To describe the clinical and imaging characteristics of spinal cord ring enhancement in multiple sclerosis (MS).
Clinical case series.
Academic referral center.
Twenty patients with MS who had spinal cord ring enhancement were retrospectively identified from 322 cervical and thoracic spinal cord magnetic resonance imaging studies during a 3-year period.
Main Outcome Measures
Demographics, disability, and pattern of enhancement on spinal cord and concomitant brain magnetic resonance imaging results.
Ring enhancement was seen in 20 patients with spinal cord enhancement, most commonly in the cervical cord. Incomplete or “open” ring enhancement was the dominant pattern in 19 of the 20 patients (95%). Concurrent enhancing brain lesions were present in 14 patients, 8 of which (57%) exhibited a ring pattern of enhancement. At the time of imaging, the Expanded Disability Status Scale scores ranged from 1.0 to 7.0 (median score, 3.0).
Ring enhancement is not an uncommon pattern for spinal cord lesions in MS, occurring with a prevalence of 6.2% (20 of 322 imaging studies). The most common pattern is incomplete ring enhancement in the cervical spinal cord. Recognition of this pattern may improve and expedite the diagnosis of MS and preclude the need for invasive diagnostic interventions.
Multiple sclerosis (MS) is a demyelinating disease affecting the brain and spinal cord. Magnetic resonance imaging (MRI) enhancement after administration of contrast in a patient with MS indicates increased blood-brain barrier permeability with active inflammation, typically persisting for weeks.1 Ring enhancement, particularly the “open” (incomplete) ring sign, is a frequently observed pattern on MRI of the brain.2 Spinal cord abnormalities have been reported in greater than 80% of patients with newly diagnosed MS.3 Ring enhancement within the spinal cord in MS has only recently been described4-6 as a rare pattern of enhancement. Recognition of this pattern has the potential to improve diagnosis of MS. We report a series of 20 patients with MS from a single center during a 3-year period who demonstrated ring enhancing lesions within the spinal cord.
Institutional review board approval was obtained for the use of human subject records for this study. A search of all clinical imaging studies at Barnes-Jewish Hospital in St Louis, Missouri, was conducted for a 37-month period from January 1, 2006, through January 31, 2009. A search that included the terms multiple sclerosis and spinal cord MRI yielded 322 patient MRIs. Cervical and thoracic spinal cord MRIs were analyzed for enhancement on T1-weighted imaging after administration of gadoversatamide. Thirty-six patient MRIs included enhancing lesions, of which 20 studies included a ring or incomplete ring pattern. Patterns that were labeled as ring enhancement were identified by the principal investigator (E.C.K.) and confirmed by a neuroradiologist (T.B.). All imaging was performed on a 1.5-T or 3.0-T scanner with a standard spine MRI protocol. Inclusion criteria consisted of (1) being aged 18 to 80 years, (2) meeting McDonald criteria7 for clinically definite MS, and (3) having a ring enhancement pattern on T1-weighted spinal cord imaging after administration of gadoversatamide. The pattern of ring enhancement was classified by the location in the axial dimension of the spinal cord, having single or multiple rings, having complete or incomplete rings, and having a ring that opened toward the center or the periphery of the spinal cord. If enhancement was incomplete (open) at any axial or sagittal section on the MRI, it was considered open for the purpose of analysis. A concurrent MRI of the brain was available in all cases and was analyzed for the presence and pattern of contrast enhancement.
Compiled patient demographics included age, sex, ethnicity, disease duration, disease subtype, use of disease-modifying therapy at the time of imaging, and disability according to the Expanded Disability Status Scale (EDSS).8 Neurologic examination results were available for 18 of the 20 patients. A Multiple Sclerosis Severity Score (MSSS) was calculated from the EDSS score and disease duration, as previously reported.9
Twenty MS patients were identified as having spinal cord ring enhancement (Table). Median age at the time of imaging was 35 years (range, 21-62 years). Median disease duration was 2.5 years (range, <1-21 years). Of the 20 patients, 19 (95%) were classified as having relapsing-remitting MS and 1 (5%, patient 11) as having secondary progressive MS. Disease-modifying therapy approved for MS was being prescribed for 8 patients (40%) at the time of the imaging study. Seventeen patients (85%) were in a clinical relapse at the time of imaging. The median EDSS score was 3.0 (range, 1.0-7.0) at the time of the imaging study, with a median MSSS of 6.46 (range, 4.57-9.84).
