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Abstract BACKGROUND While high-resolution imaging is increasingly used in guiding decisions about surgical interventions for the treatment of trigeminal neuralgia, direct assessment of the extent of vascular contact of the trigeminal nerve is still considered the gold standard for the determination of whether nerve decompression is warranted. OBJECTIVE To compare intraoperative and magnetic resonance imaging (MRI) findings of the prevalence and severity of vascular compression of the trigeminal nerve in patients without classical trigeminal neuralgia. METHODS We prospectively recruited 27 patients without facial pain who were undergoing microvascular decompression for hemifacial spasm and had undergone high-resolution preoperative MRI. Neurovascular contact/compression (NVC/C) by artery or vein was assessed both intraoperatively and by MRI, and was stratified into 3 types: simple contact, compression (indentation of the surface of the nerve), and deformity (deviation or distortion of the nerve). RESULTS Intraoperative evidence of NVC/C was detected in 23 patients. MRI evidence of NVC/C was detected in 18 patients, all of whom had intraoperative evidence of NVC/C. Thus, there were 5, or 28% more patients in whom NVC/C was detected intraoperatively than with MRI (Kappa = 0.52); contact was observed in 4 of these patients and compression in 1 patient. In patients where NVC/C was observed by both methods, there was agreement regarding the severity of contact/compression in 83% (15/18) of patients (Kappa = 0.47). No patients exhibited deformity of the nerve by imaging or intraoperatively. CONCLUSION There was moderate agreement between imaging and operative findings with respect to both the presence and severity of NVC/C.

IntroductionThe pharmacological block of the greater occipital nerve has been proven effective in numerous headache and facial pain syndromes. This clinical effect supports the hypothesis of a strong functional interaction between the occipital and trigeminal nerves which has been proposed in neurophysiological in vivo experiments in rodents. Although it is likely that the interaction has to occur in the central nervous system, the exact site and the mechanisms of the interaction remain largely unknown.MethodsFocusing on these questions we investigated in a double-blind, placebo-controlled, randomised study the influence of an occipital nerve block with lidocaine 1% on neuronal activation in the trigeminocervical complex using high-resolution functional magnetic resonance on a 3T scanner. In order to investigate potential clinical effects on the trigeminal nerve, we further performed quantitative sensory testing and analysed a potential shift in thermal detection and pain thresholds.ResultsThe pharmacological block of the greater occipital nerve induced an occipital anaesthesia ipsilateral to the block. Functional imaging revealed that the occipital injection of lidocaine but not placebo significantly reduced nociceptive trigeminal activation.ConclusionsThese data suggest that the functional inhibition of the occipital nerve block on trigeminal nociceptive activity is likely to occur at the C2 level where the occipital nerve enters the trigeminocervical complex and converges on the same central nuclei before the signal crosses the midline at that level and is then transmitted to higher processing centres.

Abstract BACKGROUND AND IMPORTANCE Hypertrophic interstitial neuropathy (HIN) is an uncommon, non-neoplastic lesion typically affecting peripheral nerves. Cranial nerve (CN) involvement is exceedingly rare. We present a case of isolated trigeminal nerve HIN manifesting with V3 distribution neuralgia. CLINICAL PRESENTATION A 50-yr-old male presented with left sided trigeminal neuralgia refractory to medical management. The patient underwent retromastoid craniectomy for possible microvascular decompression. Intra-operatively, the trigeminal nerve appeared to be focally enlarged with a sausage-like configuration. We selectively resected 1 fascicle which was predominantly involved. Histopathological examination revealed onion bulb formations composed of Schwann cells around centrally placed axons. A diagnosis of HIN was made. Postoperatively, the patient experienced complete resolution of symptoms. CONCLUSION This is the third case of isolated trigeminal nerve HIN in the literature. We performed a selective resection in a patient presenting with trigeminal neuralgia, resulting in complete resolution of symptoms. It is reported here with intraoperative microscope images, along with a review and analysis of this topic as it related to CN.

