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Initial ‘schizophrenia-like’ psychosis in Pick's disease: case study with neuroimaging and neuropathology, and implications for frontotemporal dysfunction in schizophrenia
SCHIZOPHRENIA RESEARCH ELSEVIER
Schizophrenia Research 18 (1995) 79 82
Short communications
Initial 'schizophrenia-like' psychosis in Pick's disease: case study with neuroimaging and neuropathology, and implications for frontotemporal dysfunction in schizophrenia John L. Waddington "'*, Hanafy A. Youssef b, Michael A. Farrell c, James Toland c a Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland h St. Davnet's Hospital, Monaghan, Ireland c Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland
Received 29 January 1995; accepted 19 June 1995
Abstract
'Schizophrenia-like' psychosis has not been reported previously as a prodrome of Pick's disease, a dementia of frontotemporal pathology. A woman having a consistent clinical diagnosis of typical schizophrenia who developed increasing affectivity and cognitive deficits was examined by computed tomography and brain biopsy. This presentation was found to be associated with left frontotemporal atrophy, left sylvian fissure abnormalities and enlargement of the anterior and temporal horns of the left lateral ventricle. On biopsy, all the neuropathological hallmarks of Pick's disease were present. Unusually, some specific aspect of Pick's disease in this patient appears initially to have disturbed brain function in a manner reproducing some fundamental aspect(s) of schizophrenia itself; left frontotemporal dysfunction would appear to be a relevant common denominator.
Keywords: 'Schizophrenia-like' psychosis; Pick's disease; Frontotemporal dysfunction; (Schizophrenia)
Introduction The application of contemporary neuroimaging, neuropsychological and neuropathologic techniques, has elaborated the concept of schizophrenia as a putative disorder of dysfunction in (left) frontotemporal and corticostriatopallidothalamic systems that appears to derive, at least in part, from early neurodevelopmental disturbance(s) (Weinberger et al., 1992; Waddington, 1993a,b). However, multiple aspects of the disorder remain very poorly understood, and study of the * Corresponding author. +353-( 1)-4780625.
Tel:
Elsevier Science B.V. SSDI (1920-9964 ( 95 ) 0 0 0 6 4 - X
+353-(1)-4780200;
fax:
'schizophrenia-like' organic psychoses is recognised as a valuable complementary approach to their clarification (Davison, 1990). We have previously described magnetic resonance imaging (MRI) findings in four patients with a 'schizophrenia-like' psychosis following head injury (O'Callaghan et al., 1988; Buckley et al., 1993), among whom the common denominator was left ventricular abnormalities with a preponderance of left temporal lobe pathology. It would be of considerable interest were similar findings to be demonstrated in instances of 'schizophrenia-like' psychosis among patients with other neurological disorders.
80
J.L. Waddington et al./Schizophrenia Research 18 (1995) 79-82
Pick's disease is a rare form of (pre-senile) dementia characterised neuropathologically by severe but somewhat circumscribed atrophy of the frontal and temporal lobes; in addition to this marked cell loss, there are swollen cortical neurons (achromasic neurons) which usually contain characteristic intracytoplasmic inclusion (Pick) bodies in the absence of the neurofibrillary tangles and senile plaques that are pathognomonic of Alzheimer's disease; these atrophic abnormalities are usually, but not always, symmetrical and there appears to be no specific predilection for either hemisphere. Prodromal signs of impending dementia and ultimately fatal debilities include prominent changes in personality: irritability and aggressiveness, mood disturbances that include incoherent joviality, socially disturbing behaviour and loss of social awareness; however, psychosis has not been reported previously (Rosenberg, 1983; Walton, 1985; Knopman et al., 1989). We describe here a case of biopsy-confirmed Pick's disease that presented initially as a typical 'schizophrenia-like' psychosis and was found subsequently to have circumscribed, predominantly left frontotemporal pathology on computed tomography (CT). Case report. This single woman attended school until the age of 14; she appeared to be a poor scholar, probably because of some deafness. Her social life was active up to the age of 25, after which there was a change in personality; she no longer went to local dances, became shy of men, and read books relating to religion and philosophy. However, she continued to work in a local factory until shortly before psychiatric referral. There was no known family history of psychiatric or neurological disorder. Her first psychiatric presentation and admission to St. Davnet's Hospital was at the age of 51. She was a poor historian who worried and prayed, but gave a history suggestive of auditory hallucinations for two years prior to that admission and had delusions that people at work were talking about her; these had prompted her to leave employment some 1.5 years previously. Two days after her admission she was given a provisional clinical diagnosis of paranoid schizophrenia and treatment with neuroleptics. Subsequently, she admitted hearing voices from God and also showed depres-
