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Coincidence of multiple sclerosis and glioma. Clinical and radiological remarks on two cases
Surg Neurol 1986;26:45-51
45
C o i n c i d e n c e o f M u l t i p l e Sclerosis and G l i o m a Clinical and Radiological Remarks on Two Cases H.-C. Nahser, M.D., P. Vieregge, M.D., H. E. Nau, M.D., and V. Reinhardt, M.D. Neurochirurgische Klinik and Institut for Neuropathologie, Universit~itsklinikum der Gesamthochschule Essen, Essen, West Germany
Nahser H-C, Vieregge P, Nau HE, Reinhardt V. Coincidence of multiple sclerosis and glioma. Clinical and radiological remarks on two cases. Surg Neurol 1986;26:45-51. The clinical course and computed tomographic findings in two patients suffering from multiple sclerosis and coincidental gliomatous brain tumor are presented. Both diagnoses were proven by surgical biopsy; autopsy findings of one case are reported as well. Our results demonstrate that a differentiation of both diseases is not possible by computed tomography or by clinical data alone. Surgical biopsy to establish the diagnosis is indicated during the course of suspected multiple sclerosis when computed tomographic alterations and clinical signs of a spaceoccupying lesion last for some weeks. KEY WORDS: Multiple sclerosis; Brain tumor; Glioma; Computed tomography; Astrocytoma
Cerebral features such as headache, aphasia, seizures, and organic psychosyndrome are known but are rare events in the course of disseminated encephalomyelitis-multiple sclerosis [ 14,15]. In such cases the question arises whether these symptoms are due to the progressive multiple sclerosis itself or to a coincidental spaceoccupying gliomatous process o f the brain. In 1963 Brihaye et al [3] reported on a case of multiple sclerosis with a cerebral glioma. They discussed the mutual relationship of both processes. Other reports were given by Munch-Petersen [22], Mathews and Moossy [21], Currie and Ulrich [8], and Ulrich and Wiiethrich [32]. A review o f the problem was presented by Russell and Rubinstein [27]. It is not clear whether there is a transformation to a gliomatous tumor in the scar of multiple sclerosis or a simple coincidence that could be expected based on simple statistical analysis o f both processes [13]. Since the introduction of computed tomography (CT) Address reprint requeststo: Dr. Hans-C. Nahser, Neurochirurgische Klinik, Hufelandstra/3e 55, D-4300 Essen, West Germany.
© 1986by ElsevierSciencePublishingCo., Inc.
scanning some observations of space-occupying lesions in the course of multiple sclerosis have been presented [2,20,29,30,35]. Some of them [29,35] discussed the usefulness of corticosteroids in the differential diagnosis between multiple sclerosis and a possible secondary process, but there was no confirmatory biopsy. In contrast to these authors, others [23,26,28,33] performed biopsies in patients with multiple sclerosis and CT evidence of mass lesions. N o n e of them revealed a coincidental tumor. H e r e we present two cases, each with well established multiple sclerosis, whose clinical and CT data raised the possibility of an additional mass lesion years after the onset of the demyelinating disease. Both histologic and postmortem examinations confirmed multiple sclerosis as well as the suspected neoplasm. Detailed neuropathological findings of these cases are discussed in another report [34].
Case Reports Case 1
A 43-year-old woman had a 19-year history of multiple sclerosis with bouts and relapses of predominant oculomotor symptoms and typical changes in cerebrospinal fluid (CSF) proteins. In July 1980 she was admitted to the hospital with a grand mal seizure. Cerebrospinal fluid protein was 50 mg/dl with gamma globulin fraction of 19.4%. IgG was 12.4 mg/dl. An electroencephalogram (EEG) after the seizure showed transient local changes in the right frontotemporoparietal and the left parietooccipital region. A scintigraphic brain scan was normal. A C T scan showed a large area of low attenuation in the right frontal region, limited to the white matter and 4.5 x 4 cm in size, with few signs of midline shift, but no enhancement after contrast application. Angiography of the right carotid artery showed a delayed filling of the anterior cerebral circulation by the contrast medium in the late arterial phase. The patient was given anticonvulsive therapy and continued under regular neurological observation. Five subsequent 0090-3019/86/$3.50
46
Surg Neurol 1986;26:45-51
CT scans did not show any changes in the lesion for the next 16 months, during which time the patient suffered from repeated general seizures. In the EEG a right frontotemporal delta focus developed. In N o v e m b e r 1981 the patient developed increasing headache in the right temporal region, and disturbances of concentration and memory. She developed a slight paresis of the left arm; the deep tendon reflexes were slightly increased on the left side. In the CT scan the hypodense area in the right frontal region had increased, and the signs of a space-occupying lesion were more distinct. Five days later, after high-dosage antiedematous therapy, the hypodense area was a bit smaller. A patchy contrast enhancement of cortical regions along its borders was seen for the first time (Figure 1). On the following day a cerebral biopsy through a right frontotemporal craniotomy was performed. The solid tumorlike
Figure l. Ca.~e l. The C T scan in a 4 ~-year-oldjemale u'ith Jinica//~ established multiple sclerosk after developing right hemispheriea/ fiJ~a/ sign.~ shows a right frontal hyperdense area with distinct ~igns 4 a .~pa~e-occupying pro~>~s and a borderline enhamemenl.
