Progressive Multifocal Leukoencephalopathy 1 Joel Kirsh, M.D., Leonard Rosenthall, M.D., Morrison H. Finlayson, M.D., and Roberto Wee, M.D. The radionuclide, radiographic and pathologic findings in a patient with progressive multifocal leukoencephalopathy were correlated. Radionuclide imaging demonstrated the largest two of the many lesions observed at pathology. On repeated studies, one of the lesions developed a "doughnut" sign due to central necrosis. Cerebral angiography disclosed only one lesion which was initially suggestive of tumor encasement, but four weeks later, this deteriorated into an avascular zone. There were no characteristic features of the lesions demonstrated by radionuclide imaging and cerebral angiography that could be specifically attributed to progressive multifocal leukoencephalopathy. INDEX TERMS: Brain, inflammation. Brain, necrosis. Brain, radionuclide studies. Cerebral angiography
Radiology 119:399-400, May 1976
ROGRESSIVE multifocal leukoencephalopathy (PML) is an
invariably fatal viral illness occurring in patients with Iympho- and myeloproliferative neoplasms, carcinomatosis, granulomatous inflammatory disease and is also seen following organ transplantation. These patients all have abnormalities of the immune system which may allow for opportunistic viral infection. PML was first described in 1958 by Astrom et al. (1) and the probable viral etiology proposed by Richardson in 1961 (2-4) still stands as the best explanation for this disease, the usual causative strains being of the papova viral group, ie., JC virus and the SV 40-PML virus. To date, approximately 100 cases have been reported and in these only one positive radionuclide brain scan (5) was obtained and one positive computed tomogram (CT scan) (6). To our knowledge no positive pneumoencephalograms and
branch of the middle cerebral artery due to irregular narrowing of a segment of the artery within the sylvian fissure. The appearance of the narrowed segment was similar to that seen in tumor "encasement" (Fig. 2). The internal cerebral vein was not displaced. A repeat left carotid angiogram on 28 November 1974 again showed displacement of the frontal midline vessel. The involved ascending frontal branch of the middle cerebral artery was now completely occluded and on the capillary phase of the angiogram the intermediate frontal region was relatively avascular (Fig. 3). The occluded frontal branch was subsequently opacified through collaterals and could be seen in the late venous phase. No early venous drainage or staining was seen at any time. Death occurred 28 November 1974. At autopsy, there was no recurrent lymphosarcoma in the brain or elsewhere. On external examination the brain was normal. Major cerebral arteries were patent and only slightly atherosclerotic. Two areas of white matter necrosis were seen on section of the left frontal lobe. The largest occupied the middle three fifths of the lobe and at the level of the frontal horn of the lateral ventricle it had destroyed most of the central white matter. The smaller lesion involved the white matter underlying the superior frontal gyrus in the posterior third of the frontal lobe. In addition, there were greyish demyelinated plaques about 1 cm in diameter in the left occipital, right temporal and cerebellar white matter, and in the pontine tegmentum and the quadrigeminal plate. A few smaller lesions were also found on microscopic examination. A frontal branch of the left middle cerebral artery was occluded by organized and partially recanalized thrombus. Some degree of proliferative reaction was seen in blood vessels, this being most evident in relation to the larger lesions. DISCUSSION Reports of positive radionuclide brain scans in demyelinating cerebral disease appear sporadically in the literature (710). In the only other case report of a positive brain scan in PML, the lesion initially concentrated 99mTc04, but failed to do so after one month. It was still normal immediately prior to death, but the gross and microscopic pathological findings
cerebral angiograms have appeared in the literature.
were allegedly consistent with PML (5). Vascular occlusion is not known to be a feature of PML, but no other cause for this occlusion was found at autopsy. Sizable areas of necrosis are an occasional feature of PML (11). The cause of the necrosis is uncertain, but in the present case, endothelial proliferation and vascular thickening and thrombosis may be of importance. The incidence of PML greatly exceeds the frequency of associated abnormal radionuclide brain scans and neuroradiological findings. Furthermore, the abnormalities, when present, are indistinguishable from other cerebral afflictions.
