ARE UNILATERAL RIGHT POSTERIOR CEREBRAL LESIONS SUFFICIENT TO CAUSE PROSOPAGNOSIA? CLINICAL AND RADIOLOGICAL FINDINGS IN SIX ADDITIONAL PATIENTS Theodor Landis l, Jeffrey L. Cummings3, Lisanne ChristenS, Joseph E. Bogen4, Hans-Georg Imhof2 (From the Departments of Neurologyl and Neurosurgery2, University of Zurich, Switzerland; from the Neurobehavior Unit, West Los Angeles VAMC, Brentwood Division, and Department of Neurology3 UCLA School of Medicine; from the Department of Neurological Surgery4 University of Southern California, Los Angeles, USA, and the Institute of Medical Psychology5, University of Munich, FRG) INTRODUCTION Prosopagnosia, the inability to recognize familiar faces, has recently been the subject of several extensive reviews (Hecaen et al., 1957; Hecaen and Angelergues, 1962; Gloningetal., 1966; Meadows, 1974; Damasioet al., 1982). Bilateral mesial occipito-temporallesions are known to cause prosopagnosia; but it is debated whether a unilateral right posterior lesion alone can sometimes produce this deficit. All prosopagnosic patients who had come to autopsy (for review Meadows, 1974; Damasio et al., 1982) have had bilateral lesions, and several additional cases studied with . computerized tomography (eT) were also shown to have bilateral lesions (Damasio et al., 1982; Malone et al., 1982; Nardelli et al., 1982; Bruyer et al., 1983; Assal et aI., 1984). On the other hand, a few cases suggesting that a right posterior lesion alone may be responsible for pro sop agnosia (Hecaen et aI., 1956; Assal, 1969; Meadows, 1974; Lhermitte and Pillon, 1975; Whiteley and Warrington, 1977) have been observed. We present six cases with prosopagnosia studied clinically and radiologically and suggest a reconsideration of the association between unilateral right posterior lesions and prosopagnosia. CASE REpORTS Casel A 64-year-old right-handed man was found by his neighbors attempting to leave his house through a second story window. He was partially dressed, could not put on his clothing correctly, and was completely lost in his home environCortex (1986) 22, 243-252 244 T. Landis, J.L Cummings, L Christen, J.E. Bogen, H.-G. Imhof ment. On admission he was oriented to time and location, but was easily distracted, slow in responding, and neglected left-sided stimuli_ Examination revealed a dense left homonymous hemianopia (Goldman perimetry), mild left hemisensory loss with extinction during bilateral simultaneous stimulation and broadbased unsteady gait_ There was marked asterixis of the left arm, reflexes were brisk bilaterally, and an extensor plantar response was present on the left. Observation during the first week of hospitalization revealed marked prosop agnosia, environmental disorientation, dressing disturbance, and unconcern about his illness_ He got lost on the ward, and was unable to find his bed_ He failed to recognize nurses, physicians or relatives by their faces, needing auditory clues to allow recognition. Pictures of famous individuals were not recognized. Language comprehension and repetition, confrontation naming, and praxis were normal. Reading and writing were slow but correct and verbal memory was mildly impaired. He neglected the left half of constructions and could not copy a Necker cube or a complex figure. The asterixis disappeared during the first week of hospitalization and recovery of most other functions occurred between the 5th and 8th weeks of hospitalization. His homonymous hemianopia decreased to a left homonymous superior quadrantanopia. His dressing disturbance, neglect of left-sided stimuli, and recognition of faces improved, but at the time of discharge, five months later, he remained unable to recognize most familiar faces, including relatives and friends. His environmental disorientation improved but did not disappear. Follow-up examinations 1 and 3 years later did not show any substantial improvement. CT scan (Figure 1-1) revealed an infarction in the territory of the right posterior cerebral artery. Case 2 A 58-year-old right-handed executive secretary was well until, while going to work by streetcar, she suddenly realized she could not recognize anything around her. She left the