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British Journal of Radiology (2003) 76, 662-665
© 2003 British Institute of Radiology
doi: 10.1259/bjr/85069069
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Case report

Use of serial proton magnetic resonance spectroscopy to differentiate low grade glioma from tumefactive plaque in a patient with multiple sclerosis

D J A Butteriss, MRCP 1 A Ismail, FRCPath 2 D W Ellison, FRCPath 2 and D Birchall, FRCR 1

Departments of 1 Neuroradiology and 2 Neuropathology, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK

Correspondence: Dr D Birchall


   Abstract
Top
 Abstract
Introduction
 Case report
 Discussion
 References
 
We report on the use of serial proton MR spectroscopy (1H MRS) to differentiate between glioma and tumefactive plaque in a known multiple sclerosis (MS) patient who developed a symptomatic cerebral space occupying lesion. Gliomas and acute MS plaques may have indistinguishable chemical resonance spectra, whereas that of chronic plaque is distinct. In our case 1H MRS demonstrated elevated concentrations of choline, lactate and lipid, with reduced N-acetyl aspartate, a pattern consistent with either low grade glioma or acute demyelinating plaque. A repeat study 4 months later showed no change, this was felt to be incompatible with the natural history of an acute plaque and low grade glioma was diagnosed. Surgical removal of the lesion revealed an oligodendroglioma, confirming the imaging findings.


   Introduction
Top
 Abstract
 Introduction
Case report
 Discussion
 References
 
Multiple sclerosis (MS) is one of the most common chronic neurological conditions in the developed world. Diagnosis is made from clinical signs and symptoms referable to discrete areas of the central nervous system that are disseminated in time and space, supported by paraclinical laboratory and radiological, in particular MR, findings.

MR abnormalities are best demonstrated using T2 weighted or fluid attenuated inversion recovery images, which typically demonstrate hyperintense white matter lesions with a predilection for periventricular areas and the corpus callosum. Occasionally, however, atypical plaques can develop, which because of their size, position, mass effect and surrounding vasogenic oedema, mimic intracerebral tumours clinically, radiologically and even histopathologically [1–3].

The coexistence of primary cerebral glioma and MS has been observed by several authors [3, 4] and longitudinal studies of MS patients have shown a greater than expected incidence of brain tumour [5].

With this in mind it is obvious that not all clinical and radiological changes observed in MS patients can be interpreted as progression of demyelination. Equally, not every tumefactive lesion can be biopsied for histopathological assessment, a procedure that carries a significant morbidity rate. In this case report we document the use of proton MR spectroscopy (1H MRS) to non-invasively differentiate glioma from tumefactive plaque in a patient with MS.


   Case report
Top
 Abstract
 Introduction
 Case report
Discussion
 References
 
A 40-year-old man with a 15 year history of clinically definite MS presented with a new onset of partial and complex-partial seizures involving his left arm. The seizures deteriorated despite anti-epileptic medication (sodium valproate 2.5 g) and he underwent MRI and 1H MRS. This examination revealed multiple areas of periventricular white matter abnormality consistent with the diagnosis of MS (Figure 1Go). In addition there was a large right frontal mass lesion expanding the overlying gyri (Figure 2Go), with no enhancement post intravenous gadolinium-DTPA [2]. Chemical shift 1H MRS was performed using a point resolved spectroscopy (PRESS) sequence with echo time (TE) of 14 ms and repetition time (TR) of 560 ms and regions of interest over the right frontal lesion and an area of normal contralateral hemisphere (Figure 3Go) [4]. Relative to chemical resonance intensities in normal, remote brain 1H MRS of the mass lesion showed a decrease in the concentration of N-acetyl aspartate (-59%), an increase in the concentration of choline (+120%) and the presence of lipid and lactate (Figure 4Go). The appearances and MR spectrum of the lesion were interpreted as being consistent with either low grade glioma or acute demyelinating plaque, although the lack of contrast enhancement made acute plaque less likely. Follow-up MRI and MRS 4 months later showed no change in the lesion or its 1H MR spectrum. In particular, the concentration of choline and lactate remained elevated. On this basis a presumptive diagnosis of low grade glioma was made and the patient was admitted for excision biopsy of the right frontal lesion.



