Trigeminal Neuralgia Radiosurgery

Douglas Kondziolka, M.D., M.Sc., F.R.C.S.C., F.A.C.S.,1,2,3

L. Dade Lunsford, M.D., F.A.C.S.,1,2,3 and John C. Flickinger, M.D., F.A.C.R.1,2,3

ABSTRACT

Although medical therapy is of benefit to many patients with trigeminal neuralgia,

surgical management is often performed for patients with medically refractory pain.
Gamma knife radiosurgery has been advocated as a minimally invasive alternative surgical
approach to microvascular decompression or percutaneous surgeries. In this article, we
review the safety and efficacy of this technique and discuss potential ways to improve on
results.
KEYWORDS: Trigeminal neuralgia, radiosurgery, tic douloureux

Objectives: Upon completion of this article, the reader should be able to: (1) summarize the management options for patients with
trigeminal neuralgia; (2) discuss the technical aspects of trigeminal neuralgia radiosurgery; and (3) summarize the treatment
expectations that follow this procedure.

edical therapy is the initial approach for most

patients with trigeminal neuralgia. However, many patients fail or cannot tolerate medical therapy and eventually require surgical intervention. Although often
associated with initial pain relief, all surgical procedures
are associated with variable but definite rates of recurrence and morbidity. Gamma knife radiosurgery has
been advocated as a minimally invasive alternative surgical approach to microvascular decompression (MVD)
or percutaneous surgeries. Stereotactic irradiation of the
trigeminal ganglion was first reported by Leksell.1 More
recently, numerous authors have reported their initial
results with radiosurgery using high-resolution image
guidance.29 These data testified to the accuracy of
radiosurgical targeting and the initial safety of the
technique and provided dose-response information. In
this article, we review clinical outcomes following radiosurgery and discuss indications and technical issues of
the procedure.

TECHNIQUE OF RADIOSURGERY
We use the model U or C gamma knife units interchangeably for radiosurgery at our center. Patients
undergo the entire procedure during a 23-hour hospitalization. First, the Leksell model G stereotactic frame
(Elekta Instruments, Atlanta, GA) is attached to the
head under local anesthesia. Second, the patient undergoes stereotactic magnetic resonance (MR) imaging to
identify the trigeminal nerve. Rarely, patients have
computed tomography (CT) imaging for targeting if
they cannot undergo MR imaging. MR imaging is
performed using contrast-enhanced, short repetition
time (TR) sequences and axial volume acquisitions of
512
216 matrices divided into 1-mm slices. When the
trigeminal nerve is difficult to identify on imaging
(usually because of prior MVD), additional axial long
relaxation time MR images were used. A single 4-mm
isocenter is used for targeting, although in the past some
patients have been treated with two-isocenter plans.

Pain Management for the Neurosurgeon: Part 2; Editor in Chief, Winfield S. Fisher III, M.D.; Guest Editor, Kim J. Burchiel, M.D., F.A.C.S.
Seminars in Neurosurgery, volume 15, numbers 2/3, 2004. Address for correspondence and reprint requests: Douglas Kondziolka, M.D., Ste. B-400,
UPMC Presbyterian, 200 Lothrop St., Pittsburgh, PA 15213. E-mail: kondziolkads@msx.upmc.edu. Departments of 1Neurological Surgery, and
2
Radiation Oncology, University of Pittsburgh, and 3the Center for Image-Guided Neurosurgery, Pittsburgh, Pennsylvania. Copyright # 2004 by
Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. 1526-8012,p;2004,15,02/03,
135,141,ftx,en;sns00195x.

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Figure 1 Magnetic resonance images at gamma knife radiosurgery for an 80-year-old woman with right trigeminal neuralgia. A
maximum dose of 75 Gy was delivered to the nerve using a single 4-mm isocenter. Coronal and sagittal views are shown on the right.

With a single isocenter, the target is 2 to 4 mm anterior

from the junction of the trigeminal nerve and pons
(Fig. 1). The isocenter is usually located so that brainstem surface is irradiated at the 30% isodose line. Past
patients received maximum doses of 60, 70, 80, 85, or
90 Gy, although 80 Gy is our usual dose (Fig. 2).

