External assessment of preoperative scores for predicting outcome after microvascular decompression for trigeminal neuralgia.

OBJECTIVE: Recently, two scoring systems have been developed for predicting pain-free outcomes after microvascular decompression (MVD). Evaluation of these scores on large external datasets has been limited. In this study, the authors aimed to evaluate the performance of published MVD scoring systems in predicting pain-free outcome. METHODS: A total of 458 patients who underwent MVD for trigeminal neuralgia (TN) between 2007 and 2020 and had at least 6 months of follow-up were included in this study. Hardaway and Panczykowski scores were retrospectively computed for each patient and compared with postoperative pain recurrence and pain-free duration. RESULTS: The mean ± SD area under the receiver operating characteristic curve for predicting any pain recurrence after MVD was 0.567 ± 0.081 using the Hardaway score and 0.546 ± 0.085 using the Panczykowski score. On log-rank tests and Kaplan-Meier analysis, the patients with Hardaway scores of 0-2 had significantly shorter pain-free survival times after MVD than did those with a score of 3. Patients with a Panczykowski score of 1 had a significantly shorter pain-free duration after surgery compared with both patients with scores of 2-3 and patients with scores of 4-5. Patients with Panczykowski scores of 2-3 also had significantly shorter pain-free duration compared with patients with scores of 4-5. CONCLUSIONS: Both the Hardaway and Panczykowski scores may be useful for predicting postoperative pain-free duration in TN patients, and their utility may be greatest when scores are clustered. Continued refinement of both scoring systems will help to improve our ability to predict patient outcomes after MVD.

Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells.

Previous studies of neuronal survival have primarily focused on identifying intrinsic mechanisms controlling the process. This study explored how intercellular communication contributes to retinal ganglion cell (RGC) survival following optic nerve crush based on single-cell RNA-seq analysis. We observed transcriptomic changes in retinal cells in response to the injury, with astrocytes and Müller glia having the most interactions with RGCs. By comparing RGC subclasses characterized by distinct resilience to cell death, we found that the high-survival RGCs tend to have more ligand-receptor interactions with neighboring cells. We identified 47 interactions stronger in high-survival RGCs, likely mediating neuroprotective effects. We validated one identified target, the µ-opioid receptor (Oprm1), to be neuroprotective in three retinal injury models. Although the endogenous Oprm1 is preferentially expressed in intrinsically photosensitive RGCs, its neuroprotective effect can be transferred to other subclasses by pan-RGC overexpression of Oprm1. Lastly, manipulating the Oprm1 activity improved visual functions in mice.

Synchronized Incidental Affect Changes Ambiguity Preferences.

Decisions under uncertainty are prevalent, but come under two distinct types. Risk, which has unknown outcomes but known probabilities for those outcomes and ambiguity which contains both unknown outcomes and unknown probabilities. Although there have been several studies linking affect and aversion to ambiguity, there have been no studies that have to identify how changing one's affective response can change their choices. A total of 166 adults ( M = 36.54, SD = 11.80) participated in an online study through Prolific. Participants were presented with a lottery on each trial which varied on its uncertainty type (risky vs ambiguous) and winning characteristics (winning probability and amount). Half of the ambiguous lotteries were paired with an neutral image (e.g., office supplies), while the other half was paired with an emotionally evocative image (e.g., burning house) that was hypothesized to incidentally influence their decisions. As measured by both raw choice data as well as through a computational model, participants were more averse to ambiguity when the lottery was paired with an emotionally evocative image. Follow-up analyses revealed that only lotteries in which the computational model predicted the participant would choose the lottery were affected by the images. This study highlights the phenomenon in which one's awareness of an affective stimulus can alter its impact on their decisions.

The pathophysiology of trigeminal neuralgia: a molecular review.

