Anterior cingulotomy for intractable pain

Abstract

OBJECTIVE: To review the literature on anterior cingulotomy for intractable pain and provide guidelines on its indications, surgical technique, outcomes, and complications.

CONCLUSIONS: Bilateral anterior cingulotomy is a viable surgical option for intractable pain resistant to conservative treatment, demonstrating effective pain relief in both cancer and non-cancer patients with an acceptable safety profile.

Introduction & Background

Conservative therapy is often the first-line treatment for many symptoms of various disease processes, including pain. Nevertheless, if pharmacological or medical management fails for those patients with severe and chronic pain, a surgical strategy may be a reasonable option. Amongst the surgical options there are neuromodulation or neuroablative procedures, including cingulotomy.

Initially developed for psychiatric conditions, anterior cingulotomy targets the anterior cingulate cortex—part of the limbic system—and has been adapted for pain management when conservative therapies fail. Bilateral cingulotomy targets the anterior cingulate cortex, a part of the limbic system controlling integration of feelings and emotion.

As with other ablative procedures, concern exists regarding the destructive nature of the procedure and uncertainty regarding its mechanism of action. This review examines the literature since the 1990s on anterior cingulotomy for intractable pain to provide guidelines for management and expected outcomes.

Historical Perspectives

Following the introduction of frontal lobotomy by Egas Moniz in the mid-1930s, interest in decreasing the associated morbidity and mortality of the psychiatric surgery led physicians to search for alternative approaches that would still realize the desired psychiatric changes.

The concept of a cingulotomy was introduced by American physiologist John Fulton at a meeting of the Society of British Neurosurgeons in 1947. As Fulton stated, “were it feasible, cingulectomy in man would seem an appropriate place for limited leucotomy”.

In 1948, Cairns performed the first anterior cingulectomy. The results of 15 of these operations for a variety of psychiatric illnesses by Cairns and his colleagues were reviewed by Lewin in 1961.

In 1962, Foltz and White reported a case series of patients who underwent stereotactic cingulotomy for intractable pain. Later, Ballantine et al. reported complications in a series of 12 patients with intractable pain; however, no deaths were attributable to their technique.

Finally, in 1968, Foltz and White utilized anterior bilateral stereotactic cingulotomy extensively in their report on patients in whom “incapacitating pain seemed to be significantly augmented by emotion factors.”

Surgical Technique

Originally performed using ventriculography, cingulotomy is now conducted using magnetic resonance image (MRI) guided stereotactic technique. Direct visualization of targeted tissue clearly favors MRI guided stereotactic techniques.

Preoperative preparation includes mapping out the cingulate cortex. Under intravenous sedation with local anesthesia at pin insertion sites, a stereotactic MR-compatible frame is fixed to the patient’s skull. Utilizing oblique coronal MR images, tissue of the anterior cingulate gyrus is targeted approximately 2 to 2.5 cm posterior to the tip of the frontal horn, 7 mm from the midline and 2 to 3 mm above the corpus callosum bilaterally.

The patient is then placed on the operating table in a supine or semi-reclining position and the stereotactic frame is secured into position. Following skin incision, burr holes are drilled 15 to 25 mm from the midline. The dura is opened with caution to avoid cortical vessels. The thermocoagulation electrodes are inserted under stereotactic guidance.

Fig. 1. Target localization utilizing Medtronic Stealth navigation (Medtronic Inc., Minneapolis, MN).

The target tissue is heated to 85 degrees Celsius for 90 seconds utilizing a standard thermocoagulation electrode (Radionics, Inc., Burlington, MA) with a 10 mm uninsulated tip. After cooling, the electrode is withdrawn approximately 5 to 10 mm whereby a second lesion is made in accordance with the parameters for the initial lesion.

The aforementioned procedure is then completed in an identical manner for the contralateral side. Of note, in recent years, three lesions are placed to ensure complete ablation and reduce the need for subsequent lesioning procedures.

Post-ablation coronal MRI — a) Coronal view

Post-ablation axial MRI — a) Coronal view

Methods

The authors searched the following electronic databases: PubMed, CENTRAL (The Cochrane Library), MEDLINE, and EMBASE. Search terms were “anterior cingulotomy” and “cingulotomy pain.” No language restriction was implemented. Patients must have pain refractory to pharmacological or medical management. Outcome was alleviation of symptoms per the patients.

Anterior cingulotomy search strategy flowchart — Fig. 3. Anterior cingulotomy search strategy.

The combined search strategy identified 365 records. After review, 9 articles investigating change in severity of intractable pain following anterior cingulotomy were identified (Table 1).

Results

Literature Search

The combined search strategy identified 365 records (Fig. 3). After review, 9 articles investigating change in severity of intractable pain following anterior cingulotomy were identified (Table 1).

