Olfactory-trigeminal integration in the primary olfactory cortex.

Humans naturally integrate signals from the olfactory and intranasal trigeminal systems. A tight interplay has been demonstrated between these two systems, and yet the neural circuitry mediating olfactory-trigeminal (OT) integration remains poorly understood. Using functional magnetic resonance imaging (fMRI), combined with psychophysics, this study investigated the neural mechanisms underlying OT integration. Fifteen participants with normal olfactory function performed a localization task with air-puff stimuli, phenylethyl alcohol (PEA; rose odor), or a combination thereof while being scanned. The ability to localize PEA to either nostril was at chance. Yet, its presence significantly improved the localization accuracy of weak, but not strong, air-puffs, when both stimuli were delivered concurrently to the same nostril, but not when different nostrils received the two stimuli. This enhancement in localization accuracy, exemplifying the principles of spatial coincidence and inverse effectiveness in multisensory integration, was associated with multisensory integrative activity in the primary olfactory (POC), orbitofrontal (OFC), superior temporal (STC), inferior parietal (IPC) and cingulate cortices, and in the cerebellum. Multisensory enhancement in most of these regions correlated with behavioral multisensory enhancement, as did increases in connectivity between some of these regions. We interpret these findings as indicating that the POC is part of a distributed brain network mediating integration between the olfactory and trigeminal systems. PRACTITIONER POINTS: Psychophysical and neuroimaging study of olfactory-trigeminal (OT) integration. Behavior, cortical activity, and network connectivity show OT integration. OT integration obeys principles of inverse effectiveness and spatial coincidence. Behavioral and neural measures of OT integration are correlated.

A novel indicator to predict the outcome of percutaneous stereotactic radiofrequency rhizotomy for trigeminal neuralgia patients: diffusivity metrics of MR-DTI.

Magnetic resonance-diffusion tensor imaging (MR-DTI) has been used in the microvascular decompression and gamma knife radiosurgery in trigeminal neuralgia (TN) patients; however, use of percutaneous stereotactic radiofrequency rhizotomy (PSR) to target an abnormal trigeminal ganglion (ab-TG) is unreported. Fractional anisotropy (FA), mean and radial diffusivity (MD and RD, respectively), and axial diffusivity (AD) of the trigeminal nerve (CNV) were measured in 20 TN patients and 40 healthy control participants immediately post PSR, at 6-months, and at 1 year. Longitudinal alteration of the diffusivity metrics and any correlation with treatment effects, or prognoses, were analyzed. In the TN group, either low FA (value < 0.30) or a decreased range compared to the adjacent FA (dFA) > 17% defined an ab-TG. Two-to-three days post PSR, all 15 patients reported decreased pain scores with increased FA at the ab-TG (P < 0.001), but decreased MD and RD (P < 0.01 each). Treatment remained effective in 10 of 14 patients (71.4%) and 8 of 12 patients (66.7%) at the 6-month and 1-year follow-ups, respectively. In patients with ab-TGs, there was a significant difference in treatment outcomes between patients with low FA values (9 of 10; 90%) and patients with dFA (2 of 5; 40%) (P < 0.05). MR-DTI with diffusivity metrics correlated microstructural CNV abnormalities with PSR outcomes. Of all the diffusivity metrics, FA could be considered a novel objective quantitative indicator of treatment effects and a potential indicator of PSR effectiveness in TN patients.

Central vein sign and trigeminal lesions of multiple sclerosis visualised by 7T MRI.

