Clinically Isolated Syndromes Abstracts 02

Whereas it is important to gain prognostic information in patients with Clinically Isolated Syndromes (CIS) suggestive of Multiple Sclerosis (MS), there is still a lack of definitive data about the significance of Normal-Appearing White (NAWM) and Gray (NAGM) Matter damage in these patients.

The aim of this study was to clarify the role of Magnetization Transfer Magnetic Resonance Imaging (MT MRI) in assessing "occult" damage at the earliest clinical stage of MS.

Dual echo, post-contrast T₁-weighted, and MT MRI were obtained from 43 CIS patients with paraclinical evidence of spatial disease dissemination within 3 months from disease onset and from 22 controls.

In patients, conventional MRI was obtained after 3 and 12 months from the baseline assessment, to detect disease Dissemination In Time (DIT).

A Neurologic Examination was also conducted to ascertain the occurrence of relapses for an average follow up period of 1389 (range = 420-1847) days.

MTR maps were derived and NAWM and NAGM MT ratio (MTR) Histograms were analyzed.

During the follow up, 30 patients showed MRI evidence of DIT, and 21 experienced a relapse. T₂ lesion volume (LV) was significantly higher in patients with DIT than in those without (p=0.005).

MTR Histogram variables did not significantly differ between patients with MRI or clinical DIT. T₂ LV was the only significant predictor of clinical DIT at follow-up (p=0.001).

This study shows that MT MRI-detectable damage to NAWM and NAGM may not be an important feature of all patients at presentation with a CIS highly suggestive of MS and that such a damage may develop with subsequent disease evolution.

The aim of this study is to investigate abnormalities in the Brain tissue of patients with Clinically Isolated Syndrome (CIS) suggestive of Multiple Sclerosis (MS).

In this method, Magnetization Transfer Ratio (MTR) parameter accompanied with segmentation regional measurements and Histogram analysis were used to improve the evaluation of disease progression in CIS patients.

Conventional MR imaging protocols such as T₁-weighted, T₂-weighted, T₂-FLAIR as well as MT-2DSPGR were performed on four CIS patients and four normal subjects.

White Matter, Gray Matter and lesion masks were segmented from T2-weighted images and superimposed on MTR map using FSL software.

Lesions were classified into Isontense and severely HypoIntense according to their signal intensities relative to White Matter on the T₁-weighted images.

MTR parameters of these two lesion types, Normal-Appearing White Matter (NAWM) and Normal-Appearing Gray Matter (NAGM) were analyzed in comparison with those of normal controls.

The MTR Histograms of NAWM and NAGM were also generated for each segmented Brain tissues.

A significant reduction was found in mean White Matter MTR and the Histogram peak position between CIS patients and healthy subjects.

The MTR Histogram for NAWM showed also a total shift to the left.

The MTR value for Gray Matter in CIS patients was similar to that of controls. IsoIntense lesions have significantly higher MTR values than severely HypoIntense lesions.

Significant reduction in NAWM-MTR compared to normal subjects shows that pathological changes outside visible lesions on conventional MR images occur among patients with CIS at presentation.

Objectives
The vast majority of Clinically Isolated Syndrome (CIS) patients with at least two silent Brain MRI lesions progress to Multiple Sclerosis (MS) as early as after 2 years meaning that they actually have MS, the earliest MS.

Effective therapy with Interferon-beta preparations in patients with the earliest MS demands early and accurate diagnosis of the disease.

Patients And Methods
In order to find the differentiating clinical and paraclinical characteristics of patients with the earliest MS we compared clinical, MRI, CSF and Evoked Potential findings in patients with the earliest MS and patients with Relapsing/Remitting (RR) MS.

Retrospective analysis included 149 patients (103 women), among them 40 patients with the earliest MS and 95 patients with RR MS.

Results
Patients with the earliest MS had more often predominant afferent symptoms (p=0.023) but less often predominant Cerebellar (p=0.033) and efferent symptoms (p=0.012) than patients with RR MS.

They were less likely to fulfill the Barkhof Brain MRI criteria (p=0.050) and had less often prolonged latencies of Visual Evoked Potentials (VEP) (p=0.006) than patients with RR MS.

On the other hand they were more likely to have elevated CSF cells (p=0.010) than patients with RR MS and had as often present CSF OligoClonal Bands (p=0.112).

Conclusion
The differentiating characteristics of patients with the earliest MS are predominance of afferent symptoms.

Less Brain MRI dissemination and more frequently normal VEP, but on the other hand abnormal CSF findings with elevated CSF cells and positive OligoClonal Bands.

Clinically Isolated Syndromes (CIS) are events suggestive for emerging Multiple Sclerosis (MS). A majority of patients develop MS within months or years while others remain clinically isolated.

The goal of this study was to investigate whether bioChemical metabolites detectable by 1H-Magnetic Resonance Spectroscopy (MRS) may serve to distinguish between these two groups.

We investigated 41 patients 14 years after presentation with a CIS and 21 controls with combined quantitative short echo 1H MRS and Magnetic Resonance Imaging (MRI) and assessed disability according to the Expanded Disability Status Scale (EDSS).

