J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from

Journal of Neurology, Neurosuirgery, and Psychiatry, 1973, 36, 421-430

Limbic dementia'

GENEROSO G. GASCON AND FLOYD GILLES From the Departments of Neurology and Neuropathology, Harvard Medical School, and the Children's Hospital-Peter Bent Brigham-Beth Israel Neurology Residency Program, Boston, Massachusetts, U.S.A.

SUMMARY This is the second reported case, known to the authors, of complete, but selective, limbic lobe destruction in previously normally functioning central nervous systems. Both cases had an amnestic syndrome, whose characteristics were essentially similar to amnestic syndromes pre- viously documented with less complete limbic destruction, with one difference-confabulation re- mained a prominent feature in the chronic stages of the memory disorder. Our patient exhibited a behavioural syndrome similar to that reported by Kliiver and Bucy in monkeys with bilateral anterior temporal lobectomies. Kliver-Bucy like syndromes in man have usually been reported with surgical lesions, usually in patients with pre-existent brain disorder. Our case illustrates that the syndrome can be produced by necrotizing encephalitic lesions. We suggest that the combination of the above two syndromes is essentially a 'limbic dementia'. Protected by copyright.

Permanent arrest of recent memory functions CASE REPORT has been related to bilateral hippocampal G.M., a 26 year old right-handed mother of two, damage (Scoville and Milner, 1957; Penfield and was admitted to the Peter Bent Brigham Hospital Milner, 1958; Victor, Angevine, Mancall, and for the third time on 31 October 1967 in an acute Miller-Fisher, 1961; Whitty, 1962; Drachman confusional state. and Arbit, 1966; DeJong, Itabashi, and Olson, She had graduated from high school at the age of 1969; Pribram, 1969). In the longer-known 16, had a satisfactory employment history, and was amnestic syndrome of Korsakoff's psychosis, described by her husband as a self-sufficient house- loss of mamillary bodies (Brion, 1969) and wire. Hodgkin's disease was first diagnosed in July damage of medial dorsal nuclei (Victor, 1964) 1964 by axillary lymph node biopsy. She was seen by have been implicated as the critical anatomical a psychiatrist on 28 August 1964 because of emo- deficits. These and other limbic tional lability manifested by periods of hypomanic structures behaviour alternating with crying. She demonstrated http://jnnp.bmj.com/ (Angevine, Locke, and Yakovlev, 1964) are also features of an acute anxiety reaction in a basically implicated as the anatomical substrates of healthy personality. The reaction was transient and emotion (Papez, 1937; MacLean, 1949, 1952). repeated neurological examinations during the The suggestion that a demented condition previous two admissions were within normal limits. could be an expression of damage to limbic On 24 October 1967 she developed headache, structures has been made previously (Corsellis, fever, nausea, and vomiting. These symptoms sub- Goldberg, and Norton, 1968). The clinical find- sided, but were followed on 30 October by confu- ings in our case add to the spectrum of chronic sion, inappropriate affect, antagonistic attitudes, on September 27, 2021 by guest. behavioural and intellectual and agitation. Over the next day she lapsed into changes which may somnolence and was readmitted with a temperature result from extensive limbic and paralimbic of 38 C destruction. 9° (102° F). NEUROLOGICAL EXAMINATION She was distant, hos- 1 This work was supported in part by funds provided by the United Cerebral Palsy Research and Educational Foundation (R-224-69), by tile, oriented only to person, and unable to remember the Program-Project Grant No. NSI-EP, 1 PO1 NS 09704-01 NSPA, recent or remote events. She could subtract serial 7s HD, NINDS, and the Children's Hospital Medical Center Retarda- tion and Human Development Research Program (HD 03-0773), only to 93, and proverb interpretation was de- NICHD. ficient. The rest of the examination was unremark- 421 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from 422 Generoso G. Gascon and Floyd Gilles