BACKGROUND: Although trigeminal nerve involvement is a characteristic of multiple sclerosis (MS), its prevalence across studies varies greatly due to MRI resolution and cohort selection bias. The mechanism behind the site specificity of trigeminal nerve injury is still unclear. We aim to determine the prevalence of trigeminal nerve involvement in patients with MS in a consecutive 7T brain MRI cohort. METHODS: This observational cohort originates from an ongoing China National Registry of Neuro-Inflammatory Diseases. Inclusion criteria were the following: age 18 years or older, diagnosis of MS according to the 2017 McDonald criteria and no clinical relapse within the preceding 3 months. Each participant underwent 7T MAGNETOM Terra scanner (Siemens, Erlangen, Germany), using a 32-channel phased array coil at Beijing Tiantan Hospital. T1-weighted magnetisation-prepared rapid acquisition gradient echoes, fluid-attenuated inversion recovery (FLAIR) and fluid and white matter suppression images were used to identify lesions. FLAIR* and T2* weighted images were used to identify central vein sign (CVS) within the trigeminal lesions. RESULTS: 120 patients underwent 7T MRI scans between December 2021 and May 2023. 19/120 (15.8%) patients had a total of 45 trigeminal lesions, of which 11/19 (57.9%) were bilateral. The linear lesions extended along the trigeminal nerve, from the root entry zone (REZ) (57.8%, 26/45) to the pontine-medullary nucleus (42.2%, 19/45). 26.9% (7/26) of the lesions in REZ showed a typical central venous sign. CONCLUSION: In this 7T MRI cohort, the prevalence of trigeminal nerve involvement was 15.8%. Characteristic CVS was detected in 26.9% of lesions in REZ. This suggests an inflammatory demyelination mechanism of trigeminal nerve involvement in MS.

Radiosurgical Decompression of Trigeminal Nerve and Its Correlation with Functional Outcome in Tumor-Related Trigeminal Neuralgia.

BACKGROUND: Target selection during Gamma Knife radiosurgery (GKRS) in cases of tumor-related trigeminal neuralgia is always debatable. We analyzed the correlation of regression of tumor size and degree of release of the nerve with long-term pain control. METHODS: Between March 2012 and March 2023, 50 cases of tumor-related trigeminal neuralgia were treated with GKRS (tumor was targeted). Radiological findings after GKRS were categorized into 3 types: 1) tumor volume remained same or decreased, additional segment of nerve not seen; 2) tumor volume decreased, additional segment of trigeminal nerve seen, but tumor still adherent to the nerve; 3) tumor volume decreased, adjacent nerve seen completely separated from tumor. Pain score before and after GKRS (Barrow Neurological Institute I-III: good; Barrow Neurological Institute IV and V: poor) was correlated with these subgroups. RESULTS: At median follow-up of 46.5 months, 18 cases showed type 1 radiological response, 23 showed type 2 response, and 9 showed type 3 response. Good pain control was achieved in 10 (55.5%) patients with type 1, 15 (65.21%) with type 2, and 7 (77.8%) with type 3 responses. The outcome differences among these 3 groups were not statistically significant (P = 0.519). Five patients with type 3 radiological response were off medication, which was statistically better than type 1 and type 2 radiological responses, with 3 patients (P = 0.012) and 2 patients (P = 0.002), respectively, still receiving medication. CONCLUSIONS: Tumor volume reduction after GKRS may be associated with good pain control in tumor-related trigeminal neuralgia. Further, this allows visualization of additional segment of nerve that can be targeted in a second session for treating recurrent or failed cases.

Neuronavigation-Specific Parameters for Selective Access of Trigeminal Rootlets in Radiofrequency Lesioning: A Cadaveric Morphometric Study.