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  		Figure 1. T2 weighted image at the level of the bodies of the lateral ventricles showing hyperintense periventricular white matter lesions characteristic of multiple sclerosis.

 


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  		Figure 2. T2 weighted image through the cerebral cortex showing the high signal right frontal mass lesion.

 


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  		Figure 3. Metabolite map for choline at the level of the lesion, showing the positions of the regions of interest over the lesion (1) and normal brain (2).

 


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  		Figure 4. 1H MRS spectra of a normal cortex voxel (top), and from a voxel within the frontal lesion (bottom).

 
Histopathological examination of the specimen showed a uniform infiltrating glioma with few mitoses figures or apoptotic bodies and some vascular proliferation (Figure 5Go). One area showed marked reactive astrocytosis with accompanying loss of myelin (Figure 6Go). These features were found to be diagnostic of a World Health Organization grade 2 oligodendroglioma associated with a chronic plaque of demyelination.



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  		Figure 5. High power (magnification x 200) view of uniform tumour cells with round nuclei showing artefactual perinuclear clearing; "fried egg" appearance. Haematoxylin and eosin stain.

 


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  		Figure 6. High power (magnification x 200) view showing reactive astrocytosis, loss of myelin and mild infiltration by tumour cells. Haematoxylin and eosin stain.

 

   Discussion
Top
 Abstract
 Introduction
 Case report
 Discussion
References
 
The use of 1H MRS has been previously described with respect to both brain tumours and non-neoplastic inflammatory conditions including MS, but to our knowledge MRS has not been used to diagnose brain tumour in a patient with MS.

MRS is commonly used to identify five major chemical resonances in vivo [3]. These are choline containing small molecules, including phospholipids (CHO), involved in the synthesis of cellular membranes (MR resonance at 3.2 parts per million (ppm)); phosphocreatine and creatine (CR), involved in cellular metabolism (3.0 ppm); N-acetyl aspartate (NAA), a neuronal marker thought to act as a neurotransmitter (2.0 ppm); lactate (LAC), a product of anaerobic glycolysis and indirect marker of ischaemic tissue (1.3 ppm); and lipids (LIP), which are a marker of cell membrane breakdown (0.9 ppm).

Low grade gliomas have been consistently shown to exhibit reductions in NAA and increases in CHO resonance intensity. These findings reflect the replacement of normal neuronal tissue with a proliferating cellular process [5]. Increases in LAC are not uncommon, as a result of tissue ischaemia secondary to abnormal angiogenesis and oedema within and surrounding the tumour [6, 7]. Variable increases in LIP have also been described [8].

Several authors have shown significant differences between the chemical resonance spectra of acute and chronic MS plaques. Acute plaques exhibit a spectrum similar to that of low grade glioma with reduction in NAA, consistent with neuronal loss, an increase in CHO and a variable increase in LIP consistent with axonal membrane breakdown, and a consistent elevation of the LAC resonance probably due to ischaemia secondary to the acute inflammatory component of the condition [6, 8–13]. An elevation of "marker" peaks from 2.1 ppm to 2.6 ppm has also been described in acute MS plaques [14]. 1H MRS in chronic MS plaques has been described as showing striking differences from the acute spectra [9]. The typical findings are of a persistent reduction in NAA, with a normalization of CHO, CR, LAC and LIP [9–12, 15]. There are reports, however, of elevated choline resonance intensity in chronic MS plaque, probably reflecting the associated gliotic process [16].

In this case, serial 1H MRS demonstrated consistently elevated choline and lactate resonances. This was interpreted as being most suggestive of a diagnosis of glioma rather than tumefactive plaque on two grounds. First, the persistent elevation of choline concentration was more suggestive of a neoplasm, rather than an inflammatory process, although it should be noted that reports exist of elevated choline levels in chronic MS plaque. Second and crucially, the persistence of consistently elevated lactate resonance was interpreted as being highly suggestive of glioma and atypical for a chronic tumefactive plaque. These conclusions were supported by the subsequent histopathological findings. We propose that serial 1H MRS is a useful, non-invasive method of overcoming the diagnostic dilemma of differentiating glioma from acute tumefactive demyelinating plaque in conditions such as MS, and avoiding unnecessary invasive procedures such as biopsy, with their attendant risks.

