© 1991 S. Karger AG, Basel 0014-3022/91/0314-0216S2.75/0 Eur Neurol 1991;31:216-219 Slow Progressive Bilateral Posterior Artery Infarction Presenting as Agitated Delirium, Complicated with Anton’s Syndrome W. Versiegers*-h, P.P. De Deyn *■b, J. Saerensa, P. Mariena, B. AppeP, B.A. Pickutb, A. LowenthaP Department of Neurology, Algemeen Ziekenhuis Middelheim, b Laboratory for Neurochemistry, Bom-Bunge Foundation, University of Antwerp, and c Department of Neuroradiology, Algemeen Ziekenhuis Middelheim, Antwerp, Belgium Key Words. Anton’s syndrome Cerebrovascular ischemia • Anosognosia • Occipital blindness • Posterior cerebral artery infarction ■Confusion • Delirium • Computed tomography Abstract. Three patients presented with an acute agitated delirium as the earliest sign of bilateral posterior cere­ bral artery infarction. All patients showed a unique slow progressive deterioration with a remarkably long interval between the first neuropsychological and subsequent visual and neurological symptoms, ranging from 3 to 30 days. Repeated CT scans demonstrated hypodensities in the posterior artery territory only after a long interval of 9-12 days, in case 3, and between 33 and 48 days in case 2. In the latter case MRI was still negative 33 days after onset. In 2 patients the cortical blindness was complicated with anosognosia for blindness. Clinical condition worsened pro­ gressively in all patients, leading to death, probably due to brainstem infarction. In all 3, the combination of clinical and radiological findings indicated a ‘top of the basilar’ distribution, which could be confirmed in two by autopsy. It is known that lesions in brain regions supplied by the posterior cerebral artery (PCA) can cause confusion, especially when both or the dominant PCA are involved 11]. The behavioral disturbances, characterized by agita­ tion, crying and restlessness, are more pronounced when the onset is acute [2], Depending on the involvement of other structures such as brainstem or diencephalon, the clinical presentation can be persistent, transient or fluc­ tuating. Agitation and aggressivity can be present at onset of the clinical syndrome [3], it may be delayed or even dominate the clinical picture [4], The 3 reported patients are quite unique because of the very slow progressive and long clinical course result­ ing in diagnostic difficulties, because of the remarkably long interval before additional neurological symptoms and abnormal CT findings appeared and because they all initially presented in an agitated confusional state. Case Histories Case 1. A 75-year-old right-handed women suffered from angina pectoris and arterial hypertension since the age of 60. She presented with an acute and severely agitated confusional state with diurnal variation, exhibited restlessness and, mostly at night, wandered about naked and disturbed her neighbors by calling on them. Neu­ rological examination revealed complete disorientation with respect to time and place and retrograde amnesia for several months prior to her admission. She complained at that time of vision distur­ bances only 3 days after onset. From that time she bumped into objects in her path. After 7 days she became distractable, developed slurred speech containing neologisms and paraphasias. Examination revealed a slight hemiparesis of the right side, ocular immobility whereby she did not explore the space nor respond to visual threat and objects passing along the frontal eye fields. The pupillary reac­ tions to light were positive. Clinically she was undoubtedly blind but she denied having visual problems. Hematological, biochemical and serological exam­ inations were unremarkable. EEG demonstrated a normal back­ ground activity with only slightly irritative features. CT under seda­ tion, 9 days after onset, confirmed the clinically suspected bilateral Downloaded by: Leiden University Medisch Centrum 132.229.13.63 - 10/16/2018 5:03:31 PM Introduction 217 Fig. 1. CT 9 days after onset of the ‘agitated delirium’ showed bilateral hypodensities at the top of the occipital lobes. There was also a global cortical atrophy more pronounced at the temporal lobes. Fig. 2. CT 48 days after the first signs and 14 days after the first CT showed well circumscribed lesions of both occipital branches of the occipital lobes, more on the right side, with sparing of the visual cortex bilaterally and with symmetrical lacunar infarctions in the lateral parts of both thalami. infarctions of the occipital lobes restricted to the top of