J7ournal of Neurology, Neurosurgery, and Psychiatry 1993;56:85-93 85

Severe psychiatric disturbance and abnormalities J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.1.85 on 1 January 1993. Downloaded from of the corpus callosum: review and case series

Anthony S David, Alisa Wacharasindhu, W Alwyn Lishman

Abstract palate), although other ocular and spinal The association between developmental abnormalities may occur.6 The associated defects of the corpus callosum and major brain anomalies which have been reported psychiatric disturbance is discussed with include interhemispheric cysts with hydro- a review of published cases. Seven new cephalus (Dandy-Walker malformation), lipo- cases are presented, of which four had mas of the CC or interhemispheric fissure, clear psychotic symptoms, two receiving a invariably associated with partial agenesis, diagnosis of schizophrenia. Of the absence of the inferior cerebellar vermis, and remainder, one had a developmental dis- disorders of neuronal migration."2 The cingu- order affecting social interaction and late gyrus is invariably abnormal and limbic speech which could be classed as Asper- structures may also be affected. ger's syndrome, one had a personality The main function of the CC is inter- disorder with depressive and conversion hemispheric integration: connecting corre- symptoms, and the last was an adolescent sponding regions of the cerebral cortex in the boy with severe behavioural problems. two hemispheres. Crudely, it serves as a The difficulties in determining the precise conduit for transfer of sensory informa- relevance of the callosal anomalies to tion,'3-15 although the precise nature of the these clinical manifestations are discussed information transferred and its overall influ- especially since the prevalence of such ence on the activity of the hemispheres is a anomalies in the population is uncertain. topic of continued research and speculation.'6 It has been noted repeatedly that in agenesis of (y Neurol Neurosurg Psychiatry 1993;56:85-93) the CC there is an absence of most aspects of the disconnection symptoms which affect sub- jects who have had surgical separation of The corpus callosum (CC) contains the largest the commissures-the "split-brain opera- nerve fibre tract in the human brain, connect- tion"." 1 This has been attributed to the ing the cerebral hemispheres with one another. presence of alternative pathways connecting It is estimated to contain nearly 200 million the hemispheres such as the anterior com- fibres. The CC together with the anterior and missure, which is frequently intact despite hippocampal commissures form the forebrain callosal agenesis, or subcortical channels. commissures. The tract develops intimately in Other compensatory mechanisms may also http://jnnp.bmj.com/ association with the fornix, hippocampal com- play a part such as the duplication of those missure, hippocampal formation, septum pel- specialised functions which are usually dis- lucidum and cingulate cortex, beginning to tributed asymmetrically between the hemi- form shortly after the anterior commissure. spheres, such as speech. Nevertheless, some Details of the anatomy and embryology of failures of interhemispheric communication the CC have been well described.'' Abnormal have been noted such as reduced transfer of

morphologies of the CC can be classified into maze learning from one hand to another,'9 on September 29, 2021 by guest. Protected copyright. acquired and congenital defects. Acquired impaired matching of visual patterns between changes can result from trauma, tumours, the right and left visual fields20 and reduced Department of hydrocephalus, vascular accidents and white transfer of incongruent word stimuli in a Psychological matter diseases.' Complete agenesis is a rare colour naming task,2' (but see22). Medicine, Institute of developmental anomaly of unknown cause and The prevalence of callosal agenesis is diffi- Psychiatry and King's College Hospital, is associated with a wide variety of genetic cult to quantify. Widely varying estimates in the London, UK defects, in particular trisomies of chromo- literature, ranging from 0 004% to 2-64%, A S David somes, 8, 13 and 18.67 Agenesis has also been reflect the different study populations (tables 1 A Wacharasindhu considered a marker of intrauterine metabolic and 2). Thus paediatric neurology services will Section of upsets such as and may Neuropsychiatry, hyperglycinaemia,8 give higher rates than necropsy studies of Institute of Psychiatry, result from insults such as intrauterine infec- unselected members of the population. Sim- London, UK tions and exposure to toxins.3 - The partial ilarly, the rates of associated abnormalities and W A Iishman forms of agenesis usually affect the posterior clinical problems reflect the setting in which Correspondence to: and are to reflect the action cases Dr David, Department of portions presumed are evaluated. All that can be stated is Psychological Medicine, of pathogenic influences occurring after the that certain presentations, namely learning King's College Hospital, initial of the that and are com- Denmark Hill, London SE5 development commissures, is, disability epilepsy rather 9RS, UK after the sixteenth week of gestation. mon,3 17 30 the latter usually estimated at Received 18 December 1991 Agenesis is frequently accompanied by other around 40%. Despite most cases coming to and in revised form defects. These encompass com- to a 3 April 1992. developmental light because of the need investigate Accepted 13 April 1992 mon midline abnormalities (for example, cleft manifest neurological syndrome, many series 86 David, Wacharasindhu, Lishman