OBJECTIVE: The goal of this study was to provide a comprehensive overview of the current understanding of molecular and genetic mechanisms underlying the pathophysiology of trigeminal neuralgia (TN). METHODS: The authors searched PubMed systematically for primary research literature investigating specific molecular mechanisms from samples derived from patients with TN. The genes/molecules of interest from the selected literature were then cross-referenced with corresponding studies in animal models of TN. RESULTS: From approximately 345 articles, a total of 12 articles were selected and included in the review, focusing on ionotropic channel expressivity and mutations, reactive oxygen species expressivity, inflammatory marker expressivity, and microRNA expressivity. Of the 12 included articles, only 4 had studies completed in other animal models regarding the corresponding TN mechanism found in humans. CONCLUSIONS: The current literature does not suggest a conclusive disease mechanism for TN in humans. In addition to neurovascular conflict/compression of the trigeminal nerve, recent studies have indicated that TN may be linked to inflammatory and reactive oxygen species signaling as well. Recent genetic studies in patients with TN have yet to be investigated further in animal models.

Frailty Predicts Worse Pain Outcomes for Older TN Patients Treated with Microvascular Decompression.

BACKGROUND: Trigeminal neuralgia (TN) is a debilitating orofacial pain disorder. Recent data from a national database suggest that microvascular decompression (MVD) in frail patients is associated with more postoperative complications. However, the long-term pain outcomes for frail TN patients are not known. We aimed to elucidate the relationship between frailty and long-term pain outcomes after MVD for TN. METHODS: From 2007 to 2020, 368 TN patients aged ≥60 years underwent MVD at our institution. Patient demographics, clinical characteristics, postoperative complications, and long-term pain outcomes were recorded. Frailty was assessed using the modified 5-item frailty index (mFI-5) score, and the patients were dichotomized into nonfrail (mFI-5 <2) and frail (mFI-5 >1). Differences were assessed via the t test, χ2 test, multivariate ordinal regression, and Cox proportional hazards analysis. RESULTS: Of the 368 patients analyzed, 9.8% were frail. The frail patients were significantly older (P = 0.02) with a higher body mass index (P = 0.01) and a greater incidence of comorbidities (P < 0.001). Frail patients presented with significantly higher pain levels at the final follow-up (P = 0.04). On multivariate analysis, frailty was independently associated with more pain at follow-up (P = 0.01), as was younger age, female sex, and black race. The relationship between frailty and postoperative pain recurrence showed a trend toward significance (P = 0.06), and younger age and black race were significantly associated with recurrence. CONCLUSIONS: Frail patients undergoing MVD are at risk of worse long-term pain outcomes. Our results provide clinicians with useful information pertaining to the influence of frailty on the long-term efficacy of MVD in treating TN.

Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells.

The progressive death of mature neurons often results in neurodegenerative diseases. While the previous studies have mostly focused on identifying intrinsic mechanisms controlling neuronal survival, the extracellular environment also plays a critical role in regulating cell viability. Here we explore how intercellular communication contributes to the survival of retinal ganglion cells (RGCs) following the optic nerve crush (ONC). Although the direct effect of the ONC is restricted to the RGCs, we observed transcriptomic responses in other retinal cells to the injury based on the single-cell RNA-seq, with astrocytes and Müller glia having the most interactions with RGCs. By comparing the RGC subclasses with distinct resilience to ONC-induced cell death, we found that the high-survival RGCs tend to have more ligand-receptor interactions with other retinal cells, suggesting that these RGCs are intrinsically programmed to foster more communication with their surroundings. Furthermore, we identified the top 47 interactions that are stronger in the high-survival RGCs, likely representing neuroprotective interactions. We performed functional assays on one of the receptors, µ-opioid receptor (Oprm1), a receptor known to play roles in regulating pain, reward, and addictive behavior. Although Oprm1 is preferentially expressed in intrinsically photosensitive retinal ganglion cells (ipRGC), its neuroprotective effect could be transferred to multiple RGC subclasses by selectively overexpressing Oprm1 in pan-RGCs in ONC, excitotoxicity, and glaucoma models. Lastly, manipulating Oprm1 activity improved visual functions or altered pupillary light response in mice. Our study provides an atlas of cell-cell interactions in intact and post-ONC retina, and a strategy to predict molecular mechanisms controlling neuroprotection, underlying the principal role played by extracellular environment in supporting neuron survival.

