Stereotactic Cingulotomy and Capsulotomy

Number: 0288

Policy

Aetna considers stereotactic cingulotomy medically necessary when it is used as a last resort to provide pain relief for members with terminal cancer pain.

Aetna considers stereotactic cingulotomy experimental and investigational for the following indications (not an all inclusive list) because its effectiveness (including long-term outcomes) for these indications has not been established.

• Treatment of chronic, intractable non-malignant pain (e.g., post-stroke pain)
• Treatment of drug addiction
• Treatment of intractable seizures
• Treatment of psychiatric disease (e.g., affective disorders, aggressive behavior, anxiety, depression, eating disorders, obsessive-compulsive disorders, personality disorders, schizophrenia, and Tourette's disorder).

Aetna considers anterior (ventral) capsulotomy experimental and investigational for obsessive compulsive disorder and for all other indications.

Background

Since its inception, functional neurosurgery (or psychosurgery) has been over-shadowed by ethical questions and doubts resulting from inadequate reporting of outcomes.  In the 1940s and early 1950s prior to the introduction of major psychotropic agents, psychosurgery became popular in the United States.  Pre-frontal lobotomies were indiscriminately performed for intractable mental illness, in particular, depression, anxiety, and obsessive-compulsive disorders (OCDs).  However, its side effects, especially the "frontal lobe syndrome", led to the need for more refined surgical approaches; the most important of these was the use of stereotaxis.  Cingulotomy, subcaudate tractotomy, limbic leucotomy, and anterior capsulotomy are generally the stereotactic treatments of choice today.

MRI-guided stereotactic cingulotomy consists of lesioning the white matter deep to the cingulate gyrus.  Reports suggest that pain secondary to cancer is relieved in 30 % to 90 % of patients following cingulotomy or cingulotomy combined with midbrain tractotomy.  This procedure seems to be of most benefit when there is a major element of suffering.  The results have been less encouraging in non-malignant chronic pain, but it has been suggested that cingulotomy may be useful in cases in which depressive symptoms dominate the clinical picture.

The literature on the use of neuroablative procedures performed on the brain is non-existent in regards to chronic non-malignant pain, and limited in regards to psychiatric illnesses.  Most available studies are limited by the use of retrospective designs, variations in diagnostic systems, the lack of independent clinical raters, use of a variety of psychosurgical techniques, and the lack of true control groups.  Such irreversible, modern psychosurgical techniques performed on the brain in an effort to affect the psyche require prospective long-term follow-up studies to further define the role of surgery in treating various intractable psychiatric disease.

Jung et al (2006) examined the long-term effectiveness and adverse cognitive effects of stereotactic bilateral anterior cingulotomy as a treatment for patients with refractory OCD.  A total of 17 patients suffering from refractory OCD underwent stereotactic bilateral anterior cingulotomies and were followed for 24 months.  The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Clinical Global Impression and other neuropsychological tests were used to evaluate the effectiveness and cognitive changes of cingulotomy.  The tests were taken before and 12 and 24 months after surgery.  The mean improvement rate of the Y-BOCS score achieved from the baseline was 48 %.  Eight patients (47 %) met the responder criteria.  During the 24-month follow-up, there were no significant adverse effects observed after surgery.  The authors concluded that bilateral anterior cingulotomy was effective for the treatment of refractory OCD, and no other significant adverse cognitive effects on long-term follow-up were found.  The success rate in this study was fair and its findings need to be validated by well-designed studies.

Brotis et al (2009) stated that stereotactic cingulotomy constitutes a psycho-surgical procedure nowadays advocated in the treatment of medically intractable OCD, chronic pain and drug addiction.  From its theoretical conception to the first cingulectomies performed and modern stereotactic-guided cingulotomies, various target localization methods, different surgical techniques, and numerous lesioning devices have been utilized.  These investigators performed a literature review related to cingular lesion placement in an effort to identify misconceptions of the past, recapitulate existing knowledge and recognize targets for further research.  The initial animal and human electrophysiologic experimental data regarding the role of the cingulate cortex in various behavioral and cognitive functions were meticulously reviewed.  The clinical indications, surgical technique and the clinical results and complications of open cingulectomies were examined.  The anatomic target localization methodologies, surgical technique, and the outcome of the initial stereotactic cingulotomy procedures were reviewed, and the evolution of the imaging techniques, stereotactic devices, and lesioning strategies were followed.  The modern advanced surgical techniques, clinical outcome and the procedure-associated complications were analyzed with particular emphasis on the emotional, behavioral, and cognitive procedure-induced changes.  The authors concluded that large-scale prospective studies with strict inclusion and well-defined, objective outcome criteria are needed for defining the role of stereotactic cingulotomy in the current psycho-surgical armamentarium.

