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NEUROSURGICAL TREATMENT OF NEUROPSYCHIATRIC ILLNESS
NEUROPSYCHIATRY OF THE BASAL GANGLIA
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NEUROSURGICAL TREATMENT OF NEUROPSYCHIATRIC ILLNESS Raul Marino, Jr, MD, and G. Rees Cosgrove, MD
I returned from Brazil loving that land as much as the one I was born. I do not know how I could separate myself from that country, a continuation of my own. EGAS MONIZ (LETTER TO ALMEIDA LIMA)
In 1935, Egas Moniz, a distinguished Portuguese neurologist and the discoverer of cerebral angiography, had his neurosurgeon, Almeida Lima, perform the first surgical intervention for the treatment of mental illness6 The initial procedure involved injection of alcohol into the frontal lobes and was named ”prefrontal leukotomy,” becoming the first valid attempt in the surgical treatment of mental diseases. The neurosurgical treatment of psychiatric illness had thus begun and the term psychosurgery was coined to describe this novel approach. In 1949, Egas Moniz was awarded the Nobel Prize for his contributions in the field of psychosurgery and for his study on the functions and physiology of the frontal lobes. It was undoubtedly, one of the more stimulating contributions in the field of psychiatric thinking in the last six decades. The technique of prefrontal leucotomy, used in many thousands of desperate psychiatric patients, during the first decades following its discovery, subsequently has been replaced by more modern approaches. Nonetheless, it aroused a monumental volume of investigations in neuroanatomy, neurophysiology and psychiatry. Egas Moniz’s leukotomy procedure has provoked a revolution, not only in modern psychiatric thinking but in all philosophical and social sectors that are based in a better knowledge of cerebral mechanisms. Dozens of new psychosurgical techniques were introduced after the discovery of Egas Moniz, and many structures of the brain were targeted in an
From the Department of Neurology and Neurosurgery, University of S%oPaulo Medical School, S%oPaulo, Brazil (RM); and the Neurosurgical Service, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (GC)
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attempt to reduce the mortality and morbidity rates of the early procedures. Observations regarding the response to surgery in cases of mental disease considered refractory to treatment in the prepsychopharmacologic era of psychiatry were largely empirical, but supplied valuable insights into the functioning of these areas. Many of these empirical observations then were combined with laboratory research techniques by the psychiatrist and neurophysiologist MacLean, who introduced the concept of the "limbic system" in 1952.18Subsequent investigations have stemmed from his original work, thus launching the basis for his novel concept of a "psychencephalon," a denomination of the limbic brain and related structures introduced by MacLean in 1982.*OThe psychophysiology of the limbic system and related structures, which have been better understood in recent years, constitutes the modern "triune brain" theory also proposed by MacLean. These new concepts may soon present to psychiatric thought and the new science of physiodynamics (in distinction to psychodynamics) the same significance and impact that the historical Freudian concepts had to the knowledge of the structure of human personality. The recognition of Papez's theory on the importance of the rhinencephalic structures2Rand the experimental demonstration of their functions and connections by MacLean, Nauta, and many other authors, supported the concept previously unknown to medicine that the limbic system is the likely neuroanatomic substrate responsible for behavior, emotion, and psychiatric disease. After the 1950s, psychiatric thinking was guided by the investigative neurosciences, and the limbic system started to become the link between the brain, mind, and human conduct in a functional continuum. Present day psychiatry finally has absorbed all the contributions from the neurosciences that allowed for a better understanding of affect, humor, learning, memory, motivation, sexual behavior, and the control of many visceral and neurovegetative functions. We now can demonstrate that cortical, subcortical, and basal ganglia functions, without the participation of the limbic system, would have no relevance in the daily survival of an animal in a world that is biologically organized. Without this system, the intellectual functions never would experience the limits of reality, and human thinking would be ungoverned completely. This system will, thus, determine what will prevail in an individual-psychic normality, reason, or insanity. THE BASAL GANGLIA
The term basal ganglia originally referred to all the masses of gray matter buried within the cerebrum and thus included the caudate nucleus, putamen, globus pallidus (also called paleostriaturn or pallidurn), subthalamic nucleus, substantia nigra, claustrum, and the amygdala. The term striaturn refers to the caudate nucleus and the putamen together. Corpus striaturn refers to the caudate nucleus, putamen, and globus pallidus; the term lentiforrn nucleus refers to the putamen and globus pallidus together. Some investigators include additional regions in the basal ganglia such as the ventral striatum (or limbic striatum), which includes the nucleus accumbens, olfactory tubercle, and the nucleus of the stria terminalis. All of these structures resemble the caudate and putamen in ultrastructure and histochemistry. The ventral pallidurn is a region that receives afferents from the ventral striatum and sometimes the term is meant to include the heterogeneous group of neurons found within the substantia innominata. The striatum is the major recipient of input to the basal ganglia, with three
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afferent systems: the corticostriatal, the nigrostriatal, and the thalamostriatal projections. Other minor inputs originate in the locus coeruleus and the raphe nuclei. The former use the neurotransmitter norepinephrine, and the latter contain serotonin. Disruption of these input pathways to the basal ganglia has been associated with a wide variety of movement disorders, including Parkinson’s disease, Huntington’s chorea, tics, Gilles de la Tourette’s syndrome, Sydenham’s chorea, tardive dyskinesia, Wilson‘s disease, psychic akinesia, and also cognitive and complex behavioral dysfunctions of the brain such as schizophrenia, catatonia, major depression, anorexia nervosa, and obsessive-compulsive disorder (OCD). Parkinson’s disease is a progressive idiopathic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. This results in a loss of dopaminergic terminals in the striatum, and is characterized by muscular rigidity, fine tremor, shuffling gait, and bradykinesia. L-dopa, a precursor of dopamine introduced in 1967, is used as treatment of Parkinson’s disease because it augments the release of dopamine from the remaining terminals. On the other hand, the administration of antipsychotic agents in the treatment of schizophrenia has been associated with the occurrence of tardive dyskinesia. Many antipsychotic agents are dopamine-receptor antagonists, an effect which tends to explain their movement related side effects. The basal ganglia contain by far the highest concentration of dopamine in the brain. Ascending projection systems from brain stem to basal ganglia also have dopamine as their major transmitter, such as the nigrostriatal tract and the mesolimbic system. The mesolimbic system projects to the anterior extremity of the basal ganglia or limbic striatum (ventral striatum) represented by the nucleus accumbens, olfactory tubercle and nucleus of the stria terminalis, structures that receive input from limbic cortex, amygdala, and hippocampus. Stevens, in 1973,33suggested that the dopaminergic system in the basal ganglia could be a final common pathway for the schizophrenia syndrome, representing thus a dysfunction of the mesolimbic dopamine projection system in a manner similar to dysfunction of the nigrostriatal dopamine system in Parkinson’s disease, thus putting forward the concept of Parkinson’s disease and schizophrenia as contrasting conditions. The hypothesis that Parkinson’s disease also might represent a systemic disease, involving the neuroendocrine, peripheral neurotransmitter, and sympathetic system, also was advanced by one of the present authors= based on the findings of cerebral-adrenal transplantations for severe parkinsonism. After microscopic examination with fluorescence and morphometric study of 15 normal cadaveric adrenal glands, we demonstrated that the medullary layer of parkinsonian patients was comparatively hypotrophic and difficult to dissect in order to obtain graft specimens. Their cells were also poor in catecholamine contents. Basal ganglia dysfunction also became implicated in other psychiatric illness, such as OCD. The neurobiology of this syndrome is described elsewhere in this issue (see elsewhere in this issue). The advent of advanced neuroimaging techniques, such as morphometric magnetic resonance (mMR) imaging and positron emission tomography (PET), have opened new windows to look at the brain. Thus, PET scans have shown conspicuous abnormalities in the frontal lobes, cingulum, and basal ganglia of OCD patients when compared with depressed patients and normal controls. Furthermore, volumetrically computed MR imaging scans have shown decreased caudate volumes bilaterally in OCD patients, associated or not to demonstrable lesions in the striatum. A developmental abnormality also has been suggested in these patients, characterized by significantly more gray matter and
