D G MacManus

Spinal cord MRI using multi-array coils and fast spin echo. II: Findings in multiple sclerosis

We performed MRI of brain and spinal cord on 80 patients with multiple sclerosis (MS). Using multi-array coils and fast spin echo, 139 intrinsic lesions were identified in 59 patients (74%). Lesions were more common in the cervical than in the thoracic cord. Cross-sectional areas of the cord, measured from axial images at four levels, showed atrophy in 40%. Clinical disability correlated with cord atrophy but not with cord lesion load. These results show that the use of multi-array coils and fast spin echo allows rapid and sensitive detection of spinal cord lesions in MS and that the cord is involved in the majority of patients. A lack of association between cord lesions and disability may relate to limitations in MR resolution but also suggests that the mechanisms of disability in MS are complex and multifactorial.

Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis

We performed semiautomated quantitative measurement of brain magnetic resonance imaging (MRI) abnormalities seen at presentation and at 5-year follow-up in 84 patients presenting with an acute clinically isolated syndrome of the optic nerves, brainstem, or spinal cord suggestive of multiple sclerosis (MS). At follow-up, 34 (40%) had developed clinically definite and four (5%) clinically probable MS. Patients who developed MS during follow-up had a higher lesion load at presentation than those who did not. There was a strong correlation of the MRI lesion load at presentation with both the increase in lesion load over the next 5 years and disability at follow-up. Increasing initial lesion load correlated with a decreasing time to development of MS clinically (r = −0.328, p <0.05). At follow-up, disability and brain lesion load were strongly correlated in patients who had developed MS. These results establish that MRI at presentation with clinically isolated syndromes suggestive of MS is useful in predicting the subsequent clinical course and the development of new MRI lesions. This suggests that quantitative brain MRI will be helpful in selecting patients with early clinical MS for treatment trials and for subsequent monitoring of their response to treatment.

Serial gadolinium‐enhanced MRI in relapsing/remitting multiple sclerosis of varying disease duration

In the planning of MRI protocols to monitor disease activity in multiple sclerosis (MS), the clinical subtype needs to be considered. In this serial gadolinium-enhanced MRI study, we demonstrated differences between patients with early relapsing/remitting MS and benign MS in both the production of new lesions and the occurrence of enhancement.

Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis

Although serial MRI studies of the brain in relapsing-remitting MS have demonstrated frequent asymptomatic disease activity, less is known about the spinal cord. We carried out monthly gadolinium-enhanced brain and spinal cord MRI scans over 1 year in 10 patients with relapsing-remitting MS. Six of the patients had a total of 11 clinical relapses, eight of which involved the spinal cord. A total of 167 active (enhancing or new nonenhancing) lesions in the brain and 19 in the spinal cord were present. Only one active brain lesion was symptomatic compared with six spinal cord lesions. Overall, one-third of new spinal cord lesions were symptomatic, and three-quarters of clinical spinal cord relapses were associated with a new MRI lesion in a location appropriate to the symptoms. Activity in both the spinal cord and brain was more common around the time of relapse. There was a strong association between the spinal cord and brain MRI activity. We did not detect progressive spinal cord atrophy from measurements of a spinal cord cross-sectional area. We conclude that, in relapsing-remitting MS, imaging of the brain alone will detect 90% of active lesions; spinal cord MRI using current technology will therefore provide only modest gains in treatment trials in which lesion activity is the primary outcome measure. The lack of progressive spinal cord atrophy in these patients, suggesting that significant axonal loss has not occurred, is in keeping with their good recovery after relapse. That brain and spinal cord lesions occur concurrently implies a systemic trigger for disease activity. NEUROLOGY 1996;46: 373-378.

High dose steroids in acute relapses of multiple sclerosis: MRI evidence for a possible mechanism of therapeutic effect.

The integrity of the blood-brain barrier (BBB) in multiple sclerosis (MS) was monitored by serial gadolinium-(Gd)-DTPA enhanced MRI during and after the treatment of acute relapses with a three day course of high dose intravenous methylprednisolone (IVMP). During treatment there was a rapid reduction of BBB abnormalities in 96% of enhancing lesions. In spite of sustained clinical improvement, many lesions re-enhanced within a few days of stopping IVMP, and new lesions frequently appeared within one month. It is possible that the rapid, albeit transient, reversal of BBB abnormalities contributes to the accelerated recovery from relapses associated with IVMP treatment.

