PSYCHIATRIC NEUROSURGERY

Emad N. Eskandar MD, G. Rees Cosgrove MD FRCS, and Scott L. Rauch MD
Departments of Neurosurgery and Psychiatry,
Massachusetts General Hospital
Harvard Medical School,
Boston, Massachusetts

Address for Correspondence:
Emad N. Eskandar, M.D.
Massachusetts General Hospital
WACC Suite # 331
Boston , Massachusetts
E-mail: eeskandar@partners.org
Patient Appointments: 617.724.6590
FAX: 617.724.0339

Scott L. Rauch MD
Department of Psychiatry
Massachusetts General Hospital
Building 149-13th Street-Floor 9
Charlestown , Massachusetts
(617) 726-6766

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Psychiatric Neurosurgery Overview:

Psychiatric neurosurgery involves the surgical ablation or disconnection of brain tissue with the intent of altering abnormal affective and behavioral states caused by mental illness. It is classified as a functional neurosurgical procedure because it attempts to improve or restore function by altering underlying physiology. The surgical target may be cerebral cortex, nuclei or pathways that display either normal or abnormal physiologic activity. Other functional neurosurgical procedures include the surgical treatment of epilepsy in which a temporal lobe may be removed or the surgical treatment of Parkinsons Disease in which lesions are made in the basal ganglia. Whereas the pathological substrates of these disorders are well understood and their manifestations often include physical or neurologic findings, the biological basis of most psychiatric illnesses remain poorly understood and their expression involves mental or psychic symptoms without objective physical signs. Chronic pain is similar to psychiatric illness in that symptoms are often accompanied by mental anguish without physical findings but the anatomical pathways for pain transmission are well known and surgical results are predictable.

The pathways involved in psychiatric illness are poorly defined and surgical results variable, therefore the practice of psychiatric neurosurgery has often been surrounded by controversy. At various times it has been widely accepted and at other times flatly rejected by both the medical profession and society at large. To understand this controversy one must appreciate the historical evolution of psychiatric neurosurgery . Psychiatric neurosurgery was first introduced as a treatment for severe mental illness by Egas Moniz in 1936 . At that time, no satisfactory pharmacological treatment options existed and a variety of unproven somatic therapies were being used including insulin-shock therapy, metrazol-shock therapy, and electroconvulsive therapy. Asylums for the insane were overflowing with the mentally ill and therefore, despite a lack of objective therapeutic benefit, psychiatric neurosurgery was enthusiastically adopted by practitioners of the day. At the height of enthusiasm, psychiatric neurosurgery was recommended for curing or ameliorating schizophrenia, depression, homosexuality, childhood behavior disorders, criminal behavior and uncontrolled violence. It is estimated that over 50,000 procedures were performed in the United States alone between 1936 and the mid-1950's and much of the controversy surrounding psychiatric neurosurgery may relate to its overzealous and sometimes indiscriminate application during this period.

The earliest procedures involved open operations with excision of both frontal lobes (frontal lobectomy) or disconnection of the frontal lobes from the remaining brain using a blunt instrument (frontal leucotomy). Despite technical differences, these operations were generally considered as one and the same (frontal lobotomy) and were associated with a high complication rate including intellectual impairment, personality change, seizures, paralysis and death. Despite these complications, the operations were felt to be helpful in the majority of patients and Moniz was awarded the Nobel Prize in Medicine in 1949 "for his discovery of the therapeutic value of prefrontal leucotomy in certain psychoses."
In an attempt to reduce the morbidity of the early interventions, more selective excisions of cingulate and orbito-frontal cortex (corticectomy) were employed with comparable success rates but fewer complications. Stereotactic operations were subsequently developed that allowed for accurate positioning of small electrodes in deep brain structures. However, with the introduction of chlorpromazine in 1954 along with subsequent psychotropic drugs, the role of surgery declined dramatically. Nevertheless, some patients failed to respond to appropriate pharmacological therapy and referrals to specialized centers for neurosurgical intervention continued.