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less white matter in mMR imaging scans. A neurologic hypothesis for OCD thus is supported by the combination of findings from several high-technology imaging studies (see elsewhere in this issue). PSYCHIATRIC SURGERY
The neurosurgical treatment of mental illness is performed on patients who have intractable psychiatric disease-not upon the psyche per se. The term psychosurgery, introduced in the early 1940s, thus should be considered a misnomer. Many centers prefer the term limbic system surgery but only a few currently use these procedures as a therapeutic tool for the treatment of mental illness. Some of these operations also are used for the treatment of other diseases, such as chronic pain, intractable epilepsy, Parkinson’s disease, Gilles de la Tourette’s syndrome, and abnormal movements. The goal of these procedures is always to reduce the symptoms in severely ill patients who have not responded adequately to less radical treatments. The exact mechanisms by which surgery may modify psychiatric illness is unknown. It may be related to the ablation of specific areas or the disconnection of interrelated regions. It is also quite possible that the beneficial effects may be brought about more by chemical than by purely physical or anatomic changes in the brain. The neurochemical consequences of psychosurgery may lead to important changes in the availability of neurotransmitters or trophic factors at certain critical locations and also at areas remote from the areas ablated by the neurosurgeons. Thus, it may be both neuroanatomic and neurochemical changes that will affect behavior. Ballantine et a12 and Marinozl were among the first to propose, in 1967, stereotactic cingulotomy as a treatment of choice for chronic cancer pain, depression, OCD, and anorexia nervosa. OBSESSIVE-COMPULSIVE DISORDER
Accumulated data from the literature has shown compelling evidence that the cingulate gyrus and cingulate bundle are involved in the cause of OCD. Papez himself, in 1937,28regarded the cingulate cortex as ”the receptive region for impulses concerned with emotion,” suggesting that radiation of impulses from the cingulate gyrus to other cortical regions added emotional coloring to the psychic process. This implied that the cingulum was part of a reverberatory circuit, where impulses could circulate continually and, when reinforced, cause emotional experiences to be intensified. It would be interesting to quote one of Papez’ sibylline forethoughts that will be destined to remain as a classic in neuropsychiatric literature: The central emotive process of cortical origin may then be conceived as being built up in the hippocampal formation and as being transferred to the mammilary body and thence through the anterior thalamic nuclei to the cortex of the gyrus cinguli. The cortex of the cingular gyrus may be looked on as the receptive region for the experiencing of emotion as the result of impulses coming from the hypothalamic region, in the same way as the area striata is considered the receptive cortex for photic excitation coming from the retina. Radiation of the emotive process from the gyrus cinguli to other regions in the cerebral cortex would add emotional coloring to psychic process occurring elsewhere. This circuit would explain how emotion may arise in two ways: as a result of psychic activity and as a consequence of hypothalamic activity.
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Papez described affect as emotional coloring, and this quotation was printed in 1937 when the term limbic system was not yet coined by MacLean in 1952. Grey-Walter, in 1977; proposed that overactivity of the cingulum may lead to compulsive behavior, reporting the case of a university professor compelled to confess to all local crimes, and who was cured after small surgical lesions were placed in the cingulum. Talairach et al, in 1973,34reported their studies with indwelling electrodes, implanted to locate surgically resectable seizure foci, in which stereotyped repetitive rituals were produced by electrical stimulation of the cingulum in 52 patients presenting with drug-refractory epilepsy. During cingulum stimulation, the patients could not resist the urge to perform certain motions.34 The neurologic, neurosurgical, and psychiatric literature, reinforced by psychosurgical results of frontal leukotomies, has shown that a patient with a frontal lobe lesion has blunted affect, decreased judgment, and absence of worry. The present day neurobiologic findings suggest that the OCD patient has increased frontal lobe activity; theoretically, their cingulate connections produce instead a heightened sense of judgment or guilt, intense affective responses or depression, and a tendency to worry, anticipating negative outcomes. More recent neuroanatomic studies have shown important interconnections between the striatum and the limbic and cingulate structures. The caudate receives input from the frontal lobes and cingulate cortex, and then sends inhibitory projections to the thalamus, which in turn feeds back to the cortex, comprising a corticostriatalthalamic-cortical loop that mediates this output. Automatic behaviors also are mediated by the striatum, called "subroutines" by MacLean, in 1978.19Such behaviors include phylogenetically ancient patterns of grooming and also species-specific habits. In humans, this system is thought to mediate behaviors like saying one's own name, writing one's own signature, and so on. Increased activity of this loop is probably responsible for these subroutines, exemplified by inappropriate and repetitive grooming or checking rituals exhibited by OCD patients. Model1 et al, in 1989,27also proposed a neuroanatomic-neurochemical model for OCD based on this same frontostriatal-pallidothalamic-frontalloop. This reverberating circuit has two components: an orbitofrontal-thalamic circuit mediated by the excitatory neurotransmitter glutamate, and a second interconnection-the orbitofrontal-striatal-thalamic collateral, mediated by other neurotransmitters including glutamate, as well as dopamine, gamma-aminobutyric acid (GABA), and serotonin. The second interconnection modulates the neuronal activity of the former, and according to this hypothesis, overactivity in the orbitofrontal-thalamic interconnection would produce obsessive thoughts and compulsive rituals. In a normal individual, the orbitofrontal cortex also would stimulate, concomitantly, the caudate nucleus, which, as a consequence, would stimulate the pallidum, which, in turn, would inhibit the activity of the medial thalamic nuclei, the main basal station to the frontal cortex. This thalamic structure would modulate and correct the overactivity of the orbitofrontalthalamic stations. Dysfunctions in the modulatory activity of these interconnections may arise in OCD patients. Pharmacologic or surgical interference at this level of functional activity may alter favorably the imbalance in these areas, producing a diminution of its usual symptoms. Historically, the relative success of psychiatric surgery in treating OCD and other psychiatric refractory diseases is abundant in the psychiatric literature.2,7, 12,24,37 These and other studies have shown a consistently higher rate of symptom relief in OCD, as compared with various other psychiatric disorders such as schizophrenia, anorexia nervosa, anxiety, and so on. Several different psychiatric
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surgical interventions have appeared particularly useful. These include cingulotomy, limbic leukotomy, anterior capsulotomy, and subcaudate tractomy. In all of these procedures, transection of the tracts from frontal cortex to subcortical sites (i.e., en route to striatum and thalamus) have produced impressive results not only due to the rate of improvement but also for the low frequency of adverse effects. Chiocca and Martuza, in 1990; reviewed the world literature on these psychosurgical procedures and concluded that cingulotomy has a success rate of approximately 50% and a very low complication rate. Limbic leukotomy combines bilateral cingulate lesions with lesions in the orbital medial frontal areas, the passage site of fronto-caudate-thalamic fibers, critical in the circuit formation of OC symptoms. Success rates as high as 89% have been reported for this procedure. Anterior capsulotomy and subcaudate tractotomy were reported to improve 50% and 70% of OCD patients. Nevertheless, side effects from these two procedures appear to be higher, although temporary. The lower complication rates favor stereotactic cingulotomy as the first choice of a psychosurgical procedure to be considered in patients with disabling and severe refractory OCD. Patients who show no improvement following initial cingulotomy may be submitted to a second procedure or, alternatively, a stereotactic procedure in one of the other previously mentioned targets, which may produce relief not obtained by the first intervention. SURGICAL TECHNIQUES