CASE REPORT This 60-year-old man first became ill in 1969 and a diagnosis of lymphosarcoma was made after laparotomy and biopsy. He received both chemo- and radiotherapy. Symptoms of peripheral neuropathy associated with adult onset diabetes developed in March 1974. At the time of final admission (23 October 1974) he complained of headaches, nausea, vomiting, photophobia, blurred vision, dizziness, and numbness of the right face, tongue and hand. Physical examination revealed some mental confusion, a short attention span, poor memory, and a broad-based, unsteady gait. Lumbar puncture on several occasions showed an elevated cerebrospinal (CSF) glucose (probably related to the diabetes), a slightly elevated CSF protein and 3-6 leukocytes and 10-20 red blood cells. No organisms were found in CSF smear or cultures. There were electroencephalographic abnormalities compatible with a left frontal tumor. Radionuclide brain images (Fig. 1) on 24 October 1974 showed an ill-defined area of increased uptake of radiopertechnetate (99mTc04) in the left frontal region. A slight decrease in concentration was observed on November 1, which could have been due to early postinjection imaging, but on November 6 the lesion was again clearly demonstrated. The lesion showed a central focus of absent uptake on November 22, and in addition, a second lesion in the parasagittal region of the left frontal lobe was seen for the first time. A left carotid angiogram on 31 October 1974 showed a 4mm displacement of the pericallosal artery to the contralateral side. There was marked delay in opacification of the third ascending frontal
Leonard Rosenthal!, M.D. Division of Nuclear Medicine The Montreal General Hospital 1650 Cedar Avenue Montreal, Quebec, Canada H3G 1A4 REFERENCES 1. Astrom KE, Mancall EL, Richardson EP Jr: Progressive multifocalleukoencephalopathy. Brain 81:93-111, 1958 2. Richardson EP: Progressive multifocal leukoencephalopathy. New Engl J Med 265:815-823,26 Oct 1961 3. Zu Rhein GM, Chou 8M: Particles resembling papovaviruses in human cerebral demyelinating disease. Science 148:14771479, 11 Jun 1965 4. Davies JA, Hughes JT, Oppenheimer DR: Richardson's disease (progressive multifocal leukoencephalopathy. Q J Med 42: 481-501, Jul 1973
1 From the Divisions of Nuclear Medicine (J. K., L. R.) and Neurology (M. H. F.) and Department of Radiology (R. W.), The Montreal General Hospital, Montreal, Quebec, Canada. Revised manuscript accepted for publication in October 1975. shan
JOEL KIRSH AND OTHERS
Fig. 1. Serial 99mrc04 brain images. On 22 November 1974 the frontal lobe lesion developed a "doughnut" sign corresponding to the central necrosis seen at autopsy. Arrow points to a second lesion which appeared in the parasagittaf region of the left frontal lobe in the intervening time and not demonstrated by cerebral angiography. Fig. 2. Left carotid angiogram on 31 October 1974. Marked delay in opacification of the third ascending frontal branch of the middle cerebral artery (solid arrow) is seen. Fig. 3. Left carotid angiogram on 28 November 1974. The ascending frontal branch of the middle cerebral artery is now completely occluded and is seen in the late venous phase because of collateral filling. The capillary phase shows a relatively avascular area (open arrow).
Fig. 4. The small arrows show densely stained, enlarged oligodendroglial nuclei. There is also vascular thickening (open arrow) and an atypical multinucleate astrocyte (large solid arrow). The section is from a PML lesion in the cerebral white matter and stained with hematoxylin and eosin.
5. Mosher MB, Schall GL, Wilson J: Progressive multifocal leukoencephalopathy. Positive brain scan. JAMA 218:226-228, 11 Oct 1971 6. Paxton R, Ambrose J: The EMI scanner. A brief review of the first 650 patients. Br J Radiol 47:530-565, Sep 1974 7. Halpern SE, Smith CW, Ficken V: 99mrc brain scanning in herpes virus type I encephalitis. J Nucl Med 11:548-550, Sep 1970 8. Mishkin FS: Radionuclide angiogram and scan findings in a case of herpes simplex encephalitis. J Nucl Med 608-609, Oct 1970 9. Gize RW, Mishkin FS: Brain scans in multiple sclerosis. Radiology 97:297-299, Nov 1970. 10. Weisbaum SD, Garnett ES: Brain scan in Schilder's disease. J Nucl Mad 14:291-292, May 1973 11. Zu Rhein GM: Virions in progressive multifocal leukoencephalopathy. [In] Pathology of the Nervous System. Minckler J, ed. Philadelphia, McGraw-Hili, Vol III, 1972, pp 2893-2912 12. Zu Rhein GM, Albert AE, Padgett BL, et al: Pathology of brain tumors induced in Syrian hamsters after inoculation with a papovavirus (JC) from human brain tissue. J Neuropath Exp Neurol 33:173, 1974