Neurol Med Chir (Tokyo) 42, 365¿371, 2002

Review of Long-term Results of Stereotactic

Moon-Chan KIM,Tae-KyuLEE, and Chang-Rak CHOI

Department of , Kangnam St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, R.O.K.

Abstract

Stereotactic psychosurgery is an effective method for treating some medically intractable psychiatric illnesses. However, it is unfamiliar and the long-term clinical results have not been reported in Asia. The long-term results of psychosurgery are evaluated and the neuroanatomical basis is discussed. Twenty-one patients underwent stereotactic psychosurgery for medically intractable psychiatric illnesses since 1993. All were referred from psychiatrists for these disorders. Two patients showed ag- gressive behavior, 12 had obsessive-compulsive disorder (OCD), and seven had depression with anxiety disorders. Bilateral amygdalotomy and subcaudate tractotomy were performed for aggressive behavior, limbic leucotomy was performed for OCD, and subcaudate tractotomy with or without cingulotomy was performed for depression with anxiety. OCD was evaluated with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the visual analogue scale, the Clinical Global Impression Scale, and the Overt Aggres- sion Scale (OAS). The Mini-Mental State Examination and the Wechsler Adult Intelligence Scale- Revised were used for the evaluation of aggressive behavior. The 17-item Hamilton Depression Rating Scale (HAMD) was used for evaluation of depression. Ventriculography was used in the first seven patients and magnetic resonance imaging-guided stereotaxy was used in the recent 14 cases for localiza- tion of the target. The lesions were made with a radiofrequency lesion generator. OAS scores in the two patients with aggressive behavior during follow up declined from 8 to 2 with clinical improvement. All 12 patients with OCD returned to their previous life and showed the mean YBOCS scores decreased from 34 to 3. Ten patients with OCD could be followed up (mean 45 months). All patients returned to their previous social life. In seven patients with depression with anxiety, HAMD scores declined from 28.5 to 16.5. There was no operative mortality and no significant morbidity except for one case of mild tran- sient urinary incontinence. These long-term results indicate that stereotactic psychosurgery is a safe and effective method of treating some medically intractable psychiatric illnesses.

Key words: stereotactic psychosurgery, obsessive-compulsive disorder, depression, anxiety, psychiatric illness

Introduction out of favor. However, today, as ``functional'' or ``'' surgery, neurosurgery has the Psychosurgery was defined as ``the selective surgical potential to become a more acceptable treatment for removal or destruction of nerve pathways for the psychiatric diseases.2,3) purposes of influencing behavior'' in 1976 by the More refined methods, especially the use of World Health Organization. Psychosurgery has a stereotaxy, have reduced but not eliminated the risks long and complex history. Egas Moniz won the of personality change and cognitive malfunction Nobel Prize for psychosurgery in 1949.1,21) In the after surgery. Unfortunately, evaluation at this time 1950s, with psychopharmacological advances, surgi- was mainly restricted to assessment of the psy- cal treatment of psychiatric diseases began to fall chiatric condition treated by surgery, and little at-

Professor Moon-Chan Kim delivered a very interesting lecture on stereotactic psychosurgery at the 40th Annual Meeting of the Japanese Society for Stereotactic and Functional Neurosurgery, chaired by Professor Tomokatsu Hori on October 22–23, 2001. At the request of the Editorial Board of Neurologia medico-chirurgica, the authors have kindly written this ex- cellent review article on this very important issue. On behalf of all the members of The Japan Neurosurgical Society, the Editorial Board expresses our sincere gratitude. Tomokatsu HORI, M.D., President of the 40th Annual Meeting of the JSSFN. Akira YAMAURA, M.D., Editor-in-Chief, Neurologia medico-chirurgica.

365 366 M.-C. Kim et al.

Fig. 1 Ventriculograms showing the targets for bilateral amygdalotomy and subcaudate tractotomy to treat aggressive behavior. The target for amygdalotomy were 5 mm anterior and 5 mm medial to the anterior tip of the temporal horns (left). The target for subcaudate tractotomy was 12 mm anterior from the tuberculum sellae, 10 to 15 mm over the floor of the anterior fossa, and extending laterally 6 to 14 mm from the midline (right).