Modern psychiatric surgery has experienced a profound evolution since the days of prefrontal leukotomy, and the open procedures proposed by Whitty et al,35 Le Beau,I7 P0ppen,2~Scoville et a1,3l and other authors. Practically all the achievements of modern conventional and functional neurosurgery have been incorporated into psychosurgical procedures. Ventriculograms and air studies have been replaced by CT and MR imaging, and target localization is obtained using very precise stereotactic frames, with spatial errors of fewer than 1 to 3 mm. Most procedures can be performed under local anaesthesia with mild sedation or light general anesthesia, without any pain or subjective stress to the patient during the lesioning. Knowledge of neuroanatomic structures and the use of precise anatomic atlases of the brain allow surgeons to make the lesions as small as possible in order to avoid unnecessary side effects. As this article is concerned mostly with mental illness physiopathologically related to the basal ganglia, we make a brief summary of the present state of the art procedures most commonly used for the psychosurgical treatment of OCD, Tourette’s syndrome, anorexia nervosa, anxiety, pain, and depression.’ The procedures that have been used preferentially during the last 25 years are cingulotomy, subcaudate tractotomy, limbic leukotomy, anterior capsulotomy, and thalamotomy. Cingulotomy
This procedure initially was proposed by Ballantine et a1 in 1967’ as a preferred treatment for chronic depression and cancer pain, although among the first 40 patients of this series, 10 also had OC symptoms and 10 had anorexia nervosa symptoms. Several consecutive series have been reported by these
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authors, containing more than 800 stereotactically treated patients. Techniques and results have been published elsewhere.Z,7, 11, 21, ~ 324, Cingulotomy, undoubtedly, constitutes the most commonly performed psychosurgical procedure at present, as all the reported series are associated with a very low incidence of complications and side effects. This procedure can be performed either under general anesthesia or with intravenous sedation. Burr holes or smaller twist drill holes are made bilaterally over the frontal region, and radiofrequency lesions are made following electrode penetration. No incision is necessary when a gamma-knife or a linear accelerator is used in the context of stereotactic radiosurgery. Cingulotomy lesions are placed within the cingulate bundles bilaterally, aided by CT or MR imaging. When radiofrequency is used, the thermocouple electrode tips are heated to 85°C for 60 seconds to make the coagulation lesions. Chiocca and Martuza4 recently have reviewed the worldwide literature on neurosurgical therapy of OCD and noted that cingulotomy has a success rate of approximately 50%. Jenike et all1 performed a long-term follow-up of 33 patients submitted to cingulotomy, using very conservative selection criteria. They have confirmed with this retrospective study that at least 25% to 30% of patients are markedly helped by one or more cingulotomy procedures when other proven treatments have not been successful. They relate this improvement either to cingulotomy per se or to the interaction of cingulotomy with postoperative pharmacologic or behavioral treatments. As seen previously, in the anatomic and neurophysiologic rationale presented, OCD symptoms are related to both anxiety and OC symptoms. Cingulotomy interrupts fibers of the cingulate bundle that are involved in the perpetuation of the anxiety component of this disorder. Subcaudate Tractotomy
This procedure was first described by Knight in 196414in Great Britain, and used to control depression. Lesions are made bilaterally in the substantia innominata under stereotactic guidance, in the rostra1 part of the orbital cortex, ventral to the head of caudate nucleus, between the anterior perforated substance and the striatum. The lesion interrupts the pathway between the frontal cortex, the hypothalamus, and the amygdala, which is involved in the control of anxiety, depression, and OC symptoms. According to Model1 et al,27overactivity of the frontocaudate-thalamicpathway provides the neuronal basis for OC symptoms. Interruption of these axonal fibers also would correct the abnormally increased activity of this bundle. More than 2000 patients have been submitted to this procedure and reported in the literature. Bridges et al, analysing Knight’s series, found total improvement or improvement with minimal symptoms in 67% of the patients with OCD. Subcaudate tractotomy also may be combined with anterior cingulotomy. This is a standard procedure that we have performed since 1977 for depression in 19 patients, with good results in 87.5% of the cases.23Kelly et all3 introduced this procedure in 1973 and coined the term limbic Zeukotomy to describe it. Limbic Leukotomy
The combination of the subcaudate tractotomy with cingulate lesions may lead to a better result for the treatment of OCD patients than either lesion alone. The subcaudate tractotomy interrupts the orbitofrontothalamic pathway
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involved in the pathogenesis of OCD and the cingulotomy destroys the nodal point of the Papez circuit, which interconnects hippocampus, fornix, mammilary bodies, anterior thalamic nuclei, and septa1 areas. Kelly, in 1980,12in an additional review of 49 patients operated upon by this procedure, reported 89% improvement 20 months after surgery. Postoperative symptom relief was not immediate after surgery, as we also have noted in our cingulotomy patients operated on since our 1967 report.* There was also significant reduction of anxiety and of obsessional traits. No long-term side effects were reported, but two patients commited suicide during the follow-up period. These results were interpreted by Kelly as a specific antiobsessional effect due to interruption of cingulate and frontothalamic pathways that mediate the anxiety and depressive symptoms in the OCD patients, making it in this author’s opinion, the procedure of choice in the surgical treatment of the OCD patient. Anterior Capsulotomy
This procedure entails bilateral lesions in the anterior limb of the internal capsule, thus disconnecting the limbic system from the frontal lobes. The main pathway crossing this portion of the internal capsule interconnects the orbitofrontal cortex with the midline thalamic nuclei. The fibers in the frontal lobes that were fanned were the same ones severed by the original and more empirical leukotomy procedures. Anterior capsulotomy was introduced by Leksell’O in the 1950s in Sweden. Herner, in 1961,’” was one of the first to report its efficacy in OCD, finding good or fair results in 81% of the patients undergoing this procedure. Meyerson and Mindus,Z5Fodstad et al,7Mindus and Jenike,26and KullbergI6also have reported favorable results of this procedure in OCD. Kullberg, however, reports some personality side effects of capsulotomy as compared with cingulotomy: one patient lost impulse control, with release of aggressive tendencies. Other changes included emotional shallowness, loss of initiative, diminution of inhibition, lethargy, and elevation of mood. Some of these side effects also have been observed in our former leukotomy patients but they are usually temporary in both procedures. Thalarnotorny
Several psychosurgical procedures were tried to control some of the devastating symptoms of Tourette’s syndrome: motor and phonic tics, self-injurious and self-destructive behaviors, coprolalic utterances, echolalia, echopraxia, barklike sounds, and so on. Bimedial frontal leukotomy, limbic leukotomy, cingulotomy, cerebellar surgery (dentatotomy), and thalamic surgery constitute a few of the reported techniques in the literature. The physiopathology of Tourette’s syndrome, however, remains poorly understood. Singer et a132suggest .that tics are mediated via midbrain dopaminergic systems interacting with the basal ganglia. Dopaminergic nigrostriatal projections to limbic striatum have been associated with affective illness, psychosis, and also with OCD. As previously seen, mediation of affective, cognitive, and motor functions by the basal ganglia also could represent involvement of these structures in Tourette’s syndrome. This issue of The Psychiatric Clinics has pointed to some clinical and genetic relationships between Tourette’s syndrome and OCD, models of which may be
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extended to the pathophysiology of Tourette‘s syndrome as well (see elsewhere in this issue). Neurosurgical lesions may influence these same neural systems. The intralaminar nuclei, part of the so-called diffuse thalamic-system, are small nuclei scattered throughout the intralaminar thalamic connective tissue, which separates the various subdivisions of the thalamus. These nuclei receive input diffusely from other thalamic nuclei, the reticular formation, and basal ganglia, and send their output diffusely to the frontal, motor, and premotor cortex. Lesions of these nuclei thus would interrupt the frontothalamic axis within the thalamus, leaving intact the important somatic thalamic nuclei. Hassler and Dieckmann, in 19737 reported their experience with bilateral coagulation of the rostra1 intralaminar and medial thalamic nuclei in 15 Tourette’s syndrome patients with several degrees of improvement. Other authors also have tried thalamic targets (dorsomedial and ventrolateral) apparently without S U C C ~ S S . l~5, Case reports in the literature, however, provide only anecdotal evidence in support of the efficacy and safety of the neurosurgical treatment for Tourette’s syndrome. Rauch et a130 have analysed these results reported in the literature and consider that the psychosurgical treatment of Tourette’s syndrome remains experimental, with no compelling evidence that any procedure is superior to all others.