the lobes (fig. 1). The patient’s condition deteriorated further with distur­ bances of consciousness, persistent agitation with screaming and yelling and a paresis (3/5) of the right arm and leg. A control CT 11 days after onset disclosed more extensive hypodensities in both occipital (occipital and calcarinal) lobes and in the left temporal branches. She died 17 days after onset of the first neuropsychologi­ cal signs. Examination of the brain demonstrated infarctions of the occipitotemporal lobes on the left side and occipitobasal infarctions on the right. There were confluent necrotic foci in the medial part of the pulvinar with infiltration of foam cells and necrotic foci near the central tegmental tract. The occipitobasal infarctions were above all subcortical and irregular, with pycnotic nuclei and cortical spongio­ sis. The findings were compatible with multiple embolic infarctions. Examination of the heart revealed an old posterior infarction in the lower one-third of the left ventricle, without mural thrombus. Case 2. A 68-year-old right-handed man suffered since the age of 63 from unstable angina pectoris. He was presented by his family because of sudden distractibility, verbal agitation and changes in behavior and mood. The patient himself complained only of inter­ mittent posteriorly located headache, dyssomnia and generalized tiredness. Repeated neurological examination could not reveal any abnormality. He complained for the first time of feelings of tran­ sient heaviness in the left part of the body, unsteadiness and tran­ sient visual impairment only 30 days after onset. CT and MRI per­ formed respectively 31 and 33 days after onset were normal. Because of increased angina pectoris, treatment was started with infusion of heparin and isosorbide dinitrate. Because of repeated normal neurological examination, hysteria was considered as differ­ ential diagnosis. Forty-eight days after onset he was still emotionally agitated, confused and developed a global amnesia for several months prior to his actual state. On at least 1 day he developed a right ptosis with a paresis of one-fifth of the right leg and a complete paralysis of the left leg. There was isocoria with normal pupillary reactions. Foveal pursuit movements could not be evoked and reflexes to visual threat were absent. He responded very anxiously to everything that happened in the room. He did not move his eyes nor explore the room visually. When confronted with his visual impair­ ment, he reacted angrily and denied having visual problems. Some days later he developed perseverations, sporadic echolalia and a marked flexion posture of the elbow, wrist and fingers bilaterally. Reflexes were more pronounced in the left leg with ankle clonus and Babinski. Control CT performed 48 days after onset of the delirium showed bilateral hypodensities of both tops of the occipital lobes (more pronounced at the right side), two symmetrical lacunar infarctions in the lateral parts of both thalami with sparing of the splenium and the calcarine cortex bilaterally (fig. 2). The patient’s condition deteriorated rapidly resulting in bilateral ptosis, tetraple­ gia. bilateral Babinski sign with attenuation of the decorticate rigid­ ity of the upper limbs. He shouted especially at night without prov­ ocation. A control CT with contrast injection 59 days after onset showed more extended lesions with infarctions in the territory of the posterior temporal artery, more pronounced at the right side, bilat­ eral necrosis of the parietal lobes with luxury perfusion of the right parietal lobe. He died 79 days after onset of the delirium. Autopsy was refused by the family. Case 3. A 73-year-old right-handed woman suddenly developed confused behavior with restlessness, excitability, purposeless acting and unresponsiveness to correcting attempts of her daughter al­ though speech and comprehension were normal. Five days after onset she complained of anorexia, dizziness and transient visual disturbances. All symptoms fluctuated during the daytime. No neu­ rological abnormalities could be detected. Nine days later she devel­ oped a sudden loss of consciousness with apneustic breathing, responding only to pain. The cornea reflexes and pupillary reactions to light were absent on the left with the left pupil being smaller than Downloaded by: Leiden University Medisch Centrum 132.229.13.63 - 10/16/2018 5:03:31 PM Chronic Progressive Posterior Artery Infarction Verslegers/De Deyn/Saerens/Marien/Appel/Pickut/Lowenthal Fig. 3. Control