Keywords trigeminal neuralgia - trigeminopontine angle - neurovascular conflict
Introduction
A wide variety of abnormalities can lead to trigeminal neuropathy, which include lesions
involving the trigeminal nerve itself (primary lesions) and lesions that secondarily
involve the nerve or any one of its three branches. Anatomically, trigeminal nerve
is divided into four segments, based on its course through the brain stem, prepontine
cistern, Meckel cave, and cavernous sinus, as it finally exits cranium.[1 ]
[2 ]
Trigeminal neuralgia (TN) is described as a sudden onset of severe, unilateral, paroxysmal,
and lancinating pain in one or more of the distributions of the trigeminal nerve.
Vascular compression, also known as neurovascular conflict (NVC), of the trigeminal
nerve is one of the commonest secondary known cause, as suggested by Dandy in 1932.
In his series, he reported that the superior cerebellar artery caused NVC in 30.7%
of patients.[2 ]
[3 ]
[4 ]
[5 ] In another series, it was found that only 0 to 8.5% of cases of TN were secondary
to tumors.[6 ] Studies have already been published correlating compression, displacement, and cross-sectional
area of trigeminal nerve with the severity of pain. We were not able to find any study
correlating mTPA with pain severity in a review of the literature. NVC of nerve could
be on either side of the nerve; however, since the trigeminopontine angle (TPA) forms
an acute angle over the medial aspect, we tried to find the correlation of mTPA with
mNVC (NVC over the medial aspect of nerve) pain responsiveness.
Aims and Objectives
The aim of this study was to correlate mTPA measurement with severity of TN due to
mNVC and to evaluate the reduction in pain in patients kept on medical management
and its correlation with medial TPA (mTPA).
Materials and Methods
This was a retrospective observational study conducted between May 2018 and October
2020.
Study Population
A total of 42 cases with suspected TNs referred to the Department of Radiology for
MRI scan were evaluated. Out of these patients, a total of 30 cases of TN had NVC
over medial aspect of trigeminal nerve and were included in our study, with age ranging
between 22 and 82 years, and these included 19 males and 11 females. An informed consent
was taken from each patient for their inclusion in the study. The above method of
enrolment is shown in [Fig. 1 ].
Fig. 1 Flow chart showing total number of cases included and excluded in our study.
Inclusion Criteria
Cases with TN with instigating vessel abutting/compressing over medial aspect of trigeminal
nerve and those managed conservatively on standard medical management given in our
institute constituting 600 mg of oxcarbazepine (Tablet Oxetol 300 mg [Sun Pharmaceuticals]
twice a day) for 2 weeks and evaluated on follow-up visit were included.
Exclusion Criteria
Patients who underwent prior surgical microvascular decompression, NVC over lateral
aspect of trigeminal nerve, or patients presenting with TN due to any other etiology
were excluded.
Imaging Protocol
All the patients were evaluated on MAGNETOM Skyra 3T MRI (Siemens). Sequences acquired
for evaluation were (1) T1-axial sections of whole brain; (2) T2-axial sections of
whole brain and posterior fossa (medulla to upper pons) with (3) thin slices 3D T2-SPACE
Sequence; and (4) FLAIR-axial sections of whole brain. Bilaterally, trigeminal nerves
were examined for vascular compression/contact. In multiplanar windows, point of contact
between the instigating vessel and the nerve was identified and only cases with medial
point/area of contact with the nerve and vessel were included. Later, MPA was calculated.
Relevant clinical details regarding pre- and posttreatment pain score as well as other
laboratory investigations performed for the cases were collected. Microsoft Excel
software was used to analyze the data. Charts and tables were prepared for representation
and comparison of data.
Trigeminopontine Angle Calculation
Trigeminopontine Angle Calculation
Using the two-line Cobb angle method, MPA was calculated on symptomatic side in T2
3D SPACE-axial sections of MRI brain at the level of trigeminal nerve. A line is drawn
along the medial aspect of cisternal segment of trigeminal nerve and a second line
is drawn along the anterior aspect of pons medially, and the resultant angle is taken
as mTPA ([Fig. 2 ]).
Fig. 2 T2 3D SPACE axial sections of MRI brain showing the two-line Cobb angle method for
calculation of the trigeminopontine angle. 3D, three-dimensional; MRI, magnetic resonance
imaging.
Pain Scale
Assessment of pretreatment pain intensity and posttreatment pain relief was done using
the numeric rating scale (NRS); NRS with numbers from 0 to 10 (“no pain” to “worst
pain imaginable”) were evaluated for all the patients at the time of MRI and at the
time of follow-up visit after 2 weeks of course of medical therapy. Pre- and posttreatment
pain relief response scores (0 to 10) were converted into percentages (0–100%) and
then the patients were divided into two groups. Patients with posttreatment response
of equal or more than 50%, i.e., significant response, were considered showing “good
response” and those with less than 50% of posttreatment pain relief were considered
as showing “poor response” to medical management.
Statistical Analysis
Receiver operating characteristic (ROC) curve analysis was performed to determine
and reach an optimum cut-off value for the mTPA for the response to therapy. The optimum
value was thus reached to be 45 degrees. Later, Pearson's Chi-square test was performed
considering the selected angle, which was found to be statistically significant with
a p -value of 0.007, between patients with posttreatment pain relief good response (≥50%)
and poor/bad response (<50%) groups. Pearson's correlation coefficient test was also
done for two variables using posttreatment pain relief in percentage and MPA in degrees,
and the resultant R -value was −0.3366, which showed negative correlation. Thus, patients with more acute
mTPA showed better response to medical management.
Results
A total 30 cases of TN due to NVC over medial aspect of trigeminal nerve were evaluated.
Presenting age of patients varied between 22 and 82 years, including 19 males and
11 females. Majority of our patients were in 41 to 50 years (30%) and 51 to 60 years
(23.3%) age groups.
Pretreatment pain intensity and posttreatment pain relief of each patient were assessed
by using NRS. NRS with numbers from 0 to 10 (“no pain” to “worst pain imaginable”)
was used in subjective assessment of pain. As described, the posttreatment pain relief
response score (0–10) was converted into percentages (0–100%) and then patients divided
into two groups, of those showing significant or “good response” and those showing
“poor response.” These pain relief findings were correlated with the mTPA. ROC curve
analysis was performed to determine and reach an optimum cut-off value for the mTPA
for the response to therapy. The optimum value was thus reached to be 45 degrees,
and considering the same, 7 out of 8 (87.5%) patients >45° mTPA showed bad/poor response
and 15/22 (68.2%) patients ≤45° mTPA showed good response to medical management, and
found statistical significance with a p -value of 0.007. The Pearson correlation coefficient test was done for posttreatment
pain relief in percentage and mTPA, which showed a resultant R -value of −0.3366, suggesting negative correlation ([Fig. 3 ]).
Fig. 3 Statistical analytic table showing comparison data between patients with posttreatment
pain relief good response and poor/bad response groups with a trigeminopontine angle
threshold of 45 degrees, showing statistically significant correlation of the trigeminopontine
angle with the percentage reduction of pain relief, after standard medical therapy.
Discussion
A wide variety of abnormalities can lead to TN, including pathologies involving the
trigeminal nerve itself (primary) and etiologies that secondarily involve the nerve
or any one of its three branches.[1 ]
[2 ] NVC is one of the commonest causes of TN involving the cisternal portion of the
nerve. Other resultant pathologies causing TN include demyelinating diseases like
multiple sclerosis, vascular insults leading to infarcts, and tumors like glioma involving
the trigeminal nerve at any level. Trigeminal neuropathy involving the canalicular
(Meckel cave and cavernous sinus) segment are frequently due to meningiomas, trigeminal
schwannomas, epidermoid cysts, metastases, pituitary adenomas, and aneurysms. The
most common extracranial cause of TN is perineural spread of malignant tumors.[1 ]
[2 ]
The clinical findings do not permit accurate localization of pathologies; therefore,
MRI is the modality of choice to visualize the entire course of the fifth cranial
nerve and localize the pathology.[1 ]
[4 ]
[6 ]
[7 ] Commonly recognized NVC syndromes encountered in clinical practice are TN, hemifacial
spasm, and glossopharyngeal neuralgia. The first-line treatment of patients with the
aforementioned symptoms is based on conservative medical management. Patients refractory
to conservative treatment later undergo microvascular decompression with good success
rates. A long-term study of the results on TN after microsurgical vascular decompression
(Kaplan–Meier curves at 20 years) showed that cure was achieved in 88.1% of the patients
with a NVC producing a large groove on the nerve (Grade III), 78.3% of the patients
with a NVC with nerve distortion or displacement (Grade II), and 58.3% of the patients
with a NVC with simple contact on the nerve (Grade I). Therefore, preoperative visualization
of the NVC by MRI and determination of its grading are important for the therapeutic
decision.[8 ]
[9 ] There are few studies evaluating these above parameters with patient outcome on
medical management.
In our study, we correlated the degree of mTPA with posttreatment pain reduction in
medically managed patients of TN due to NVC.
The well-known visual analogue scale (VAS) and NRS for assessment of pain intensity
agree well and are equally sensitive in assessing acute pain after surgery, and they
are both superior to a four-point verbal categorical rating scale. An NRS with numbers
from 0 to 10 (“no pain” to “worst pain imaginable”) is more practical than a VAS,
easier to understand for most people, and does not need clear vision, dexterity, paper,
and pen. One can even determine the intensity of pain accurately using telephone interview,
a computerized telephone interview, and recording of NRS data by the patient directly
into the database of a computer via the telephone keyboard.[10 ] In our study we have used the NRS method for assessment of pretreatment pain intensity
and posttreatment pain relief in each patient separately. Posttreatment pain relief
response score (0–10) was converted into percentages (0–100%) and then divided into
two groups as described.
In our study, the Pearson correlation coefficient test was done for two variables
using posttreatment pain relief in percentages and MPA in degrees, which resulted
in an R -value of −0.3366, thus confirming negative correlation of mTPA with percentage of
pain relief. This finding is helpful in predicting the pain relief that could be expected
in patients with TN, by studying the mTPA. By keeping the MPA threshold of 45 degrees,
patients with more than >45° mTPA showed bad/poor response, while those with less
than or equal ≤45° mTPA showed good response to medical management for TN, which was
statistically significant at p -value of 0.007 (p < 0.01) ([Figs. 4 ] and [5 ]). Possible hypothesis of better medical management response in patients with more
acute mTPA could be attributed to shorter course of the nerve in the cistern or parallel
course of vessels along the nerve; however, this needs further research and multicenter
studies.
Fig. 4 A 46 year-old female came with complaint of electric shock like sensation on the
right side of face. (A ) Vascular loop seen compression over medial aspect of left trigeminal nerve (white arrow ). (B ) Left trigeminopontine angle 34.4°. Pretreatment pain scale: 7; posttreatment scale:
2; and posttreatment pain reduction scale: 5 (71.4%).
Fig. 5 A 39 year-old male came with complaint of electric shock like sensation on the right
side of face, very severe in intensity even with blow of air, inability to speak.
(A ) Vascular loop seen compression over medial aspect of right trigeminal nerve (arrow ). (B ) Right trigeminopontine angle 59.6°. Pretreatment pain scale: 6; posttreatment scale:
4; and posttreatment pain reduction scale: 2 (33.3%).
Limitations of our study were single institutional evaluation of patients, small sample
size, and subjective variation in pain relief scoring.
Conclusion
The high-resolution MRI directs the physicians to decision making in the plan of action
for management of TN due to NVC. Our study is a step-in direction of predicting the
outcome of medical management in patients presenting with TN, based on the mTPA. We
found a negative correlation between the mTPA and percentage pain relief in patients
kept on medical management. We realized that by keeping an angle threshold of 45 degrees,
statistically significant correlation was achieved in predicting pain relief in patients
kept on medical management, hence mTPA becoming an important parameter to be considered
for the same.
