Psychological Medicine, 1975, 5, 249-254
Factors influencing the occurrence of schizophrenia-like psychosis in patients with temporal lobe epilepsy DAVID C. TAYLOR From the Human Development Research Unit, Park Hospital for Children, Oxford
SYNOPSIS From a series of 255 patients who had undergone temporal lobectomy for the relief of intractable psychomotor epilepsy, all 47 patients with 'alien tissue' (small tumours, hamartomas, focal dysplasia) in the resected temporal lobe were contrasted with a group of 41 patients who showed mesial temporal sclerosis in their resected lobe. Five per cent of the mesial temporal sclerosis group and 23% of the alien tissue group were psychotic. A marked interaction occurred between psychosis and 'left handedness'. In the alien tissue group, females, especially left-handed females, were the most likely to have developed a schizophrenia-like psychosis. Most authorities agree that schizophrenia-like states are over-represented among patients with temporal lobe epilepsy (Slater et al., 1963). Some doubt remains whether this is a spurious effect due to sampling problems and the tendency to investigate more serious disorders more thoroughly (Small et al, 1962; Small et al., 1966; Mignone et al., 1970; Currie et al., 1971). If it could be shown that the psychotic patients predominated within a particular group of the generality of patients with temporal lobe epilepsy, and the characteristics of that group were described, then these problems would be clarified and some light thrown on the mechanism of psychosis. Such a mechanism might have general significance in schizophrenia. Flor-Henry (1969) has shown that the schizophrenia-like states predominate in epileptic patients with left and bilateral temporal foci. There is evidence (Falconer and Taylor, 1968; Taylor, 1972) of a negative correlation between psychosis and mesial temporal sclerosis, and a slight positive association with hamartomas, being found in the resected temporal lobes of patients treated surgically for temporal lobe epilepsy. Malamud (1967) described the association between schizophrenic states and other limbic tumours. Further connections between epilepsy, schizophrenia, and the limbic system
were recently succinctly reviewed {Lancet, 1974). Taylor (1971) noted the relative preponderance of females in series of epileptic patients with psychoses. They also tend to become psychotic younger than males. The modal age of onset of epilepsy is at puberty. In this study the schizophrenic illness associated with temporal lobe epilepsy is explored through two groups of patients submitted to surgical treatment. METHODS PATIENTS The patients had undergone unilateral temporal
lobectomy for intractable psychomotor epilepsy. The operations were all performed by Mr. Murray Falconer at the Neurosurgical Unit of Guys, Kings, and the Maudsley Hospitals in London. His technique was standard (Falconer, 1965). The anterior portion of the temporal lobe is removed en bloc from about 7 cm back from the pole (usually marked by the vein of Labbe), usually retaining at least the posterior part of the superior temporal gyrus on the left. This block of tissue is then examined in detail by the neuropathologists. The criteria of case selection have often been described (Falconer et al., 1955; Falconer et al., 1964; Taylor and Falconer, 1968). The principal components are failure to respond to medical treatment and clear-cut unilateral emphasis in the EEG studies. The series includes only patients
249
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David C. Taylor
treated for epilepsy; patients treated for tumours are excluded. In no case was surgical treatment aimed at improving behaviour, though this was a frequent concomitant of seizure relief. Detailed neuropathological study of the resected specimen was always made. The results of this have become a basis for classification. Before operation the work-up in the unit is undertaken jointly by the neurosurgeon and psychiatric colleagues. Afterwards the follow-up is also undertaken jointly by the neurosurgeon and psychiatrists. Readmission for a few days one year after the operation is usual. Retesting and reappraisal is then undertaken. Follow-up for 10 years by at least annual visits is standard but research contact is re-established as necessary (up to 23 years in this study). At the time of this study, 255 operations had been performed. TECHNIQUE
This study compares two groups of patients selected on the basis of the pathological changes in the resected temporal lobes. Group 1. Mesial temporal sclerosis This cerebral lesion has been described in various ways since the early 19th century. Its occurrence in about half the patients with intractable temporal lobe epilepsy has been fully described by our group (Falconer and Taylor, 1968). It is a gliotic cerebral scarring also called Ammon's horn sclerosis or incisural sclerosis. It is most prominent in the mesial temporal areas and usually occurs unilaterally. It probably results from a local, cellular, consumptive hypoxia which is often caused by prolonged febrile fits in early childhood. The lesion can be reproduced in animals (McLardy, 1969; Meldrum and Brierley, 1972). The 41 patients with mesial temporal sclerosis were drawn from a previous study of 100 consecutive patients seen personally in a follow-up study (Taylor and Falconer, 1968; Taylor, 1972). Forty-seven patients in that study had mesial temporal sclerosis but in six it was associated with another lesion and these cases have been excluded. These patients numbered from case 50 to case 162 in the series, which is numbered according to date of operation. Group 2. Alien tissue It is necessary to introduce this new rubric Jo cover that group of cases previously referred to in our papers as 'small focal tumours' (Cavanagh, 1958), 'hamartomas' (Falconer et al., 1964), and 'focal dysplasia' (Taylor et al., 1971). These lesions were 'unsuspected' and were revealed only in the course
