BACKGROUND: OnabotulinumtoxinA (onabotA), is assumed to achieve its therapeutic effect in migraine through blocking activation of unmyelinated meningeal nociceptors and their downstream communications with central dura-sensitive trigeminovascular neurons in the spinal trigeminal nucleus (SPV). The present study investigated the mechanism of action of onabotA by assessing its effect on activation and sensitization of dura-sensitive neurons in the SPV by cortical spreading depression (CSD). It is a follow up to our recent study on onabotA effects on activation and sensitization of peripheral trigeminovascular neurons.
METHODS: In anesthetized male and female rats, single-unit recordings were used to assess effects of extracranial injections of onabotA (five injections, one unit each, diluted in 5 μl of saline were made along the lambdoid (two injection sites) and sagittal (two injection sites) suture) vs. vehicle on CSD-induced activation and sensitization of high-threshold (HT) and wide-dynamic range (WDR) dura-sensitive neurons in the SPV.
RESULTS: Single cell analysis of onabotA pretreatment effects on CSD-induced activation and sensitization of central trigeminovascular neurons in the SPV revealed the ability of this neurotoxin to prevent activation and sensitization of WDR neurons (13/20 (65%) vs. 4/16 (25%) activated neurons in the control vs. treated groups, p = 0.022, Fisher\'s exact). By contrast, onabotA pretreatment effects on CSD-induced activation and sensitization of HT neurons had no effect on their activation (12/18 (67%) vs. 4/7 (36%) activated neurons in the control vs. treated groups, p = 0.14, Fisher\'s exact). Regarding sensitization, we found that onabotA pretreatment prevented the enhanced responses to mechanical stimulation of the skin (i.e. responses reflecting central sensitization) in both WDR and HT neurons. In control but not treated WDR neurons, responses to brush (p = 0.004 vs. p = 0.007), pressure (p = 0.002 vs. p = 0.79) and pinch (p = 0.007 vs. 0.79) increased significantly two hours after CSD. Similarly, in control but not treated HT neurons, responses to brush (p = 0.002 vs. p = 0.79), pressure (p = 0.002 vs. p = 0.72) and pinch (p = 0.0006 vs. p = 0.28) increased significantly two hours after CSD. Unexpectedly, onabotA pretreatment prevented the enhanced responses of both WDR and HT neurons to mechanical stimulation of the dura (commonly reflecting peripheral sensitization). In control vs. treated WDR and HT neurons, responses to dural stimulation were enhanced in 70 vs. 25% (p = 0.017) and 78 vs. 27% (p = 0.017), respectively.
CONCLUSIONS: The ability of onabotA to prevent activation and sensitization of WDR neurons is attributed to its preferential inhibitory effects on unmyelinated C-fibers. The inability of onabotA to prevent activation of HT neurons is attributed to its less extensive inhibitory effects on the thinly myelinated Aδ-fibers. These findings provide further pre-clinical evidence about differences and potentially complementary mechanisms of action of onabotA and calcitonin gene-related peptide-signaling neutralizing drugs.

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.

UNASSIGNED: This case report describes the Marcus Gunn phenomenon (MGP), an infrequent type of congenital unwanted contractions of facial muscles that occurs in 4%-6% of patients with congenital ptosis. The defining characteristic of MGP is the affected eyelid lifting in a manner similar to the opening of the mouth.
UNASSIGNED: It addresses a 45-year-old man who was examined in the dental clinic with a severely decayed tooth. He exhibited evidence of normal vision and synchronous movement of his lips and eyelid.
UNASSIGNED: The conditions matched those of the autosomal dominant disorder with incomplete penetration, the MGP. The carious tooth was restored without the necessity for any surgical intervention.
UNASSIGNED: The patient was given appropriate dental treatment without any surgical intervention for Marcus Gunn Syndrome.
UNASSIGNED: After receiving routine fillings to treat dental caries, the patient stopped complaining of pain.
UNASSIGNED: This case report reveals insight into a situation that has been speculated to be an example of neural redirection syndrome, in which impulses from the trigeminal nerve\'s motor unit are naturally redirected into the levator palpebrae superioris muscles of the upper eyelid and the superior pterygoid muscle.