BACKGROUND AND OBJECTIVE: Radiofrequency lesioning (RFL) is a safe and effective treatment for medically refractory trigeminal neuralgia. Despite gaining mainstream neurosurgical acceptance in the 1970s, the technique has remained relatively unchanged, with the majority of series using lateral fluoroscopy over neuronavigation for cannula guidance. To date, there are no studies describing neuronavigation-specific parameters to help neurosurgeons selectively target individual trigeminal rootlets. In this cadaveric study, we sought to provide a neuronavigation-specific morphometric roadmap for selective targeting of individual trigeminal rootlets. METHODS: Embalmed cadaveric specimens were registered to cranial neuronavigation. Frontotemporal craniotomies were then performed to facilitate direct visualization of the Gasserian ganglion. A 19-gauge cannula was retrofit to a navigation probe, permitting real-time tracking. Using preplanned trajectories, the cannula was advanced through foramen ovale (FO) to the navigated posterior clival line (nPCL). A curved electrode was inserted to the nPCL and oriented inferolaterally for V3 and superomedially for V2. For V1, the cannula was advanced 5 mm distal to the nPCL and the curved electrode was reoriented inferomedially. A surgical microscope was used to determine successful contact. Morphometric data from the neuronavigation unit were recorded. RESULTS: Twenty RFL procedures were performed (10R, 10L). Successful contact with V3, V2, and V1 was made in 95%, 90%, and 85% of attempts, respectively. Mean distances from the entry point to FO and from FO to the clival line were 7.61 cm and 1.26 cm, respectively. CONCLUSION: In this proof-of-concept study, we found that reliable access to V1-3 could be obtained with the neuronavigation-specific algorithm described above. Neuronavigation for RFL warrants further investigation as a potential tool to improve anatomic selectivity, operative efficiency, and ultimately patient outcomes.

Efficacy of MR Neurography of Peripheral Trigeminal Nerves: Correlation of Sunderland Grade versus Neurosensory Testing.

BACKGROUND AND PURPOSE: The current reference standard of diagnosis for peripheral trigeminal neuropathies (PTN) is clinical neurosensory testing (NST). MR neurography (MRN) is useful for PTN injury diagnosis, but it has only been studied in small case series. The aim of this study was to evaluate the agreement of Sunderland grades of nerve injury on MRN and NST by using surgical findings and final diagnoses as reference standards. MATERIALS AND METHODS: A total of 297 patient records with a chief complaint of PTN neuralgia were identified from the university database, and 70 patients with confirmed NST and MRN findings who underwent surgical nerve repair were included in the analysis. Cohen weighted kappa was used to calculate the strength of the agreement between the 3 modalities. RESULTS: There were 19 men and 51 women, with a mean age of 39.6 years and a standard deviation of 16.9 years. Most (51/70, 73%) injuries resulted from tooth extractions and implants. MRN injury grades agreed with surgical findings in 84.09% (37/44) of cases, and NST injury grades agreed with surgical findings in 74.19% (23/31) of cases. MRN and NST both showed similar agreement with surgery for grades I to III (70% and 71.43%). However, MRN showed a higher rate of agreement with surgery (88.24%) for injury grades IV and V than did NST (75%). CONCLUSIONS: MRN can objectively improve preoperative planning in patients with higher-grade nerve injuries.

Application of Sequential Thresholding-Based Automated Reconstruction of the Trigeminal Nerve in Trigeminal Neuralgia.

OBJECTIVE: High-resolution magnetic resonance imaging (MRI) of the trigeminal nerve is indispensable for workup of trigeminal neuralgia (TN) before microvascular decompression; however, the evaluation is often subjective and prone to variability. We aim to develop and assess sequential thresholding-based automated reconstruction of the trigeminal nerve (STAR-TN) as an algorithm for segmenting the trigeminal nerve and contacting structures that will allow for a structured method for assessing neurovascular conflict. METHODS: A total of 42 patients with TN who underwent high-resolution MRI before microvascular decompression in 2022 were included in our study. Segmentation of the trigeminal nerve and contacting structures was performed on preoperative MRI scans using STAR-TN. The segmentations were then evaluated for neurovascular conflict and compared to the preoperative radiology and operative notes. Geometric features, including the area of contact and distance to conflict, were extracted. RESULTS: Of the 42 patients, 32 (76.2%) were found to show neurovascular conflict based solely on their STAR-TN segmentations and 10 (23.8%) were found to not show neurovascular conflict. Compared with the intraoperative findings, this resulted in a sensitivity of 78.0% and specificity of 100%. In contrast, assessments of neurovascular conflict by radiologists using only 2-dimensional MRI views had a sensitivity of 68.3% and specificity of 100%. Of the 32 patients with neurovascular conflict, 29 (90.9%) had conflict within the root entry zone. Overall, the patients had a median area of contact of 10.66 mm2. CONCLUSIONS: STAR-TN allows for 3-dimensional visualization and identification of neurovascular conflict with improved sensitivity compared with neuroradiologist assessments from MRI slices.

