Journal of Neuro-Ophthalmology, September 1987, Volume 7, Issue 3

Recurrent scintillating scotoma and homonymous hemianopia due to metastatic melanoma.

Acute left homonymous hemianopia and recurrent scintillating scotoma occurred in a 43-year-old woman due to metastases from a cutaneous malignant melanoma that had been resected 5 years previously. Computed tomography initially demonstrated small, probably embolic, areas of occipital lobe infarction. Five months after the onset of her visual symptoms, massive cerebral hemorrhage occurred from a large right occipital lobe tumor that had not been present initially. Autopsy demonstrated malignant melanoma. Visual symptoms related to tumor embolization and/or cerebral hemorrhage may be the presenting features of metastatic cutaneous malignant melanoma.

/ournal of Clillical Neuro-ophthalmology 7(3):155-160, 1987. Recurrent Scintillating Scotoma and Homonymous Hemianopia Due to Metastatic Melanoma Joel M. Weinstein, M.D., Richard E. Appen, M.D., Lanning Houston, M.D. and Gabriele ZuRhein, M.D. '0 1987 Raven Press, Ltd., New York Acute left homonymous hemianopia and recurrent scin­tillating scotoma occurred in a 43-year-old woman due to metastases from a cutaneous malignant melanoma that had been resected 5 years previously. Computed tomography initially demonstrated small, probably em­bolic, areas of occipital lobe infarction. Five months after the onset of her visual symptoms, massive cerebral hemorrhage occurred from a large right occipital lobe tumor that had not been present initially. Autopsy dem­onstrated malignant melanoma. Visual symptoms re­lated to tumor embolization and/or cerebral hemorrhage may be the presenting features of metastatic cutaneous malignant melanoma. Key Words: Hemianopia-Malignant melanoma-Mi­graine. From the Departments of Ophthalmology (J.M.W., R.E.A.), Neurology (J.M. W.), Radiology (L.H.), and Pathology (G.Z.R.) and the Division of Neurosurgery (J.M.W.), University of Wis­consin, Clinical Science Center, Madison, WI, U.S.A. Address all correspondence and reprint requests to J. M. Weinstein, M.D., the University of Wisconsin School of Medi­cine, Department of Ophthalmology, Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, U.S.A. 155 Recurrent scintillating scotoma may be due to a variety of causes, including migraine (1-4), verte­brobasilar artery disease (5), systemic lupus ery­thematosus (6,7), and epilepsy, either primary or due to structural lesions involving the visual system, e.g., arteriovenous malformations of the occipital lobes (8,9). We encountered a patient whose recurrent scintillating scotoma and head­ache were the only manifestations of a cutaneous malignant melanoma metastatic to the occipital lobe. The acute onset of the deficit, the patient's computed tomographic scan appearance, and pathologic examination of the brain were consis­tent with embolization by tumor. This occurrence emphasizes the necessity for an intensive search for metastatic disease when patients with a known history of malignancy develop visual or neurologic symptoms. CASE REPORT In January of 1984 a 43-year-old woman experi­enced the abrupt onset of blurred vision in the lower left hemifield of each eye. She described a sensation of "glittering psychedelic lights" with a "whirling" appearance, The visual abnormality lasted approximately 3 min and was followed by a mild bioccipital headache which lasted 1 h, There were no other neurologic symptoms, Three hours later the visual symptoms recurred and a biocci­pital headache began about 3 min later. The bright scintillations decreased in intensity within 2-3 min but a permanent visual deficit remained. Over the next 2 weeks she complained of distortion in the lower left hemifield as well as recurrence of her scintillations 1-3 times daily. The patient had nO prior history of transient vi- 156 2 0.100 J 0.31' • 1.00 • OAO J. M. WEINSTEIN ET AL. 00 I I I I I I I I FIG. 1. Left inferior quadrantanopia sparing central field and monocular temporal crescent. NOm41rl 30 \ sual abnormalities or of migraine headaches. In 1979 she underwent complete excision of a cuta­neous malignant melanoma (Clark Grade III) over the right scapula. No recurrence had been evident during the ensuing 5 years. In April of 1983 she underwent lumpectomy of an infiltrating ductal carcinoma of the right breast. Eighteen lymph nodes were resected and none were positive for tumor. On neuro-ophthalmologic examination 8 days after the onset of symptoms, visual acuity was 20/20 in each eye. Visual field examination with Goldmann perimetry demonstrated a left homon­ymous inferior defect sparing the monocular tem­poral crescent in the left eye (Fig. 1). The re­mainder of the neurologic and neuro-ophthalmo­logic examination was normal. In particular, physical examination disclosed no indication of re­currence of malignant melanoma or breast tumor. Initial computed tomographic scan with intrave­nous contrast was interpreted as normal. Retro­spective review of the films showed three subtle, very small, nonenhancing low-density lesions in the right occipital lobe (Fig. 2). Routine blood studies were normal, including complete blood count, platelet count, prothrombin and partial thromboplastin time, electrolytes, liver enzymes, serum calcium, alkaline phosphatase, anti-nuclear antibody, and sedimentation rate. ~ ·,·'''',hn'nnic anti~en was elevated at 3.7 " "'2;/ml) Cardiac echography I eli" Nellro-ophthall1lo1, Vol. 