Diagnosis of neurovascular conflict Sindou grade 1 in patients with trigeminal neuralgia using diffusion-tensor MRI

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OBJECTIVE

To diagnose microstructural changes following neurovascular conflict (NVC) Sindou grade 1 using diffusion-tensor imaging (DTI) with measurement of fractional anisotropy (FA).

MATERIAL AND METHODS

The study included 20 patients with trigeminal neuralgia, NVC Sindou grade 1 and no secondary causes of disease according to MRI data. There was no contralateral NVC. Twenty patients without facial pain comprised the control group (14 patients with unilateral NVC Sindou grade 1, 6 ones with NVC Sindou grade 2, no contralateral NVC). All patients underwent MRI (protocol of the European Academy of Neurology) with DTI and assessment of FA index. We assessed the difference in FA index between intact and symptomatic sides (∆FA). In the study group, we analyzed the relationship between ∆FA and clinical parameters. Moreover, we assessed anatomical features of pontomesencephalic cistern and structures of NVC on both sides. Qualitative data are presented in percentages. Statistical analysis included means and medians, 25 and 75 quartiles (John Tukey method). Distributions were compared using the Kruskal-Wallis and Mann-Whitney tests. We assessed the relationship between clinical parameters using the Spearman’s coefficient.

RESULTS

The ∆FA index significantly differed between both groups (p<0.001). The median ∆FA was 0.083 and 0.031, respectively. In the control group, ∆FA differed for various grades of NVC (0.013 for Sindou grade I and 0.060 for Sindou grade II).

CONCLUSION

DTI can be used as a clarifying technique to analyze microstructural changes in symptomatic trigeminal nerve in patients with classical trigeminal neuralgia and NVC Sindou grade I.

Keywords:

trigeminal neuralgia

neurovascular conflict

diffusion tensor imaging

fractional anisotropy

magnetic resonance imaging

Authors:

E.N. Rozhnova

Sklifosovsky Research Institute for Emergency Care

ORCID: 0000-0003-0521-4836

V.G. Dashyan

Sklifosovsky Research Institute for Emergency Care;
Evdokimov Moscow State University of Medicine and Dentistry

ORCID: 0000-0002-5847-9435

A.S. Tokarev

Sklifosovsky Research Institute for Emergency Care

ORCID: 0000-0002-8415-5602

O.L. Evdokimova

Sklifosovsky Research Institute for Emergency Care

ORCID: 0000-0001-8099-9544

D.A. Talypova

Sklifosovsky Research Institute for Emergency Care

ORCID: 0000-0001-7188-450X

M.V. Sinkin

Sklifosovsky Research Institute for Emergency Care;
Evdokimov Moscow State University of Medicine and Dentistry

ORCID: 0000-0001-5026-0060

Received:

02.05.2023

Accepted:

14.05.2023

List of references:

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Introduction

The International Classification of Headache Disorders (2018) determines classic trigeminal neuralgia (TN) as a nosology with MR signs of structural lesions of trigeminal root (displacement and atrophy). Idiopathic TN is diagnosed in patients with typical clinical pattern and no structural lesions. Surgical treatment differs in these situations. There is a Sindou grading system for neurovascular conflict (NVC) with 3 grades [1]. The main subject of discussion is grade 1. These patients have NVC over a short distance, but trigeminal root structure is not changed (no displacement and local atrophy). Diagnosis can be complicated by the lack of a consistent approach to slice thickness when performing MRI in FIESTA (Fast Imaging Employing Steady-State Acquisition) or CISS (Constructive Interference in Steady-State) modes.

We used diffusion-tensor imaging (DTI) with measurement of fractional anisotropy (FA) to understand true severity of NVC and diagnose microstructural changes in NVC Sindou grade 1. Anatomical features of the structures making up NVC were also taken into account.

Thus, we expected unilateral microstructural changes due to compression that is manifested by decrease of FA index [2, 3]. We also analyzed the relationship between FA and such signs as duration of disease, age, gender, VAS score of pain syndrome, duration of remission, root thickness, severity of anxiety and depression, type of pain, localization of pain syndrome.

Material and methods

The study included 20 TN patients without previous neurosurgical interventions. TN was diagnosed according to appropriate criteria (ICHD-3, 2018). VAS score of pain syndrome ranged from 0 to 10 points, age of patients — from 49 to 76 years. Male-to-female ratio was 50%/50%.

Pain syndrome Burchiel type 1 was found in 85% of patients, combination of types 1 and 2 — in other 15% of patients. Pain in the area of innervation of the third branch of trigeminal nerve was detected in 45% of patients, the 2^nd branch — 20% of patients, several branches — 35% of patients. We found right- and left-sided symptoms in 80% and 20% of cases, respectively. MRI of the brain (GE Signa HDxt 3.0 T MRI scanner) was performed according to the protocol recommended by the European Academy of Neurology [4]. The radiologist had no information about the side of disease. Scans revealed no cause for symptomatic TN. Unilateral NVC Sindou grade I was found in all patients. There were no signs of contralateral NVC.