Table 1 Proportion (%) of individuals with callosal agenesis from necropsy and invasive invasive studies such as air encephalog- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.1.85 on 1 January 1993. Downloaded from encephalography than raphy (AEG), we would anticipate a increase in Authors Proportion (%) Setting the identification of relatively symptom-free Carpenter and 7/3770 (0 2%) Paediatric cases. Druckniller (1953)23 A male preponderance of cases has been Thierffry et al, (1958)24 8/1349 (0-6%) Paediatric claimed especially in developmentally disabled Gross and Hoff groups6 though some large series have failed to (1959)25 12/455 (2-64%) Severely mentally retarded institutionalised confirm this.3 12 Grogono (1968)26 50/6450 (0 7%) Another related problem is case definition. 1/19000 (0 0053%) - Paediatric - Necropsy series (unselected) Surveys differ as to whether they accept partia! Courville (1950)2' 2/40000 (0 005%) - Necropsy series (unselected) agenesis as "cases". Again, this issue is liable to cited in 1/20074 (0.005%) WHO study Myrianthopoulos (1987)28 - Czechoslovakia: case had multiple result in differences between early and late congenital abnormalities studies since "focal attenuation" is especially 1/24700 (0.004%) - Mexico City: stillbirth 3/40100 (0.0075%) NCPP (Collaborative Perinatal likely to be identified using modern neuroim- Project) aging techniques, in particular MRI. McLeod - 1 child with multiple abnormalities and 2 cases detected during 7 year et al,5 report that as many as 112/450 (24X8%) follow up of their patients who were scanned had sig- nificant attenuations, defined as a 50% or greater thinning of the CC. Table 2 Proportion of individuals with callosal agenesis This paper considers the association from CT and MRI scanning between developmental abnormalities of the CC and severe psychiatric disturbances. Authors Proportion (%) Setting McLeod (1987)'5 10/450 (2 22%) - 2 complete agenesis Neurology Methods - 5 partial agenesis A review of the literature based upon Index - 3 callosal cysts Aicardi et al Medicus and review articles published since (1987)3 3/4097 (0 073%) Paediatric neurology the 1969 edition of the Handbook of Neurology Swayze et al (1990)29 8/7240 (0-11%) Adult neuroradiology was carried out. Four cases of schizophrenia, - 5 agenesis one of an atypical psychosis and two in whom - 3 lipoma significant depression is mentioned, have been reported to date. Four out of the seven were female. The cases are summarised in table 3. In include a number of "asymptomatic" cases. addition, Njiokiktjien,7 mentions 4 children in Slager et al3' collected 23 asymptomatic cases his personal series with behavioural distur- from 170 reviewed in the literature (13-5%), bances leading to psychiatric care and men- and a recent survey from a children's hospital tions one in whom there was a "temporary reported 23/105 (21%) such individuals.12 psychosis". Of the cases in table 3 described in Nowadays, most cases are identified from CT, detail, at least 4 could be regarded as having MRI brain scans or ultrasonography in preg- normal or near normal intelligence and none nancy. Since the "threshold" for carrying out had epilepsy, although Lehmann and Lampe's these non-invasive investigations is much lower second case had paroxysmal activity in her http://jnnp.bmj.com/