Nahser et al
tissue could be removed only subtotally. Histologic examination revealed a grade-II astrocytoma with partial cyst formation (Figure 2). In the same specimen, an old plaque of demyelination outside of the tumor region was seen. The patient underwent postoperative radiation of the brain with 6000 rads and cytostatic therapy with lomustine in three courses. Until October 1982 there were various complaints of headache, vertigo, paresthesia, and intermittent signs of nystagmus attributed to the known multiple sclerosis. The symptoms from the resection of the tumor consisted of slightly increased tendon reflexes on the left side and an organic psychosyndrome. The clinical state improved with the repeated application of dexamethasone. In October 1982 hemiparesis on the right side and motoric aphasia developed in the course of a few days, so that the patient was bedridden. The CT scan showed a ventricular enlargement as compared with earlier scans. A homogenous hypodense area with fingerlike boundaries was seen in the left frontoparietal area with a midline shift (Figure 3). The sharply delineated hypodense area in the right frontal region showed no changes in comparison with
Multiple Sclerosis and Glioma
Surg Neurol 1986;26~45-51
47
Figure 2. Case 1. Top: Low-power photomicrograph of the grade II astrocytoma. Moderately dense tumor tissue with cysts. (Elastica van Gieson stain, × 110.) Bottom: Higher magnification shows rounded chroraa~in-rich nuclei of the tumor cells. Microcystic architecture. (Elastica van Gieson stain, × 280.)
the earlier preoperative and postoperative examinations. An acute demyelination was assumed as the reason for the clinical deterioration, documented also in the CT scan. Therapy consisted of administering steroids be* cause there was no indication for an operative approach to the left hemisphere. The patient died in February 1983 at home. An autopsy was not performed. Case 2
A 49-year-old man had an 8-year history of multiple sclerosis with bouts and relapses of predominant sensorimotor symptoms in the lower limbs and typical
changes in CSF proteins. Since April 1980 he had suffered from intermittent amnestic aphasia. In October 1980 he experienced a series of generalized tonic-cl0nic seizures with predominance in the right limbs. On admission there was a slight paresis of the right arm with slightly increased deep tendon reflexes, hyperreflexia of the lower limbs, pyramidal signs on both sides, slight ataxia and dysdiadochokinesia on the left side, and impairment of vibration sense in the right limb. The patient was disoriented, listless, and superficially euphoric and showed amnestic aphasia. Cerebrospinal fluid contained 10/3 cells, protein was 80.7 mg/dl. Levels of gamma globulin and IgG were elevated. Electroencephalogra-
48
Surg Neurol 1986;26:45-51
Figure 3. (Case 2) 12 months after combined treatment, when focal signs of the contralateral hemisphere were recorded. Nonenhanced C T scan points out a right frontal scar formation and a left frontoparietal hypodense area with space occupation.
