Basal ganglia calcification and psychosis in mongolism.

Eur. Neurol. 17: 300-3 1 4 (1978)

Basal Ganglia Calcification and Psychosis in Mongolism Irene Jakab Department of Psychiatry, University of Pittsburgh, John Merck Program, Pittsburgh, Pa.

Key Words. Basal ganglia calcification • Down’s syndrome • Psychotic depression in a teenager •

Milieu therapy Abstract. An 18-year-old mongoloid girl (trisomy 21) of Asian descent presented two symp

Introduction

An 18-year-old mongoloid girl (trisomy 21) of Asian descent presented two conditions rare ly associated with mongolism (Down’s syn drome): (1) brain stem calcification; the first case diagnosed in vivo in mongolism on com puterized axial tomography (CAT)1; (2) halluci natory psychotic depression; the first case successfully treated, to full recovery from the 1 A neuroradiologica! study of these findings is being submitted separately for publication in collaboration with the neuroradiologists who have performed and interpreted the CAT scan.

psychosis, in a mongoloid child with known brain stem calcification. The psychotic depression was related to moderate environmental stress (changes in family constellation) and remained unrespon sive to tranquilizers for more than 1 year, while being treated in her parent’s home in their native land. Following hospital admission in the USA, rapid improvement was obtained within a few weeks, through intensive milieu therapy, which was designed specifically to overcome the cultural and language barrier. The demonstration of calcium deposits on CAT provides a new, objective finding in the

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toms rarely associated with mongolism (Down’s syndrome). (1) Brain stem calcification; the first case diagnosed in vivo in mongolism on computerized axial tomography. (2) Hallucinatory psychotic depression; the first case successfully treated, to full recovery from the psychosis, in a mongoloid child with known brain stem calcification. The psychotic depression was related to moderate environmental stress. While being treated in her parent’s home, in their native land, for more than 1 year, the psychosis remained unresponsive to tranquilizers. Following hospital admission in the USA, rapid improvement was obtained within a few weeks through intensive milieu therapy.

Basal Ganglia Calcification and Psychosis in Mongolism

a baseline for a planned long-term follow-up with re-evaluations scheduled at 2-year inter vals, to determine changes - if any - in the levels of intellectual, emotional or social func tioning, and in the status of the cerebral calcifi cation.

Case History Mane (name has been changed) was admitted to the University Hospital of Psychiatry in Pittsburgh, Pa. for diagnosis and treatment on November 8, 1977. She was discharged, free of psychotic symptoms, on Janu ary 27, 1978. She was an inpatient during the first 2 weeks and continued in partial hospitalization for the rest of her treatment. Present Illness About 1 year before Marie’s admission her two sisters left home to study abroad and a favored domestic help had also left. These changes in the home constellation coincided with a corrective surgery for congenital anomaly of the head of the left radius. (During the same general anesthesia, tubal cauteriza tion was also performed, but Marie was kept unaware of the sterilization.) Her first symptoms were sadness, crying, and with drawal from her formerly enjoyable activities of reading, piano playing, TV, and bicycling. It became very difficult for the parents to engage her in a conversation. She was depressed but not psychotic. The abrupt change to severe psychotic depressive state came about in a seemingly paradox situation, when the parents took Marie overseas to visit her sisters. They expected an improvement of the depression through the temporary reunion with the ‘lost’ persons. However, during that visit anger and disappointment were openly manifested when one of her sisters, who has joined a different religion and an extremely differ ent social life style, clashed over traditional values with the parents. Marie was bewildered by this show of emotions, unusual both in her cultural environment in general, and specifically in her family, where nega tive feelings were not openly expressed. During this visit Marie showed marked anxiety and refused to sleep alone; she would only sleep in the parent’s bedroom on an extra bed. She was observed giggling


assessment of cerebral pathology in Down’s syndrome. Further CAT research is necessary to evalu ate the prognostic implications of cerebral cal cification regarding early prediction of the potential levels of tire intellectual, emotional and motor development to be expected in a given case of mongolism. Severe regression, psychotic anxiety and hallucinations of about 1 year’s duration in spite of treatment with tranquilizers, prompted the parents and the attending physician of this girl, who resides in an Asian country, to seek consultation with this author, in the United States, regarding diagnosis and treatment. Following our differential diagnostic studies it was concluded that the patient suffered from reactive psychotic depression due to environ mental stress and not caused by the brain stem calcification or by the genetic disease of mongolism itself. However, the simultaneous occurrence of these two organic conditions — each of which is known to be associated occa sionally with psychosis —is considered to con stitute a cluster of vulnerability factors decreas ing the ability of this child to cope with environmental stress. It is of special interest that this Asian re tarded child who only spoke her native lan guage was treated successfully through intensive milieu therapy in the USA (at the John Merck Program, directed by this author, at the Uni versity Hospital for Psychiatry in Pittsburgh, Pa.) in spite of the alien cultural setting and language barrier. Her individual programs and group treatment modalities were specially designed to require minimal verbal communica tion, relying essentially on demonstration by staff and peers. The case history of this patient is presented in detail in order to substantiate the differential diagnostic considerations, as well as to serve as

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and gesturing to herself, and she stated having ‘pleas ant thoughts’ at such times. This condition continued after the trip was interrupted and the parents returned with Marie to their home. Treatment with tranquil izers did not alleviate the symptoms. Past History Marie is the fourth child of, at that time, a 26-year-old mother and a 41-year-old father. The first two girls (ages 23 and 19) are of normal intelligence. The third child, a boy, died at age 11 months of medulloblastoma. There is no mental retardation, psychosis or Alzheimer’s disease in tire family. Marie was essentially a physically healthy and emotionally stable mongoloid child up to the present illness. Normal, full-term pregnancy, 2,800 g at deliv ery, no neonatal problems. She had no childhood illness, menarche at 12 years, and corrective surgery for bilateral-metatarsal anomalies (pigeon toed and flat feet) at 12 years of age. The left radial head was removed because of congenital anomaly at 17 years of age, and a small keloid has developed at the operative site. During her psychotic episode Marie was obsessive ly preoccupied with this scar, asking incessantly, ‘When will it disappear?’. Developmental milestones were slow: she walked and talked at age 3. In general she has always been a clumsy child unable to learn to use a bicycle or go up and down steps without holding onto a rail. With intensive home tutoring she learned to read and write in her native language. She also learned to play the piano by reading special ‘lettered notes’. She is righthanded, with mixed dominance (right hand, left foot, left eye). Physical Examination Head circumference 19'/2 in, height 51 in, weight 79 pounds. Limited supination of left forearm; physi cally mature oriental girl with numerous stigmata of Down’s syndrome: a brachycephalic head, small cshaped ears, large tongue with abnormal papillae and rugae, epicanthal folds (not oriental type), mongoloid slant of the eyes, malformed teeth, short neck, wide spread nipples, prominent abdomen, short extremities, abnormal palmar prints, in-curved little fingers with single crease, widespread great toes and abnormal plantar prints. She lias a grade 1-2/4 systolic murmur, heard best at the third and fourth left interspace close to the sternal border; this was not accompanied by a trill, abnormal pulsation or evidence of cardiohepato-

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splenomegaly. EKG: normal. Wears corrective lenses. Audiometry: left ear: normal hearing; right ear: pro found deficit with no response to speech testing. Otoadmittance testing indicated no change in trans mission with changes in pressure. The stapedial reflex was absent, bilaterally, consistent with flat tympanometric curves caused by very tortuous ear canals. There was no middle ear pathology. (Similar hearing loss is frequent in mongolism; Brooks et al., 1972.) Neurological Examination Essentially normal status except for transitory cxtrapyramidal side effects (caused by minimal doses of 2 mg Stelazine per day administered to the patient in her native country, before coming to the USA): fine hand tremor and slight rigidity but no cogwheel sign. Her tongue showed frequent cheeking and she made clicking sounds while showing some restlessness of the perioral muscles. Historically, she had occasionally ‘stiffened'. These symptoms disappeared within a few days after the discontinuation of Stelazine. Marie has not shown any cortical neuropsychological deficit o f localizing value. Chromosome Study Female karyotype with trisomy 21, typical for Down’s syndrome. Laboratory tests They were within normal limits, including CBC, differential, Ca and Ph values. Thyroid and parathy roid functions were also within normal limits. Choles terol, 223 mg/dl; triglycerides, 159 mg/dl; lactate, 1.8 mEq/dl; pyruvate kinase in RBCs, 4.3 IU/g Hb; pyruvate kinase (serum), 1.8 umol/h/ml; T4, 8.6 mg/ dl; TTBC, 29.3 mg/dl; UTBC, 22.9 mg/dl; %TS, 29%; EET, 1.73 mg/dl; TSH, less than 12 IU/ml; SCOT, 25/1.0; SGPT, 20/0.9; Na, 141 mEq/1; K, 4.2 mEq/1; Cl, 116 mEq/1; CO., 34 mEq/1; albumin, 5.4 mg/dl; Glucose, 100 mg/dl; creatinine, 1.1 mg/dl; T. bili., 1.5 mg/dl; alkali, phosphatase, 135 mU/rnl; RPR, nonreactive. Other Examinations Skull X-ray: slightly enlarged S-shaped sella,judged to be a normal variant. Radioisotope brain scan was normal. EEG: moderately generalized abnormal record w'ith diffuse high amplitude theta. No epileptic focus. Computer assisted tomogram (CAT) of the brain (fig. 1): Symmetrical basal ganglia calcification.


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Fig. 1. Symmetrical brain stem calcification in an 18-year-old mongoloid girl.

Fig. 2. Spontaneous painting during the psychotic depression, in purple and brown - ‘an egg’ and ‘the ceiling in my parent’s bedroom’. Fig. 3. Spontaneous drawing after recovery - ‘blue flower’.

Psychiatric Evaluation The psychiatric evaluation was performed in sever al sessions with the help of a translator. Marie was oriented as to time, space and person. She knew that she was in Pittsburgh. Attention span: average. Memory for past and recent events: average. Her thought processes were narrowed down to a very concrete level and were very slowed down. She did not initiate any conversation, and answered questions in a very low voice, occasionally her mumbling remained unintelligible to the translator. Reading and writing skills: She can read and write in her native Thai language. She has used successfully a booklet, into which her parents wrote down some words and brief sentences in her native language and in English, for communicating with the staff by pointing to the appropriate words. She learned rather fast to read and write some English words, using the English alphabet. She can tell time by reading the clock. Constructive praxis: She demonstrated that she can do large puzzles easily. According to the parents she completed a 200-piece puzzle before her illness. Figure

drawings are under the 7-year mental age level. She has not been trained to draw' people. She was able to enter into a graphic dialogue with me: without verbal in structions, she understood from my drawings what I expected her to do and complied with it, completing certain drawings with missing parts. Spontaneously, she painted a purple oval form and called it ‘egg’ (and said, T like to eat eggs’). A rectangular outline in brown was called ‘the ceiling in my parent’s bedroom’ (figure 2). The brown and purple colors are of specific diagnostic value in retarded children’s drawings, indicating depression (Jakab, 1967). She drew ‘a girl who was making a trip and going to the movies to see a picture about ghosts’. She was weary and preoccupied with getting her hands dirty; she washed her hands frequently. Her behavior and the content of her art products reveal egocentric associa tions and anxiety related to the situation on a ‘trip’.



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Psychological Testing (with Interpreter) l.eiter International Performance Scale: CA, 18-3; MA, 7 -6 ; basal age, 6 -0 ; ceiling age, 10-0. It is esti mated that her mental age falls between 8 and 10 years since some of the test items were probably failed due to the cultural bias of this test. Projective tests: Rorschach and TAT: Marie quickly lost interest and kept commenting that there were ‘too many’ cards. All of her projections were to the whole card and only one response per card was given. The content of the Rorschach projections were conceptually at a high level and reality oriented. Some anxiety surrounding medical operations and proce dures were present in her TAT stories. Educational Testings (with Interpreter) Marie functions on the third grade level on reading, writing skills and concept formation, and on the second grade levc on the Key Math Test. She has awareness of quantity; she recognized and labeled the numbers up to 100, also in English; she labeled com mon geometric shapes and identified parts of objects. She recognized all computational symbols. She can add two two-digit numbers requiring regrouping, she can do simple subtraction, but multiplication and divi sion tests were refused. She was unable to solve two computations presented in sequence and to recognize or use fractional numbers. She labeled time intervals to the quarter hour. She identified the calendar, but showed limited functional use of clock and calendar. Diagnosis Down’s syndrome (trisomy 21) with mild mental retardation. Bilateral brain stem calcification. Reactive depressive psychosis with high degree o f anxiety.

for requesting the light to be kept on all night. Her evaluation and treatment was carried out at the John Merck Program for disturbed retarded children. Her small stature and level of retardation was an advantage in integrating her into the milieu with younger chil dren. Milieu therapy was considered to be the main therpaeutic modality. Her program was individually designed to consist of activities requiring minimal or no verbal language skills. By using gestures and demonstrations as the main vehicles for communication we have bridged the foreigh language barrier. In therapeutic education Marie was included into a second grade self-manage ment program setting working on auditory perception: sound picture association; visual discrimination: dan ger signs, traffic signals, classification of objects by shape and function; eye-hand coordination, fine motor dexterity and socialization skills: setting table, making a snack, and dancing. Individual tutoring in mathe matics was supported by sessions of arts and crafts and cooking, designed to teach her measurements and to deal with fractions as a concrete concept. Body image training, physical therapy, recreational and prcvocational activities completed the milieu therapy. Drug treatment consisted of Mellaril increased from 30 to 120 mg/day for 2 weeks then gradually decreased again to maintenance dose of 30 mg/day. Psychotherapy Only three sessions of supportive therapy have been provided by a child psychiatrist who spoke Marie’s language. Issues of her anxiety about the sister’s leaving home and the altercation within the family, due to the new lifestyle of one sister, were fore most on Marie’s mind and required clarification and proper perspective. The alienation of the sister from the family values made her 'loss’ to appear more irrev ocable. Marie felt very threatened and anxious about becoming the next target of the parental rejection, probably based on her feelings of inadequacy and of being ‘different’. This led to a regression into a state of infantile demands of being cared for intensively by her parents. Sleeping in the parental bedroom provided control over their whereabouts and reassured her of their continued presence.

Treatment and Course o f Illness Marie was admitted to an adult ward where she slept in a separate room without undue anxiety except

Family Counseling After the first 2 weeks of inpatient treatment, Marie was discharged to the home of her parents, who


Hallucination has not been observed during the psychi atric evaluation, but was reported in the first days of hospitalization by the staff. Affect: Marie was withdrawn, anxious and de pressed. She was unable to name any wishes or needs. She just wanted to be left alone to lie on her bed and sleep. Her psychomotor activity was almost at a stand still.


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have rented an apartment in Pittsburgh for the time of Marie’s treatment. Several home visits were made by Marie before her discharge, in order to familiarize her with the apartment. She adapted well without undue anxiety or regression to sleeping alone in her room. Occasional brief periods of hallucinations were sus pected by the parents during the first couple of weeks. This phase of Marie’s rehabilitation, aimed at her early reintegration into the changed family environ ment, was an essential aspect of our therapeutic goals. During this phase Marie has spent daily 4 - 6 h in our program, while the parents kept in close contact with this author and the staff working jointly on the same goals in the home environment. The parents learned a new style of interacting with Marie, treating her more like and adult member of the family (with a handicap) and not as a helpless child. They have skillfully carried out the activities pre scribed for Marie’s home program. Rapid improvement has been recorded by the staff and Marie's parents. The improvement continued steadily, after an ini tial period of withdrawal, crying, refusal to speak and manifest anxiety. Her mood gradually lifted, she be came interested in her environment and interacted freely with staff and children. Hallucinations have ceased, and she participated eagerly in all activities. Marie learned several English words and the names of many children and staff members. While at the beginning Marie was a completely passive target of any occasional aggression of other children (pushing, hitting), later she learned to avoid aggressive kids or defend herself appropriately or call on staff for protection. Her motor skills, and motiva tion for it, improved substantially. She learned to jump and walk the balance beam. Her figure drawings became more proportionate and she produced several multicolored, w'ell-balanced pictures of flowers (fig. 3). She cooperated in interactive games and ini tiated interaction with staff and peers spontaneously. Good eye contact and pleasant social manners were regained. At the time of her discharge Marie has appropriately expressed verbally both her sadness of leaving the program and the people of whom she grew very fond and her happiness of looking forward to going home with her parents to their native country.

maintenance dose of 30 mg Mellaril a day has been discontinued. She is accepting the fact that her sisters are studying ‘away from home’. She continues, with the help of home teachers, most of the educational and recreational programs she started here. Her mood is generally cheerful.

Discussion

Differential Diagnostic and Etiological Considerations

Is Brain Stem Calcification an Independent Entity Occurring in this Mongoloid Individual? (a) Familial striopiallidodentate calcification (Strobos et al., 1957; Bruyn et al, 1964; Schafroth, 1958) and idiopathic cerebral calcifi cation (Malamud, 1957) are to be considered. However, there is no proof of familial occur rence in our case. (b) Idiopathic hypoparathyroidism (Selye et ai, 1964) and Albright’s hereditary osteodys trophy (including both the pseudo- and the pseudo-pseudohypoparathyroidism (Albright et al, 1942, 1952), which present several similar clinical features to our case (De Muelemeester, 1961), have been excluded through the labora tory tests which were all within normal limits. (c) Jancar’s cerebrometacarpometatarsal dys trophy (Jancar, 1965) might be considered as a possible diagnostic entity, associated with Down’s syndrome in Marie’s case, since she presented both cerebral calcification and meta Follow-Up (6 Months after Discharge) Marie’s trip home was uneventful. She is symp tarsal dystrophy. Nonetheless, without further tom-free and adjusted well to her home situation. The research on the occurrence of cerebral calcifica


An attempt is made to reveal a possible etiological relationship between any combina tion of two, or all three diagnostic entities found in this case: the basal ganglia calcifica tion, Down’s syndrome, and psychosis.

