Exploring biomarkers in trigeminal neuralgia patients operated with microvascular decompression: A comparison with multiple sclerosis patients and non-neurological controls.

BACKGROUND: Trigeminal neuralgia (TN) is a severe facial pain condition often associated with a neurovascular conflict. However, neuroinflammation has also been implicated in TN, as it frequently co-occurs with multiple sclerosis (MS). METHODS: We analysed protein expression levels of TN patients compared to MS patients and controls. Proximity Extension Assay technology was used to analyse the levels of 92 proteins with the Multiplex Neuro-Exploratory panel provided by SciLifeLab, Uppsala, Sweden. Serum and CSF samples were collected from TN patients before (n = 33 and n = 27, respectively) and after (n = 28 and n = 8, respectively) microvascular decompression surgery. Additionally, we included samples from MS patients (n = 20) and controls (n = 20) for comparison. RESULTS: In both serum and CSF, several proteins were found increased in TN patients compared to either MS patients, controls, or both, including EIF4B, PTPN1, EREG, TBCB, PMVK, FKBP5, CD63, CRADD, BST2, CD302, CRIP2, CCL27, PPP3R1, WWP2, KLB, PLA2G10, TDGF1, SMOC1, RBKS, LTBP3, CLSTN1, NXPH1, SFRP1, HMOX2, and GGT5. The overall expression of the 92 proteins in postoperative TN samples seems to shift towards the levels of MS patients and controls in both serum and CSF, as compared to preoperative samples. Interestingly, there was no difference in protein levels between MS patients and controls. CONCLUSIONS: We conclude that TN patients showed increased serum and CSF levels of specific proteins and that successful surgery normalizes these protein levels, highlighting its potential as an effective treatment. However, the similarity between MS and controls challenges the idea of shared pathophysiology with TN, suggesting distinct underlying mechanisms in these conditions. SIGNIFICANCE: This study advances our understanding of trigeminal neuralgia (TN) and its association with multiple sclerosis (MS). By analysing 92 protein biomarkers, we identified distinctive molecular profiles in TN patients, shedding light on potential pathophysiological mechanisms. The observation that successful surgery normalizes many protein levels suggests a promising avenue for TN treatment. Furthermore, the contrasting protein patterns between TN and MS challenge prevailing assumptions of similarity between the two conditions and point to distinct pathophysiological mechanisms.

Posterior Fossa Volume and Dimensions: Relation to Pathophysiology and Surgical Outcomes in Classic Trigeminal Neuralgia.

OBJECTIVE: A small posterior fossa (PF) has been hypothesized to explain the increased incidence of trigeminal neuralgia (TN) in females and could make microvascular decompression (MVD) more challenging. The aim of this study was to investigate the association between the PF volume and dimensions in relation to biological sex, type of neurovascular conflict (NVC), and outcome after MVD in classic TN. METHODS: In this observational study, 84 patients with TN operated on with MVD with a preoperative head computed tomography(CT) scan were included. Eighty-two adults without TN who had undergone head CT for other reasons were included as controls. PF volume and dimensions (x-axis, y-axis, and z-axis) were evaluated on the CT scans. For the patients with TN, Barrow Neurological Institute (BNI) grade was evaluated 6 months after MVD. RESULTS: There was no difference in PF volume or dimensions between the patients with TN and controls. Women showed a smaller volume and narrower (x-axis) PF than men, but these differences did not manifest when comparing patients with TN and controls within each sex. Patients with an NVC involving the superior cerebellar artery had a narrower (x-axis) and shorter (y-axis) PF than did patients with an NVC resulting from other arteries. PF volume or dimensions were not associated with BNI grade after MVD. CONCLUSIONS: PF anatomy was related to the NVC type but did not differ between patients with TN and controls and was not related to the surgical outcome after MVD.

Outcome after microvascular decompression for trigeminal neuralgia in a single center-relation to sex and severity of neurovascular conflict.

