Spinal Cord MR In Multiple Sclerosis

Spinal Cord imaging is important in the evaluation of patients with MS. There are several techniques available which provide satisfactory images of lesions in the Spinal Cord.

Conventional measures used in the assessment of damage to the Spinal Cord include quantification of:

1. High intensity on T₁ weighted images
2. Spinal Cord enhancement
3. Spinal Cord Atrophy

Although not presently implemented, newer methods including Magnetization Transfer, Diffusion, and Proton Spectroscopy offer the potential for more specific classification of Spinal Cord MS.

Assessment of Spinal Cord damage using MR still remains behind the development of Brain methodology and represents both a challenge and an opportunity.

Magnetization Transfer (MT) imaging has been successfully applied to patients with Multiple Sclerosis (MS), showing lesion heterogeneity, subtle changes in the Normal-Appearing White Matter, and a better correlation with disability, in comparison with conventional Magnetic Resonance Imaging.

MT imaging is a fairly simple technique, which allows a quantitative analysis with high spatial resolution to delicate structures like the Optic Nerve and Spinal Cord.

In the Spinal Cord, MT imaging can be applied as a contrast augmentation technique.

Using the MT Ratio (MTR), two studies have reported a mild, but significant, reduction in MT Ratio in the Cervical Spinal Cord, compared with healthy controls.

In one study, clinical disability correlated independently of Cord Atrophy with MTR, which may relate to preliminary findings of a correlation between Axonal loss and MTR in the Spinal Cord.

In the Optic Nerve, two studies reported strongly decreased MTR in affected Nerves, even in the absence of lesions on conventional imaging; unaffected Nerves showed values similar to White Matter in the Brain.

In one study, MTR was significantly correlated with ElectroPhysiological parameters, but not with Vision.

In conclusion, MT imaging provides a quantifiable parameter that can be applied with high spatial resolution to delicate structures, such as the Spinal Cord and the Optic Nerve.

Further work is needed to correlate MTR measurements with pathology and, most importantly, with the functional status.

Such relationships being established, a quantitative technique such as MTR could be useful in monitoring disease progression in MS.

We describe the dynamics and the nature of the presymptomatic phase of Multiple Sclerosis (MS) in a patient for whom MR abnormalities suggestive of MS were found before the development of clinical symptoms.

The patient was monitored with serial monthly MR imaging of the Brain and Spinal Cord for 5 months.

Disease activity during the presymptomatic phase showed imaging characteristics comparable to that of early Relapsing/Remitting MS in terms of enhancing lesions, duration of enhancement, and new lesions depicted by T₂ weighted imaging.

Measurements derived from Magnetization Transfer imaging suggested that the amount and degree of tissue destruction within and outside the lesions revealed by T₂ weighted imaging were mild.

This, together with the fact that only one of the 43 new lesions that developed during the presymptomatic phase was located in a Neurologically eloquent area.

May be the reason why, for a relatively long period, the patient had no clinical manifestations of MS despite the marked MR findings of disease activity.

Objectives
Conventional T₁ weighted MRI studies have highlighted the fact that the presence of clinically silent Brain lesions increases the risk of developing Clinically Definite Multiple Sclerosis after an Isolated Syndrome of the Optic Nerve, BrainStem, or Spinal Cord.

The objectives of the present study are to:
1. Show whether or not these patients also have asymptomatic abnormalities of the Spinal Cord, and
2. Recruit a new cohort of such patients using high resolution MRI of both Brain and Spinal Cord

Methods
The Brain was imaged in the Axial plane with 3 mm thick contiguous slices using a Proton Density and T₂ weighted Fast Spin Echo (FSE) sequence; a T₂ weighted sequence after the injection of Gadolinium-DTPA; and a fast Fluid Attenuated Inversion Recovery (FLAIR) sequence.

The Spinal Cord was imaged in the Sagittal plane with 3 mm thick slices using a T₂ weighted FSE and a T₁ weighted Gadolinium enhanced sequence.