streetcar when the conductor announced a streeet well known to her, but she was soon lost and had to ask directions to a pharmacy she had visited on many occasions. At home, her apartment of 20 years seemed totally unfamiliar, and she could recognize relatives only by their voice. Initially she could not visualize familiar places, faces, or pictures. On inquiry, she also reported the inability to recognize familiar handwritings, including her own, and the inability to recognize familiar pet animals. At the time of admission, she had a left visual field defect involving all of the superior quadrant and a portion of the adjacent inferior quadrant (Goldman perimetry). Her gait was unsteady and she extinguished left-sided stimuli during double simultaneous stimulation. Mental status testing revealed her to be alert and oriented with normal behavior and appropriate concern. Language comprehension, repetition, naming and writing were normal. She read slowly but correctly and she performed normally on tests of verbal memory and praxis. She could copy complex constructions and could even draw a map of Switzerland without difficulty. Her performance on tests requiring matching of facial expressions (Landis et al., 1979) was severely impaired, whereas other facial recognition (Benton and VanAllen, 1968) and matching tests (Tzavaras et al., 1970) were performed in the lower range of normal. In hospital she could not recognize her doctors, nurses or relatives without auditory clues. She quickly learned to orient herself with the help of verbal cues, but the ward Posterior cerebral lesions and prosopagnosia 245 never became familiar tQ her, and she never experienced the sense of having been there before. CT scan (Figure 1-2) showed an infarction in the territory of the right posterior cerebral artery, and EEG showed slowing over the right posterior temporal area. Four months later she experienced visual hallucinations including unformed light flashes and formed hallucinations of a man repeatedly walking from her left to right. Palinopsia also occurred, and on one occasion she noted that after looking at a dog in the lap of a fellow bus passenger, everybody on the bus seemed to have the dog's face! Two and a half years after the initial event, profound loss of environmental familiarity and prosopagnosia persisted, and she still had difficulties recognizitig familiar hand writings. She had, however, recovered the ability of "inner visualization". On request, she was able to visualize the face of her daughter or her house, and she reported these evoked images to be familiar. When directly confronted with real images the sense of familiarity was invariably absent. The results of extensive tachistoscopic testing are resported elsewhere (Christen et al., 1985). Case 3 A 46-year-old right-handed factory worker of Turkish origin and 4th grade education, suddenly experienced an event which he was unable to describe other than "I can't understand it, everything looks different". Since then, he complained about dimness of vision and realized that he was not able to recognize friends and relatives by their face but knew them immediately when they spoke. Initially he got lost in the factory where he worked for ten years and had to be guided even to familiar places of his home town. Five months later he presented with depression and headache. Examination revealed a complete left upper quadrantanopia (Goldman perimetry) and mild left hemihypesthesia. He was alert, and oriented but not appropriately concerned about his deficits. There were no abnormalities of language, praxis, or verbal memory. Constructions were poor, and he had difficulty naming and matching colors. He could not recognize familiar faces and performed poorly on tests of facial recognition and face matching. Recognition of familiar places was also impaired. CT scan (Figure 1-3) showed an area of hypodensity in the territory of the right posterior cerebral artery. Several EEGs were normal. In the next two years his ability to find his way in circumscribed areas improved but his prosopagnosia persisted. The results of tachistoscopic testing are reported elsewhere (Christen et al., 