BACKGROUND: Trigeminal neuralgia (TN), a severe type of facial pain, is mainly caused by a neurovascular conflict (NVC). The severity of the NVC seems associated with the outcome following microvascular decompression (MVD) surgery. This study aimed to investigate the outcome after MVD and whether it is affected by NVC severity and sex. METHODS: TN patients (n = 109) were followed for 5 to 10 years after MVD. Barrow Neurology Index (BNI), Patients Global Impression of Change (PGIC), complications, and time to relapse were evaluated. The NVC severity was retrospectively reviewed from presurgical MRI. Demographic and clinical factors and NVC severity were analyzed for potential association with outcome after MVD. RESULTS: The success rate (BNI ≤ 2) was 80% after 5 to 10 years follow-up for TN patients with severe NVC (grade 2-3) and 56% for TN patients with mild NVC (grade 0-1, P = 0.003). No sex difference was observed in outcome for patients with both mild (P = 0.924) and severe NVC (P = 0.883) respectively. Three patients (2.8%) during the hospital stay, and two patients (1.8%) at 6 weeks, experienced a complication requiring invasive treatment. At long-term 52/109 patients (47.7%) reported some type of persistent adverse event, of which the majority were mild and required no treatment. CONCLUSIONS: MVD offers an 80% probability of long-term pain relief in TN patients with severe NVC, with low frequency of serious complications. NVC severity significantly affects outcome after MVD, while no sex differences in outcome were found. In consistency with previous work, the results stress the importance of adequate neuroradiological assessment of the NVC for preoperative patient selection.

Incidence of trigeminal neuralgia: A population-based study in Central Sweden.

BACKGROUND: The primary aim of this observational study was to determine the incidence of trigeminal neuralgia (TN) in a county in central Sweden. The secondary aim was to investigate TN characteristics including the affected side and nerve branches. METHODS: Patients that received the ICD-10 diagnostic codes TN (G50.0), atypical facial pain (G50.1) and other/unspecified disorder of the trigeminal nerve (G50.8 and G50.9) in Uppsala County, between 2009 and 2017, were eligible for inclusion. Case ascertainment was conducted by the authors by review of the medical records. RESULTS: The incidence of TN was estimated to be 5.5 (95% confidence interval 4.7-6.4) per 100,000 person-years. The incidence increased with age, from 0.1 in 0- to 19-year-olds to 23.1 per 100,000 person-years in 80+-year-olds. Females exhibited a higher incidence at 7.3 than males at 3.7 per 100,000 person-years. Most of the trigeminal neuralgia cases were diagnosed in the Neurology department (47%). Trigeminal neuralgia was most frequently right sided (59%) and limited to one cranial nerve V-branch, of which V2 was the most common. CONCLUSIONS: Trigeminal neuralgia incidence was estimated to be 5.5 per 100,000 person-years. The incidence was higher for females and increased with older age. SIGNIFICANCE: There is limited knowledge about the true incidence of trigeminal neuralgia. This manuscript provides an estimate of 5.5 cases per 100,000 person-years, by using a thorough case ascertainment methodology.

Cerebrospinal Fluid in Classical Trigeminal Neuralgia: An Exploratory Study on Candidate Biomarkers.

Trigeminal neuralgia (TN) is a severe type of facial pain. A neurovascular conflict between cranial nerve V and a nearby vessel is the main pathophysiological mechanism, but additional factors are likely necessary to elicit TN. In this study, the primary aim was to explore differences in protein expression in the cerebrospinal fluid (CSF) of TN patients in relation to controls. Methods: Sixteen TN patients treated with microvascular decompression and 16 control patients undergoing spinal anesthesia for urological conditions were included. Lumbar CSF was collected preoperatively for the TN patients and before spinal anesthesia for the controls. A multiplexed proximity extension analysis of 91 CSF proteins was conducted using Proseek Multiplex Development 96, including biomarkers of cell communication, cell death, neurogenesis, and inflammation Results: The TN patients and the controls were of similar age, sex, and burden of co-morbidities. The TN patients exhibited higher concentrations of Clec11a, LGMN, MFG-E8, and ANGPTL-4 in CSF than the controls (q < 0.05). Conclusions: TN patients exhibited increased CSF biomarkers indicative of peripheral demyelinating injury (Clec11a), immune tolerance and destruction of myelin (LGMN), neuronal cell death (MFG-E8), and disturbances in myelin clearance (ANGPTL-8). Our findings are hypothesis-generating for candidate biomarkers and pathophysiological processes in classical TN.