Jimenez et al (2012) performed a preliminary study on the safety and effectiveness of bilateral cingulotomy and anterior capsulotomy in patients with aggressive behavior.  Twenty-three psychiatric patients showing aggressive behavior refractory to conventional treatment were initially evaluated.  The subjects were clinically selected using the Overt Aggression Scale (OAS) and the Global Assessment of Functioning Scale (GAF).  Each case was carefully reviewed by the Ethics Committee of Mexico's General Hospital.  Once selection criteria were met, stereotactic lesions were made using radiofrequency on the anterior limb of the internal capsule and supragenual cingulum.  Statistical differences were evaluated with a Wilcoxon test at 6 months and at 4 years.  A total of 10 patients underwent surgery.  Their OAS and GAF scores decreased after the procedure at the 6-month (p < 0.05) and at the 4-year (p = 0.068) follow-up; 4 patients showed mild and transitory post-surgical complications (hyperphagia and somnolence).  The authors concluded that bilateral anterior capsulotomy in combination with cingulotomy may reduce aggressive behavior and improve clinical evaluations.  Very strict clinical and ethical evaluations were applied prior to considering patients for this treatment.  These preliminary findings were confounded by the combinational use of cingulotomy and capsulotomy.  Well-designed studies are needed to confirm the effectiveness of cingulotomy in the treatment of individuals with aggressive behavior.

Leveque and colleagues (2013) stated that radiosurgery for psychiatric disorders had been performed for more than 50 years.  The use of deep brain stimulation has recently been expanded to the investigational treatment of specific psychiatric disorders.  A literature review of past studies incorporating radiosurgical stereotactic lesions for psychiatric disorders was performed to provide historic context and possible guidance for current and future attempts at treating psychiatric disorders, especially by gamma capsulotomy.  The anatomic target localization, dose selection, and the outcome of the radiosurgical procedures were reviewed, and the evolution of lesioning strategies were analyzed with particular emphasis on the dose selection.  The authors concluded that large-scale prospective studies with strict inclusion and well-defined, objective outcome criteria are needed for defining the role of radiosurgery for the treatment of psychiatric disorders.  Cingulotomy and gamma capsulotomy were among the keywords used in this review.

Nuttin and associates (2014) noted that for patients with psychiatric illnesses remaining refractory to "standard" therapies, neurosurgical procedures may be considered.  Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups.  To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines.  These were intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments.  The proposed consensus document highlighted that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and OCD are considered "established" in some countries, they still lack level I evidence.  Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioral disorder, still remains at an investigational stage.  Researchers are encouraged to design randomized controlled trials, based on scientific and data-driven rationales for disease and brain target selection.  The authors concluded that experienced multi-disciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multi-faceted pre-operative as well as post-operative long-term follow-up evaluation, and reporting of effects and side effects for all patients.

Cingulotomy for Intractable Seizures

Cosgrove and Cole (2005) noted that stereotactic lesions of deep cerebral structures have been carried out for a variety of generalized and focal forms of epilepsy in the past.  Bilateral cingulotomies, amygdalotomies, lesions in the Field of Forel and thalamic lesions have all been tried.  Results are scattered and too few for any conclusions to be made although generally they are unimpressive.  While some lesions may have an initial good result, seizures tend to recur in virtually all patients and stereotactic ablations of subcortical structures are no longer in use.

Furthermore, an UpToDate review on "Seizures and epilepsy in children: Refractory seizures and prognosis" (Wilfong, 2018) does not mention stereotactic cingulotomy as a therapeutic option.

Cingulotomy for Eating Disorders

Guerrero Alzola and colleagues (2020) stated that anorexia nervosa (AN) is a serious disease with a high rate of chronification.  In chronic and serious cases, psychotherapeutic and pharmacological treatments are insufficient to control the disease.  These researchers presented the case of a female patient with severe chronic restrictive anorexia nervosa resistant to psycho-medical treatment.  During the 31 years the illness evolved, the patient required multiple hospital admissions. With a body mass index (BMI) of 12.8 kg/m2 and consequent risk of death, stereotactic cingulotomy was performed comprising bilateral blocking of the anterior cingulate cortex by stereotactic radiofrequency thermocoagulation, confirmed by tractography 5 years later.  After 10 years of follow-up, the patient was clinically stable with an increased BMI and improved neuropsychological indicators.  The authors concluded that stereotactic surgery may be an option for patients with chronic AN where conventional treatments have proved insufficient.

