Stereotactic Cingulotomy and Capsulotomy

Number: 0288

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses stereotactic cingulotomy and capsulotomy.

1. Medical Necessity

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

2. Experimental, Investigational, or Unproven

   The following interventions are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established:

   1. Stereotactic cingulotomy for treatment of the following conditions (not an all inclusive list), including long-term outcomes for these indications:
      
      
      1. Chronic, intractable non-malignant pain (e.g., post-stroke pain);
      2. Drug addiction;
      3. Intractable seizures;
      4. Psychiatric diseases (e.g., affective disorders, aggressive behavior, anxiety, depression, eating disorders, obsessive-compulsive disorders, personality disorders, schizophrenia, and Tourette's disorder);

   2. Anterior (ventral) capsulotomy for obsessive compulsive disorder and for all other indications.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
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]

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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.

Magnetic resonance imaging (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.

Marques and colleagues (2021) noted that one of the few resources for treating medically intractable pain is ablative surgery; however, its indications have fallen dramatically over the last decades.  One such procedure is mesencephalotomy.  In a retrospective study, these researchers examined current risks and benefits of MR-guided semidirect targeting-based stereotactic mesencephalotomy.  This trial was based on a review of the medical records of 22 patients with nociceptive (n = 5), neuropathic (n = 10), or mixed (n = 7) refractory pain treated with unilateral mesencephalotomy alone (17 patients) or associated with bilateral anterior cingulotomy (5 patients) between 2014 and 2021 in the authors' institutions.  The confidence interval (CI) adopted in this study was 95 %.  The sample included 12 women and 10 men with ages ranging from 23 to 80 years (mean of 55.1 ± 17.1 years).  Using MR-guided semidirect targeting, the following structures were targeted: spinoreticulothalamic (neuropathic/mixed pain, n = 17), trigeminothalamic (nociceptive/mixed pain in the face, n = 5), and neospinothalamic (nociceptive/mixed pain in the body, n = 7) pathways.  The most common response to macro-stimulation was central heat/moderate discomfort.  Radiofrequency thermocoagulation was made with 70° C to 75° C/60 sec.  A total of 86.3 % (3 months) and 76.9 % (12 months) of the patients achieved excellent or good results (improvement of pain of greater than 50 %), presenting with a significant mean pain relief of 80.1 % at 3 months and 71.4 % at 12 months post-operatively.  The addition of bilateral anterior cingulotomy did not improve the results.  Patients with upper limb, cervicobrachial, and face pain did significantly better than those with trunk pain.  The worst results were observed in patients with neuropathic and/or trunk pain.  The surgical failure (pain relief of less than or equal to 25 %) and recurrence rates were 9.1 % each, apparently related to the use of lower lesioning parameters (70° C/60 sec) and to the presence of neuropathic and/or trunk pain.  The morbidity rate was 8 %, with both complications (vertical diplopia and confusion/agitation) happening in patients lesioned with 75° C/60 sec.  There were no deaths in this series.  The authors concluded that the findings of these results showed that contemporary stereotactic mesencephalotomy was an effective, relatively low-risk, and probably under-used procedure for treating medically intractable pain.  Careful semi-direct determination of the target coordinates associated with close attention to electrical macro-stimulation responses certainly played an important role in avoiding complications in most of the procedures.  A higher lesioning temperature (75° C) apparently prevented recurrence, but at the cost of an increased risk of complications.

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.

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.

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 (2021) 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.

Galkin et al (2022) stated that the treatment of mental illnesses that are resistant to conservative therapy poses a serious problem.  Surgical methods with proven effectiveness have been proposed for only a small group of psychiatric diseases, while in practice non-classical clinical situations were observed rather often.  These investigators reported on the case of a 36-year-old man with a 18-year history of "schizophrenia with a predominant obsessive-compulsive syndrome", who was referred to the Burdenko National Medical Research Center of Neurosurgery for consideration of neurosurgical treatment.  Based on results of longitudinal independent evaluations of the patient in several specialized clinical centers the disease was considered resistant to medical therapy.  Radio-surgical procedure was carried out using the Leksell Gamma Knife Perfexion.  Ventral portion of the anterior limb of internal capsule was targeted with two 4-mm isocenters on each side, with prescription dose at 50 % isodose line of 80 Gy and a maximal dose of 160 Gy.  No obvious complications or side effects were noted during 13-month follow-up following radiosurgery.  Gradual clinical improvement was observed with 25 % reduction of the Y-BOCS score at 13 months after treatment.  Similarly, the Hospital Anxiety and Depression Scale (HADS) anxiety and depression scores decreased by 24 % and 58 %, respectively.  This was the 1st published case of radio-surgical treatment of a psychiatric disorder in Russia.  It showed the potential effectiveness of Gamma Knife capsulotomy for non-classical forms of OCD co-morbid with schizophrenia.  Nevertheless, definitive conclusions regarding the reliability of this radio-surgical indication could only be rendered based on the results of larger studies.

