ORIGINAL CONTRIBUTION

Gamma Knife Radiosurgery

for Trigeminal Neuralgia
Results and Expectations
Douglas Kondziolka, MD, MSc, FRCSC; Bernardo Perez, MD; John C. Flickinger, MD;
Michael Habeck, PA-C; L. Dade Lunsford, MD

Background: Trigeminal neuralgia is a disabling pain

syndrome responsive to both medical and surgical therapies. Stereotactic radiosurgery using the gamma knife can
be used to inactivate a specified volume in the brain by
cross firing 201 photon beams. We evaluated pain relief
and treatment morbidity after trigeminal neuralgia radiosurgery.
Methods: All evaluable patients (n = 106) had medi-

cally or surgically refractory trigeminal neuralgia. A single

4-mm isocenter of radiation was focused on the proximal trigeminal nerve just anterior to the pons. For follow-up an independent physician who was unaware of
treatment parameters contacted all patients.
Results: After radiosurgery, 64 patients (60%) became

free of pain and required no medical therapy (excellent

result), 18 (17%) had a 50% to 90% reduction (good result) in pain severity or frequency (some still used medications), and 9 (9%) had slight improvement. At last fol-

low-up (median, 18 months; range, 6-48 months), 77%

of patients maintained significant relief (good plus excellent results). Only 6 (10%) of 64 patients who initially attained complete relief had some recurrent pain.
Radiosurgery dose (70-90 Gy), age, surgical history, or
facial sensory loss did not correlate with pain relief.
Poorer results were found in patients with multiple
sclerosis. Twelve patients developed new or increased
facial paresthesias after radiosurgery (10%). No patient
developed anesthesia dolorosa. There was no other procedural morbidity.
Conclusions: Gamma knife radiosurgery is a minimally invasive technique to treat trigeminal neuralgia. It
is associated with a low risk of facial paresthesias, an approximate 80% rate of significant pain relief, and a low
recurrence rate in patients who initially attain complete
relief. Longer-term evaluations are warranted.

Arch Neurol. 1998;55:1524-1529

From the Departments of

Neurological Surgery and
Radiation Oncology and
The Center for Image-Guided
Neurosurgery, University of
Pittsburgh Medical Center,
Pittsburgh, Pa.

EDICAL management
remains the mainstay
of treatment for trigeminal neuralgia. 1
Several effective surgical techniques exist and are used when
medical therapy is ineffective or associated with significant adverse effects.2-10 Despite high rates of initial success for virtually all surgical procedures, most
physicians and patients choose medical
therapy first because of potential surgical
morbidity, the risk for loss of facial sensation after surgery, or recurrent pain despite initial surgical success. The use of an
external energy source as a surgical tool
to manage trigeminal neuralgia has a long
history. Various techniques include radiofrequency, generated thermal energy
(percutaneous rhizotomy), mechanical energy (balloon compression), and physical energy (surgical nerve section). Microvascular decompression aimed at

removing the cause of trigeminal neuralgia or chemical manipulation of the nerve,

such as that performed in glycerol rhizotomy, are other techniques with proven
efficacy. Despite these options, significant problems continue to permeate the
management of this pain. Despite medical or surgical therapy, these problems
range from persistent or recurrent typical trigeminal neuralgia to the tendency
for pain to occur in elderly patients. Elderly patients are prone to have concurrent medical illnesses that warrant a minimally invasive approach. In addition, a
spectrum of pain disorders exists, with
some patients having typical neuralgic pain
and others reporting constant or atypical
facial pain.
Initially, we sought to reevaluate the
early anecdotal success of trigeminal neuralgia radiosurgery reported by Leksell.11
During the 1970s and 1980s, several
surgeons irradiated the trigeminal gan-