METHOD OF PATIENT EVALUATION

Following radiosurgery, we evaluate patients for the
degree of pain relief, latency interval to pain relief,
need for further surgical procedures, use of medication,
and complications. In addition, up-to-date clinical information is obtained by telephone interview at periodic
intervals.10 To evaluate effectiveness over time (besides
the typical measure of the proportion of patients with
pain relief at initial or last follow-up), we calculate the
time to initial response from radiosurgery and the duration of pain relief using the product limit method of
Kaplan and Meier.11 The time to onset of complications
after radiosurgery (new or increased sensory disturbance)
is also calculated using the same methods. Pain relief
duration is calculated from the time when the level

of pain relief being studied (complete or > 50%) was

achieved. To identify any correlation of outcomes (time
to initial response, duration of benefit, and complications) with treatment parameters that include sex, age,
duration of symptoms, presence or absence of preoperative paresthesia or additional atypical features, number
of prior surgeries, maximum dose, and number of isocenters, stepwise (forward conditional) multivariate
analyses using the Cox proportional hazards model are
performed.

UNIVERSITY OF PITTSBURGH
EXPERIENCE
Our current experience included 513 patients. There
were 305 (60%) women and 208 men. The mean age
was 68 years (range, 1692). The mean duration of
symptoms was 8 years.
Our last detailed review studied patients managed
between December 1992 and December 1998 (n 264
consecutive radiosurgery procedures for trigeminal neuralgia).10 Of these 264 procedures, 25 were performed for
nonidiopathic trigeminal neuralgia (19 were associated

TRIGEMINAL NEURALGIA RADIOSURGERY/KONDZIOLKA ET AL

Figure 2 Magnetic resonance images at gamma knife radiosurgery for a 78-year-old woman with right trigeminal neuralgia. Note the
prominent arteries surrounding the nerve. A maximum dose of 80 Gy was delivered using a single 4-mm isocenter. She had relief of pain
and tapered her medications.

with multiple sclerosis, three were secondary to tumors,

and three were secondary to other pathological conditions such as a herpetic infection, Lyme disease, or
Wallenbergs syndrome). These 25 procedures were
excluded from this study. Of the 239 procedures performed for idiopathic trigeminal neuralgia, 19 were
a repeated radiosurgery after an initially successful
procedure. For these 19 patients, the outcome after
initial radiosurgery was included in this study as a poor
result (subsequent outcomes of the repeated procedure
were excluded). Thus, 220 procedures in 220 patients
were available for analysis. All 220 patients had trigeminal neuralgia that was idiopathic, long standing, and
refractory to medication therapy such as carbamazepine,
phenytoin, baclofen, or gabapentin as well as a variety of
analgesic medications.
Of these 220 patients, 94 were male and 126 were
female. The median age of the patients was 70 years
(range 2692). Most of the patients had long history of
medical treatment with a median symptom duration of
96 months (range 3564 months). Pain was predominantly distributed in the V2 and V3 distributions of the

trigeminal nerve (29.5%), followed by V2 alone (22.3%)

and V3 alone (13.2%). Patients with first-division
pain often had radiosurgery as an alternative to other
procedures. Although all patients complained of the
typical trigeminal neuralgia features of a sharp, lancinating, or shooting electric shock type of pain triggered by a
variety of events, 16 (7.3%) complained of additional
features such as a more constant dull, aching, or burning
pain. Eighty patients (36.4%) had some sensory disturbance (usually paresthesias) preoperatively, and three
patients (1.4%) had partial deafferentation pain caused
by prior ablative procedures.
Prior surgery was performed in 135 patients
(61.4%), including MVD, glycerol rhizotomy, radiofrequency rhizotomy, balloon microcompression, peripheral neurectomy, or ethanol injections. Of these
135 patients, 86 (39.1%) had one, 39 (17.7%) had two,
and 10 (4.5%) had three or more procedures prior to
radiosurgery. Thus, the majority of patients represented
both medical and surgical failures. In the remaining
85 patients (38.6%), radiosurgery was the first surgical
procedure performed.