7. No.3, 1987 revealed no abnormalities. Electroencephalog­raphy performed in the waking state was normal. Cerebrospinal fluid examination was not per­formed. Over the next 5 months her field defect was un­changed on serial examinations. She continued to FIG. 2. Initial computed tomographic scan shows three low density lesions (White arrows) in the right occipital lobe with no enhancement. These may repre­sent small infarcts caused by tumor emboli. SCOTOMA AND HEMIANOPIA DUE TO MELANOMA 157 have episodic scintillations in the left lower hemi­field, occurring between once monthly and several times weekly. On July 3, 1984 she was admitted to the hospital because of the sudden onset of severe headache, lethargy, and left hemiparesis. Com­puted tomographic scan without contrast showed a large right occipital lobe hemorrhage with marked mass effect and shift of the ventricles from right to left, as well as a small amount of blood in the atrium of the left lateral ventricle (Fig. 3). On July 4, 1984 the hematoma was subtotally evacuated via a right occipital craniotomy. Cyto­pathologic examination of the evacuated specimen was not performed since no abnormal tissue was observed at surgery and the hemorrhage was pre­sumed to be due to a small arteriovenous malfor­mation. The patient made an uneventful postoper­ative recovery and follow-up computed tomo­graphic scans demonstrated partial resolution of the hematoma. On August 26, 1984 she noted a lump in her left axilla. Axillary dissection revealed a lymph node containing metastatic malignant melanoma. Subsequently, contrast enhanced com­puted tomographic scan demonstrated multiple intracranial lesions, one of which was located at the site of the previous right occipital hematoma (Fig. 4). She was started on chemotherapy with 10­mustine and received 4,000 rads of whole brain ir­radiation. FIG. 3. Melanoma bleeding into occipital lobe. Non­contrast computed tomographic scan shows hemor­rhage (H) in the right occipital lobe that has extended into the atrium of the right lateral ventricle (V). FIG. 4. Contrast computed tomographic scan demon­strates bilateral enhancing occipital lobe lesions. The patient deteriorated rapidly and died 3 months later of disseminated metastatic disease involving the lungs, liver, and brain. Pathologic examination of the brain disclosed solid metas­tases to the right frontal and occipital lobes. The lesion in the right occipital lobe (Fig. 5) occupied a very large area that eventually measured 5 cm in horizontal width and 5 cm in anteroposterior di­ameter. More than one-half of this lesion was me­sially located and consisted of a hard multinodular area of metastatic melanoma containing several foci of necrosis and hemorrhage. Laterally and posteriorly there was a collapsed, previously hem­orrhagic cavity showing extensive hemosiderotic pigmentation and surrounding areas of encepha­lomalacia extending throughout the white matter of the occipital lobe and also involving the cerebral cortex up to the occipital pole. At a level close to the trigone, approximately two-thirds of the genic­ulocalcarine radiations were destroyed either by the old hemorrhage and malacia or by the neo­plastic lesion. Mesially within the left occipital lobe there was a recent 3.5 cm hematoma with extensive collateral edema. Although no tumor tissue was seen grossly, there were several clusters of dispersed tumor cells visible by microscopy. The right cere­bellar hemisphere contained a recent 2.5 cm sub­cortical hemorrhage that neither grossly nor by routine microscopy revealed any evidence of met­astatic tumor. f eli" Nellro-ophthalmo/' Vol. 7. No.3. 1987 158 J. M. WEINSTEIN ET AL. A := FIG. 5. Axial sections of cerebrum. (A). Level of basal ganglia demonstrating massive recent hematoma in left occipital lobe (left) and old hemorrhage cavity in right occipital lobe (right) containing small amount of gray tumor. (B). Section below level of basal ganglia revealing bulk of tumor tissue and associated old hemorrhage in right occipital lobe. Also shown is re­cent hemorrhage in right cerebellar hemisphere. DISCUSSION Cutaneous malignant melanoma commonly me­tastasizes to the brain. Cerebral involvement was observed in 45% of 85 patients dying with mela­noma in one autopsy study (10). Other authors have suggested that melanomas eventually cause brain metastases in 50-90% of cases (11-13), but the rarity of the tumor results in melanomas repre­senting only about 5% of cerebral metastases (11). The melanoma metastasis usually involves the pa­renchvma of the brain, but may spread to the me- .: .,:)\ SC'I',,'fal ye;Hs may elapse between "'S: ''',,,1' and discovery of .:.J.. = :;r,..,- B metastatic disease, but rapid deterioration is the rule once metastatic disease is present (10,12-14). Cerebral or subarachnoid hemorrhage may be caused by these metastases and may be the pre­senting feature in some patients (15,16). The present case was instructive because the pa­tient experienced permanent stable visual loss, along with recurrent scintillating scotoma and headache, before the recognition of metastatic dis­ease to the right occipital lobe. Physical examina­tion and laboratory studies revealed no evidence of metastatic disease, with the exception of slightly elevated carcinoembryonic antigen. We presume that the small lucent areas present on the SCOTOMA AND HEMIANOPIA DUE TO MELANOMA 159 initial computed tomographic scan represent