sive features. She was discharged on neuroleptic and antidepressant medication. Two years later she was readmitted having walked out of the family home complaining that her brothers and sisters would not let her marry a man whom the 'Holy Spirit' had told her to marry so as to prevent the world being destroyed; she had seen the 'Holy Lady' many times. There were now also some hypomanic features (elation and hyperactivity) with poor memory for past events, and she was again treated with neuroleptics prior to discharge. Her third admission, just over a year later, followed her leaving the family home once again; both her mother and 'Our Lady' had appeared to her. Furthermore, she was agitated, euphoric and talkative, with incoherent speech and memory lapses. There was impulsive behaviour following the prompting of the 'Holy Spirit' in her heart; she freely expressed a series of auditory and visual hallucinations together with inappropriate affect and some paranoid ideation. The clinical diagnosis was schizoaffective disorder and she was discharged once again on neuroleptic medication. Over the subsequent decade she lived with various family members and finally alone. A relative noticed increasing memory disturbances and she was referred for detailed neurological examination. Now aged 65, she had over the past year shown poor concentration and attention, loss of interest in her personal habits, poor hygiene, inappropriate behaviour such as getting up during the night to go shopping, and some urinary incontinence. On examination she was a very cheerful woman, hard of hearing, with sensory dysphasia, echolalia and naming difficulties. Otherwise, cranial nerve, motor, sensory, cardiovascular and respiratory examinations and full biochemical investigations were all normal, as was CSF analysis. Cerebral CT revealed prominent widening of frontal lobe sulci in the area of the interhemispheric fissure, with quite marked enlargement of the anterior and temporal horns of the left lateral ventricle and widening of the left sylvian fissure (Fig. 1); these frontotemporal abnormalities appeared predominantly left sided, but there was also some widening of sulci in the medial aspect of the right frontal lobe and of the right sylvian fissure. Frontal lobe biopsy (left) and neuropathologic examination
J.L. Waddington et al./Schizophrenia Research 18 (1995) 79-82
Fig. 1. Axial CT image at the level of the lateral ventricular system
thereof revealed a preserved cortical laminar pattern but with a moderate degree of astrogliosis in layer I; the remaining cortical layers were unremarkable with neither senile plaques nor neurofibrillary tangles evident, and blood vessels did not contain amyloid. Spongiform degeneration was not present. Numerous neurons were found to contain spherical intracytoplasmic inclusion bodies which were tau-positive with rare neurofilament positivity; these bore a striking resemblance to classical Pick bodies. Immunohistochemistry for glial fibrillary acidic protein revealed dense pancortical astrogliosis with additional subcortical gliosis. The neuropathologic diagnosis was Pick's disease with subpial astrogliosis. In the postoperative period, following biopsy, ventilation perfusion scan indicated multiple pulmonary emboli and the patient was discharged on anticoagulant therapy. On her readmission to St. Davnet's hospital she showed prominent affective changes with incongruity of affect, self-absorbing smile, thought disorganisation with irrelevant and incoherent speech, and cognitive disturbances; aspects of this overall clinical picture were likened to hebephrenic schizophrenia, and symptomatic management of the underlying Pick's disease was attempted with thioridazine and hydergine. Fifteen months following readmission she evidenced a generalised seizure. Over the next four years she became extremely restless and doubly incontinent, with gross cognitive deficits. In the latter stages of her illness increasing disability necessitated full care for all her needs and
81
