Prospective Long-Term Follow-Up of 44 Patients Who Received Cingulotomy for Treatment-Refractory Obsessive-Compulsive Disorder

Guidelines for assessing candidacy for clinical intervention specified that each patient must have 1) met DSM-III-R criteria for OCD, 2) had severe OCD symptoms and functional impairment, and 3) failed a specific and rigorous regimen of medication and behavior therapy trials. In addition, the referring psychiatrist was required to agree to follow the patient after release from the hospital after cingulotomy. The patients were referred by their local psychiatrists to the Massachusetts General Hospital Cingulotomy Assessment Committee for limbic system surgery for severe OCD. The assessment committee, which consisted of three psychiatrists, a neurosurgeon, and a neurologist, reviewed each patient’s records and determined whether preliminary approval for surgery was appropriate. Next, patients were directly interviewed and examined by a psychiatrist, a neurologist, and a neurosurgeon, and they completed additional tests and evaluations. They were then assessed at the Massachusetts General Hospital OCD Clinic and Research Unit, where the Structured Clinical Interview for DSM-III-R for diagnosis of axis I disorders (5) was administered. They were also assessed with additional standardized instruments, including the Yale-Brown Obsessive Compulsive Scale (6), the Beck Depression Inventory (7), and the Sickness Impact Profile (8).

Most surgical candidates have OCD that has been unresponsive to all available and appropriate psychotropic medication trials and behavior treatments. Each patient was required to have had adequate trials (at least 10 weeks at the maximally tolerated dose) of at least three of the serotonin reuptake inhibitors (clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, or citalopram) and augmentation of at least one of the previous drugs for 1 month with at least two of the following medications: lithium, clonazepam, buspirone, or a neuroleptic. All patients also must have had an adequate trial of behavior therapy consisting of at least 20 hours of exposure and response prevention. Information regarding medication compliance history was obtained from the patient’s referring psychiatrist and the patient’s records, in addition to the history provided by the patient. The maximum dose tolerated was a subjective measure, in large part influenced by the patient’s ability or willingness to tolerate adverse effects. The team attempted to ensure, through its communication with the patient and the referring physician, that previous treatment trials were not abandoned prematurely due solely to mild side effects. In a more general sense, patients who were characterized as poorly compliant (e.g., missing appointments, not taking their medications as prescribed, not genuine in their effort to participate in behavior therapy) were not deemed appropriate candidates for surgery. Patients who were accepted for cingulotomy provided informed consent for surgery and clinical follow-up.

Forty-four patients (28 men and 16 women) were approved for and underwent one or more cingulotomy procedures at Massachusetts General Hospital. The mean age of the patients at the time of the operation was 34.4 years (SD=11.8, range=16–69).

Through bilateral burr holes, 1.2 cm in diameter, 9.5 cm posterior to the nasion, and 1.5 cm to either side of the midline, electrically insulated thermistor electrodes were positioned in each cingulate gyrus with magnetic resonance imaging (MRI) stereotactic guidance. The initial targets were located 0.7 cm lateral to the midline bilaterally, 2 cm posterior to the most anterior portions of the frontal horns, and 1.0 mm above the roof of the ventricles. Typically lesions are created by heating the uninsulated 1.0-cm tip of the electrode to 80–85 degrees Centigrade for 90 seconds by radiofrequency current. The electrode is then withdrawn 1.0 cm and the lesion is enlarged superiorly by using the same lesion parameters. These steps are repeated for the opposite hemisphere. This produces symmetrical lesions in the anterior cingulate cortex bilaterally. A recent morphometric magnetic resonance imaging study involving a subset of patients (N=9) undergoing cingulotomy for treatment-refractory OCD at Massachusetts General Hospital demonstrated that the mean total lesion volume for the cohort was 3.58 cm³ (SD=1.24, range=1.97–5.83), with the average center of the lesions lying 9 mm lateral from the midsagittal plane, 18 mm anterior to the anterior commissure, and 30 mm superior to the intercommissural plane (9). When repeated cingulotomies were required, additional lesions were placed 8–10 mm anterior to the initial lesions.