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Pain Relief
The outcome of the intervention was graded in four
categories: excellent, good, fair, and poor. Complete pain
relief without the use of any medication was defined as
an excellent outcome. We recommended that all patients
with complete pain relief taper off their medications, and
some patients were in the process of tapering at the time
of evaluation (or refused to taper because of fear of a
recurrence). The patients with complete pain relief who
were still using some medication were considered as
having good outcomes. Patients with partial pain relief
(more than 50% pain relief) were considered to have a
fair outcome.2 No pain relief or less than 50% pain relief
was considered as poor. Placement within a category was
decided by the patient rather than by the physician.
Criteria for improvement included a reduction in both
the frequency and severity of pain attacks. Of the 220
patients, 47 (25.1%) required further additional surgical
procedures because of poor pain control. These patients
were considered as treatment failures (poor outcome),
and the results after the additional procedure were
excluded from this analysis.
Most of the patients responded to radiosurgery
within 6 months of the procedure (median 2 months).
The first evaluation was performed for all patients within
6 months after radiosurgery. At the initial follow-up
assessment, excellent results were obtained in 105 patients (47.7%), and excellent plus good results were
found in 139 patients (63.2%). More than 50% pain
relief (excellent, good, or fair) was noted in 181 patients
(82.3%). At the last follow-up evaluation, 88 patients
(40%) had excellent outcomes, 121 patients (55.9%) had
excellent plus good outcomes, and 152 were fair or better
(69.1%). Thirty patients (13.6%) had recurrence of pain
after the initial achievement of pain relief (25 patients
after complete relief, 5 patients after more than 50%
relief) between 2 and 58 months after radiosurgery.
Recurrences occurred at a mean of 15.4 months from
irradiation.

Time to the Initial Response

The time to response after radiosurgery was analyzed
using the product limit method of Kaplan and Meier.
The median time to achieving more than 50% pain relief
(excellent, good, or fair) was 2 months (2.0  0.05), and
median time to achieving complete pain relief (good or
excellent) was also 2 months (2.0  5.1). At 6 months
after treatment, 81.4  2.6% of patients had achieved
more than 50% pain relief, and by 12 months, 85.6 
2.47% of patients had (actuarial statistics). Complete
pain relief (good or excellent) was achieved in 64.9 
3.2% of the patients at 6 months, 70.3  3.16% by 1 year,
and 75.4  3.49% of patients by 33 months.
Prior authors including our group noted a latency
interval to pain relief of approximately 1 to 2 months.2,4,9

However, about 15% of patients had no improvement in

their pain even after 12 months. Because no patient
achieved complete or even more than 50% pain relief
after 12 months follow-up, we believe that patients with
unchanged pain at 1 year cannot expect any improvement afterward. In reality, this is an uncommon situation
because most patients would not wait so long to attain
pain relief. Patients who have continued disabling
pain after radiosurgery are managed with other surgical
procedures. We advocate repeated radiosurgery only if
complete pain relief had been achieved with subsequent
recurrence.
Complete pain relief was achieved at a median
time of 2 months, with most patients achieving this level
of relief within 6 months. Interestingly, a further 10% of
patients achieved complete pain relief 6 to 33 months
after radiosurgery. All of these patients obtained partial
pain relief within 6 months and then had complete resolution of pain afterward. Thus, it appears that patients
with partial pain relief may go on to complete relief over
time. This finding provides some ideas regarding the
mechanism of response to radiosurgery. Because most
patients responded in the initial months, electrophysiologic blocking of ephaptic transmission after nerve
irradiation, which has been discussed as a possible
mechanism by some authors,4,9 is possible. On the other
hand, because some patients responded or improved in a
later phase (more than 6 months after radiosurgery), a
later radiation effect with axonal degeneration may be
present.

Maintenance of Pain Relief

The duration of pain relief after the initial response in
all patients was also analyzed. Patients who never responded to radiosurgery were recorded as having a relief
duration of zero months. More than 50% pain relief
(excellent, good, or fair) was achieved and maintained in
75.8  2.9% of patients at 1 year, 71.3  3.3% of patients
at 2 years, 67.2  3.9% of patients at 3 years, 65.1  4.3%
of patients at 3.5 years, and 55.8  9.3% of patients at
5 years. Complete pain relief (excellent or good) was
achieved and maintained in 63.6  3.3% of patients
at 1 year, 59.2  3.5% of patients at 2 years, and
56.6  3.8% of patients at 3 years. A history of no prior
surgery was the only factor significantly associated
(p .01) with achieving and maintaining complete
pain relief.