at the age of 71 she died of respiratory failure. There was no postmortem examination. Discussion. The generally unremarkable early history of this patient followed, in her mid-20s, by a personality change in the direction of asociality, heterophobia and religious preoccupations suggests the emergence of a schizoid/schizotypal state; this appeared to endure over some two decades before the emergence of florid psychotic symptoms and the typicality of the delusions and hallucinations, on such a background, readily accounts for the initial diagnosis of schizophrenia. Over her second and third admissions, during each of which these schizophrenic symptoms re-appeared, the additional emergence of incoherence and inappropriate affect would be consistent with continuing recourse to this diagnosis (American Psychiatric Association, 1987); it is only with the benefit of the 'retrospectoscope' that their emergence together with 'hypomanic' features, impulsive behaviour and memory lapses might be recognised as more typical prodroreal signs of the fundamental neuropathological process. Thereafter, the domination of the clinical picture by 'frontal' disinhibition phenomena (inappropriate affectivity, impulsive behaviour and loquaciousness), dysphasia and echolalia on a background of increasing cognitive impairment, and progressing to profound dementia, convulsions and a terminal near-vegetative state, are entirely typical of the later course of Pick's disease (Rosenberg, 1983; Walton, 1985), as confirmed neuropathologically on biopsy. Given the confidence of the diagnosis of Pick's disease, the initial 'schizophrenia-like' psychosis can be interpreted in at least three ways: Firstly, this psychosis may actually be schizophrenia, in a patient who was unfortunate enough to acquire two independent (though perhaps ultimately interactive) disease processes; however, the temporal relationship between emergence of psychosis and of more typical behavioural prodromes of Pick's disease argues against such a dual eventuality. Secondly, the early changes in personality towards schizoid/schizotypal features might reflect some pre-existing vulnerability to schizophrenia, with elements of the later neurodegenerative changes precipitating initially a 'schizophrenia-like' psychosis in a manner that does not appear to occur among patients with Pick's disease who have no
82
J.L. Waddington et al./Schizophrenia Research 18 (1995) 79-82
such pre-existing vulnerability; however, the relative frequency of schizoid/schizotypal features in the general population would, despite the greater rarity of Pick's disease, predict 'schizophrenia-like' psychosis to be more than an occasional prodrome thereof when we are not aware of such an association having been reported previously. The third interpretation, which we favour, is that some specific aspect of the pathology of Pick's disease in this patient has, early in its course, disturbed brain function in a manner that reproduces some fundamental aspects of the pathophysiology of schizophrenia. In this regard, there is a striking concordance between structural pathology primarily of the left frontal and temporal cortex together with left sylvian fissure abnormality and dilatation of the left anterior and temporal horns of the lateral ventricular system in the present instance, and structural pathology of the (left) temporal lobe and sylvian fissure with associated ventricular abnormalities and frontal lobe dysfunction in schizophrenia (Waddington, 1993a,b). Current perspectives of schizophrenia also indicate corticostriatopallidothalamic dysfunction, and it may be relevant that when the somewhat circumscribed frontotemporal abnormalities of Pick's disease do encompass other brain regions, it is the basal ganglia and thalamus that are affected (Rosenberg, 1983). Furthermore, frontotemporal abnormalities can be evident early in the course of Pick's disease, around the time of early prodromes of the disorder (Knopman et al., 1989). It must therefore be considered whether the yet earlier schizotypal personality changes in the present case might reflect the subtle onset of left frontotemporal dysfunction; these personality changes might endure until some critical threshold of cellular disturbance is exceeded to precipitate 'schizophrenia-like' psychosis prior to those more prominent neurodegenerative changes that result in the more typical symptoms of Pick's disease. This overall interpretation of the present case would be complementary to our recent report that each of a small series of cases of 'schizophrenia-like' psychosis following head injury also showed left temporal or left frontotemporal pathology on MRI (Buckley et al., 1993). In summary, this report emphasises both the
difficulty in excluding (at least initially) specific neurological disease in the differential diagnosis of schizophrenia, and the importance of left frontotemporal dysfunction as a relevant common denominator linking 'schizophrenia-like' psychosis in diverse neurological circumstances to schizophrenia itself.