CONCLUSION Patient selection criteria and indications for psychosurgical procedures are best understood for the treatment of depression and OCD, although therapeutic benefit has been evident for a limited number of other psychiatric conditions. Severe and enduring psychiatric illness that is unresponsiveness to all available contemporary therapies constitutes the main selection criterion for considering a psychosurgical procedure. Informed consent always must be obtained from the patients and their families.
References 1. Apo M, Laitinen L, Vickki J: Stereotactic cingulotomy in schizophrenia. Psychiatria Fennica 2:105-110, 1971 2. Ballantine HT Jr, Cassidy WL, Flanagan NB, et al: Stereotaxic anterior cingulotomy for neuropsychiatric illness and intractable pain. J Neurosurg 26:488495, 1967 3. Bingley T, Leksell L, Meyerson BA, et al: Long-term results of stereotactic anterior capsulotomy in chronic obsessive-compulsive neurosis. In Sweet WH, Obrador S, Martin-Rodrigues JG (eds): Neurosurgical Treatment in Psychiatry, Pain and Epilepsy. Baltimore, University Park Press, 1977, pp 287-300 4. Chiocca EA, Martmza RC: Neurosurgical therapy of the obsessive-compulsive disorder. In Jenike MA, Baer L, Minichiello WE (eds): Obsessive-Compulsive Disorders: Theory and Management. St. Louis, Mosby-Year Book, 1990, pp 283-294 5. Divitiis E, DErrico A, Cerillo A: Stereotactic surgery in Gilles de la Tourette syndrome. Acta Neurochir 24(suppl):73, 1977 6. Egas Moniz E: Tentatives Operatoires dans le Traitement de Certaines Psychoses. Paris, Ed. Masson & Cie, 1936, pp 248 7. Fodstad H, Strandman E, Karlsson B, et al: Treatment of chronic obsessive-compulsive states with stereotactic anterior capsulotomy of cingulotomy. Acta Neurochir 621-23, 1982
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8. Grey-Walter WG: Viewpoints of mental illness: Neurophysiologic aspects. Semin Psy-
chiatry 14:211-231, 1977 9. Hassler R, Dieckmann G: Relief of obsessive-compulsive disorders, phobias and tics by stereotactic coagulation of the rostra1 intralaminar and medial-thalamic nuclei. In Laitinen LV, Livingston KE (eds): Surgical Approaches in Psychiatry. Proceedings of the Third International Congress of Psychosurgery. Baltimore, University Park Press, 1973, pp 206212 10. Hemer T Treatment of mental disorders with frontal stereotaxic thermo-lesions: A follow-up study of 116 cases. Acta Psychiatr Neurol Scand 158(suppl):140, 1961 11. Jenike MA, Baer L, Ballantine HT, et al: Cingulotomy for refractory obsessive-compulsive disorder: A long-term follow-up of 33 patients. Arch Gen Psychiatry 48:548-555, 1991 12. Kelly D: The limbic system, sex, and emotions. In Anxiety and Emotions: Physiologic Basis and Treatment. Springfield, IL, Charles C Thomas, 1980, pp 197-300 13. Kelly P, Richardson A, Mitchell-Heggs N: Stereotactic limbic leukotomy: Neurophysiological aspects and operative technique. Br J Psychiatry 123:133-140, 1973 14. Knight G: The orbital cortex as an objective in the surgical treatment of mental illness: The results of 450 cases of open operation and the development of the stereotactic approach. Br J Surg 51314-124, 1964 15. Korzen AV, Pushkov VV, Kharitonou RA: [Stereotactic thalamotomy in the combined treatment]. Zh Nevropatol Psikhiatr 3:lOO-101, 1991 16. Kullberg G: Differences in effects of capsulotomy and cingulotomy. In Sweet WII, Obrador S, Martin-Rodrigues JG (eds): Neurosurgical Treatment in Psychiatry, Pain and Epilepsy. Baltimore, University Park Press, 1977, pp 301-308 17. Le Beau J: The cingular and precingular areas in psychosurgery (agitated behavior, obsessive-compulsive states, epilepsy). Acta Psychiatr Neurol Scand 27305-316, 1952 18. MacLean PD: Some psychiatric implications of physiological studies on the frontotemporal portion of the limbic system (visceral brain). Electroencephalogr Clin Neurophysiol 4:407-418, 1952 19. MacLean PD: Effects of lesions of globus pallidus on species-typical display behavior of squirrel monkeys. Brain Res 149:175-196, 1978 20. MacLean P D On the origin and progressive evolution of the triune brain. In Amstrong E, Falk D (eds): Primate Brain Evolution. New York, Plenum Press, 1982 21, Marino R Jr: Stereotactic cingulotomy for chronic neuropsychiatric disturbances and intractable pain [doctoral thesis] [Portuguese]. Sao Paulo, Brazil, University of Sao Paulo Medical School, 1971, 101 pp 22. Marino R Jr: Is parkinsonism a systemic disease [French]? Med et Hyg 46:1612-1614, 1988 23. Marino R Ir, Marques E, Marchetti RL, et al: Cinnulo-innominatotomy and Depression: A Contribution of Functional Neurosurgery of &e Limbic System & the Treatment of Refractory Depression [Portuguese] Monograph, 1986 Egas Moniz Prize Winner 24. Martuza RL, Chiocca EA, Jenike MA, et a1 Stereotactic radiofrequency thermal cingulotomy for obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 2331-336, 1990 25. Meyerson BA, Mindus P: The role of anterior internal capsulotomy in psychiatric surgery. In Hansford LD (ed): Modem Stereotactic Neurosurgery. Boston, Martinus Nijhoff, 1988, pp 353-364 26. Mindus P, Jenike MA: Neurosurgical treatments of malignant obsessive-compulsive disorder. Psychiatr Clin North Am 15:921-938, 1992 27. Model1 JG, Mountz JM, Curtis GC, et al: Neurophysiologic dysfunction in basal ganglia limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessivecompulsive disorder. J Neuropsychiatry 127-36,1989 28. Papez JW: A proposed mechanism of emotion. Arch Neurol Psychiatry 38:725743, 1937 29. Poppen JL: Technique of prefrontal lobotomy. J Neurosurg 5:514-520, 1948 30. Rauch SL, Baer L, Cosgrove GR, et a1 Neurosurgical treatment of Tourette’s disorder: A critical review. Compr Psychiatry 36:141-156,1995
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31. Scoville WB, Wilk EK, Pepe AJ: Selective cortical undercutting: Results in a new method of fractional lobotomy. Am J Psychiatry 107730-738, 1951 32. Singer HS, Walkup J T Tourette syndrome and other tic disorders: Diagnosis, pathophysiology and treatment. Medicine 70:15-32, 1991 33. Stevens J R An anatomy of schizophrenia? Arch Gen Psychiatry 29:177-189, 1973 34. Talairach J, Bancaud J, Geier S, et al: The cingulate gyrus and human behavior. Electroencephalogr Clin Neurophysiol3445-52, 1973 35. Whitty CWM, Duffield JE, Tow PM, et al: Anterior cingulectomy in the treatment of mental disease. Lancet k475-481, 1952
Address reprint requests to G. Rees Cosgrove, MD Neurosurgical Service Massachusetts General Hospital 15 Parkman Street Boston, MA 02114
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NEUROSURGICAL TREATMENT OF NEUROPSYCHIATRIC ILLNESS Raul Marino, Jr, MD, and G. Rees Cosgrove, MD
I returned from Brazil loving that land as much as the one I was born. I do not know how I could separate myself from that country, a continuation of my own. EGAS MONIZ (LETTER TO ALMEIDA LIMA)
In 1935, Egas Moniz, a distinguished Portuguese neurologist and the discoverer of cerebral angiography, had his neurosurgeon, Almeida Lima, perform the first surgical intervention for the treatment of mental illness6 The initial procedure involved injection of alcohol into the frontal lobes and was named ”prefrontal leukotomy,” becoming the first valid attempt in the surgical treatment of mental diseases. The neurosurgical treatment of psychiatric illness had thus begun and the term psychosurgery was coined to describe this novel approach. In 1949, Egas Moniz was awarded the Nobel Prize for his contributions in the field of psychosurgery and for his study on the functions and physiology of the frontal lobes. It was undoubtedly, one of the more stimulating contributions in the field of psychiatric thinking in the last six decades. The technique of prefrontal leucotomy, used in many thousands of desperate psychiatric patients, during the first decades following its discovery, subsequently has been replaced by more modern approaches. Nonetheless, it aroused a monumental volume of investigations in neuroanatomy, neurophysiology and psychiatry. Egas Moniz’s leukotomy procedure has provoked a revolution, not only in modern psychiatric thinking but in all philosophical and social sectors that are based in a better knowledge of cerebral mechanisms. Dozens of new psychosurgical techniques were introduced after the discovery of Egas Moniz, and many structures of the brain were targeted in an
From the Department of Neurology and Neurosurgery, University of S%oPaulo Medical School, S%oPaulo, Brazil (RM); and the Neurosurgical Service, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (GC)