Side Effects of Radiosurgery

No patient sustained an early complication after any
radiosurgery procedure. Seventeen patients (7.7%) developed increased facial paresthesia and/or facial numbness that lasted more than 6 months. The median
time to developing paresthesia was 8 months (range

TRIGEMINAL NEURALGIA RADIOSURGERY/KONDZIOLKA ET AL

119 months). After 19 months, no patient developed

any new sensory symptoms. No patient developed a
mastication deficit after radiosurgery or noted problems
in facial motor function. One patient (0.4%) developed
deafferentation pain after radiosurgery. This patient had
recurrent trigeminal neuralgia previously treated by
MVD. Following her MVD she had some decrease in
facial sensation, and her recurrent pain had some additional atypical features such as constant burning. Eight
years after initial surgery, radiosurgery was performed to
a maximum dose of 75 Gy using two isocenters. Eight
months later, she developed increased constant burning
pain with numbness consistent with deafferentation
pain.

Comparing Radiosurgery with

Other Procedures
The results of radiosurgery do not appear to be as good as
those observed after a first MVD but appear to be as
good or better as a second procedure. Barker et al, in
reporting on Jannettas series of 1185 patients, found
that complete pain relief was maintained in 70% of
patients at 10 years.12,13 Thus, we continue to advocate
MVD for appropriate younger patients with trigeminal
neuralgia because of the potential for longer duration
pain relief. Nevertheless, the possible risks of MVD
make it unsuitable for some patients. In addition, the
benefit of MVD is less when performed a second time or
for recurrent trigeminal neuralgia. We consider radiosurgery a good choice for patients with recurrent pain
after MVD or percutaneous surgery has failed, even
though prior surgical failure reduces the radiosurgical
success rate.
Other investigators have reported long-term results following different percutaneous techniques for
trigeminal neuralgia. Percutaneous retrogasserian thermal rhizotomy, first described in 1974 by Sweet and
Wepsic, has been widely performed.14 In Broggi and
Flanzinis series of 1000 patients with 9.3 years of mean
follow-up, they found an initial pain relief rate of 95%,
with recurrence in 18.1%.15 Scrivani et al reported their
series of 215 patients and found that 83% maintained
pain relief at a mean interval of 32 months.16 Percutaneous retrogasserian glycerol rhizotomy, first reported by
Hakanson, is also widely used.17 Jho and Lunsford
reported that 90% of 523 patients achieved complete
pain relief initially and that 77% maintained longer term
pain control, sometimes requiring multiple procedures.18
The pain recurrence rate was estimated to be between 30
and 50% over 2 to 10 years. Others reported a longer
term pain control rate of 50 to 90%.14,19,20 Results
following percutaneous trigeminal nerve balloon compression indicated a high rate of initial pain relief,
but that pain recurred in 26% (50 patients with average
3-year follow-up).21

The low incidence of complications is the greatest

advantage of stereotactic radiosurgery compared with all
other surgeries. Paresthesia or numbness of varying
magnitude is observed in 20 to 70% of patients after
percutaneous thermorhizotomy, glycerol rhizotomy,
or balloon nerve compression.12,1421 In this study, 17
patients (10.2  2.35% at 2 years) developed increased
facial paresthesia and/or facial numbness. The majority
of our patients described their numbness or paresthesia
as minor and not bothersome. Some authors advocated
percutaneous balloon nerve compression as advantageous for management of first-division trigeminal neuralgia because of the lower risk for postoperative corneal
analgesia. In the present radiosurgery study, no patient
developed this complication. The reduced rate of facial
sensory deficits or symptoms indicates that the effects
on nerve tissue may be less than after other ablative
surgeries. Thus, the mechanistic effect of radiosurgery is
probably a combination of both histologic and electrophysiologic responses.
Radiosurgery can be repeated if pain returns after
initial relief. We advocate a maximum dose of 50 to
60 Gy at a second procedure and usually target a more
anterior section of the nerve. Doing so has led to a pain
response similar to that after primary radiosurgery in
properly selected patients.22