Acknowledgements These studies were supported by the Health Research Board. Dr. Michael Farrell, Consultant Neuropathologist, Beaumont Hospital, Dublin, is thanked for his advice and for kindly making available his original neuropathological findings in this case.
References American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd edn, revised. American Psychiatric Association, Washington, DC. Buckley, P., Stack, J.P., Madigan, C., O'Callaghan, E., Larkin, C., Remond, O., Ennis, J.T. and Waddington, J.L. (1993) Magnetic resonance imaging of schizophrenia-like psychoses associated with cerebral trauma: clinicopathological correlates. Am. J. Psychiatry 150, 146-148. Davison, K. (1990) Organic schizophrenia-like psychoses. In: M.P.I. Weller (Ed.), Perspectives In Schizophrenia. Libbey, London. Knopman, D.S., Christensen, K.J., Schut, L.J., Harbaugh, R.E., Reeder, T., Ngo, T. and Frey, W. (1989) The spectrum of imaging and neuropsychological findings in Pick's disease. Neurology 39, 362-368. O'Callaghan, E., Larkin, C., Redmond, O.,Stack, J., Ennis, J.T. and Waddington, J.L. (1988) Early-onset schizophrenia after teenage head injury: a case report with magnetic resonance imaging. Br. J. Psychiatry 153, 394-396. Rosenberg, R.N. (1983) The Clinical Neurosciences: Neuropathology. Churchill Livingstone, New York. Waddington, J.L. (1993a) Schizophrenia: developmental neuroscience and pathobiology. Lancet 341,531-536. Waddington, J.L. (1993b) Neurodynamics of abnormalities in cerebral metabolism and structure in schizophrenia. Schizophr. Bull. 19, 55-69. Walton, J. (1985) Brain's Diseases of the Nervous System. Oxford University Press, Oxford. Weinberger, D.R., Berman, K.F., Suddath, R. and Torrey, E.F. (1992) Evidence for dysfunction of a prefrontal-limbic network in schizophrenia: an MRI and rCBF study of discordant monozygotic twins. Am. J. Psychiatry 149, 890-897.
Schizophrenia Research 18 (1995) 79 82
Short communications
Initial 'schizophrenia-like' psychosis in Pick's disease: case study with neuroimaging and neuropathology, and implications for frontotemporal dysfunction in schizophrenia John L. Waddington "'*, Hanafy A. Youssef b, Michael A. Farrell c, James Toland c a Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland h St. Davnet's Hospital, Monaghan, Ireland c Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland
Received 29 January 1995; accepted 19 June 1995
Abstract
'Schizophrenia-like' psychosis has not been reported previously as a prodrome of Pick's disease, a dementia of frontotemporal pathology. A woman having a consistent clinical diagnosis of typical schizophrenia who developed increasing affectivity and cognitive deficits was examined by computed tomography and brain biopsy. This presentation was found to be associated with left frontotemporal atrophy, left sylvian fissure abnormalities and enlargement of the anterior and temporal horns of the left lateral ventricle. On biopsy, all the neuropathological hallmarks of Pick's disease were present. Unusually, some specific aspect of Pick's disease in this patient appears initially to have disturbed brain function in a manner reproducing some fundamental aspect(s) of schizophrenia itself; left frontotemporal dysfunction would appear to be a relevant common denominator.
Keywords: 'Schizophrenia-like' psychosis; Pick's disease; Frontotemporal dysfunction; (Schizophrenia)
Introduction The application of contemporary neuroimaging, neuropsychological and neuropathologic techniques, has elaborated the concept of schizophrenia as a putative disorder of dysfunction in (left) frontotemporal and corticostriatopallidothalamic systems that appears to derive, at least in part, from early neurodevelopmental disturbance(s) (Weinberger et al., 1992; Waddington, 1993a,b). However, multiple aspects of the disorder remain very poorly understood, and study of the * Corresponding author. +353-( 1)-4780625.