BACKGROUND: Intranasal trigeminal function is important in detecting environmental stimuli. The impact of age-associated chemosensory dysfunction upon taste and olfaction is well described, but an understanding of trigeminal loss (chemesthesis) is lacking.
OBJECTIVE: The goal of this study was to characterize trigeminal function in a cohort of older adults and explore potential impacts.
METHODS: Twenty-eight participants over 50 years of age were recruited from the community as part of an aging cohort study. This nested cohort completed chemosensory questionnaires, patient-reported outcome measures (PROMs), and psychophysical testing for taste (taste strips), olfaction (Sniffin\' Sticks), and trigeminal function (eucalyptol lateralization). Data were analyzed for associations between trigeminal function, olfactory, and taste psychophysical performance, patient-reported metrics, and demographic risk factors.
RESULTS: Patient-reported trigeminal impairment is less severe than other chemosensory loss, with mean visual analog scores (VAS, rated 0-100 from least to most severe) for smell (32.9 ± 34.2), taste (20.6 ± 28.4), and trigeminal sensation (9.5 ± 12.8). Despite low VAS scores, psychophysical trigeminal dysfunction was present in 10 (35.7%) subjects. Psychophysical olfactory and taste dysfunction were present in 16 (57.1%) and eight (28.6%) participants respectively. Hypercholesterolemia was associated with psychophysical trigeminal dysfunction (mean lateralization performance in hypercholesterolemia 57.7% ± 17.1 vs. 74.1% ± 10.4, p = .008).
CONCLUSIONS: Intranasal trigeminal impairment is present in nearly one-third of aging adults when assessed by psychophysical methods but is under-recognized. Hyperlipidemia may be associated with trigeminal impairment. Future inquiries should better characterize these findings in larger and prospective cohorts.

Recently developed optogenetic technology, which allows high-fidelity control of neuronal activity, has been applied to investigate the neural circuits underlying sensory processing and behavior. The nasal cavity is innervated by the olfactory nerve and trigeminal nerve, which are closely related to common symptoms of rhinitis, such as impairment of smell, itching, and sneezing. The olfactory system has an amazing ability to distinguish thousands of odorant molecules at trace levels. However, there are many issues in olfactory sensing mechanisms that need to be addressed. Optogenetics offers a novel technical approach to solve this dilemma. Therefore, we review the recent advances in olfactory optogenetics to clarify the mechanisms of chemical sensing, which may help identify the mechanism of dysfunction and suggest possible treatments for impaired smell. Additionally, in rhinitis patients, alterations in the other nerve (trigeminal nerve) that innervates the nasal cavity can lead to hyperresponsiveness to various nociceptive stimuli and central sensitization, causing frequent and persistent itching and sneezing. In the last several years, the application of optogenetics in regulating nociceptive receptors, which are distributed in sensory nerve endings, and amino acid receptors, which are distributed in vital brain regions, to alleviate overreaction to nociceptive stimuli, has gained significant attention. Therefore, we focus on the progress in optogenetics and its application in neuromodulation of nociceptive stimuli and discuss the potential clinical translation for treating rhinitis in the future.

BACKGROUND: Assessment of taste and somatosensory perception in clinical practice lacks fast tests that are validated and reliable. Recently, a 12-item identification test for taste and oral trigeminal perception, and its shorter version, the Seven-iTT, was developed. The objectives of this study were to evaluate its test-retest reliability and establish normative data.
METHODS: Two-hundred participants (120 women, 80 men) with a good sense of taste performed a whole-mouth identification test using 12 filter-paper strips impregnated with low and high concentrations of sweet, sour, salty, bitter, astringency, and spiciness. Fifty of them repeated the task, with a median interval of 122 days from the first visit. Test-retest reliability was determined using Spearman correlation and the Bland-Altman plot method.
RESULTS: There was a significant correlation in identification score between the first and the second session for both versions of the test (r ≥ 0.28; p ≤ 0.048). The Bland-Altman plot reflected a good congruence between the results of the two sessions. Additionally, frequencies of correct identification were consistent between sessions, with women outperforming men (p = 0.005). Hypogeusia was established at Seven-iTT score of 3 of less.
METHODS: The identification test combines taste and somatosensory perception, thus creating a more detailed diagnosis tool. Scores were correlated with self-rated taste perception.
CONCLUSIONS: The present results confirmed the applicability of Seven-iTT for a reliable, fast evaluation of taste and somatosensory perception in the general population, that can be extended to clinical practice.