Furthermore, an UpToDate review on "Eating disorders: Overview of prevention and treatment" (Yager, 2020) does not mention cingulotomy as a therapeutic option.

Anterior Capsulotomy for Obsessive Compulsive Disorder

Anterior capsulotomy, which targets the anterior limb of the internal capsule, is thought to disrupt communication among the orbitofronta cortex, dorsal anterior cingulate cortex, ventral striatum, and thalamus (Brown, et al., 2016).

Rasmussen, et al. (2018) reported on a registered prospective uncontrolled observational study of the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD (ClinicalTrials.gov NCT01849809). Fifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging. Thirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state.

Lopes, et al. (2014) reported on a controlled clinical trial to determine the efficacy and safety of a radiosurgery (gamma ventral capsulotomy [GVC]) for intractable OCD. In a double-blind, placebo-controlled, randomized clinical trial, 16 patients with intractable OCD were randomized to active (n = 8) or sham (n = 8) GVC. Blinding was maintained for 12 months. After unblinding, sham-group patients were offered active GVC. Patients randomized to active GVC had 2 distinct isocenters on each side irradiated at the ventral border of the anterior limb of the internal capsule. The patients randomized to sham GVC received simulated radiosurgery using the same equipment. The primary outcomes were scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression-Improvement (CGI-I) Scale at 1 year. Response was defined as a 35% or greater reduction in Y-BOCS severity and "improved" or "much improved" CGI-I ratings. Two of 8 patients randomized to active treatment responded at 12 months, and none of the 8 sham-GVC group patients responded (the absolute difference was not statistically significant: 0.25; 95% CI, −0.05 to 0.55; P = .11). At 12 months, median Y-BOCS scores were 23.5 in the active group vs 31 in the sham patients (P = .01). The median Y-BOCS scores decreased 28.6% in the active treatment group and 5.8% in the sham group (P = .04988). The median CGI-I scores were 3 and 4 in the active and sham treatment groups, respectively. At 54 months, 3 additional patients in the active group had become responders. Of the 4 sham-GVC patients who later received active GVC, 2 responded by post-GVC month 12. The most serious adverse event was an asymptomatic radiation-induced cyst in 1 patient. The investigators concluded that, in this preliminary trial, patients with intractable OCD who underwent GVC may have benefitted more than those who underwent sham surgery although the difference did not reach statistical significance. The investigators stated that additional research is necessary to determine if GVC is better than deep-brain stimulation.

Brown, et al. (2016) performed a systematic review, according to Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) and Agency for Healthcare Research and Quality (AHRQ) guidelines, of the clinical efficacy and adverse effect profile of dorsal anterior cingulotomy compared with anterior capsulotomy for the treatment of severe, refractory obsessive-compulsive disorder (OCD). The authors included studies comparing objective clinical measures before and after cingulotomy or capsulotomy (surgical and radiosurgical) in patients with OCD. Only papers reporting the most current follow-up data for each group of investigators were included. Studies reporting results on patients undergoing one or more procedures other than cingulotomy or capsulotomy were excluded. Case reports and studies with a mean follow-up shorter than 12 months were excluded. Clinical response was defined in terms of a change in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. The authors searched MEDLINE, PubMed, PsycINFO, Scopus, and Web of Knowledge through October 2013. English and non-English articles and abstracts were reviewed. Ten studies involving 193 participants evaluated the length of follow-up, change in the Y-BOCS score, and postoperative adverse events (AEs) after cingulotomy (n = 2 studies, n = 81 participants) or capsulotomy (n = 8 studies, n = 112 participants). The average time to the last follow-up was 47 months for cingulotomy and 60 months for capsulotomy. The mean reduction in the Y-BOCS score at 12 months' follow-up was 37% for cingulotomy and 55% for capsulotomy. At the last follow-up, the mean reduction in Y-BOCS score was 37% for cingulotomy and 57% for capsulotomy. The average full response rate to cingulotomy at the last follow-up was 41% (range 38%-47%, n = 2 studies, n = 51 participants), and to capsulotomy was 54% (range 37%-80%, n = 5 studies, n = 50 participants). The rate of transient AEs was 14.3% across cingulotomy studies (n = 116 procedures) and 56.2% across capsulotomy studies (n = 112 procedures). The rate of serious or permanent AEs was 5.2% across cingulotomy studies and 21.4% across capsulotomy studies. The authors stated that this systematic review of the literature supports the efficacy of both dorsal anterior cingulotomy and anterior capsulotomy in this highly treatment-refractory population. The authors noted, however, that the observational nature of available data limits the ability to directly compare these procedures. The authors stated that controlled or head-to-head studies are necessary to identify differences in efficacy or AEs and may lead to the individualization of treatment recommendations.