phy revealed slight general disturbances that were focally marked in the left temporooccipital region. Scintigraphic brain scan showed abnormal density in the left temporooccipital region. A computed tomography scan showed a large, sharply demarcated area of low attenuation in the left parietal region surrounded by an nonhomogenous hyperdense area in the frontal region and a small but distinct midline shift (Figure 4). Patchy contrast enhancement was seen in the frontal border of the area. Angiography of the left carotid artery displayed signs of a space-occupying lesion. The patient was treated with anticonvulsive, antibiotic, and antiedematous drugs. Nevertheless, he developed a slight dysarthria and a slight paresis of the right leg. At that time, the EEG showed a constant spike wave focus in the left frontoparietotemporal area, while the CT scan showed increased signs of mass lesion. In November 1980 a previously postponed biopsy
Nahser et al
was performed in the left frontoprecentral region. A cystic astrocytoma of slight malignancy was diagnosed microscopically. In March 1981 a CT scan showed no signs of an expanding mass lesion. In June 1981 the patient became drowsy and experienced a subsequent severe generalized tonic-clonic seizure, during which he expired. Necropsy showed characteristic plaques of demyelination in the periventricular white matter, and several solitary plaques were seen in the white matter and on the borders between the gray and white matter of the cerebrum. The solid, macroscopically reddish tumor occupied the corpus striatum, the insertion of the corpus callosum, and the cingulate gyrus on the left side. Tumor cells, however, were detected not only in these regions, but also in other areas of the cerebrum and even in the cerebellum and brainstem, far from the macroscopically seen tumor. These tumor cells presented hyperchromatic, often multinucleated, giant cells with several mitoses lying solitarily or in clusters in otherwise normal central nervous tissue. There was no evidence of a continuous transformation of reactive glial cells of a plaque toward nearby tumor cells (Figure 5).
Multiple Sclerosis and Glioma
Surg Neurol 1986;26:45-51
49
Figure 4. (Case 2) C T scan of 49-year-old man with an 8-year history of multiple sclerosis, who developed left hemispheric deficits, shows a more pronounced uptake of contrast medium in a parasagittal area of hypodensity invading the corpus callosum and showing a mass effect.
Discussion Computed tomography has been widely used to study abnormalities in patients with multiple sclerosis [6,12,28]. Several studies correlated CT findings with clinical data and other standard investigations at the time of CT scan-
ning [5,18,19,24,15,31]. None of the alterations on the CT scan, however, revealed any pathognomonic features for the diagnosis of the demyelinating disease in its different stages. This difficulty is stressed by the conflicting results of reports comparing CT and morphological findings in multiple sclerosis. In the acute demyelinating
50
Surg Neurol 1986;26:45-51
A
B
Figure 5. (A) Two foci of demyelination in the cerebellar white matter. (Sudanblack Nuclear Fast Red, × 5.) (B) Astrocytoma with mainly bipolar tumor cells, many multinucleated giant cells, and sinusoidlike vessel formation. (H & E, × 175.)
bouts o f multiple sclerosis, contrast enhancement is attributed to a lack o f blood-brain barrier [10]; but there are cases o f acute demyelination that have been proven microscopically without contrast enhancement in any stage o f the clinical course [4,7,9,16,18,36]. However, contrast enhancement was also seen in a case o f acute demyelinating leukoencephalitis [20]. A strong correlation between contrast enhancement and demyelination in multiple sclerosis was seen by W~iethrich et al [37], Lebow et al [17], and Tritschler et al [31]. The discussion o f the mechanisms and the value of contrast enhancement in different stages of demyelinating diseases continues. Sears et al [30] recommended delayed CT scanning after administration of high doses o f contrast medium to "maximize the harvest of contrast enhancing lesions" in multiple sclerosis. On the other hand, it was shown that high dose o f iodine in cases o f disturbed blood-brain barrier led to hemorrhages in previously anemic cerebral infarctions. It is accepted that the blood-brain barrier is disturbed in acute demyelinating processes as well. Therefore the use of high doses of iodine may not only maximize the amount of visible lesions in CT, but also cause the clinical status of the patient to deteriorate. The delayed scanning seems to
Nahser et al