CT 12 days after onset of the confusion showed bilateral hypodensities of both occipital lobes. the right. Pharyngeal reflexes were absent. Hematological and bio­ chemical screening were normal. A CT performed 9 days after onset of the delirium showed only periventricular leukomalacia. A second CT twelve days after onset demonstrated symmetrical infarctions of both occipital lobes and the visual cortex especially on the right side (fig. 3). There were also bilateral hypodensities of the parietal white matter and a triangular infarction at the pontocerebellar level of the left cerebellum. The patient’s clinical condition remained un­ changed until death, 3 weeks after onset of confusion. Autopsy revealed complete destruction of both cerebellar lobes, the medio­ basal part of both occipital lobes and the striate cortex. There were numerous cribriform cavities in the caudate nucleus, the thalamus and the intralamellar formation at the left side. The heart was dilated without thrombus. Discussion It is known that ‘agitated delirium’ may result from disconnection of anterior limbic structures from neocortical inputs, from destruction of posterior limbic struc­ tures or from disconnection of dominant temporal neo­ cortex from the limbic system [5], Bilateral PCA infarc­ tions generally result in more severe confusional states, suggesting that disconnection from nondominant limbic structures aggravates the confusion. Unilateral infarc­ tions of the dominant temporal lobe of the PCA can also cause confusion [6]. The degree of confusion may de­ pend on differences in lesion size and localization, later­ alization of cognitive functions and absence or presence of threatening hallucinations [7], In the majority of the cases, the clinical picture is complicated by hom­ onymous hemianopia, cortical blindness, sensory deficit, pure alexia without agraphia, anomia and amnesia, hemiplegia, transcortical sensory aphasia, memory im­ pairment, release hallucinations in blind parts of the visual fields [8], metamorphopsia [9], visual agnosia, color dysnomias, third nerve palsy, thalamic symptom­ atology, Kluver-Bucy [10], Anton’s [11], Balint [12, 13] and Charco-Witbrand [14] syndrome. Because of the variability in the clinical picture, toxic or metabolic encephalopathies, psychiatric diseases or middle cere­ bral artery ischemia are frequently the first proposed diagnoses [1, 3]. In all our cases, confusion, agitation and disturbances in behavior and mood were the initial symptoms. While 1 patient (case 3) showed only a mild confusion, the oth­ ers (cases 1 and 2) showed a severely agitated delirium that required sedation to protect them against injuries. A remarkable feature is the long interval between the first neuropsychological symptoms and the subsequent neu­ rological and visual symptoms. The interval ranged be­ tween 3 (case 1) and 30 days (case 2). All cases showed a slowly progressive course in which new symptoms ap­ peared, all together leading to death. The long interval accounts also for the CT abnormalities. CT was still nor­ mal 9 days (case 3) and 31 days (case 2) after onset. Also MRI was normal 33 days after onset in case 2. The first CT abnormalities appeared between 9 and 12 days (case 3) and between 33 and 48 days (case 2) after onset. In cases 2 and 3 it is undoubtedly demonstrated that CT was normal respectively 9 and 31 days after onset. The progressive course, absence of neurological signs, fluc­ tuating symptoms and normal neuroimaging even sug­ gested a diagnosis of hysteria in a 68-year-old man with­ out psychiatric history. It seems possible that symptoms in the beginning were due to hemodynamic changes, rather than infarction. This may explain the fluctuating symptomatology and the early negative structural neu­ roimaging. Although consciousness was not completely lost, pa­ tient 2 showed, 48 days after onset, decorticate rigidity of the upper limbs due to biparietal white matter lesions. He also presented a Weber syndrome suggesting involve­ ment of the interpeduncular branches. Cases 1 and 2 with the most pronounced ‘agitated delirium’ showed signs of fear and anxiety about everything that happened in their environment. All 3 patients showed infarctions at the ‘top of the basilar’ [15] with great variability in size and number of the occipital infarctions. At autopsy (cases 1, 3) destruc­ tion of the occipital and cerebellar lobes was much more Downloaded by: Leiden University Medisch Centrum 132.229.13.63 - 10/16/2018 5:03:31 PM 218 219 