Even though the frontal lobotomy of earlier years had been abandoned in favor of more selective stereotactic interventions and the number of procedures performed were greatly reduced, the concern about the use of psychiatric neurosurgery grew during the 1960's and 1970's. This was due to questions about efficacy, reports of permanent sequelae and the potential for abuse all fueled by publications in the lay press. Public debate in the United States, England and Australia prompted the formation of national commissions to investigate psychiatric neurosurgery and encouraged legislation to regulate its use. Many of the social, political and moral issues at the heart of the controversy surrounding psychiatric neurosurgery have since been addressed but some scientific and philosophical issues remain.

In the United States, the report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research indicated that psychiatric neurosurgery was efficacious in more than half of the 400 operations performed annually between 1971-1973 and that no psychological deficits could be attributed to the procedures. Fears that psychiatric neurosurgery was being used on minority and disadvantaged populations for social control were unsubstantiated. Preoperative and postoperative studies by independent observers of smaller groups of patients undergoing cingulotomy demonstrated excellent results in the majority and significant improvement in full scale, verbal and performance IQ. Detailed neuropsychological testing of patients undergoing a variety of more extensive psychosurgical procedures also failed to demonstrate any worsening except in a single category (Wisconsin card sorting) and over half of the patients experienced a marked improvement in their psychiatric symptoms. These independent evaluations of outcome and side effects appear to corroborate the prevailing published experience. More modern clinical series report similar success rates of 25 - 60% depending on the psychiatric diagnosis and methodology. These results argue against the initial public perception that psychiatric neurosurgery was dangerous, ineffective and experimental but opposition remains despite its formal acceptance in position statements by organized psychiatry in many countries around the world.

One valid criticism of psychiatric neurosurgery is that the theoretical basis of the treatment is not well established. Neuropyschological, physiological and neuroimaging studies have supplied some evidence to implicate the limbic system and its interconnections with the basal ganglia and forebrain in the pathophysiology of major affective illness, obsessive-compulsive disorder and other anxiety disorders. Electrical stimulation of specific areas within the limbic system (i.e. the anterior cingulum), has been shown in humans to alter both autonomic responses and anxiety levels. Abnormalities of glucose metabolism have been found in the caudate nucleus, orbitofrontal cortex and cingulum in patients with OCD on positron emission tomography (PET). Similarly, PET studies have shown reduced glucose metabolism in the lateral frontal cortex as a correlate of the depressive state in certain patients. But while it is intuitively appealing to think that these disorders might reflect a final common pathway of limbic dysregulation, the neuroanatomical and neurochemical basis of emotion in health and disease remains undefined. It is possible that as the understanding of the pathophysiology improves, the medical community and society at large will become more accepting of these procedures.

Currently the accepted therapeutic approach to most psychiatric disease involves a combination of psychotherapy, pharmacotherapy and, in some instances, electroconvulsive therapy. However, despite these modern treatment methods, some patients fail to respond adequately and remain severely disabled. In these patients, surgical intervention might be considered appropriate despite a firm theoretical basis, if the therapeutic result and overall level of functioning could be improved. On the other hand, there is no consensus amongst practitioners about the duration, intensity or degree to which other therapies should be tried before resorting to psychiatric neurosurgery .

Critics of psychiatric neurosurgery suggest that surgery may often be performed before other alternative therapies are sufficiently tried. Currently, only patients with chronic, severe and disabling psychiatric illness that are completely refractory to all conventional therapy are considered for surgery. This implies that well documented systematic trials of pharmacologic, psychologic and when appropriate, electroconvulsive therapy have been tried both singly and in combination before neurosurgical intervention is considered. The severity of the patient's illness must be manifest both in terms of subjective distress and a decrement in psycho-social functioning. Chronicity refers to the enduring nature of the illness and in some cases may be less important than severity but generally requires several years duration.

Although the number of psychosurgical procedures performed in the world today is unknown, it is estimated that fewer than 25 patients are operated upon annually in the United States and Great Britain, while only 1-2/year undergo psychiatric neurosurgery in Australia. Claims that psychiatric neurosurgery is being overutilized seem exaggerated.