1985). Case 4 A 48-year-old right-handed woman suffering from diabetes mellitus and under treatment with oral anticoagulant was admitted after a minor head injury with a right parieto-occipital epidural hematoma (CT scan Figure 1-4). Examination revealed a dense left homonymous hemianopia, a severe left hemisensory loss and a mild left hemiparesis involving primarily the arm. She was oriented in time and location but denied any illness. She was unable to recognize friends, relatives, nurses, and physicians by their faces but immediately recognized them by their voices. Strikingly, she denied the propopagnosia as well as her environmental disorientation. She performed poorly on facial recognition and facial 246 T. Landis, J.L Cummings, L Christen, J.E. Bogen, H. -G. Imhof Case 1 Case 2 Case 3 Fig. 1 - CT images of the lesions in the six cases presented in the text. Case 1, Case 2 and Case 3 all show areas of hypodensity (ischemic infarction) in the territory of the right posterior cerebral artery. These lesions are very similar in {ocation. They extendfrom the postero-medial temporal lobe into the inferior occipital lobe and involve structures such as the parahippocampal gyrus, fusiform gyrus and lingual gyrus as well as fibres from the optic radiation, the inferior longitudinal fasciculus and splenial callosal fibres (forceps major, tapetum). Case 4 shows an epidural right parieto-occipital hematoma (marker) with surrounding brain edema involving the white matter of the corona radiata, forceps major and parts of the superior occipital lobe and posterior parietal lobe compressing the posterior part of the right lateral ventricle. Case 5 has a large right parieto-temporo-occipital brain tumor involving the entire peritrigonal region, the posterior temporal and parietal lobes and most of the lateral and parts of the medial occipital lobe. Case 6 shows a postoperative right posterior parietal-anterior occipital lucency but no signs of tumor recurrence. Posterior cerebral lesions and prosopagnosia Case 4 Case 5 Case 6 247 248 T. Landis, J.L Cummings, L Christen, J.E. Bogen, H.-G. Imhof matching tests. She could copy a Necker cube but neglected the left half of constructions and had poor non-verbal memory. Language comprehension and repetition, confrontation naming, color naming and matching, reading, writing, praxis and verbal memory were normal. Because of the cerebral edema she received steroids and within two weeks all symptoms disappeared. Follow-up examinations three and eight months later were normal. Case 5 A 56-year-old ambidextrous man complained that everything looked strange and unfamiliar, that he had difficulties in finding his way in familiar surroundings and that he frequently ran into obstacles on his left side. A dense left homonymous hemianopia (Goldman perimetry) was found and CT scan (Figure 1-5) revealed a large right sided occipito-temporo-parietal tumor. The tumor, histologically a glioblastoma, was surgically removed (by HGI). During the operation no tumor was seen crossing into the left hemisphere. Postoperative examination revealed a dense left homonymous hemianopia, left hemifacial dysesthesias and mildly impaired rapid alternating movements of the left hand. He was unable to recognize nurses, physicians, or relatives by their faces, but easily recognized them by their voices. He denied his prosopagnosia. He experienced dimness of vision, was only mildly impaired on facial matching tests, and could copy a cube and complex figures. Map drawing and reading, recognition of familiar loca~ons as well as his nonverbal memory were impaired. Color naming and matching were intact, and language, reading, writing and praxis were normal. Verbal memory was mildly impaired. Tachistoscopic testing is reported elsewhere (Christen et al., 1985). He died two months later. An autopsy was not performed. Case 6 A 49-year-old right-handed man with a graduate school education was well until 1972 when after a Valsalva maneuver he suddenly "felt funny" and saw "spots" in front of him. He noted that he bumped into objects on his left side and veered toward the left side of the road when driving. Because of increasing pain in his