DOI: 10.1148/radiol.2382042214
(Radiology 2006;238:689-692.)
© RSNA, 2006
Nerve Atrophy in Severe Trigeminal Neuralgia: Noninvasive Confirmation at MR Imaging—Initial Experience1
Sami H. Erbay, MD,
Rafeeque A. Bhadelia, MD,
Mark O'Callaghan, MD,
Punita Gupta, MD, MPH,
Ron Riesenburger, MD,
Warren Krackov, MD and
Joseph F. Polak, MD, MPH
1 From the Departments of Radiology (S.H.E., R.A.B., M.O., P.G., W.K., J.F.P.) and Neurosurgery (R.R.), Tufts-New England Medical Center, 750 Washington St, Boston, MA 02467. Received December 30, 2004; revision requested March 3, 2005; revision received April 13; accepted May 9. Supported in part by grants NIH 5RO1AG021790-03 and RO1-HL-0690036-02.
Address correspondence to S.H.E. (e-mail: serbay{at}tufts-nemc.org).
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ABSTRACT
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Purpose: To retrospectively evaluate the size of the trigeminal nerve on magnetic resonance (MR) images of patients with unilateral trigeminal neuralgia.
Materials and Methods: Institutional review board approval was obtained and informed consent was waived for this HIPAA-compliant study. The sizes of the trigeminal nerves in 31 patients (18 men and 13 women; mean age, 68 years; age range, 44–84 years) with clinically confirmed intractable unilateral trigeminal neuralgia were measured before treatment with gamma knife radiosurgery. Images were analyzed separately by two neuroradiologists who were blinded to the side of the face with symptoms. Coronal projection images were used to determine the diameter and cross-sectional area of the trigeminal nerves at 5 mm from the entry point of the nerve into the pons. Comparisons were made by using a paired t test. Interobserver variability was assessed by using the Pearson correlation coefficient.
Results: The mean diameter of the trigeminal nerve on the symptomatic side was significantly smaller than the mean diameter on the asymptomatic side in 30 of 31 patients (2.11 mm ± 0.40 [standard deviation] and 2.62 mm ± 0.56, P < .001, 95% confidence interval: –0.35, –0.67 mm). The mean cross-sectional area on the symptomatic side was significantly smaller than the area on the asymptomatic side in 27 of 31 patients (4.50 mm2 ± 1.75 and 6.28 mm2 ± 2.19, P < .001, 95% confidence interval: –2.41, –1.16 mm2).
Conclusion: The results indicate that trigeminal nerve atrophy can be depicted noninvasively in patients with trigeminal neuralgia.
© RSNA, 2006
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INTRODUCTION
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There is strong evidence that trigeminal neuralgia is related to structural changes in the trigeminal nerve, which are likely a result of neurovascular compression (1–5). Morphologic changes in the nerve include nerve distortion, deviation, atrophy, and groove formation. Atrophy of the nerve is seen in most cases of trigeminal neuralgia and is likely secondary to structural abnormalities, such as axonal loss and demyelination (2,3). Atrophy is believed to be the source of abnormal contacts among nerve fibers and the cause of the paroxysmal pain experienced by patients with trigeminal neuralgia. Nerves on the affected side of the face appear small at surgery or when measured on pathologic specimens.
We hypothesized that nerve atrophy should be detectable at magnetic resonance (MR) imaging in patients known to have trigeminal neuralgia. Thus, the purpose of our study was to retrospectively evaluate the size of each trigeminal nerve on MR images of patients with unilateral trigeminal neuralgia.
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MATERIALS AND METHODS
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Patients
Our study initially included 36 consecutive patients scheduled to undergo gamma knife radiosurgery for trigeminal neuralgia over a 24-month period (December 1999 to December 2001). All of the patients had been evaluated at MR imaging, and trigeminal neuralgia was diagnosed in all of the patients on the basis of neurologic evaluation results and typical symptoms, such as intermittent lancinating pain in the distribution of a division of the trigeminal nerve. All patients had been symptomatic for a minimum of 6 months, and prior medical therapy had failed.
Among the initial 36 patients, we excluded one patient who previously underwent posterior fossa exploration and trigeminal nerve decompression and one patient with bilateral symptoms. In three patients, the measurements could not be obtained because there was no clear-cut separation of the nerve from the surrounding vessels. The study cohort therefore was composed of 18 men and 13 women with a mean age of 68 years (range, 44–84 years). None of the patients had clinical or imaging evidence of any posterior fossa mass or of multiple sclerosis. Our institutional review board approved this study and waived the requirement of informed consent. The study was compliant with the regulations of the Health Insurance Portability and Accountability Act.
Imaging Examinations
All patients were imaged with a 1.5-T magnet (Symphony; Siemens, Erlangen, Germany) with 20 mT/m gradients. The routine gamma knife planning protocol consisted of gadolinium-enhanced (Magnevist; Berlex Laboratories, Wayne, NJ) T1-weighted coronal and sagittal localizer imaging, followed by transverse constructive interference in steady state (CISS) and magnetization-prepared rapid acquisition gradient-echo imaging. In this study, only transverse CISS images (repetition time, 17 msec; echo time, 8.3 msec [17/8.3]; flip angle, 70°; section thickness, 1 mm; slab thickness, 60 mm; matrix, 256 x 256; and field of view, 180 x 180 mm) were used to obtain coronal reformatted images for evaluation of nerve size. Although the CISS images are T2 weighted and do not require gadolinium enhancement, gadolinium-based contrast material was injected before the patient was placed in the MR imager, to avoid possible patient motion that could interfere with gamma knife radiosurgery planning.
Image Analysis
Images were transferred to a workstation for postprocessing and analysis. Coronal reformatted images of the trigeminal nerve were generated with a section thickness of 0.5 mm and without an intersection gap. The reformatted images were magnified to facilitate measurements of diameter and cross-sectional area of each trigeminal nerve by using a mouse-driven cursor. No adjustments for magnification were required because the measurement program of the workstation automatically corrects for magnification. Two neuroradiologists (S.H.E., R.A.B.) with 8–12 years of experience interpreting MR images were blinded to the side of the face with symptoms and independently obtained maximum diameter and cross-sectional area measurements of both trigeminal nerves on the same section of the coronal reformatted image at 5 mm from the entry of the trigeminal nerve into the pons. The neuroradiologists followed the trigeminal nerves to their entry into the pons to distinguish nerves from vessels in the region. If the nerve was not clearly shown as separate from the adjacent vasculature at 5 mm from its entry into the pons, the immediately adjacent image was used. The two neuroradiologists independently determined the coronal section used for measurements.
Statistical Analysis
The measurements made by each observer were averaged. Comparisons of diameters and cross-sectional areas were made between the symptomatic trigeminal nerves and asymptomatic trigeminal nerves by using a paired t test. Standard statistical software (JMP, version 4.0.2; SAS Institute, Cary, NC) was used. Interobserver variability was assessed by using the Pearson correlation coefficient. P values of .05 or less were considered to indicate statistically significant differences.
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RESULTS
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Diameter
The mean diameter of the trigeminal nerves (Table 1, Fig 1) on the symptomatic side was significantly smaller than the mean diameter of the trigeminal nerves on the asymptomatic side (2.11 mm ± 0.40 [standard deviation] compared with 2.62 mm ± 0.56, P < .001). In 30 of the 31 patients, the diameter of the nerve on the symptomatic side was smaller than the diameter of the nerve on the asymptomatic side (mean difference, –0.51 mm ± 0.43; 95% confidence interval: –0.35, –0.67 mm).
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Figure 1: Coronal reformatted image of the brain. CISS MR image (17/8.3) at the level of the ambient cistern reveals trigeminal nerve on right (left arrow) is smaller than trigeminal nerve on left (right arrow).
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Cross-sectional Area
The mean cross-sectional area of the trigeminal nerves (Table 2, Fig 2) on the symptomatic side was significantly smaller than the mean cross-sectional area of the trigeminal nerves on the asymptomatic side (4.50 mm2 ± 1.75 compared with 6.28 mm2 ± 2.19; P < .001). In 27 of the 31 patients, the cross-sectional area of the nerves on the symptomatic side was smaller than the cross-sectional area of the nerves on the asymptomatic side (mean difference, –1.78 mm2 ± 1.7; 95% confidence interval: –2.41, –1.16 mm2).
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Table 2. Trigeminal Nerve Cross-sectional Areas in 31 Patients as Measured on Coronal Reformatted Images by Two Observers
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Figure 2: Detail view of coronal reformatted image of the brain. CISS MR image (17/8.3) at the level of the ambient cistern shows the regions of interest used to measure the trigeminal nerve cross-sectional area. 1 = contralateral unaffected nerve, 2 = affected nerve.
