Key points

Introduction

Since the initial report by Dr Leksell in 1971 and early reports from the 1990s, the role of Gamma Knife surgery (GKS) in patients with intractable trigeminal neuralgia (TN) has been growing exponentially. GKS is a minimally invasive surgical approach for TN, within the armamentarium of a neurosurgeon, along with more invasive procedures including percutaneous ablative procedures (thermal rhizotomy, glycerol rhizotomy, or balloon microcompression) and craniotomy for microvascular decompression (MVD).

To date, greater than 450 articles have been published looking at the safety and effectiveness of GKS in the treatment of TN or recurrent TN. This report summarizes the literature on the effectiveness of GKS for pain relief, the latency until pain relief, the durability of pain relief, and predictors of its success.

Introduction

Since the initial report by Dr Leksell in 1971 and early reports from the 1990s, the role of Gamma Knife surgery (GKS) in patients with intractable trigeminal neuralgia (TN) has been growing exponentially. GKS is a minimally invasive surgical approach for TN, within the armamentarium of a neurosurgeon, along with more invasive procedures including percutaneous ablative procedures (thermal rhizotomy, glycerol rhizotomy, or balloon microcompression) and craniotomy for microvascular decompression (MVD).

To date, greater than 450 articles have been published looking at the safety and effectiveness of GKS in the treatment of TN or recurrent TN. This report summarizes the literature on the effectiveness of GKS for pain relief, the latency until pain relief, the durability of pain relief, and predictors of its success.

Effectiveness of gamma knife surgery for idiopathic trigeminal neuralgia

There are 4 key studies published within the last 5 years that report on the effectiveness of GKS in a large population of type I TN patients and with long-term outcomes ( Table 1 ). By 1 year’s time, 75% to 90% of patients will have obtained pain relief, defined as Barrow Neurological Institute (BNI) grades I to IIIB. Achieving BNI I may prove more challenging because of the reluctance of some patients to discontinue their medication for fear of the pain recurring. Fig. 1 depicts a treatment plan of a 54 year old woman with right-sided TN who underwent GKS to the right trigeminal nerve at a maximum dose of 80 Gy.

Treatment plan targeting the right trigeminal nerve.

Although there are no randomized control studies directly comparing GKS to other surgical procedures for TN, the pain relief rates in the studies listed in Table 1 are similar to those reported for MVD. A select few studies have directly compared GKS to either MVD or rhizotomy. Similar improvements in pain were reported between rhizotomy and GKS, however, with faster onset of pain relief and higher morbidities after rhizotomy. Collectively, MVD offers higher rates of longer-term, pain-free outcomes, compared with GKS, however, at a higher complication rate, including cerebrospinal fluid leak, cranial neuropathies, wound infection, deep vein thrombosis, and pulmonary embolism.

Latency until pain relief after gamma knife surgery

Multiple studies have confirmed a median latency period of 1 to 2 months before the onset of pain relief after GKS. In the largest study of 503 patients, Kondziolka and colleagues found that 89% of patients responded to treatment at a median of 1 month, and total pain relief was achieved at a median of 5 months. Predictors of faster pain relief included GKS as the initial surgical procedure, within 3 years of pain onset.

In patients with severe pain that is intractable to all medical therapies, a lengthy delay between treatment and pain relief may be intolerable, and thus, other surgical treatments that provide immediate pain relief may be desirable, such as glycerol rhizotomy, with which pain relief is felt to be immediate within days.

Durability of pain relief with gamma knife surgery and predictors of success

From Table 1 , by 5 years after GKS, 46% to 65% of type 1 TN patients remain with well-controlled pain (BNI I–IIIb). According to a multivariate analysis performed by the group at Wake Forest, predictors of the durability of GKS in TN patients include the presenting Burchiel pain type, the post-GKS BNI score, and the presence of post-GKS facial numbness. Post-GKS numbness has been identified as a major predictor of the success in multiple series. Another report found that patients who responded to GKS within the first 3 weeks predicted a longer duration of complete pain relief. Multiple studies have identified that type 2 TN patients are at greater risk of pain relapse after GKS. Nevertheless, patients with multiple sclerosis (or symptomatic TN based on Burchiel’s classification) may benefit from GKS with response rates reported between 57% and 97% and long-term pain relief outcomes potentially similar to patients with idiopathic TN.

One study suggested that neurovascular conflict resulted in improved outcomes after GKS. However, the underlying pathophysiology of TN and relationship to microvascular compression remain to be elucidated. TN appears to be a complex disorder with subtypes that may manifest at different ages, such that younger patients are less likely to have neurovascular conflict. Whether different subtypes of idiopathic TN may respond better to Stereotactic radiosurgery (SRS) is unknown at this time.

Side effects of gamma knife surgery for trigeminal neuralgia

The most common side effect reported is trigeminal nerve sensory disturbance, and this appears to be dose-dependent. Reported rates of persistent sensory dysfunction range from 10% to 42% (see Table 1 ). Matsuda and colleagues followed patients every 3 months after GKS and assessed trigeminal nerve dysfunction using the Barrow Neurological Institute Numbness scale (BNI-N). They reported trigeminal nerve dysfunction of 49% at 3 months, which reduced to 41.3% at a median time of 37 months; 25% were categorized as BNI-N Score II, 12.5% as BNI-N Score III, and 3.8% as BNI-N Score IV. This trend of decreasing incidence of sensory dysfunction over time fits with many prior reports. The vast majority of patients often do not find the post-GKS numbness bothersome or disabling. However, a trigeminal sensory deficit may rarely be associated with a reduced corneal reflex, and thus, patients may be at risk of a corneal injury.

The placement of the target isocenter may be associated with the development of sensory dysfunction. Rates of numbness were reported as low as 10% at 12 months after radiosurgery, when placing the target in the anterior cisternal portion of the nerve. However, in another study also targeting the anterior cisternal portion of the trigeminal nerve, their rates for sensory deficit was 34%. However, their radiation dose was higher. A radiation dose of 90 Gy to the trigeminal nerve and higher doses to the brainstem may be associated with increased incidence of bothersome sensory dysfunction and/or numbness.

In addition to target location and radiation dose, other factors that may predispose to post-GKS sensory neuropathy are the dose to the brainstem and the length of nerve included within the target zone. In a prospective randomized study comparing 1 or 2 isocenters in patients with TN who underwent GKS, longer nerve irradiation with 2 isocenters resulted in a higher complication rate with no significant difference in effectiveness.

As noted in one report using Cyberknife for TN, other complications may occur, although infrequently, including masticator weakness, diplopia, and decreased hearing. In this study, the investigators identified that higher radiation doses and treating longer segments of the nerve resulted in an increased rate of complications.

The role of repeat gamma knife surgery for trigeminal neuralgia

The effectiveness of repeat GKS has been investigated in numerous retrospective, single-institution, small sample studies (see Ref. for systematic review). Only 2 studies to date have looked at outcomes of repeat SRS in more than 100 patients ( Table 2 ). In a recent systematic analysis reviewing 20 published studies on repeat GKS in TN, the median time between first and second GKS was 17 months. Outcomes after second GKS were variable, with a median rate of pain cessation of 88% (60%–100%) after second GKS and a median hypesthesia rate of 33% (11%–80%). Park and colleagues reviewed outcomes of 119 patients and identified predictors of success for recurrent TN after having failed initial GKS. They found that development of sensory loss and recurrent pain in a reduced facial distribution compared with initial GKS predicted long-term pain control. These results were corroborated by another study looking at predictors of success for repeat SRS, which included facial numbness after the first GKS and a positive pain response.

Table 2

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