Patient Outcomes

Half of the patients in the studies reviewed received bilateral anterior cingulotomy for non-cancer pain (41 patients) versus cancer pain (41 patients). A wide variety of non-cancer indications for cingulotomy were reported and included post-traumatic neuropathic pain, atypical facial pain, diabetic neuropathy, and phantom pain.

The majority of studies reviewed used MRI for localization, although two reported use of computed tomography (CT). Quantification of pain improvement was uneven between studies – two studies used the Visual Analog Scale (VAS), one used a 10 point Likert scale, and one used the McGill pain scale.

Improvement in pain following cingulotomy was reported to range from 50 to 100% overall with similar results between cancer pain and non-cancer patients.

Authors & year	Study design	Number of patients	Type(s) of pain	Mean age at surgery	Localization	Laterality	Follow up	Outcome
Hassenbusch et al., 1990	Case series	4	Cancer	56.3 years	MRI	Bilateral	2, 4, and 6 weeks for 3 of 4 patients. 4 months for 1 patient	4 of 4 (100%) reported significant pain relief at all time points
Pillay et al., 1992	Case series	10	Cancer (8) Noncancer – neurofibromatosis and thalamic stroke (2)	51.9	MRI	Bilateral	6 month for cancer patients, 1 year for noncancer patients	5 of 8 (62.5% of cancer patients reported good to excellent pain relief, 1 of 2 (50%) of noncancer patients reported good pain relief
Wong et al., 1997	Case report	3	Cancer	46.0 years	MRI	Bilateral	Unclear	3 of 3 (100%) of patients reported significant pain relief immediately following their procedure and were discharged on significantly lighter pain medication regimens.
Cohen et al., 1999	Controlled trial	12	Noncancer – noncerebral traumatic injury	Range: 40–58 years	CT	Bilateral	1 year	8 of 12 (66%) experienced improvement on a 10 point Likert scale
Wilkinson et al., 1999	Case series	18	Wide variety of noncancer pain including lumbar or sciatic pain, phantom pain, and atypical facial pain	Range: 32 to 77 years	A few early cases used air ventriculography and the remainder used CT	Bilateral	Mean follow up of 7.7 years	13 of 18 (72%) reported sustained improvement at via a VAS questionnaire
Yen et al., 2005	Case series	22	Cancer (15) Noncancer including diabetic neuropathy, post-spinal cord injury pain, and trigeminal neuralgia (7)	58.3 years	MRI	Bilateral	1 week and 6 months for all patients	50–80% of cancer patients reported relief at some time point and 71–100% of patients with other causes of pain reported relief per the VAS
Yen et al., 2009	Case series	10	Cancer	64.4 years	MRI	Bilateral	1 week and 3 months	6 of 10 (60%) of patients had fair to good pain relief at both time points per the McGill pain questionnaire
Tsai et al., 2013	Case report	2	Neuropathic pain secondary to cervical and thoracic spine trauma	Not reported	MRI	Bilateral	Unclear	2 of 2 (100%) reported pain relief – one patient experienced transient exacerbation of pain before gradual improvement
Pereira et al., 2014	Case report	1	Cancer	67 yo	MRI	Bilateral	5 months	1 of 1 reported pain relief

Table 1: Results of literature review for anterior cingulotomy.

Discussion

Postoperative pain relief following anterior cingulotomy has been cited as temporally bimodal. Following their procedure, patients may be confused and ignore their pain. However, as the confusion clears the pain may return. Ultimately, patients may become habituated towards their pain.

Patients must be carefully followed with serial neurological examinations for early detection of any complications. An immediate, postoperative MRI scan is recommended to document the lesion site, lesion volume, and detect any complications. Patients recover well enough for discharge from the procedure after approximately 4 days, but some report recovery in as little as 48 h postoperatively.

Although anterior cingulotomy demonstrates effectiveness in pain control, surveillance for adverse effects is important. Observed side effects include headaches, nausea, vomiting, and seizures. While a spectrum of cognitive side effects have been reported following cingulotomy, cases with no adverse effects have been documented.

In a controlled trial on patients treated with cingulotomy for intractable pain, Cohen et al. reported postoperative executive and attention impairments. On one-year follow-up, the aforementioned deficits mostly resolved, with residual impairments of intention, attention, and spontaneous response production.

Additional reports have cited cognitive side effects with defects in visual-spatial processing and simple motor skills.

Conclusion

Bilateral anterior cingulotomy is generally used when more conservative medical, surgical, and pharmacological methods have not succeeded. First utilized for patients with psychiatric problems such as anxiety, obsessive-compulsive disorders, and depression, anterior cingulotomy has for several decades been a treatment option for chronic pain.

Given its ability to provide relief to any body region, anterior cingulotomy proves to be a versatile therapeutic strategy. Patients often recover relatively quickly with self-limited complications.

Overall, stereotactic bilateral anterior cingulotomy has been demonstrated to be efficacious for the treatment of refractory and intractable pain.

Disclosure

The authors have no personal financial or institutional interest in any of the drugs, material, or devices described in this article.

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