Staged cingulotomy and capsulotomy for trigeminal neuropathic pain: A case report

Introduction

Central lesioning (i.e., the neuromodulation of functional targets in the central nervous system) has been proven to be effective for chronic pain treatment, especially for patients with cancer (1). However, several reports have indicated that these techniques may also offer benefits for non-cancer patients (2,3). More specifically, through modulating anxiety caused by chronic pain, cingulotomy was found to have an additional effect when the pain had a suffering component (4). A recent review that investigated anterior cingulotomy procedures conducted for cancer pain found meaningful pain relief varying between 32 and 83%, with a good safety profile (5). The review concluded that cingulotomy is a valid option for patients with cancer pain with diffuse pain syndromes, head and neck malignancies, and marked emotional distress. The identified possible adverse events included a decline in focus, plus apathy and hypoactivity; however, these effects were frequently limited to the early postoperative period and serious side effects were generally evaluated as rare (5). While cingulotomy (creating a lesion at the anterior cingulate cortex) and capsulotomy (creating a lesion at the anterior limb of the internal capsule) are well-described techniques (6-8), available reports on their application for refractory trigeminal neuralgia are scarce (3,9). In the present case, these techniques were chosen due to their previously identified associations with pain syndromes (10-12). The present study reports the case of a patient who achieved good pain control after stereotactic radiofrequency (RF) cingulotomy and GammaKnife capsulotomy (GKC). To the best of our knowledge, this is the first report regarding the combined use of cingulotomy and capsulotomy for trigeminal neuropathic pain.

Case report

A 39-year-old female patient presented to the outpatient clinic of Department of Neurosurgery, Ankara University School of Medicine (Ankara, Türkiye) in October 2022 with severe left-sided facial non-paroxysmal continuous pain that had started 12 months previously. The pain was categorized as neuropathic and/or of atypical origin. Medications, such as analgesics, gabapentin, carbamazepine and antidepressants, at various doses were ineffective to relieve the pain. The patient had not undergone any prior invasive interventions. At the initial presentation, the pain was rated as 9/10 according to the Numeric Rating Scale (NRS) (13) and was located in the distribution of the left trigeminal V2 and V3 areas, involving the ear and retro-auricular region. Left V3 hypoalgesia was also observed upon examination. Cranial magnetic resonance imaging (MRI) scans revealed no abnormality. After psychiatric assessment, only a coexisting anxiety disorder was diagnosed. There were no signs of pain somatisation or additional psychiatric disorder. No contraindication was identified against a psychosurgical procedure (specifically, cingulotomy) for pain relief. Pain levels were monitored using the NRS, treatment response was evaluated using the Barrow Neurological Institute (BNI) pain intensity score (14) and neurological assessment was conducted using standard detailed neurological examination protocols, which included evaluations of cranial nerve function, motor and sensory systems, reflexes and coordination. Written informed consent was obtained from the patient. A bilateral stereotactic RF cingulotomy was performed under local anaesthesia, as described in the literature (15). The cingulate bundle was targeted using computed tomography-MRI fusion images. With a 1.6-mm thick electrode (uninsulated tip, 7 mm), three lesions (-2 mm, target and +2 mm) were produced at 85˚C for 90 sec. A detailed description of the target was previously defined in cadavers and published (16). At 1-month post-procedure, the pain NRS was reduced to 1/10. The patient reported high patient satisfaction and did not show any signs of neurological or cognitive deficits. The pain-free condition lasted for the subsequent 3 months. Afterwards, the patient described pain recurrence scoring 4-5/10 according to the NRS; analgesic and anti-depressant treatments were administered under the control of the Department of Psychiatry. Medical treatment was ineffective, and at the end of the 12th month post-treatment, the patient had complete pain recurrence scoring 9/10 according to the NRS. Since the initial result after cingulotomy was satisfactory until the relapse, a radio-surgical bilateral capsulotomy was recommended.