in­farcted brain and that her permanent homony­mous visual field defect was due primarily to in­farction. The acute onset of the hemianopia would also suggest a vascular event. The lucencies them­selves may not be large enough to account for the entire area of visual loss. It is possible that a zone of dysfunction, due to ischemia or microscopic tumor infiltration, surrounded the lucencies. In view of the patient's age and lack of risk factors for cerebrovascular disease, it seems reasonable to conclude that the probable pathogenesis was tumor embolization. The later development of a large metastatic lesion in the area of infarction also supports this hypothesis. The cause of the recurrent scintillations that oc­curred initially is uncertain, but may have been re­lated to chronic ischemia of the area surrounding the infarct, to "release" phenomenon (17), or perhaps to epileptiform discharge (18) due to tumor in this area. The unformed nature of the "hallucinations" would suggest involvement of primary visual cortex rather than release of asso­ciative visual areas. The normal electroencephalo­gram would seem to mitigate against an epileptic focus as the cause for the intermittent scintilla­tions. However, the scintillations were not present during the recording session and intermittent epi­leptic activity could have been missed. Since the early lesions appear to have involved primarily subcortical white matter, it is possible that adja­cent deafferentated cortex was the source of inter­mittent epileptic discharges. This hypothesis, which we favor, would account for the presence of positive visual phenomena in a scotomatous area. It would seem unlikely that axons within the area corresponding to the scotoma were firing because the density of the scotoma suggests that these axons were incapable of responding. We cannot exclude the possibility that axons adjacent to the severely involved area were discharging spontane­ously, however. The size of the metastatic lesion in the right hemisphere at the time of intracranial hemorrhage is uncertain because the most recent computerized tomographic scan was performed 5 months ear­lier. However, the lesion found in the left occipital lobe at autopsy points out the disproportion that may exist between size of tumor (microscopic) and volume of hemorrhage. The cerebellar hemor­rhage also suggests that significant bleeding may Occur without grossly visible tumor. On the basis of these findings, we would suggest that tumor embolization of the right occipital lobe resulted in implantation of cells, growth of tumor, and even-tually hemorrhage. Moreover, we would suggest on the basis of the left occipital lesion that hemor­rhage may occur from microscopic tumor inva­sion. The hematoma found at autopsy in the left (opposite) occipital lobe contained tumor cells which, if viable, might in time have led to a solid metastasis similar to the more advanced lesion on the right. This hypothesis is further supported by prior clinical, radiologic, and histopathologic ob­servations that are described below. Spontaneous intracranial hemorrhage due to metastatic tumor is an uncommon occurrence that may present a confusing clinical picture. Hemor­rhages may occur from large as well as small me­tastases, and have been described most frequently in patients with cutaneous malignant melanoma (16,19-25), bronchogenic carcinoma (16,21-24), cutaneous malignant melanoma, choriocarcinoma (16,20,21,24,26), and hypernephroma (20,21,24). Mandybur reviewed 15 cases of massive subarach­noid, intracerebral, or intraventricular hemor­rhage due to metastatic brain tumors (24). In ten patients, a stroke syndrome was the presenting feature. The other four patients presented with a gradual onset with progressive neurologic signs and/or symptoms. Weisberg retrospectively studied computed tomographic scans of patients with hemorrhagic cerebral metastatic lesions. In eight patients with malignant melanoma (some of whom had multiple lesions) peritumoral hemor­rhage occurred in association with 40% of lesions (16). Massive intracerebral hemorrhage has been reported in areas with no gross tumor but only mi­croscopic vascular invasion in patients with cho­riocarcinoma (24,26) and bronchogenic carcinoma (24). Perivascular tumor cuffing (24) and invasion of the vasa vasorum have been noted in patients with metastatic melanoma to the brain, though not in direct association with cerebral hemorrhage. In patients with malignant melanoma, a tumor nodule has usually been found on computed to­mographic scan or at autopsy (19,20,23,25). The lesion in our patient's left occipital lobe however suggests that microscopic vascular invasion in pa­tients with malignant melanoma may lead to cere­bral hemorrhage. In addition to microscopic vascular invasion, several other factors have been postulated to ex­plain intracranial hemorrhage in patients with metastatic lesions: (a) In patients with broncho­genic carcinoma, large, fragile, irregular, sinusoid­like, thin-walled vessels may rupture (20); (b) hemorrhages often develop at the border of tumor and adjacent necrotic brain tissue where tumor growth and vasculogenesis are most exuberant JClin Neuro-ophthalmol, Vol. 7, No.3, 1987 160 j. M. WEINSTEIN ET AL. (24); (c) fibrinolysins may be released from in­vaded brain (27); and (d) inadvertent head trauma may precipitate hemorrhage in some patients (24). 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