Effect of interferon‐β1b on magnetic resonance imaging outcomes in secondary progressive multiple sclerosis: Results of a European multicenter, randomized, double‐blind, placebo‐controlled trial

A randomized placebo‐controlled trial of interferon‐β1b was performed on 718 patients with secondary progressive multiple sclerosis with follow‐up of up to 3 years. In addition to clinical variables, serial magnetic resonance imaging (MRI) studies were performed to determine the effect of treatment on the pathological evolution of the disease. All patients eligible for MRI had annual proton density/T2‐weighted brain scans from which total lesion volume was measured and the number of new and enlarging lesions noted. A subgroup of 125 patients also underwent monthly gadolinium‐enhanced and proton density/T2‐weighted brain MRI from months 0 to 6 and 18 to 24 to determine the effect of treatment on the frequency of new lesion activity, defined as new enhancing lesions and new/enlarging T2 lesions not enhancing with gadolinium. The difference in total lesion volume between treatment groups was highly significant. In the placebo group, there was an increase of 15% from baseline to last scan, whereas in the interferon‐β1b group, a reduction of 2% was seen. Within the placebo group, there was a significant year‐on‐year increase in total lesion volume, with a mean increase of 16% at year 3 compared with baseline. In the treated group, there was a significant reduction at year 1 (4%) and year 2 (5%) compared with baseline; the 2% decrease at year 3 was not significant. The number of new or enlarging proton density/T2 lesions was also significantly reduced by treatment. In the frequent MRI subgroup, treatment was associated with a significant 65% reduction in new lesion activity between months 1 and 6, and 78% reduction from months 19 to 24. Interferon‐β1b has a substantial and sustained effect on reducing the accumulation of new inflammatory disease foci in secondary progressive MS. This therapeutic mechanism may contribute to the positive clinical benefits of treatment on the progression of sustained neurological disability and relapse activity that were also identified in this trial.

Quantitative MRI in patients with clinically isolated syndromes suggestive of demyelination

OBJECTIVE To assess the long-term predictive value of quantitative lesion load measurement on brain MRIs in patients after a 10-year follow-up who presented initially with a clinically isolated syndrome of the optic nerve, brainstem, or spinal cord. BACKGROUND Quantitative MRI measurement is being used in treatment trials as a surrogate marker in MS, but there is a lack of long-term MRI follow-up data in assessing the natural course of the disease from the earliest stages. METHODS Using a semiautomated threshold technique, the total lesion volume (TLV), the course of the disease, and disability were assessed in 58 patients at onset and after 5 and 10 years. RESULTS The TLV at presentation correlated significantly (r = 0.81, p = 0.0001) with the TLV and also with the Expanded Disability Status Scale (EDSS) score (r = 0.45, p = 0.001) at 10-year follow-up. In contrast there was no correlation of the TLV at 5 years with subsequent change in EDSS score over the next 5 years (r = 0.18, p = 0.12). The change in TLV over the first 5 years in patients who developed clinically definite MS (CDMS) differed significantly according to the type of disease course (relapsing-remitting with disability, secondary progressive, or benign) manifesting at 10-year follow-up. CONCLUSION Quantification of changes detected by T2-weighted brain MRI at the earliest clinical stages is strongly predictive of the subsequent development of CDMS as well as the clinical course and level of disability 10 years later.

Trigeminal neuralgia in patients with multiple sclerosis: Lesion localization with magnetic resonance imaging

We performed conventional T2-weighted brain MRI examinations in six patients with multiple sclerosis (MS) and trigeminal neuralgia. In all patients brainstem lesions in positions expected to involve trigeminal fibers, particularly the entry zone of sensory fibers, were demonstrated. Compression of the trigeminal nerve by ectatic vessels, a recognized cause of idiopathic trigeminal neuralgia, was not observed. We conclude that in MS trigeminal neuralgia is usually caused by demyelinating lesions affecting pontine trigeminal pathways.

Magnetic resonance imaging in central nervous system sarcoidosis

We performed brain MRIs on 21 patients with CNS sarcoidosis. Brain CTs were performed in 18 of these. Parenchymal lesions were seen in 17 of 21 with MRI, compared with 9 of 18 with CT. MRI detected a greater number of parenchymal lesions in cases where both CT and MRI were positive, and some lesions appeared more extensive with MRI than with CT. The most common MRI pattern was one of periventricular and multifocal white matter lesions (14 cases). Such a pattern is not specific, and other recognized causes for it were identified in four cases. It is likely, however, that sarcoid tissue causes this pattern in some cases, and confirmation was obtained from cerebral biopsy in one. In six patients, the white matter changes were indistinguishable from those seen in multiple sclerosis. Contrast-enhanced CT in two patients showed diffuse meningeal involvement not seen with MRI. MRI is the investigation of choice in detecting parenchymal changes in the brain of patients with CNS sarcoidosis and may prove useful in monitoring treatment in such cases.

Asymptomatic spinal cord lesions in clinically isolated optic nerve, brain stem, and spinal cord syndromes suggestive of demyelination

OBJECTIVES Conventional T2 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, brain stem, or spinal cord. The objectives of the present study are: (1) to show whether or not these patients also have asymptomatic abnormalities of the spinal cord, and (2) to 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 T1 weighted sequence after the injection of gadolinium-DTPA; and a fast fluid attenuated inversion recovery (fFLAIR) 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 emphasises that asymptomatic demyelinating lesions may also involve clinically eloquent pathways. Follow up studies are required to determine their prognostic importance.