The patient was referred to the GammaKnife Unit, Department of Neurosurgery, Gazi University Faculty of Medicine (Ankara, Türkiye) for GKC, 1.5 years after the initial cingulotomy. The bilateral anterior limbs of the internal capsules were targeted with 150 Gy at the 100% prescription isodose in two separate matrices as described in the previous literature (8). Two shots ~5 mm apart from each other were used for each target. Following this, the targets were identified by planning MRI as 20 mm lateral to the midline, 5 mm behind the tip of the frontal horns of the lateral ventricles at the level of the inter-commissural plane. The targets were then manually refined to cover the anterior third of the anterior limb of the internal capsule within the 50% isodose line, between the lentiform nucleus and the head of the caudate nucleus, above the nucleus accumbens. A GammaKnife® Icon (Elekta Instrument AB) device was used for treatment. Total beam-on-time lasted 184 min. Fig. 1, constructed using the Slicer 5.0.3(17) software and the SlicerRT (18) add-on, shows the radiosurgery targeting and dose distribution.

Figure 1 GammaKnife capsulotomy planning image 1.5 years after the radiofrequency cingulotomy. Images are reconstructed using Slicer 5.0.3(17) software to present old cingulotomy lesions and new capsulotomy targets in the same coronal slice. Dose plans were reconstructed using the SlicerRT (18) add-on. The first isodose line covers 20 Gy, the inner ring marks 90 Gy and the white core is ≥105 Gy. (A) T2-weighted image. (B) T1-weighted image.

During the follow-up, the patient reported gradual improvement of neuropathic pain. At 12 months post-capsulotomy and 24 months post-cingulotomy, the patient had marked pain reduction to a score of 2-3/10. Neurological and psychiatric examination showed neither neurological complication nor cognitive decline. A control MRI scan confirmed the presence of the capsulotomy lesions in addition to the previous cingulotomy lesions (Fig. 2). In the end, the patient was reduced to BNI grade III at the latest follow-up from BNI grade V at the initial presentation.

Figure 2 Control magnetic resonance imaging scans obtained at the latest follow-up. T2-weighted axial images showing (A) cingulotomy lesions (arrows) at 2 years post-radiofrequency and (B) capsulotomy lesions (arrowheads) at 1-year post-radiosurgery.

Discussion

Classical interventional treatment options for trigeminal neuralgia in cases when medical therapy proves ineffective involve the following three techniques: i) Microvascular decompression; ii) percutaneous rhizotomy; or iii) stereotactic radiosurgery to the affected trigeminal nerve (19). Trigeminal tractotomy (20) or deep brain stimulation (DBS) of various targets (21) has been used in more complex cases. These modalities are mainly considered and investigated for nociceptive pain that is frequently associated with the classical type of trigeminal neuralgia. Neuropathic pain is a more difficult concept to understand, particularly in the complex setting of trigeminal neuralgia. The method described in the present report can provide additional benefits in the presence of coexisting psychiatric conditions, thus giving the treatment an edge over traditional modalities used for trigeminal neuralgia. Although there are no specific reports, the present case suggest that the modulation of central pain may be beneficial for patients with pain refractory to well-established treatments such as microvascular decompression or percutaneous rhizotomy. Notably, disadvantages include complication risks associated with deep intra-axial interventions, along with various possible unforeseen side effects due to the novelty of the approach. Yet, while these methods may be novel for trigeminal neuralgia, they are widely used for other pain conditions and psychiatric disorders, and have been reported to have minimal known side effects (6,7).

After numerous ablative interventions, if adequate pain control is not achieved, classical neuralgic pain may transform, thus developing a neuropathic component associated with deafferentation (22), which is the pain perceived due to the loss of sensory nerve fibres. Alternatively, as observed in the current case, the initial presentation can be atypical neuropathic pain. Intractable pain causes a massive reduction in quality of life for these patients. In laboratory studies, trigeminal neuropathy was demonstrated to cause disruptions in the anterior cingulate cortex (23). Taking into account the recent evidence on the use of cingulotomy for non-cancer pain, in the current case, the techniques usually reserved for chronic cancer pain were considered. However, at present, reported instances of using cingulotomy for facial pain are extremely rare. For instance, one study that reported on seven non-cancer pain patients, only included one trigeminal neuralgia patient who had successful pain reduction (9). There were also two older case series involving one atypical facial pain case each (in addition to a few post-herpetic cases); however, the outcomes of those patients were not reported individually. Overall, to the best of our knowledge, there are no dedicated studies on using cingulotomy for facial pain. In a previous study, DBS of the anterior cingular cortex showed promising long-term results for chronic neuropathic pain (24). Although it was considered to exhibit potential, there have been no reports of anterior cingular cortex DBS for chronic trigeminal neuropathy in the literature (25).