Warnke, et al. (2019) reported on the first case series in the literature applying high energy interstitial laser ablation (LITT) to treat refractory OCD. Four patients with OCD underwent bilateral LITT capsulotomy from 2015 to 2019. All patients were reviewed by the Psychiatric Neurosurgery Board of the institution Inclusion criteria were based upon Yale-Brown Obsessive Compulsive Scale (YBOCS) score above 30 and inability to function in daily life. Each patient's pre- and postoperative partial and full Y-BOCS scores were collected. The partial Y-BOCS score was assessed 24 h post surgery. Ablation parameters such as total energy delivered, average power, and ablation volume were collected. Extent of connectome disruptions were assessed with volumetric diffusion tensor MRI. The investigators reported that all patients had YBOCS scores between 31 and 40. Immediate improvement on partial Y-BOCS was noted in all patients 25 hours post surgery. (Mean reduction of 83.3 + 20.1%) YBOCS scores after 3 months went from 35.6 + 3.8 to 17.6 + 4.7, a more than 50% reduction. Lesion volumes were large with an average of 3.13 + 1.1 cc on T2 MRI. Energy deposited ranged from 402.75 to 868.5 Watts (700 C) consistently higher on the right side to create symmetric lesions (P < .01) .Orbito-frontal thalamic connections were reduced by more than 85% on DTI 24 hours post surgery and consistently 3 months postoperatively. The investigators concluded that LITT is capable of creating large targeted lesions with real time MR monitoring leading to unprecedented almost immediate and extensive improvement in refractory OCD. Larger lesions due to higher energy deposition resulting in maximum disruption of the hyperactive circuitry underlying OCD are possible with LITT. The investigators also stated that symptom reduction is superior to alternative techniques.

International consensus guidelines on stereotactic neurosurgery for psychiatric disorders (Nuttin, et al., 2014) stated that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered "established" in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation for any psychiatric or behavioral disorder still remains at an investigational stage. The consensus guidelines stated that researchers are encouraged to design randomized controlled trials, based on scientific and data-driven rationales for disease and brain target selection. The guidelines noted that experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-up evaluation, and reporting of effects and side effects for all patients.

Davidson and associates (2020) noted that magnetic resonance-guided focused ultrasound (MRgFUS) anterior capsulotomy (AC) is a novel therapeutic option for patients with refractory OCD or major depressive disorder (MDD); however, there is concern that lesional psychiatric surgery procedures may have adverse effects on cognition.  These researchers examined if MRgFUS capsulotomy causes cognitive decline in patients with psychiatric illness.  A total of 10 patients with refractory OCD (n = 5) or MDD (n = 5) underwent MRgFUS capsulotomy.  Cognitive functioning was measured at baseline as well as 6 months and 12 months post-operatively, with a battery of neuropsychological tests evaluating domains of executive function, memory, and processing speed.  Scores were analyzed at the individual-level, and changes of greater than or equal to 2 standard deviations (SDs) were considered clinically significant.  These investigators also examined if changes in clinical symptoms were associated with changes in cognitive performance.  At baseline, intellectual functioning was in the average to high-average range for the group.  Following MRgFUS capsulotomy, there were no deteriorations in cognition that reached greater than or equal to 2 SDs at 6 or 12 months; 8 out of the 10 patients demonstrated a greater than or equal to 2 SDs improvement in at least 1e cognitive score at 6 or 12 months post-operatively.  Improvements in clinical symptoms correlated significantly with self-reported improvements in frontal lobe function (p < 0.05), but not with objective measures of cognitive functioning.  The authors concluded that MRgFUS capsulotomy did not result in cognitive decline in this cohort of patients with refractory OCD or MDD, suggesting that this procedure could be offered to patients with a very low risk of cognitive side effects.

The authors stated that this study had several drawbacks.  First, the sample size was relatively small (n = 5 in the OCD group) and they did not include a control group.  Additional studies with larger sample sizes and control groups are needed to obtain a more comprehensive understanding of the impact of MRgFUS-AC on cognitive functioning.  Second, although these researchers tried to minimize practice effects by employing alternate versions of tests where possible, they could not rule out the possibility that repeat testing impacted the results.  third, only 4 of the 10 patients in this cohort met responder status, which limited the ability to evaluate correlations with clinical improvement.

