Neoplasm or Demyelinating Lesion?
A 32-year-old left-handed woman presented with a 4-week history of progressive left hand numbness, tingling, and clumsiness. Symptoms worsened until she found it difficult to write and perform fine motor tasks. She reported having no transient neurological symptoms in the past. Her medical history was significant only for Dengue fever acquired several years ago while on a visit to Southeast Asia. She was taking no medications, and a review of systems was noncontributory.
Figure 1. Axial T2-weighted image (A) showing a large hyperintenselesion in the right parietal lobe. There is perilesional T2 hyperintensityand a mass effect. On the corresponding axial postcontrast T1-weighted image (B) the lesion is characterized by ring enhancement.
Figure 2. Axial dynamic T2*-weighted image (A). The same imageoverlaid with the relative cerebral blood volume (rCBV) color map (B).Perfusion analysis demonstrates hypoperfusion of the lesion rCBV(rCBV: 0.4) compared with contralateral normal-appearing whitematter (rCBV: 1.05). There is also hypoperfusion demonstrated withinthe perilesional T2 signal abnormality (rCBV: 0.2).
HISTORY
A 32-year-old left-handed woman presented with a 4-week history of progressive left hand numbness, tingling, and clumsiness. Symptoms worsened until she found it difficult to write and perform fine motor tasks. She reported having no transient neurological symptoms in the past. Her medical history was significant only for Dengue fever acquired several years ago while on a visit to Southeast Asia. She was taking no medications, and a review of systems was noncontributory.
PHYSICAL EXAMINATION
The results of mental status, fundoscopic, and cranial nerve examinations were normal. A left sensory arm drift and mild intrinsic hand weakness manifested in the left hand. Decreased temperature and vibration sense also characterized the same hand and forearm. Biceps, triceps, and brachioradialis reflexes were exaggerated in the left arm compared with the right arm. Other aspects of the examination, including motor strength in other limbs, gait, and cerebellar function, were unremarkable.
LABORATORY TESTS
Basic metabolic panel values, complete blood count, erythrocyte sedimentation rate, angiotensin-converting enzyme level, B12 level, antiphospholipid panel, and rapid plasma reagin were within normal ranges; the antinuclear antibody titer was elevated at 160 (speckled). Results of liver function tests were normal, and findings from HIV and Cysticercus antibody tests were negative. The evoked potentials battery was unremarkable. Cerebrospinal fluid studies were declined.
IMAGING STUDIES
A brain MRI with contrast performed at 1.5 tesla revealed a large ring-enhancing lesion in the right parietal lobe. The lesion was associated with a perilesional T2 hyperintensity and mass effect (Figure 1). Subcentimeter foci of a white matter abnormality were noted within the periventricular/pericallosal and subcortical white matter bilaterally. Perfusion analysis demonstrated hypoperfu- sion within the large lesion and the perilesional T2 signal abnormality (Figure 2).
DIAGNOSIS: Clinically isolated syndrome withtumefactive demyelinating lesion
The so-called tumefactive demyelinating lesions (TDLs) or tumor-like multiple sclerosis (MS) lesions are large (2 cm or more in diameter) single plaques with a mass effect and ring enhancement that can simulate a tumor and may represent a considerable diagnostic challenge for neurologists, radiologists, and pathologists.
Clinically, TDLs can cause symptoms suggestive of a mass lesion.1 On MRI, TDLs are often indistinguishable from high-grade glial neoplasms, demonstrating ill-defined borders, mass effect, perilesional edema, central necrosis, ring enhancement, and variable involvement of gray matter.1 The exact cause of primary demyelinating plaques is unknown. In the largest published series of TDLs,2 researchers followed up with 31 patients with a biopsy-proven TDL from 9 months to 12 years. All patients improved significantly after corticosteroid therapy. Three patients developed additional lesions consistent with MS during the follow-up period.
It was suggested that TDLs might occupy an intermediate position between MS and postinfectious/ postvaccination encephalitis. Nonetheless, even in the setting of established MS, the atypical appearance of a large lesion can suggest a concurrent neoplasm.
The difficulty in diagnosing TDLs often leads to surgical biopsy, and even the histopathological findings can be confused with those of high-grade glial neoplasms because of the presence of hypercellularity, atypical reactive astrocytes, and mitotic figures.3 This, in turn, can result in unnecessary and potentially harmful surgical resection or radiation therapy. Although specific stains for myelin and axons are needed to make the correct diagnosis, a key histopathological feature of TDLs is the absence of frank angiogenesis.
QUANTITATIVE MRI
New MRI techniques, such as proton MR spectroscopy (1H-MRS) and diffusion and perfusion imaging, have been tested in search of modalities able to help differentiate TDLs from tumors. 1H-MRS is a noninvasive tool for measuring the biochemical abnormalities in various intracranial disease processes. A study using 1H-MRS that sought to differentiate 6 TDLs from 10 high-grade gliomas found that the only significant difference between these 2 entities was the N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) ratio in the central region of the lesions.4
Because NAA is predominantly located in neurons, it is decreased in neoplasms that cause neurons to be displaced by or replaced with malignant cells. In MS, the reduction of NAA in acute lesions may be due to either axonal degeneration or neuronal mitochondrial dysfunction. The latter is supported by the reduction in NAA that has been found to be reversible over time in some lesions. In the histopathological examination of most high-grade gliomas, the area of central necrosis observed on MRI correlates with necrosis of the brain parenchyma, including neurons.