One mechanism by which transcranial direct current stimulation (tDCS) has been proposed to improve attention is by transcutaneous stimulation of cranial nerves, thereby activating the locus coeruleus (LC). Specifically, placement of the electrodes over the frontal bone and mastoid is thought to facilitate current flow across the face as a path of least resistance. The face is innervated by the trigeminal nerve, and the trigeminal nerve is interconnected with the LC. In this study, we tested whether stimulating the trigeminal nerve impacts indices of LC activity and performance on a sustained attention task. We replicated previous research that shows deterioration in task performance, increases in the rate of task-unrelated thoughts, and reduced pupil responses due to time on task irrespective of tDCS condition (sham, anodal, and cathodal stimulation). Importantly, tDCS did not influence pupil dynamics (pretrial or stimulus-evoked), self-reported attention state, nor task performance in active versus sham stimulation conditions. The findings reported here are consistent with theories about arousal centered on a hypothesized link between LC activity indexed by pupil size, task performance, and self-reported attention state but fail to support hypotheses that tDCS over the trigeminal nerve influences indices of LC function.

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.

Port-wine stains (PWSs), also called port-wine birthmarks or nevus flammeus, are hamartomatous vascular capillary malformations that clinically appear as erythematous areas on the buccal mucosa, vermilion border of the lip, gingiva, or pink to port-wine-colored patches on skin since birth and persist throughout life. On the face, they occur in the area supplied by the trigeminal nerve. PWSs have structural abnormalities of the intradermal capillaries. PWSs on the skin and oral mucosa contain ectatic capillaries in the dermis and submucosa, respectively. PWSs occur anywhere, and the oral mucosa is no exception. PWSs on the facial skin lead to cosmetic disfigurement and create social stigma. Clinically, PWSs start as flat, pink, or red patches and may darken, thicken, and develop nodules over time. The diagnosis of PWSs is primarily clinical. PWSs are complex vascular malformations with significant clinical, psychosocial, and therapeutic challenges. This article enlightens a series of cases of PWSs on the facial skin and capillary hemangioma on the gingiva, buccal mucosa, and lip diagnosed by a diascopy test, etiopathogenesis, differential diagnosis, and management of PWSs.

BACKGROUND: Von Hippel-Lindau disease (VHL) is an autosomal dominant tumor predisposition syndrome caused by mutations in the VHL gene. Patients with VHL are predisposed to developing numerous neoplasms, including central nervous system hemangioblastomas that typically arise within the cerebellum, brainstem, or spinal cord. The authors present the unusual case of a 69-year-old patient with a hemangioblastoma of the trigeminal nerve as his initial presentation of VHL.
METHODS: A 69-year-old male presented with progressive right-sided V3 paresthesias, gait disturbance, and diplopia. Magnetic resonance imaging demonstrated an enhancing 0.5-cm nodule within the right trigeminal nerve and an associated peritumoral cyst exerting mass effect on the cerebral peduncle. Neural axis imaging demonstrated pia-based enhancing lesions concerning for multiple spinal hemangioblastomas. The patient underwent an uncomplicated retrosigmoid craniotomy for trigeminal nerve hemangioblastoma resection. The patient had postoperative improvement in his gait, diplopia, and facial paresthesias. Genetic testing revealed that the patient was heterozygous for a pathological mutation in the VHL gene.
CONCLUSIONS: Hemangioblastomas in adults over 50 years of age should prompt a workup for VHL. Recognizing that cranial nerves are a possible site of hemangioblastoma occurrence is important for neurosurgeons and radiologists alike. Resection of cranial nerve hemangioblastomas is technically challenging but can lead to symptom improvement for patients. https://thejns.org/doi/10.3171/CASE24149.