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SUBJECTS, MATERIALS,
AND METHODS
One hundred twenty-one consecutive patients underwent
gamma knife radiosurgery for typical trigeminal neuralgia.
The mean patient age was 67 years (age range, 32-92
years) and the mean duration of pain was 11 months. All
patients underwent comprehensive trials of medical
therapy that included carbamazepine. Many patients also
received phenytoin sodium, baclofen, and/or gabapentin,
alone or in combination with carbamazepine. Prior surgeries included microvascular decompression(n = 42),
glycerol rhizotomy (n = 57), or radiofrequency rhizotomy
(n = 19). No patient had anesthesia dolorosa. The right
side of the face was affected in 72 patients (59.5%) and
the left side in 49 (40.5%). Pain involved the V1, V2, or
V3 distributions, alone or in combination. The most common distribution was combined V2 and V3 pain. Fortysix patients described some degree of facial numbness
(Table).
Indications for radiosurgery included failure of pharmacologic treatment to provide significant pain relief, failure of prior surgery, or significant adverse effects from
medication. Failure of previous therapy was defined as
persistent disabling pain lasting a minimum of 1 month
since initiation of the prior therapy. Radiosurgery was
performed with informed consent and different surgical
alternatives were explained to the patients. All patients in
this series had idiopathic trigeminal neuralgia or trigeminal neuralgia secondary to multiple sclerosis. We excluded from this analysis patients with trigeminal neuralgia related to tumors. All patients underwent brain imaging
scans (computed tomographic or MRI) to exclude the presence of a mass lesion prior to radiosurgery. Vascular compression of the trigeminal nerve was not a contraindication to radiosurgery.
RADIOSURGERY TECHNIQUE
All patients underwent stereotactic radiosurgery using a
gamma knife (Leksell Gamma Knife, Elekta Instruments,
Atlanta, Ga). One gamma knife (model U) was used to operate on 79 patients and another gamma knife (model B)
in 42 patients. The dose profile of the 4-mm isocenter is
only slightly different between the 2 units, with the superiorinferior radiation volume being slightly larger in the U unit.
Radiosurgery was performed with patients receiving local
anesthesia and supplemented with mild oral or intravenous sedation.

glion12-14 using the gamma knife. In 1996 we reported a

multicenter study using gamma knife radiosurgery for
irradiation of the proximal trigeminal nerve near the
pons.15 At this location, the nerve could be seen with highresolution magnetic resonance imaging (MRI) scan and
was suitable for small-volume radiosurgery targeting. In
that 50-patient study with 18-month median follow-up,
29 (58%) were free of pain, 18 (36%) had significant improvement (50%-90% relief), and 3 (6%) had pain. The
main purpose of that study was to identify an appropri-

After application of the stereotactic frame (Leksell model

G stereotactic frame, Elekta Instruments), all patients underwent stereotactic MRI to identify the trigeminal nerve. Magnetic resonance imaging sequences were performed using short
repetition time sequences and contrast enhancement in multiple planes. Volume acquisition sequences using 512 3 256
matrices were divided into 1-mm image slices to provide
graphic depiction of the trigeminal nerve (Figure 1). The
nerve was identified as it followed its course from the pons
into the Meckel cave. In some patients who had undergone
prior surgery (microvascular decompression or percutaneous surgery), the nerve was difficult to identify (either because of nerve atrophy or regional perineural fibrosis) and
thus long repetition time MRI sequences were used to identify the nerve against the high-signal background of cerebrospinal fluid. Stereotactic coordinates were calculated for a
single 4-mm isocenter placed 2 to 4 mm anterior to the junction of the trigeminal nerve and pons (Figure 1). The isocenter was positioned so that the brainstem surface was usually irradiated at no more than the 30% isodose. Dose planning
was performed using a high-speed work station and computer image integration. Radiosurgery planning and dose selection were performed by the neurologic surgeon, radiation oncologist, and medical physicist. The range of maximum
radiosurgery dose was between 70 and 90 Gy; 70 Gy commonly was used for patients who had not undergone prior
surgery and 80 to 90 Gy was prescribed for patients with recurrent pain after prior surgery, although a strict protocol did
not exist. We acknowledged the potential for selection bias
for a higher dose in patients believed to have more refractory pain.
All patients were discharged within 24 hours after radiosurgery. Patients were studied according to the degree
of pain relief, latency interval to pain relief, onset of paresthesia, need for further surgical treatment, and complications. Patient evaluations were made by a physician who
did not participate in the procedure and who was blinded
to radiation dose. Since all patients had lancinating pain,
pain relief was determined by the outcome of this pain type
both in terms of its severity and frequency.
STATISTICAL ANALYSIS
Univariate comparisons of response rates were made using the Pearson x2 test or 2-tailed Fisher exact test, depending on the number of patients in the matrix. Multivariate analysis of response rates was performed with
stepwise logistic regression. The percentage of patients with
pain control was calculated as a product of the response
rates and freedom from relapse rate.16,17 Significance was
defined as P,.05.

ate radiation dose that might eliminate pain more rapidly and still maintain facial sensation. We found that a
maximum radiosurgery dose higher than 70 Gy (70-90
Gy) was associated with a greater chance of complete pain
relief than 60 or 65 Gy (P = .0003).15 In our study, we
report our longer-term experience in patients with typical trigeminal neuralgia who had gamma knife radiosurgery to a maximum dose of 70 to 90 Gy. We also evaluate factors associated with pain relief and rates of
morbidity.