have disadvantages as well as advantages, because multiple lesions can lead to a wrong differential diagnosis (metastasis, abscess formation, multicentric gliomas) and will not alter the therapeutic management of multiple sclerosis. The diagnosis of multiple sclerosis cannot be made by computed tomography, but is a clinical diagnosis confirmed by CSF and electrophysiological investigations. The influence of corticoid therapy on hyperdense and hypodense lesions in acute multiple sclerosis is not yet clear [1,18]. Perhaps it depends on an interaction between the given amount of the contrast medium and the stabilization o f the defective blood-brain barrier by steroids. It is generally accepted [23,33] that the mass effect in acute demyelinating disease disappears during the course of some weeks. In these cases the hypodense area diminishes, as does the contrast enhancement, [9] and the resulting scar does not enhance. In our cases there was no reduction in size of the mass lesion during a considerable time o f CT and clinical observation. There was no difference in either of our cases, although one received corticoids. Furthermore, contrast administration in our cases did not lead to differentiation between mass effect caused by an acute bout of demyelination and that caused by a tumorous process. This can be explained by the fact that low-grade astrocytomas generally do not show pronounced enhancement. In those cases of demyelinating disease without CT evidence of decreasing mass effects and simultaneous clinical deterioration, we recommend biopsies in order to get valid information. As calculated by J/inisch et al [13], the coincidence of multiple sclerosis and brain tumor must be higher than the number o f cases in the literature. We think that more biopsies may lead to more diagnoses of coincidence o f the two diseases. Some of the reported cases of multiple sclerosis with mass lesions might have shown an underlying tumor, because pathologic investigation makes a continuous transformation of reparative glia into tumor cells unlikely. The small number of reports seems to indicate certain immunological factors in the rise o f gliomatous tumors during the course of multiple sclerosis [24,32]. It also remains to be seen whether irradiation or combined therapy, as was performed in one o f our patients, improves the clinical course. Compared with the survival rate in a study o f patients treated with the same combined treatment [11] as in our case 1, the survival time of our patient seems to be in the usual range. References 1. Aita JF. Cranial CT and multiple sclerosis: contrast enhancing lesions. Arch Neurol 1978;35:183. 2. AitaJF. Atypicalcontrast enhancement in computed tomography of demyelinatingdisease [letter]. Arch Neurol 1982;39:194-5.
Multiple Sclerosis and Glioma
3. Brihaye J, Perier O, Stenuit J. Multiple sclerosis associated with a cerebral glioma. J Neuropathol Exp Neurol 1963;22:128-37. 4. Brown WJ. The capillaries in acute and subacute multiple sclerosis plaques: a morphometric analysis. Neurology 1978;28:84-92. 5. Confavreux C, Aimard G, Deuc M. Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain 1980;103:281-300. 6. Cala LA, Mostaglia FL. Computerized axial tomography in multiple sclerosis. Lancet 1976;ii:689. 7. Cole M, Ross RJ. Plaque of multiple sclerosis seen on computerized transaxial tomogram. Neurology 1977;27:890-1. 8. Currie S, Urich H. Concurrence of multiple sclerosis and glioma. J Neurol Neurosurg Psychiatry 1974;37:598-605. 9. Davis KR, Taveras JM, Robeson GH, Ackerman RH. Some limitations of computed tomography in the diagnosis of neurological diseases. AJR 1976;127:111-23. 10. Gado MH, Phelps ME, Coleman RE. An extravascularcomponent of contrast enhancement in cranial computed tomography. Radiology 1975;117:589-93. 11. Grote W, Nahser HC. Die operative Behandlung der Grosshirntumoren, insbesondere der Grosshirngliome.Verh Dtsch Krebsges 1984;5:199-206. 12. Glydenstedt C. Computer tomography of the brain in multiple sclerosis. Acta Neurol" Scand 1976;53:386-9. 13. J/inisch W, Giithert H, Schreiber D. Pathologie der Tumoren des Zentralnervensystems. Jena: VEB Gustav Fischer, 1976. 14. Kahana E, Leibowitz U, Alter M. Cerebral multiple sclerosis. Neurology 1971;21:1179-85. 15. Kurtzke JF. Clinical manifestations of multiple sclerosis. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology. Vol. 9. New York: Elsevier, 1970:161-216. 16. Lane B, Carroll BA, Pedlay TA. Computerized cranial tomography in cerebral diseases of white matter. Neurology 1978;28:534-44. 17. Lebow S, Anderson DC, Mastri A, Leson D. Acute multiple sclerosis with contrast enhancing plaques. Arch Neurol 1978;35:435-9. 18. Loisan LA, Cole G. Acute cerebral demyelination: clinical and pathological correlation with computed tomography. J Neurol Neurosurg Psychiatry 1982;45:725-8. 19. Loisan LA, Rolfe EB, Hewazy H. Cranial computed tomography in the diagnosis of multiple sclerosis. J Neurol Neurosurg Psychiatry 1982;45:905-12. 20. Marano MD. Atypical contrast enhancement in computerized tomography of demyelinatingdisease. Arch Neurol 1980;37:523-4.