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attempt to reduce the mortality and morbidity rates of the early procedures. Observations regarding the response to surgery in cases of mental disease considered refractory to treatment in the prepsychopharmacologic era of psychiatry were largely empirical, but supplied valuable insights into the functioning of these areas. Many of these empirical observations then were combined with laboratory research techniques by the psychiatrist and neurophysiologist MacLean, who introduced the concept of the "limbic system" in 1952.18Subsequent investigations have stemmed from his original work, thus launching the basis for his novel concept of a "psychencephalon," a denomination of the limbic brain and related structures introduced by MacLean in 1982.*OThe psychophysiology of the limbic system and related structures, which have been better understood in recent years, constitutes the modern "triune brain" theory also proposed by MacLean. These new concepts may soon present to psychiatric thought and the new science of physiodynamics (in distinction to psychodynamics) the same significance and impact that the historical Freudian concepts had to the knowledge of the structure of human personality. The recognition of Papez's theory on the importance of the rhinencephalic structures2Rand the experimental demonstration of their functions and connections by MacLean, Nauta, and many other authors, supported the concept previously unknown to medicine that the limbic system is the likely neuroanatomic substrate responsible for behavior, emotion, and psychiatric disease. After the 1950s, psychiatric thinking was guided by the investigative neurosciences, and the limbic system started to become the link between the brain, mind, and human conduct in a functional continuum. Present day psychiatry finally has absorbed all the contributions from the neurosciences that allowed for a better understanding of affect, humor, learning, memory, motivation, sexual behavior, and the control of many visceral and neurovegetative functions. We now can demonstrate that cortical, subcortical, and basal ganglia functions, without the participation of the limbic system, would have no relevance in the daily survival of an animal in a world that is biologically organized. Without this system, the intellectual functions never would experience the limits of reality, and human thinking would be ungoverned completely. This system will, thus, determine what will prevail in an individual-psychic normality, reason, or insanity. THE BASAL GANGLIA
The term basal ganglia originally referred to all the masses of gray matter buried within the cerebrum and thus included the caudate nucleus, putamen, globus pallidus (also called paleostriaturn or pallidurn), subthalamic nucleus, substantia nigra, claustrum, and the amygdala. The term striaturn refers to the caudate nucleus and the putamen together. Corpus striaturn refers to the caudate nucleus, putamen, and globus pallidus; the term lentiforrn nucleus refers to the putamen and globus pallidus together. Some investigators include additional regions in the basal ganglia such as the ventral striatum (or limbic striatum), which includes the nucleus accumbens, olfactory tubercle, and the nucleus of the stria terminalis. All of these structures resemble the caudate and putamen in ultrastructure and histochemistry. The ventral pallidurn is a region that receives afferents from the ventral striatum and sometimes the term is meant to include the heterogeneous group of neurons found within the substantia innominata. The striatum is the major recipient of input to the basal ganglia, with three
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afferent systems: the corticostriatal, the nigrostriatal, and the thalamostriatal projections. Other minor inputs originate in the locus coeruleus and the raphe nuclei. The former use the neurotransmitter norepinephrine, and the latter contain serotonin. Disruption of these input pathways to the basal ganglia has been associated with a wide variety of movement disorders, including Parkinson’s disease, Huntington’s chorea, tics, Gilles de la Tourette’s syndrome, Sydenham’s chorea, tardive dyskinesia, Wilson‘s disease, psychic akinesia, and also cognitive and complex behavioral dysfunctions of the brain such as schizophrenia, catatonia, major depression, anorexia nervosa, and obsessive-compulsive disorder (OCD). Parkinson’s disease is a progressive idiopathic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. This results in a loss of dopaminergic terminals in the striatum, and is characterized by muscular rigidity, fine tremor, shuffling gait, and bradykinesia. L-dopa, a precursor of dopamine introduced in 1967, is used as treatment of Parkinson’s disease because it augments the release of dopamine from the remaining terminals. On the other hand, the administration of antipsychotic agents in the treatment of schizophrenia has been associated with the occurrence of tardive dyskinesia. Many antipsychotic agents are dopamine-receptor antagonists, an effect which tends to explain their movement related side effects. The basal ganglia contain by far the highest concentration of dopamine in the brain. Ascending projection systems from brain stem to basal ganglia also have dopamine as their major transmitter, such as the nigrostriatal tract and the mesolimbic system. The mesolimbic system projects to the anterior extremity of the basal ganglia or limbic striatum (ventral striatum) represented by the nucleus accumbens, olfactory tubercle and nucleus of the stria terminalis, structures that receive input from limbic cortex, amygdala, and hippocampus. Stevens, in 1973,33suggested that the dopaminergic system in the basal ganglia could be a final common pathway for the schizophrenia syndrome, representing thus a dysfunction of the mesolimbic dopamine projection system in a manner similar to dysfunction of the nigrostriatal dopamine system in Parkinson’s disease, thus putting forward the concept of Parkinson’s disease and schizophrenia as contrasting conditions. The hypothesis that Parkinson’s disease also might represent a systemic disease, involving the neuroendocrine, peripheral neurotransmitter, and sympathetic system, also was advanced by one of the present authors= based on the findings of cerebral-adrenal transplantations for severe parkinsonism. After microscopic examination with fluorescence and morphometric study of 15 normal cadaveric adrenal glands, we demonstrated that the medullary layer of parkinsonian patients was comparatively hypotrophic and difficult to dissect in order to obtain graft specimens. Their cells were also poor in catecholamine contents. Basal ganglia dysfunction also became implicated in other psychiatric illness, such as OCD. The neurobiology of this syndrome is described elsewhere in this issue (see elsewhere in this issue). The advent of advanced neuroimaging techniques, such as morphometric magnetic resonance (mMR) imaging and positron emission tomography (PET), have opened new windows to look at the brain. Thus, PET scans have shown conspicuous abnormalities in the frontal lobes, cingulum, and basal ganglia of OCD patients when compared with depressed patients and normal controls. Furthermore, volumetrically computed MR imaging scans have shown decreased caudate volumes bilaterally in OCD patients, associated or not to demonstrable lesions in the striatum. A developmental abnormality also has been suggested in these patients, characterized by significantly more gray matter and
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less white matter in mMR imaging scans. A neurologic hypothesis for OCD thus is supported by the combination of findings from several high-technology imaging studies (see elsewhere in this issue). PSYCHIATRIC SURGERY
The neurosurgical treatment of mental illness is performed on patients who have intractable psychiatric disease-not upon the psyche per se. The term psychosurgery, introduced in the early 1940s, thus should be considered a misnomer. Many centers prefer the term limbic system surgery but only a few currently use these procedures as a therapeutic tool for the treatment of mental illness. Some of these operations also are used for the treatment of other diseases, such as chronic pain, intractable epilepsy, Parkinson’s disease, Gilles de la Tourette’s syndrome, and abnormal movements. The goal of these procedures is always to reduce the symptoms in severely ill patients who have not responded adequately to less radical treatments. The exact mechanisms by which surgery may modify psychiatric illness is unknown. It may be related to the ablation of specific areas or the disconnection of interrelated regions. It is also quite possible that the beneficial effects may be brought about more by chemical than by purely physical or anatomic changes in the brain. The neurochemical consequences of psychosurgery may lead to important changes in the availability of neurotransmitters or trophic factors at certain critical locations and also at areas remote from the areas ablated by the neurosurgeons. Thus, it may be both neuroanatomic and neurochemical changes that will affect behavior. Ballantine et a12 and Marinozl were among the first to propose, in 1967, stereotactic cingulotomy as a treatment of choice for chronic cancer pain, depression, OCD, and anorexia nervosa. OBSESSIVE-COMPULSIVE DISORDER
