Key-words:
Inferior alveolar - infraorbital nerve - peripheral neurectomy - trigeminal neuralgia
Introduction
Trigeminal neuralgia (TN) is a sudden, sharp, severe, intermittent, lancinating, usually
unilateral facial pain in the distribution of one or more divisions of the trigeminal
nerve,[[1]] lasting from a fraction of a second to minutes and is triggered by trivial cutaneous
or intraoral stimuli.[[2]] The estimated annual incidence of TN is about 13 per 100,000 persons/year.[[3]] It most commonly occurs over the age of 40 years with a slight female predilection.[[4]] Spending adequate time in the patient interview and physical examination of the
regions supplied by the trigeminal nerve is important to reach a proper diagnosis
of TN.[[5]]
The medical treatment fails in 30% of the patients, either through inadequate pain
control or due to intolerable side effects;[[6]] therefore, surgical management is indicated in these patients. There are many available
surgical procedures used for the treatment of TN.[[7]] Peripheral neurectomy is a simple, low-risk procedure that involves surgical avulsion
of the postganglionic part of the trigeminal nerve divisions, usually performed under
local anesthesia for managing peripheral pain in TN.[[8]] Despite it is one of the oldest surgical procedures for TN, none of the previous
studies about peripheral neurectomy for treatment of TN had been subjected to good
statistical analysis.[[7]]
This study aims to evaluate the clinical outcome and the recurrence rate following
peripheral neurectomy for the management of TN. To the best of our knowledge, this
is the first study to use Kaplan–Meier analysis for the time to recurrence to predict
the probability of recurrence at any given time following the procedure. The severity
of the disease and the anxiety and depression status of the patients before and after
the procedure were also discussed.
Patients and Methods
This was a retrospective cohort study of 17 patients with classical TN treated by
peripheral neurectomy, operated on in Royal Commission Hospital, Jubail and Southern
Armed Forces Hospital, KSA from January 2013 to December 2018. The study was approved
by the local ethical committee. The classical TN was diagnosed according to Sweet's
criteria (the pain is paroxysmal, may be provoked by light touch to the face, confined
to trigeminal distribution, unilateral and the clinical sensory examination is normal).
The patients in the study included those who are resistant to medical treatment or
developed intolerance to medications due to their side effects and those who are unfit
because of either old age or co-morbidity or reluctant to have invasive neurosurgical
procedures. Patients younger than 30 years old, those with symptomatic TN (a causative
lesion, other than vascular compression like multiple sclerosis or tumor), those with
an atypical presentation like bilateral involvement, and the patients with follow-up
periods <1 year were excluded from the study.
The patients were assessed preoperatively including a detailed history, clinical general
and neurological examination, and the response of pain to carbamazepine was detected.
Diagnostic block with 2% lignocaine was used to confirm the involved division of the
nerve in the patients after detecting the site of the pain by history and clinical
examination when it gave complete relief from the symptoms. All patients underwent
magnetic resonance imaging of the brain to rule out underlying structural lesions
such as tumors or vascular malformations. Carbamazepine tablets 600–1200 mg daily
were prescribed for all patients. It was used continuously or intermittently for an
average of one to 3 years, sometimes alone and sometimes with other drugs to treat
the condition. The visual analogue scale (VAS) was used for pain assessment preoperatively
and during the follow-up period.
Informed written consent was obtained from all the patients included in this study
for peripheral neurectomy of the involved branch of the trigeminal nerve. Regarding
the surgical technique used, the supraorbital nerve was accessed under local anesthesia
through an upper eyebrow incision. The nerve was avulsed, while its remnants were
cauterized. The supraorbital foramen was blocked by bone wax. Double layer closure
was done at the conclusion of surgery. The infraorbital nerve was approached through
an intraoral vestibular incision under local anesthesia where the infraorbital foramen
was identified. The infraorbital nerve was avulsed from the soft tissues and the infraorbital
canal while the remnants of the nerve were cauterized deeply in the foramen. The foramen
was blocked by bone wax and suturing the wound in layers was done. For inferior alveolar
neurectomy, an incision about 1.5 inches long was made along the anterior border of
the ascending ramus to expose a point on the mandible midway between the last molar
tooth and the angle of the jaw. After the fibers of the masseter muscle have been
separated to expose the bone, a burr hole was placed in the outer table of the mandible
to expose the mandibular canal. The perforator was applied carefully to prevent nerve
damage. By deepening the burr hole, the thin cortical roof of the canal was removed
to expose the large nerve within it. A blunt hook is passed around the nerve and slightly
distracted from the canal so that two hemostatic forceps can be applied to the full
thickness of the nerve. Without allowing the nerve to fray, the forceps were applied.
The entire length of the nerve was withdrawn from the mandibular canal. Traction was
then applied proximally to drag about 1 cm of nerve down into the wound before cutting
it. The proximal part of the nerve was divided rather than avulsed to avoid possible
traction damage to the ganglion with undesirable anesthesia, especially to the lingual
nerve. The distal end of the nerve was avulsed and its remnants were cauterized deep
in the foramen. The mental foramen was blocked by bone wax and suturing of the wound
in layers was done. Antibiotics and anti-inflammatory drugs were prescribed for all
patients postoperatively for 5–7 days. The initial postoperative relief of pain was
assessed during the 1st week after surgery.
The patients were followed up after surgery at 1 month, 3 months, 6 months then annually
or if a change of pain severity appeared. VAS was used for pain assessment during
the follow-up period. The outcome of surgery was graded as (A) Marked improvement
(reduction of pain more than 85% of preoperative pain without medications for TN);
(B) Moderate improvement (50%–84.9% reduction of preoperative pain, treatment with
low doses of Carbamazepine was allowed in this group); and (C) Mild improvement (reduction
of pain <50% compared to preoperative pain, long-term medication was resumed, or an
additional procedure was performed for TN). Recurrence was defined as a transition
from marked improvement group to either the moderate or mild improvement group during
the follow-up period. Kaplan–Meier analysis was used for the time to recurrence to
predict the probability of recurrence at any given time. Hospital Anxiety and Depression
Scale (HADS) was used for the assessment of anxiety and depression status of the patients
during the follow-up visits in comparison to the preoperative status. The degree of
relief of pain, recurrence of pain, postoperative complications, the need for additional
procedures in case of recurrent pain were recorded during the follow-up visits.
Statistical analysis
Data were statistically described in terms of mean ± standard deviation, median and
range, or frequencies (number of cases), and percentages when appropriate. Numerical
data were tested for the normal assumption using the Shapiro–Wilk test. Comparison
between pre- and post-operative data was done using the Wilcoxon signed-rank test
for paired (matched) samples. Survival analysis for the time to recurrence was done
using Kaplan–Meier statistics calculating the mean and median survival time for each
group with their 95% confidence interval and the corresponding survival graphs. Two-sided
P < 0.05 was considered statistically significant. All statistical calculations were
done using the computer program IBM Statistical Package for the Social Science (SPSS)
(SPSS; IBM Corp, Armonk, NY, USA) release 22 for Microsoft Windows.
Results
The study included 17 patients who fulfilled the inclusion criteria. The mean age
of the patients was 54.4 ± 10 (range, 31–67) years. The female/male ratio was 2.4:1.
The characteristics of the patients in the study are shown in [[Table 1]] [[Figure 1]], [[Figure 2]], [[Figure 3]].
Table 1: The characteristics of the patients in the study (n=17)
Figure 1: Supraorbital neurectomy in a 31-year-old male patient who had all the three divisions
involved on the right side and refused more invasive neurosurgical procedures: (a)
Sterilization of the skin, (b) Exposure of the supraorbital nerve before avulsion,
and (c) Closure of skin at the conclusion of surgery
Figure 2: Right infraorbital neurectomy in the same patient illustrated in (a) Exposure of
the infraorbital nerve branches through a vestibular incision, (b) The infraorbital
nerve stump, and (c) The avulsed branches of the infraorbital nerve
Figure 3: Right inferior alveolar neurectomy in a 52-year-old female patient who had only V3
involvement: (a) Exposure of the angle of the mandible and preparation for the burr
hole, (b) Exposure of the mental nerve, and (c) The avulsed nerve specimen
The mean preoperative VAS was 7.47 ± 0.8 (range, 6–9). Initially, the pain was relieved
in all patients following the procedure. The mean pain-free interval was 29.3 ± 16.3
(range, 14–85) months. The mean follow-up period was 44.9 ± 23.2 (range, 14–90) months.