of the surgical treatment of epilepsy. The term alien tissue encompasses all those cases where the surgical approach to treatment brought to light the existence of a small locus of cells alien from their context. These patients numbered from case 1 to case 255 in the series, but the patients who were psychotic were confined between case 1 and case 163. A new study was made of the alien tissue group. The entire series of patients who had undergone operations was searched for patients with this type of pathology. Only those cases in which the pathological changes could be verified now by Dr. C. Bruton and Dr. J. A. N. Corsellis were included. Forty-seven patients were found whose operation had taken place at least one year before the time of follow up. This type of lesion was discovered in about 25% of patients in the series. Only residents in the United Kingdom were considered for the follow-up study. The notes of all 47 patients were examined and a schedule similar to that used previously (Taylor and Falconer, 1968) was completed. All 47 patients were traced. Ten patients were dead. All but one1 of the remainder were seen personally, accompanied by a research assistant. Thirty-three patients were seen in their own home or institution. One psychotic patient living alone at home, who refused to be seen by me, was interviewed by my research assistant. Two patients would be interviewed only at the hospital, and two others were seen there for their convenience. At the interview, a schedule identical with that completed on the preoperative notes was completed and the mental state assessed clinically. Where it was deemed clinically wise, and with the patients' permission, the interviews were tape recorded. Subsequently, all this material and the notes of the follow-up period were taken in to consideration before a final diagnosis of schizophrenia-like psychosis was made. A similar procedure had already been undertaken with the 41 patients in the mesial temporal sclerosis group (Taylor and Falconer, 1968). DATA
The factors considered in this study were: pathological findings in the resected temporal lobes; sex; side of operation; age at onset of epilepsy; handedness; and the presence or absence of schizophrenialike psychosis at any time before or after operation. The pathological findings had been described by a number of different neuropathologists but these were all rechecked by Dr. Bruton and Dr. Corsellis independently of any knowledge of the clinical state lOne patient was seen by Mr. Murray Falconer (Falconer, 1973) but the mental state had been kindly described by the late Professor J. G. Gibson.
The occurrence of schizophrenia-like psychosis in patients with temporal lobe epilepsy
251
ALIEN TISSUE IEFT
#
OPERATION
Q
O
O
O
Factors influencing the occurrence of schizophrenia-like psychosis in patients with temporal lobe epilepsy DAVID C. TAYLOR From the Human Development Research Unit, Park Hospital for Children, Oxford
SYNOPSIS From a series of 255 patients who had undergone temporal lobectomy for the relief of intractable psychomotor epilepsy, all 47 patients with 'alien tissue' (small tumours, hamartomas, focal dysplasia) in the resected temporal lobe were contrasted with a group of 41 patients who showed mesial temporal sclerosis in their resected lobe. Five per cent of the mesial temporal sclerosis group and 23% of the alien tissue group were psychotic. A marked interaction occurred between psychosis and 'left handedness'. In the alien tissue group, females, especially left-handed females, were the most likely to have developed a schizophrenia-like psychosis. Most authorities agree that schizophrenia-like states are over-represented among patients with temporal lobe epilepsy (Slater et al., 1963). Some doubt remains whether this is a spurious effect due to sampling problems and the tendency to investigate more serious disorders more thoroughly (Small et al, 1962; Small et al., 1966; Mignone et al., 1970; Currie et al., 1971). If it could be shown that the psychotic patients predominated within a particular group of the generality of patients with temporal lobe epilepsy, and the characteristics of that group were described, then these problems would be clarified and some light thrown on the mechanism of psychosis. Such a mechanism might have general significance in schizophrenia. Flor-Henry (1969) has shown that the schizophrenia-like states predominate in epileptic patients with left and bilateral temporal foci. There is evidence (Falconer and Taylor, 1968; Taylor, 1972) of a negative correlation between psychosis and mesial temporal sclerosis, and a slight positive association with hamartomas, being found in the resected temporal lobes of patients treated surgically for temporal lobe epilepsy. Malamud (1967) described the association between schizophrenic states and other limbic tumours. Further connections between epilepsy, schizophrenia, and the limbic system
were recently succinctly reviewed {Lancet, 1974). Taylor (1971) noted the relative preponderance of females in series of epileptic patients with psychoses. They also tend to become psychotic younger than males. The modal age of onset of epilepsy is at puberty. In this study the schizophrenic illness associated with temporal lobe epilepsy is explored through two groups of patients submitted to surgical treatment. METHODS PATIENTS The patients had undergone unilateral temporal