Table 3 Summary ofpublished reports on psychiatric patients with callosal abnormalities Age Age of Psycho- Epilepsy Authors (years) Sex onset Clinicalfeatures Diagnosis metry IEEG CT/MRI scan Lehmann and Lampe (1970)'9 Case 1 60 F 47 Recurrent Depression VIQ 88 Normal complete

episodes PIQ 90 agenesis on September 29, 2021 by guest. Protected copyright. (AEG) Case 2 50 F 49 Insomnia Depression VIQ 85 Paroxysmal h complete Suicidal PIQ 83 both temporal agenesis Family history regions (AEG) MacPherson 18 M ? Midline Admitted with ? ? Lipoma of CC et al (1987)32 facial defects psychosis Calcification of L eye enucleated falx Lewis et al 55 M 30 Paranoia Schizophrenia VIQ 75 Normal Agenesis (1988)33 Hallucinations PIQ 93 L fronto- Violent and suicidal temporal cyst behaviour Treatment responsive Velek et al 24 F 24 Persecution Schizophrenia VIQ 103 Normal Subtotal (1988)34 Passivity (acute) PIQ 97 agenesis Auditory R > L hallucination Partial response to treatment Swayze et al (1990)29 Case 1 39 F 33 Hallucinations Schizophrenia "border- Normal "Nearly since childhood line" complete Delusions agenesis" Refractory to treatment Case 2 33 F 24 Persecution Schizophrenia College Normal Lipoma Auditory student replacing hallucination CC Refractory to treatment Severe psychiatric disturbance and abnormalities of the corpus callosum: review and case series 87

EEG. The two cases described by Swayze et diagnosis of chronic paranoid schizophrenia J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.1.85 on 1 January 1993. Downloaded from al29 were poorly responsive to treatment while was made. the cases of Lewis et al33 and Velek et al34 did Neuropsychological investigations testing respond to some extent. The symptom profiles with the WAIS-R at age 30 showed a full scale of these cases do not point to any clear IQ of 72, a fall of 32 IQ points compared with distinguishing characteristics which clinicians his score at age 21. Tachistoscopic testing could identify. showed normal cross-field matching of colours and simple line drawings. Detailed assessment Case series was repeated when his mental state improved A register of abnormal CT scans from the but the IQ remained unchanged. He had Maudsley hospital radiology unit was used to scored poorly on the similarities sub-test indi- trace all psychiatric cases with agenesis or cating poor ability to form abstract concepts. partial agenesis of the CC over a 7 year period Memory testing, using the Weschler logical (see table 4). Six were referred to a specialist memory test, paired associate learning, Rey- neuropsychiatric unit at the Maudsley hospital. Osterrieth and the Benton Visual Retention One of these was investigated for possible test were carried out. The results showed pseudo-seizures when unsuspected callosal overall poor memory especially spatial mem- agenesis was revealed. The seventh case was ory. The performance on the Trail MakingTest seen in the children's department of the was also poor while performance on word Maudsley hospital. Only one was female. fluency showed minor impairment. Perform- ance on the Wisconsin Card Sort test was Case 1 A 35 year old man. Childhood and abnormal with a high number ofpreserverative development were unremarkable. He attended errors, suggesting frontal lobe impairment. normal schooling and left at the age of 15 with CT showed a lipoma in the posterior aspect no qualifications but was numerate and liter- of the corpus callosums (figure 1). An EEG ate. He held casual jobs between the age of 15 was performed twice at age 30; the first showed and 16 but has not worked subsequently. There no abnormalities while the second showed was no clear family history of psychiatric some minor dysfunction (see table 4). disorder although his mother had multiple sclerosis and was said to suffer from mood Case 2 A 29 year old man was bom six weeks swings. prematurely, experienced lack of oxygen at Psychiatric history started at age 17 when he birth and was of low birth weight. Motor was diagnosed as having "an adolescent development was slow: at twelve months he identity crisis", and was treated with out- had to be propped up to sit and was noticed by patient psychotherapy. The first psychiatric his mother to sit with his legs in a scissored admission was at age 19, when the patient was position. The diagnosis of cerebral palsy was noted to be vague, perplexed, hallucinated and made. He could not crawl until aged five, and was treated with phenothiazines. There was a had surgical operations on leg tendons at the further admission in the same year when he ages of 10 and 12 enabling him to walk with was depressed and deluded and possibly crutches. The patient had episodes of febrile thought disordered. Antipsychotic medication convulsions between the ages of 2 and 4 which and ECT were given with good response. were characterised by generalised twitching. There were 3 further admissions yearly due to He attended schools for the physically handi- http://jnnp.bmj.com/ similar problems. He was noted early on to capped. Academically he was hampered by have a destructive propensity. "severe spatial problems" and he was poor at At the age of 25 he had his sixth admission maths and woodwork. when he was compulsorily detained following Epileptic fits began at age eight. He was an assault on a police officer. Since then he has treated with a combination of phenytoin and required almost continuous inpatient care and phenobarbitone and achieved relatively good