Chronic Progressive Posterior Artery Infarction extensive than suspected by CT. Case 2 also had bilateral lacunar infarctions in the lateral parts of both thalami suggesting that the thalamogeniculate arteries arise from the same PCA. Although CT demonstrated sparing of the visual cortex, case 2 showed total cortical blindness possibly due to a disconnecting lesion between the geni­ culate bodies and the occipital cortex. Since heparin started 30 days after onset, did not alter deterioration in case 2, and because clinical condition in cases 1 and 3 was too bad at the moment of the CT abnormalities, further investigation as for cardiogenic embolic source were not considered as warranted because they would not have altered diagnosis or treatment. In cases 1 and 2, denial of visual deficits and pretend­ ing they see ‘things’ suggest that the cortical blindness was complicated by anosognosia (Anton’s syndrome) [11] and visual confabulation, despite initial complaints about visual disturbances. They wandered about in their rooms, bumping into objects in their paths. They were indeed blind since patients with an apperceptive visual agnosia, described by Benson and Greenberg [ 16], do not hit objects. At the time of their blindness they showed ocular immobility which cand be explained by the blind­ ness and in case 2 by the parietal lesions similar to the pathology in Balint syndrome [12, 13]. Indeed, lesions in the posterior part of the parietal lobe [ 17] and disruption of colliculo-pulvinar-parietal projection [18] may result in ocular immobility and impairment of visually guided eye movements. Acknowledgements This investigation was supported by the Medical Research Foun­ dation, OCMW, Antwerp, and the Bom-Bunge Foundation, Labora­ tory of Neurochemistry, University of Antwerp, Belgium. 4 Medina JL, Rubino FA, Ross E: Agitated delirium caused by infarctions of the hippocampal formation and fusiform and lin­ gual gyri: A case report. J Neurol Neurosurg Psychiatry 1974;24: 1181-1183. 5 Efron R: Temporal perception, aphasia, and déjà vu. Brain 1963;86:403-424. 6 Fisher CM: Unusual vascular events in the territory of the pos­ terior cerebral artery. Can J Neurol Sei 1986;13:1-7. 7 Devinsky O, Bear D, Volpe BT: Confusional states following posterior cerebral artery infarction. Arch Neurol 1988;45:160— 163. 8 Cogan DG: Visual hallucinations as release phenomena. Graefes Arch Clin Exp Ophthalmol 1973; 188:139. 9 Brust JCM, Behrens MM: ‘Release hallucinations' as the major symptoms of posterior cerebral artery occlusion: A report of 2 cases. Ann Neurol 1973;2:432. 10 Klüver H: The temporal lobe syndrome produced by bilateral ablations; in Wolstenholme GEW, O’Connor CM (eds): Ciba Foundation of the Neurological Basis of Behavior. Boston. Lit­ tle, Brown, 1958, pp 175-182. 11 Anton G: Über die Selbstwahrnehmungen der Herderkrankun­ gen des Gehirns durch den Kranken bei Rindenblindheit und Rindentaubheit. Arch Psychiat 1899;32:86-127. 12 Balint R: Seelenlähmung des ‘Schauens’, optische Ataxie, räum­ liche Störung der Aufmerksamkeit. Monatsschr Psychiatr Neu­ rol 1909;25:51-81. 13 Holmes B, Horrax G: Disturbances of spatial orientation and visual attention with loss of stereoscopic vision. Arch Neurol Psychiatry 1919;1:385-407. 14 Charcot JM: Clinical Lectures on Diseases of the Nervous Sys­ tem. Lecture XL London, New Syndenham Society, 1889, vol 3. 15 Caplan LR: ‘Top of the basilar’ syndrome. Neurology (NY) 1980;30:72-79. 16 Benson D, Greenberg J: Visual form agnosia. Arch Neurol 1969; 20:82-89. 17 Pierrot-Deseilligny Ch, Gray F, Brunet P: Infarction of both inferior parietal lobules with impairment of visually guided eye movements, peripheral visual inattention and optic ataxy. Brain 1986;109:81-97. 18 Zihl J, Von Cramon D: The contribution of the second visual system to directed visual attention in man. Brain 1979; 102:835856. References Received: July 24, 1990 Accepted after revision: November 5, 1990 Werner Verslegers, MD Department of Neurology Algemeen Ziekenhuis Middelheim Lindendreef 1 B-2020 Antwerpen (Belgium) Downloaded by: Leiden University Medisch Centrum 132.229.13.63 - 10/16/2018 5:03:31 PM 1 Horenstein S, Chamberlain W, Conomy J: Infarctions of the fusiform and calcarine regions: Agitated delirium and hemianopia. Trans Am Neurol Assoc 1967;92:85-89. 2 Symonds C, MacKenzie I: Bilateral loss of vision from cerebral infarction. Brain 1957;80:415-455. 3 Mehler MF: The rostral basilar artery syndrome: Diagnosis, eti­ ology, prognosis. Neurology 1989;39:9-16.