head, he presented to a hospital emergency room where he was found to have left homonymous hemianopia, left extensor plantar response, and skull x-rays that demonstrated calcification in the right parieto-occiptal area. He had surgery (by JEB) nine days after admission and was found to have an intracerebral hematoma adjacent to an oligodendroglioma in the right occipital lobe posterior to the occipital hom of the lateral ventricle. The tumor and adjacent brain tissue were removed. After surgery he had mild left sided weakness that gradually improved and a persistent dense left homonymous hemianopia. The patient was able to recognize his family immediately after surgery but noted that he was more dependent on contextual cues. For example, he sometimes misidentified his mother if he met her away from her home, and he failed to recognize a cousin until he heard his voice. When attending a reunion of his high school class, he recognized only 5 of 85 members by their faces but remembered many of the others by their voices or actions. Likewise, he had trouble recognizing his neighbors of many years and described how he depended on identifying their Posterior cerebral lesions and prosopagnosia 249 car if the met them in local shops. He experienced no difficulties distinguishing cars, pets, or individual pieces of luggage. He failed to recognize 9 of 18 familiar faces and recognized many of the remaining people by use of specific clues (e.g. "big ears", "needs a shave", "messed up hair"). He also was moderately impaired in the matching of faces (Benton and VanAllen, 1968), but there was no aphasia nor apraxia, and he was of average intelligence with a lower performance than verbal score (PIQ 72, VlQ 116). Four years after surgery a contrast enhanced CT scan demonstrated a lucency in the posterior parieto-occipital region on the right. There was no evidence of tumor recurrence and no left hemisphere abnormality. Six years after surgery, his ability to recognize familiar faces had improved but was still imperfect. Performance (PIQ 92) and verbal scores (VIQ 129) both improved but his non-verbal memory was still impaired. Constructional tests, manual dexterity tasks, and double simultaneous stimulation were all unremarkable. Twelve years after surgery, the patient continued to have mild difficulties with recognition of familiar faces. He occasionally misidentified family members and although he recognized most famous faces he could not distinguish the leaders of the USA and the USSR. A CT scan (Figure 1-6) again showed a right posterior lesion but no left hemisphere lesion. DISCUSSION The production of prosopagnosia by bilateral medial occipito-temporallesions is well documented. Controversy remains, however, whether bilateral lesions are always necessary to cause prosopagnosia. Since Bomstein and Kidron (1959) described a patient with clinical evidence of a right unilateral lesion who was found at autopsy to have bilateral occipital lesions (Pevzner et al., 1962) there has been general agreement that, by themselves, clinical studies are not sufficient to exclude bilateral .lesions in patients with prosopagnosia. However, in addition to the purely clinical case descriptions, there have been a number of reports with supporting information, such as surgical and CT findings. Although such cases are important in the search for clinico-pathological correlations, they have been given less consideration in the several extensive reviews of prosopagnosia. Hecaen et al. (Hecaen et al., 1956; Hecaen et al., 1957; Hecaen and Angelergues, 1962) report 2 patients with prosopagnosia following surgery in the right posterior hemisphere for epilepsy. One patient (their case 4) developed prosopagnosia after parieto-temporooccipital surgery, and one patient (their case 6) was prosopagnosic prior to right occipital and temporal surgery. In the latter case, prosopagnosia resolved within a few weeks. Assal (1969) and Meadows (1974) both report patients who developed pro sop agnosia subsequent to the evacuation of right posterior intracerebral hematomas. In the case described by Assal, the hematoma was parieto-temporal in location and the prosopagnosia of several months duration. In the case of Meadows, the hematoma j T. Landis, J.L Cummings, L Christen, J.E. Bogen, H.