Executive and cognitive functions in patients with extreme obsessive-compulsive disorder treated by capsulotomy.

All patients treated with thermocapsulotomy for obsessive-compulsive disorder (OCD) at Karolinska Hospital between 1978 and 1990 were examined at follow-up with a comprehensive neuropsychological test battery. For comparative reasons the same test battery was applied to current patients with OCD, approved for capsulotomy. Both groups performed within the normal to subnormal range on most tests. In a subgroup of operated patients who did not complete all categories on the Wisconsin Card Sorting Test (WCST), there was a significant positive correlation between time elapsed after capsulotomy and number of categories completed on the WCST. The results would indicate that neuropsychological performance, in general, remains intact after capsulotomy. In some patients executive function is affected, but restoration may take place over time.

Neurosurgical approaches to intractable obsessive-compulsive disorder.

Although significant progress has been made over the last decade in the treatment of obsessive-compulsive disorder (OCD), approximately 20% of OCD patients remain refractory to nonsurgical therapies, including pharmacologic and cognitive-behavioral therapy. Because a number of neural circuits involving the basal ganglia, thalamus, limbic system, and frontal lobes have been implicated in the pathophysiology of OCD, the need for an effective intervention in these patients has brought the focus on surgical approaches, including cingulotomy and capsulotomy procedures. Unlike free-hand surgical approaches used in the past, current neurosurgical interventions have been greatly enhanced by advances in technology, which allow lesioning to an accuracy of 1 mm. Today's neurosurgical approaches have shown significant benefit in as many as 60% of refractory patients, while preserving personality and cognitive functioning and limiting morbidity. A study of gamma knife capsulotomy conducted at Brown University School of Medicine showed that 40% of patients undergoing two lesioning procedures were much or very much improved 2 years postsurgery. The inherent obstacles to conducting placebo-controlled studies in these severely ill patients mean that further study is required to identify optimal candidates for surgical intervention.

Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere.

OBJECTIVES: Obsessive-compulsive disorder is a common mental disorder, notorious for its chronicity and intractability. Stereotactic lesions within the anterior limb of the internal capsule have been shown to provide symptomatic relief in such refractory cases, but only few systematic evaluations have correlated anatomic lesion location with individual postoperative outcome. PATIENTS AND METHODS: Between 1976 and 1989, extremely disabled and otherwise intractable patients with a chronic deteriorating clinical course of obsessive-compulsive disorder underwent bilateral thermocapsulotomy (n = 22) or radiosurgical gamma knife capsulotomy (n = 13) at the Karolinska Hospital, Stockholm. Clinical morbidity was monitored prospectively pre- and postoperatively by using standardized psychiatric rating scales. In 29 patients (thermocapsulotomy, n = 19; gamma knife capsulotomy, n = 10), both psychiatric and magnetic resonance imaging follow-up data (median, 8.4 yr) were available. RESULTS: A right-sided anatomically defined lesion volume was identified in all successfully treated patients. This common topographic denominator was defined in the approximate middle of the anterior limb of the internal capsule on the plane parallel to the anterior commissure-posterior commissure line at the level of the foramen of Monro and 4 mm above on the plane defined by the internal cerebral vein. This region was unaffected in patients with poor outcomes. On the left side, no particular lesion topography was associated with clinical outcome. Topographic differences of lesion overlap between good and poor outcome groups were significant for the right side (Fisher's exact test, P < 0.005). CONCLUSION: The current anatomic long-term analysis after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder reveals common topographic features within the right-sided anterior limb of the internal capsule independent of treatment modality.

A prospective, long-term study of personality traits in patients with intractable obsessional illness treated by capsulotomy.

