BACKGROUND: Percutaneous balloon compression (PBC) is an effective, low-cost, and simple treatment for primary trigeminal neuralgia (TN). However, PBC has poor efficacy and no better solution for the third branch (V3) of TN.
METHODS: Clinical data of 52 patients with trigeminal neuralgia treated with PBC were retrospectively analyzed. Postoperative numbness of the patient was evaluated by facial numbness at the Barrow Neurological Institute (BNI-N). The main observation was the incidence of higher numbness in the V3 than in the other two branches or equally strong numbness in the three branches in the immediate postoperative period.
RESULTS: The efficacy values in the pear-shaped balloon group at the first postoperative day (T1), the first month (T2), in the third month (T3), and the sixth month (T4) were 96.7%, 93.3%, 93.3%, and 90%, respectively, and 1 patient (3.3%) had recurrence. The efficacy value for the extracapsular capsule group was 95.5% at all times and there were no patients with recurrence within 6 months after surgery. In the immediate postoperative period, the effective compression rate of V3 in the pear-shaped balloon group was 43.3%, and 86.4% in the extracapsular capsule group (P = 0.020). At six months of follow-up, the effective compression rate of V3 was higher in the extracapsular capsule group than in the pear-shaped balloon group.
CONCLUSIONS: The riveted structure of the extracapsular capsule can effectively compress V3, thus performing PBC with a balloon shaped as an extracapsular capsule is a new, effective, and safe treatment option for TN V3.
BACKGROUND: ClinicalTrials.gov ChiCTR2300067313.

BACKGROUND: The olfactory and trigeminal system are closely interlinked. Existing literature has primarily focused on characterizing trigeminal stimulation through mechanical and chemical stimulation, neglecting thermal stimulation thus far. The present study aimed to characterize the intranasal sensitivity to heat and the expression of trigeminal receptors (transient receptor potential channels, TRP).
METHODS: A total of 20 healthy participants (aged 21-27 years, 11 women) were screened for olfactory function and trigeminal sensitivity using several tests. Under endoscopic control, a thermal stimulator was placed in 7 intranasal locations: anterior septum, lateral vestibulum, interior nose tip, lower turbinate, middle septum, middle turbinate, and olfactory cleft to determine the thermal threshold. Nasal swabs were obtained in 3 different locations (anterior septum, middle turbinate, olfactory cleft) to analyze the expression of trigeminal receptors TRP: TRPV1, TRPV3, TRPA1, TRPM8.
RESULTS: The thermal threshold differed between locations (p = 0.018), with a trend for a higher threshold at the anterior septum (p = 0.092). There were no differences in quantitative receptor expression (p = 0.46) at the different sites. The highest overall receptor RNA expression was detected for TRPV1 over all sites (p<0.001). The expression of TRPV3 was highest at the anterior septum compared to the middle turbinate or the olfactory cleft. The thermal sensitivity correlated with olfactory sensitivity and results from tests were related to trigeminal function like intensity ratings of ammonium, a questionnaire regarding trigeminal function, nasal patency, and CO2 thresholds. However, no correlation was found between receptor expression and psychophysical measures of trigeminal function.
CONCLUSIONS: This study provided the first insights about intranasal thermal sensitivity and suggested the presence of topographical differences in thermal thresholds. There was no correlation between thermal sensitivity and trigeminal mRNA receptor expression. However, thermal sensitivity was found to be associated with psychophysical measures of trigeminal and olfactory function.