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21. Mathews T, MoossyJ. Mixed glioma, multiple sclerosis, and Charcot-Marie-Tooth disease. Arch Neurol 1972;27:263-8. 22. Munch-Petersen CJ. A case of disseminated sclerosis and glioma of the brain in the same patient. Acta Psychiatr Neurol Scand 1949;24:599-605. 23. Nelson MJ, Miller SL, McLainJR, Gold LHA. Multiple sclerosis: large plaque causing mass effect and ring sign. J Comput Assist Tomogr 1981;5:892-4. 24. Paty DW, Blume WT, Brown WF, Jaarcul N, Kertesz A, Mclnnio W. Chronic progressive myelopathy. Investigation with CSF electrophoresis, evoked potentials and CT scan. Am Neurol 1979;6:419-24. 25. Reisner T, Maida E. Computerized tomography in multiple sclerosis. Arch Neurol 1980;37:475-7. 26. Rieth KG, DiChiro G, Cromwell LD, McKeever P, Kornblith PL, Kufta CV, Pleet B. Primary demyelinating disease simulating glioma of the corpus callosum. J Neurosurg 1981;55:620-4. 27. Russell DS, Rubinstein LJ. Pathology of tumours of the nervous system. 4th ed. London: Arnold, 1977:103, 151 f., 240 f. 28. SagarHJ, Wariow CP, Sheldon PWE, Esiri MM. Multiple sclerosis with clinicaland radiologicalfeatures of cerebral tumour.J Neurol Neurosurg Psychiatry 45:802-8. 29. Sears ES, Tindall RSA, Zarnow H. Active multiple sclerosis. Arch Neurol 1978;35:426-34. 30. Sears ES, McCammon A, Bigelow R, Haymann LA. Maximizing the harvest of contrast enhancing in multiple sclerosis. Neurology 1982;32:815-20. 31. Tritschler JL, Delouvrier JJ, Masson M, Nahum H, Cambier J. Apport de la tomodensidometrie cerebrale au diagnostic de la scl6rose en plaques. Rev Neurol 1979;135:455-66. 32. Ulrich J, Wiithrich R. Multiple sclerosis: reticulum cell sarcoma of the nervous system in a patient treated with immunosuppressire drugs. Eur Neurol 1974;12:65-78. 33. Van der Velden M, Bots GTAM, Endtz LJ. Cranial CT in multiple sclerosis showing a mass effect. Surg Neurol 1979;12:307-10. 34. Vieregge P, Nahser HC, Gerhard L, Reinhardt V, Nau HE. Multiple sclerosis and cerebral tumor. Clin Neuropathol 1984;3:10-21. 35. Wang AM, Morris JH, Hickey WF, Hammerschlag SB, O'Reilly GV, Rumbangh CL. Unusual patterns of multiple sclerosis. AJNR 1983;4:47-50. 36. Warren KJ, Ball MJ, Paty DW. Computer tomography in disseminated sclerosis. J Can Neurol 1976;3:211-6. 37. Wiithrich R, Gigli H, Wiggli K, Miiller HR, Elhe M, Hiinig K. CT scanning in demyelinating diseases. In: Lanksch W, Kazner E, eds. Cranial computerized tomography. New York: SpringerVerlag, 1976:239-43.
45
C o i n c i d e n c e o f M u l t i p l e Sclerosis and G l i o m a Clinical and Radiological Remarks on Two Cases H.-C. Nahser, M.D., P. Vieregge, M.D., H. E. Nau, M.D., and V. Reinhardt, M.D. Neurochirurgische Klinik and Institut for Neuropathologie, Universit~itsklinikum der Gesamthochschule Essen, Essen, West Germany
Nahser H-C, Vieregge P, Nau HE, Reinhardt V. Coincidence of multiple sclerosis and glioma. Clinical and radiological remarks on two cases. Surg Neurol 1986;26:45-51. The clinical course and computed tomographic findings in two patients suffering from multiple sclerosis and coincidental gliomatous brain tumor are presented. Both diagnoses were proven by surgical biopsy; autopsy findings of one case are reported as well. Our results demonstrate that a differentiation of both diseases is not possible by computed tomography or by clinical data alone. Surgical biopsy to establish the diagnosis is indicated during the course of suspected multiple sclerosis when computed tomographic alterations and clinical signs of a spaceoccupying lesion last for some weeks. KEY WORDS: Multiple sclerosis; Brain tumor; Glioma; Computed tomography; Astrocytoma
Cerebral features such as headache, aphasia, seizures, and organic psychosyndrome are known but are rare events in the course of disseminated encephalomyelitis-multiple sclerosis [ 14,15]. In such cases the question arises whether these symptoms are due to the progressive multiple sclerosis itself or to a coincidental spaceoccupying gliomatous process o f the brain. In 1963 Brihaye et al [3] reported on a case of multiple sclerosis with a cerebral glioma. They discussed the mutual relationship of both processes. Other reports were given by Munch-Petersen [22], Mathews and Moossy [21], Currie and Ulrich [8], and Ulrich and Wiiethrich [32]. A review o f the problem was presented by Russell and Rubinstein [27]. It is not clear whether there is a transformation to a gliomatous tumor in the scar of multiple sclerosis or a simple coincidence that could be expected based on simple statistical analysis o f both processes [13]. Since the introduction of computed tomography (CT) Address reprint requeststo: Dr. Hans-C. Nahser, Neurochirurgische Klinik, Hufelandstra/3e 55, D-4300 Essen, West Germany.