The Sagittal Angle of the Trigeminal Nerve at the Porus Trigeminus is a Radiologic Predictor of Surgical Outcome in Microvascular Decompression for Classical Trigeminal Neuralgia.

BACKGROUND AND OBJECTIVES: Classical trigeminal neuralgia (cTN) is a painful disease. Microvascular decompression (MVD) provides immediate and durable relief in many patients. A variety of positive and negative prognostic biomarkers for MVD have been identified. The sagittal angle of the trigeminal nerve at the porus trigeminus (SATNaPT) is an MRI biomarker that can identify a subset of patients with cTN whose trigeminal nerve anatomy is different from normal controls. The purpose of this case-control study was to determine whether an abnormally hyperacute SATNaPT is a negative prognostic biomarker in patients with cTN undergoing MVD. METHODS: Preoperative MRIs from 300 patients with cTN who underwent MVD were analyzed to identify patients with a hyperacute SATNaPT (defined as less than 3 SDs below the mean). The rate of surgical success (pain-free after at least 12 months) was compared between patients with a hyperacute SATNaPT and all other patients. RESULTS: Patients without a hyperacute SATNaPT had an 82% likelihood of surgical success, whereas patients with a hyperacute SATNaPT had a 58% likelihood of surgical success ( P < .05). Patients with a hyperacute SATNaPT who also had no evidence of vascular compression on preoperative MRI had an even lower likelihood of success (29%, P < .05). CONCLUSION: In patients with cTN being considered for MVD, a hyperacute SATNaPT is a negative prognostic biomarker that predicts a higher likelihood of surgical failure. Patients with a hyperacute SATNaPT, particularly those without MRI evidence of vascular compression, may benefit from other surgical treatments or a modification of MVD to adequately address the underlying cause of cTN.

Independent association of the Meckel's cave with trigeminal neuralgia and development of a screening tool.

PURPOSE: To 1) investigate the association of the properties of the Meckel's cave (MC) with TN occurrence (i.e., affected vs. unaffected nerves) and whether such association was independent of neurovascular contact (NVC); and 2) develop an objective screening tool for TN. MATERIALS AND METHODS: Two hundred and nineteen trigeminal nerves were included. (The severity of) NVC was identified for individual nerve, and a set of 107 radiomic features were extracted to characterize various properties of each MC. Both procedures were primarily based on magnetic resonance imaging sequences. A radiomic score (Rad-score) was constructed for each MC to integrate the features associated with TN occurrence. Independent t-test and logistic regression were conducted to assess the association and develop the screening tool mentioned above. RESULTS: Twelve features were selected to build the Rad-score, with the Inverse Difference Moment Normalized (IDMN) having the greatest weight. The Rad-score was significantly (p ≤ 0.05) higher in the affected compared to the unaffected nerves, irrespective of NVC. The Rad-score and NVC were incorporated in the regression model/screening tool, which demonstrated an acceptable discriminating ability (C-statistic = 0.84). CONCLUSION: This study has identified a potential association of the properties/features of the MC with TN occurrence, probably involving the demyelination and axonal injury of the trigeminal ganglion within the MC as suggested by the IDMN. Such association may be independent of NVC. This finding may provide new insight into the etiology and/or pathophysiology of TN. The screening tool, which demonstrated an acceptable discriminating ability, may contribute to an improvement in its diagnosis.