Objectives MR neurography has the ability to detect and depict peripheral nerve injuries. This study evaluated the potential of MR neurography in the diagnosis of post-traumatic trigeminal neuropathy. Methods Forty-one participants prospectively underwent MR neurography of the lingual and inferior alveolar nerves using a 3D TSE STIR black-blood sequence. Two blinded and independent observers recorded the following information for each nerve of interest: presence of injury, nerve thickness, nerve signal intensity, MR neurography Sunderland class, and signal gap. Afterwards, the apparent nerve-muscle contrast-to-noise ratio and apparent signal-to-noise ratio were calculated. Clinical data (neurosensory testing score and clinical Sunderland class) was extracted retrospectively from the medical records of patients diagnosed with post-traumatic trigeminal neuropathy. Results Compared to neurosensory testing, MR neurography had a sensitivity of 38.2% and specificity of 93.5% detecting nerve injuries. When differentiated according to clinical Sunderland class, sensitivity was 19.1% in the presence of a low class injury (I to III) and improved to 83.3% in the presence of a high class (IV to V). Specificity remained unchanged. The area under the curve using the apparent nerve-muscle contrast-to-noise ratio, apparent signal-to-noise ratio, and nerve thickness to predict the presence of an injury was 0.78 ( p  < .05). Signal intensities and nerve diameter increased in injured nerves ( p  < .05). Clinical and MR neurography Sunderland scores positively correlated (correlation coefficient = 0.53; p  = .005). Conclusions This study shows that MR neurography can accurately differentiate between injured and healthy nerves, especially in the presence of a more severe nerve injury. Clinical relevance statement MR neurography is not only able to detect trigeminal nerve injuries, but it can also provide information about the anatomical specifications of the injury, which is not possible with clinical neurosensory testing. This makes MR neurography an added value in the management of post-traumatic trigeminal neuropathy. Key Points • The current diagnosis of post-traumatic trigeminal neuropathy is mainly based on clinical examination. • MR neurography is able to visualize and stratify peripheral trigeminal nerve injuries. • MR neurography contributes to the diagnostic process as well as to further decision-making.

This study compared the degree of secondary hyperalgesia and somatosensory threshold changes induced by topical capsaicin between spinal and trigeminal innervation. This crossover clinical trial included 40 healthy individuals in which 0.25 g of 1% capsaicin cream was randomly applied for 45 minutes to a circular area of 2 cm 2 to the skin covering the masseter muscle and forearm in 2 different sessions, separated by at least 24 hours and no more than 72 hours (washout period). The main outcome variables were the area of allodynia and pinprick hyperalgesia, as well as electrical and mechanical pain thresholds within the area of pinprick hyperalgesia. Mixed ANOVA models and McNemar tests were applied to the data ( p  = 0.050). The occurrence of allodynia and pinprick hyperalgesia was higher in the forearm than in the masseter ( p  < 0.050). Additionally, the areas of pinprick hyperalgesia and allodynia were larger in the forearm compared to the masseter ( p  < 0.050). The electrical and mechanical pain thresholds demonstrated a loss of somatosensory function following capsaicin application to the masseter ( p  < 0.050). However, no significant somatosensory threshold changes were observed at the forearm after capsaicin ( p  > 0.050). In conclusion, these findings indicate potential differences compatible with central sensitization related to secondary hyperalgesia between trigeminal and spinal innervation.

Abstract Background Nerve atrophy results in trigeminal nerve (TN) asymmetry detectable by magnetic resonance imaging (MRI) in humans, but similar studies have not been performed in horses with idiopathic trigeminal-mediated headshaking (ITMHS). Hypothesis Horses with ITMHS show greater MRI-detected trigeminal-nerve asymmetry than controls. Animals A total of 20 adult horses with ITMHS and six unaffected control horses. Methods Retrospective case-control study of the TN cross-sectional area (TNCSA) based on 3-Tesla MRI scans of the equine brain. TNCSA and its side-to-side differences at four defined measurement points were compared within the two study groups using a linear mixed model. Intraclass correlation coefficient analysis was used to evaluate intra-rater repeatability. The primary outcome was side-to-side TNCSA asymmetry, minimizing confounding effects such as body size. Results Significantly greater TNCSA side-to-side differences (asymmetry of TN) were detected in horses with ITMHS (F(3,70) = 11.271, p < 0.001). Horses with ITMHS exhibited a 4.1 to 7.6-fold greater TN asymmetry compared to control horses. Absolute TNCSA did not differ significantly between groups but was influenced by body weight. Measurements demonstrated excellent repeatability, and tentative cut-off values could be calculated to discriminate between ITMHS and control horses based on TNCSA asymmetry. Conclusions and Clinical Importance The asymmetry of the TNCSA in horses with ITMHS indicates unilateral or asymmetric disease of the TN. The present study highlights the value of MRI examinations in ITMHS and could pave the way for targeted therapeutic approaches.