Khattab et al (2022) noted that effective therapeutic options for refractory depression are needed.  Recent advancements allow both precise ablative radiation and functional neurologic connectome analysis using standard MRI.  In a prospective, observational, single-arm, single-center, pilot study, these researchers combined these innovations to perform stereotactic radio-surgical capsulotomy for the treatment of medically refractory MDD and examined connectome response using a novel tractography-based approach.  Patients with medically refractory MDD were enrolled in this trial from 2020 to 2021 at an academic tertiary referral center.  Bilateral ablation of the anterior limb of the internal capsule was accomplished by mask-based linear accelerator stereotactic radiosurgery; Beck's Depression Inventory measured effectiveness.  Montreal Cognitive Assessment evaluated cognition.  A total of 3 patients were enrolled.  Depression burden improved by 88 % at 12-month follow-up and by 55 % at 18-month follow-up for patient 1 and 2, respectively.  Patient 1 discontinued ketamine therapy, and patient 2 discontinued electro-convulsive therapy (ECT).  Patient 3 reported global improvement in symptoms and function at 3 months.  All 3 patients had reduction or resolution of suicidal ideation.  No patient experienced cognitive decline or neurologic toxicity, and Montreal Cognitive Assessment score, as well as subjective patient-reported evaluations of concentration and attention, were superior following treatment.  Tractography confirmed intended disruption of the cortico-striatal-thalamo-cortical loop with structural re-organization in the connectome.  Connectome change was consistent between patients.  Observed increases in caudate and putamen connectivity and decreases in thalamic connectivity may explain improved concentration, attention, and depression.  The diversity and magnitude of connectome change may correlate with degree of clinical response.  The authors concluded that in 3 patients with refractory MDD, radio-surgical capsulotomy significantly reduced the burden of depression.  Functional connectome re-organization offered neurobiological evidence to support further investigations of the role of radiosurgery in depression.

Strouphauer et al (2023) noted that OCD is a neuropsychiatric condition featuring patterns of obsessions, compulsions, and avoidant behaviors that are often time-consuming and distressing to affected individuals.  Cognitive-behavioral therapy (CBT) with exposure and response prevention and/or serotonin re-uptake inhibitors are 1st-line treatments for OCD; although other therapeutic interventions may serve as economically practical modalities under various circumstances.  Exploring and understanding the cost-effectiveness of all indicated OCD interventions are important to inform therapeutic decisions and provide quality patient-centered care at a cost that is not burdensome to the patient and/or healthcare system.  These investigators carried out a systematic literature review; and studies were extracted from PubMed, Embase, Ovid Medline, and Cochrane.  All cost-effectiveness studies that included economic analyses with respect to OCD treatment modalities and were written in English and published between January 2010 and July 2022 were eligible for inclusion in this analysis.  These investigators reported a narrative synthesis of the findings and quality appraisal of the selected references.  Of the 707 references returned in the literature search, a total of 18 cost-effectiveness studies were included for review.  Compared with treatment as usual, several studies reported clinical superiority and cost-effectiveness of Internet-based CBT programs for adults and children with OCD at various willingness-to-pay thresholds and economic reference indicators, although cost-effectiveness relative to in-person CBT with exposure and response prevention is unclear and estimates of efficacy are likely lower for Internet-based CBT.  One study favored the cost utility of serotonin re-uptake inhibitor monotherapy over CBT with exposure and response prevention although efficacy estimates of the former tend to be lower, and relative cost-differences were low.  A total of 5 studies examined the cost-effectiveness of high-intensity neuro-augmentation, including deep brain stimulation (DBS) and stereotactic radio-surgical capsulotomy, in the context of treatment-refractory OCD.  The authors concluded that despite the relatively high prevalence of OCD worldwide, cost-effectiveness data for therapeutic modalities remain sparse.  Because of the chronic nature of OCD, the cost of treatment accumulates and may result in a significant financial burden over time, especially when non-evidence-based interventions are used.  However, several alternative therapeutic modalities hold promise for economic practicality without significant sacrifice in clinical efficacy.  Moreover, these researchers stated that further investigations are needed to directly compare the cost-effectiveness of such therapeutic alternatives with the current standard of care (SOC), CBT with exposure and response prevention.