Received for publication August 6, 2002. Revision received January 2, 2003. Accepted for publication February 6, 2003.


   References
Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 

  1. Dagher AP, Smiriniotopoulos J. Tumefactive demyelinating lesions. Neuroradiology 1996;38:560–5.[Medline]
  2. Khan OA, Bauserman SC, Rothman MI, Aldrich EF, Panitch HS. Concurrence of multiple sclerosis and brain tumour: clinical considerations. Neurology 1997;48:1330–3.[Abstract/Free Full Text]
  3. Hunter SB, Ballinger WE, Rubin JJ. Multiple sclerosis mimicking primary brain tumour. Arch Pathol Lab Med 1987;111:464–8.[Medline]
  4. Vieregge P, Nahser HC, Gerhard L, Reinhardt V, Nau HE. Multiple sclerosis and cerebral tumour. Clin Neuropathol 1984;3:10–21.[Medline]
  5. Moller H, Kneller RW, Boice JD, Olsen JH. Cancer incidence following hospitalization for multiple sclerosis in Denmark. Acta Neurol Scand 1991;84:214–20.[Medline]
  6. Poptani H, Gupta RK, Roy R, Pandey R, Jain VK, Chhabra DK. Characterization of intracranial mass lesions with in vivo proton MR spectroscopy. AJNR Am J Neuroradiol 1995;16:1593–603.[Abstract]
  7. Preul MC, Caramanos Z, Collins DL, Villemure J-G, Leblanc R, Olivier A et al. Accurate, noninvasive diagnosis of human brain tumours by using proton magnetic resonance spectroscopy. Nat Med 1996;2:323–5.[CrossRef][Medline]
  8. Rand SD, Prost R, Haughton V, Mark L, Strainer J, Johansen J et al. Accuracy of single-voxel proton MR spectroscopy in distinguishing neoplastic from nonneoplastic brain lesions. AJNR Am J Neuroradiol 1997;18:1695–704.[Abstract]
  9. Miller DH, Austin SJ, Connelly A, Youl BD, Gadian DG, McDonald WI. Proton magnetic resonance spectroscopy of an acute and chronic lesion in multiple sclerosis. Lancet 1991;337:58–9.[CrossRef][Medline]
  10. De Stefano N, Matthews PM, Antel JP, Preul M, Francis G, Arnold DL. Chemical pathology of acute demyelinating lesions and its correlation with disability. Ann Neurol 1995;38:901–9.[CrossRef][Medline]
  11. Davie CA, Hawkins CP, Barker GJ, Brennan A, Tofts PS, Miller DH, et al. Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain 1994;117:49–58.[Abstract/Free Full Text]
  12. Grossman RI, Lenkinski RE, Ramer KN, Gonzalez-Scarano F, Cohen JA. MR proton spectroscopy in multiple sclerosis. AJNR Am J Neuroradiol 1992;13:1535–43.[Abstract]
  13. Filippi M, Grossman RI. MRI techniques to monitor MS evolution: The present and the future. Neurology 2002;58:1147–53.[Abstract/Free Full Text]
  14. Hirsch JA, Lenkinski RE, Grossman RI. MR spectroscopy in the evaluation of enhancing lesions in the brain in multiple sclerosis. AJNR Am J Neuroradiol 1996;17:1829–36.[Abstract]
  15. Mader I, Seeger U, Weisert R, Klose U, Naegele T, Grogg W. Short echo proton MR spectroscopy of macromolecules in white matter disease. Proc Intl Soc Magn Reson Med 1999;2:1459.
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This Article
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Right arrow Articles by Butteriss, D J A
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Right arrow Articles by Butteriss, D J A
Right arrow Articles by Birchall, D

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