Efficacy and Quality of Life Outcomes in Patients With Atypical Trigeminal Neuralgia Treated With Gamma-Knife Radiosurgery

 

Anil Dhople, M.D. University of Maryland School of Medicine, Baltimore, MD    IJROBP 2007;69:397

Purpose: To assess efficacy and quality of life (QOL) outcomes associated with gamma-knife radiosurgery (GK-RS) in treating atypical trigeminal neuralgia (ATN) compared with classic trigeminal neuralgia (CTN).

Methods and Materials: Between September 1996 and September 2004, 35 cases of ATN were treated with GK-RS. Patients were categorized into two groups: Group I comprised patients presenting with ATN (57%); Group II consisted of patients presenting with CTN then progressing to ATN (43%). Median prescription dose 75 Gy (range, 70–80 Gy) was delivered to trigeminal nerve root entry zone. Treatment efficacy and QOL improvements were assessed with a standardized questionnaire.

Results: With median follow-up of 29 months (range, 3–74 months), 72% reported excellent/good outcomes, with mean time to relief of 5.8 weeks (range, 0–24 weeks) and mean duration of relief of 62 weeks (range, 1–163 weeks). This rate of pain relief is similar to rate achieved in our previously reported experience treating CTN with GK-RS (p = 0.36). There was a trend toward longer time to relief (p = 0.059), and shorter duration of relief (p = 0.067) in patients with ATN. There was no difference in rate of, time to, or duration of pain relief between Groups I and II. Of the patients with ATN, 88% discontinued or decreased the use of pain medications. Among the patients with sustained pain relief, QOL improved an average of 85%.

Conclusion: This is the largest reported GK-RS experience for the treatment of ATN. Patients with ATN can achieve rates of pain relief similar to those in patients with CTN. Further follow-up is necessary to assess adequately the durability of response.

Introduction

The symptoms compromising the syndrome of trigeminal neuralgia (TN) may have first been described by Aretaeus of Cappodocia in the second century. Since that time, TN has gone through a variety of definitions and classifications. More recently, the International Headache Society has defined TN pain as the following: (1) paroxysmal attacks, lasting from 1 s to 2 min, affecting one or more divisions of the trigeminal nerve; (2) pain that is intense, sharp, superficial, or stabbing, precipitated from trigger areas or factors; (3) attacks stereotyped in the individual patient; (4) no clinically evident neurologic deficit; and (5) pain not attributed to another disorder (3).

This classic form of TN (CTN) can be debilitating, often interfering with a patient’s activities of daily living and thus negatively affecting quality of life (QOL). There is a wide variety of treatment modalities for CTN. Pharmacologic management is generally accepted as the first line of therapy in patients diagnosed with CTN. Although a variety of medications or combination of medications may be effective, they are often associated with undesirable side effects. More invasive procedures, such as percutaneous rhizotomies, may offer immediate pain relief in severe cases, but duration of response can be lacking. Microvascular decompression (MVD) has been associated with initial response rates of 75–95% , but this is an invasive procedure requiring open craniotomy and hospitalization. Radiosurgical treatment of CTN was first performed by Lars Leksell in 1951 . Since the multi-institutional experience demonstrating its effectiveness, stereotactic radiosurgery has since become a mainstay in the treatment options offered to patients with CTN. Given its minimal invasiveness, radiosurgery has become an ideal treatment option for patients, who have become refractory to medical management, cannot tolerate a surgical procedure, or who have failed previous invasive procedures. Initial response rates of 50% to 90% have been reported with radiosurgery with low complication rates for patients with CTN

Atypical TN (ATN) has been described as early as 1950. This form of TN, like the classic form, is usually characterized by pain that is confined to the trigeminal domains. However, it is often described as continuous pain, occurring during all hours of the day, without definite triggers. Rather than a lancinating or electric-like pain, it is most commonly described as burning pain. The phenomenon of ATN is far less common than CTN, and has been reported to be a poor prognostic factor in patients treated with MVD . Various studies have also indicated the presence of ATN features to be associated with poor response to radiosurgery. However, small numbers of patients with ATN were included in these studies.