Twenty patients without facial pain comprised the control group (14 patients with unilateral NVC Sindou grade 1, 6 ones with NVC Sindou grade 2, no contralateral NVC).

In both groups, NVC was due to superior cerebellar artery. Sex ratio and age of patients were similar in both groups. MRI protocol included DTI of trigeminal root. Axial slices passed through the middle of both nerves. We have previously described MRI technique in TN patients [5]. The region of interest (ROI) for measuring the FA index was the widest part of the middle third of trigeminal nerve. The choice of ROI was determined by localization of target area for further radiosurgery. We assessed FA index and FA difference (∆FA) between asymptomatic and symptomatic sides in both groups. ∆FA increment following lower FA in trigeminal root on one of the sides was expectable.

In both groups, we estimated trigeminal root thickness in the middle third on both sides (FIESTA axial scans) and difference in these values between asymptomatic and symptomatic sides. We also analyzed certain anatomical parameters including trigeminal root length, localization of NVC in cisternal part of trigeminal nerve, diameter of the vessel involved in NVC and anteroposterior size of pontomesencephalic cistern.

Statistical analysis

When performing analysis, we compared qualitative and quantitative indicators in both groups. Qualitative data are presented in percentages. To assess quantitative parameters, we used descriptive statistics, i.e. means, medians, 25 and 75 quartiles, 95% confidence interval. Quartiles were calculated using the John Tukey method (the 1^st quartile is the median of the lower half of data, the 3^rd quartile is the median of the upper half of data) [6]. Distributions of quantitative variables were tested for normality by the Shapiro–Wilk test. We compared 3 independent groups using the Kruskal–Wallis test, two independent groups — Mann–Whitney test. Spearman's nonparametric rank correlation coefficient (ρ) was used to assess the relationship between age, depression and anxiety.

Results

Reduced FA index on symptomatic side was detected in 90% of patients with TN and NVC Sindou grade 1 (Fig. 1). ∆FA differed significantly in both groups (p<0.001) (Fig. 2). In the main group, trigeminal nerve thinning on the side of NVC was detected in 80% of patients. Other patients had similar thickness of trigeminal nerve on both sides. However, between-side difference of trigeminal nerve thickness was similar in both groups. We found no significant differences in this value among patients of the control group with NVC Sindou grade 1 and 2. Nevertheless, we found significant difference in trigeminal nerve thickness between symptomatic side in the main group and side of NVC in the control group (p = 0.026) (Fig. 3).

Fig. 1. Correlation of FA on the damaged side in two groups is modulated by a linear trend according to the formula (figure for each curve).

At the same time, slope of the line for the main group is higher due to more significant difference in FA index.

Fig. 2. ∆FA in both groups (Me 0.083 [0.050; 0.122] and 0.031 [0.009; 0.041], respectively).

Fig. 3. Thickness of unilateral trigeminal root in both groups (Me 2.65 [2.2; 3.0] and 2.9 [2.7; 3.3] mm, respectively).

There were significant between-group difference in length of trigeminal nerve on the side of NVC (13.2 [12.3; 13.9] and 10.9 [9.5; 11.9] mm, respectively, p=0.01). Length of this nerve on symptomatic and contralateral sides was similar in the main group. No significant differences were found in anteroposterior size of pontomesencephalic cistern in the main group on the side of clinical manifestations of NVC and contralateral side. Similarly, we found no significant between-group difference in this indicator on the side of NVC. Diameter of the vessel responsible for compression was different in both groups (1.35 [1.2; 1.6] and 0.88 [0.75; 0.98] mm, respectively, p=0.01). When analyzing localization of NVC in the thirds of cisternal part on symptomatic side in the main group and side of NVC in the control group, we obtained similar data in both groups (Table).

Localization of NVC in thirds of cisternal portion in both groups

Thirds of cisternal part of trigeminal nerve	Main group	Control group
Proximal	35%	25%
Middle	45%	50%
Distal	20%	25%

Note. NVC — neurovascular conflict; rTN — root of trigeminal nerve.

In the main group, we found no significant relationship between ∆FA and such clinical parameters as gender, age, duration of disease and remission, Burchiel type of pain syndrome and lateralization of symptoms. The same data were obtained for relationship of these indicators with between-side difference of trigeminal nerve thickness. However, there was a positive correlation between localization of pain syndrome in the zone of innervation of the third branch of trigeminal nerve and ∆FA (p=0.02) (Fig. 4).

Fig. 4. Positive correlation between ∆FA and localization of pain in the zone of innervation of the third branch of trigeminal nerve (Me ∆FA = 0.058 [0.013; 0.081]). In patients with pain in the zone of innervation of the second branch — ∆FA = 0.111 [0.088; 0.133], zone of several branches — ∆FA = 0.114 [0.074; 0.202].

