Periaqueductal gray connectivity in spinal cord injury-induced neuropathic pain.

BACKGROUND AND PURPOSE: Neuropathic pain (NP) is a debilitating condition following spinal cord injury (SCI). The role of periaqueductal gray (PAG) in NP development following SCI remains underexplored. Using resting-state functional MRI (rsfMRI), our study aimed to demonstrate the alterations in functional connectivity (FC) of PAG in NP following SCI. METHODS: Ten SCI patients (SCI + NP, n = 7, and SCI - NP, n = 3), alongside 10 healthy controls (HCs), were enrolled. rsfMRI was conducted followed by seed-to-voxel analysis using PAG as the seed region and then group-based analysis comprising three groups (SCI + NP, SCI - NP, and HC). Age and gender were considered as confounding variables. RESULTS: Compared to HCs, SCI + NP demonstrated decreased FC between PAG and right insula, right frontal orbital cortex, right pallidum, dorsal raphe nucleus (DRN), red nuclei (RN), substantia nigra (SN), and ventral posterolateral (VPL) thalamic nuclei. Compared to SCI - NP, SCI + NP demonstrated increased FC between PAG and posterior cingulate cortex (PCC), hippocampus, cerebellar vermis lobules IV and V, and thalamic structures (posterior and lateral pulvinar, the mediodorsal nuclei, and the ventral lateral nuclei). Additionally, decreased FC between the PAG and VPL, geniculate bodies, intralaminar nuclei of thalamus, DRN, RN, SN, and prefrontal cortex was observed in this comparison. CONCLUSIONS: Altered FC between PAG and right anterior insula, VPL, DRN, RN, SN, cerebellar vermis lobules IV and V, frontal cortex, and PCC was associated with NP sequelae of SCI. Additionally, SCI was independently associated with decreased FC between PAG and right posterior insula, cerebellar lobules IV and V, and cerebellar vermis lobules III, IV, and V.

Evaluating ChatGPT as a Patient Education Tool for COVID-19-Induced Olfactory Dysfunction.

Objective: While most patients with COVID-19-induced olfactory dysfunction (OD) recover spontaneously, those with persistent OD face significant physical and psychological sequelae. ChatGPT, an artificial intelligence chatbot, has grown as a tool for patient education. This study seeks to evaluate the quality of ChatGPT-generated responses for COVID-19 OD. Study Design: Quantitative observational study. Setting: Publicly available online website. Methods: ChatGPT (GPT-4) was queried 4 times with 30 identical questions. Prior to questioning, Chat-GPT was "prompted" to respond (1) to a patient, (2) to an eighth grader, (3) with references, and (4) no prompt. Answer accuracy was independently scored by 4 rhinologists using the Global Quality Score (GCS, range: 1-5). Proportions of responses at incremental score thresholds were compared using χ 2 analysis. Flesch-Kincaid grade level was calculated for each answer. Relationship between prompt type and grade level was assessed via analysis of variance. Results: Across all graded responses (n = 480), 364 responses (75.8%) were "at least good" (GCS ≥ 4). Proportions of responses that were "at least good" (P < .0001) or "excellent" (GCS = 5) (P < .0001) differed by prompt; "at least moderate" (GCS ≥ 3) responses did not (P = .687). Eighth-grade level (14.06 ± 2.3) and patient-friendly (14.33 ± 2.0) responses were significantly lower mean grade level than no prompting (P < .0001). Conclusion: ChatGPT provides appropriate answers to most questions on COVID-19 OD regardless of prompting. However, prompting influences response quality and grade level. ChatGPT responds at grade levels above accepted recommendations for presenting medical information to patients. Currently, ChatGPT offers significant potential for patient education as an adjunct to the conventional patient-physician relationship.

CPAP-induced sphenoid sinus pressures after endoscopic sinus surgery.

KEY POINTS: Positive pressure transmitted from continuous positive airway pressure (CPAP) to the sinuses and skull base in the early post-operative period has not been studied in live subjects and controversy exists in when to restart this post-operatively. This study found that approximately 32.76% and 13.52% of the delivered CPAP pressures reached the post-surgical sphenoid sinus and the mid-nasal cavity, respectively, suggesting that surgical factors such as tissue edema, nasal packing, blood, and nasal secretions may provide a protective effect.

Transoral Robotic Surgery Versus Hypoglossal Nerve Stimulation for OSA: A Cost Analysis Study.