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Interobserver Agreement
The Pearson correlation coefficients for measurements made by both observers were 0.60 for nerve diameter measurements and 0.78 for estimated nerve cross-sectional area.
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DISCUSSION
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Our study indicates that trigeminal nerves on the side of symptoms are smaller than trigeminal nerves on the side without symptoms in patients with severe trigeminal neuralgia. These observed differences, obtained noninvasively, concur with observations made during surgery and from pathologic samples of diseased trigeminal nerves (2,3,5).
Trigeminal neuralgia is the most frequent cranial neuralgia; it manifests as episodic and recurrent facial pain and has an incidence of four or five cases per 100,000 (6,7). A typical patient is 50–70 years old and more commonly a woman. The excruciating pain lasts for seconds and usually is located in the maxillary or mandibular branch distribution of the trigeminal nerve (8). A younger age at the onset of symptoms, sensory-motor deficits, or atypical distribution of pain may indicate the presence of an underlying lesion, such as a tumor (9).
Trigeminal neuralgia frequently poses a diagnostic dilemma due to the limited understanding of its pathophysiology and the lack of a diagnostic reference standard (10). MR imaging has been used in the diagnosis of trigeminal neuralgia refractory to medical therapy (11–15). MR imaging helps in the diagnosis of trigeminal neuralgia by excluding mass lesions or lesions typical of multiple sclerosis as a cause of trigeminal neuralgia.
MR imaging has been used to investigate whether neurovascular contact by an artery or a vein at the root entry zone of the trigeminal nerve (11–14) is linked to trigeminal neuralgia. Innocent juxtaposition of the trigeminal nerve and vessels, however, has been clearly shown in cadaver studies and MR imaging studies (5,12). These findings make such an evaluation unreliable for diagnostic purposes.
Pathologic findings of nerve samples from patients with trigeminal neuralgia show evidence of axonal loss, axonopathy, demyelination, dysmyelination, residual myelin debris, and collagen deposition (3,5). The resulting structural disarray and electrical instability are hypothesized to cause abnormal contacts between nerve fibers and to cause the pain paroxysms. The electrophysiologic manifestations of trigeminal neuralgia, such as ectopic impulse discharge, spontaneous and triggered after-discharge, and cross-excitation among neighboring afferents, can be explained by this hypothesis (2).
In the majority of cases, the loss of nerve tissue is believed to be secondary to chronic compression of the nerve by aging and tortuous vessels along the course of the nerve after its point of exit from the brainstem. Up to 42% of symptomatic nerves have gross atrophy that can be directly visualized at surgery (2).
The average diameter of the unaffected trigeminal nerve has been estimated on transverse MR images to be 4 mm, with the range being 2–6 mm (15). Our diameter measurements obtained on coronal images, although within this range, are on the lower side. We believe that this is most likely a result of differences in measurement technique between our study and that of Jawahar et al. In our study, we found nerves on the symptomatic side to be approximately 20% smaller than those on the asymptomatic side.
Cross-sectional area measurements of the nerves might be more valuable than diameter measurements given the higher interobserver agreement of the former observed in our study. In our study, the mean cross-sectional area of nerves on the asymptomatic sides was 6.3 mm2, and the mean cross-sectional area of the nerves on the symptomatic sides was 4.5 mm2. In four of 31 patients, however, cross-sectional areas of the affected trigeminal nerve were larger than cross-sectional areas of the unaffected trigeminal nerve, whereas only one patient had a diameter of the affected trigeminal nerve that was larger than the diameter of the unaffected trigeminal nerve. This loss of specificity may be a result of our small sample size or may be due to difficulties in properly finding an image plane perfectly perpendicular to the course of the nerve. Further improvements in image resolution might correct this limitation.
Another study limitation may be a selection bias in our patient population. The entry criteria for acceptance for possible gamma knife radiosurgery was a history of at least 6 months of persistent symptoms and a lack of response to other medical interventions. As such, we may have evaluated patients with a more advanced form of the disease. Larger studies with a prospective design are needed to confirm our findings.
In conclusion, noninvasive measurements of trigeminal nerve size obtained from MR images show evidence of nerve atrophy on the side affected by severe trigeminal neuralgia.
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FOOTNOTES
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Abbreviations: CISS = constructive interference in steady state
Author contributions: Guarantor of integrity of entire study, S.H.E., M.O.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, S.H.E., R.A.B.; clinical studies, all authors; statistical analysis, S.H.E., M.O., P.G., J.F.P.; and manuscript editing, all authors
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ABSTRACT
INTRODUCTION