Fig. 2 Postoperative magnetic resonance images after bilateral amygdalotomy and subcaudate trac- totomy showing bilateral triangular shaped lesions.

tempt was made to study alterations in other aspects chiatric disorder since 1993 was undertaken. This of behavior. Only a minority of outcome studies approach further offered the advantage of determin- used formal testing. The aim of the present review is ing the long-term effects of the psychosurgical inter- to elucidate the effects of specific lesion sites in ventions. Usually, follow up of such patients covers patients with psychiatric disorders undergoing psy- at most a few years, thus posing serious difficulties chosurgery in order to anatomically specify the an- for the evaluation of the stability of therapeutic tipsychotic effect and to better define the structure- effects. function relationships of cognitive and behavioral functions. A long-term follow up of patients who had undergone psychosurgery for refractory psy-

Neurol Med Chir (Tokyo) 42, September, 2002 Review of Long-term Results of Stereotactic Psychosurgery 367

Fig. 3 Magnetic resonance images showing the Fig. 4 Postoperative magnetic resonance images targets for limbic leucotomy to treat obses- after limbic leucotomy. sive-compulsive behavior. Limbic leu- cotomy combines subcaudate tractotomy and cingulotomy for depression. The target for subcaudate tractotomy was 12 mm an- patients, written informed consent was obtained. terior from tuberculum sellae, 10 to 15 mm over the floor of the anterior fossa, and ex- II. Surgical procedure tending laterally 6 to 14 mm from the mid- Bilateral amygdalotomy and subcaudate trac- line (upper row). The target for cingulotomy totomy were performed in the two patients with ag- was 20 to 30 mm posterior from the anterior gressive behavior (Figs. 1 and 2), limbic leucotomy part of frontal horn, 5 to 10 mm above the was performed in the 12 patients with OCD (Figs. 3 plane, and 10 mm lateral from the midline and 4), and subcaudate tractotomy with or without (lower row). cingulotomy was performed in the seven patients with depression with anxiety. Ventriculography was used in the first seven Materials and Methods patients and magnetic resonance (MR) imaging- guided stereotaxy was used in the recent 14 cases for I. Patients localization of the target. A triangular shaped lesion Twenty-one patients underwent stereotactic psy- was always made bilaterally with a radiofrequency chosurgery for medically intractable psychiatric lesion generator (Radionics, Burlington, Mass., illnesses since 1993. All were referred from psy- U.S.A.). chiatrists for these disorders. Two patients showed Our targets for amygdalotomy were 5 mm anterior refractory aggressive behavior, seven patients had and 5 mm medial to the anterior tip of the temporal depression with anxiety disorders, and 12 patients horns. The target for subcaudate tractotomy was 12 had obsessive-compulsive disorder (OCD). mm anterior from the tuberculum sellae, 10 to 15 The 12 patients with OCD were treated by limbic mm over the floor of the anterior fossa, and extend- leucotomy. They did not want to be reminded of the inglaterally6to14mmfromthemidline.Thetarget worst time of their lives and feared new exacerba- for cingulotomy was 20 to 30 mm posterior from the tion of symptoms, but provided self-ratings of im- anterior part of frontal horn, 5 to 10 mm above the provement. These 12 OCD patients were compared plane, and 10 mm lateral from the midline. Limbic with seven matched nonleucotomized patients leucotomy combined bilateral cingulotomy with recruited from hospital inpatients and outpatients subcaudate tractotomy. who had severe OCD of at least 10 years' duration. After complete description of the study to the

Neurol Med Chir (Tokyo) 42, September, 2002 368 M.-C. Kim et al.

III. Neuropsychological testing sive Compulsive Scale (YBOCS), the visual analogue OCD was evaluated with the Yale-Brown Obses- scale, the Clinical Global Impression Scale, and the Overt Aggression Scale (OAS). The Mini-Mental State Examination and the Wechsler Adult Intelli- Table 1 Neuropsychological testing in two gence Scale-Revised were used for the evaluation of patients with aggressive behavior aggressive behavior. The 17-item Hamilton Depres- sion Rating Scale (HAMD) was used for evaluation Preoperative 7 Yrs postoperative of depression.

Mini-Mental impossible 17/30 State Examination IV. Clinical assessment Wechsler Adult Intelligence Scale impossible 70 The Structured Clinical Interview for DSM-III-R- Clinical Global Impairment disabled partially disabled Patient Version was administered to assess current Overt Aggression Scale* 12/16 2/16 and previous psychiatric diagnoses. Symptoms were rated for the present and were retrospectively as- Aggressive behavior decreased markedly within 2 sessed for the preoperative state using the YBOCS. A weeks after surgery. *Overt Aggression Scale scores during follow up declined from 8 to 2 with clinical im- detailed history of the pre- and postoperative course provement. of illness and the current level of psychosocial func-

Table 2 Serial follow up of Yale-Brown Obsessive Compulsive Scale (YBOCS) in 12 patients with obsessive- compulsive disorder

Postoperative Case Preoperative No. 6 mos 1 yr 2 yrs 3 yrs 4 yrs 5 yrs 6 yrs 7 yrs 8 yrs

130151176744 2401211877 5 335251399222 4 33 14 10 14 8 14 13 4 4 53464 2 6366 6 73412108 835121276 932101012 10 36 14 12 11 34 12 14 12 36 10

Long-term follow up (mean 45 months) in 10 patients showed mean YBOCS scores declined from 34 to 3 (n ＝ 12). All patients returned to their previous social life.

Table 3 Serial follow up of 17-item Hamilton Depression Rating Scale (HAMD) in seven patients with depres- sion with anxiety

Postoperative Case Preoperative No. 1mo 6mos 1yr 2yrs 3yrs 4yrs

13 41 15 13 11 11 13 11 14 38 16 15 13 15 12 15 39 30 25 25 25 16 42 34 32 24 24 17 38 11 15 12 18 45 17 14 14 19 35 11 14 11

HAMD scores declined from 28.5 to 16.5 (n ＝ 7).

Neurol Med Chir (Tokyo) 42, September, 2002 Review of Long-term Results of Stereotactic Psychosurgery 369 tioning were recorded. The patients rated severity replaced with MR imaging-guided stereotactic tech- and improvement of obsessive-compulsive symp- niques. In the cingulotomy procedure, thermistor toms on visual analogue scales. The case notes and electrodes are placed in the bilaterally and information were obtained from the current psy- heated to 859C for 90 seconds, producing lesions.1,8,9) chotherapists. The primary indication for this procedure has been medically intractable OCD, but some patients with Results chronic anxiety and major affective disorders refractory to treatment have also been considered. The two patients with aggressive behavior showed More than 1000 patients have reportedly been treat- marked improvement within 2 weeks after surgery. ed with cingulotomy for affective and anxiety OAS scores during follow up declined from 8 to 2 disorders. The procedure has been found to be with clinical improvement (Table 1). These two effective, with 13% of patients described as fully patients returned to their previous social life. recovered and stable, 23% as requiring ongoing psy- All 12 patients with OCD returned to their previ- chiatric care but functioning well, and 26% as show- ous life and showed the mean YBOCS scores ing continued disability but improved.8,10) Evalua- decreased from 34 to 3 (Table 2). Ten patients with tion of patients with OCD revealed that various OCD could be followed up (mean 45 months). psychiatric symptoms were better in 30% to 40% but In seven patients with depression with anxiety, that 11% had committed suicide.11–13) The percen- HAMD scores declined from 28.5 to 16.5 (Table 3). tages of patients functioning ``normally,'' either with The symptoms improved in a month, were much or without the need for continued psychiatric care, improved by 6 months, and better condition was also were determined for different disorders: major maintained. There was no operative mortality and depression with psychotic features, 49 (41%) of 120 no significant morbidity except one case of mild patients; anxiety disorders, seven (50%) of 14 transient urinary incontinence. patients; OCD, eight (25%) of 32 patients; schizo- phrenia, two (18%) of 11 patients; and personality Discussion disorders, one (11%) of nine patients. Stereotactic subcaudate tractotomy was in- In the 1990s, only a few centers around the world troduced in 1964.15) This procedure was developed performed neurosurgical operations for psychiatric from previous experience with restricted orbital un- disorders. Each center tended to perform and study dercutting, in which the goal was to interrupt white one type of psychosurgical procedure for specific matter tracts between the orbitofrontal cortex and psychiatric indications. subcortical limbic structures. The original stereotac- The selection of lesion sites in psychiatric disor- tic subcaudate tractotomy involved implantation of ders was greatly influenced by the proposal of an a row of radioactive yttrium (90Y) seeds to destroy anatomic basis of emotions in 1937 by Papez.4,22) tissue in the region of the substantia innominata, Major circuits for the limbic circuit have been de- below the head of the caudate nucleus, in the ven- scribed: the medial, basolateral, and defense reac- tromedial frontal lobes. This destruction would tion circuits. Of these circuits, only the first two were presumably interrupt relays to and from the postulated to be involved in affective and anxiety posterior orbital cortex and subcortical structures disorders; the defense reaction circuit appeared to such as the cingulate gyrus, , , have little relevance to such illnesses. The medial and hypothalamus. Improvements after this proce- limbic circuit is the classic Papez circuit and in- dure were initially observed for two-thirds of volves connections from the cingulate gyrus to the patients with depression or OCD. With 2- to 4-year , fornix, mamillary body, and anterior follow up, subcaudate tractotomy appeared to pro- thalamic nucleus, and then to the orbitofrontal cor- vide significant improvement in patients with bipo- tex and septal nuclei.4,5) The basolateral circuit in- lar disorders,23) especially for the manic symp- volves the anterior temporal lobe, amygdala, dorso- toms.15,16) Although short-term changes in memory medial thalamic nucleus, and orbitofrontal cortex.7) have been ascribed to perilesional edema, there The anterior cingulum was first suggested as a appeared to be no long-lasting changes from this psychosurgical target in 1947,6,23) on the basis of procedure with the use of radiofrequency tech- evidence that stimulation of the anterior cingulum niques.15) in monkeys produced autonomic responses of a type Limbic leucotomy combined bilateral cingulo- associated with emotion and that lesions in this tomy with subcaudate tractotomy, which was in- region resulted in less fearful and aggressive troduced in 1973.13,14) The idea was that this dual- animals. Ventriculography has more recently been lesion technique would produce better functional

Neurol Med Chir (Tokyo) 42, September, 2002 370 M.-C. Kim et al. results than either single-lesion method alone. The 5) Ebmeier KP, Besson JA, Smith FW: Visualization of ventromedial frontal lesion was targeted to inter- subcaudate tractotomy lesions by magnetic rupt frontolimbic connections (as with subcaudate resonance imaging. Psychiatry Res 29: 291–292, 1989 tractotomy), whereas the cingulum lesion was tar- 6) Fodstad H, Strandman E, Karlsson B, West KA: geted to interrupt the Papez circuit.25) Original sur- Treatment of chronic obsessive compulsive states with stereotactic anterior capsulotomy or cingulo- gical indications included OCD, anxiety states, and tomy. Acta Neurochir (Wien) 62: 1–23, 1982 depression, as well as some other psychiatric diag- 7) Fulton JF, Jacobsen CF: The functions of the frontal noses. This procedure demonstrated improvement lobes: A comparative study in monkeys, chimpan- rates as high as 89% in patients with obsessional zees, and man, in: Abstracts of the Second Internation- neurosis, 66% in patients with anxiety, 78% in pa- al Neurological Congress. London, 1935, pp 70–71 tients with depression, and 80% in patients with 8) Gildenberg PL: Functional neurosurgery, in schizophrenia.17,18) Postoperativeintelligencequo- Schmidek HH, Sweet WH (eds): Operative Neuro- tient scores were also noted to improve.17) Neither surgical Techniques: Indications, Methods and Re- adverse personality changes nor epilepsy were seen sults. Orlando, Grune & Stratton, 1988, pp 1035– following these operations, and overall improve- 1068 ment was reported in 84% of patients at 20 months 9) Hay P, Sachdev P, Cumming S, Smith JS, Lee T, Kitchener P, Matheson J: Treatment of obsessive- postoperatively.17,19) Long-term side effects of lim- compulsive disorder by psychosurgery. Acta Psy- bic leucotomy are rare, but transient effects such chiatr Scand 87: 197–207, 1993 as , confusion, lethargy, sphincter dis- 10) Jenike MA, Baer L, Ballantine T, Martuza RL, Tynes 17,20) turbances, and perseveration are documented. S, Giriunas I, Buttolph ML, Cassem NH: Cin- A few studies have attempted to directly compare gulotomy for refractory obsessive-compulsive disor- different procedures. The three cingulotomy proce- der. A long-term follow-up of 33 patients. Arch Gen dures and subcaudate tractotomy have been com- Psychiatry 48: 548–555, 1991 bined to provide possibly better results. Limbic 11) Kartsounis LD, Poynton A, Bridges PK, Bartlett JR: leucotomy is the combination of cingulotomy and Neuropsychological correlates of stereotactic sub- subcaudate tractotomy. Improvements in patient caudate tractotomy: A prospective study. Brain 114: symptoms have been determined for OCD (84%) and 2657–2673, 1991 12) Kelly D: The limbic system, sex, and emotions, in for schizophrenia (63%).19,26) Cingulotomy has also Kelly D (ed): Anxiety and Emotions: Physiological been described in combination with anterior cap- Basis and Treatment. Springfield, Charles C Thomas, sulotomy in the treatment of uncontrolled aggres- 1980, pp 197–300 sive behavior, although improved efficacy over 13) Kelly D, Mitchell-Heggs N: Stereotactic limbic leu- either procedure alone remains unproved.8,20) cotomy: A follow-up study of thirty patients. Postgrad These long-term results indicate that stereotactic Med J 49: 865–882, 1973 psychosurgery is a safe and effective method of 14) Kelly D, Richardson A, Mitchell-Heggs N: Stereotac- treating some medically intractable psychiatric tic limbic leucotomy: neurophysiological aspects and illnesses. Modern functional neurosurgical proce- operative technique. Br J Psychiatry 123: 133–140, dures can treat psychiatric disorders and are applic- 1973 able to a subset of psychiatric patients with condi- 15) Knight GC: Stereotaxic tractotomy in the surgical treatment of mental illness. J Neurol Neurosurg Psy- tions refractory to all other therapies. chiatry 28: 304–310, 1965 16) Kullberg G: Differences in effect of capsulotomy and References cingulotomy, in Sweet WH, Obrador S, Martin- Rodriguez JG (eds): Neurosurgical Treatment in Psy- 1) Ballantine HT, Bouckoms AJ, Thomas EK, Giriunas chiatry, Pain and Epilepsy. Baltimore, University IE: Treatment of psychiatric illness by stereotactic Park Press, 1977, pp 301–308 cingulotomy. Biol Psychiatry 22: 807–819, 1987 17) Martuza RL, Chiocca EA, Jenike MA, Giriunas IE, 2) Ballantine HT, Giriunas IE: Advances in psychiatric Ballantine HT: Stereotactic radiofrequency thermal surgery, in Rasmussen T, Marino R (eds): Functional cingulotomy for obsessive compulsive disorder. J Neurosurgery. New York, Raven Press, 1982, pp Neuropsychiatry Clin Neurosci 2: 331–336, 1990 154–164 18) Meyerson BA: Surgical treatment of mental disor- 3) Chiocca EA, Martuza RL: Neurosurgical therapy of ders: Introduction and indications, in Gildenberg obsessive-compulsive disorder, in Jenike MA, Baer L, PhL, Taskar RF (eds): Textbook of Stereotactic and Minichiello WE (eds): Obsessive-Compulsive Disor- Functional Neurosurgery. New York, McGraw-Hill, ders: Theory and Management. St Louis, Mosby-Year 1996, pp 1955–1963 Book, 1990, pp 283–289 19) Mitchell-Heggs N, Kelly D, Richardson A: Stereotac- 4) Cosgrove GR, Rauch SL: Psychosurgery. Neurosurg tic limbic leucotomy — a follow-up at 16 months. Br J Clin N Am 6: 167–176, 1995

Neurol Med Chir (Tokyo) 42, September, 2002 Review of Long-term Results of Stereotactic Psychosurgery 371

Psychiatry 128: 226–240, 1976 affective disorder treated by stereotactic subcaudate 20) Mitchell-Heggs N, Kelly D, Richardson AE: tractotomy. Br J Psychiatry 152: 354–358, 1988 Stereotactic limbic leucotomy: Clinical, psychologi- 25) Richardson A: Stereotactic limbic leucotomy: Surgi- cal and physiological assessment at 16 months, in cal technique. Postgrad Med J 49: 860–864, 1973 Sweet WH, Obrador S, Martin-Rodriguez JG (eds): 26) Yakovlev PI: Motility behavior in the brain: Stereo- Neurosurgical Treatment in Psychiatry, Pain and dynamic organization in neural coordinates of be- Epilepsy. Baltimore, University Park Press, 1977, pp havior. J Nerv Ment Dis 107: 313, 1948 367–379 21) Moniz E: Prefrontal leucotomy in the treatment of mental disorders. Am J Psychiatry 93: 1379–1385, 1937 Address reprint requests to: M.-C. Kim, M.D., Professor & 22) Papez JW: A proposed mechanism of emotion. Arch Chairman, Department of Neurosurgery, Kangnam Neurol Psychiatry 38: 725–743, 1937 St. Mary's Hospital, Catholic University Medical 23) Pribram KH, Fulton JF: An experimental critique of College, ＃505, Banpo–Dong, Seocho–Ku, Seoul the effects of anterior cingulated ablations in 137–040, R.O.K. monkey. Brain 77: 33–44, 1954 e-mail:mckim＠cmc.cuk.ac.kr. 24) Poynton A, Bridges PK, Bartlett JR: Resistant bipolar

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