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tion in mongoloids it does not seem justifiable (1956) and Murofushi (1974) and rarely (1 in to conclude that Marie has Jancar’s syndrome 100 cases) also in tire hemispheric white matter superimposed on mongolism, since metatarsal (iOstertag, 1929). In his very carefully studied anomaly occurs in many mongoloids, quite case, Murofushi (1974) defined the deposited frequently among other common stigmata. material to be pseudo-calcium, based on its (d) Other pathological entities: Toxoplas histological properties under specific staining mosis, cytomegalovirus, echinococcosis, tumor procedures. He relates its occurrence to chronic and tuberosclerosis can be excluded through anoxia, as a probable secondary phenomenon the finding of symmetrical, circumscribed and due to circulatory deficiency. Murofushi (1974) dense shadows of the brain stem calcification calls attention to the circulatory insufficiency and through the lack of other diagnostic data of mongoloid children in general, and compares indicative of any of these conditions. its consequences to those of neonatal encephalomalacies caused by various other etiological Is Brain Stem Calcification Caused by or factors. Related to D ow n’s Syndrome? Biochemical-Metabolic Anomalies. In Down’s There are two groups of pathological condi syndrome the central nervous system does tions which may provide an etiological link: not reveal typical gross deformations or (a) vascular anomalies, and (b) biochemical even microscopic changes of sufficient diag nostic value in themselves, however, a substan anomalies. Vascular and Circulatory Anomalies. They tial data collection of various biochemical are known to have an essential role in brain anomalies found in mongoloid individuals is stem calcification (,Norman and Urich, 1960) now steadily growing in the literature (Kaina, and also to occur with great frequency in 1977; Whittaker and Berry, 1977; Arnaud et Down’s syndrome. Cardiac malformations were al., 1976; Schlesinger et al, 1976; Schmidt et described by Benda (1960) in 75% of mongol- al., 1977; Murdoch et al., 1977a; Williams et al., oid children who died before age 1 year and in \91\\Spatz, 1922).' 35% of those who lived beyond 1 year of age. Matuso et al. (1972) found cardiac anomalies in Impaired mucopolysaccharide metabolism 55% of Japanese children with Down’s syn could be considered as a possible link between drome. Jacob (1956) found a hypoplastic cere mongolism and cerebral calcification, since it bral vascular system in mongoloids. Extensive has been described in cases of mongolism vascular involvement was described by Rosen- (Michejda and Menolascino, 1975) as well as in gart and Isabel-Jones (1976), Sakauchi et al. cerebral calcification (Lowenthal and Bruyn, (1977), and Park et al. (1977). Atherosclerosis 1968) and it is assumed to be involved in the was found by Hughes (1977) and Murdoch et formation of pseudo-calcium and calcium al. (1977b). Moya-moya disease in a 3-year- deposits. Unfortunately, in Michejda andMenoold mongoloid girl was diagnosed by arteriog lascino's (1975) case no CAT evaluation of the raphy and CAT, in vivo, and confirmed by brain has been performed. In future research it would be worth search autopsy by Schrager (1977). On autopsy material, diffuse calcification ing for simultaneous occurrence of vascular has been described in the brain stem of mongol anomalies and of impaired mucopolysaccharide oids by Ostertag (1929), Beyme (1945), Jacob metabolism in mongoloids as a possible cluster


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of vulnerability factors that may increase the changes of brain stem calcification. In Marie's case there were no gross vascular anomalies nor a history o f anoxia, neither do we have proof o f impaired mucopolysaccharide metabolism, to provide some etiological clues to the occurrence o f the brain stem calcifica tion. We must consider the brain stem cal cification in this case to be o f unknown etiology. Is Psychosis Related to Brain Stem Calcification? There are several publications of non-mongoloid patients with striopallidar calcification who manifested psychotic episodes during the course of their illness (Pope and Demetrescu, 1930; Pierach, \93S\ Mortell, 1946; Mulder and Denst, 1950). Lowenthal and Bruyn (1968) in their exceedingly comprehensive paper stated that: ‘Mental deficiency or mental deterioration has been noted in 60% of the cases. Psychosis, schizophrenia, hallucinatory paranoid states, depression, stupor, ideas of reference and delu sions are quite common.’ Furthermore, they found that ‘the psychoses tend to regress with adequate therapy’ and should be regarded as symptomatic diagnosis. Based on tire critical review of the literature regarding the psychiat ric conditions related to brain stem calcifica tion, Lowenthal and Bruyn (1968) state that: ‘A full psychiatric analysis o f the mental changes in this disorder is still extant. ’ It is hoped that Marie’s case will bring at least some new details in the understanding of psychotic states in brain stem calcification and in mongolism. In this case the calcification has been visualized on CAT scan in vivo, and thus there is a chance for follow-up evaluations (scheduled at 2-year intervals) to determine the course of the clinical picture and the state of the brain stem calcification.

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Are we Dealing with an Organic Psychosis Associated to, but not Caused by Down's Syndrome? Among the degenerative diseases leading to psychosis and dementia. Alzheimer’s disease is known for its high frequency in mongoloids (Olson and Shaw, 1969; Cropper et al., 1975; Ellis et al., 1974; Malamud. 1957; Dalton et al., 1974). Heston and Mastri (1977) made the statement that, ‘in Down’s syndrome the reward for survival, beyond age 40, is presenile dementia’. These authors believe also in the ultrastructural identity of Alzheimer’s and Down’s syndrome. On the other hand, Rees (1977) writes of the quantitative examination of the cerebral cortex of two severely defective mongoloids: ‘It has not been possible to detect any specific abnormality in the ultrastructure of the cortical parenchyma.’ In vivo the differ ential diagnosis is even more difficult. Seltzer and Frazier (1978) have noted that in diagnos ing Alzheimer’s disease, ‘laboratory investiga tion is singularly uninformative, except for the contrast procedures or computer assisted tomogram’. There is also some controversy about the extent of ‘dementia’ in cases of Down’s syndrome with Alzheimer’s disease. Owens et al. (1971) proclaims that it is ‘un common’. In the two cases reported by Burger and Vogel (1973) dementia did not occur. Similarly, in the two cases of Down’s syndrome of Schochet et al. (1973) there was no demen tia in spite of severe neurofibrillosis. It is of course, very difficult to assess the extent of dementia when it is superimposed to a more or less severe mental retardation. Only by repeated use of standardized tests could one accurately assess the gradual downhill course of the performance o f a mongoloid person, as it is planned to be done in Marie’s case at follow-up evaluations. In Marie’s case the lack of cortical atrophy



and the lack of actual ‘dementia’ on psychologi cal testing paired with her ability to learn new material after the rapid disappearance of the psychotic symptoms (under appropriate psychi atric treatment) have excluded, at least for the time being, the concomitant diagnosis of Alzheimer’s disease. Are we Dealing with a Case o f Reactive Psychosis Unrelated, but Superimposed on Mongolism? ‘Psychosis in mongolism is, it itself, an uncommon finding as compared to psychotic symptoms o f retardates in general’ (Cytrin and Lurie, 1967). K ety (1978), discussing the biochemical aspects of schizophrenia, mentions Down’s syndrome and other selected genetic disorders including ‘some single gene defects leading to mental retardation with psychosis’ (PKU, galac tosemia, maple syrup disease, Hartnup’s disease). However, he does not list mongolism within this later category. Catatonic psychosis was described in a few cases in mongoloids (Rollin, 1946; Earl, 1934). Emotional distur bance of lesser than psychotic degree is quite frequent, ‘in spite of the long accepted cliché about the loveable, cheerful, docile mongoloid’ {Bernstein, 1978). Reactive depressive psychosis in retardates is less commonly diagnosed than other psychotic syndromes. Keegan et al. (1974) have published two cases of mongoloid women (ages 23 and 25) with acute psychotic episodes diagnosed at first as autistic psychosis (with symptoms similar to Marie’s). Unfortunately, in their brief case description no details are given regarding any environmental stresses or changes in the patient’s life at the time of the psychotic episode. No do they mention any radiological anomalies, and whether or not a CAT study of the brain has been performed in their cases.

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Neither of their two patients showed any improvement on trifluoperazine — actually their psychosis even worsened, and in one of the cases severe extrapyramidal symptoms occurred on a trial on 8 mg haloperidol per day. Both their patients showed dramatic improve ment on amitryptyline, which led the authors to speculate on the underlying depressive com ponent. The specific intolerance of even low doses of tranquilizers in these cases is very similar to Marie’s experience with trifluopera zine. The brain stem calcification (demon strated on CAT) may be one of the factors to account for her vulnerability to phenothiazines. No causal relationship could be demon strated between Marie’s psychotic symptoms and the organic condition o f Down’s syndrome, or the brain stem calcification. Therefore, the relevance o f psychosocial factors in the etiology o f the psychotic depression have been explored. At the onset of the psychotic symptoms, the home constellation of this very close knit fami ly has been altered dramatically through the departure of three caring persons (her two sisters and a maid) to whom Marie was emo tionally attached. Furthermore, this loss was aggravated when Marie was recuperating from orthopedic surgery and was more vulnerable to the frustration of her dependency needs. The loss of caretakers can lead to a period of prolonged grief in any retarded child, who has few emotional ties outside of the family. The social isolation of retardates being extreme in Marie’s native land, she had essentially no social-emotional relations, or support, outside of the members of her immediate family and the household employees. Marie’s loss was therefore relatively more severe than the loss due to comparable environmental changes in a different cultural milieu. Her psychotic reaction caused by minor physical stress (surgery) and concomitant


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moderate emotional stress, would support Rahe and Arthur's (1978) appealing theoretical model of the interpretation of the influence of recent life events on tire appearance of illness symptoms and disease. The diagnosis o f reactive psychotic depres sion is corroborated by the correlation in time o f the symptoms with the stressful environ mental events, as well as by the rapid and complete recovery through intensive milieu therapy.

Her education, rehabilitation and recreational programs were carefully designed to consist essentially of activities requiring minimal verbal interaction and relying substantially on demon stration by staff, or by peers in group activities, in order to overcome the language barrier. The positive transference toward staff members helped motivating this girl to cooper ate with the treatment tean. Positive staff atti tude was successfully communicated in a non verbal way and made her feel liked and appreci ated. The parent’s full understanding of the thera peutic goals and their genuine warmth and skillful cooperation in the treatment program was an essential element in the success of Marie’s treatment. Marie’s case can serve as an example o f docu menting that the low mental age, with a con crete level o f thinking, as well as the known perceptual processing deficiencies o f mongoloids (Schroth, 1975; Heionayer-Stritek, 1975; Kohlmann and Rett, 1975; Gliddon et al., 1975; Cicchetti and Sroufe, 1976; McDonald and Mackay, 1977), is a substantial liability that makes them vulnerable to even minor stresses related to life events. Based on the accurate assessment of her level of functioning, the elements of the milieu therapy have been adapted to meet her emotional needs for envi ronmental predictability and for successful achievements at her own level, thus rebuilding her self-confidence and trust in the parents and the environment.

An unusual fact in this particular case is that the milieu therapy has been carried out success fully in an alien cultural setting and a foreign language environment, in spite o f communica tion difficulties. First, we had to overcome the difficulties o f achieving reliable psychological testing in this case. Through the careful data analysis of the items failed and of the concomitant behavior during testing, as compared to her performance levels outside of the test situation, it was possible to discriminate actual intellectual deficits from temporary failures due to emo tional disturbance and from failures due to the cultural bias of our tests, standardized on middle class western population. Bleuler’s (1976) remarks about testing of retardates are very relevant in Marie’s case: ‘Test examina tions furnish very good occasions (italics by Bleuler), for the state of intelligence to reveal itself... but it does not necessarily do so.’ The predictability and stability o f the envi ronment and the concretely understandable programming o f the milieu therapy provided a feeling o f security which decreased Marie’s anxiety and psychotic anticipation o f rejection.

Clinical Conclusions (1) In this case of an 18-year-old mongoloid girl no proof of direct etiological correlation could be found between the basal ganglia calci fication and the mongolism itself, nor between


Therapeutic Ingredients in the Successful Psychiatric Intervention

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the psychosis and the brain stem calcification, or the psychosis and the mongolism. (2) It is assumed that the clustering of the retardation caused by the genetic disorder and of the cerebral calcification, as a possible sign of earlier undetected anoxic encephalopathy, increased this patient’s vulnerability to environ mental stress. (3) It is also assumed that her adverse reac tion to phenothiazines was correlated to in creased vulnerability of the basal ganglia due to the calcification. (4) The psychotic depression was caused by changes in the family constellation for which the patient was not prepared and which she could not understand because of her concrete level of thinking. (5) Rapid improvement was achieved through intensive multimodality milieu therapy and psychotherapy, which decreased her anxi ety and depression through clarification and reality orientation. (6) Short-term supportive drug treatment with small amounts of Mellaril was used in the initial phases of the total treatment.

Clinical Recommendations (1) Retardates (especially retarded children) must be prepared carefully for any changes in the environment leading to loss of caretakers, since their inability to understand tire reasons for the changes, and their generally low self esteem and guilt for their intellectual handicap, makes them prone to interpret this loss as rejection. Psychohygienic intervention methods could prevent the development of pathological reactions to mild or moderate environmental stress. (2) The treatment of psychotic retardates must provide intensive structured milieu thera

py, and if possible it should include psycho therapy to help the patient deal with real or fantasized losses. (3) Short-term drug treatment may be indi cated to supplement the psychodynamic inter vention in its initial phase. (4) The success of intensive milieu therapy, of psychotic retardates in general, will be en hanced through judicious use of nonverbal com munication. (5) The development of anoxic encephalop athy in mongoloids with cardiovascular anoma lies must be prevented through vigorous methods of corrections at the earliest possible time, since anoxic damage could play a role in enhancing the potential for cerebral calcifica tion, which in turn could further decrease the level of functioning of these individuals and in the meantime increase their vulnerability to phenothiazines. (6) The prescription of phenothiazines for psychotic symptoms in mongoloids requires close clinical observation for the early detection of extrapyramidal side effects, as a sign of possibly increased vulnerability to such com pounds. Most mongoloids are unlikely to complain of drug side effects because of their low intellectual level, which may be further aggravated by deficient expressive language. Therefore, objective observation is essential. A positive CAT scan would be a very valuable indicator of basal ganglia vulnerability in such cases.

Prognostic Implications and Need fo r Future Research One of the most difficult tasks facing a neurologist or psychiatrist is the prediction, at an early infant or toddler stage, of the expected levels of intellectual, emotional-social and


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motor functioning of an individual mongoloid correlations of the cerebral calcification with child. the level of intellectual deficit, as well as with The wide range of the differences in the the level of the emotional vulnerability. If, following appropriate evaluation o f the severity of the intellectual deficit is well known in the literature on Down’s syndrome (Gordon hypothesis, these correlations could be substan and Panagos, 1976; Brink and Grundlingh, tiated, then the CAT o f the brain could even 1976; Fishier et al, 1976; Prior and Chen, tually provide the clinician with the long 1976; Montague, 1976). Other publications awaited objective diagnostic and prognostic attest to the variety of motor deficiencies and tool, not only in Down's syndrome, but also in ill-defined ataxias and tremors in mongoloids several other entities o f retardation with sus (Frith and Frith, 1974; Carr, 1970; Crome et pected but clinically not documented anoxic encephalopathy. al, 1966; Crome and Stem, 1967). The typical chromosomal anomaly itself certainly falls short of explaining the individual References differences in mongoloids. Neither the clinical neurological examina tion, nor the psychological testing can be Albright, F.; Burnett, C.H.; Smith, P.H., and Parson, W.: Pseudohypoparathyroidism. Example of Searegarded as reliable prognostic tools in predict bright-Bantam syndrome: report of 3 cases. Endo ing, at a very early age, the expected levels of crinology 30: 922-932 (1942). development in a given case of mongolism Albright, F.; Forbes, A.P., and Henneman, P.H.: Pseudo-pseudohypoparathyroidism. Trans. Ass. (Down’s syndrome). Am. Physns 63: 337-350 (1952). It is tempting to postulate the hypothesis Arnaud, P.; Burdash, N.M.; Wilson, G.C., and Fudenthat the frequently suspected (Jakab, 1959, bcrg, H.H.: Alpha-l-antitrypsin (Pi) types in 1965) but rarely documented anoxic enceph Down’s syndrome. Clin. Genet. 10: 239-243 alopathy is responsible fo r many o f the individ (1976). ual differences in the levels o f functioning o f Benda, C.E.: The child with mongolism (congenital acromicria) (Gruñe & Stratton, New York 1960). Down's syndrome subjects. Bernstein, N.R.: Mental retardation; in Nicholi, The Proof o f cerebral calcifications may be thy Harvard guide to modern psychiatry, pp. 551-567 only tangible clinical finding indicating chronic (Belknap Press of Harvard University Press, Cam (anoxic) encephalopathy in a mongoloid sub bridge 1978). Beyme, F.: Über das Gehirn einer familiären Oligoject. phrenen mit symmetrischen Kalkablagerungen, This hypothesis could be tested through besonders in den Stammganglien. Schweizer Arch. large-scale comparative studies based on CAT o f Neurol. Psychiat. 56: 1 (1945). mongoloids to determine the frequency of oc Bleuler, E.: Textbook of psychiatry, p. 620 (Amo currence of cerebral calcifications in cases with Press, New York 1976). or without cardiovascular anomalies or history Brink, M. and Grundlingh, E.M.: Performance of persons with Down’s syndrome on two projective of acute anoxia. techniques. Am. J. ment. Defic. 81: 265-270 The reliability of the prognostic value of (1976). brain stem calcification in Down’s syndrome Brooks, D.N.; Wooley, H., and Kanjilal, G.C.: Hearing requires — of course — further large-scale re loss and middle ear disorders in patients with search screening of mongoloid subjects on CAT, Down’s syndrome (mongolism). J. ment. Defic. Res. 16: 21-27 (1972). regarding the assumed clinical-neuroradiological



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Received: July 8, 1978 Accepted: July 12, 1978 Prof. Irene Jakab, University of Pittsburgh, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15261 (USA)


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Basal ganglia calcification in schizophrenia.

Rapid postanoxic calcification of the basal ganglia.

Cooccurrence of Multiple Sclerosis and Idiopathic Basal Ganglia Calcification.

Familial idiopathic basal ganglia calcification (Fahr`s disease).

Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder.

Basal ganglia calcification as a late radiation effect.

Effect of basal ganglia calcification on its glucose metabolism and dopaminergic function in idiopathic hypoparathyroidism.

SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia.

Asymptomatic moyamoya syndrome, atlantoaxial subluxation and basal ganglia calcification in a child with Down syndrome.

Neuroleptic malignant syndrome-like state in a patient with Down syndrome and basal ganglia calcification.

Quetiapine responsive catatonia in an autistic patient with comorbid bipolar disorder and idiopathic basal ganglia calcification.

Paroxysmal kinesigenic dyskinesia in pseudohypoparathyroidism: is basal ganglia calcification a necessary finding?

PDGF, pericytes and the pathogenesis of idiopathic basal ganglia calcification (IBGC).

Genetic screening and functional characterization of PDGFRB mutations associated with basal ganglia calcification of unknown etiology.

Basal ganglia calcification in a patient with beta-propeller protein-associated neurodegeneration.

Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification in Japan.

A diagnosis of idiopathic basal ganglia calcification in an 82-year-old man.

Developmental Venous Anomaly With Asymmetrical Basal Ganglia Calcification: Two Case Reports and Review of the Literature.

Mutation Analysis of SLC20A2 and SPP2 as Candidate Genes for Familial Idiopathic Basal Ganglia Calcification.

Neurological disorders in 166 patients with basal ganglia calcification: a statistical evaluation.

Acute Psychosis Associated with Subcortical Stroke: Comparison between Basal Ganglia and Mid-Brain Lesions.

Idiopathic basal ganglia calcification-associated PDGFRB mutations impair the receptor signalling.

Idiopathic Basal Ganglia Calcification Presented with Progressive Supranuclear Palsy-like Features.

Pseudohypoparathyroidism with basal ganglia calcification: A case report of rare cause of reversible parkinsonism.