Patients with pain localized in the zone of innervation of the third branch of trigeminal nerve predominate in the main group (45%), but this cannot unequivocally explain our results. Interestingly, ∆FA did not differ significantly depending on the area of pain syndrome.

We compared ∆FA among patients of the control group with different Sindou grades of NVC. ∆FA differed significantly in both groups (p=0.003) (Fig. 5).

Fig. 5. Different ∆FA in the control group depending on NVC Sindou grade (grade I — Me ∆FA = 0.013 [0.007; 0.036], grade II — ∆FA = 0.060 [0.032; 0.076]).

Importantly, ∆FA is 0.083 in the study group with Sindou grade I that is higher than in the group without clinical manifestations. There were more severe morphological changes of trigeminal root in this group (FIESTA imaging).

Discussion

Among the hypotheses about the causes of classical TN, the prevailing opinion is vascular compression of trigeminal nerve (artery or vein). Neuroimaging and intraoperative data, as well as positive outcomes after microvascular decompression in most cases confirm this assumption. FIESTA imaging supplemented with 3D TOF is highly sensitive in diagnosis of NVC and its severity [2, 4]. Higher resolution of imaging was followed by appearance of data on NVC without association with clinical symptoms [7]. Many authors studied anatomical features of posterior cranial fossa to identify possible predictors of TN and its recurrence. In one of these studies, the authors compared some anatomical parameters on the side of symptoms with data on the contralateral side and in the control group. Significantly larger diameter of arteries responsible for compression was found on the side of clinical manifestations [8]. The smallest distance between the vessel and trigeminal nerve was obtained on the side of neuralgia. Length of compression was also greater on the symptomatic side. Minimal length of trigeminal nerve between trigeminal root entry zone and contact with the vessel was significant. In another study, authors identified the following anatomical risk factors of TN: smaller size and asymmetry of pontomesencephalic cistern on the side of clinical manifestations compared to the control group, larger intertrigeminal angle and shortening of trigeminal nerve on the symptomatic side compared to the contralateral side [9]. Data on diameter of the vessel responsible for NVC are contradictory. However, many authors agree on such a significant factor for TN as severity of compression [10–12]. Some authors emphasize an importance of NVC localization for TN. Root entry zone is especially sensitive, although another localization of NVC in cisternal segment is not excluded [13, 14].

Local atrophy is a sign of demyelination following long-standing compression. FA is an integral value of diffusion in certain ROI. Many studies devoted to this biomarker define FA as a sign of microstructural changes [15, 16]. Reduced FA on the side of clinical manifestations is assumed due to local demyelination under the influence of pulsating vessel [2, 17]. Some authors described pain relief after microvascular decompression despite no obvious neuroimaging data in favor of NVC [2]. Moreover, FA decrease on the side of symptoms was confirmed in patients with TN. The authors recognized this fact as a sign of microstructural disorders and indirect confirmation of NVC. Accordingly, elimination of immediate cause of disease after surgery led to clinical improvement. In their study, the authors describe absolute values of FA on each side.

In our study, we evaluated ∆FA in patients with minimum nerve compression and no visible morphological changes in trigeminal root (3D FIESTA imaging). We also tried to take into account anatomical features of posterior cranial fossa as much as possible. Of these, diameter of the vessel responsible for compression on the side of NVC differed significantly between groups. Indeed, this vessel had a larger diameter in the main group. There were no significant differences in trigeminal nerve length on the side of clinical manifestations and contralateral side. However, some authors found shorter trigeminal nerve on the side of TN [9]. The authors also described smaller dimension of pontomesencephalic cistern on the side of disease compared to the control group. In our study, dimension of cistern on the side of pain syndrome did not significantly differ from that on the contralateral side in main group and on the side of NVC in the control group. Perhaps, combination of narrow cistern and trigeminal nerve shortening can lead to more severe structural changes in trigeminal root visible during MRI and classified as Sindou grade II and III. In neurovascular conflict Sindou grade 1, the majority of anatomical parameters of posterior cranial fossa did not differ from contralateral side or side of NVC in the control group.

In the control group, ∆FA in patients with NVC Sindou grade II was significantly lower than in patients with clinical manifestations and less visible structural changes (Sindou grade I). This suggests that NVC itself may be one of the predisposing factors for TN, and not the cause. This issue requires further study. This looks especially realistic on the background of data on genetically determined channelopathies determining disruption of transport ion systems. These abnormalities are common in patients with clinical manifestations of TN [18].

Conclusion

DTI with FA measurement can be used as a clarifying technique to analyze microstructural changes in symptomatic trigeminal nerve in patients with classical trigeminal neuralgia and NVC Sindou grade I. Median ∆FA between intact side and side of clinical manifestations is 0.083 [0.050; 0.122]. The causes of reduced FA in the absence of visible morphological changes in trigeminal nerve require further study.

The authors declare no conflicts of interest.