Patient Demographics and MRI Characteristicsa
Analysis of the spinal cord enhancement pattern showed an open ring pattern in 19 patients (95%) (Figure). Of the 19 incomplete ring enhancements, 12 (63%) opened toward the outer edge and 7 (37%) opened toward the center of the spinal cord within its axial plane. Nine patients (45%) had multiple spinal cord ring enhancements that were located at the same or different spinal cord levels. The most common location in the axial plane was lateral, appearing in 8 patients (40%), followed by dorsal in 6 (30%), dorsolateral in 3 (15%), anterolateral in 2 (10%), and anterior in 1 (5%). Ring enhancement was located within the cervical region in 15 of the 20 patients (75%), the thoracic region in 3 (15%), and both the cervical and thoracic regions in 2 (10%). A concurrent MRI of the brain showed contrast enhancement in 14 patients (70%), 8 (57%) of which demonstrated a ring enhancing pattern in at least 1 of the areas of brain enhancement. All patients had white matter T2 hyperintensities in a pattern that was diagnostic for MS.
Spinal cord ring enhancement patterns in multiple sclerosis. A, Patient 1. Axial T1-weighted image after administration of gadoversatamide (repetition time [TR], 908 ms; echo time [TE], 14.0 ms) demonstrates closed ring enhancement at the level of C4. B, Patient 1. Sagittal T1-weighted image after administration of gadoversatamide (TR, 828 ms; TE, 9.7 ms) shows multiple ring enhancements at different levels (C1 and C4) and within the same lesion (C4). C, Patient 2. Sagittal T1-weighted image after administration of gadoversatamide (TR, 500 ms; TE, 14.0 ms) shows a ring extending longitudinally and opening superiorly at the level of C2-3. D, Patient 3. Axial T1-weighted image after administration of gadoversatamide (TR, 615 ms; TE, 11.0 ms) demonstrates ring enhancement opening outward dorsally at the level of C4. E, Patient 14. Sagittal T1-weighted image after administration of gadoversatamide (TR, 600 ms; TE, 16.4 ms) shows open ring enhancement opening outward dorsally at the level of C4-5. F, Patient 17. Axial T1-weighted image after administration of gadoversatamide (TR, 460 ms; TE, 14.0 ms) demonstrates ring enhancement opening toward the center of the spinal cord at the level of C2.
The 20 reported patients highlight the pattern of spinal cord ring enhancement in MS. Previous reports4-6 would indicate that this enhancement pattern is rare in the spinal cord even though ring enhancement in the brain of MS patients has been commonly reported.2 However, this case series of 20 patients from a 3-year period at a single institution suggests that this pattern is not uncommon in the spinal cord of MS patients, occurring with a prevalence of 6.2% (20 of 322 MRI studies). This pattern has been previously underrecognized or underreported. Another possible explanation is that imaging of the spine is more routinely conducted because of improved acquisition time and greater recognition of its clinical importance. The differential diagnoses for spinal cord ring enhancement should include MS in addition to neoplasm, abscess, and granulomatous disease. Ring enhancement, particularly an incomplete ring pattern, should prompt further workup for demyelinating diseases that may include MRI of the brain, examination of the cerebrospinal fluid, and determination of visual evoked potentials. Further evidence supporting the diagnosis of MS might then preclude a need for spinal cord biopsy in patients in whom other diagnoses are suspected.
The imaging characteristics of this series are similar in location and appearance to those of previously reported cases.4-6 Lesions typically were asymmetrically placed, were dorsal or lateral in the axial plane, and spanned 1 vertebral segment or less. The cervical region was preferentially involved and is the region previously noted to contain the most overall enhancement.3 The high prevalence of coexisting ring enhancements in the brains of these 20 patients suggests a common pathophysiologic process occurring throughout the central nervous system.
All patients in this series had relapsing MS, and 19 of the 20 were diagnosed as having relapsing-remitting MS and estimated to be relatively early in their disease course. Six patients (30%) were African American, which may be a high proportion for our patient population and is notable because African Americans may be at increased risk for disability owing to spinal cord disease.10 Overall, a high level of disability was found relative to disease duration according to the MSSS. However, neurologic examinations were performed at the time of spinal cord enhancement and during a relapse in most cases. We cannot speculate whether spinal cord ring enhancement has prognostic significance because of the lack of long-term follow-up in this cohort.