At follow-up, 32 had developed MS, and 9 still had CIS. Compared with controls, MS patients demonstrated significantly higher concentrations of myo-Inositol (Ins) in Normal-Appearing White Matter (NAWM) and lesions.

Lesions also demonstrated a reduced N-AcetylAspartate (NAA) level and an increase in Choline-containing compounds (Cho). The NAWM Ins concentration was correlated with EDSS (r = 0.48, p = 0.005).

MS Normal-Appearing Cortical Gray Matter (CGM) exhibited a decreased NAA. Patients who remained CIS did not differ significantly from controls in any MRS measure.

Metabolite changes in Normal-Appearing White and Gray Matter in MS indicate diffuse involvement of the entire MS Brain, which was not seen in the persisting CIS patients.

Elevated Ins in MS NAWM appeared functionally relevant It may indicate Glia Cell proliferation or Gliosis.

Clinically Isolated Syndromes (CIS), such as Optic Neuritis, BrainStem or Spinal Cord Syndromes are frequently the first clinical presentations of Multiple Sclerosis.

However, not all CIS patients develop Multiple Sclerosis and in those who do, Disability is highly variable.

In previous follow-up studies, Brain lesions on T₂-weighted MRI are associated with increased risk of Multiple Sclerosis and to an extent disability.

We evaluated the longitudinal relationships between the MRI lesions and clinical course over a period of 20 years.

CIS patients were recruited between 1984 and 1987 and previously followed up after 1, 5, 10 and 14 years.

Of the 140 subjects who were initially recruited with a CIS for a baseline MRI study, we followed up 107 patients after a mean of 20.2 years (range 18-27.7).

Multiple Sclerosis was diagnosed as clinically definite on clinical grounds only and disability determined using the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) score.

Clinically definite Multiple Sclerosis developed in 67 out of 107 (63%) overall: 60 out of 73 (82%) with abnormal and 7 out of 34 (21%) with normal baseline MRI.

Multiple Sclerosis was still Relapsing/Remitting in 39 (58%)-including 26 (39%) with a 'Benign' course (EDSS < /= 3)-whilst 28 (42%) had developed secondary progression.

T₂ Lesion Volume at all time-points correlated moderately with 20-year EDSS (r(s) values 0.48 to 0.67; P < 0.001) and MSFC z-score [r(s) values (-0.50) to (-0.61); P < 0.001].

In those developing Multiple Sclerosis, a concurrent correlation of change in T₂ lesion volume with change in EDSS was most evident in years 0-5 (r(s) = 0.69, P < 0.001).

The estimated rate of lesion growth over 20 years was 0.80 cm(3)/year in those who retained a Relapsing/Remitting Multiple Sclerosis course.

And 2.89 cm(3)/year in those who developed Secondary/Progressive Multiple Sclerosis, a difference of 2.09 cm(3)/year (95% CI: 0.77, 2.96; P < 0.001).

This study extends previous follow-up of CIS patients and sheds new light on how the lesions evolve according to the natural history.

Baseline MRI findings are predictive for development of Clinically Definite Multiple Sclerosis.

Lesion Volume and its change at earlier time points are correlated with Disability after 20 years.

Lesion volume increases for at least 20 years in Relapse-Onset Multiple Sclerosis and the rate of lesion growth is three times higher in those who develop Secondary/Progressive than in those who remain Relapsing/Remitting Multiple Sclerosis.

Background And Purpose
Current MR imaging criteria for Multiple Sclerosis (MS) do not specify the magnetic field strength (T [Tesla]).

The aim of this study was to investigate whether different MR imaging field strengths, specifically high-field MR imaging, have an impact on the classification of patients with Clinically Isolated Syndromes suggestive of MS, according to MR imaging and diagnostic criteria.

Methods
In a prospective intraindividual comparative study, we examined 40 patients with Clinically Isolated Syndromes (CIS) consecutively with a 1.5T and 3T MR imaging system.

Including axial sections of T2 Turbo Spin-Echo, Fluid-Attenuated Inversion Recovery, and T1 Spin-Echo, before and after injection of Gadolinium-Diethylene-Triaminepentaacetic Acid. Constant resolution parameters were used for both field strengths.

High-signal-intensity White Matter Lesions with a size of > 3 mm were counted and categorized according to their anatomic location in InfraTentorial, Callosal, JuxtaCortical, PeriVentricular, and other White Matter areas.

Assessment of the fulfilled Barkhof MR imaging and McDonald diagnostic criteria was made separately for both field strengths in every patient.

Results
Eleven patients fulfilled more MR imaging criteria at 3T. Two of these patients fulfilled the criterion of Dissemination In Space (DIS) according to the first definition of McDonald criteria, which is based on imaging criteria alone.

Another patient had DIS only at 3T, according to the second definition of the McDonald Criteria including CSF parameters.

Conclusion
MR field strength, specifically high-field MR imaging, has a substantial influence on the classification of patients with CIS according to imaging.

And a mild influence on the classification according diagnostic criteria for MS, leading to consequences for prognostic classification, imaging guidelines, and clinical trials.