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Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis

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Lucchinetti, C. F., Gavrilova, R. H., Metz, I., Parisi, J. E., Scheithauer, B. W., Weigand, S., Thomsen, K., Mandrekar, J. +8 more·2008·Brain
DOI 10.1093/brain/awn098PMC PMC2442427
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Abstract

Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as 'tumefactive multiple sclerosis'. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2 : 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing-remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5-12), with a discernible size of 2.1 cm (range 0.5-7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases.

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  • While some patients presenting with atypical demyelinating lesions have a monophasic course, 30-60% develop MS.

    “While some patients presenting with atypical demyelinating lesions have a monophasic course, 30-60% develop MS. 38,40”

    From Diagnosis of multiple sclerosis: progress and challenges (2017) · cites this paper as [40]

    The Results (Clinical characteristics of the cohort; page not provided) report that 24% had a monophasic course, supporting the first part of the claim. They report that 70% developed definite multiple sclerosis, not 30–60%; they also note that a monophasic course did not preclude an MS diagnosis. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Occasionally, MS presents with an atypical demyelinating lesion characterised by large size (>2cm diameter, sometimes with peri-lesional oedema and mass effect), enhancement pattern (open or closed-ring enhancement) or morphology (infiltrative or heterogeneous appearance including concentric rings).

    “Occasionally, MS presents with an atypical demyelinating lesion characterised by their large size (>2cm diameter, sometimes with peri-lesional oedema and mass effect), enhancement pattern (open or closed-ring enhancement) or morphology (infiltrative or heterogeneous appearance including concentric rings).[38][39][40]”

    From Diagnosis of multiple sclerosis: progress and challenges (2017) · cites this paper as [40]

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Authors
Lucchinetti, C. F., Gavrilova, R. H., Metz, I., Parisi, J. E., Scheithauer, B. W., Weigand, S., Thomsen, K., Mandrekar, J., Altintas, A., Erickson, B. J., Konig, F., Giannini, C., Lassmann, H., Linbo, L., Pittock, S. J., & Bruck, W.
Affiliations
  • Mayo Clinic (US)
  • Istanbul University (TR)
Corresponding author
Lucchinetti, C. F.
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2008-06-05
Volume
131
Issue
7
Pages
1759-1775
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awn098
PMC
PMC2442427
OpenAlex
W2109879652
Cited by
493
References
1
Citations by year
2026: 20 · 2025: 22 · 2024: 28 · 2023: 25 · 2022: 25 · 2021: 36 · 2020: 26 · 2019: 28 · 2018: 34 · 2017: 26 · 2016: 33 · 2015: 43 · 2014: 24 · 2013: 26 · 2012: 30
FWCI
15.66
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Brain (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion, cc-by-nc)
Funders
  • Multiple Sclerosis Society
  • Gemeinnützige Hertie-Stiftung
  • National Institutes of Health (RR24150)
  • National Institute of Neurological Disorders and Stroke (NS049577, R01NS049577)
  • National Center for Research Resources (UL1RR024150, UL 1 RR24150-01)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
Keywords
tumefactive multiple sclerosis, lesion size, mass effect, edema, ring enhancement, Barkhof criteria, relapsing-remitting multiple sclerosis, progressive multiple sclerosis, lesion evolution, multifocality, clinical features, disease duration, sex differences
MeSH terms
Adolescent, Adult, Aged, Biopsy, Brain, Brain Edema, Child, Epidemiologic Methods, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Disease Progression

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