Accumulated data from the literature has shown compelling evidence that the cingulate gyrus and cingulate bundle are involved in the cause of OCD. Papez himself, in 1937,28regarded the cingulate cortex as ”the receptive region for impulses concerned with emotion,” suggesting that radiation of impulses from the cingulate gyrus to other cortical regions added emotional coloring to the psychic process. This implied that the cingulum was part of a reverberatory circuit, where impulses could circulate continually and, when reinforced, cause emotional experiences to be intensified. It would be interesting to quote one of Papez’ sibylline forethoughts that will be destined to remain as a classic in neuropsychiatric literature: The central emotive process of cortical origin may then be conceived as being built up in the hippocampal formation and as being transferred to the mammilary body and thence through the anterior thalamic nuclei to the cortex of the gyrus cinguli. The cortex of the cingular gyrus may be looked on as the receptive region for the experiencing of emotion as the result of impulses coming from the hypothalamic region, in the same way as the area striata is considered the receptive cortex for photic excitation coming from the retina. Radiation of the emotive process from the gyrus cinguli to other regions in the cerebral cortex would add emotional coloring to psychic process occurring elsewhere. This circuit would explain how emotion may arise in two ways: as a result of psychic activity and as a consequence of hypothalamic activity.
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Papez described affect as emotional coloring, and this quotation was printed in 1937 when the term limbic system was not yet coined by MacLean in 1952. Grey-Walter, in 1977; proposed that overactivity of the cingulum may lead to compulsive behavior, reporting the case of a university professor compelled to confess to all local crimes, and who was cured after small surgical lesions were placed in the cingulum. Talairach et al, in 1973,34reported their studies with indwelling electrodes, implanted to locate surgically resectable seizure foci, in which stereotyped repetitive rituals were produced by electrical stimulation of the cingulum in 52 patients presenting with drug-refractory epilepsy. During cingulum stimulation, the patients could not resist the urge to perform certain motions.34 The neurologic, neurosurgical, and psychiatric literature, reinforced by psychosurgical results of frontal leukotomies, has shown that a patient with a frontal lobe lesion has blunted affect, decreased judgment, and absence of worry. The present day neurobiologic findings suggest that the OCD patient has increased frontal lobe activity; theoretically, their cingulate connections produce instead a heightened sense of judgment or guilt, intense affective responses or depression, and a tendency to worry, anticipating negative outcomes. More recent neuroanatomic studies have shown important interconnections between the striatum and the limbic and cingulate structures. The caudate receives input from the frontal lobes and cingulate cortex, and then sends inhibitory projections to the thalamus, which in turn feeds back to the cortex, comprising a corticostriatalthalamic-cortical loop that mediates this output. Automatic behaviors also are mediated by the striatum, called "subroutines" by MacLean, in 1978.19Such behaviors include phylogenetically ancient patterns of grooming and also species-specific habits. In humans, this system is thought to mediate behaviors like saying one's own name, writing one's own signature, and so on. Increased activity of this loop is probably responsible for these subroutines, exemplified by inappropriate and repetitive grooming or checking rituals exhibited by OCD patients. Model1 et al, in 1989,27also proposed a neuroanatomic-neurochemical model for OCD based on this same frontostriatal-pallidothalamic-frontalloop. This reverberating circuit has two components: an orbitofrontal-thalamic circuit mediated by the excitatory neurotransmitter glutamate, and a second interconnection-the orbitofrontal-striatal-thalamic collateral, mediated by other neurotransmitters including glutamate, as well as dopamine, gamma-aminobutyric acid (GABA), and serotonin. The second interconnection modulates the neuronal activity of the former, and according to this hypothesis, overactivity in the orbitofrontal-thalamic interconnection would produce obsessive thoughts and compulsive rituals. In a normal individual, the orbitofrontal cortex also would stimulate, concomitantly, the caudate nucleus, which, as a consequence, would stimulate the pallidum, which, in turn, would inhibit the activity of the medial thalamic nuclei, the main basal station to the frontal cortex. This thalamic structure would modulate and correct the overactivity of the orbitofrontalthalamic stations. Dysfunctions in the modulatory activity of these interconnections may arise in OCD patients. Pharmacologic or surgical interference at this level of functional activity may alter favorably the imbalance in these areas, producing a diminution of its usual symptoms. Historically, the relative success of psychiatric surgery in treating OCD and other psychiatric refractory diseases is abundant in the psychiatric literature.2,7, 12,24,37 These and other studies have shown a consistently higher rate of symptom relief in OCD, as compared with various other psychiatric disorders such as schizophrenia, anorexia nervosa, anxiety, and so on. Several different psychiatric
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surgical interventions have appeared particularly useful. These include cingulotomy, limbic leukotomy, anterior capsulotomy, and subcaudate tractomy. In all of these procedures, transection of the tracts from frontal cortex to subcortical sites (i.e., en route to striatum and thalamus) have produced impressive results not only due to the rate of improvement but also for the low frequency of adverse effects. Chiocca and Martuza, in 1990; reviewed the world literature on these psychosurgical procedures and concluded that cingulotomy has a success rate of approximately 50% and a very low complication rate. Limbic leukotomy combines bilateral cingulate lesions with lesions in the orbital medial frontal areas, the passage site of fronto-caudate-thalamic fibers, critical in the circuit formation of OC symptoms. Success rates as high as 89% have been reported for this procedure. Anterior capsulotomy and subcaudate tractotomy were reported to improve 50% and 70% of OCD patients. Nevertheless, side effects from these two procedures appear to be higher, although temporary. The lower complication rates favor stereotactic cingulotomy as the first choice of a psychosurgical procedure to be considered in patients with disabling and severe refractory OCD. Patients who show no improvement following initial cingulotomy may be submitted to a second procedure or, alternatively, a stereotactic procedure in one of the other previously mentioned targets, which may produce relief not obtained by the first intervention. SURGICAL TECHNIQUES
Modern psychiatric surgery has experienced a profound evolution since the days of prefrontal leukotomy, and the open procedures proposed by Whitty et al,35 Le Beau,I7 P0ppen,2~Scoville et a1,3l and other authors. Practically all the achievements of modern conventional and functional neurosurgery have been incorporated into psychosurgical procedures. Ventriculograms and air studies have been replaced by CT and MR imaging, and target localization is obtained using very precise stereotactic frames, with spatial errors of fewer than 1 to 3 mm. Most procedures can be performed under local anaesthesia with mild sedation or light general anesthesia, without any pain or subjective stress to the patient during the lesioning. Knowledge of neuroanatomic structures and the use of precise anatomic atlases of the brain allow surgeons to make the lesions as small as possible in order to avoid unnecessary side effects. As this article is concerned mostly with mental illness physiopathologically related to the basal ganglia, we make a brief summary of the present state of the art procedures most commonly used for the psychosurgical treatment of OCD, Tourette’s syndrome, anorexia nervosa, anxiety, pain, and depression.’ The procedures that have been used preferentially during the last 25 years are cingulotomy, subcaudate tractotomy, limbic leukotomy, anterior capsulotomy, and thalamotomy. Cingulotomy
This procedure initially was proposed by Ballantine et a1 in 1967’ as a preferred treatment for chronic depression and cancer pain, although among the first 40 patients of this series, 10 also had OC symptoms and 10 had anorexia nervosa symptoms. Several consecutive series have been reported by these
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authors, containing more than 800 stereotactically treated patients. Techniques and results have been published elsewhere.Z,7, 11, 21, ~ 324, Cingulotomy, undoubtedly, constitutes the most commonly performed psychosurgical procedure at present, as all the reported series are associated with a very low incidence of complications and side effects. This procedure can be performed either under general anesthesia or with intravenous sedation. Burr holes or smaller twist drill holes are made bilaterally over the frontal region, and radiofrequency lesions are made following electrode penetration. No incision is necessary when a gamma-knife or a linear accelerator is used in the context of stereotactic radiosurgery. Cingulotomy lesions are placed within the cingulate bundles bilaterally, aided by CT or MR imaging. When radiofrequency is used, the thermocouple electrode tips are heated to 85°C for 60 seconds to make the coagulation lesions. Chiocca and Martuza4 recently have reviewed the worldwide literature on neurosurgical therapy of OCD and noted that cingulotomy has a success rate of approximately 50%. Jenike et all1 performed a long-term follow-up of 33 patients submitted to cingulotomy, using very conservative selection criteria. They have confirmed with this retrospective study that at least 25% to 30% of patients are markedly helped by one or more cingulotomy procedures when other proven treatments have not been successful. They relate this improvement either to cingulotomy per se or to the interaction of cingulotomy with postoperative pharmacologic or behavioral treatments. As seen previously, in the anatomic and neurophysiologic rationale presented, OCD symptoms are related to both anxiety and OC symptoms. Cingulotomy interrupts fibers of the cingulate bundle that are involved in the perpetuation of the anxiety component of this disorder. Subcaudate Tractotomy
This procedure was first described by Knight in 196414in Great Britain, and used to control depression. Lesions are made bilaterally in the substantia innominata under stereotactic guidance, in the rostra1 part of the orbital cortex, ventral to the head of caudate nucleus, between the anterior perforated substance and the striatum. The lesion interrupts the pathway between the frontal cortex, the hypothalamus, and the amygdala, which is involved in the control of anxiety, depression, and OC symptoms. According to Model1 et al,27overactivity of the frontocaudate-thalamicpathway provides the neuronal basis for OC symptoms. Interruption of these axonal fibers also would correct the abnormally increased activity of this bundle. More than 2000 patients have been submitted to this procedure and reported in the literature. Bridges et al, analysing Knight’s series, found total improvement or improvement with minimal symptoms in 67% of the patients with OCD. Subcaudate tractotomy also may be combined with anterior cingulotomy. This is a standard procedure that we have performed since 1977 for depression in 19 patients, with good results in 87.5% of the cases.23Kelly et all3 introduced this procedure in 1973 and coined the term limbic Zeukotomy to describe it. Limbic Leukotomy
The combination of the subcaudate tractotomy with cingulate lesions may lead to a better result for the treatment of OCD patients than either lesion alone. The subcaudate tractotomy interrupts the orbitofrontothalamic pathway
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involved in the pathogenesis of OCD and the cingulotomy destroys the nodal point of the Papez circuit, which interconnects hippocampus, fornix, mammilary bodies, anterior thalamic nuclei, and septa1 areas. Kelly, in 1980,12in an additional review of 49 patients operated upon by this procedure, reported 89% improvement 20 months after surgery. Postoperative symptom relief was not immediate after surgery, as we also have noted in our cingulotomy patients operated on since our 1967 report.* There was also significant reduction of anxiety and of obsessional traits. No long-term side effects were reported, but two patients commited suicide during the follow-up period. These results were interpreted by Kelly as a specific antiobsessional effect due to interruption of cingulate and frontothalamic pathways that mediate the anxiety and depressive symptoms in the OCD patients, making it in this author’s opinion, the procedure of choice in the surgical treatment of the OCD patient. Anterior Capsulotomy
This procedure entails bilateral lesions in the anterior limb of the internal capsule, thus disconnecting the limbic system from the frontal lobes. The main pathway crossing this portion of the internal capsule interconnects the orbitofrontal cortex with the midline thalamic nuclei. The fibers in the frontal lobes that were fanned were the same ones severed by the original and more empirical leukotomy procedures. Anterior capsulotomy was introduced by Leksell’O in the 1950s in Sweden. Herner, in 1961,’” was one of the first to report its efficacy in OCD, finding good or fair results in 81% of the patients undergoing this procedure. Meyerson and Mindus,Z5Fodstad et al,7Mindus and Jenike,26and KullbergI6also have reported favorable results of this procedure in OCD. Kullberg, however, reports some personality side effects of capsulotomy as compared with cingulotomy: one patient lost impulse control, with release of aggressive tendencies. Other changes included emotional shallowness, loss of initiative, diminution of inhibition, lethargy, and elevation of mood. Some of these side effects also have been observed in our former leukotomy patients but they are usually temporary in both procedures. Thalarnotorny
Several psychosurgical procedures were tried to control some of the devastating symptoms of Tourette’s syndrome: motor and phonic tics, self-injurious and self-destructive behaviors, coprolalic utterances, echolalia, echopraxia, barklike sounds, and so on. Bimedial frontal leukotomy, limbic leukotomy, cingulotomy, cerebellar surgery (dentatotomy), and thalamic surgery constitute a few of the reported techniques in the literature. The physiopathology of Tourette’s syndrome, however, remains poorly understood. Singer et a132suggest .that tics are mediated via midbrain dopaminergic systems interacting with the basal ganglia. Dopaminergic nigrostriatal projections to limbic striatum have been associated with affective illness, psychosis, and also with OCD. As previously seen, mediation of affective, cognitive, and motor functions by the basal ganglia also could represent involvement of these structures in Tourette’s syndrome. This issue of The Psychiatric Clinics has pointed to some clinical and genetic relationships between Tourette’s syndrome and OCD, models of which may be
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extended to the pathophysiology of Tourette‘s syndrome as well (see elsewhere in this issue). Neurosurgical lesions may influence these same neural systems. The intralaminar nuclei, part of the so-called diffuse thalamic-system, are small nuclei scattered throughout the intralaminar thalamic connective tissue, which separates the various subdivisions of the thalamus. These nuclei receive input diffusely from other thalamic nuclei, the reticular formation, and basal ganglia, and send their output diffusely to the frontal, motor, and premotor cortex. Lesions of these nuclei thus would interrupt the frontothalamic axis within the thalamus, leaving intact the important somatic thalamic nuclei. Hassler and Dieckmann, in 19737 reported their experience with bilateral coagulation of the rostra1 intralaminar and medial thalamic nuclei in 15 Tourette’s syndrome patients with several degrees of improvement. Other authors also have tried thalamic targets (dorsomedial and ventrolateral) apparently without S U C C ~ S S . l~5, Case reports in the literature, however, provide only anecdotal evidence in support of the efficacy and safety of the neurosurgical treatment for Tourette’s syndrome. Rauch et a130 have analysed these results reported in the literature and consider that the psychosurgical treatment of Tourette’s syndrome remains experimental, with no compelling evidence that any procedure is superior to all others.