-G. Imhof 250 was due to a small arteriovenous malfonnation (AVM) in the posterior temporal region and the prosopagnosia was not severe. Lhermitte and Pillon (1975) described a patient in whom prosopagnosia was documented one month after a right occipital lobectomy for intractable seizures, and Whiteley and Warrington (1977) provide CT and surgical TABLE I Clinical and Radiological Findings in 13 Prosopagnosic Patients with Presumed Unilateral Right Posterior Lesions Authors Operation or CT findings Hecaen et al., 1956, operation, removal of right case 4 posterior temporal, parietal and occipital epileptic wne Visual field defect left homonymous hemianopia Associated clinical findings dressing disturbance, constructional apraxia, unilateral spatial neglect, disturbance of topographic memory and orientation Hecaen et al., 1956, operation, removal of right left homonymous mild constructional apratemporo-occipital epileptic hemianopia case 6 xia, unilateral spatial agnosia, disturbance of topowne graphic memory Assal, 1969 operation, evacuation of left homonymous dressing apraxia, construcright parieto-occipital he- hemianopia tional apraxia, unilateral spatial agnosia, topogramatoma phic memory loss Meadows, 1974, case operation, evacution of left upper homony- topographical disorienta4 right posterior-temporal he- mous quadrantano- tion pia matoma Lhermitte and Pillon, operation, right occipital 10- left homonymous topographical disorienta1975 tion bectomy hemianopia Whiteley and WarCT-scan, right occipital he- incongruent left horington, 1977, case 2 matoma monymous hemianopia Whiteley and WarCT-scan, operation, remo- left homonymous transient distorted vision rington, 1977, case 3 val of right parieto-occipital hemianopia astrocytoma Landis et al., case lCT-scan, right occipito-temporal infarctionleft homonymous hemianopiadressing apraxia, constructional apraxia, topographical disorientation, left unilateral neglect and asterixis case 2 CT-scan, right occipito- incomplete left ho- topographical disorientatemporal infarction monymous hemia- tion, visual hallucinations nopia case 3 CT-scan, right occipito- left upper homony- topographical disorientatemporal infarction mous quadrantano- tion, constructional apraxia, impaired color matchpia ing, depression case 4 Cf-scan, right parieto-occi- left homonymous denial of prosopagnosia, anosognosia, transient pital epidural hematoma hemianopia symptoms case 5 operation, CT-scan, right left homonymous topographical disorientahemianopia temporo-parieto-occipital tion, unconcern about illness glioblastoma case 6 operation, CT-scan, right left homonymous impaired non-verbal memory and visuo-spatial skills occipital oligodendroglio- hemianopia ma Posterior cerebral lesions and prosopagnosia 251 evidence of unilateral right posterior lesions in 2 of their 3 patients with prosopagnosia. Case 2 developed prosopagnosia subsequent to a right occipital intracerebral hematoma, and case 3 developed transient prosopagnosia after an occipital lobectomy for the removal of a right posterior astrocytoma. During surgery, the tumor was observed not to cross into the left hemisphere. Of the 7 cases reported in the literature and the 6 patients presented here (see Table I), a unilateral right posterior lesion was observed in 8 cases by operation (in 3 combined with CT) and in 5 cases by CT. The etiology in 3 cases was an ischemic stroke in the territory of the right posterior cerebral artery, in 4 cases an intracerebral or epidural hematoma, in 3 cases a tumor, and in 3 cases brain removal for intractable epilepsy. Although operative and radiological findings together with clinical evidence are not conclusive proof of the unilaterality of lesion, the data from the 13 patients reviewed here is quite persuasive. With unilateral lesions, the prosopagnosia is often transient, but can be long lasting. These cases suggest that unilateral right posterior lesions may be sufficient in some cases to produce enduring deficits in the recognition of familiar faces. The defect may reflect isolation of