© 1986by ElsevierSciencePublishingCo., Inc.
scanning some observations of space-occupying lesions in the course of multiple sclerosis have been presented [2,20,29,30,35]. Some of them [29,35] discussed the usefulness of corticosteroids in the differential diagnosis between multiple sclerosis and a possible secondary process, but there was no confirmatory biopsy. In contrast to these authors, others [23,26,28,33] performed biopsies in patients with multiple sclerosis and CT evidence of mass lesions. N o n e of them revealed a coincidental tumor. H e r e we present two cases, each with well established multiple sclerosis, whose clinical and CT data raised the possibility of an additional mass lesion years after the onset of the demyelinating disease. Both histologic and postmortem examinations confirmed multiple sclerosis as well as the suspected neoplasm. Detailed neuropathological findings of these cases are discussed in another report [34].
Case Reports Case 1
A 43-year-old woman had a 19-year history of multiple sclerosis with bouts and relapses of predominant oculomotor symptoms and typical changes in cerebrospinal fluid (CSF) proteins. In July 1980 she was admitted to the hospital with a grand mal seizure. Cerebrospinal fluid protein was 50 mg/dl with gamma globulin fraction of 19.4%. IgG was 12.4 mg/dl. An electroencephalogram (EEG) after the seizure showed transient local changes in the right frontotemporoparietal and the left parietooccipital region. A scintigraphic brain scan was normal. A C T scan showed a large area of low attenuation in the right frontal region, limited to the white matter and 4.5 x 4 cm in size, with few signs of midline shift, but no enhancement after contrast application. Angiography of the right carotid artery showed a delayed filling of the anterior cerebral circulation by the contrast medium in the late arterial phase. The patient was given anticonvulsive therapy and continued under regular neurological observation. Five subsequent 0090-3019/86/$3.50
46
Surg Neurol 1986;26:45-51
CT scans did not show any changes in the lesion for the next 16 months, during which time the patient suffered from repeated general seizures. In the EEG a right frontotemporal delta focus developed. In N o v e m b e r 1981 the patient developed increasing headache in the right temporal region, and disturbances of concentration and memory. She developed a slight paresis of the left arm; the deep tendon reflexes were slightly increased on the left side. In the CT scan the hypodense area in the right frontal region had increased, and the signs of a space-occupying lesion were more distinct. Five days later, after high-dosage antiedematous therapy, the hypodense area was a bit smaller. A patchy contrast enhancement of cortical regions along its borders was seen for the first time (Figure 1). On the following day a cerebral biopsy through a right frontotemporal craniotomy was performed. The solid tumorlike
Figure l. Ca.~e l. The C T scan in a 4 ~-year-oldjemale u'ith Jinica//~ established multiple sclerosk after developing right hemispheriea/ fiJ~a/ sign.~ shows a right frontal hyperdense area with distinct ~igns 4 a .~pa~e-occupying pro~>~s and a borderline enhamemenl.
