Is Tumefactive Demyelination Different from MS?
By Susan Gauthier, DO, MPH, Assistant Professor of Neurology, Weill Cornell Medical College. Dr. Gauthier reports she receives research support from EMD Serono, Biogen Idec, and Novartis Pharmaceuticals, and is on the speakers bureau for Biogen Idec and Teva Neurosciences.
Synopsis: Patients presenting with tumefactive demyelinating lesions have MRI characteristics indistinguishable from a primary central nervous system tumor. Many patients go on to have relapsing-remitting disease and may have recurrence of tumefactive lesions.
Source:Nagappa M, et al. Tumefactive demyelination: Clinical, imaging, and follow-up observations in thirty-nine patients. Acta Neurol Scand 2013;128:39-47.
Large, atypical demyelinating lesions on mri can be difficult to distinguish between primary central nervous system tumors and are referred to as "tumefactive" demyelinating lesions. Our understanding of these lesions and how they relate to multiple sclerosis (MS) has been described in only a few key publications. The largest series was reported by Lucchinetti et al, in which the clinical and MRI features of 168 patients with biopsy-proven tumefactive demyelinating disease were described.1 That report highlighted that the majority of these patients went on to have a typical relapsing course of MS and therefore presented a broader spectrum of the disease. In this current study by Nagappa et al, the authors similarly describe a cohort of patients with tumefactive demyelinating disease.
Thirty-nine patients with a monophasic or relapsing-remitting neurologic illness, an intracranial "mass" lesion > 2 cm suggestive of demyelination, and/or clinical-radiological resolution following steroid therapy were diagnosed as having a tumefactive demyelinating lesion. Categorization for lesion site/number, edema pattern, and enhancement pattern were based on previously published criterion.1 The most common presenting symptoms were hemiparesis, cerebellar symptoms, and signs of increased intracranial pressure (headache, vomiting, papilledema, and altered sensorium). Seizures and aphasia, which are uncommon for a typical MS relapse, were noted to occur in a small number of patients. The most commonly involved sites on MRI were frontal lobe, parietal lobe, and corpus callosum; in addition, only a minority had a solitary lesion (35.8%). The most common pattern of enhancement was partial ring enhancement; however, complete ring, patchy, uniform, and lack of enhancement also were found. A moderate level of edema (extending 1-3 cm from the lesion) was present in about one-third of the patients with the remaining having minimal or no edema. The results of 19 biopsies revealed typical cellular infiltrates of acute demyelinating lesions, well demarcation of myelin loss, and a relative preservation of axons. Limited follow-up of 13/22 monophasic patients over a mean of 8.3 months revealed that complete neurological recovery occurred in only 53.5%. Serial imaging in only eight monophasic patients revealed significant resolution in 75% of patients. However, two had evidence of new demyelinating lesions. Of the 17 with a relapsing-remitting course, 10 were reported to have relapse symptoms prior to the presentation, although never given the diagnosis of MS. Twelve of these patients were followed for a mean of 37.8 months, and within this time, 13 relapses occurred. Interestingly, MRI revealed new tumefactive lesions for 10 of these subsequent relapses and 60% occurred in the same location. All but one patient received steroids and three patients required additional treatment with plasmapheresis. There were no distinguishing features between the monophasic and relapsing-remitting subgroups.
We tend to approach patients with tumefactive demyelinating lesions differently, but in fact, these types of lesions fall within the clinical spectrum of MS. Is there any way to spare a patient a brain biopsy? Interestingly, in both this series and that reported by Lucchinetti, the majority of patients had multiple lesions; thus, with this feature, as well as any history of prior relapse, there should be a suspicion for demyelination and an attempt to avoid a biopsy.
What should we expect from these patients moving forward? Unfortunately, the main limitation of this study was the limited follow-up, especially within the monophasic group. The majority of the patients who presented with a first episode in the series published by Lucchinetti went on to have MS. Therefore, I suspect that the number considered monophasic for this study is overestimated. Interestingly, in this study, there were recurrences of tumefactive lesions, and even more intriguing is that they occurred within the same region. Lucchinetti reported that the presence of tumefactive lesions (including the small minority with recurrence of these lesions) did not dictate a worse disease course as compared to a population-based matched MS cohort. In summary, it appears that tumefactive lesions occur as part of MS and must be considered when facing potential biopsy for a cranial lesion and once identified, treated as typical MS.
1. Lucchinetti CF, et al. Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis. Brain 2008;131(PT 7):1759-1775.