At the University of Maryland, the Gamma-Knife Radiosurgery (GK-RS) unit has been used since 1996 to treat a variety of facial pain syndromes. We have previously reported on our experience treating CTN and have demonstrated an initial rate of pain relief of 78%, which is consistent with other institutions’ rates of initial pain relief. The goal of this retrospective study was to assess the efficacy and quality of life (QOL) outcomes in patients with ATN who undergo GK-RS.

Discussion

The GK-RS technique has been used for many years to treat a wide variety of facial pain syndromes, including those in patients with ATN. Because of the burning and continuous nature of the symptoms associated with ATN, it can be a tremendously stressful condition to live with. Many retrospective studies investigating the efficacy of GK-RS in treating TN have included patients who have had the atypical variety. However, the numbers of patients with ATN included in these retrospective studies have been small.

Pain outcomes

This is the largest reported experience using GK-RS to treat ATN. Excellent and good responses (BNI I–III) were achieved in 72% of patients. This result was not statistically different from our previously reported experience using GK-RS to treat CTN. Numerous institutions have reported their experience treating trigeminal neuralgia with GK-RS. Pollack reported excellent and good outcomes in 59% and 16% of their patients treated for TN. However, only 8 patients had atypical features. Maesawa reported excellent or good results in 63% of patients treated for TN, but only 16 patients had atypical features. The presence of atypical features was the most important predictor for poor response to GK-RS. However, these patients may have had refractory pain secondary to multiple previous invasive interventions. Rogers reported an initial dramatic response rate (BNI I–II) of 49% in patients with CTN compared with only 9% in the 11 patients with ATN. Tawk  described excellent or good pain relief in 70% of patients with CTN within 3 months of undergoing GK-RS; however, patients with ATN were not included in this analysis. Finally, in the classic multi-institutional experience treating patients with CTN with GK-RS, Kondziolka  reported excellent or good outcomes in 56% and 32% respectively. However, the presence of atypical features of TN rendered the patients ineligible for this study.

The mean time to pain relief in patients treated with GK-RS for ATN was 5.8 weeks. Although this was not statistically different from the mean time to pain relief of 3 weeks in patients treated with GK-RS for CTN, there was a trend toward significance (p = 0.058). In our experience, 91% of patients who responded to GK-RS achieved pain relief within 6 months of their procedure. If a patient has not achieved pain relief within the first 6 months after GK-RS, they are unlikely to respond at all.

Historically, ATN has been regarded as a relatively “radio-resistant” facial pain syndrome. For this reason, many patients are treated with more invasive procedures such as MVD. Tyler-Kabara  reported on one of the largest experiences using MVD to treat both CTN and ATN. Excellent or good postoperative pain relief was achieved in 96% of patients with CTN, compared with only 87% in patients with ATN. However, in patients followed for more than 5 years, excellent long-term pain relief was achieved in 73% of patients with CTN, compared with only 35% in patients with ATN. In another series reported by Li  98% of patients with CTN experienced complete pain relief within 6 months of undergoing MVD, compared with only 29% in patients with ATN. In our series, 16% of the patients had previously undergone MVD before receiving GK-RS. Despite a population of patients with ATN that is likely more refractory to intervention, we still noted an overall response rate of 72%. We did note, however, that a history of prior surgical intervention decreased the chances of durable pain relief after undergoing GK-RS. Tyler-Kabara  and associates describe a continuum of trigeminal neuralgia symptoms ranging from classic symptoms to atypical symptoms. They propose classifying patients with typical and atypical symptoms as transitional TN. They further suggest that patients with transitional TN may still respond to MVD, although their chance of initial and durable response may be less when compared with patients with CTN. This highlights the difficulty in classifying patients with ATN, and makes comparisons between institutional experiences difficult. We have used a rather strict definition of ATN, which includes the following: (1) pain occurring in trigeminal nerve distribution; (2) continuous pain without pain-free periods; (3) no definite triggers; and (4) burning or aching in nature, rather than the typical lancinating or electrical pain more commonly described with CTN. Despite using strict criteria when classifying our patients into the classic or atypical groups, we did not find a statistical difference in the overall response rate between patients with ATN vs. CTN.