The VAS had significantly improved during the follow-up period. At 2 and 5 years of
follow-up period, the mean VAS was 0.81 ± 1.276 and 1.6 ± 0.894 (P < 0.001 and P =
0.042 respectively) [[Table 2]] and [[Figure 4]].
Table 2: Comparison of Visual Analogue Scale over time in the study patients (n=17)
Figure 4: Mean visual analog scale score over the time in the study sample. (PROP ‒ Preoperative)
Thirteen patients (76.5%) had marked improvement of pain until their last follow-up
visit. The duration of pain relief was <2 years in seven patients (53.8%), between
2 and 5 years in 5 patients (38.5%), and more than 5 years in only 1 patient (7.7%).
There was a recurrence of pain in four patients (23.5%). Three of them had both V2
and V3 involved while one case had V3 only involved. The mean time of recurrence in
these cases was 3.5 ± 1.3 (range, 2–5) years. Three of these cases (17.6%) had declined
to moderate improvement group during the follow-up period. These patients were managed
by a lower dose of carbamazepine (400 mg daily). The fourth patient (5.9%) has declined
to the mild improvement group 2 years after the procedure. He was referred for microvascular
decompression (MVD). Three patients out of seventeen who have been lost to follow-up
for reasons other than death were included as censored data as they had the same distribution
of outcomes as assessed on their last follow-up visit. By Kaplan–Meier analysis, the
survival rate without recurrence at 2, 3, 4, and 5 years following the procedure were
92.9%, 79.6%, 59.7%, and 29.8%, respectively [[Figure 5]].
Figure 5: Kaplan‒Meier curve for the recurrence over the time in the study sample
The mean preoperative HADS-Anxiety score was 11.59 ± 2.12, which significantly improved
to 6.35 ± 1.77 on the last follow-up visit following the procedure (P < 0.001). Likewise,
the mean HADS-Depression score was 11.12 ± 1.9 which significantly improved to 6.24
± 1.72 on the last follow-up visit (P < 0.001) [[Table 3]].
Table 3: Comparison of preoperative anxiety and depression versus on the last follow.up visit
in the study patients
All patients had the expected sensory loss in the distribution of the avulsed division
of the trigeminal nerve. It was less annoying than the stress of pain in 12 patients
(70.6%). Despite five patients (29.4%) were initially unpleasant with this facial
anesthesia, they were reassured and they reported that they became adaptive with it
over time. Two patients (11.8%) developed postoperative facial swelling which was
managed conservatively and resolved gradually over days.
Discussion
TN is a neuropathic facial pain syndrome, described as a sudden, severe, brief, stabbing,
usually unilateral, recurring pain in the distribution of one or more divisions of
the trigeminal nerve. The pain lasts from seconds to minutes and is triggered by trivial
stimuli such as shaving, brushing the teeth, washing the face, talking, and eating.
These patients are usually in constant fear that the pain will recur taking into consideration
that the attacks of pain increase in frequency, severity, and duration as time passes
unless definitive treatment is started.[[9]] They typically seek medical advice from different medical practitioners seeking
to alleviate their pain.
The peak age of onset of TN is reported to be after the fourth decade of life with
a slight predilection for females ranging from 2:1 to 3:2. The condition usually affects
the right side of the face.[[10]] Similar results were obtained in our study as 76.5% of the patients were above
50 years old, the female/male ratio was 2.4:1, and the right side of the face was
involved in 76.5% of the patients. TN may be classical or symptomatic resulting from
compression of the trigeminal nerve root or nucleus by tumors, multiple sclerosis
plaques, aneurysms, or vascular malformations.[[11]] The pathophysiology of classic TN is associated with neurovascular compression
in the trigeminal root entry zone resulting in demyelination and dysregulation of
voltage-gated sodium channel expression in the membrane, leading to pain attacks in
patients with TN.[[12]] A recent study found that pathological vascular changes in peripheral vasculature
leading to demyelination of the inferior alveolar nerve may have a role in the initiation
and precipitation of pain in patients with TN.[[13]] In this study, the mandibular division (V3) was involved in about 35% whereas both
V2 and V3 were involved in about 41% of the patients. The mandibular division is the
most commonly involved and the ophthalmic division (V1) was less commonly involved
in patients with TN.[[10]],[[14]] Farooq et al. reported that V3 was involved either alone or in combination with
V2 in 62.5% of the patients in their study of 72 patients with idiopathic TN.[[15]] Shankland reported that both V2 and V3 were involved in one-third of the patients
in their study.[[16]]
Peripheral neurectomy is a minor, safe, and minimally invasive, daycare surgical procedure.