Probabilistic tractography of the extracranial branches of the trigeminal nerve using diffusion tensor imaging.

PURPOSE: The peripheral course of the trigeminal nerves is complex and spans multiple bony foramen and tissue compartments throughout the face. Diffusion tensor imaging of these nerves is difficult due to the complex tissue interfaces and relatively low MR signal. The purpose of this work is to develop a method for reliable diffusion tensor imaging-based fiber tracking of the peripheral branches of the trigeminal nerve. METHODS: We prospectively acquired imaging data from six healthy adult participants with a 3.0-Tesla system, including T2-weighted short tau inversion recovery with variable flip angle (T2-STIR-SPACE) and readout segmented echo planar diffusion weighted imaging sequences. Probabilistic tractography of the ophthalmic, infraorbital, lingual, and inferior alveolar nerves was performed manually and assessed by two observers who determined whether the fiber tracts reached defined anatomical landmarks using the T2-STIR-SPACE volume. RESULTS: All nerves in all subjects were tracked beyond the trigeminal ganglion. Tracts in the inferior alveolar and ophthalmic nerve exhibited the strongest signal and most consistently reached the most distal landmark (58% and 67%, respectively). All tracts of the inferior alveolar and ophthalmic nerve extended beyond their respective third benchmarks. Tracts of the infraorbital nerve and lingual nerve were comparably lower-signal and did not consistently reach the furthest benchmarks (9% and 17%, respectively). CONCLUSION: This work demonstrates a method for consistently identifying and tracking the major nerve branches of the trigeminal nerve with diffusion tensor imaging.

Diffusion tensor and kurtosis imaging reveal microstructural changes in the trigeminal nerves of patients with trigeminal neuralgia.

OBJECTIVES: To evaluate the use of diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) for detection of microstructural changes in the trigeminal nerves of trigeminal neuralgia (TN) patients. METHODS: Forty TN patients and 40 healthy controls were examined using 3 T magnetic resonance imaging (MRI) to evaluate DTI and DKI parameters in trigeminal nerves. One-way ANOVA was used to test the differences in age, sex, and DTI and DKI parameters between the TN-affected sides, TN-unaffected sides, and controls. For parameters with inter-group differences, pairwise comparisons were performed. Then, the difference ratios (DRs) of the parameters with statistical differences were calculated and used for the receiver operating characteristic (ROC) analysis to assess their diagnostic performance. In addition, for the DTI and DKI parameter values with differences, we used pure DTI and DKI values to perform the ROC analysis. RESULTS: Compared to the unaffected sides and controls, the FA, MK, and Kr of the affected sides of TN patients were significantly reduced, while ADC was significantly increased (p < 0.05). The diagnostic efficiency of the FA DRs (AUC: 0.974; cutoff value: 0.038; sensitivity: 100%; specificity: 95.0%) was the highest among all DTI and DKI parameters. The DRs of FA and MK more efficiently diagnosed TN than pure FA and MK values. CONCLUSIONS: DTI and DKI allowed detection of microstructural changes in TN-affected trigeminal nerves. FA DR was the best independent predictor of microstructural changes in TN. CLINICAL RELEVANCE STATEMENT: Both DTI and DKI can be used for noninvasive quantitative evaluation of the changes in the microstructure of the cisternal segment of the cranial nerves in clinical practice. KEY POINTS: • Diffusion tensor imaging (DTI) can be used to evaluate the in vivo integrity of white matter and nerve fiber pathway. • Diffusion kurtosis imaging (DKI) has been shown to be considerable sensitive to microstructural changes. • DTI combined with DKI can comprehensively evaluate the status of the TN-affected trigeminal nerve.

Comparative Anatomic Study Between Intradural Suboccipital Retrosigmoid and Extradural Transzygomatic Middle Fossa Approaches to Expose the Trigeminal Nerve.