In conclusion, spinal cord ring enhancement can be seen in MS and is often an incomplete ring. Recognition of open ring enhancement in the spinal cord may help to expedite the diagnosis of MS. The specificity of the open ring sign has been determined for the brain.11 Further studies to determine the specificity of the incomplete ring pattern in the spinal cord are warranted.
Correspondence: Eric C. Klawiter, MD, Department of Neurology, Massachusetts General Hospital, 15 Parkman St, Wang Ambulatory Care Center, Ste 835, Boston, MA 02114 (firstname.lastname@example.org).
Accepted for Publication: December 2, 2009.
Author Contributions: Dr Klawiter had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Klawiter and Benzinger. Acquisition of data: Klawiter, Benzinger, and Roy. Analysis and interpretation of data: Klawiter, Benzinger, Naismith, Parks, and Cross. Drafting of the manuscript: Klawiter and Cross. Critical revision of the manuscript for important intellectual content: Benzinger, Roy, Naismith, Parks, and Cross. Statistical analysis: Klawiter. Administrative, technical, and material support: Benzinger. Study supervision: Benzinger, Parks, and Cross.
Financial Disclosure: Dr Klawiter has received speaking honoraria from Bayer HealthCare and Teva Neuroscience Inc. Dr Benzinger reports receiving travel expenses from Siemens AG and consulting fees from Biomedical Systems. Dr Parks reports being an investigator in clinical trials for Biogen Idec, BioMS Medical Corp, Genzyme Corporation, the National Institutes of Health (NIH), Novartis AG, and Teva Neuroscience Inc. She also reports receiving consulting fees or speaking honoraria from Bayer HealthCare, Biogen Idec, EMD Serono Inc, Pfizer Incorporated, and Teva Neuroscience Inc. Dr Naismith reports being an investigator in clinical trials sponsored by Acorda Therapeutics. He also reports receiving consulting fees and speaking honoraria from Bayer HealthCare, Biogen Idec, Elan Pharmaceuticals, and Teva Neuroscience Inc and research funding from the National Multiple Sclerosis (MS) Society USA and the NIH. Dr Cross reports receiving research funding, clinical trial funding, honoraria, or consulting fees from Acorda Therapeutics Inc, Bayer HealthCare, Biogen Idec, BioMS Medical Corp, the Consortium of Multiple Sclerosis Centers, Eli Lilly and Company, EMD Serono Inc, Genentech Inc, Hoffman–La Roche Ltd, the National MS Society USA, the NIH, and Teva Neuroscience Inc.
Funding/Support: This study was supported in part by grants UL1RR024992 (Dr Klawiter) and K23NS052430-01A1 (Dr Naismith) from the NIH and grant CA-1012 from the National MS Society USA (Dr Cross). Dr Klawiter was supported by an American Academy of Neurology Foundation Clinical Research Training Fellowship; Dr Benzinger, by a Bracco/American Roentgen Ray Society Scholar Award; and Dr Cross, by the Manny and Rosalyn Rosenthal–Dr John L. Trotter Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation.
CR MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals. Neurology
640- 646PubMedGoogle ScholarCrossref
M The open ring: a new imaging sign in demyelinating disease. J Neuroimaging
104- 107PubMedGoogle Scholar
et al. Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. Neurology
226- 233PubMedGoogle ScholarCrossref
K Multiple sclerosis with open-ring enhancement in the cerebrum and spinal cord. Intern Med
273- 276PubMedGoogle ScholarCrossref
et al. Tumefactive demyelinating lesions: nine cases and a review of the literature. Neurosurg Rev
171- 179PubMedGoogle ScholarCrossref
et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.” Ann Neurol
840- 846PubMedGoogle ScholarCrossref
JF Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology
1444- 1452PubMedGoogle ScholarCrossref
et al. Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology
1144- 1151PubMedGoogle ScholarCrossref
AH Phenotype and prognosis in African-Americans with multiple sclerosis: a retrospective chart review. Mult Scler
775- 781PubMedGoogle ScholarCrossref
P Open-ring imaging sign: highly specific for atypical brain demyelination. Neurology
1427- 1433PubMedGoogle ScholarCrossref