Tel:
Elsevier Science B.V. SSDI (1920-9964 ( 95 ) 0 0 0 6 4 - X
+353-(1)-4780200;
fax:
'schizophrenia-like' organic psychoses is recognised as a valuable complementary approach to their clarification (Davison, 1990). We have previously described magnetic resonance imaging (MRI) findings in four patients with a 'schizophrenia-like' psychosis following head injury (O'Callaghan et al., 1988; Buckley et al., 1993), among whom the common denominator was left ventricular abnormalities with a preponderance of left temporal lobe pathology. It would be of considerable interest were similar findings to be demonstrated in instances of 'schizophrenia-like' psychosis among patients with other neurological disorders.
80
J.L. Waddington et al./Schizophrenia Research 18 (1995) 79-82
Pick's disease is a rare form of (pre-senile) dementia characterised neuropathologically by severe but somewhat circumscribed atrophy of the frontal and temporal lobes; in addition to this marked cell loss, there are swollen cortical neurons (achromasic neurons) which usually contain characteristic intracytoplasmic inclusion (Pick) bodies in the absence of the neurofibrillary tangles and senile plaques that are pathognomonic of Alzheimer's disease; these atrophic abnormalities are usually, but not always, symmetrical and there appears to be no specific predilection for either hemisphere. Prodromal signs of impending dementia and ultimately fatal debilities include prominent changes in personality: irritability and aggressiveness, mood disturbances that include incoherent joviality, socially disturbing behaviour and loss of social awareness; however, psychosis has not been reported previously (Rosenberg, 1983; Walton, 1985; Knopman et al., 1989). We describe here a case of biopsy-confirmed Pick's disease that presented initially as a typical 'schizophrenia-like' psychosis and was found subsequently to have circumscribed, predominantly left frontotemporal pathology on computed tomography (CT). Case report. This single woman attended school until the age of 14; she appeared to be a poor scholar, probably because of some deafness. Her social life was active up to the age of 25, after which there was a change in personality; she no longer went to local dances, became shy of men, and read books relating to religion and philosophy. However, she continued to work in a local factory until shortly before psychiatric referral. There was no known family history of psychiatric or neurological disorder. Her first psychiatric presentation and admission to St. Davnet's Hospital was at the age of 51. She was a poor historian who worried and prayed, but gave a history suggestive of auditory hallucinations for two years prior to that admission and had delusions that people at work were talking about her; these had prompted her to leave employment some 1.5 years previously. Two days after her admission she was given a provisional clinical diagnosis of paranoid schizophrenia and treatment with neuroleptics. Subsequently, she admitted hearing voices from God and also showed depres-
sive features. She was discharged on neuroleptic and antidepressant medication. Two years later she was readmitted having walked out of the family home complaining that her brothers and sisters would not let her marry a man whom the 'Holy Spirit' had told her to marry so as to prevent the world being destroyed; she had seen the 'Holy Lady' many times. There were now also some hypomanic features (elation and hyperactivity) with poor memory for past events, and she was again treated with neuroleptics prior to discharge. Her third admission, just over a year later, followed her leaving the family home once again; both her mother and 'Our Lady' had appeared to her. Furthermore, she was agitated, euphoric and talkative, with incoherent speech and memory lapses. There was impulsive behaviour following the prompting of the 'Holy Spirit' in her heart; she freely expressed a series of auditory and visual hallucinations together with inappropriate affect and some paranoid ideation. The clinical diagnosis was schizoaffective disorder and she was discharged once again on neuroleptic medication. Over the subsequent decade she lived with various family members and finally alone. A relative noticed increasing memory disturbances and she was referred for detailed neurological examination. Now aged 65, she had over the past year shown poor concentration and attention, loss of interest in her personal habits, poor hygiene, inappropriate behaviour such as getting up during the night to go shopping, and some urinary incontinence. On examination she was a very cheerful woman, hard of hearing, with sensory dysphasia, echolalia and naming difficulties. Otherwise, cranial nerve, motor, sensory, cardiovascular and respiratory examinations and full biochemical investigations were all normal, as was CSF analysis. Cerebral CT revealed prominent widening of frontal lobe sulci in the area of the interhemispheric fissure, with quite marked enlargement of the anterior and temporal horns of the left lateral ventricle and widening of the left sylvian fissure (Fig. 1); these frontotemporal abnormalities appeared predominantly left sided, but there was also some widening of sulci in the medial aspect of the right frontal lobe and of the right sylvian fissure. Frontal lobe biopsy (left) and neuropathologic examination
J.L. Waddington et al./Schizophrenia Research 18 (1995) 79-82
Fig. 1. Axial CT image at the level of the lateral ventricular system
thereof revealed a preserved cortical laminar pattern but with a moderate degree of astrogliosis in layer I; the remaining cortical layers were unremarkable with neither senile plaques nor neurofibrillary tangles evident, and blood vessels did not contain amyloid. Spongiform degeneration was not present. Numerous neurons were found to contain spherical intracytoplasmic inclusion bodies which were tau-positive with rare neurofilament positivity; these bore a striking resemblance to classical Pick bodies. Immunohistochemistry for glial fibrillary acidic protein revealed dense pancortical astrogliosis with additional subcortical gliosis. The neuropathologic diagnosis was Pick's disease with subpial astrogliosis. In the postoperative period, following biopsy, ventilation perfusion scan indicated multiple pulmonary emboli and the patient was discharged on anticoagulant therapy. On her readmission to St. Davnet's hospital she showed prominent affective changes with incongruity of affect, self-absorbing smile, thought disorganisation with irrelevant and incoherent speech, and cognitive disturbances; aspects of this overall clinical picture were likened to hebephrenic schizophrenia, and symptomatic management of the underlying Pick's disease was attempted with thioridazine and hydergine. Fifteen months following readmission she evidenced a generalised seizure. Over the next four years she became extremely restless and doubly incontinent, with gross cognitive deficits. In the latter stages of her illness increasing disability necessitated full care for all her needs and
81
at the age of 71 she died of respiratory failure. There was no postmortem examination. Discussion. The generally unremarkable early history of this patient followed, in her mid-20s, by a personality change in the direction of asociality, heterophobia and religious preoccupations suggests the emergence of a schizoid/schizotypal state; this appeared to endure over some two decades before the emergence of florid psychotic symptoms and the typicality of the delusions and hallucinations, on such a background, readily accounts for the initial diagnosis of schizophrenia. Over her second and third admissions, during each of which these schizophrenic symptoms re-appeared, the additional emergence of incoherence and inappropriate affect would be consistent with continuing recourse to this diagnosis (American Psychiatric Association, 1987); it is only with the benefit of the 'retrospectoscope' that their emergence together with 'hypomanic' features, impulsive behaviour and memory lapses might be recognised as more typical prodroreal signs of the fundamental neuropathological process. Thereafter, the domination of the clinical picture by 'frontal' disinhibition phenomena (inappropriate affectivity, impulsive behaviour and loquaciousness), dysphasia and echolalia on a background of increasing cognitive impairment, and progressing to profound dementia, convulsions and a terminal near-vegetative state, are entirely typical of the later course of Pick's disease (Rosenberg, 1983; Walton, 1985), as confirmed neuropathologically on biopsy. Given the confidence of the diagnosis of Pick's disease, the initial 'schizophrenia-like' psychosis can be interpreted in at least three ways: Firstly, this psychosis may actually be schizophrenia, in a patient who was unfortunate enough to acquire two independent (though perhaps ultimately interactive) disease processes; however, the temporal relationship between emergence of psychosis and of more typical behavioural prodromes of Pick's disease argues against such a dual eventuality. Secondly, the early changes in personality towards schizoid/schizotypal features might reflect some pre-existing vulnerability to schizophrenia, with elements of the later neurodegenerative changes precipitating initially a 'schizophrenia-like' psychosis in a manner that does not appear to occur among patients with Pick's disease who have no