Durability of response and pain recurrence

Pain recurrence is feared by most patients who have experienced TN. Maesawa reported a 13.6% rate of pain recurrence after some form of pain relief. Tawk  reported 70% of treated patients had excellent or good pain relief within 3 months of their GK-RS procedure. However, this rate fell to only 21% by the 2-year mark, indicating a nearly 50% rate of pain recurrence in original responders. Rogers  reported a 21% recurrence rate after GK-RS for CTN, with a median time to recurrence of 6.7 months. The actuarial 2.5-year pain recurrence rate for their group of patients was 36%. Pollack reported a 22% recurrence rate with a median time to recurrence of 8 months in patients who initially achieved excellent or good outcomes after GK-RS. Factors associated with pain recurrence after GK-RS include a history of prior surgery  less than excellent initial pain response , lack of trigeminal nerve dysfunction , and presence of atypical features

It is important to recognize the effectiveness of MVD when discussing durability of response. There are a number of publications assessing the efficacy of MVD in the treatment of CTN with substantially longer reported follow-up. Broggi et al. reported a 75% rate of complete pain relief with 5 years of follow up after MVD . Tronnier et al. retrospectively reviewed the pain outcomes of 225 patients with CTN and reported a 65% chance of being pain-free after MVD at 10 years. Barker  described the outcomes of 1,155 patients who underwent MVD for CTN and had greater than 1 year of follow-up (median follow-up, 6.2 years). Ten years after surgery, 68% still had excellent or partial relief from their CTN. In the previously mentioned studies, patients with ATN were not included in the analyses. Tyler-Kabara reported on 974 patients with CTN treated with MVD who had more than 5 years of follow-up. Nearly 81% achieved excellent or partial long-term pain relief; however, when compared with 220 patients with ATN with similar length of follow-up, only 51% had long-term excellent or partial pain relief. So, despite excellent outcomes in patients with CTN, MVD appears to be less effective in achieving and maintaining pain relief in patients with ATN.

Our results indicate that the recurrence rates during this follow-up period for patients with ATN (39%) and those with CTN (38%) are similar. Predictors for recurrence included less than BNI class I response and history of prior surgery. The time to recurrence for patients with ATN trended toward being significantly shorter when compared with that in patients with CTN who experienced recurrence. Despite most recurrences in patients with ATN occurring within 6 months of the GK-RS procedure, 33% were still able to have at least 1 year of pain relief before experiencing recurrence. We, therefore, believe the shorter time to recurrence should not be used as a contraindication when recommending GK-RS as a treatment option for patients with ATN.

Complications

There were no serious complications reported in this series of patients with ATN. However, the incidence of bothersome facial numbness (19%) is higher than what has typically been reported in the CTN literature. For example, in the multi-institutional experience reported by Kondziolka , increased facial paresthesia was reported in 6% of patients with CTN undergoing GK-RS. We previously reported a 3% incidence of bothersome facial numbness among patients who received GK-RS for CTN. This increased incidence of bothersome facial numbness in patients undergoing GK-RS for ATN may be attributed to higher rates of facial numbness before receiving treatment. In one report, 45% of patients with ATN had pre-existing sensory loss compared with 39% (p < 0.001) in patients with CTN. Although we did document pre-existing facial numbness at time of consultation for GK-RS, we unfortunately did not categorize the severity. Thus, it is difficult for us to make comparisons between pre- and post-treatment rates of bothersome facial numbness.

In this series, 56% of the patients with ATN found GK-RS to be effective in treating their pain syndrome, with an average 50% improvement in their QOL as a direct result of GK-RS. These results are similar to our series of patients with CTN where 68% believed GK-RS to be successful in treating their pain with a mean 63% improvement in QOL. As would be expected, a greater percentage of patients who had durable pain relief believed GK-RS to be successful in treating their pain syndromes, and similarly reported higher QOL improvements.