It can be done as an outpatient procedure under local anesthesia. It involves the
transsection of the branches of the trigeminal nerve after their exit through their
foramina on the facial skeleton. It interrupts the conduction of afferent impulses
thereby aborting the episodes of pain.[[17]] The demyelination of involved nerve fibers due to peripheral vascular changes as
seen on both histopathological and immunohistochemical examination gives a rationale
for peripheral neurectomy in alleviating the pain in the patients with TN.[[2]],[[13]] It is particularly carried out in old aged or debilitated patients in whom other
invasive neurosurgical procedures are contraindicated.
In our study, the pain of TN had significantly improved during the follow-up period.
The mean pain-free interval was 29 months. This is similar to the results of Quinn
who reported a retrospective case series of 63 patients with 112 neurectomies. A Pain
relief period of 24–32 months was reported within a follow-up period of 0–9 years.
He concluded that the total pain-free period obtained from repeated peripheral neurectomies
is significant and justifies the use of the procedure.[[18]] This is not so varied from the results of Freemont too who studied 146 patients,
of whom 26 patients underwent neurectomy and noted an average pain-free period of
26.5 months following a single peripheral neurectomy. Twenty of these patients had
remained pain-free until death or the end of the study.[[19]] Despite this pain-free period is less than reported in the study of Grantham who
reported an average pain relief period of 33.2 months in a case series of 55 patients
with 55 neurectomies during a follow-up period of 6 months to 8 years, their study
included only supraorbital and infraorbital nerves.[[20]] Cerovic et al. reported a pain-free interval of 12–15 months for infraorbital neurectomy
and 15–18 months for mandibular neurectomy.[[7]],[[21]] Khanna and Galinde reported a pain relief period of 24 months following infraorbital
neurectomy and 26 months following mental neurectomy.[[22]] Mason observed that infraorbital neurectomy was likely to be more successful than
inferior alveolar neurectomy.[[23]] We could not analyze the pain-free period of each division separately in our study
as multiple nerve divisions were involved in the majority of cases.
In this study, 76.5% of the patients had marked improvement of pain until their last
follow-up visit. Four patients (23.5%) developed a recurrence of pain. The mean time
of recurrence in these cases was 3.5 years. Three of these cases had declined to the
moderate improvement group during the follow-up period. They were managed by a lower
dose of carbamazepine which is consistent with other studies.[[19]],[[24]] One patient (5.9%) has declined to the mild improvement group and was referred
for MVD. These results are comparable to the results of Chandan et al. who reported
that 80% of patients had excellent pain relief lasting for 3 years without any medication
following peripheral neurectomy done for 20 Indian patients with TN.[[25]] This is also near to the results of Shah et al.'s study on fifty patients with
70% of the patients having excellent pain relief lasting for 2–5 years without any
medications and a recurrence rate of 12% uncontrolled even with medication.[[26]] Murali and Rovit reported an excellent (79% of the patients) or good pain relief
for at least 5 years following peripheral neurectomy for the recurrent pain who had
previously undergone radiofrequency thermocoagulation. Six patients out of 40 had
a recurrence of pain after 2 years but responded well to a second neurectomy.[[27]] Cerovic et al. reported that the recurrence of pain following the first surgery
on the infraorbital nerve was seen in 41% of the cases, 35% of the patients had recurrence
after the second surgery between 9 and 12 months and the recurrence was seen in 44%
of the patients after the third surgery with pain-free period no longer than 12 months.
They conclude that the remission time after repetitive peripheral neurectomy decreases,
hence there is no point in repeating the surgery on the same nerve division more than
three times.[[21]]
To the best of our knowledge, this is the first study to use Kaplan–Meier analysis
for the time to recurrence to predict the probability of recurrence at any given time
following peripheral neurectomy for TN. The postoperative survival rate was 92.9%
after 2 years and 59.7% after 4 years. Zakrzewska used the Kaplan–Meier plots to analyze
all the recurrence rates during his study. He found a median pain relief period of
6 months and a mean time to recurrence of 10 months in a 10-year follow-up series
of 145 patients treated with cryotherapy for TN and as compared with the median pain
relief period of 24 months in 265 patients treated with radiofrequency thermocoagulation.