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T5-01( 5OJJvL 1 Sec. FIG. 1. EEG on 10th day of illness. Bilaterally there are spikefoci in posterior temporal regions. Background activity is generally slowed. able. Cerebrospinal fluid examination on 1 November 1). A pneumoencephalogram revealed a dilated right 1967 showed 11,648 erythrocytes per c. mm, no temporal horn. leucocytes, a sugar concentration of 54 mg/100 ml., From 13 November to 4 December, repeated bed- and protein concentration of 28 mg/100 ml., with side testing showed that she spoke fluently and slightly positive Pandy test. spontaneously in short, grammatically correct,Protected by copyright. From 1 to 10 November 1967 the level of con- sentences, and showed no gross motor or coordina- sciousness waxed and waned. No elementary neuro- tion deficits. She was oriented only to person. The logical signs were seen, except for an abnormal left place was 'your apartment' or 'here' or 'a res- plantar response, at a time when there was evidence taurant', and the date was 'last Sunday'. She was of midline shift to the left by A-scan echoencephalo- unsure about the number of her children. She did not graphy (4-6 mm) and right internal carotid arterio- remember the examiner's face or name after three graphy. The latter also revealed elevation of the right minutes' absence. She had excellent comprehension middle cerebral artery and stretching of the anterior of speech, but found it difficult to name objects. A temporal artery. Electroencephalograms first showed thermometer was 'a needle' and a watch was 'a bilateral widespread delta background activity, then clock'. In her conversation the same themes fre- bilateral posterior temporal periodic spike foci (Fig. quently returned, and she often confabulated. She http://jnnp.bmj.com/

FIG. 2. Examiner's drawings of common geometrical figures are at the bottom. Arrows point to G.M.'s interest is copies. Ofgreatest on September 27, 2021 by guest. her copy of the cube. Her initial attempts are seen within the top surface. Con- tinuity with the external human figure is apparent. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from Limbic dementia 423 smiled automatically in response to the examiner's regressive behaviour manifested by alternate negativ- smiles, but without affective participation. ism and petulance. However, there were distortions She named colours correctly. She could repeat the in the few Bender-Gestalt figures which she attempted names of three objects immediately, but after a to reproduce from memory after a five second view- minute could not spontaneously recall them or ing. She could count backwards from 20 in 17 recognize them when given multiple choices. She seconds with one error (omitted 11). Counting by exhibited a marked retrograde amnesia, with islands 3's and starting at 1, she reached 22 after 90 seconds. of preservation. The furthest point was difficult to She recalled six digits forward, but could not reverse define but seemed to extend back at least four years, them. With the Rorschach test she went through only for she did not seem to be aware of President seven cards, taking seven minutes. Perseveration Kennedy's assassination. She had an anterograde occurred starting with card IV. amnesia for events beginning with her hospitaliza- Over the next two weeks, an additional behavioural tion. She correctly read aloud a paragraph on the aberration was observed. She frequently and indis- Russian educational system, but immediately after- criminately put food and objects, even faeces on one wards described what she had read as 'school'. occasion, into her mouth. She was also frequently After looking at a two-page spread of photographs found searching aimlessly through other patients' for one minute, she could not tell the examiner the dressers. When eating she often used fingers instead relative locations of various pictures. She wrote her of utensils. name, address, and a sentence describing the Formal speech and language testing (Table) on 7 weather correctly and legibly with her right hand She copied geometrical figures in a bizarre fashion. She drew a triangle with aimless graphic persevera- tion, and, with a square, she showed the 'closing in' phenomenon. She drew a girl when asked to copy a Protected by copyright. cube (Fig. 2). She denied that anything was wrong with her health or memory. Proverb interpretation was meaningful. Formal psychological testing could not be com- pleted fully because of impaired attention span and

TABLE SUMMARY OF SPEECH AND LANGUAGE EVALUATION ON G.M., SIX WEEKS AFTER ACUTE CONFUSIONAL STATE

Spontaneous speech: fluent without dysarthria Peabody Picture Vocabulary Test: consistent with educational back- ground

Auditory conmprehension: intact for short oral questions, deteriorated http://jnnp.bmj.com/ on long paragraphs read aloud to her correctly matched pictures, colours, forms, numbers, letters, words, and sentences to oral verbal stimuli pointed to named body parts identified all presented non-verbal sounds Visual comprehension: matched printed words to pictorial counterpart Repetition: correctly repeated all numbers, words, and sentences Serial speech: correctly counted to 20, recited days of week, months of years, alphabet Naming: correctly named body parts and pictures of common objects on September 27, 2021 by guest. Reading: correctly read aloud two passages of moderate difficulty, though could not answer questions about them unable to answer questions related to paragraphs of greater than three sentences which she had read silently Writing: no impairment, including FIG. 3. Posterior surface of coronal slabs of brain. spelling and punctuation There is marked destruction Arithmetic: no gross deficits. Could tell time, set a model clock, do of posterior orbital, complicated reasoning problems and simple arithmetic insular, and anterior and medial temporal lobes, Drawing: drew circle, square, and cross on command. Drew a triangle including amygdalae. The inferior and lateral surfaces when asked to draw a diamond of the left (left lower slab) were utilized for viral cultures. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from 424 Generoso G. Gascon and Floyd Gilles

'-V4... -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~..l FIG. 4. (H and E. Marker= 015 mm). cinguli above, below. Laminar central total cystic necrosis is surrounded by a layer ofmacrophages and 'p-'~~~ ~~~~~~~~.~~~0 ~ ~ ~ ~Av 4' astrocytes. Mineralized neural debris (arrow) is located at right. Protected by copyright.

FIG. 5. (Luxolfast blue- Cresyl violet. Marker= 0-25 cm). There is total necrosis ofhippocampal (small arrow), parahippo- campal (large arrow), and fusiform gyri. http://jnnp.bmj.com/

December revealed, in addition to previous clinical She sustained a right retinal detachment, further bedside testing, frequent circumlocutions and increase of Hodgkin's infiltrate in the lungs, and lung illogical train of thought. She had exhibited bizarre abscess, and died in February 1968. on September 27, 2021 by guest. naming before the formal testing, but now she After death the following viral antibody titres correctly named all body parts and pictures of com- were received. mon objects. She was also able to name subordinates Cytomegalovirus antibody titres: to class words; for example, 'car' then 'Cadillac'. 9 January 1967 1:16 Subsequently, there was no essential change in her lOApril 1967 1:16 mental status. Neither the retrograde nor antero- 11 December 1967 1:256 grade amnesia improved. She continued to show Herpes simplex: marked hyperphagia, much wandering around the 9 January 1967 1:256 ward, and inappropriate jocularity. 11 December 1967 1:4096 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from Limbic dementia 425

FIG. 6. (PTAH. Marker= 0-1 cm). The gyri cinguli are necrotic bilaterally. The corpus callosum lies below.

NECROPSY FINDINGS The general necropsy findings venule and an occasional plasma cell. The latter Protected by copyright. included residual Hodgkin's granuloma in lung, were frequently bizarre and contained multiple spleen, and vertebral bodies as well as broncho- nuclei. The process ended abruptly at its borders and pneumonia. She had a severe depletion of bone frequently within the space of one or two micro- marrow and splenic lymphoid tissue. Fresh left scopic fields normal cortex was encountered. In spite temporal lobe tissue obtained at necropsy was of a diligent search no intranuclear inclusion bodies inoculated into Wi-38, human embryonic kidney and were identified. In the border of these lesions small monkey kidney media. All cultures were negative. foci of mineralized neurones or glial cells were The brain was fixed in 15% unbuffered formalin, sometimes encountered. No inflammatory response slabbed, blocked, and processed by standard methods was encountered in small necroses at the depths of and 15 ,u sections were stained by haematoxylin and sulci in the lateral, temporal, or occipital lobes. eosin or Luxol Fast Blue with Cresyl Violet. The bilateral damage of the anterior perforated Widespread destruction of limbic and paralimbic space and substantia innominata extended into the structures bilaterally was characterized, for the most septal cortex medially, the ventral portion of the part, by its symmetry, with the general exceptions nucleus accumbens septi superiorly, the posterior that temporal and insular isocortex was somewhat orbital isocortex anteriorly, as well as the inferior http://jnnp.bmj.com/ more extensively damaged on the right. In most insular isocortex laterally, the latter more so on the regions the destructive process included juxta- right. Several preserved portions of the nucleus allocortex and isocortex adjacent to damaged limbic basalis were bilaterally present posteriorly and structures (Fig. 3). medially. Insular damage on the right extended into The regions of damage were characteristically the isocortex of the superior tip of the Sylvian fissure, cystic centrally and bordered by a layer of hyper- on the inferior surface of the right third frontal gyrus trophic astrocytes and astroglial fibrils. Large in its middle third, and deep into the extreme capsule numbers of foamy macrophages were present and peripheral parts of the right claustrum. on September 27, 2021 by guest. centrally, as well as in the border, and were par- The entire as well as the ticularly prominent around blood vessels where they parahippocampal gyri bilaterally had been destroyed widely distended the perivascular space (Fig. 4). (Fig. 5). The destructive process included the pyri- Frequently, astrocytic nuclei were large and bizarre form cortex and subjacent amygdalae bilaterally. All and, while often containing nuclear bodies (Krishan, of the adjacent juxta-allocortex and the adjacent Uzman, and Hedley-Whyte, 1967), no intranuclear isocortex of the temporal lobe were involved. The inclusions could be identified. An inflammatory process had extended to the on the response was, at best, minimal. It usually consisted left, and the fusiform and third temporal gyri on the of several lymphocytes lying around a capillary or a right anteriorly. The temporal tips had been destroyed J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from 426 Generoso G. Gascon and Floyd Gilles bilaterally. The anterior commissure had undergone congenital anomalies, such as arhinencephaly, severe degeneration and was gliotic. The right fornix nearly always end in early death but, if the was markedly atrophic; the left much less so. Both infants survive, the clinical picture has usually mamillary bodies were intact; the right was modera- been that ofprofound mental deficiency, although tely atrophic. The gyrus cinguli was partially destroyed anteriorly there have been rare exceptions (Nathan and bilaterally (Fig. 6); the destruction extended from Smith, 1950). There are no specific degenerative the subrostral gyri to the level of the splenium. The diseases of the as a whole. One damage was more prominent on the right. The possible exception is the report by Corsellis, adjacent hippocampal rudiment was shrunken. Goldberg and Norton (1968) suggesting de- Isolated cortical necroses were present around the generation of limbic structures as a distant effect depths of sulci in the right medially of carcinoma. and at the depths of the right first temporal . The left thalamus was intact throughout. In the REPORTS OF COMPLETE LIMBIC DESTRUCTION In right thalamus there was a thin layer medially of the past decade evidence has accumulated that total necrosis which extended from the ventral anterior nucleus anteriorly, through the medial an infectious disease, acute inclusion body aspect only of the dorso-medial nuclei to the medial encephalitis, an illness whose viral agent was portion of the pulvinar posteriorly. Lateral dorsal unidentified in early cases, but shown to be nuclei bilaterally appeared to be normal as did the Herpes simplex in later cases, often has a intralaminar nuclei. No other lesions were found in specific predilection for limbic structures (Rose the thalamus. and Symonds, 1960; Brierley, Corsellis, Hierons, and Nevin, 1960; Drachman and Adams, 1962).

Only one report correlating extensive, but Protected by copyright. DISCUSSION selective, pathological lesions largely limited to REPORTS OF INCOMPLETE LIMBIC DESTRUCTION the limbic system with behavioural and mental Most human cases reported with behavioural or changes is known to us (Friedman and Allen, intellectual aberrations and correlated with 1969). We present the findings in this case of lesions of the limbic system have shown, on post- probable herpes simplex encephalitis as an mortem examination, incomplete involvement addition to the spectrum of chronic behavioural of limbic structures. We submit that this is be- and intellectual changes which may result from cause there are relatively few disease processes extensive limbic lobe destruction in man. that would account for selective but complete involvement. The vascular supply is multiple, CLINICAL-PATHOLOGICAL ANALYSIS OF OUR PATIENT involving mostly branches of the posterior For purposes of discussion, we can divide the cerebral, anterior cerebral, and posterior com- patient's chronic clinical neurological status into municating arteries, so that involvement of the the behavioural aberrations and the memory major part of limbic structures by occlusive deficit. A third area of concern, her naming http://jnnp.bmj.com/ vascular disease is unlikely, though partial difficulty, was prominent only in the acute stage involvement has been reported (Glees and of her illness, and was felt to be a non-aphasic Griffith, 1952; Victor et al., 1961; DeJong et al., misnaming syndrome secondary to the initial 1969; Faris, 1969). Neoplasm would have to be widespread cerebral dysfunction (Weinstein and widespread to infiltrate the whole system, and, in Keller, 1964; Geschwind, 1967). fact, has not been reported, to our knowledge,

