Radiological findings as well as clinical presentations in patients with multiple sclerosis (MS) are sometimes misleading, resulting in an erroneous diagnosis of brain or spinal cord tumor (1–4). On contrast-enhanced MR images, MS lesions usually appear as homogeneous ovoid areas. Rarely, however, demyelinating diseases show large contrast-enhancing ring lesions that can be mistaken for glioma (1–6).

Ring enhancement associated with demyelination is often incomplete or open and has been classified as an open-ring sign. It has been proposed that this sign could help differentiate demyelinating lesions from nondemyelinating lesions (5, 6).

We treated a rare case of biopsy-proven MS with open-ring enhancement observed on MR images in the spinal cord, right cerebrum, and the contralateral hemisphere, appearing sequentially over a seven-month period with poor response to high-dose methylprednisolone or plasmapheresis.

A 67-year-old, previously healthy woman developed numbness in the right upper and lower extremities and unsteady gait in October 1998. Three months later, the patient noticed right-sided visual disturbance. She visited a local hospital and was diagnosed as having MS. She was successfully treated with prednisolone at the initial dose of 40 mg daily. During the subsequent two years she experienced relapsing of visual disturbance and numbness and weakness in her extremities, which responded well to steroid therapy. The responsible lesions could not be identified on brain and spinal MR images.

By February 2000, the patient's numbness and weakness had expanded to both lower extremities and she was unsteady on her feet. She was referred to Suwa Red Cross Hospital on February 22. On admission, neurological examinations revealed transverse myelopathy at the level of Th5 and neurogenic bladder. Analysis of cerebrospinal fluid showed no pleocytosis with normal levels of protein, IgG, glucose, LDH, β2-microglobulin and adenosine deaminase, but myelin basic protein was elevated to 13.9 ng/ml (normal <4 ng/ml). Spinal MR images revealed a gadolinium-enhanced open-ring lesion between the Th 5 and Th 7 levels (Fig. 1). Relapses of visual loss and weakness in the extremities, and their responsiveness to steroid were important for the diagnosis of MS. After administration of intravenous methylprednisolone at the dose of 1,000 mg per day for three days, the patient became ambulatory and continent. She was started on prednisolone at the dose of 40 mg per day, which was tapered off over a period of four months.

On August 9, gait disturbance recurred. There was severe muscle weakness in the left leg and mild weakness in the other leg with normal sensation. Deep tendon reflex was hyperactive in the right leg. Babinski and Chaddock signs appeared bilaterally, and voiding was difficult. Cerebrospinal fluid was normal except for mild elevation of the level of myelin basic protein (9.2 ng/ml), and no oligoclonal band was detected. When the patient became derilious, mizoribin was substituted at the dose of 75 mg daily for probable steroid-induced psychosis. However, her weakenss gradually exacerbated, and one month later she developed complete paralysis in the left arm and both legs. We started two series of high-dose methylprednisolone therapy followed by plasmapheresis without any improvement. Brain MR images demonstrated a newly developed, large ring-enhancing lesion in the right centrum semiovale (Fig. 2). A diagnosis of MS was strongly suggested, but brain tumor could not be ruled out, because the ring-enhancing lesion was atypical for MS, the patient was relatively old for rapidly progressive MS to occur (7), and steroid therapy combined with plasmapheresis failed to stop lesions from expanding to the other hemisphere. We therefore performed a stereotaxic brain biopsy which revealed the lesion to meet the criteria for MS (Fig. 3). In October the patient became totally bedridden, and tube feeding was introduced. Only minimal voluntary movements were seen in the left limbs. On December 8 we started 9.6 million units of interferon β twice a week. There had been no remarkable changes in her condition and the lesion at the high part of the left centrum semiovale had remained enhanced by gadolinium.

We consider that the present case had clinically definite MS on the basis of Poser's diagnostic criteria because of several relapses and separate lesions in the central nervous system observed on MR images (8). However, there were several features not usually encountered in MS. The patient poorly responded to steroid therapy and plasmapheresis. Her age of onset was relatively high for rapidly progressive MS (7). And contrast-enhanced MR images revealed large ring-enhancing lesions in the spinal cord and in both cerebral hemispheres.

Neuroradiologically, ring enhancement on MR images has been reported in brain abscess (4) or brain tumor (3). The present case did not include fever as a part of the clinical pictures; the blood examinations showed no inflammatory signs. Ring enhancement in cerebral abscess is generally uniformly thin and spherical (3), but our case presented with irregular rims, which made it less likely to be ascribed to brain abscess. Glioblastoma was not a likely candidate for diagnosis in radiological terms because the pattern of ring enhancement observed in glioblastoma is usually a closed ring, not open ring, associated with moderate edema (1, 6). The poor response to steroid therapy and ring enhancement associated with minimal edema or mass effect placed low-grade astrocytoma and lymphoma highest on the list of possible differential diagnoses. Low-grade astrocytoma is a slow-growing tumor with only slight vascular proliferation or necrosis, and imaging characteristics include a well-defined margin, no significant enhancement with minimal edema (9). Primary central nervous system lymphomas show a wider spectrum on MR images and ring enhancement has been reported in 15 of 17 patients with AIDS (10). Demyelinating disease rarely presents with ring enhancement, but atypical open-ring enhancement is more likely to be associated with demyelinating lesions than nondemyelinationg lesions (1, 2, 4–6). Approximately 66 to 90% of ring enhancement in demyelination has an open-ring pattern compared with 6 to17% in abscess or tumor (1, 6). Rings of enhancement in demyelination are usually thicker in the adjacent cerebral white matter, and thinner in the area facing the gray matter or basal ganglia (1, 6).

The present patient became quadriplegic within four months and such a fulminating form of MS is associated with high mobility and mortality. The correlation between measures of disease activity seen on conventional MR images and clinical disability in MS is inconclusive, but ring-enhancing lesions may reflect a more destructive pathology (11, 12). The morphological correlate of gadolinium enhancement has been reported to be activated macrophages in the zone of myelin destruction at the plaque border (4). Patients with MS who show a numerous enhanced lesions reflecting more extensive tissue damage, are said to have a higher rate of atrophic changes in the brain (13). MS patients showing ring-enhancement on MR images may need more intensive immunomodulatory therapy.