82
J.L. Waddington et al./Schizophrenia Research 18 (1995) 79-82
such pre-existing vulnerability; however, the relative frequency of schizoid/schizotypal features in the general population would, despite the greater rarity of Pick's disease, predict 'schizophrenia-like' psychosis to be more than an occasional prodrome thereof when we are not aware of such an association having been reported previously. The third interpretation, which we favour, is that some specific aspect of the pathology of Pick's disease in this patient has, early in its course, disturbed brain function in a manner that reproduces some fundamental aspects of the pathophysiology of schizophrenia. In this regard, there is a striking concordance between structural pathology primarily of the left frontal and temporal cortex together with left sylvian fissure abnormality and dilatation of the left anterior and temporal horns of the lateral ventricular system in the present instance, and structural pathology of the (left) temporal lobe and sylvian fissure with associated ventricular abnormalities and frontal lobe dysfunction in schizophrenia (Waddington, 1993a,b). Current perspectives of schizophrenia also indicate corticostriatopallidothalamic dysfunction, and it may be relevant that when the somewhat circumscribed frontotemporal abnormalities of Pick's disease do encompass other brain regions, it is the basal ganglia and thalamus that are affected (Rosenberg, 1983). Furthermore, frontotemporal abnormalities can be evident early in the course of Pick's disease, around the time of early prodromes of the disorder (Knopman et al., 1989). It must therefore be considered whether the yet earlier schizotypal personality changes in the present case might reflect the subtle onset of left frontotemporal dysfunction; these personality changes might endure until some critical threshold of cellular disturbance is exceeded to precipitate 'schizophrenia-like' psychosis prior to those more prominent neurodegenerative changes that result in the more typical symptoms of Pick's disease. This overall interpretation of the present case would be complementary to our recent report that each of a small series of cases of 'schizophrenia-like' psychosis following head injury also showed left temporal or left frontotemporal pathology on MRI (Buckley et al., 1993). In summary, this report emphasises both the
difficulty in excluding (at least initially) specific neurological disease in the differential diagnosis of schizophrenia, and the importance of left frontotemporal dysfunction as a relevant common denominator linking 'schizophrenia-like' psychosis in diverse neurological circumstances to schizophrenia itself.
Acknowledgements These studies were supported by the Health Research Board. Dr. Michael Farrell, Consultant Neuropathologist, Beaumont Hospital, Dublin, is thanked for his advice and for kindly making available his original neuropathological findings in this case.
References American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd edn, revised. American Psychiatric Association, Washington, DC. Buckley, P., Stack, J.P., Madigan, C., O'Callaghan, E., Larkin, C., Remond, O., Ennis, J.T. and Waddington, J.L. (1993) Magnetic resonance imaging of schizophrenia-like psychoses associated with cerebral trauma: clinicopathological correlates. Am. J. Psychiatry 150, 146-148. Davison, K. (1990) Organic schizophrenia-like psychoses. In: M.P.I. Weller (Ed.), Perspectives In Schizophrenia. Libbey, London. Knopman, D.S., Christensen, K.J., Schut, L.J., Harbaugh, R.E., Reeder, T., Ngo, T. and Frey, W. (1989) The spectrum of imaging and neuropsychological findings in Pick's disease. Neurology 39, 362-368. O'Callaghan, E., Larkin, C., Redmond, O.,Stack, J., Ennis, J.T. and Waddington, J.L. (1988) Early-onset schizophrenia after teenage head injury: a case report with magnetic resonance imaging. Br. J. Psychiatry 153, 394-396. Rosenberg, R.N. (1983) The Clinical Neurosciences: Neuropathology. Churchill Livingstone, New York. Waddington, J.L. (1993a) Schizophrenia: developmental neuroscience and pathobiology. Lancet 341,531-536. Waddington, J.L. (1993b) Neurodynamics of abnormalities in cerebral metabolism and structure in schizophrenia. Schizophr. Bull. 19, 55-69. Walton, J. (1985) Brain's Diseases of the Nervous System. Oxford University Press, Oxford. Weinberger, D.R., Berman, K.F., Suddath, R. and Torrey, E.F. (1992) Evidence for dysfunction of a prefrontal-limbic network in schizophrenia: an MRI and rCBF study of discordant monozygotic twins. Am. J. Psychiatry 149, 890-897.