Resection of Condylar Skull Base Tumor via Combined Far Lateral and Infrajugular Approaches with Single-Stage Occipitocervical Fusion.

Epithelioid hemangioma is a rare vascular mesenchymal tumor with a paucity of reports of cranial involvement. In particular, guidance on treatment for lateral skull base lesions is lacking, despite this being a highly technically challenging location. Nuances in the management decisions for this tumor type are discussed. Two major challenges with this location are proximity to critical neurovascular structures and managing secondary craniocervical instability. We present a patient with a lateral skull base epithelioid hemangioma treated with transcondylar resection, single-stage occipitocervical fusion, and adjuvant radiation and chemotherapy. The patient consented to both the procedure and the published report of her case including imaging. Obtaining tissue was necessary for diagnosis. Maximal safe resection, resection of a tumor such that the greatest clinical benefit is achieved with the minimum risk, was favored given the location and vascularity of the lesion. Occipitocervical fusion was recommended given ongoing bony destruction by the tumor and further expected iatrogenic instability upon resection. This was performed as a single stage given expected need for postoperative adjuvant radiation therapy and dynamic neck pain (Video 1). Surgical planning and decision making are detailed, including rationale and potential risks and benefits. We discuss positioning, equipment needs, and the importance of a multidisciplinary surgical team. Park bench positioning was used for part 1, left-sided extended far lateral and infratemporal fossa presigmoid approaches. For part 2, occipitocervical fusion, the patient was transitioned to prone position. The anatomy is highlighted in labeled pictures of the approach and dissection, and surgical video is presented for key surgical steps. Preoperative and postoperative imaging is analyzed. A desirable clinical outcome was obtained.

In vivo glial trans-differentiation for neuronal replacement and functional recovery in central nervous system.

The adult mammalian central nervous system (CNS) is deficient in intrinsic machineries to replace neurons lost in injuries or progressive degeneration. Various types of these neurons constitute neural circuitries wired to support vital sensory, motor, and cognitive functions. Based on the pioneer studies in cell lineage conversion, one promising strategy is to convert in vivo glial cells into neural progenitors or directly into neurons that can be eventually rewired for functional recovery. We first briefly summarize the well-studied regeneration-capable CNS in the zebrafish, focusing on their postinjury spontaneous reprogramming of the retinal Müller glia (MG). We then compare the signaling transductions, and transcriptional and epigenetic regulations in the zebrafish MGs with their mammalian counterparts, which perpetuate certain barriers against proliferation and neurogenesis and thus fail in MG-to-progenitor conversion. Next, we discuss emerging evidence from mouse studies, in which the in vivo glia-to-neuron conversion could be achieved with sequential or one-step genetic manipulations, such as the conversions from retinal MGs to interneurons, photoreceptors, or retinal ganglion cells (RGCs), as well as the conversions from midbrain astrocytes to dopaminergic or GABAergic neurons. Some of these in vivo studies showed considerable coverage of subtypes in the newly induced neurons and partial reestablishment in neural circuits and functions. Importantly, we would like to point out some crucial technical concerns that need to be addressed to convincingly show successful glia-to-neuron conversion. Finally, we present challenges and future directions in the field for better neural function recovery.

Lin28 Signaling Supports Mammalian PNS and CNS Axon Regeneration.

RNA-binding proteins Lin28a/b regulate cellular growth and tissue regeneration. Here, we investigated the role of Lin28 in the control of axon regeneration in postmitotic neurons. We find that Lin28a/b are both necessary and sufficient for supporting axon regeneration in mature sensory neurons through their regulatory partners, let-7 microRNAs (miRNAs). More importantly, overexpression of Lin28a in mature retinal ganglion cells (RGCs) produces robust and sustained optic nerve regeneration. Additionally, combined overexpression of Lin28a and downregulation of Pten in RGCs act additively to promote optic nerve regeneration, potentially by reducing the backward turning of regenerating RGC axons. Our findings not only reveal a vital role of Lin28 signaling in regulating mammalian axon regeneration but also identify a signaling pathway that can promote axon regeneration in the central nervous system (CNS).