Background Trigeminal schwannoma is a rare type of tumor that arises from the Schwann cells of the trigeminal nerve. Method We present a case of a patient with a giant V2 trigeminal schwannoma with painful swelling in the left maxilla. A complete resection using a combined open maxillectomy and endoscopic endonasal approach was performed. Conclusion This case highlights the importance of a multidisciplinary approach to perform a combined open and endoscopic approach for safe resection while preserving adequate speech and swallowing.

Background Cranial neuropathy is a principal disease manifestation of neurosarcoidosis, but many forms remain poorly described, including trigeminal nerve disease despite its frequency in reported cohorts (5–12%). Herein, we characterize the clinical course of patients with neurosarcoidosis involving the trigeminal nerve. Methods A single-center retrospective cohort analysis of patients with biopsy-proven sarcoidosis involving the trigeminal nerve was conducted between 1/1/2000-3/7/2023. Results The trigeminal nerve was affected in 14/245 (5.7%) patients, being clinically symptomatic in 5/245 (2.0%) and asymptomatic with radiographic involvement in 9/245 (3.7%). 14/14 (100.0%) patients had systemic sarcoidosis. In the symptomatic group, trigeminal neuropathy was an inaugural feature in 4/5 (80.0%), unilateral in 5/5 (100.0%) with the V1 subdivision most affected (4/5, 80.0%), and associated with neuralgia in 2/5 (40.0%). On MRI, the cisternal nerve roots (9/14, 64.3%), Meckel’s cave (7/14, 50.0%), and cavernous sinus (5/14, 35.7%) were most commonly affected, and 14/14 (100.0%) patients had extra-trigeminal neuroinflammation on cranial MRI. CSF was abnormal in at least one dimension in 11/12 (91.7%) tested. All three treated patients with symptomatic trigeminal neuropathy responded to immunomodulatory treatment, and symptomatic treatments for trigeminal neuralgia were helpful in two patients. After a median follow-up period of 63 months, the median modified Rankin scale score was 1 for both subgroups. Conclusion Neurosarcoidosis may involve any portion of the trigeminal apparatus, and when affected, it frequently demonstrates a mismatch in radiographic involvement from its clinical manifestations of facial numbness and pain, and typically occurs in association with other clinical or radiographic manifestations of neurosarcoidosis.

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. Discussion 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. Trial registration : ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325 .

Objective Trigeminal schwannomas are rare benign tumors originating from the Schwann cells of the trigeminal nerve. Despite the common occurrence of trigeminal neuropathy in trigeminal schwannomas, a detailed analysis has not yet been performed because of the rarity of this disease. This study aimed to analyze trigeminal neuropathy in trigeminal schwannoma resection and identify the risk factors for postoperative worsening of trigeminal neuropathy. Methods A retrospective analysis of 86 surgical cases was performed at our institution between 1975 and 2018. Obtained parameters included age, sex, diagnosis, reoperation, tumor size, tumor location, presence or absence of cysts, surgical approach, degree of tumor removal, and pre/postoperative trigeminal neuropathy. Uni- and multivariate analyses were performed to identify the risk factors for worsening postoperative sensory disturbances. Results Of 83 patients, 58.1% had preoperative trigeminal neuropathy. Postoperative sensory disturbance occurred in 27.9%, with worsening in two cases and de novo symptoms in 22 cases. Regarding risk factors for worsening postoperative sensory disturbances, older age, smaller tumor size, middle and posterior (MP) type, gross total removal (GTR), and anterior transpetrosal approach were identified in the univariate analysis, while MP type and GTR were identified in the multivariate analysis. Conclusions This study analyzed trigeminal neuropathy in trigeminal schwannomas in detail and identified tumor location and removal rate as risk factors for worsening postoperative sensory disturbances. Treatment strategies to reduce the risk of trigeminal neuropathy should be considered.