has received various forms of antipsychotic control. During adolescence he began to on September 29, 2021 by guest. Protected copyright. medication and further courses of ECT. The experience more complex seizures. These introduction of carbamazepine showed a mar- began when he saw a vision of the "judgement ginal effect on his outbursts of aggression. The day" and occasionally, the "whole world's mental state has fluctuated although thought grave opening". This was associated with the disorder, persecutory delusions and bizarre thought that he was dying and a sense of losing hypochondriacal delusions have all been prom- contact with reality. The fits began with the inent. At the age of 30 he was transferred to a patient calling out followed by twitching of the secure unit because of serious aggression left side of the mouth, then eyelids, and finally towards staff. The mental state examination at generalised jerking of all four limbs. He would this time showed disordered thinking with also shout quotations from the Bible or plead many shifting persecutory themes, for exam- to God to take him. These occurred approx- ple, "People make me do things I don't want imately monthly. to... to kill... I'm going... what's this Psychiatric illness began in adolescence. At backtracking ... TV and radio". He had ideas 13 he was noted to be anxious and having of persecution and bizarre somatic delusions difficulty "distinguishing reality and unreal- such as, "All the bones in my hands are ity". At 15, he was admitted to hospital crushed and broken". His attention and con- experiencing auditory hallucinations, and pre- centration were poor. He is now undergoing occupied with religious and sexual ideas. He continued treatment and rehabilitation but was treated with a combination of antidepres- remains symptomatic and a danger to others. A sants and neuroleptics. When assessed at age 88 David, Wacharasindhu, Lishman

25 he believed that he had been chosen by God left disorientation or finger agnosia. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.1.85 on 1 January 1993. Downloaded from and described the experience of God speaking The diagnoses were: cerebral palsy, complex to him. partial seizures with secondary generalisation Physical examination showed a divergent and chronic schizophrenia. squint and a defect in his iris. There was facial CT scan at age 25 showed agenesis of the asymmetry and he had marked spastic diplegia corpus callosum and left hemiatrophy affecting with tendon reflexes increased bilaterally. principally the anterior hemisphere where Mental state examination at age 29 revealed an there was a CSF-containing cyst within the left anxious and irritable man, occasionally over- frontal lobe. Adjacent to this there was some familiar. He showed some thought disorder atrophy of the sulci extending into the insular and was incoherent at times with circum- region. In addition there was relative dilatation stantial and tangential speech. There was of the posterior horns and bodies of the marked interpenetration of themes reflecting a ventricles adjacent to the upward extension of preoccupation with religious and grandiose the widened third ventricle. The EEG was delusions. He reported no auditory and visual diffusely abnormal with sharp waves over both hallucination apart from those at the time of temporal regions particularly on the right. seizures. Case 3 A 41 year old man. He was a twin, Cognitive testing showed good orientation born 3 weeks premature after a forceps delivery but some difficulty with concentration. He was and needed oxygen for one week. The birth unable to do serial 7s but could perform both was also complicated by Rhesus incompatibil- serial 3s and naming the months of the year ity. His co-twin died at one week. Macroceph- backward slowly and accurately. Digit span aly was noted during early childhood. His was 5 forwards and 4 backwards. He could parents reported that he had temper tantrums name 16 T-words and 3 four-legged animals on and breath holding attacks, but no convulsions. a test of verbal fluency. His writing was poorly He was said to be a happy child with friends in formed and done with great difficulty. He was the local village. He left school at age 17 with 5 unable to write a sentence of his own creation. CSEs and then worked as a clerk for 6 months. His verbal memory was unimpaired but there He began basic training for the armed forces was some impairment of visual memory with but failed and left after 2 months. Since then evidence of constructional apraxia. There was he has had several unskilled jobs, each lasting some evidence of concrete thinking on word short periods, followed by long periods of association and proverbs. Comprehension was unemployment due to psychiatric illness. normal. There was no nominal aphasia, right- There is no family history of psychiatric illness or epilepsy. From age 18 he has experienced brief, bifrontal headaches of moderate severity. In addition he has had a total of 6 seizures. These are stereotyped, starting with an abrupt loss of consciousness, followed by tonic-clonic movements. Psychiatric history started at age 24 with alternating periods of "up" and "down" mood swings. "Up" swings manifest as restless, http://jnnp.bmj.com/ overactive, irritable and noisy behaviour with pressure of speech. "Down" swings manifest as feeling tired, listless, low in mood, tearful, anhedonic and retarded. He has had numerous hospital admissions due to mood disorder and epilepsy and has been treated with a variety of