Cingulotomy for Intractable Pain Caused by Thalamic Glioma

Kostiuk and Tevzadze (2024) noted that stereotactic bilateral anterior cingulotomy, including lesions in the anterior and midcingulate cortex, is one of the methods used for the treatment of thalamic pain syndrome.  In cases of non-ischemic thalamic lesions, simultaneous stereotactic biopsy of the lesion can be carried out in combination with cingulotomy.  These investigators described the case of a 45-year-old man with a lesion in the right thalamus, resulting in a severe contralateral hemi-pain syndrome.  Bilateral radiofrequency (RF) anterior cingulotomy and stereotactic biopsy were conducted during a single operation.  Pain completely subsided within a few days after the anterior cingulotomy.  Histological examination identified a diffuse astrocytoma (WHO grade II, ICD-O 9400/3), and the patient was subsequently referred for LINAC-based radiosurgery.  The pain syndrome was controlled for 4 years, after which the pain syndrome returned with an increase in tumor size.  The authors concluded that simultaneous anterior cingulotomy and stereotactic biopsy of the thalamic lesion was a safe approach for the management of thalamic pain syndrome, resulting in the alleviation of pain, verification of the lesion's etiology, as well as the use of appropriate treatment.

Cingulotomy with Gamma Knife Radiosurgery for the Treatment of Non-Oncologic Intractable Chronic Pain

Molina-Romero et al (2024) stated that according to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage.  Pain is the main reason for consulting healthcare services and its chronic form is among the leading causes of years lost to disability.  The QOL of patients with chronic pain can be severely affected not only by its sensitive component, transmitted via the spinothalamic pathway, but also by other components that can contribute to the disability generated due to pain, such as cognitive, behavioral, and emotional, which are conducted and processed by other pathways and structures.  The anterior cingulate cortex has a critical role in pain processing, primarily in the emotional meaning of pain.  Available evidence including cases of ablative management in the cingulum via stereotactic surgery have been reported for the management of intractable chronic pain (ICP).  These investigators described the findings of 5 cases of patients with ICP who were treated with bilateral anterior cingulotomy via Gamma Knife radiosurgery (GKR); they stated that no previous studies have described this technique in patients with ICP.

The 5 cases entailed a 62-year-old woman with burning mouth syndrome; a 45-year-old man with radicular pain after L4 fracture and instrumentation from L3 to L5; a 48-year-old woman with L4 to L5 disc herniation and persistent lumbo-sacral pain following percutaneous discectomy; a 56-year-old woman with a history of lipo-myelomeningocele and chronic pain at the lumbo-sacral level of the spine and left greater trochanter; and a 40-year-old man with continuous pain following complete spine cord injury (SCI) in a road accident.  All of the subjects with a high-intensity (10/10) and incapacitating pain.  Multiple strategies like open surgeries, epidural blocks, pulsed RF, as well as spinal cord neuromodulation, all failed.  All 5 subjects presented a marked affective component, with depressive symptoms, anxiety, sleep disorders, and suicidal ideas, for which they were additionally followed-up by psychiatry.  In each one of the cases, GKR was carried out in both anterior cortex cingulum with Gamma Knife Perfexion.  With a 4-mm collimator, 2 shots of 120 Gy were applied on each anterior cortex cingulum.  The maximum dose was 120 Gy, with a coverage dose of 60 Gy and isodose of 50 %.  In all procedures, the dose received by the anterior cerebral artery was less than 30 Gy, to protect anterior brain circulation.  The range of duration per fraction was from 120 to 222 mins.  All the procedures were conducted in a single fraction and the patients were discharged on the same day of the procedure.  No patients reported AEs during the procedure and there were no acute complications during the 1st-month post-treatment.  Follow-up data were obtained with a mean period of 37 months (SD 29).  The intensity of pain was assessed with the VAS (on a 0 to 10 scale ).  Reduction in pain intensity was reported in 3 patients (50 % in lumbo-sacral discogenic syndrome, 60 % in radicular pain after L4 fracture, and 80 % in lumbo-sacral and trochanteric pain), whereas the other 2 patients reported no intensity changes in pain.  In 4 patients, the doses and frequency of analgesics decreased, and depressive symptoms also improved significantly in 4 patients.  There was no recurrence of pain in patients who reported an initial improvement, and no long-term complications were described.  The authors concluded that anterior cingulotomy with GKR was a non-invasive technique that might be safe and effective for the treatment of patients with ICP.  Not only could this technique lower the intensity of pain, but it could also alleviate emotional symptoms which are a hallmark in patients with ICP.  Moreover, these researchers stated that further investigations in a larger cohort of patients are needed to examine the safety and effectiveness of cingulotomy with GKR as adjunctive therapy in cases of chronic intractable pain.