the right posterior cortex from the ipsilateral temporal and contralateral occipital lobes. ABSTRACT Controversy has arisen regarding the neuropathological basis of prosopagnosia. Some investigators suggest that bilateral lesions are needed to cause the deficit, whereas others felt that a unilateral right poterior lesion is sufficient. Six patients with prosopagnosia with clinical and radiological evidence of unilateral right posterior lesions are presented. Our observations together with evidence from similar cases described in the literature suggest that an appropriately placed right hemispheric lesion may be sufficient to produce prosopagnosia. Acknowledgment. This study was supported in part by the Swiss National Science Foundation Grant 3.884.-0.83, the DFG Grant RE 337/3-1, and the Veterans Administration. We thank Professor Aaron Smith for his kind permission to report his neuropsychological assessment of case 6 and Dr. M. Regard for her help in the preparation of this paper. 252 T. Landis, J.L. Cummings, L. Christen, J.E. Bogen, H.-G. Imhof REFERENCES ASSAL, G. Regression des troubles de la reconnaissance des physiognomies et de la memoire topographique chez un malade opere d'un hematome intracerebral parietotemporal droit Revue Neurologique, 121: 184-185, 1969. ASSAL, G., FAVRE, C. et ANDERES, J.P. Non-reconnaissance d'animaux familiers chez un paysan. Revue Neurologique, 140: 580-584, 1984. BENTON, AL., and VANALLEN, M.W. Impairment in facial recognition in patients with cerebral disease. Cortex, 4: 334-358, 1968. BORNSTEIN, B., and KIDRON, D.P. Prosopagnosia.Journal of Neurology, Neurosurgery and Psychiatry, 22: 124-131, 1959. BRUYER, R., LATERRE, c., SERON, X., FEYEREISEN, P. STRYPSTEIN, E., PIERRARD, E., and RECfEM, D. A case of prosopagnosia with some preserved covert remembrance of familiar faces. Brain and Cognition, 2: 257-284, 1983. CHRISTEN, L., LANDIS, T., and REGARD, M. Left hemispheric functional compensation in prosopagnosia? A tachistoscopic study with unilaterally lesioned patients. Human Neurobiology, 4: 9-14, 1985. DAMASIO, AR, DAMASIO, H., and VANHOESEN, G.W. Prosopagnosia: anatomic basis and behavioral mechanisms. Neurology, 32: 331-341, 1982. GLONING, I., GLONING, K., HOFF, H., and TSCHABITSCHER, H. Zur Prosopagnosie. Neuropsychologia, 4: 113-132, 1966. HECAEN, H., and ANGELERGUES, R. Agnosia for faces (prosopagnosia). Archives of Neurology, 7: 92-100, 1962. HECAEN, H., ANGELERGUES, R, BERNHARDT, C., et CHIARELLI, J. Essai de distinction des modalites cliniques de l'agnosie des physiognomies. Revue Neurologique, 96: 125-144, 1957. HECAEN, H., PENFIELD, W., BERTRAND, W. and MALMO, R The syndrome of apractagnosia due to lesions of the minor cerebral hemisphere. Archives of Neurology and Psychiatry, 75: 400-434, 1956. LANDIS, T., ASSAL, G., and PERRET, E. Opposite cerebral hemispheric superiorities for visual associative ,processing of emotional faces and objects. Nature, 278: 739-740, 1979. LHERMITTE, F., et PILLON, B. La prosopagnosie. Role de l'hemisphere droit dans la perception visuelle. Revue Neurologique, 131: 791-812, 1975. MALONE, D.R., MORRIS, H.H., KAY, M.C., and LEVIN, H.S. Prosopagnosia: a double dissociation between the recognition of familiar and unfamiliar faces. Journal of Neurology, Neurosurgery and Psychiatry, 45: 820-822, 1982. MEADOWS, J.C. The anatomical basis of prosopagnosia. Journal of Neurology, Neurosurgery and Psychiatry, 37: 489-501, 1974. NARDELLI, E., BUONANNO, F., COCCIA, G., FlASCH!, A, TERZIAN, H., and RIzzUTO, N. Prosopagnosia. European Neurology, 21: 289-297, 1982. PEVZNER, S., BORNSTEIN, B., and LOEWENTHAL, M. Prosopagnosia. Journal of Neurology, Neurosurgery and Psychiatry, 25: 336-338, 1962. TZAVARAS, A, HECAEN, H., et LEBRAS, H. Le probleme de la specificite du deficit de la reconaissance du visage humain lors des lesions hemispheriques unilaterales. Neuropsychologia, 8: 403-416, 1970. WHITELEY, AM., and WARRINGTON, E.K. Prosopagnosia: a clinical, psychological, and anatomical study of three patients. Journal of Neurology, Neurosurgery and Psychiatry, 40: 395-403, 1977. Theodor Landis, Neurologische IGinik, Universitiitsspital CH-8091 Ziirich, Switzerland.