Results
Thirty three patients, mean age 31 (16-46) were recruited. There were 14 men and 19 women.

Brain MRI was abnormal in 22 (67%); no patient was seen with abnormalities on only one or other sequence. Six patients (18%) displayed one or more Gadolinium enhancing lesions on Brain MRI.

In the Spinal Cord, nine (27%) patients displayed one or more Clinically Silent lesions on FSE. Two patients showed one and two Gadolinium enhancing lesions in the Spinal Cord respectively.

Conclusion
This high incidence of Spinal Cord lesions emphasizes that asymptomatic DeMyelinating lesions may also involve clinically eloquent pathways. Follow up studies are required to determine their prognostic importance.

Purpose
Although MR findings in Multiple Sclerosis (MS) are well known, the relationship between MR-detected lesions and clinical activity has not been studied in the Spinal Cord.

The purpose of this study was to determine whether serial MR imaging provides evidence of disease activity unsuspected on clinical examination and to determine whether it is useful in monitoring patients with MS primarily affecting the Spinal Cord.

Methods
Twenty-five consecutive patients with MS and with signs and symptoms of myelopathy underwent a full Neurologic Examination and contrast-enhanced MR imaging of the Spinal Cord at intervals of 0, 2, 6, and 12 months.

Disability was rated according to Kurtzke's Functional Systems and the Expanded Disability Status Scale (EDSS). Clinical status of Myelopathy (improved, deteriorated, or stable) was also assessed.

HyperIntense lesions were counted on T₂-weighted images and a weighted lesion load was calculated for each patient. The number of enhancing lesions was also determined.

Results
We found a moderate correlation between Lesion Load and Sensory Function and EDSS. Seventy percent of patients with new clinical manifestations of Myelopathy had one or more enhancing lesions.

Agreement between MR findings and clinical examination in evincing disease activity was found in 60% of follow-up examinations.

MR images showed lesion progression in seven (44%) of 16 occurrences of clinical deterioration and in 21 (35%) of 60 occurrences of clinical improvement or stability.

Conclusion
Serial MR imaging provides evidence of disease activity unsuspected on clinical examination and could be useful in monitoring patients with MS primarily affecting the Spinal Cord.

We analyzed the prevalence of severely HypoIntense lesions on T₂ weighted MRI in the BrainStem, Spinal Cord, and Optic Nerve from 65 patients with MS.

About half of 1,274 SupraTentorial lesions were classified as severely HypoIntense. Severe HypoIntensity was not seen in the Optic Nerve and Spinal Cord, and in only one of 168 chronic BrainStem lesions.

Tissue destruction in the BrainStem, Spinal Cord, and Optic Nerve of MS patients does not usually result in severely HypoIntense lesions.

Purpose
To compare the rates of enhancement and changes in lesion burden in patients with Multiple Sclerosis (MS) and varying levels of disability.

Methods
Monthly enhanced MR images of the Brain were obtained for 6 months from seven patients with mildly disabling Relapsing/Remitting MS and from seven patients with Secondary/Progressive MS and severe disability.

At entry and 1 year later, two unenhanced T₂ weighted images of the Brain were also obtained.

Results
Despite the fact that both groups had clinically active disease and had similar increases in unenhanced MR lesion load:

1. Total number of enhancing lesions was 239 in patients with Relapsing/Remitting MS
   •   42 on the baseline images
   • 151 new
   •   46 persistent during follow-up
2.   68 - average number of lesions per patient per year

1. Total number of lesions per patient per year was 21 in those with Secondary/Progressive MS
   •     5 on the baseline images
   •   13 new
   •     3 persistent during follow-up
2.      7 - average number of lesions per patient per year

Conclusion
Our data indicate that the rate of enhancement significantly decreases in the more advanced phases of MS.

This is important when planning clinical trials, and suggests that mechanisms underlying lesion formation might be dissimilar in different MS patient groups.

Purpose
To determine whether the MR appearance of the Spinal Cord in patients with Multiple Sclerosis (MS) differs according to clinical subtype.

Methods
The Spinal Cords of 20 healthy control subjects and 60 patients with MS (22 with Relapsing/Remitting disease, 22 with Secondary/Progressive disease, and 16 with Primary/Progressive disease) were examined with Sagittal Dual-Echo Spin-Echo MRI and with axial T₂-weighted gradient-echo MR imaging.

Two interpreters scored the images for focal lesions and for diffuse abnormalities. Cross-Sectional Areas of the Cords were measured at the C-2 level.

Results
No abnormalities were found in any of the control subjects nor in two of the patients. Fifty (83%) of 60 patients had focal Lesions.

Diffuse abnormality and focal lesions were found in 50% of patients with Secondary/Progressive MS, in 25% of patients with Primary/Progressive disease, and in 18% of patients with Relapsing/Remitting disease.

Diffuse abnormality without Focal lesions was found in seven patients with Primary/Progressive MS and in one patient with Secondary/Progressive MS.

Patients with diffuse abnormalities had a smaller cross-sectional area of the Spinal Cord and they suffered from more disability than did patients without diffuse abnormalities.

Conclusion
The MR appearance of the Spinal Cord differs among clinical subgroups of MS. Diffuse abnormality of the Spinal Cord is associated with a Progressive clinical course and greater Disability.

Recent MRI studies in Multiple Sclerosis have highlighted the potential importance of Spinal Cord Atrophy (implicating Axonal loss) in the development of disability.

However, the techniques applied in these initial studies have poor reproducibility which limits their application in the serial monitoring of patients.

The aim of this study was to develop a highly reproducible and accurate method for the quantification of Atrophy. The technique we describe demonstrates an intra-observer coefficient of variation (scan-rescan) of only 0.8%.

When applied to 60 patients with Clinically Definite Multiple Sclerosis there was a strong correlation between Spinal Cord Area and disability measured by Kurtzke's Expanded Disability Status Scale (EDSS) (r = -0.7, P < 0.001).

The correlation was graded providing evidence for a causal connection. At levels 3 and 8 of the EDSS we observed a reduction in average Cord area of 12 and 35%, respectively.

Given its reproducibility, the magnitude of the change detected and the strong correlation with Disability, this new technique should prove to be a sensitive measure of progressive Neurological deterioration.

And, could be readily incorporated into imaging protocols aimed at monitoring therapy.

Study Design & Objective
Retrospective examination. To define the clinical characteristics and response to therapy of Spinal Multiple Sclerosis (MS).

Setting & Methods
Italy. Retrospective review was performed on 563 patients with clinical definite MS.

Selection criteria were two or more Spinal Cord lesions in the presence of normal Magnetic Resonance Imaging of the Brain.

Results
Spinal MS was diagnosed in 13 patients (2.3%) out of 563 with clinical definite MS. There were seven female and six male patients; nine had a Relapsing/Remitting (RR) and four, a Primary/Progressive (PP) course.

All patients were treated with ImmunoSuppressive or ImmunoModulatory therapy.

Mean disease duration in patients with RR-MS was 13.1+/-10.1 years with a mean age at onset of 29.5+/-14.3 years; the mean Expanded Disability Status Scale (EDSS) at the time of the study was 3.5+/-2.5 with a progression index of 0.28.

Mean disease duration in patients with PP course was 7+/-6.2 years with a mean age at onset of 56.7+/-10.4 years; the mean EDSS at the time of the study was 6.2+/-2.0 with a progression index of 1.48.

Conclusions
Patients with Spinal RR-MS are characterised by an early disease onset with minimal or moderate disability progression; patients with Spinal PP-MS show a late disease onset and more rapid disability progression.

In our series of Spinal MS patients, disability progression seems to be mainly due to the disease course and age at onset rather than to the site of lesion.

Background
Pathology in the Cervical Spinal Cord is considered an important cause of disability in Multiple Sclerosis.

However, the majority of serial studies have failed to find a correlation between Spinal Cord Atrophy and disability.