Changes in pain perception after capsulotomy (10) and an application of capsulotomy for somatic symptom disorder (11) have been reported in the literature. DBS of the anterior limb of the internal capsule has also been shown to provide relief for post-stroke pain (26). However, none of these studies focused on trigeminal pain.

Regarding combining central targets, only one report combined capsulotomy and cingulotomy in the treatment of a single patient (12). The main indication for that patient was schizoaffective disorder with heavy suicidal thoughts; however, it was also reported that the patient had an altered sensation of temperature and a change in the perception of temperature-associated pain after the treatments (12). In addition, there was one case series that combined bilateral cingulotomy with contralateral mesencephalotomy. Not all patients underwent the combined approach and, in the whole series, only one patient with facial nociceptive pain underwent combined lesioning. While individual results for that patient were not reported, it was noted that all patients with nociceptive pain had excellent pain relief (27).

Unlike microvascular decompression (MVD) and percutaneous rhizotomy, which primarily target peripheral pain transmission through direct neural interventions, cingulotomy and capsulotomy modulate the central processing of pain (8). This approach may be particularly beneficial for patients with coexisting psychiatric conditions, as both procedures have established effects on anxiety and mood regulation (6,7). While traditional methods such as MVD and rhizotomy may provide immediate pain relief in classical trigeminal neuralgia, they are less effective in cases with atypical or neuropathic pain components. Additionally, repeated rhizotomy procedures carry a risk of anaesthesia dolorosa, a severe and often intractable complication (28), whereas the central lesioning approach described in the present report does not share this specific risk. However, the major disadvantages of central lesioning include the potential for cognitive or emotional side effects, which, although generally minimal, require further study in the context of trigeminal neuropathic pain.

In the present case, while the initial cingulotomy provided good pain relief, the achieved effect diminished over time. At this point, a repeat cingulotomy would usually be considered. Repeat cingulotomies were previously reported to be beneficial, especially when the first treatment provided short-lasting pain control (3). However, considering the patient's additional conditions and the previously documented capsulotomy success for various psychiatric conditions (29), a decision was made to proceed with a capsulotomy in the present case. At the end of the first year after the capsulotomy treatment, the patient had >60% pain reduction and still did not have a relapse. The single-case nature of the present report prevents generalizing this outcome, although the proposed approach may be considered for select patients with similar conditions. Current evidence does not support replacing classical treatment methods due to the lack of a control group and randomization. However, future trials may investigate the efficacy of this method and compare the outcomes with those afforded by classical treatment modalities. Until then, the approach described in the present report may only be considered for select patients with psychiatric comorbidities. We duly acknowledge the experimental nature of the proposed method.

In conclusion, the current study presents the unique case of a trigeminal neuralgia patient with atypical neuropathic pain who underwent combined RF cingulotomy and GKC. The patient experienced >60% pain reduction after capsulotomy, which was performed 1 year after cingulotomy. The results suggest that cingulotomy and capsulotomy are beneficial for refractory trigeminal neuropathic pain and could be offered, independently or in combination, to patients requiring advanced tier treatments. Cingulotomy may be recommended as an initial neurosurgical treatment for select cases with intractable severe non-malignant pain; if needed, capsulotomy may be recommended as a sequential treatment occurring at least 1 year after the initial treatment. Although this approach may only be suggested for select cases, future studies may investigate various potential advantages and pitfalls associated with this approach.

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

Authors' contributions

ASa, HE and HDO conceptualised and designed the paper. ASa and MEY confirm the authenticity of all the raw data. ASa, HE and HDO advised on patient treatment. Cingulotomy was performed by ASa and EG, Capsulotomy was performed by MEY, AK and ASo. Medical images were obtained by EG and ASa, and edited by ASo. The first draft of the manuscript was written by ASo and critically revised by MEY, HE, AK, EG, HDO and ASa. All authors read and approved the final version of the manuscript.

Ethics approval and consent to participate

Ethical approval was not required for this case report in accordance with local and national guidelines. This study fully complies with the 1964 Helsinki Declaration and its later amendments. The patient consented to the presented medical treatment and provided written informed consent.

Patient consent for publication

The patient provided written informed consent for the publication of this case report and accompanying images.

Competing interests

The authors declare that they have no competing interests.

References