There was a time when any patient with a severe psychiatric illness might be considered a candidate for surgical intervention, with the only major criterion being that the patient be in a "fixed state of tortured self concern ". This global inclusion criterion created a very heterogeneous subject population which made comparison of outcomes difficult. The lack of accurate psychiatric diagnosis made it impossible to predict outcome based upon clinical syndromes. To be fair to practitioners of the day, psychiatric diagnosis was less well defined and certain diagnoses such as OCD did not yet exist as distinct entities.

It is now clear that the indications for psychiatric neurosurgery are much more restrictive. There is general agreement that patients with major affective disorder, chronic anxiety states and obsessive compulsive disorder are the best candidates for surgery. These patients must meet DSM for the respective diagnostic categories. Despite the fact that the majority of patients who underwent psychiatric neurosurgery in the past were diagnosed as schizophrenic, schizophrenia is not currently considered an indication for surgery. Personality disorders or psychoactive substance use disorder are significant relative contraindications to surgery.

Appropriate selection of patients for surgery remains a major issue and the responsibility of the psychiatrist, guided by the informed and expert opinions of the other members of the psychosurgical team. Ethical objections about the use of psychiatric neurosurgery have been addressed in all centers by insuring an informed consent from the patient and family without coercion, along with unanimous agreement amongst the referring and treating physicians.

Since the scientific rationale for psychiatric neurosurgery is lacking, observations and conclusions regarding its use have been largely empirical and accumulated over many years from a variety of institutions. Although many psychosurgical techniques have been used in the past, four procedures have evolved as the safest and most effective. These are all performed bilaterally under modern stereotactic conditions to allow for precise identification and accurate lesioning of the target structures. The contemporary procedures are anterior cingulotomy, subcaudate tractotomy, limbic leucotomy, and anterior capsulotomy. All involve lesions of limbic or paralimbic territories or interruptions of their connections with deeper brain structures. In fact, all psychosurgical procedures have been directed at some component within this system and therefore some authors prefer the term limbic system surgery to psychiatric neurosurgery . With currently available data, it is impossible to determine whether there is one optimal surgical technique or strategy. All forms of these modern procedures seem to be safe and well tolerated with few side effects or complications.

Subjective evaluations of outcome in the past have allowed critics of psychiatric neurosurgery to challenge the overall results with some validity. Given the difficulty of assessing outcome in functional mental and behavioral disorders, the criteria for cure or significant improvement are not clear and have never been universally agreed upon. There also exist many obstacles that prevent a direct comparison of results across centers including diagnostic inaccuracies, nonstandardized presurgical evaluation tools, center bias and varied outcome assessment scales. However, if a global outcome rating of symptom free or much improved is considered a satisfactory response, then in a recent review of modern surgical series of patients with OCD, cingulotomy was effective in 56%, subcaudate tractotomy in 50%, limbic leucotomy in 61% and capsulotomy in 67%. In patients with major affective disorder, cingulotomy was effective in 65%, subcaudate tractotomy in 68%, limbic leucotomy in 78% and capsulotomy in 55%.

Based upon these methods of comparison, the clinical superiority of any one procedure is not convincing although there is a suggestion that anterior capsulotomy and limbic leucotomy may be slightly more effective in patients with OCD. Cingulotomy is most commonly used in the United States whereas in Europe, capsulotomy and limbic leucotomy are more prevalent. They all appear roughly equivalent from a therapeutic standpoint but in terms of unwanted side effects, cingulotomy appears to be the safest of all procedures currently performed.

Another criticism of psychiatric neurosurgery has been that no matter which structure in the limbic system is chosen for ablation, the clinical outcome appears similar. This lack of specificity is not necessarily evidence against its use since many psychotropic agents and even ECT can have benefit across a wide range of mental disorders. It more likely underlines our incomplete understanding of the neurobiological basis of psychiatric disease and our failure to perform careful controlled trials comparing different surgical techniques within the same center.
Many psychiatrists would readily accept an empirical treatment if the available clinical data supporting a favorable outcome were substantial and convincing. To date only a few prospective long term follow-up trials have been completed but these do appear to support the contention that even using the most stringent outcome criteria, cingulotomy and anterior capsulotomy are helpful in 25 - 50% of patients with intractable OCD. Using less stringent outcome criteria, improvement is seen in 50 - 70% of patients which is similar to earlier studies.