OBJECTIVE: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two major demyelinating diseases affecting the central nervous system (CNS). The objective of this study is to evaluate the prevalence of pontine trigeminal nerve lesions in patients diagnosed with MS and NMOSD using MRI.
METHODS: This retrospective study included patients diagnosed with MS or NMOSD between July 2018 and July 2023. MS patients were clinically diagnosed using the 2017 McDonald criteria, while NMOSD patients were those who met the 2015 International Panel for NMO Diagnosis (IPND) criteria and were positive for Aquaporin-4 Antibody (AQP4-Ab).
RESULTS: The study included a total of 90 patients, with 45 diagnosed with MS and another 45 with NMOSD. Pontine trigeminal nerve lesions were observed in both MS and NMOSD, but were more prevalent in MS patients (20 % vs. 2 %, p = 0.008). Root entry zone (REZ) lesions were found in 4 of 45 MS patients, accounting for 9 % (95 % CI: 3 %-17 %), and were absent in the NMOSD group; however, there was no significant difference between the two groups (p = 0.12). Of the MS patients with pontine trigeminal nerve lesions, 6 out of 9 (63 %; 95 % CI, 36 %-98 %) exhibited bilateral lesions, which was significantly more prevalent compared to the NMOSD group (13 % vs. 0 %, p = 0.03).
CONCLUSIONS: The presence of pontine trigeminal nerve lesions, particularly when bilateral, are significantly more prevalent in MS patients than in those with NMOSD, suggesting their utility as a distinctive marker and potential diagnostic indicator specifically for MS.

BACKGROUND: 3D-Slicer is an open-source medical image processing and visualization software. In the surgical treatment of trigeminal neuralgia, it is commonly used to predict the responsible vessels. However, there are few reports on the use of 3D-Slicer software to quantitatively measure the bilateral trigeminal nerve volume in patients with primary trigeminal neuralgia (PTN) based on the three-dimensional images. Therefore, this study aims to explore the role of three-dimensional fused images processed by 3D-Slicer in the evaluation of trigeminal nerve atrophy, providing an objective basis for the diagnosis of PTN.
METHODS: 57 PTN patients who underwent microvascular decompression (MVD) or percutaneous balloon compression (PBC) surgery in Hebei general hospital between January 2020 and April 2023 were included. Additionally, 30 patients with facial spasms(HFS) were included as a control group. All patients underwent 3D-TOF-MRA and 3D-FIESTA sequence examinations. Comparisons of bilateral trigeminal nerve volumes within and between groups were conducted by performing image fusion using 3D-slicer.
RESULTS: The volume of the affected trigeminal nerve in the MVD group (33.96 mm³±12.61 mm³) and PBC group (23.05 mm³±7.71 mm³) was smaller than that of the unaffected trigeminal nerve in the MVD group (39.61 mm³±12.83 mm³) and PBC group (26.14 mm³±6.42 mm³), as well as the average volume of the trigeminal nerve in the control group (40.27 mm³±10.25 mm³) (P<0.05). The differences in bilateral trigeminal ganglion volume (∆V) was significant between the MVD group (∆V=23.59 %±14.32 %) and the control group (∆V=14.64 %±10.00 %) (P<0.05). There was no statistical difference in the trigeminal nerve volume difference between the MVD group (∆V=23.59 %±14.32 %) and the PBC group (∆V=26.52 %±15.00 %) (P>0.05).
CONCLUSIONS: Trigeminal nerve atrophy is correlated with primary trigeminal neuralgia. 3D-slicer software can quantitatively measure trigeminal nerve volume and assist in the diagnosis of primary trigeminal neuralgia based on the difference in bilateral trigeminal nerve volumes. However, trigeminal nerve atrophy is not associated with postoperative pain recurrence in patients.

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action.
METHODS: A confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment.
CONCLUSIONS: This multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD.
BACKGROUND: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325 .

BACKGROUND: Cranial autonomic symptoms (CASs) include lacrimation, conjunctival injection, rhinorrhea, nasal congestion, facial flushing or sweating, ptosis, and myosis. These symptoms may be associated with trigeminal autonomic cephalalgias (TACs) and migraine.
OBJECTIVE: The aim of the study was to assess whether CASs are also reported by patients with frequent episodic tension-type headache (eTTH).
METHODS: A cross-sectional online survey of a large Polish population was conducted between August 2021 and June 2022. The analysis assessed diagnostic criteria for migraine and eTTH, as well as the presence of allodynia, headache-related disability and symptoms of depression.
RESULTS: The survey involved 3,225 respondents (age: 13-80 years, mean (M) = 38.9 years; 87.1% female). A total of 166 individuals met the diagnostic criteria for isolated frequent eTTH without migraine or probable migraine with or without aura. Allodynia was present during the majority of attacks in 40 (24.1%) eTTH subjects, while 86 (51.8%) eTTH respondents reported at least 1 CAS during their headache attacks. The presence of at least 1 CAS was more prevalent in migraine than in eTTH (p = 0.001). The respondents with at least 1 CAS during eTTH attacks reported a higher burden associated with pain (p = 0.024) and higher Patient Health Questionnaire-9 (PHQ-9) scores (p = 0.016).
CONCLUSIONS: The prevalence of retrospectively reported CASs was high among individuals with eTTH, which may potentially contribute to diagnostic errors. Cranial autonomic symptoms in eTTH do not appear to be caused by severe pain or central sensitization.