Nahser et al
tissue could be removed only subtotally. Histologic examination revealed a grade-II astrocytoma with partial cyst formation (Figure 2). In the same specimen, an old plaque of demyelination outside of the tumor region was seen. The patient underwent postoperative radiation of the brain with 6000 rads and cytostatic therapy with lomustine in three courses. Until October 1982 there were various complaints of headache, vertigo, paresthesia, and intermittent signs of nystagmus attributed to the known multiple sclerosis. The symptoms from the resection of the tumor consisted of slightly increased tendon reflexes on the left side and an organic psychosyndrome. The clinical state improved with the repeated application of dexamethasone. In October 1982 hemiparesis on the right side and motoric aphasia developed in the course of a few days, so that the patient was bedridden. The CT scan showed a ventricular enlargement as compared with earlier scans. A homogenous hypodense area with fingerlike boundaries was seen in the left frontoparietal area with a midline shift (Figure 3). The sharply delineated hypodense area in the right frontal region showed no changes in comparison with
Multiple Sclerosis and Glioma
Surg Neurol 1986;26~45-51
47
Figure 2. Case 1. Top: Low-power photomicrograph of the grade II astrocytoma. Moderately dense tumor tissue with cysts. (Elastica van Gieson stain, × 110.) Bottom: Higher magnification shows rounded chroraa~in-rich nuclei of the tumor cells. Microcystic architecture. (Elastica van Gieson stain, × 280.)
the earlier preoperative and postoperative examinations. An acute demyelination was assumed as the reason for the clinical deterioration, documented also in the CT scan. Therapy consisted of administering steroids be* cause there was no indication for an operative approach to the left hemisphere. The patient died in February 1983 at home. An autopsy was not performed. Case 2
A 49-year-old man had an 8-year history of multiple sclerosis with bouts and relapses of predominant sensorimotor symptoms in the lower limbs and typical
changes in CSF proteins. Since April 1980 he had suffered from intermittent amnestic aphasia. In October 1980 he experienced a series of generalized tonic-cl0nic seizures with predominance in the right limbs. On admission there was a slight paresis of the right arm with slightly increased deep tendon reflexes, hyperreflexia of the lower limbs, pyramidal signs on both sides, slight ataxia and dysdiadochokinesia on the left side, and impairment of vibration sense in the right limb. The patient was disoriented, listless, and superficially euphoric and showed amnestic aphasia. Cerebrospinal fluid contained 10/3 cells, protein was 80.7 mg/dl. Levels of gamma globulin and IgG were elevated. Electroencephalogra-
48
Surg Neurol 1986;26:45-51
Figure 3. (Case 2) 12 months after combined treatment, when focal signs of the contralateral hemisphere were recorded. Nonenhanced C T scan points out a right frontal scar formation and a left frontoparietal hypodense area with space occupation.
phy revealed slight general disturbances that were focally marked in the left temporooccipital region. Scintigraphic brain scan showed abnormal density in the left temporooccipital region. A computed tomography scan showed a large, sharply demarcated area of low attenuation in the left parietal region surrounded by an nonhomogenous hyperdense area in the frontal region and a small but distinct midline shift (Figure 4). Patchy contrast enhancement was seen in the frontal border of the area. Angiography of the left carotid artery displayed signs of a space-occupying lesion. The patient was treated with anticonvulsive, antibiotic, and antiedematous drugs. Nevertheless, he developed a slight dysarthria and a slight paresis of the right leg. At that time, the EEG showed a constant spike wave focus in the left frontoparietotemporal area, while the CT scan showed increased signs of mass lesion. In November 1980 a previously postponed biopsy
Nahser et al
was performed in the left frontoprecentral region. A cystic astrocytoma of slight malignancy was diagnosed microscopically. In March 1981 a CT scan showed no signs of an expanding mass lesion. In June 1981 the patient became drowsy and experienced a subsequent severe generalized tonic-clonic seizure, during which he expired. Necropsy showed characteristic plaques of demyelination in the periventricular white matter, and several solitary plaques were seen in the white matter and on the borders between the gray and white matter of the cerebrum. The solid, macroscopically reddish tumor occupied the corpus striatum, the insertion of the corpus callosum, and the cingulate gyrus on the left side. Tumor cells, however, were detected not only in these regions, but also in other areas of the cerebrum and even in the cerebellum and brainstem, far from the macroscopically seen tumor. These tumor cells presented hyperchromatic, often multinucleated, giant cells with several mitoses lying solitarily or in clusters in otherwise normal central nervous tissue. There was no evidence of a continuous transformation of reactive glial cells of a plaque toward nearby tumor cells (Figure 5).
Multiple Sclerosis and Glioma
Surg Neurol 1986;26:45-51
49
Figure 4. (Case 2) C T scan of 49-year-old man with an 8-year history of multiple sclerosis, who developed left hemispheric deficits, shows a more pronounced uptake of contrast medium in a parasagittal area of hypodensity invading the corpus callosum and showing a mass effect.