Kramska and colleagues (2020) stated that AC is one of the last therapeutic options for OCD refractory to conservative treatments.  Several forms of cognitive dysfunction have been identified following assessment of neuropsychological outcomes in OCD patients; however, few studies focused on cognitive changes in OCD patients after surgery.  These researchers examined the effects of AC on cognitive performance and mood status in patients with refractory OCD.  A total of 12 patients underwent bilateral AC between 2012 and 2019 at the authors’ institution.  Subjects (n = 12, female : male 5:7; mean age of 39.7 years; duration greater than or equal to 5 years) were evaluated before and 6 months after intervention.  The diagnosis of treatment-refractory OCD was based on recommended criteria for surgical treatment.  Subjects were examined using a neuropsychological battery and questionnaires focused on anxiety-depressive symptomatology.  The YBOCS was administered as a measure of severity of OCD symptoms.  These investigators detected a significant decrease of OCD, and anxiety and depressive symptomatology assessed by YBOCS, Beck Depression Inventory, and Beck Anxiety Inventory (p < 0.05) 6 months after AC in 8 patients, and a partial decrease in 4 patients; and 4 patients underwent repeated AC with more pronounced improvement achieved after the 1st procedure.  These researchers did not detect decline in cognitive performance in any patients; however, they did find better visual memory performance (p < 0.05).  The authors concluded that AC reduced OCD and anxiety-depressive symptoms, and did not appear to influence cognitive performance, even after repeated surgery.  These researchers stated that long‐term follow-ups of patients after AC were infrequent and potentially biased, because patients were evaluated and followed by the same treating specialist.  These investigators are convinced there must be strict inclusion criteria for patients considering potential complications and the irreversibility of this procedure.  They stated that these findings support AC as a promising option for patients suffering from severe, refractory OCD.  The authors stated that the present study reflected the Czech population, and results of their area of interest; however, inconsistent findings of co-morbid disorders in OCD across studies complicated generalization.  Considering the significant impact of co-morbidities, especially depression, the quality of life (QOL) is negatively influenced.  They stated that although the sample size of evaluated patients was relatively small, these findings may support future research regarding the suitability of AC for patients with refractory OCD.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
61720	Creation of lesion by stereotactic method, including burr hole(s) and localizing and recording techniques, single or multiple stages; globus pallidus or thalamus
61735	Creation of lesion by stereotactic method, including burr hole(s) and localizing and recording techniques, single or multiple stages; subcortical structure(s) other than globus pallidus or thalamus
CPT codes not covered for indications listed in the CPB:
Anterior capsulotomy - no specific code
ICD-10 codes covered if selection criteria are met:
G89.3	Neoplasm related pain (acute) (chronic) [used as a last resort to provide pain relief for members with terminal cancer pain]
Z51.5	Encounter for palliative care [terminal care]
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
F11.20 - F11.21, F12.20 - F12.21 F13.20 - F13.21, F14.20 - F14.21 F15.20 - F15.21, F16.20 - F16.21	Drug dependence
F20.0 - F21	Schizophrenic disorders
F30 - F39	Mood [affective] disorders
F34.1	Dysthymic disorder
F41.0 - F41.9	Other anxiety disorders
F42.2 - F42.9	Obsessive-compulsive disorders
F50.2 - F50.9	Eating disorders
F60.0 - F60.9	Specific personality disorders
F95.2	Tourette's disorder
G40.011 - G40.019	Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable
G40.111 - G40.119, G40.211 - G40.219	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes, intractable
G40.211 - G40.219	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable
G40.311 - G40.319	Generalized idiopathic epilepsy and epileptic syndromes, intractable
G40.411 - G40.419	Other generalized epilepsy and epileptic syndromes, intractable
G40.803 - G40.804	Other epilepsy, intractable
G40.813 - G40.814	Lennox-Gastaut syndrome, intractable
G40.823 - G40.824	Epileptic spasms, intractable
G40.911 - G40.919	Epilepsy, unspecified, intractable
G40.A11 - G40.A19	Absence epileptic syndrome, intractable
G40.B11 - G40.B19	Juvenile myoclonic epilepsy, intractable
G89.21 - G89.29	Chronic pain
G89.4	Chronic pain syndrome
R52	Pain [chronic pain NOS]

The above policy is based on the following references: