Psychosurgery-Old and New

Despite its wretched history, psychosurgery is back with a new name-neurosurgery for mental disorders-and with renewed confidence in its benefits.¹ Two technologies are now available that produce small lesions in the brain: stereotactic microablation and gamma knife radiation (no burr holes necessary). Concomitant functional imaging allows for precision targeting that makes these procedures state of the art, but it is possible that deep brain stimulation (DBS), which has shown early promise in clinical trials and is an exciting research tool, may replace ablative procedures that destroy brain cells. Both new stereotactic neurosurgery and old psychosurgery were the focus of recent mass media reports.

A carefully documented front-page story in the Wall Street Journal described an "outbreak" of stereotactic neurosurgery in China.² The news story contrasted the careful interdisciplinary screening procedures and limited use in model US programs, such as that in place at Massachusetts General Hospital (MGH) in Boston, with the money-driven exploitation in China.

Chinese physicians have been thrust into the sink-or-swim market economy, and standards of care are being undermined by economic self-interest.³ Market forces are present everywhere in medicine, and the companies that make the state-of-the-art neurosurgical devices have added their muscle to the pressure to perform more procedures both here and abroad (Yang Shao, personal communication, January 2008). In that environment, stereotactic neurosurgery in China became a profit-driven enterprise. Neurosurgeons apparently offered the procedure to any patient whose family had the money, without any psychiatric screening.

Schizophrenia is not an accepted target for the new neurosurgery, as it was for the old psychosurgery; however, in the money-driven outbreak in China, the procedure was offered to a patient with schizophrenia whose poor outcome included adverse neurological consequences. His case history was the centerpiece of the original Wall Street Journal article.² Within weeks of the first story, a second report announced that the Chinese authorities would be regulating these new neurosurgical procedures.⁴ The proposed standards were similar to those in place at MGH (Bin Xie and Yang Shao, personal communication, December 2007).

The old psychosurgery

Recently, the American public was again exposed to the most appalling practices of that old era of psychosurgery on public television's presentation of "The Lobotomist" on the American Experience with the bone-chilling documentary of transorbital frontal lobotomy (the so-called ice pick operation) by Walter Freeman.⁵ Freeman, like Ant-nio Egas Moniz (who was awarded the Nobel Prize in physiology or medicine for his discovery of prefrontal lobotomy), was not a neurosurgeon or a disciplined scientist. However, he introduced and adapted Moniz's lobotomy in the United States while working with James Watts, who was a qualified surgeon.

Freeman and Watts began operating on patients with schizophrenia who were selected from Saint Elizabeths Hospital in Washington, DC. Freeman believed that patients with violent and aggressive tendencies would be pacified by the procedure.⁶ As early as 1939, Freeman and Watts began operating on children with schizophrenia, including a 4-year-old boy.⁶ Freeman, who was a "showman" and far more zealous than Watts, argued for psychosurgery early in the patients' illnesses rather than reserving it for patients with intractable illnesses.

In his zeal to make lobotomy more widely available, Freeman experimented with cadavers and, adapting the work of an Italian psychosurgeon, invented and personally performed the first transorbital lobotomy in his own office. It was a blind procedure, since he never visualized the field. He used an actual ice pick inserted via the tear duct through the orbital plate into the frontal brain. His target was the frontal thalamic tracts, which he attacked by moving the instrument "15 to 20 degrees medially and about 30 degrees laterally."⁶ Watts rejected Freeman's cavalier approach to neurosurgery, but transorbital lobotomy (the ice pick procedure) was widely heralded as the new cure for mental illness by the media whom Freeman assiduously courted. Without the need for a surgical suite and using unmodified electroconvulsive therapy as anesthesia, Freeman went on to perform the procedure on almost 3000 patients in hospitals all over the United States.

In the infamous newsreel footage shown in movie theaters in the early 1950s and included in "The Lobotomist," Freeman can be seen performing the ice pick procedure without even using the standard precaution of sterile surgical gloves. (Freeman was famously annoyed with sterile procedures and refused to wear a surgical mask or gloves.⁶) Like most doctors during that era, he provided no informed consent and his fee was what the traffic would bear. Freeman operated on Rosemary Kennedy-his most famous, or perhaps infamous, failure. However, his most shameful legacy may be that he performed psychosurgery on children as young as 4 years as well as on rebellious adolescents.

Both the Freeman documentary and the abuse of the new neurosurgery in China brought me back to earlier periods in my own career. During my years as a student at Yale Medical School, I attended a Grand Rounds at which Freeman presented and showed the infamous newsreel footage. He apparently took pleasure in shocking his medical audience. It was the most horrifying experience of my entire medical education, made worse by the fact that none of the professors whom I admired raised any objections to the radical procedure or criticized Freeman for his cavalier disregard of sterile precautions. But it was also an important learning experience for me, and it demonstrated the insidious power of Irving Janus's "groupthink" etiquette in medicine. One did not criticize other doctors in public. In fact, I later learned that John Fulton, Yale's legendary professor of neurophysiology, had protected Freeman from professional censure, although he had very serious reservations about his scientific approach.⁶

Although Freeman's transorbital approach was eventually discredited and abandoned, various modified and more limited versions of the old psychosurgery continued. During the years leading up to DSM-III in 1980, the generally accepted indication was "intractable tortured self-concern."¹ That may be an apt generic description of the intractable disorders for which neurosurgery is now offered: obsessive-compulsive disorder (OCD), major depressive disorder, and chronic anxiety disorder. However, in those early years during the transition from the old psychosurgery to the new neurosurgery, many other symptoms and conditions were targeted; for example, there were reports of the successful treatment of anorexia nervosa and temporal lobe epilepsy that lead to violence.

It was during this transitional era that the Massachusetts Department of Mental Health asked me to chair a committee and to develop regulations for psychosurgery for the state. One of the crucial criteria I proposed was that an outside consultant, not a member of the hospital staff, review and approve each case. That provision was rejected by the MGH neurologist who was a member of my committee, by all the other physicians, and by the Massachusetts Department of Mental Health. Some states subsequently made outside consultation a legal requirement,⁷ and the 1991 United Nations' (UN) resolution on the protection of persons with mental illness requires that an "independent external body" must be "satisfied" that there is informed consent and that the "treatment best serves the health needs of the patient."⁸

The Freeman era and the unwillingness of psychosurgeons to accept the discipline of external review left me with a negative impression of the entire enterprise. My own clinical experience with patients who had been subjected to these procedures did nothing to reassure me. Colleagues with more experience agreed that such surgical procedures definitely helped some patients, but it was difficult to identify who would benefit in advance or to explain why in hindsight.

The new neurosurgery

The transition from the old psychosurgery to the new, more discrete ablative neurosurgery for psychiatric disorders has been documented in several publications.⁹ At the technical level, one important innovation was the stereotactic approach and the use of implantable electrodes to perform minute ablative procedures on selected targets. At the ethical level was the US National Commission report on the use of psychosurgery in practice and research¹⁰ that suggested guidelines and not, as many had expected, abolition or outside consultation.

MGH began psychosurgery early on and played an important role during the transitional era. Dr Thomas Ballantine, a neurosurgeon at MGH who had been an influential member of the National Commission shaping the guidelines, continued over the years to perform bilateral cingulotomies. A retrospective report of the 198 patients who had a variety of psychiatric disorders and on whom he had performed cingulotomies was published in 1987.¹¹

In fact, a target of choice at MGH and elsewhere in the United States was the anterior cingulate gyrus that Ballantine¹¹ had emphasized. The Neurological Service Web site at MGH claims that staff members have performed more than 800 cingulotomies since 1962.¹ Cingulotomy is now the primary neurosurgical procedure used in the United States, while anterior capsulotomy and limbic leukotomy are more prevalent in Europe and elsewhere. However, multiple brain sites have been targeted, and Chinese surgeons believe simultaneous microlesions in several locations produce better results.¹²

The introduction of ablative stereotactic surgery at MGH in the late 1960s as a treatment for patients who were violent made headlines and created much of the controversy that led to the establishment of the National Commission. Three MGH doctors (a neurologist, psychiatrist, and neurosurgeon) had suggested in letters to the New York Times and the Journal of the American Medical Association that in understanding the race riots of that era it was important to consider the causative contributing factor of biological impairment of the brain among its most violent participants.¹³