MRI scans were obtained for all patients within 48–72 hours after the cingulotomy to confirm placement of lesions. An attempt was made to follow-up all patients at approximately 6 months after their first cingulotomy, and follow-up of the entire cohort has been initiated approximately every 5 years. The initial 6-month follow-up point was chosen because it corresponds to the clinical practices of the Massachusetts General Hospital Cingulotomy Assessment Committee. Specifically, the committee typically will not consider a patient for a second cingulotomy until 6 postoperative months have passed. Consequently, a patient whose referring psychiatrist suggests a second cingulotomy will typically initiate contact with the assessment committee at the 6-month time point, thereby facilitating the follow-up assessment. At this re-evaluation point, the assessment committee reviews the patient’s progress since the first evaluation, reviews the referring physician’s report, and determines whether a second cingulotomy is indicated because of enduring severe symptoms. Because almost all patients lived some distance from Massachusetts General Hospital, only those patients who were scheduled to return to the Neurosurgery Service for evaluation before a second cingulotomy procedure were followed-up in person. All other patients were followed-up through interviews by telephone. The following rating scales were administered during these follow-up visits or telephone calls: the Yale-Brown Obsessive Compulsive Scale, the clinical global improvement scale, the Beck Depression Inventory, and the Sickness Impact Profile.

The Yale-Brown Obsessive Compulsive Scale (6) score has been used as the main dependent variable in multicenter treatment trials for OCD and has demonstrated reliability and validity.

To assess outcome in a variety of areas, we used a series of clinical global improvement scales that had been used in our previous studies (3, 4). Patients were asked, “Compared to how you felt before your first neurosurgical operation, circle a number to describe how you are feeling now in each of the following areas.” The three areas included in the assessment were OCD symptoms, depression, and anxiety. Each area was rated on the following scale: 1=much better, 2=moderately better, 3=slightly better, 4=no change, 5=slightly worse, 6=moderately worse, 7=much worse.

The Beck Depression Inventory (7), a widely used 21-item self-report scale, was used to assess severity of depression. This scale has demonstrated good reliability and validity for this purpose.

The Sickness Impact Profile (8), a 136-item self-administered checklist, was used to assess functional status. The Sickness Impact Profile yields a total score, 12 subscale scores for individual categories of functional status, and three dimensional scores (including physical, psychosocial, and other effects, such as impact on work, rest, recreational pastimes, and sleep). The total, subscale, and dimensional scores have demonstrated excellent reliability, discriminant validity, and sensitivity to change.

The major clinical criterion pertaining to severity of illness was functional impairment, with patients’ preoperative functioning typically corresponding to a DSM-III-R Global Assessment of Functioning score of less than 60. Although the Yale-Brown Obsessive Compulsive Scale score is a general guide to symptom severity, the score on this scale may underestimate the severity of symptoms in some patients, such as those with obsessions only, for whom the scale score would reflect approximately one-half of their true symptom severity. In general, however, most patients who are approved for cingulotomy have Yale-Brown Obsessive Compulsive Scale scores of greater than 25.

For clinical ratings of OCD and depression symptoms, we analyzed data at four times: 1) at baseline, before the first cingulotomy; 2) at the first postsurgical follow-up (a mean of 6.7 months after the first cingulotomy), at which point no patient had yet undergone a second cingulotomy; 3) at the first postsurgical follow-up after a second cingulotomy (a mean of 7.0 months after the second cingulotomy) for those patients who had multiple cingulotomies; and 4) at the most recent follow-up (a mean of 32 months after the first cingulotomy), at which time 17 patients (39%) had undergone two cingulotomies and one patient (2%) had undergone three cingulotomies. Analyses of functional status, measured by the Sickness Impact Profile, at the most recent follow-up compared to the baseline incorporated two-tailed, paired t tests.

To classify patient response we employed the same conservative criteria that were used in our previous prospective studies (3, 4). Responders had an improvement of 35% in the Yale-Brown Obsessive Compulsive Scale score and a clinical global improvement score less than or equal to 2 and did not attribute the improvement to a treatment other than cingulotomy. Partial responders had either improvement of 35% in the Yale-Brown Obsessive Compulsive Scale score or a clinical global improvement score less than or equal to 2 or had adequate improvement on both scales but attributed improvement to another treatment.