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Patient Characteristics Before Trigeminal Neuralgia

Radiosurgery (N = 121)
Characteristics

Value

Mean age, y (range)

Mean duration of pain, mo
No. of prior surgeries
Microvascular decompression
Glycerol rhizotomy
Radiofrequency rhizotomy
Patients with no prior surgery, %
Patients with facial numbness, %
Trigeminal division(s) affected, %
V1
V2
V3
V1, 2
V2, 3
V1, 2, 3

67 (32-92)
11
42
57
19
22
38
3
22
19.5
14
36
5.5

RESULTS

PAIN RELIEF
Median follow-up after radiosurgery was 18 months
(range, 6-48 months). Relief from pain was coded by
the patients into 4 categories.12,13 These included no
response, slight improvement (10%-50% improved),
good response (50%-90% improved but still using
medications if used preoperatively), and excellent
response (100% free of pain and not taking medication). No response or slight improvement was referred
to as a treatment failure. Criteria for improvement
included a reduction in both the frequency and severity
of trigeminal neuralgia (lancinating pain) attacks.
Patients with good results continued to take medication
(although usually reduced) if they had done so before
radiosurgery. These patients described either a significant decrease in the frequency of attacks and/or
decreased intensity of individual attacks. Median time
to response was 4 weeks (range, 1 day to 3 months).
One hundred six (87%) of 121 patients were examined
and complete follow-up data about pain relief and morbidity are summarized as follows:
Pain Result*
Excellent (no pain)
Good (50%-90% decrease)
Poor (,50% relief)

No. (%) of Patients

64 (60)
18 (17)
24 (23)

*Patients description of change in the frequency or severity of lancinating

pain.

Initial improvement in trigeminal neuralgia was

noted in 91 patients (86%). At last follow-up, significant pain relief was noted by 77% of patients (good
plus excellent results). Relapse in pain was noted in
only 6 (10%) of 64 patients who attained complete
relief from 2 to 10 months after onset of complete
relief.

Figure 1. Axial magnetic resonance imaging scan from a 74-year-old woman

after a prior microvascular decompression with recurrent trigeminal
neuralgia. Top, Note the tissue mass (arrow) just lateral to the trigeminal
nerve. Gamma knife radiosurgery was performed with one 4-mm isocenter
targeted to the proximal trigeminal nerve. Bottom, Serial 1-mm axial images
are shown. The white circle represents the 50% isodose line. After a
maximum dose of 80 Gy, she had complete relief of pain.

months and median follow-up after radiosurgery, 19

months. Five patients had multiple sclerosis.
Sixty patients received a maximum dose of 80 Gy.
The median duration of prior pain was 10 months, and
median follow-up after radiosurgery, 16 months. Five of
these patients had multiple sclerosis.
Five patients received a maximum dose of 85 Gy.
Two patients received a maximum dose of 90 Gy. One
of these patients had multiple sclerosis and the other multiple prior surgeries. There was no significant difference
in pain relief when we compared 70 Gy (10.80 Gy)
(P = .57) for complete pain relief and P = .37 for good plus
excellent results).
OTHER CRITERIA

PAIN RESPONSE AND RADIOSURGERY DOSE

A maximum dose of 70 Gy was delivered to 54 patients.
The median duration of trigeminal neuralgia was 12

We compared specific factors with degree of pain relief.