Effect of Radiation on Nerves:

A Primate Model of Radiosurgery
Peripheral nerves are considered highly radioresistant. A
dose that produces delayed radiation necrosis of spinal
cord may have no effect on peripheral nerves. To study
the effects of radiosurgery on trigeminal nerve fibers,
we used a baboon radiosurgery model and delivered
either 80 or 100 Gy to the nerve using a single 4-mm
isocenter.23 Trigeminal nerves that received 80 Gy
radiosurgery had no inflammation. Focal myelin pallor
and vacuolation without fibrosis was noted with Masson
trichrome in the preganglionic nerve segments.
Immunoreactivity for neurofilament revealed substantial axonal loss, fragmentation, and some swellings.
Plastic sections and ultrastructural studies revealed a
focal region near the center of the nerve exhibiting
acutely degenerating axons with preservation of some
identifiable myelinated axons admixed with small foci of
tissue necrosis (Fig. 3). Schwann cell nuclei were also
necrotic. The surrounding region contained only rare
degenerating axons in which the trigeminal ganglia
appeared normal, as did the distal nerve beyond the
radiosurgery target.
Trigeminal nerves that received 100 Gy exhibited
axonal degeneration with myelin vacuolation and expansion of the endoneurial intercellular matrix consistent
with edema. In one specimen, nearly the entire nerve
width was necrotic. The ganglion remained normal.

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Figure 3 Electron micrograph of a baboon trigeminal nerve 6 months following 80 Gy radiosurgery

(top). Note the partial nerve degeneration. Distal to
the target, the nerve appeared normal (bottom).

On plastic sections, axonal degeneration was noted outside the necrotic zone, but the histology normalized
toward the ganglion (Fig. 3). Ultrastructural studies
revealed that the axonal degeneration around the irradiated targets affected large and small myelinated axons
similarly at both radiosurgery doses. Only rare primary
demyelination (vesicular demyelination) was noted outside the necrotic zones. Only rare intact unmyelinated
axons were identified within and surrounding the major
foci of nerve injury in both the 80 and 100 Gy groups.23
We know from rat brain parenchymal experiments that doses of 100 Gy or more will lead to tissue
necrosis after a 3-month time interval.24 In an attempt to
avoid nerve necrosis and maintain facial sensation, we
have chosen doses below 100 Gy in patients. As this
study showed, the histologic effect was dose related.
Radiosurgery at 100 Gy was followed by nerve necrosis
in each animal and with a more pronounced axonal effect
than radiosurgery at 80 Gy. The hypothesis that radiosurgery might affect different fiber types selectively (i.e.,
those conducting pain rather than light touch) was not

substantiated by the findings of our experiments. We

could not detect a substantial difference in axonal injury
among small myelinated, large myelinated, and unmyelinated fibers. Through partial (focal) axonal degeneration, radiosurgery probably relieves trigeminal neuralgia
pain by affecting an axon population large enough
to result in pain relief. On the other hand, the low
incidence of lost facial sensation indicates that the
remaining intact axonal population is enough to maintain neurologic function in the majority of patients. This
balance between pain relief and preservation of sensation
is dose related.

Improving Radiosurgery Technique

We compared radiosurgery using two 4-mm isocenters
with that using one isocenter with a maximum dose of
75 Gy. Our hypothesis was that irradiation of a longer
nerve segment may have led to an improved rate of pain
relief. This randomized, blinded trial found no pain
benefit to two-isocenter radiosurgery but a higher rate

TRIGEMINAL NEURALGIA RADIOSURGERY/KONDZIOLKA ET AL

of facial sensory loss.25 Regis et al advocate a maximum

dose of 90 Gy and a more anterior radiosurgery target.26
With this approach, they have reported a low rate of
facial sensory loss despite using a higher dose. Reports
from Pollock et al found a higher rate of sensory loss at
90 Gy, although they used the more traditional posterior
nerve target.27,28 These questions, dose and target, are
appropriate considerations for randomized clinical trials.

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