive group it was low.

Cross-Sectional Areas of the Cord decreased at the C5 level in both groups, implying progressive Atrophy of fiber tracts.

There was no relation between either Brain or Cord MRI activity and change in Disability over the study period.

Conclusions
Although the detection of new lesions by frequent Cord imaging using current technology has little role in the monitoring of disease activity in Progressive Multiple Sclerosis, the serial measurement of Cord cross sectional area may be important.

There is also evidence to suggest that the mechanism underlying irreversible Disability in patients with Progressive Multiple Sclerosis may be different in patients who continue to relapse than in those who do not.