The crux when contemplating neurosurgery for otherwise intractable mental illness is whether there is a price which the patient may have to pay, in terms of adverse personality changes, for symptom relief. In the present study of 19 patients undergoing thermo-capsulotomy for intractable obsessional illness, personality characteristics were studied pre-operatively, and at 1-year and 8-year follow-up, using the Karolinska Scales of Personality (KSP). Small mean score changes toward normalization were apparent on all 15 KSP scales at the 1-year follow-up, and significant improvements in anxiety proneness were noted at the 8-year follow-up. One patient who sustained a surgical complication showed deviant postoperative scores on scales related to psychopathic traits. There were no such deviant scores for the remaining subjects. The incidence of adverse personality changes following capsulotomy is low and does not increase with time. This conclusion, based on groups of patients, does not of course preclude the possibility that adverse personality changes may occur in individual patients.

Radiosurgical lesions in the normal human brain 17 years after gamma knife capsulotomy.

OBJECTIVE: To our knowledge, this is the first long-term follow-up study of high-dose single-session irradiation to the human brain and provides new data concerning late tissue reactions after irradiation to small target volumes. The long-term lesional brain changes in 14 patients subjected to bilateral gamma knife capsulotomy for otherwise intractable anxiety disorders were retrospectively analyzed by magnetic resonance imaging. METHODS: The prototype gamma unit was used for the radiosurgical procedure, and the collimators provided rectangular cross-sectional fields with an anteroposterior diameter of 3 mm and a transverse diameter of 5 or 11 mm. Maximum target doses were 120 to 180 Gy. Magnetic resonance imaging was performed 15 to 18 years (mean, 17 yr) after treatment, and dose-volume histograms were calculated for the dose distributions. RESULTS: One patient had been irradiated twice on one side. In all but one of the remaining 27 targets, lesions with a volume of less than 100 mm3 were revealed by magnetic resonance imaging. The volumes of the lesions were confined within the volume corresponding to a minimum dose of approximately 110 Gy, with one exception. In one of three targets receiving a maximum dose of 120 Gy, no lesion was detected. There were no late radiation effects such as cyst formations, telangiectasias, hemorrhagic infarctions, or neoplasms. CONCLUSION: This investigation indicates that a minimum dose of 110 Gy, with the currently used 4-mm collimator, to the edge of the target volume is required to create a lesion. The results prove that gamma knife surgery can be used in functional neurosurgery for producing small permanent lesions in the normal human brain.

Obsessive compulsive disorder and the right hemisphere: topographic analysis of lesions after anterior capsulotomy performed with thermocoagulation.

Considerable but uncontrolled evidence suggests that stereotactic capsulotomy by means of thermolesions may provide symptomatic relief for patients with otherwise therapy refractory "malignant" obsessive compulsive disorder (OCD). Unlike in other functional stereotactic interventions, target localization for capsulotomy is based upon anatomical definition only. Few systematic attempts have been made to correlate the site and size of the capsular lesions with postoperative clinical outcome. Between 1976 and 1989 bilateral thermo-capsulotomy (TC) was performed in 22 OCD patients. In 19 patients complete quantitative pre- and postoperative psychiatric rating of OCD symptoms and long-term postoperative MRI studies were available. Cohorts of patients fulfilling criteria for good or poor outcome were contrasted, cases with intermediate treatment effect being excluded. Median postoperative MRI follow-up was 8.4 years (2.4-20.3 y). 9/19 patients fulfilled criteria for good postoperative outcome. In these patients all lesion sites overlapped covering a small area within the right anterior limb of the internal capsule. Lesions within the group of patients with poor outcome (n = 5) were located elsewhere, mostly further anterior in the internal capsule. Differences of lesion overlap between the two outcome groups were significant for the right side (Fisher's Exact Test: p < 0.005). Common topographic features of lesion sites within the right internal capsule were identified in OCD patients responding favourably to capsulotomy.

Radiobiology of radiosurgery for refractory anxiety disorders.

The neuroradiological manifestations of bilateral single-session gamma (gamma)-irradiation to normal tissue contained in the internal capsule after gamma knife capsulotomy for otherwise intractable anxiety disorders were studied. In nine consecutive patients, a target maximum dose of 200 Gy was administered in a target volume of 276 +/- 42 mm3 (mean +/- SD) within the 50% isodose level. Serial computed tomographic and magnetic resonance imaging scans were undertaken from 3 to 44 months after irradiation. After surgery, a necrotic lesion appeared on computed tomographic scans, reaching its maximum volume (900 +/- 800 mm3) at 6 to 9 months, then decreasing (to 457 +/- 400 mm3) over the first postoperative year. This volume correlated with the mean isodose level of 91 (range, 41-143) Gy. On T2-weighted magnetic resonance imaging scans, the reaction tissue volumes were considerably larger and took longer to disappear than expected. In 15 targets, maximum reaction volumes were recorded at 1 to (approximately) 2 years after irradiation. In the remaining seven targets, smaller reaction volumes were observed, with no clear maxima appearing during 3 years of observation. In a pilot case, a lower target maximum dose of 160 Gy and a radiation volume of 275 mm3 within the 50% isodose gave only minimal surrounding tissue reactions. This report serves to alert clinicians that the tissue reaction volumes and the time course of their development after high irradiation doses may be less predictable than expected from previous observations in smaller radiation volumes. For this reason, lower irradiation doses and smaller volumes should be used in the future, and the time factor should be taken into account when interpreting computed tomographic and magnetic resonance images of gamma-knife-induced lesions.

Neuropsychological correlates of intractable anxiety disorder before and after capsulotomy.

A comprehensive neuropsychological test battery was administered to 10 consecutive patients undergoing neurosurgical intervention, capsulotomy, as a last resort treatment for chronic, incapacitating, and otherwise intractable illness, either obsessive-compulsive disorder (OCD; n = 5) or non-OCD anxiety disorder (n = 5). The aim was to study the neuropsychology of severe anxiety disorders before and after a defined neurosurgical intersection of connections between the frontal lobes and related brain regions. Although extremely disabled by their illness before surgery, the patients performed within the normal range on most tests. After capsulotomy, there was significant improvement on measures of clinical morbidity and of psychosocial functioning, and the general neuropsychological performance remained remarkably intact. In a subgroup of 5 patients, however, perseverative responses were more common postoperatively, possibly indicating dysfunction of systems involving the frontal lobes. Although admittedly sparse, these data can be interpreted as suggesting that in vulnerable individuals, capsulotomy may give rise to increased perseverative behaviour in the laboratory, and possibly in the real world as well. This risk must be weighed against the potential clinical benefit of capsulotomy in this extremely disabled, sometimes suicidal patient population.

Neurosurgical treatment for refractory obsessive-compulsive disorder: implications for understanding frontal lobe function.

A minority of patients with obsessive-compulsive disorder (OCD) have a chronic course and extreme disability, with symptoms refractory to pharmacological and psychological treatment. Considerable uncontrolled evidence suggests such cases may respond to neurosurgical intervention. The authors update current stereotactic procedures and their efficacy, safety, and side effect profiles. The design of an ongoing placebo-controlled trial of Gamma Knife capsulotomy for refractory OCD is outlined. Drug treatment of OCD may be assumed to affect a proposed functional imbalance between the frontal lobes and other parts of the brain. As for neurosurgical treatments, both the effects and side effects may be viewed as expressions of their influence on this functional imbalance.

Present-day indications for capsulotomy.

Although the majority of patients with anxiety disorders respond well to behavioural techniques of exposure and response prevention, to pharmacotherapy, or, more commonly, to combinations of the two approaches, a small percentage of patients remain refractory and are severely disabled by their symptoms. Some of these individuals constitute candidates for neurosurgical intervention, e.g. cingulotomy and capsulotomy. Therefore, such operations are performed, if to a very limited extent, both in the United States and in Europe to-day. At the Karolinska, patients are accepted for capsulotomy who suffer from chronic, severe, incapacitating, and otherwise intractable anxiety disorders, i.e. obsessive-compulsive disorder, generalized anxiety disorder and phobias. The present-day inclusion and exclusion criteria are described, and the safety and the efficacy of capsulotomy in these extreme forms of anxiety disorders are discussed.

Normalization of personality characteristics in patients with incapacitating anxiety disorders after capsulotomy.

The personality characteristics of 24 consecutive patients undergoing psycho-surgery for incapacitating anxiety disorders were assessed prospectively using a self-report personality inventory. The main findings were: absence of negative personality changes after surgery, significant postoperative changes towards normalization on the majority of the scales, and significant symptomatic relief in 80% of the cases. The changes on scales reflecting anxiety proneness were conspicuous in patients suffering from "pure" anxiety disorders, as compared with those suffering from obsessive-compulsive disorder (OCD). In OCD patients, correlations were obtained between changes in brain metabolism studied with positron emission tomography and changes in personality scores. It is concluded that negative personality changes are not likely to occur after capsulotomy.

Aspects of personality in patients with anxiety disorders undergoing capsulotomy.

Capsulotomy is an established psychosurgical intervention for anxiety disorders. While the effectiveness of the intervention in reducing target symptoms is undisputed, the issue of negative personality changes following capsulotomy is of great concern. We studied prospectively personality traits in nine consecutive patients undergoing capsulotomy for anxiety disorder, using the Rorschach test and a personality inventory, the Karolinska Scales of Personality (KSP), administered before and one year after operation. The protocols were evaluated under blind conditions by an independent assessor who had access to no data other than the age and sex of the patients. The Rorschach findings were used in two main comparison procedures: between the patients pre- and postoperative scores, and between that group and three reference groups. The KSP data were compared both with an age-stratified non-patient control group and with data obtained from groups of neurotic patients. In summary, the capsulotomy patients' personalities, as expressed in their Rorschach interpretations, remained intact, and significant reductions were noted in scales reflecting anxiety and hospitality. Statistically significant changes were also noted after operation in 10 of the 17 scales included in the KSP. While pathological scores were observed preoperatively in many scales, all the postoperative scores but one (Socialization) were within the normal range. Scores on the Socialization scale remained low, which is often the case in chronic patients. It is concluded that the patients displayed more normal personality features after operation than before and that adverse personality changes are not likely to occur after capsulotomy.

Anxiety, pain and sedation: some psychiatric aspects.

Whereas pain is an important factor that brings the patient to the dental office, fear and anxiety about pain are common reasons for patients to delay or avoid dental care. The relation between anxiety and pain is discussed in view of recent neuroanatomical and pharmacological findings obtained through modern research techniques, including positron emission tomography. Mechanisms behind sedation induced by the benzodiazepines and through psychological management of the apprehensive patient are discussed. It is concluded that the optimal quality of treatment may be obtained through the combined use of pharmacological and psychological treatment modalities.

Magnetic resonance images related to clinical outcome after psychosurgical intervention in severe anxiety disorder.

Postoperative verification of radiosurgical lesions in white matter has been difficult to obtain with CT. With magnetic resonance (MR) imaging, however, lesions could be demonstrated in patients undergoing a psychosurgical procedure, gamma capsulotomy, for anxiety disorder. The appearance and location of the lesions were related to the irradiation dose and to the long-term clinical outcome studied prospectively by two independent evaluators who had not been involved in the selection or the treatment of the patients. Seven consecutive cases were examined. CT was also included for comparison reasons. Lesions were clearly visible with MR in patients who improved after surgery. Conversely, lesions were inadequate in cases who did not benefit. MR proved to be more accurate than CT both in detecting the lesions and in defining their configuration. The observations argue for the use of MR for post-operative verification of radiosurgical lesions. MR may facilitate the determination of a clinically effective radiation threshold estimate for radiosurgical lesions, which should be of value for the planning of studies of this type of limbic system surgery.