Mark and Ervin,¹⁴ who were proponents of this philosophy, had little real neuroscientific understanding of the limbic system or the neural substrate of violence. Nonetheless, they suggested that in certain cases, violence was an epileptic equivalent (temporal lobe epilepsy) and that stereotactic microlesioning of the trigger of violence in the amygdala was a viable treatment for those forms of violence. Mark and Ervin's 1970 publication Violence and the Brain¹⁴ was unfairly attacked on racial and political grounds; however, in retrospect they demonstrated the same failings as Freeman: their surgical leap into the brain was based on a woefully incomplete understanding of neuroscience, and they shared Freeman's publicity-seeking hubris. Their preliminary research was publicized in Life magazine-the most important weekly of that era. It is now well recognized that patients with temporal lobe epilepsy are characterized by irritability rather than by violence.¹⁵ Extraordinary gains have been made in our understanding of the amygdala-all demonstrating how poorly conceived this surgical intervention was, but the stereotactic approach was used for other disorders and for microablations in many other regions of the brain.

Advances in technology and engineering design have led to the gamma knife procedure, which uses a device capable of irradiating small intracranial targets with gamma ray photons. This ablative procedure does not require surgical incision and claims increased accuracy. Instead of burning or freezing brain particles to achieve the desired lesion, gamma radiation deranges molecules in the target cells so that they can no longer survive. This means that the lesions develop over months and must be monitored through the repeated use of MRI. A preliminary study of gamma knife capsulotomy in cases of severe OCD at Brown University School of Medicine found that 40% of patients who had undergone 2 lesioning procedures were significantly improved 2 years postsurgery.¹⁶

In patients with severe treatment-refractory OCD, none of these procedures is clearly more beneficial. The gamma knife procedure, however, has the advantage over stereotactic surgery and DBS of not requiring burr holes and of lacking other rare neurosurgical risks involved in implanting electrodes. MGH established the efficacy of the stereotactic ablative procedure as a treatment for refractory OCD in a landmark article published in the American Journal of Psychiatry in 2002; the authors included the then-chairman of the MGH department of psychiatry.¹⁷ It can be considered the launching pad of the new era of neurosurgery for mental disorders. This follow-up study reported significant improvement in one-third of patients and modest improvement in others.

Cause for Concern

As one reviews the careful selection criteria and procedures at a center such as MGH, which is considered the model for China, after the recent scandal, important ethical questions remain unanswered. A major concern is that there is still no system of extra- institutional review. MGH was never required to seek the opinion of an expert who was not a member of the hospital's own staff. Despite the interdisciplinary participation of psychiatrists, neurologists, and neurosurgeons, if they function within one hospital, there exist well-known psychological constraints and pressures for conformity. A second concern is whether a patient with intractable OCD can provide his or her informed consent to the procedure. (MGH involves the family in the informed consent process, but it is the patient who must provide the formal written consent.) The UN's convention sees the external review as a check both on the need for this treatment and on the validity of the informed consent.

A third problem is that although doctors who refer to MGH must attest that their patients have been "refractory" both to medication and to cognitive-behavioral therapy (CBT) before they are accepted for surgery, it is difficult to determine without direct supervision whether there was real adherence to these treatments. Even more problematic, MGH's Web site offered the possibility of neurosurgical treatment to patients who are 18 years and older.¹ Given what is now known about continuing brain development, this seems inappropriate and unwarranted. Thus, in my opinion, even if one accepts the practices in place at MGH, this should not be considered a model program for centers around the world.

As to the efficacy of the new neurosurgery, perhaps the most carefully studied patients are those who have been treated for intractable OCD with stereotactic cingulotomy. In its recent guidelines for the treatment of OCD, the American Psychiatric Association considered the efficacy of the procedures and of the ongoing changes in technology. "Improvement rates [in intractable cases] have ranged from 35% to 50%. . . . the unblinded nature of these studies and the ongoing treatment [eg, medications and CBT postsurgery] of many patients limit interpretation of these results."¹⁸ The guidelines go on to say that the recent development of less invasive DBS makes it harder to consider ablative neurosurgery as an alternative to highly treatment-resistant or intractable OCD. This seems to be a sensible and prudent judgment.

DBS represents a potential advance over traditional lesioning techniques in that neural tissue is not permanently burned or destroyed in the procedure. It involves surgically implanting tiny electrical stimulators on either side of the brain that are connected to a pacemaker-like generator. When turned on, the impulse generator delivers low-voltage electrical pulses to specific targets in the brain. The procedure is both reversible and adjustable. Early studies at MGH and elsewhere have demonstrated that DBS may provide significant relief to those with severe, treatment-refractory OCD, with improvement rates ranging from 25% to 50%.¹⁶

A further scientific benefit of DBS research is the possibility of using sham-controlled studies and within-patient designs. DBS for OCD is still in its infancy; neurosurgeons and the medical community are not fully certain about how the stimulation works, but it appears that the electrical stimulation disrupts the abnormal neural firings. During an invited lecture at Harvard University, the well-known neuroscientist Antonio Damasio, in answer to a question, said that in principle he had no objection to psychosurgery. Presumably, he was suggesting that there is no reason to consider the brain as a sacred organ and not as an object of scientific scrutiny. It may not be sacred in principle, but there is still the question of whether we know enough neuroscience to comprehend what we are doing when we produce small ablative lesions in this extraordinarily complex organ.

The overarching ethical question remains: do we know enough neuroscience to know that we are not doing more harm than good in the long run? Indeed, that is what makes the introduction of DBS such an appealing alternative; it promises to increase our scientific understanding while providing comparable benefits without destroying brain cells. Given the historical burden of the old psychosurgery, the new neurosurgeons have a special obligation to proceed with utmost scientific caution.

References:

References

1. Cosgrove GR, Rauch SL. Psychosurgery. Mas- sachusetts General Hospital Web site. http:// neurosurgery.mgh.harvard.edu/functional/psysurg. htm. Accessed April 22, 2008.

2. Zamiska N. Harsh treatment: in China, brain surgery is pushed on the mentally ill. Wall Street Journal. November 2, 2007:A1.

3. Stone AA. The plight of Falun Gong. Psychiatr Times. 2004;XXI(13):1, 52-57.

4. Zamiska N. Politics and economics: China to regulate use of brain procedure. Wall Street Journal. February 5, 2008:A7.

5. Pies R. The lobotomist [DVD review]. Psychiatr Times. 2008;XXV(1):12.

6. El-Hai J. The Lobotomist: A Maverick Medical Genius and His Tragic Quest to Rid the World of Mental Illness. Hoboken, NJ: John Wiley & Sons Inc; 2007.

7. Oregon Senate. Oregon Psychosurgery Bill (SB) 298. Portland, OR: Oregon Legislative Assembly, 1973.

8. Principles for the protection of persons with mental illness and the improvement of mental health care. United Nations Enable Web site. http://www.un.org/ esa/socdev/enable/rights/wgrefa11/htm. Accessed April 21, 2008.

9. Feldman RP, Alterman R, Goodrich JT. Contemporary psychosurgery and a look to the future. J Neurosurg. 2001;95:944-956.

10. United States National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Psychosurgery: Report and Recommendations. Washington, DC: US Government Printing Office; 1977. DHEW publication (OS) 77-0001.

11. Ballantine HT Jr, Bouckoms AJ, Thomas EK, Giriunas IE. Treatment of psychiatric illness by stereotactic cingulotomy. Biol Psychiatry. 1987;22:807-819.

12. Jiang CC. A preliminary report on stereotactic multi-target limbic leucotomy [in Chinese]. Zhonghua Shen Jing Jing Shen Ke Za Zhi. 1989;22:152-154.

13. Valenstein ES. Brain Control: A Critical Examination of Brain Stimulation and Psychosurgery. New York: John Wiley & Sons Inc; 1973.

14. Mark VH, Ervin FR. Violence and the Brain. New York: Harper & Row; 1970.

15. Restack R. Complex partial seizures present diagnostic challenges. Psychiatr Times. 1995;XII(9): 27-28.

16. Greenberg BD, Malone DA, Friehs GM, et al. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006;31:2384-2393.

17. Dougherty DD, Baer L, Cosgrove GR, et al. Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder. Am J Psychiatry. 2002; 159: 269-275.

18. Koran LM, Hanna GL, Hollander E, et al. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164 (7 suppl):5-53.