Objectives
To use a highly reproducible and accurate method to quantify Spinal Cord Area change on three dimensional Magnetic Resonance Imaging and relate this to disability change in patients with Multiple Sclerosis.

Methods
38 patients with Multiple Sclerosis (20 with the Relapsing/Remitting (RRMS) form and 18 with the Secondary/Progressive (SPMS) form) were imaged at baseline.

And, at months 6, 12, 18, and 48 during two treatment trials of the high dose subcutaneous thrice weekly Interferon beta-1a (IFN-ß, Rebif).

Thirty one healthy subjects were also imaged at baseline. Upper Cervical Cord Area (UCCA) was measured using Sobel edge detection.

Results
The intraobserver coefficient of variation of the method was 0.42%.

A significant reduction in UCCA was detected at month 6 in the placebo group (p = 0.04) and at month 12 for INF-ß (p = 0.03).

The mean reduction of UCCA at month 48 was 5.7% for patients initially on placebo who received treatment at 24 months (RRMS) or at 36 months (SPMS).

And 4.5% for those on IFN-ß throughout the study (p = 0.35).

The change in UCCA was significantly correlated with change in the Expanded Disability Status Scale at month 12 (r = 0.4, p = 0.016), month 18 (r = 0.32, p = 0.05), and month 48 (r = 0.4, p = 0.016) in the total cohort.

Conclusions
Despite the small number of patients studied and the possible confounding effects of Interferon treatment, this study showed that edge detection is reproducible and sensitive to changes in Spinal Cord Area.

And that this change is related to changes in clinical disability.

This suggests a role for measurement of Spinal Cord Atrophy in monitoring disease progression and possible treatment effects in clinical trails.

Background And Purpose
DeMyelinating lesions in Spinal Cord in Multiple Sclerosis (MS) are found in Magnetic Resonance Imaging (MRI) in 47-90% of patients.

Spinal Cord Atrophy, however, which is a measure of Axonal Loss and correlates with disability, is found in 13-41% of patients.

Presence and character of lesions depend on the duration and progression of the disease.

The aim of this study was to estimate the presence, character and location of lesions and Cervical Cord Atrophy in MRI performed 10 years after the onset of MS in relation to the clinical course.

Material And Methods
60 patients (41 females and 19 males) with definite MS according to McDonald's criteria were studied.

The age of patients ranged from 29 to 62 years and disease duration ranged from 11 to 40 years.

The MS group comprised 20 patients with Secondary/Progressive MS (SPMS), 20 patients with Primary/Progressive MS (PPMS) and 20 patients with Benign form of MS (BMS).

Spinal cord MRI was performed in conventional T₁ and T₂-weighted sequences.

Results
DeMyelinating lesions were found in 62% of patients (50% of patients with BMS, 60% with PPMS and 75% with SPMS).

42 intrinsic focal lesions were identified in 18 patients and diffuse lesions of Spinal Cord were noted in 19 patients.

Focal lesions were seen in patients with BMS, whereas SPMS patients had diffuse Cervical Cord abnormalities, and PPMS patients exhibited both forms of changes.

60% of intrinsic focal lesions were located at C3-C5 levels. Medium-sized lesions prevailed in BMS form.

In PPMS form small and medium-size lesions, and in SPMS form large lesions (>10 mm) were more frequent.

The Spinal Cord was Atrophic in 8% of patients (10% of patients with PPMS and 15% with SPMS).

In BMS no Atrophy of the Cervical Cord was observed. We did not find focal DeMyelinating lesions in the Cervical segment of patients with Spinal Cord Atrophy.

Conclusions
Presence and character of DeMyelinating lesions in Cervical Cord ten years after onset of MS is significantly related to the clinical form of the disease.

The Mid-Cervical region of the Spinal Cord appeared to be the commonest location of the focal lesions.

Cervical Cord Atrophy was more frequent in patients with PPMS and SPMS, but it was not accompanied with intrinsic focal Cord lesions.