In another study,5 4 TDLs demonstrated the appearance of necrosis or cystic degeneration on MRI (seen at histopathological analysis as well). These lesions had lower NAA/Cr ratios than those without necrosis. Because some TDLs demonstrate complete resolution on follow-up MRI, the extent of neuronal damage in the center is unlikely to match that found in the center of high-grade gliomas.
Spectroscopic findings at a single time-point do not allow an unequivocal diagnosis. The temporal sequence of metabolic changes found on 1H-MRS can be more helpful. In particular, the normalization of initial increases in lipid, choline, and lactate peaks within 3 to 4 weeks strongly argues against the presence of a tumor.5 The conclusion of the study was that TDLs and high-grade gliomas share many similar features at both conventional MRI and 1H-MRS, emphasizing the need for the cautious interpretation of spectroscopic findings.
Perfusion MR imaging is a more promising diagnostic tool in differentiating TDLs from intracranial neoplasms. The assessment of cerebral hemodynamics has been made possible through MRI by using dynamic susceptibility contrast-enhanced T2*-weighted MRI.6 This technique uses signal changes that accompany a tracer passing through the cerebral vasculature, which enables a quantitative estimation of cerebral blood flow and volume. It has become a valuable diagnostic tool in the evaluation of intracranial neoplasm and has been useful in grading and monitoring treatment response to antiangiogenic agents.7
Using dynamic contrast-enhanced T2*-weighted MRI, 12 TDLs and 11 brain tumors that appeared to be similar on conventional MRI images were studied.8 The relative cerebral blood volume (rCBV) calculated from dynamic data and expressed as a ratio to contralateral normal white matter differed between the 2 groups, with significantly lower rCBV values in TDLs than in high-grade glial neoplasms. This reflects the different vascularity between high-grade neoplasms and TDLs in which florid angiogenesis is distinctly absent. Interestingly, in 4 patients with TDLs, the dynamic set of images acquired during bolus injection of contrast agent showed a linear "vessel-like" structure through the center of the lesion not seen on conventional MRI.
TREATMENT
TDLs usually respond to high-dose intravenous corticosteroids. Plasma exchange may be an effective therapy when corticosteroids fail.9
THE CASE: COURSE AND OUTCOME
The patient received a 5-day course of high-dose intravenous methylprednisolone sodium succinate (Solu-Medrol), with rapid resolution of hand weakness and improvement of sensory symptoms. She was subsequently given subcutaneous interferon b1b (Betaseron) 250 µg every other day to reduce the risk of conversion to clinically definite MS.10 However, the risk of developing clinically definite MS when the clinically isolated episode is attributed to a TDL is not known. After 3 months of follow-up the patient has not had new episodes of neurological dysfunction.
IN SUMMARY
Although the exact cause of TDL is unknown, TDLs may occupy an intermediate position between MS and postinfectious encephalitis. rCBV measurements can be valuable in differentiating TDLs from high-grade neoplasms. The morbidity and mortality rates for a stereotactic biopsy are relatively low, but biopsy is not without risk. Recognition of the imaging features of a TDL might spare the patient a biopsy procedure. There is an obvious need to clarify the clinical course of and prognosis for patients with TDL and to develop an evidence-based approach to treatment.
References:
REFERENCES
1.
Dagher AP, Smirniotopoulos J. Tumefactive demyelinating lesions.
Neuroradiology.
1996;38:560-565.
2.
Kepes JJ. Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients.
Ann Neurol.
1993;33:18-27.
3.
Zagzag D, Miller DC, Kleinman GM, et al. Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis.
Am J Surg Pathol.
1993;17:537-545.
4.
Saindane AM, Cha S, Law M, et al. Proton MR spectroscopy of tumefactive demyelinating lesions.
AJNR Am J Neuroradiol.
2002;23:1378-1386.
5.
Enzinger C, Strasser-Fuchs S, Ropele S, et al. Tumefactive demyelinating lesions: conventional and advanced magnetic resonance imaging.
Mult Scler.
2005;11:135-139.
6.
Ostergaard L, Sorensen AG, Kwong KK, et al. High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part II: Experimental comparison and preliminary results.
Magn Reson Med.
1996;36:726-736.
7.
Aronen HJ, Gazit IE, Louis DN, et al. Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings.
Radiology.
1994;191:41-51.
8.
Cha S, Pierce S, Knopp EA, et al. Dynamic contrast-enhanced T2*-weighted MR imaging of tumefactive demyelinating lesions.
AJNR Am J Neuroradiol.
2001;22:1109-1116.
9.
Mao-Draayer Y, Braff S, Pendlebury W, Panitch H. Treatment of steroid- unresponsive tumefactive demyelinating disease with plasma exchange.
Neurology.
2002;59:1074-1077.
10.
Kappos L, Polman CH, Freedman MS, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.
Neurology.
2006;67:1242-1249.