anticonvulsants, antidepressants, mood stabi- on September 29, 2021 by guest. Protected copyright. lisers, antipsychotics, and ECT. Mental state examination at age 39 revealed tearfulness, low mood and early morning wakening. Speech was odd, pedantic, circum- locutory and metaphorical, but there was no clear evidence of thought disorder and he showed neither delusions nor hallucinations. Cognitive testing was reported to show no abnormalities. At that time his epilepsy was well controlled. The diagnoses were, manic depressive psy- chosis, epilepsy and tension headaches. Also, in view of some obsessional features, social avoidance, and his use of language, the possi- bility of the diagnosis of Asperger's syndrome (or "schizoid personality") was suggested but felt to be inconsistent with his sociability as a child. Figure I Case I CT axial brain scan showing lipoma immediately to the right of the Psychometric testing at age 39 revealed a midline within the posterior aspect of the corpus callosum. WAIS-R full scale IQ of 86. Verbal score was Severe psychiatric disturbance and abnormalities of the corpus callosum: review and case series 89

the same as previous testing at age 26 but ships. There is no history of drug or alcohol J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.1.85 on 1 January 1993. Downloaded from performance showed a significant fall of 20 abuse. The only family history of psychiatric points. Sub-test scores showed that he per- disorder is alcohol dependence in the patient's formed well on tasks involving rote learning mother. and poorly on tasks involving abstract reason- Psychiatric history started at age 24 follow- ing. ing the end of a long homosexual relationship. CT and MRI scans showed agenesis of the He started attending a monastery and on one anterior part of the corpus callosum (fig 2). He occasion while he was praying he heard "the had a series of EEGs which showed bursts of voice of god" talking close to him saying generalised rhythmic delta activity and some "Heaven". He felt from that point that he had evidence of left anterior quadrant dysfunc- been chosen as a disciple of Christ. He also tion. described waking one morning with a terrify- ing sensation of strangulation and the feeling of Case 4 A 33 year old man. Birth was normal an evil presence. He had a strange feeling that but he showed slow development, only learn- he was "meant to commit suicide". He rushed ing to walk at the age of 3. There were also out of bed, looked in the mirror and saw a face some behavioural disturbances. At age 5 he set which seemed not to belong to him. He fire to an armchair and at other times he described hearing loud noises which he felt attacked neighbours. He was described as represented good and evil coming into conflict. "slow" at school and was advised to have He also described second person auditory special education. He had no friends and was hallucinations and symptoms of acute deper- constantly bullied and "in trouble". He left at sonalisation. age 15 with no qualifications, and had several Mental state examination during his admis- different menial jobs; the longest period of sion revealed some mannerisms: repeated rais- employment was three and a half years. All his ing his eyebrows, flapping his hands around. jobs terminated in him being sacked, mostly He showed a combination of fear and anxiety due to incompetence. He was involved in but occasionally seemed to be unconcerned several heterosexual and homosexual relation- and confused. Grandiose religious delusions were elicited as well as hallucinations of "voi- ces", and visual hallucinations of seeing bright lights flashing in the sky and hallucinations of the smell of oranges. Cognitive testing showed good orientation in time and place but poor concentration tested by digit span and serial 7s. He showed good immediate memory but poor recent memory when tested by using name and address. Within a week of admission his symptoms had improved completely with no medication except occasional anxiolytics. The diagnosis was of an acute anxiety state although schizophreniform psychosis must be considered. He was felt to have a dependent