BACKGROUND: Meckel cave tumors are relatively rare, especially trigeminal nerve (TN) schwannomas. These tumors frequently project through the trigeminal pore, occupying the middle and posterior fossae. The most used routes to this region are the suboccipital retrosigmoid intradural approach (SORSA) and the transzygomatic middle fossa approach (TZMFA). Both approaches allow further exposure by adding intraoperative techniques, such as removing the suprameatal tubercle (retrosigmoid intradural suprameatal approach [RISA]) and the petrous apex (TZMFA-PA), respectively. This study aims to understand how TN exposure differs between both surgical approaches and how it increases by adding specific surgical maneuvers to these techniques. METHODS: Five formalin-fixed adult cadaver heads were submitted to high-resolution computed tomography and their images were loaded into the neuronavigation device. Anatomic key points were defined along the outline of the TN, and their three-dimensional spatial locations were collected following each surgical approach. This process allowed the calculation of the TN exposed area obtained through each technique. RESULTS: The mean areas of exposure of the TN were 125.9 mm2 with SORSA and 208.9 mm2 with RISA, which represents an additional mean gain of 61.92% (P = 0.047). Using TZMFA, a mean exposure of 419.24 mm2 was obtained. When TZMFA-PA was used, the mean exposed area was 486.03 mm2, representing a mean gain in the exposure area of 16.81% (P = 0.072). CONCLUSIONS: Our study suggests that TZMFA allows better exposure of TN ganglionic and postganglionic segments, and the removal of the PA adds the preganglionic segment visualization, although with less TN exposed area compared with RISA. With SORSA, the additional suprameatal tubercle removal shows the trigeminal pore and the medial margin of the central portion of the TN ganglionic segment, making it possible to expose the mouth of the Meckel cave and part of its contents.

Trigeminal hybrid nerve sheath tumor - a case report and literature review.

BACKGROUND: Hybrid nerve sheath tumors (HNST) contain elements of more than one established sub-type of nerve sheath tumor and have been recently recognized in the 2016 WHO classification of central nervous system tumors. While common in the peripheral nerves and extracranial branches of cranial nerves, only one case has been previously documented of an intracranial HNST arising from a cranial nerve. CASE DESCRIPTION: We describe a large, multi-compartmental intracranial hybrid nerve sheath tumor arising from the trigeminal nerve in a 22-year-old lady who presented with clinical and radiological features suggestive of a right cerebellopontine angle mass. Histopathological examination following retrosigmoid excision of the tumor revealed histological and immunohistochemical features of a schwannoma and a perineurioma. CONCLUSIONS: HNSTs are likely to be underreported in the intracranial region. The clinical course of these tumors and the reason for their occurrence in this location are not known.

Primary neurolymphomatosis of the trigeminal nerve.

We report a case of a primary malignant lymphoma of the trigeminal nerve that was associated with facial pain. A 65-year-old man was examined at another hospital for unilateral facial pain. Carbamazepine was prescribed, but his symptoms did not improve. Magnetic resonance imaging (MRI) revealed swelling of the trigeminal nerve and a mass lesion in Meckel's cave. The patient was referred to our hospital at this point. Gadolinium-enhanced MRI and F18-Fluorodeoxyglucose-position emission tomography suggested a likely malignant tumour and a biopsy was performed. Histopathological examination showed diffuse a large B cell lymphoma. The patient was treated with high-dose methotrexate (HD-MTX) and radiotherapy. Despite responding well to initial treatment, the patient relapsed, with lymphoma observed throughout the body. He died of pneumonia 18 months after the initial diagnosis. Facial pain is a symptom that is commonly managed in general practice. If symptoms do not improve, repeated imaging studies, including contrast MRI, is warranted. This is the first reported case of primary neurolymphomatosis (NL) of the trigeminal nerve associated with facial pain alone. Furthermore, HD-MTX and radiotherapy may be considered for the management of primary NL of a cranial nerve.