While controversy exists regarding the exact choice of surgical procedure to be employed, there is unanimous agreement that the presurgical evaluation must be performed by committed multi-disciplinary teams with expertise and experience in the surgical treatment of psychiatric illness. Diagnosis based upon a formal classification scheme is essential. Although it is impossible to mandate across all centers , prospective trials employing standardized clinical instruments with long term follow-up are needed.

Comparisons of preoperative and postoperative functional status remain an important parameter in addition to target psychiatric symptoms, in characterizing outcome. The operation is not curative and should be considered as only one aspect in the overall management of these patients. All centers with experience emphasize the importance of rehabilitation postoperatively and the need for ongoing psychiatric follow-up. It appears that many patients are greatly improved after surgery and the complications or side effects are few.
Despite the advent of new and effective psychopharmacologic agents, it is generally felt by centers employing this form of surgical intervention, that psychiatric neurosurgery remains an important therapeutic option for disabling psychiatric disease and is probably underutilized. Caution must be urged however regarding its use, to ensure that the overzealous and indiscriminate application of this form of therapy never recurs. Hopefully, as our understanding of the neurobiological basis of psychiatric illness improves, the rationale and theoretical basis for surgical intervention will become apparent. Until then, only carefully controlled, prospective long term follow up studies by independent observers can improve our empirical assessment of psychiatric neurosurgery .

Further Reading:

Ballantine HT,Jr., Bouckoms AJ, Thomas EK, et al (1987): Treatment of psychiatric illness by stereotactic cingulotomy. Biol Psychiatry 22:807-819

Corkin S, Twitchell TE, Sullivan EV (1979): Safety and efficacy of cingulotomy for pain and psychiatric disorders. In Hitchcock ER, Ballantine HT, Myerson BA, (eds): Modern Concepts in Psychiatric Surgery, Elsevier, Amsterdam

Cosgrove GR, Rauch SL. (2003) Stereotactic cingulotomy. Neurosurg Clin N Am. 14(2):225-35.

Cosgrove GR and Rauch SL (1995): Psychiatric neurosurgery . In Gildenberg PH, (ed): Functional Neurosurgery, W.B.Saunders Co, Philadelphia

Diering SL, Bell WO (1991): Functional Neurosurgery for psychiatric disorders: a historical perspective. Stereotact Funct Neurosurg 57:175-194

Dougherty DD, Baer L, Cosgrove GR, Cassem EH, Price BH, Nierenberg AA, Jenike MA, Rauch SL. (2002) Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder. Am J Psychiatry. 2002 159(2):269-75.

Greenberg BD, Price LH, Rauch SL, Friehs G, Noren G, Malone D, Carpenter LL, Rezai AR, Rasmussen SA. (2003) Neurosurgery for intractable obsessive-compulsive disorder and depression: critical issues. Neurosurg Clin N Am. 14(2):199-212.

Mindus P, Rasmussen SA, Lindquist C (1994): Neurosurgical treatment for refractory obsessive-compulsive disorder: implications for understanding frontal lobe function. J Neuropsychiatry 6(4):467-477

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1979): Report and Recommendations: Psychiatric neurosurgery . Department of Health and Human Services, Pub No (OS) 77-002. Washington DC: US Government Printing Office

Poyton AM, Kartsounis LD, Bridges PK (1995): A prospective clinical study of stereotactic subcaudate tractotomy. Psychological Med 25:763-770

Price BH, Baral I, Cosgrove GR, Rauch SL, Nierenberg AA, Jenike MA, Cassem EH. (2001) Improvement in severe self-mutilation following limbic leucotomy: a series of 5 consecutive cases. J Clin Psychiatry. 2001 62(12):925-32.

Rauch SL, Kim H, Makris N, Cosgrove GR, Cassem EH, Savage CR, Price BH, Nierenberg AA, Shera D, Baer L, Buchbinder B, Caviness VS Jr, Jenike MA, Kennedy DN. (2000) Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study. J Neurosurg. 93(6):1019-25.

Rauch SL. (2003) Neuroimaging and neurocircuitry models pertaining to the neurosurgical treatment of psychiatric disorders. Neurosurg Clin N Am. 14(2):213-23

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