Decompression of the greater occipital nerve improves outcome in patients with chronic headache and neck pain - a retrospective cohort study.

BACKGROUND: Compression of the greater occipital nerve (GON) may contribute to chronic headache, neck pain, and migraine in a subset of patients. We aimed to evaluate whether GON decompression could reduce pain and improve quality of life in patients with occipital neuralgia and chronic headache and neck pain. METHODS: In this retrospective cohort study, selected patients with neck pain and headache referred to a single neurosurgical center were analyzed. Patients (n = 22) with suspected GON neuralgia based on nerve block or clinical criteria were included. All patients presented with occipital pain spreading frontally and to the neck in various degree. Surgical decompression was performed under local anesthesia. Follow-up was made by an assessor not involved in the treatment of the patients, by telephone 2-5 years after the surgical procedure and an interview protocol was used to collect information. The data from the follow-up protocols were then analyzed and reported. RESULTS: When analyzing the follow-up protocols, decreased headache/migraine was reported in 77% and neck pain was reduced in 55% of the patients. CONCLUSIONS: Decompression of GON(s) may reduce neck pain and headache in selected patients with persistent headache, neck pain, and clinical signs of GON neuralgia. Based on the limitations of the present retrospective study, the results should be considered with caution.

Increased CSF Levels of Apolipoproteins and Complement Factors in Trigeminal Neuralgia Patients-In Depth Proteomic Analysis Using Mass Spectrometry.

The main cause of trigeminal neuralgia (TN) is compression of a blood vessel at the root entry zone of the trigeminal nerve. However, a neurovascular conflict does not seem to be the only etiology and other mechanisms are implicated in the development of the disease. We hypothesized that TN patients may have distinct protein expression in the CSF. In this study, lumbar CSF from TN patients (n = 17), scheduled to undergo microvascular decompression, and from controls (n = 20) was analyzed and compared with in depth mass spectrometry TMTbased quantitative proteomics. We identified 2552 unique proteins, of which 46 were significantly altered (26 increased, and 20 decreased, q-value < .05) in TN patients compared with controls. An over-representation analysis showed proteins involved in high-density lipoprotein, such as Apolipoprotein A4, Apolipoprotein M, and Apolipoprotein A1, and the extracellular region, including proteins involved in the complement cascade to be over-represented. We conclude that TN patients have distinct protein expression in the CSF compared to controls. The pathophysiological background of the protein alterations found in this study warrants further investigation in future studies. PERSPECTIVE: In this article, cerebrospinal fluid from patients with trigeminal neuralgia was analyzed using in depth shotgun proteomics, revealing 46 differentially expressed proteins compared to controls. Among these, apolipoproteins and proteins involved in the complement system were elevated and significantly over-represented, implying an inflammatory component in the pathophysiology of the disease.

Cerebrospinal fluid biomarkers of inflammation in trigeminal neuralgia patients operated with microvascular decompression.

Compression of the trigeminal root entry zone by a blood vessel can cause trigeminal neuralgia (TN). However, a neurovascular conflict does not explain all cases of TN, and TN can exist without a neurovascular contact. A common observation during microvascular decompression surgery to treat TN is arachnoiditis in the region of the trigeminal nerve. Thus, aberrant inflammatory mechanisms may be involved in the pathophysiology of TN but information about the role of inflammation in TN is scarce. We used Proximity Extension Assay technology to analyse the levels of 92 protein biomarkers related to inflammation in lumbar cerebrospinal fluid from patients with TN (n = 27) before and after microvascular decompression compared to individuals without TN. We aimed to analyse the pattern of inflammation-related proteins in order to improve our understanding of the pathophysiology of TN. The main finding was that immunological protein levels in the cerebrospinal fluid from patients with TN decreased after surgery towards levels observed in healthy controls. Two proteins seemed to be of specific interest for TN: TRAIL and TNF-ß. Thus, inflammatory activity might be one important mechanism in TN.