Animal models remain necessary tools to study neuropathic pain. This manuscript describes the distal infraorbital nerve chronic constriction injury (DIoN-CCI) model to study trigeminal neuropathic pain in mice. This includes the surgical procedures to perform the chronic constriction injury and the postoperative behavioral tests to evaluate the changes in spontaneous and evoked behavior that are signs of ongoing pain and mechanical allodynia. The methods and behavioral readouts are similar to the infraorbital nerve chronic constriction injury (IoN-CCI) model in rats. However, important changes are necessary for the adaptation of the IoN-CCI model to mice. First, the intra-orbital approach is replaced by a more rostral approach with an incision between the eye and the whisker pad. The IoN is thus ligated distally outside the orbital cavity. Secondly, due to the higher locomotor activity in mice, allowing rats to move freely in small cages is replaced by placing mice in custom-designed and constructed restraining devices. After DIoN ligation, mice exhibit changes in spontaneous behavior and in response to von Frey hair stimulation that are similar to those in IoN-CCI rats, i.e., increased directed face grooming and hyperresponsiveness to von Frey hair stimulation of the IoN territory.

BACKGROUND: Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body.
METHODS: A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen\'s were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae).
RESULTS: Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group.
CONCLUSIONS: People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine.

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.
CONCLUSIONS: 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.

OBJECTIVE: Operative interposition of material between the trigeminal nerve and offending artery for surgical treatment of drug-resistant trigeminal neuralgia (TGN), following the Jannetta method, has been proven to be the most successful invasive treatment. Reexplorations of patients with recurrence of TGN have revealed nerve root irritations and scarring due to interposed material. To prevent these complications, modifications of microvascular decompression (MVD) aim at transposing the vessel away from the trigeminal nerve, without attachment of additional material to the nerve root. Given that both techniques (interposition and transposition) have been performed in the authors\' institution, they decided to analyze them for the short- and midterm outcomes.
METHODS: All patients who had undergone MVD for drug-resistant TGN in the authors\' institution between 2008 and 2022 were analyzed retrospectively. Outcome at discharge and follow-up was evaluated using the Barrow Neurological Institute pain intensity score. Additionally, complications and pain recurrence were assessed.
RESULTS: A total of 114 patients were operated on using transposition and 110 patients were treated using interposition. For transposition 102 patients were followed up for a median of 31.5 months, and for interposition 100 patients were followed up for a median of 95 months. At discharge 92.1% versus 94.5% of patients in the transposition and interposition groups, respectively, experienced a good outcome (Barrow Neurological Institute pain intensity scores I-III). At follow-up, 83.3% versus 85% of patients in the transposition and interposition groups, respectively, continued to demonstrate a good outcome. In 4.9% of patients in the transposition group and in 6% of patients in the interposition group, recurrence of pain occurred. Complications occurred in 24.6% of patients in the transposition and in 27.3% of those in the interposition group. The most frequent complications were facial hypesthesia (10.5% vs 11.8%, transposition vs interposition), followed by CSF leaks (2.6% vs 8.2%).
CONCLUSIONS: Transposition for MVD is an elegant way of solving vessel-nerve conflicts at the cerebellopontine angle. Similar to interposition, transposition shows positive short- and midterm outcomes for patients experiencing drug-resistant TGN. However, the main objective of transposition, which is improved prevention of recurrence and reduction of complications at the trigeminal nerve, could not be confirmed in this study.