For onset of complete pain relief, age proved insignificant (P = .75) as did sex (P = .22) or history of prior sur-

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gery (P = .34). These factors also were insignificant for

the onset of any improvement in pain. A history of
facial numbness before radiosurgery did not correlate
with pain relief (P = .32). We also compared degree of
pain relief with the gamma knife model used. No difference was identified (P = .46). The model B unit had a
greater radiation volume in the left-right dimension and
the model U unit, in the superior-inferior dimension.
We also coded the surgeons ability to identify clearly
the nerve on high-resolution MRI scans. Poorer trigeminal nerve resolution was found in some patients
(n = 11) with multiple prior surgeries. However, better
nerve identification did not correlate with pain relief
(P = .62). None of these factors was significant in multivariate analysis.
FACIAL PARESTHESIAS
Twelve patients developed new or increased trigeminal
paresthesias or sensory loss (numbness) after radiosurgery (10%). Because many patients lived far from Pittsburgh, Pa, we were not able to perform a detailed sensory examination and code this finding. Rather, patients
were surveyed for their own description of numbness.
The factors of age, multiple sclerosis, sex, radiosurgery
dose, gamma knife model, or nerve identification did not
correlate with the onset of sensory findings (P..05). There
was a trend for a lower rate of sensory findings in patients with no prior surgery (P = .08). No patient developed anesthesia dolorosa (constant deafferentation pain)
after radiosurgery.
OTHER MORBIDITY
All patients were discharged from the hospital within
24 hours. A few patients had an increase in trigeminal
neuralgia pain within the first few hours after radiosurgery that may have been related to an acute irradiation effect. No patient developed nausea or headache
after stereotactic radiosurgery. No patient developed
new neurologic deficits or other systemic complications.
COMMENT

Stereotactic radiosurgery was conceived for the management of functional brain disorders. Leksell and Larsson
developed a radiosurgical tool, the gamma knife, as a
method for cerebral lesion generation without opening the
skin and skull. Initial functional applications included lesion generation for Parkinson disease (ventrolateral thalamotomy), pain (medial thalamotomy), affective disorders (anterior capsulotomy and cingulotomy), trigeminal
neuralgia, and later, epilepsy.12,13,18-20 As a lesion generator, the gamma knife has proved to be a reliable tool. Singlesession doses from 50 to 200 Gy can cause tissue necrosis
within 6 months, depending on target volume.21,22 Smaller
volumes require more radiation. There exists a therapeutic range in which nerve or brain parenchyma can be affected without requiring total parenchymal injury. This
range differs with brain location, target volume, and desired response time.

Radiosurgery is the least invasive surgical procedure for trigeminal neuralgia.15,23 In the present series,
and in both our multi-institution study and the report
by Young et al,23 no systemic morbidity was found. No
patient sustained any form of neurologic morbidity
other than a low risk for facial numbness. In the multiinstitution study, 3 (6%) of 50 patients developed
increased facial paresthesia after radiosurgery. Young et
al23 noted that only 1 of 60 patients had increased facial
sensory loss. This occurred in a patient with a trigeminal schwannoma.23 In our study we found a 10% rate of
partial facial numbness. We initially believed this
slightly higher rate was because of some higher radiosurgery doses (80-90 Gy), and selection of patients who
already had some numbness. However, these factors did
not prove to be significant. All patients were contacted
for an evaluation of pain relief and adverse effects every
6 to 12 months. Although use of a randomized treatment schema that incorporates preoperative and postoperative pain rating scales would have been a more
powerful tool to evaluate the response to radiosurgery,1
we used an independent physician blinded to the radiation parameters for data collection from patients. All
data were from the patients own descriptions of their
clinical status. The absence of infection, cerebrospinal
fluid leakage, anesthesia complications, hearing loss,
facial hematoma, facial weakness, or brainstem injury
has established radiosurgery as an attractive surgical
alternative for many patients.
Despite these advantages, the use and evaluation of
radiosurgery has proceeded slowly. Leksell first used radiosurgery techniques for trigeminal nerve irradiation in
1953.11,24 Results from these 2 patients (both were free
of pain after delays of 1-5 months) were not published
until 1971. Leksell concluded that from these observations no definite conclusion should be drawn concerning the optimal dose of radiation or the exact mechanism in site of action in the route or ganglion, or even
the general applicability of the method.11 In 1983, Leksell12 noted that 63 patients had undergone gamma knife
radiosurgery for trigeminal neuralgia. He did not describe the surgical method or results. Lindquist et al13
(n = 46) and Rand et al14 (n = 12) reported on the use of
gasserian ganglion radiosurgery but inconsistent results
were obtained. These authors concluded that the ganglion was probably not appropriate as the primary radiosurgery target.
DEVELOPMENT OF THE TECHNIQUE
During the last 5 years, we and others have worked to
determine the kind of patient who would benefit from
trigeminal neuralgia radiosurgery, determine the appropriate radiation dose, and clarify expectations. It was not
known how much radiation was necessary to relieve pain
quickly, maintain that relief over the long-term, and do
so with no systemic morbidity and minimal chance for
facial sensory loss. To answer this question, we formed
a multicenter study group and compared data from patients who had undergone radiosurgery at doses from 60
to 90 Gy. All groups selected the proximal nerve and root
entry zone as the radiation target that could be identi-