although partial involvement is recognized Behavioural aberrations These consisted of on September 27, 2021 by guest. (Malamud, 1967). Surgical lesions have been denial of illness, inappropriate jocularity, nega- partial ones, such as cingulectomies and frontal tivism, hyperactivity, short attention span, dis- lobotomies performed for schizophrenia, and tractability, searching, and mouthing (hyper- with bilateral medial temporal lobectomies, phagia and bulimea). Like patients with which led to the recent intensive neuropsycho- Korsakoff's syndrome and unlike most with logical interest in memory (Scoville, 1954; bilateral surgical lesions of the hippocampal Terzian and Dalle Ore, 1955; Scoville and region, she was unaware of her memory deficits Milner, 1957; Penfield and Milner, 1958). The and denied any difficulty in remembering. In J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from Limbic dementia 427 fact, she denied that she was ill at all at a time but the difficulties with 'agnosia' as an explana- when she was no longer acutely ill or obtunded, tion in a monkey have already been pointed out as in the syndrome described by Weinstein (Geschwind, 1965). and Kahn (1955). Our patient exhibited the first four of these She was an amusing patient to talk to because characteristics. Although she was never observed the content of her speech was often inappropri- to have overtly increased autosexual, hetero- ately jocular, reminiscent of Witzelsucht. sexual, or homosexual behaviour, a psychiatrist Although she was apathetic shortly after the thought there was suggestive sexual connotation acute confusional state had ceased, she was in her conversation, and that she exhibited con- unlike the patient with chronic Korsakoff's fused courting of the examiner. Her responses syndrome who usually exhibits lack of initiative on Rorschach testing to the first two cards were and apathy, inertia, and indifference. She be- sexual associations. came quite hyperactive with much wandering Terzian and Dalle-Ore (1955) reported a 19 about the ward, and exhibited motor restlessness year old male, an epileptic with bilateral inde- such as constant swinging of her legs while pendent temporal foci, who underwent left, then sitting. Because she could not sustain attention right, anterior temporal lobectomy, including and was so distractable, she was unable to sus- and , as a case of the tain goal-directed activity. The quality of the Kliiver-Bucy syndrome in man. The patient did patient's investigation of her surroundings- not recognize anyone at first ('psychic blind- specifically the mouthing and oral tendencies- ness'). He showed near-catatonia -for the first is not part of the usual syndrome of motor two weeks after operation, but then reacted to restlessness, hyperactivity, and distractability every stimulus. He had an insatiable appetite, Protected by copyright. seen after encephalitis (Byers and Meyer, 1952). and complete loss of any emotional behaviour, Similar symptoms were reported in only one with indifference and amimia. Speech was of the survivors of herpes simplex encephalitis normal, except that language was 'composed of seen by Drachman and Adams (1962). The cases very elementary sentences within the limits of of memory defect after encephalitis reported by his natural needs'. He had a serious disorder of Rose and Symonds (1960) showed hyperactivity, present and past memory, which it was not but no specific mention of global attentional dis- possible to delineate fully. Up to this point their order was made. patient resembles ours. In addition, however, Many of the behavioural aberrations are simi- their patient showed a partial alexia and no lar to the syndrome resulting from bilateral spontaneous writing. His chronological sense of ablation ofthe anterior temporal lobes, including time was preserved, unlike ours. Also unlike uncus, , and hippocampus, in macaque ours, he had sexual exhibitionism, though no monkeys, described by Kliiver and Bucy (1939). sexual aggression, and homosexual tendencies. Their monkeys exhibited: (1) 'psychic blind- He did not show oral tendencies or mouthing http://jnnp.bmj.com/ ness', (2) strong oral tendencies, (3) a strong behaviour. tendency to attend and react to every visual The patient of Friedman and Allen (1969) had stimulus, (4) absence of the motor and vocal repetitious motor activity, such as patting his reactions generally associated with anger and knee and tapping his feet, and frequent impulsive fear, and (5) increased sexual activity. By 'psy- behaviour, such as tactless, inappropriate re- chic blindness' Kliiver and Bucy meant that the marks and mischievousness, though no specific animals responded indiscriminately to animate mention of short attention span and distractabil- on September 27, 2021 by guest. and inanimate objects and behaved as if all ity was made. The patient's mood was felt to be available objects belonged to one general class- compatible with his premorbid personality, un- something to be approached and examined. In like our patient who underwent a definite multiple object tests, pulling-in tests, and random personality change. Unlike our patient, their cage behaviour, the animals would pick up, patient lost calculation ability, his sleep habits, mouth, and contact objects over and over again, thirst, and appetite were unchanged, and he as if they had not examined them before. At first lacked oral compulsions. this behaviour was equated with visual agnosia, In addition to the fact that our patient J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from 428 Generoso G. Gascon and Floyd Gilles showed the behavioural components of the concretely. The Peabody Picture Vocabulary Kliiver-Bucy monkeys, the bilateral anterior Test, the one IQ test which she could complete, temporal lesions resemble those of the monkeys. was consistent with her previous highest educa- We propose, therefore, that her behaviour can tional level (high school). be characterized as an instance of the Kliiver- The features which clearly distinguish our Bucy syndrome in man. patient from the Scoville-Milner group I patients (those with the most radical bilateral medial Memory deficit Our patient showed a con- temporal lobe ablation) and those with Korsa- fabulatory-amnestic syndrome with anterograde koff's psychosis, are not the quality of the and retrograde amnesia; the prototype of which amnestic syndrome per se. Unlike both those is Korsakoff's psychosis (Talland, 1965). groups, our patient exhibited the additional Her deficit differed in that confabulation per- severe behavioural aberrations previously dis- sisted as strongly in the chronic stages as it was cussed. Moreover, although her lesions included in the acute stage, and remained easy to evoke those of the Scoville-Milner patients, she had (as with Friedman's and Allen's patient). With little involvement of those areas said to be respect to memory difficulty, however, our crucial for Korsakoff's psychosis-the mamillary patient and those with Korsakoff's syndrome bodies, or dorsomedial nucleus of thalamus. are qualitatively similar. Because of her short attention span and Limbic dysjunction In a provocative article distractability, it was difficult to test her in a way Yakovlev (1948) viewed behaviour as three that would prove conclusively to all observers different spheres of movement-the sphere of that the inability to remember both verbal and visceral motility; the sphere of motility of theProtected by copyright. non-verbal items was due to a specific deficit in outward expression of internal states, which memory processing, and not to the inability to includes the gamut of emotions (internal motions concentrate. This criticism is especially relevant brought out which affect the animal or man but, to those operational tasks which presented new per se, effect no change in the world of matter material to learn. about it); and the sphere of motility of effectua- However, it is difficult to accept an inability to tion, which creates changes in the world of concentrate as the entire explanation for defec- matter by use of parts of the body as tools. He tive responses, because even highly overlearned, postulated three anatomical systems which familiar, and automatized items such as her mediated the three spheres of behaviour. The birthdate, marriage date, and the number and entopallium mediates visceral motility, the meso- names of her children could not be reproduced. pallium the emotions, and the ectopallium the Also, it would be difficult to account for her sphere of motility of effectuation. The meso- extensive retrograde amnesia, repeatedly docu- pallium extends from olfactory forebrain through mented by questions concerning past news- the neuraxis and lies intermediate between the http://jnnp.bmj.com/ worthy events, such as her inability to recall one innermost system, the entopallium, and the of the most emotionally traumatic events of the outermost system the ectopallium. In the cerebral 1960s, President Kennedy's assassination. hemispheres the mesopallium includes the Her responses to other cognitive testing stand cingulate gyrus, retrosplenial and hippocampal in contrast to her defective responses on memory gyri (collectively the limbic lobe of Broca), the testing. She could not complete the WAIS, so orbito-mesial wall of the , and the that firm conclusions about her intellectual island of Reil. on September 27, 2021 by guest. functioning, based on psychometric data, cannot Papez (1937) proposed a theory that 'the be made. The main limitations that prevented hypothalamus, anterior thalamic nuclei, gyrus completion of tests was attention span as well as cinguli, the hippocampus and their connections negativism. However, to dismiss her as demented constitute a harmonious mechanism which may in the sense of marked loss of previous level of elaborate the functions of central emotion, as intellectual functioning is inaccurate. She could well as participate in emotional expression'. read, write, and do simple arithmetic. After the MacLean (1949, 1952) reviewed subsequent acute stage, she did not interpret proverbs developments in neurophysiology which sup- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.3.421 on 1 June 1973. Downloaded from Limbic dementia 429 ported the Papez theory, with special implica- sphere-damaged patients with 'indifference tions for psychosomatic disease. The Kliiver- reactions', consisting of jokes, mockeries, Bucy monkeys were selected as most striking. disinhibition, anosognosia, and minimization Based on our case and that of Friedman and (Gainotti, 1972). Allen, the manifestations of complete limbic We cannot make specific clinical-anatomical lobe destruction in previously normal brains correlations in our patient with regard to dis- seem to be an amnestic syndrome and a Kliuver- crete behavioural aberrations, as, for example, Bucy-like syndrome. In the latter the most con- relating decreased attention span and distract- sistent feature seems to be, first, the emotional ability to the bilateral hippocampal lesions as an non-reactivity, manifested by lack of rage, and example of the release of inhibitory functions of indifference, and second, a global attentional the hippocampus (Grastyan, 1959), or relating disorder manifested by short attention span, the lack of rage and anger to the bilateral marked distractability, and impulsiveness. The amygdala lesions. She had too many other presence of increased sexual expression and anatomical structures involved to make this kind mouthing oral tendencies is inconsistent. of traditional clinical-pathological correlation. Teleologically speaking, complete limbic lobe However, we propose that the structures in- destruction destroys a basic requisite for survival volved do fall into a functionally interrelated -the ability to detect and remember relevant unit, essentially that of Yakolev's mesopallium, (dangerous-safe) from irrelevant environmental Papez's and MacLean's visceral brain, or the stimuli. Subsequently, one of the manifestations limbic system. There was a right anterior of attempts to survive-anger or rage-dis- temporal neocortical lesion (as in Friedman and appear. Increased sexual expression may only Allen's case) and, although not strictly part of Protected by copyright. indicate the reciprocal relationship between the limbic system, this area interconnects with instinctive rage and sexual emotions-one more medial limbic structures such as amygdala ordinarily cannot have pleasurable sexual feelings and hippocampus. No significant permanent while angry, and vice-versa. lesions were demonstrated in neocortical associa- Bilateral lesions of hippocampal region are tion areas. sufficient, though not necessary, to produce We therefore suggest that this patient's syn- memory disorder, since other lesions-for drome was a 'limbic dementia', to emphasize example, mamillary bodies-can also produce it. that, although on superficial examination she The added destruction of other limbic areas does may have appeared demented in the usual sense, not seem to alter the memory disorder except to the functions primarily lost were not those make it more difficult to document because the cognitive functions usually associated with general prerequisites for memory disorder, con- 'intelligence', usually measured by psycho. centration and attention, are not intact. metric tests, and often based on language, but Nevertheless, it was still possible to document those which imprint an affective quality, thereby http://jnnp.bmj.com/ that the limbic system is essential for transfer to giving meaning, to daily survival interactions long-term memory, or early consolidation, and with the environment and imprinting them also for retrieval of memories dating months to into memory. Moreover, the neuropathological years back, though not essential for immediate, lesions were not those of the usual cortical unconsolidated memory, which is probably dementias, but were confined essentially to mediated through the . Although hemispheral structures within the limbic system. the limbic system is probably not necessary for on September 27, 2021 by guest. The authors are indebted to Mr. Jack Corrigan for long-term memories dating to early childhood, photographic assistance, Dr. Norman Geschwind and we were not able to document this in our patient. Dr. H. Richard Tyler for critical suggestions, and The fact that the right temporal lobes were Miss Susan Leonard for preparation of the more completely destroyed than the left in both manuscript. our case and that of Friedman and Allen raises the question of the effect of dominance on REFERENCES Angevine, J. B., Jr., Locke, S., and Yakovlev, P. 1. (1964). emotional behaviours. 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