lobectomy for intractable psychomotor epilepsy. The operations were all performed by Mr. Murray Falconer at the Neurosurgical Unit of Guys, Kings, and the Maudsley Hospitals in London. His technique was standard (Falconer, 1965). The anterior portion of the temporal lobe is removed en bloc from about 7 cm back from the pole (usually marked by the vein of Labbe), usually retaining at least the posterior part of the superior temporal gyrus on the left. This block of tissue is then examined in detail by the neuropathologists. The criteria of case selection have often been described (Falconer et al., 1955; Falconer et al., 1964; Taylor and Falconer, 1968). The principal components are failure to respond to medical treatment and clear-cut unilateral emphasis in the EEG studies. The series includes only patients
249
250
David C. Taylor
treated for epilepsy; patients treated for tumours are excluded. In no case was surgical treatment aimed at improving behaviour, though this was a frequent concomitant of seizure relief. Detailed neuropathological study of the resected specimen was always made. The results of this have become a basis for classification. Before operation the work-up in the unit is undertaken jointly by the neurosurgeon and psychiatric colleagues. Afterwards the follow-up is also undertaken jointly by the neurosurgeon and psychiatrists. Readmission for a few days one year after the operation is usual. Retesting and reappraisal is then undertaken. Follow-up for 10 years by at least annual visits is standard but research contact is re-established as necessary (up to 23 years in this study). At the time of this study, 255 operations had been performed. TECHNIQUE
This study compares two groups of patients selected on the basis of the pathological changes in the resected temporal lobes. Group 1. Mesial temporal sclerosis This cerebral lesion has been described in various ways since the early 19th century. Its occurrence in about half the patients with intractable temporal lobe epilepsy has been fully described by our group (Falconer and Taylor, 1968). It is a gliotic cerebral scarring also called Ammon's horn sclerosis or incisural sclerosis. It is most prominent in the mesial temporal areas and usually occurs unilaterally. It probably results from a local, cellular, consumptive hypoxia which is often caused by prolonged febrile fits in early childhood. The lesion can be reproduced in animals (McLardy, 1969; Meldrum and Brierley, 1972). The 41 patients with mesial temporal sclerosis were drawn from a previous study of 100 consecutive patients seen personally in a follow-up study (Taylor and Falconer, 1968; Taylor, 1972). Forty-seven patients in that study had mesial temporal sclerosis but in six it was associated with another lesion and these cases have been excluded. These patients numbered from case 50 to case 162 in the series, which is numbered according to date of operation. Group 2. Alien tissue It is necessary to introduce this new rubric Jo cover that group of cases previously referred to in our papers as 'small focal tumours' (Cavanagh, 1958), 'hamartomas' (Falconer et al., 1964), and 'focal dysplasia' (Taylor et al., 1971). These lesions were 'unsuspected' and were revealed only in the course
of the surgical treatment of epilepsy. The term alien tissue encompasses all those cases where the surgical approach to treatment brought to light the existence of a small locus of cells alien from their context. These patients numbered from case 1 to case 255 in the series, but the patients who were psychotic were confined between case 1 and case 163. A new study was made of the alien tissue group. The entire series of patients who had undergone operations was searched for patients with this type of pathology. Only those cases in which the pathological changes could be verified now by Dr. C. Bruton and Dr. J. A. N. Corsellis were included. Forty-seven patients were found whose operation had taken place at least one year before the time of follow up. This type of lesion was discovered in about 25% of patients in the series. Only residents in the United Kingdom were considered for the follow-up study. The notes of all 47 patients were examined and a schedule similar to that used previously (Taylor and Falconer, 1968) was completed. All 47 patients were traced. Ten patients were dead. All but one1 of the remainder were seen personally, accompanied by a research assistant. Thirty-three patients were seen in their own home or institution. One psychotic patient living alone at home, who refused to be seen by me, was interviewed by my research assistant. Two patients would be interviewed only at the hospital, and two others were seen there for their convenience. At the interview, a schedule identical with that completed on the preoperative notes was completed and the mental state assessed clinically. Where it was deemed clinically wise, and with the patients' permission, the interviews were tape recorded. Subsequently, all this material and the notes of the follow-up period were taken in to consideration before a final diagnosis of schizophrenia-like psychosis was made. A similar procedure had already been undertaken with the 41 patients in the mesial temporal sclerosis group (Taylor and Falconer, 1968). DATA
The factors considered in this study were: pathological findings in the resected temporal lobes; sex; side of operation; age at onset of epilepsy; handedness; and the presence or absence of schizophrenialike psychosis at any time before or after operation. The pathological findings had been described by a number of different neuropathologists but these were all rechecked by Dr. Bruton and Dr. Corsellis independently of any knowledge of the clinical state lOne patient was seen by Mr. Murray Falconer (Falconer, 1973) but the mental state had been kindly described by the late Professor J. G. Gibson.
The occurrence of schizophrenia-like psychosis in patients with temporal lobe epilepsy
251
ALIEN TISSUE IEFT
#
OPERATION
Q
O
O
O