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tastases, using the same 4-m gamma knife collimator.22

From these findings, we examined a large series of patients using standard techniques and a narrow radiosurgery dose range (70-90 Gy).
Current studies at our center include a randomized trial that compares 1 with 2 radiosurgery isocenters (with 2 isocenters, a greater length of nerve is irradiated) to determine the effect of nerve length on pain
relief. We have also begun a study of the histological and
ultrastructural effects of trigeminal nerve radiosurgery
in a large animal model.
MECHANISMS OF PAIN RELIEF
AFTER RADIOSURGERY

Figure 2. Axial magnetic resonance imaging scan showing the radiosurgery

plan to manage left trigeminal neuralgia in a man whose neuralgia did not
respond to prior glycerol and radiofrequency rhizotomy and was intolerant of
medication. Top, A maximum dose of 80 Gy was administered. The white
circle represents the 50% isodense line. Bottom, Nine months after
radiosurgery, a magnetic resonance imaging scan shows contrast
enhancement within the trigeminal nerve target volume (arrow).

fied on MRI scans and targeted with the gamma knife.

Because the nerve was myelinated by oligodendrocytes
and perhaps was more sensitive to irradiation than myelin from Schwann cells, we hypothesized that a stronger radiobiological effect would occur at this portion of
the nerve.15,25,26 We also believed that the compact union
of fibers from different nerve divisions would facilitate
irradiation of a smaller volume target. We attributed the
observation of good or excellent results to highresolution identification of the trigeminal nerve near the
pons and accurate radiosurgical targeting.27 In that study,
a maximum dose of at least 70 Gy was identified for a
higher rate of pain relief. Radiosurgical targeting was found
to be accurate as previously identified in rat and primate brain models and in the clinical use of radiosurgery for the management of other disorders, such as
acoustic tumors, pituitary microadenomas, and brain me-

It is unclear why trigeminal nerve irradiation causes

relief of trigeminal neuralgia pain. We speculate that
nerve irradiation leads to functional electrophysiologic
block of ephaptic transmission since most patients
maintain normal trigeminal function.28 Although we do
not perform follow-up imaging routinely, MRI studies
performed 6 to 24 months after radiosurgery show contrast enhancement at the target (Figure 2). Radiosurgery performed on patients with cavernous sinus
tumors has been associated with low rates of trigeminal
dysfunction. 29 Radiosurgery may have an effect on
ephaptic transmission but not on normal axonal conduction. Young et al23 theorized that radiofrequency
energy may interrupt both abnormal transmission and
normal axonal conduction in such a way that loss of
normal facial sensation is required for long-lasting pain
relief. Perhaps radiation energy has a larger therapeutic
ratio between pain relief and sensory loss. Our group
recently reported pain relief from sphenopalatine neuralgia after radiosurgery. In this procedure the sphenopalatine ganglion was irradiated with an 8-mm collimator to a maximum dose of 90 Gy.30
It has been our goal to manage pain and yet try to
maintain normal facial sensation. Dysaesthetic pain syndromes and anesthesia dolorosa are disabling, with virtually no effective options. In some patients, this new
pain can be worse than the prior trigeminal neuralgia.
For this reason, our surgical armamentarium includes
procedures with lower rates of facial sensory loss (microvascular decompression, glycerol rhizotomy, and
stereotactic radiosurgery). We rarely perform radiofrequency rhizotomy or nerve section. Radiosurgery is a
minimally invasive method to manage trigeminal neuralgia that is associated with a low risk of facial paresthesias, an approximate 80% rate of significant pain
relief, and a low recurrence rate in patients who attain
complete relief.
Accepted for publication April 3, 1998.
This study was supported by grant K08NS01723
(Dr Kondziolka) from the National Institutes of Health,
Bethesda, Md.
Reprints: Douglas Kondziolka, MD, MSc, FRCSC, Department of Neurological Surgery, Suite B-400, University
of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh,
PA 15213.

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