personality, with difficulty in relating to other http://jnnp.bmj.com/ people. Follow up over 2 years showed only discrete episodes of acute anxiety occurring once every 3 to 4 weeks, lasting an hour or so. These were precipitated by interpersonal stres- ses or vivid images in magazines or on tele- vision, and responded to behaviour therapy. Psychometric test gave a full scale IQ of 78. The score of Mill Hill was 82 and Progressive on September 29, 2021 by guest. Protected copyright. matrices was 92. Neuropsychological tests showed some incoordination involving fine motor control and opposing hand movements. Somato-sensory evoked potentials showed no significant abnormality or delay between right and left impulses. CT scan showed partial agenesis of the anterior part of the corpus callosum. EEG which was done twice, showed no significant abnormality (table 4). Case 5 A 22 year old man. Birth was normal but he was noted to be slow to develop in comparison with his sister. At school at the age of five years he was reported by the teacher to be an odd and lonely boy, who was teased frequently. He finished schooling with 2 CSEs. work he showed poor initiative Figure 2 Case 3 Coronal MRI scan showing dysgenesis of the anterior part of the During training corpus callosum and deformity of the frontal horns. and failed because of poor concentration, 90 David, Wacharasindhu, Lishman

turning up in the wrong places and inability to right eye was poor - 6/24 (left, 6/6). There was J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.1.85 on 1 January 1993. Downloaded from communicate. He was described as a loner a short metacarpal, a long thin upper lip and who had poor social skills, drive and motiva- long philtrum. Tone on his left side was mildly tion. He was in good physical health. increased in a cogwheel pattern resulting in Family history revealed that his father had poor coordination. Power and sensation were been a quiet and self-contained man but normal, and reflexes normal and symmet- "rather aloof'. Maternal grandfather had a rical. phobic disorder. Mental state examination revealed a cooper- At the age of 6 he was referred to a Child ative boy with normal speech. He was sociable Guidance Clinic. He showed anxiety about and smiled occasionally. Short and long term school, self-absorption, wandering, an "odd" memory appeared normal but writing and manner, "in a daydream most of the time". He copying skills were poor. He played imag- was solitary and enjoyed being on his own with inatively. imaginary friends. At the age of 10 he devel- He has had severe behavioural problems. At oped obsessional and manneristic symptoms. times he appeared vacant and was destructive His talk was difficult to follow and he had at home. His conduct had become progres- paranoid ideas about school as well as hypo- sively more disruptive to family life. He would chondriacal preoccupations. The diagnosis of not join in family activities such as games and schizoid personality was made and he was meals and set himself apart from the others. In treated with social skills training. addition he destroyed his belongings including At age 18 he was referred for psychiatric favourite toys. Feeding had been messy, and he treatment and has attended a day hospital had the habit of eating anything he could get since then. He was noted to be withdrawn, hold of, such as soil, rubbish, and grass. He mumbling, smiling to himself, picking up soiled and wet himself deliberately on occa- litter, bumping into walls, trees and fences, and sion. wandering. Diagnosis was of a non-progressive congeni- Mental state examination showed some odd- tal neurological lesion. His behaviour prob- ities of manner and social interaction. Talk was lems were treated by standard behavioural hesitant and hard to understand at times techniques for 8 weeks during which time there because of disjointedness and mumbling. Writ- was some improvement. ten productions were similarly disordered. Psychological testing revealed a full scale IQ There was no evidence of abnormal mood, of 88 (WISC-R). He scored below his age level delusions or hallucinations. He was competent on the Oseretsky motor test35 and had diffi- in all aspects of self-care. culty with fine motor movements and biman- The diagnosis was uncertain. Asperger's ual co-ordination. syndrome or simple schizophrenia were con- CT scan showed partial agenesis of the sidered. He was treated with antipsychotic corpus callosum with a moderately large medication, attended day hospital with occu- lipoma. The caudate nuclei were small and pational therapy, individual and group activ- poorly defined. There was also dilation of both ities. the temporal and posterior horns of the third Neuropsychological testing showed a full ventricle. EEG was normal. No chromosomal scale IQ of 85 by the WAIS-R. This was felt to abnormalities (including fragile X) were

be lower than expected from his reading ability detected. http://jnnp.bmj.com/ and educational history. Memory for both verbal and visual-spatial material was also Case 7 A 31 year old woman. She had found to be poorer than expected. undergone special education because of read- CT scan at age 18 showed a lipoma in the ing problems. Since the age of 12 she reported splenium of the corpus callosum. EEG showed "'epileptic attacks" and periods of altered an excess of slow activity, more over the left consciousness. Psychiatric assessment began at side but there were neither specific abnor- age 29 when she was admitted because of malities nor evidence of epileptogenic activ- depression and suicidal thoughts, some on September 29, 2021 by guest. Protected copyright. ity. months after her fiance had died. She des- cribed insomnia, early morning wakening, Case 6 A 12 year old boy. He was born by anorexia, poor concentration and low energy. normal delivery. He was fostered at the age of Mental state examination revealed an two and had several different foster homes. He expressionless woman who showed little evi- attended school regularly though he required dence of depression, but at times joked inap- extra tuition. His mother was emotionally propriately and made fatuous remarks. There disturbed when he was taken into care. She was no evidence of delusions or hallucinations. had been an inpatient in a psychiatric hospital Cognitive testing revealed good orientation in for a few years and had a diagnosis of possible time, place and person, normal memory and Huntington's disease. The maternal grand- general knowledge, but poor concentration. mother died from a similar disorder. The The diagnosis was of a personality disorder patient had two sibs who were well but also in in that she had a long history of histrionic and care. attention seeking behaviour. "Seizures" were At age eight he was referred to a child observed in the absence of EEG abnormality. psychiatrist. On physical examination he was She had no medication during admission, and just below average weight and height. There finally discharged herself against advice. was macrocephaly (head circumference The patient had neuropsychological testing 58.5cms above the 99th centile). Vision in his at age 28 (see table 4). She was mildly Severe psychiatric disturbance and abnormalities of the corpus callosum: review and case series 91

Table 4 Clinical details ofpsychiatric patients with callosal abnormalities J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.1.85 on 1 January 1993. Downloaded from Age Perinatal Case (years) Sex /development Clinical features Diagnosis Psychometry EpilepsylEEG CT scan 1 35 F Long labour Persecutory and Schizophrenia VIQ 74 No seizures. Lipoma of bizarre delusions PIQ 73 Excess e, 1 a splenium Hallucinations right temporo Violent behaviour occipital 2 29 M Premature Early onset Schizophrenia "Mild Complex partial Agenesis. Hallucinations mental seizures. L anterior and delusions Cerebral palsy handicap" Diffuse hemiatrophy abnormality L frontal Cognitive deficits cyst 3 41 M Premature Mood swings Manic depressive VIQ 91 Generalised Partial Odd speech psychosis PIQ 81 epilepsy. agenesis Macrocephaly Tension headaches ? Lanterior (anterior) Fits as teenager dysfunction 4 33 M "Slow" at Early onset ?Anxiety state VIQ 86 Normal Partial school Prominent anxiety ?Schizophreniform PIQ 71 agenesis Psychotic psychosis (anterior) symptoms 5 22 M "Slow Anxiety age 6 Asperger's VIQ 91 Excess slow Lipoma of developer" Mannerisms syndrome PIQ 79 activity splenium Poor social Paranoid ideas ?schizophrenia L > R relationships 6 12 M Minor Behavioural ?Juvenile WISC- Normal Partial physical problems, pica Huntington's VIQ 81 agenesis with anomalies soiling. Family Disease PIQ 99 large lipoma Macrocephaly history of HD.* Conduct disorder 7 31 F Reading Pseudo-seizures Personality disorder VIQ 87 "Within normal Agenesis impairment Depression Conversion PIQ 106 limits" Parasuicide symptoms * HD = Huntington's Disease

impaired on tests ofverbal memory, immediate line" scores (IQ between 80 and 90)- spatial recall and memory spans; new learning although evidence for deterioration in IQ, of verbal and non-verbal materials and long- presumably as a consequence ofpsychosis, was term spatial memory were intact. She was also present in cases 1 and 3. Similarly, cohorts in impaired in reading with a pattern consistent which psychosis and epilepsy coexist, may with surface dyslexia (L Goldstein, personal include more cases with abnormal callosa. The communication). same applies to cerebral palsy and patients CT scan showed agenesis of the corpus with other obvious neurological disorders. callosum. The lateral ventricles were widely The cases in table 4 show that the psychiat- separated by the continuous upward expansion ric syndromes associated with callosal abnor- of the third ventricle between them. EEG was malities are heterogeneous. Case 4 had a highly within normal limits. atypical disorder characterised by extensive anxiety and psychotic symptoms. Another (case 3), had a classical bipolar affective illness Discussion with some features of disordered social inter- Schizophrenia was the most frequent syn- action and idiosyncratic use of language. The

drome reported in the new cases and those patient described by Lewis et al,33 although http://jnnp.bmj.com/ reviewed. However, we cannot make any defin- diagnosed as suffering from chronic schizo- itive statements about the relative risk of phrenia, also had experienced marked affective schizophrenia in callosal agenesis. Firstly, esti- symptoms. Unlike case 3, however, he had a mates of the prevalence of the condition in the positive family history of manic depression. general population differ widely (tables 1 and Case 5 had a more striking, pervasive disorder 2). Secondly, the reported cases do not come of social development than case 3. This would from a defined population so it is impossible to fit into the rubric of Asperger's syndrome36 or know the "denominator". Even Swayze et al,29 schizoid personality disorder.37This syndrome on September 29, 2021 by guest. Protected copyright. who attempted to give some idea of the has been described in association with right number of callosal abnormalities seen at the hemisphere deficits38 but neurological anoma- same hospital, were not surveying a defined lies involving the CC could also have a population and did not take into account the potential aetiological role. Both these cases had selection factors for MRI scanning in general. significant reductions in performance vs verbal One important criterion which will exert a IQ, which, while not unique in our series (see major influence on the rates of callosal abnor- case 4), are somewhat unusual for "uncompli- malities reported is the exclusion from scan- cated" agenesis.'7This may relate to functional ning of patients with IQ less than 80.29 impairment of the right hemisphere. The 7 new cases were all tertiary referrals to The finding of agenesis in case 7 who was a specialist neuropsychiatric unit and so our finally diagnosed as having a personality dis- experience cannot be considered representa- order with depressive and conversion symp- tive. Again, no meaningful calculation of rates toms, may have been a coincidence. However, can be made only to mention that agenesis is a it is conceivable that the patient's specific rare accompaniment of psychosis. However, learning disability, possibly a direct conse- when criteria for normal intellectual function- quence of callosal agenesis could have contrib- ing are relaxed, more cases are to be antici- uted to her poor self-esteem through academic pated. Two of our cases had mild mental failure35 setting off a chain of negative experi- impairment (IQ < 80) and three had "border- ences. Other cases in whom early devel- 92 David, Wacharasindhu, Lishman

opmental problems were noted, ma-y also have develop in the absence of a functioning CC, suffered from distorted social and family rela- may be especially susceptible to misconnec- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.1.85 on 1 January 1993. Downloaded from tionships as a result. This may have influenced tion, a proposed mechanism for producing the onset, course, and form of the eventual psychotic symptoms.6' 62 Finally, the asso- psychiatric syndrome, interacting with the ciated cerebral anomalies such as those involv- "endogenous" brain abnormality. It is not ing limbic structures, which occur in tandem possible to state with any confidence the with callosal agenesis, could be of specific potential influence of CC abnormalities on aetiological importance for psychiatric illnes- non-psychotic psychiatric disorders since ses. In any event, further studies of psychiatric patients so diagnosed rarely undergo compre- disorders in patients with callosal anomalies hensive neurological evaluation. should increase our understanding of the Are abnormalities of the CC relevant in the cerebral basis of many psychiatric conditions. understanding of severe psychiatric distur- We thank Drs J Bird, P Taylor, P Fenwick and E Taylor for their bances? Such disturbances, particularly schizo- permission to report on their patients, and Dr Laura Goldstein phrenia, have been shown to be associated with who carried out some of the neuropsychological assessments. a number of disparate abnormalities of brain structure.39-4' Deviant brain development, 1 Rakic P, Yakovlev PI. Development of the corpus callosum pre-dating the onset ofgross disorder is attract- and cavum septi in man. J Comp Neurol 1986;132: 45-72. ing the attention of those who favour a 2 Loeser JD, Alvord EC. Agenesis of the corpus callosum. 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