Sixty-two percent of 65 patients were pain-free 5 years after MVD.[[28]] Barker et al. have reported a long-term (20 years) prospective longitudinal study
on the outcome of MVD for TN in 1185 patients. By Kaplan–Meier analysis, they found
that the postoperative survival was 93% after 10 years and 70% after 20 years.[[29]]
We cauterized the nerve remnants and occluded the related foramina with bone wax to
reduce the recurrence rate in our study. This is consistent with other studies.[[2]] The recurrence of pain following peripheral neurectomy for TN may be from the main
ascending trunk remaining after the neurectomy, other branches of the same division
of trigeminal nerve, or from the intact collateral branches, neuroma formation in
the avulsed nerve, and demyelination and central sensitization which is increased
excitability of neurons in adjacent spinal segments and cortical areas.[[30]],[[31]],[[32]] Peripheral neurectomy for TN followed by obscuration of the foramen with fat, stainless
screw, titanium screws, and gold foils were tried with variable success rates.[[19]],[[23]],[[24]],[[33]] Despite obturation with fat gives good results, it usually causes distant site
morbidity. In a comparative study, the pain-free period following the procedure ranged
from 15 to 24 months in cases without placing a stainless screw in the foramen, while
none of the patients had recurrent pain after 2 years of follow-up when placement
of stainless screws in the foramina was applied.[[33]] Hong-Sai reported that in 4 patients the infraorbital and mental foramina were
occluded with titanium screws out of 12 cases that underwent peripheral neurectomies.
There was no recurrence in these patients in 4 years.[[34]]
In our study, the anxiety and depression levels on HADS on the last follow-up visits
had significantly improved in comparison to the preoperative levels. To the best of
our knowledge, this is the first study to assess the anxiety and depression states
before and after the peripheral neurectomy done for patients with TN. This was done
as a step to try to evaluate the quality of life in these patients following the procedure.
Zakrzewska found that 39% were depressed and 42% were anxious out of 24 patients before
undergoing cryotherapy for the treatment of TN. Following the procedure, only 15%
were depressed and 30% were anxious.[[28]]
The complications of the procedure in this study included sensory loss in the area
supplied by the avulsed nerve and temporary facial swelling. Lamichhane et al. reported
the same complications.[[8]] Other complications reported in the literature included weakness of masseter muscles
and very rarely, loss of the corneal reflex. In comparison with other peripheral procedures
for TN, alcohol injection can cause local edema, dysesthesia, and necrosis with the
surrounding tissues with a risk of pain recurrence.[[35]] Despite radiofrequency thermocoagulation usually provides longer pain-free interval
than the peripheral procedures, yet moderate dysesthesia in 5%–25% of patients, anesthesia
dolorosa occurring in 1%–5%, keratitis in 1%–3%, and very low mortality rate are among
the possible complications.[[36]] Recurrences may also occur after MVD, although the time interval appears to be
much longer. Its major complications included deaths (0.2%), brain-stem infarction
(0.1%), and ipsilateral hearing loss (1%).[[29]]
There are trials for advancement in the technique of peripheral neurectomy for TN.
In a recent study, Ward et al. described a technique for endoscopic microdissection
of the infraorbital nerve in two patients with medically refractory V2 TN localized
to the lateral midface and concluded that infraorbital microdissection is a safe and
effective technique for symptomatic management of V2 TN while sparing sensation in
asymptomatic portions of the dermatome.[[37]] Huang et al. concluded that endoscope-assisted neurectomy and avulsion of the inferior
alveolar nerve is effective in pain relief in patients with TN involving the mandibular
division, with limited invasiveness and speedy recovery.[[38]]
Peripheral neurectomy is recommended to do for the patients with TN who are refractory
to medical treatment, refuse, or are unfit for major neurosurgical interventions;
providing short to medium-term good pain control. It is a simple, safe, and effective
procedure for the treatment of TN.
The limitations of this study include that it is a retrospective one with a relatively
small number of patients. Prospective studies with a larger sample size with more
concern about the quality of the life of the patients following peripheral neurectomy
for TN are recommended to authenticate the results.
Conclusion
Peripheral neurectomy provides short to medium-term good pain control for patients
with TN. The preoperative severity of pain, anxiety, and depression levels improved
markedly after the procedure.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