Discussion Computed tomography has been widely used to study abnormalities in patients with multiple sclerosis [6,12,28]. Several studies correlated CT findings with clinical data and other standard investigations at the time of CT scan-
ning [5,18,19,24,15,31]. None of the alterations on the CT scan, however, revealed any pathognomonic features for the diagnosis of the demyelinating disease in its different stages. This difficulty is stressed by the conflicting results of reports comparing CT and morphological findings in multiple sclerosis. In the acute demyelinating
50
Surg Neurol 1986;26:45-51
A
B
Figure 5. (A) Two foci of demyelination in the cerebellar white matter. (Sudanblack Nuclear Fast Red, × 5.) (B) Astrocytoma with mainly bipolar tumor cells, many multinucleated giant cells, and sinusoidlike vessel formation. (H & E, × 175.)
bouts o f multiple sclerosis, contrast enhancement is attributed to a lack o f blood-brain barrier [10]; but there are cases o f acute demyelination that have been proven microscopically without contrast enhancement in any stage o f the clinical course [4,7,9,16,18,36]. However, contrast enhancement was also seen in a case o f acute demyelinating leukoencephalitis [20]. A strong correlation between contrast enhancement and demyelination in multiple sclerosis was seen by W~iethrich et al [37], Lebow et al [17], and Tritschler et al [31]. The discussion o f the mechanisms and the value of contrast enhancement in different stages of demyelinating diseases continues. Sears et al [30] recommended delayed CT scanning after administration of high doses o f contrast medium to "maximize the harvest of contrast enhancing lesions" in multiple sclerosis. On the other hand, it was shown that high dose o f iodine in cases o f disturbed blood-brain barrier led to hemorrhages in previously anemic cerebral infarctions. It is accepted that the blood-brain barrier is disturbed in acute demyelinating processes as well. Therefore the use of high doses of iodine may not only maximize the amount of visible lesions in CT, but also cause the clinical status of the patient to deteriorate. The delayed scanning seems to
Nahser et al
have disadvantages as well as advantages, because multiple lesions can lead to a wrong differential diagnosis (metastasis, abscess formation, multicentric gliomas) and will not alter the therapeutic management of multiple sclerosis. The diagnosis of multiple sclerosis cannot be made by computed tomography, but is a clinical diagnosis confirmed by CSF and electrophysiological investigations. The influence of corticoid therapy on hyperdense and hypodense lesions in acute multiple sclerosis is not yet clear [1,18]. Perhaps it depends on an interaction between the given amount of the contrast medium and the stabilization o f the defective blood-brain barrier by steroids. It is generally accepted [23,33] that the mass effect in acute demyelinating disease disappears during the course of some weeks. In these cases the hypodense area diminishes, as does the contrast enhancement, [9] and the resulting scar does not enhance. In our cases there was no reduction in size of the mass lesion during a considerable time o f CT and clinical observation. There was no difference in either of our cases, although one received corticoids. Furthermore, contrast administration in our cases did not lead to differentiation between mass effect caused by an acute bout of demyelination and that caused by a tumorous process. This can be explained by the fact that low-grade astrocytomas generally do not show pronounced enhancement. In those cases of demyelinating disease without CT evidence of decreasing mass effects and simultaneous clinical deterioration, we recommend biopsies in order to get valid information. As calculated by J/inisch et al [13], the coincidence of multiple sclerosis and brain tumor must be higher than the number o f cases in the literature. We think that more biopsies may lead to more diagnoses of coincidence o f the two diseases. Some of the reported cases of multiple sclerosis with mass lesions might have shown an underlying tumor, because pathologic investigation makes a continuous transformation of reparative glia into tumor cells unlikely. The small number of reports seems to indicate certain immunological factors in the rise o f gliomatous tumors during the course of multiple sclerosis [24,32]. It also remains to be seen whether irradiation or combined therapy, as was performed in one o f our patients, improves the clinical course. Compared with the survival rate in a study o f patients treated with the same combined treatment [11] as in our case 1, the survival time of our patient seems to be in the usual range. References 1. Aita JF. Cranial CT and multiple sclerosis: contrast enhancing lesions. Arch Neurol 1978;35:183. 2. AitaJF. Atypicalcontrast enhancement in computed tomography of demyelinatingdisease [letter]. Arch Neurol 1982;39:194-5.
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