CONCLUSION Patient selection criteria and indications for psychosurgical procedures are best understood for the treatment of depression and OCD, although therapeutic benefit has been evident for a limited number of other psychiatric conditions. Severe and enduring psychiatric illness that is unresponsiveness to all available contemporary therapies constitutes the main selection criterion for considering a psychosurgical procedure. Informed consent always must be obtained from the patients and their families.
References 1. Apo M, Laitinen L, Vickki J: Stereotactic cingulotomy in schizophrenia. Psychiatria Fennica 2:105-110, 1971 2. Ballantine HT Jr, Cassidy WL, Flanagan NB, et al: Stereotaxic anterior cingulotomy for neuropsychiatric illness and intractable pain. J Neurosurg 26:488495, 1967 3. Bingley T, Leksell L, Meyerson BA, et al: Long-term results of stereotactic anterior capsulotomy in chronic obsessive-compulsive neurosis. In Sweet WH, Obrador S, Martin-Rodrigues JG (eds): Neurosurgical Treatment in Psychiatry, Pain and Epilepsy. Baltimore, University Park Press, 1977, pp 287-300 4. Chiocca EA, Martmza RC: Neurosurgical therapy of the obsessive-compulsive disorder. In Jenike MA, Baer L, Minichiello WE (eds): Obsessive-Compulsive Disorders: Theory and Management. St. Louis, Mosby-Year Book, 1990, pp 283-294 5. Divitiis E, DErrico A, Cerillo A: Stereotactic surgery in Gilles de la Tourette syndrome. Acta Neurochir 24(suppl):73, 1977 6. Egas Moniz E: Tentatives Operatoires dans le Traitement de Certaines Psychoses. Paris, Ed. Masson & Cie, 1936, pp 248 7. Fodstad H, Strandman E, Karlsson B, et al: Treatment of chronic obsessive-compulsive states with stereotactic anterior capsulotomy of cingulotomy. Acta Neurochir 621-23, 1982
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8. Grey-Walter WG: Viewpoints of mental illness: Neurophysiologic aspects. Semin Psy-
chiatry 14:211-231, 1977 9. Hassler R, Dieckmann G: Relief of obsessive-compulsive disorders, phobias and tics by stereotactic coagulation of the rostra1 intralaminar and medial-thalamic nuclei. In Laitinen LV, Livingston KE (eds): Surgical Approaches in Psychiatry. Proceedings of the Third International Congress of Psychosurgery. Baltimore, University Park Press, 1973, pp 206212 10. Hemer T Treatment of mental disorders with frontal stereotaxic thermo-lesions: A follow-up study of 116 cases. Acta Psychiatr Neurol Scand 158(suppl):140, 1961 11. Jenike MA, Baer L, Ballantine HT, et al: Cingulotomy for refractory obsessive-compulsive disorder: A long-term follow-up of 33 patients. Arch Gen Psychiatry 48:548-555, 1991 12. Kelly D: The limbic system, sex, and emotions. In Anxiety and Emotions: Physiologic Basis and Treatment. Springfield, IL, Charles C Thomas, 1980, pp 197-300 13. Kelly P, Richardson A, Mitchell-Heggs N: Stereotactic limbic leukotomy: Neurophysiological aspects and operative technique. Br J Psychiatry 123:133-140, 1973 14. Knight G: The orbital cortex as an objective in the surgical treatment of mental illness: The results of 450 cases of open operation and the development of the stereotactic approach. Br J Surg 51314-124, 1964 15. Korzen AV, Pushkov VV, Kharitonou RA: [Stereotactic thalamotomy in the combined treatment]. Zh Nevropatol Psikhiatr 3:lOO-101, 1991 16. Kullberg G: Differences in effects of capsulotomy and cingulotomy. In Sweet WII, Obrador S, Martin-Rodrigues JG (eds): Neurosurgical Treatment in Psychiatry, Pain and Epilepsy. Baltimore, University Park Press, 1977, pp 301-308 17. Le Beau J: The cingular and precingular areas in psychosurgery (agitated behavior, obsessive-compulsive states, epilepsy). Acta Psychiatr Neurol Scand 27305-316, 1952 18. MacLean PD: Some psychiatric implications of physiological studies on the frontotemporal portion of the limbic system (visceral brain). Electroencephalogr Clin Neurophysiol 4:407-418, 1952 19. MacLean PD: Effects of lesions of globus pallidus on species-typical display behavior of squirrel monkeys. Brain Res 149:175-196, 1978 20. MacLean P D On the origin and progressive evolution of the triune brain. In Amstrong E, Falk D (eds): Primate Brain Evolution. New York, Plenum Press, 1982 21, Marino R Jr: Stereotactic cingulotomy for chronic neuropsychiatric disturbances and intractable pain [doctoral thesis] [Portuguese]. Sao Paulo, Brazil, University of Sao Paulo Medical School, 1971, 101 pp 22. Marino R Jr: Is parkinsonism a systemic disease [French]? Med et Hyg 46:1612-1614, 1988 23. Marino R Ir, Marques E, Marchetti RL, et al: Cinnulo-innominatotomy and Depression: A Contribution of Functional Neurosurgery of &e Limbic System & the Treatment of Refractory Depression [Portuguese] Monograph, 1986 Egas Moniz Prize Winner 24. Martuza RL, Chiocca EA, Jenike MA, et a1 Stereotactic radiofrequency thermal cingulotomy for obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 2331-336, 1990 25. Meyerson BA, Mindus P: The role of anterior internal capsulotomy in psychiatric surgery. In Hansford LD (ed): Modem Stereotactic Neurosurgery. Boston, Martinus Nijhoff, 1988, pp 353-364 26. Mindus P, Jenike MA: Neurosurgical treatments of malignant obsessive-compulsive disorder. Psychiatr Clin North Am 15:921-938, 1992 27. Model1 JG, Mountz JM, Curtis GC, et al: Neurophysiologic dysfunction in basal ganglia limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessivecompulsive disorder. J Neuropsychiatry 127-36,1989 28. Papez JW: A proposed mechanism of emotion. Arch Neurol Psychiatry 38:725743, 1937 29. Poppen JL: Technique of prefrontal lobotomy. J Neurosurg 5:514-520, 1948 30. Rauch SL, Baer L, Cosgrove GR, et a1 Neurosurgical treatment of Tourette’s disorder: A critical review. Compr Psychiatry 36:141-156,1995
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31. Scoville WB, Wilk EK, Pepe AJ: Selective cortical undercutting: Results in a new method of fractional lobotomy. Am J Psychiatry 107730-738, 1951 32. Singer HS, Walkup J T Tourette syndrome and other tic disorders: Diagnosis, pathophysiology and treatment. Medicine 70:15-32, 1991 33. Stevens J R An anatomy of schizophrenia? Arch Gen Psychiatry 29:177-189, 1973 34. Talairach J, Bancaud J, Geier S, et al: The cingulate gyrus and human behavior. Electroencephalogr Clin Neurophysiol3445-52, 1973 35. Whitty CWM, Duffield JE, Tow PM, et al: Anterior cingulectomy in the treatment of mental disease. Lancet k475-481, 1952
Address reprint requests to G. Rees Cosgrove, MD Neurosurgical Service Massachusetts General Hospital 15 Parkman Street Boston, MA 02114