McBenedict et al (2024) noted that pain management is a critical aspect of cancer treatment and palliative care, where pain can significantly impact QOL.  Chronic pain, which affects a significant number of people globally, remains a prevalent and challenging symptom for patients.  While medications and psychosocial support systems play a role in pain management, surgical as well as radiological interventions, including cingulotomy, may be necessary for refractory cases.  Cingulotomy aims to disrupt neural pathways associated with emotional processing and pain sensation; thus, decreasing the affective component of pain.  Although cingulotomy has shown promise in providing pain relief, especially in patients refractory to traditional medical treatment, its use has declined in recent years as a result of advancements in non-destructive therapies and concerns regarding long-term effectiveness and patient suitability.  Modern stereotactic methods have enhanced the precision and safety of cingulotomy, reducing associated complications and mortality rates.  Despite these advancements, questions remain regarding its long-term effectiveness and suitability for patients with limited life expectancy, especially those with cancer.  These researchers carried out a comprehensive systematic review following the PRISMA 2020 guidelines, aimed at providing insights into the effectiveness, potential benefits, as well as limitations of this neurosurgical procedure in the management of individuals with intractable pain.  An electronic search of PubMed, Embase, Scopus, and Web of Science was performed with open data-base coverage dates.  The review focused on outcomes such as pain intensity and QOL.  The inclusion criteria entailed human studies of any age experiencing intractable cancer or non-cancer pain, with cingulotomy as the primary intervention.  Various study designs were considered, including observational studies, clinical trials, and reviews focusing on pain and cingulotomy.  Exclusion criteria included non-human studies, non-peer-reviewed articles, and studies unrelated to pain or cingulotomy.  This review highlighted the effectiveness of stereotactic anterior cingulotomy in the management of intractable pain, especially when conventional treatments have failed.  Advanced MRI-guided techniques enhance precision, but challenges like cost and expertise persist.  Studies included in this review showed significant pain relief with minimal adverse effects, although the optimal target remains debated.  Neurocognitive risks exist, but outcomes are generally favorable.  Expected AEs include transient effects like urinary incontinence and confusion.  Re-operation may be necessary for inadequate pain control, with a median pain relief duration of 3 months to 1 year.  A double stereotactic cingulotomy appeared to be safe and effective for refractory pain.  The authors concluded that despite the remaining challenges and controversies surrounding cingulotomy, especially regarding target definition and neurocognitive outcomes, the collective evidence suggested that it represents a valuable therapeutic option for patients suffering from intractable oncological pain.  These investigators stated that continued research and technological advancements hold the potential to further optimize outcomes and minimize adverse effects, ultimately improving the QOL for patients experiencing debilitating pain conditions.

The authors stated that some studies included in this review had limitations.  For example, in 1 study, the optimal targets, suitable candidates, and outcome measures were not clearly defined.  In all studies, the demographic information could have been more comprehensive, going beyond just age and sex.  The shortest follow-up duration ranged from 1 to 11 months, making it difficult to compare the long-term outcomes of the procedure among participants.  In another study, the inclusion and exclusion criteria were not clearly stated, and scales for objectively measuring outcomes were not well defined.  The follow-up time for participants was also not clearly indicated.  In addition, the use of subjective measures such as fair, poor, and excellent for characterizing the study outcome was prone to bias.

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References