Table 1 summarizes the treatment response categories and clinical rating scale results for all patients at baseline, the first follow-up, and long-term follow-up after one cingulotomy. Five of the 44 patients (11%) met the criteria for being a responder at the first follow-up point. Another four patients (9%) were classified as partial responders at the first follow-up. At the first follow-up, mean improvement in OCD as measured by the Yale-Brown Obsessive Compulsive Scale score was 20.4%, and the mean clinical global improvement score for OCD was 3.6. Correlations of the clinical global improvement ratings for OCD with the scores for depression (r=0.54, N=26, p=0.004) and the scores for anxiety (r=0.63, N=26, p=0.001) were also significant.

At the most recent follow-up, 14 of the 44 patients (32%) met the conservative criteria for responders at a mean follow-up time of 32 months. Six additional patients (14%) met the more liberal criteria for partial responders. Thus, a total of 20 patients (45%) met criteria for at least partial response. At the most recent follow-up, the mean improvement in OCD as measured by the Yale-Brown Obsessive Compulsive Scale score was 28.7%, and the mean clinical global improvement score for OCD was 2.8. The correlations of the clinical global improvement scores for OCD with the scores for depression (r=0.55, N=39, p<0.001) and the scores for anxiety (r=0.75, N=39, p<0.001) were significant.

Among the patients who received more than one cingulotomy, only one responder (6%) and two partial responders (11%) were seen at initial follow-up after the first cingulotomy. However, in the initial follow-up after the second cingulotomy, there were four responders (22%) and no partial responders (Table 1). Both patients who were partial responders after a single cingulotomy became full responders after a second cingulotomy.

At the most recent follow-up for the 18 patients who underwent multiple cingulotomies, five patients (28%) were responders and two (11%) were partial responders. Thus, seven patients (39%) met criteria for at least partial response.

A two-by-three chi-square analysis of single versus multiple cingulotomies by responder status (full response, partial response, no response) revealed no difference in responder status at the most recent follow-up between those who received a single cingulotomy and those who received multiple cingulotomies (χ²=0.54, df=2, p=0.76).

Table 2 shows patients’ scores on the Sickness Impact Profile at baseline (rated retrospectively) and at the most recent follow-up (N=28) for each specific area of functional status and for overall status. For the group as a whole, there were improvements in most functional areas measured by subscales of the Sickness Impact Profile as well as in the total score. The improvement was significant for one of the 11 subscales, for one of the three dimensions, and for the total score. Moreover, no individual area of functioning showed significant worsening.

Nine patients (20%) reported at least one adverse effect after cingulotomy. Two patients (5%) reported memory deficits, which resolved within 6–12 months. One patient demonstrated resolution of memory deficits as measured by neuropsychological testing, and one patient self-reported resolution of memory deficits. One patient (2%) exhibited apathy with decreased energy after cingulotomy. This effect resolved within 6 months. In addition, three patients (7%) had urinary disturbances after surgery. Two patients (5%) experienced urinary retention. Both cases of urinary retention resolved within a few days postoperatively; one patient required catheterization, and the other did not. The third patient had received a diagnosis of prostate cancer before undergoing the cingulotomy and had been experiencing urinary incontinence before the surgery; this patient reported that the urinary incontinence worsened after the cingulotomy. After cingulotomy one patient (2%) developed a seizure disorder that has required ongoing treatment with anticonvulsant medication. One patient (2%) developed postoperative edema with resulting hydrocephalus. The hydrocephalus resolved after placement of a ventriculostomy. One patient (2%) committed suicide approximately 6 years after undergoing cingulotomy. Before the suicide, this patient’s OCD symptoms had improved after cingulotomy. However, this patient had a long history of major depression with almost continuous suicidal ideation for more than 8 years and a history of one previous suicide attempt. Although nine patients (20%), excluding the patient who committed suicide, reported at least one adverse effect, only two (5%) patients reported enduring sequelae.