BACKGROUND: Transoral robotic surgery (TORS) lingual tonsillectomy and hypoglossal nerve stimulation (HGNS) are effective surgical interventions for well-selected patients with obstructive sleep apnea (OSA) intolerant to continuous positive airway pressure (CPAP) therapy. Previous publications have demonstrated that HGNS patients have a lower postoperative apnea-hypopnea index (AHI) and length of hospital stay than TORS patients. No prior study has investigated the differences in costs between HGNS and TORS. OBJECTIVES: This study aims to compare surgery-related costs in patients undergoing HGNS versus TORS lingual tonsillectomy for OSA intolerant to CPAP. METHODS: A retrospective study on OSA patients intolerant to CPAP that underwent HGNS or TORS from 2015 to 2022 at a tertiary care center. Cost was defined as the dollar amount associated with providing a specific service prior to the application of insurance. RESULTS: This study included 395 patients (375 UAS and 20 TORS). Average total cost was significantly higher in the UAS group than the TORS group (UAS: $25,582.60; TORS: $5832.60; p < 0.001). Operating room costs were also significantly higher in the UAS group (UAS: $1978.20; TORS: $1490.90; p = 0.001). The TORS cohort averaged higher costs for pharmacy (UAS: $201.30; TORS: $416.60; p < 0.001) and anesthesia (UAS: $139.00; TORS: $307.60; p < 0.001). DISCUSSION: The total cost was significantly higher in the UAS group compared to the TORS group. When making management decisions, it is important to consider the cost of care provided as well as patient-centered outcomes to optimize the value of care. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Gender-based linguistic differences in letters of recommendation for rhinology fellowship over time: A dual-institutional follow-up study using natural language processing and deep learning.

KEY POINTS: This follow-up dual-institutional and longitudinal study further evaluated for underlying gender biases in LORs for rhinology fellowship. Explicit and implicit linguistic gender bias was found, heavily favoring male applicants.

A novel staging system to consolidate silent sinus syndrome and chronic maxillary atelectasis: A systematic review and case series.

KEY POINTS: Silent sinus syndrome (SSS) and chronic maxillary atelectasis (CMA) represent an overlapping clinical entity, both likely lying on the spectrum of one disease process. There is widespread inconsistency of diagnosis in the literature of reported cases of SSS and CMA. We propose a novel, comprehensive staging system to simplify diagnosis and inform management.

Exploring Functional Connectivity in Chronic Spinal Cord Injury Patients With Neuropathic Pain Versus Without Neuropathic Pain.

The great majority of spinal cord injury (SCI) patients have debilitating chronic pain. Despite decades of research, these pain pathways of neuropathic pain (NP) are unknown. SCI patients have been shown to have abnormal brain pain pathways. We hypothesize that SCI NP patients' pain matrix is altered compared to SCI patients without NP. This study examines the functional connectivity (FC) in SCI patients with moderate-severe chronic NP compared to SCI patients with mild-no NP. These groups were compared to control subjects. The Neuropathic Pain Questionnaire and neurological evaluation based on the International Standard Neurological Classification of SCI were utilized to define the severity and level of injury. Of the 10 SCI patients, 7 (48.6 ± 17.02 years old, 6 male and 1 female) indicated that they had NP and 3 did not have NP (39.33 ± 8.08 years old, 2 male and 1 female). Ten uninjured neurologically intact participants were used as controls (24.8 ± 4.61 years old, 5 male and 5 female). FC metrics were obtained from the comparisons of resting-state functional magnetic resonance imaging among our various groups (controls, SCI with NP, and SCI without NP). For each comparison, a region-of-interest (ROI)-to-ROI connectivity analysis was pursued, encompassing a total of 175 ROIs based on a customized atlas derived from the AAL3 atlas. The analysis accounted for covariates such as age and sex. To correct for multiple comparisons, a strict Bonferroni correction was applied with a significance level of p < 0.05/NROIs. When comparing SCI patients with moderate-to-severe pain to those with mild-to-no pain, specific thalamic nuclei had altered connections. These nuclei included: medial pulvinar; lateral pulvinar; medial geniculate nucleus; lateral geniculate nucleus; and mediodorsal magnocellular nucleus. There was increased FC between the lateral geniculate nucleus and the anteroventral nucleus in NP post-SCI. Our analysis additionally highlights the relationships between the frontal lobe and temporal lobe with pain. This study successfully identifies thalamic neuroplastic changes that occur in patients with SCI who develop NP. It additionally underscores the pain matrix and involvement of the frontal and temporal lobes as well. Our findings complement that the development of NP post-SCI involves cognitive, emotional, and behavioral influences.

Stellate ganglion block for treating post-COVID-19 parosmia.

BACKGROUND: Post-COVID parosmia may be due to dysautonomia and sympathetic hyperresponsiveness, which can be attenuated by stellate ganglion block (SGB). This study evaluates SGB as a treatment for post-COVID olfactory dysfunction (OD). METHODS: Retrospective case series with prospective data of patients with post-COVID OD undergoing unilateral (UL) or bilateral (BL) SGB. Patients completed Brief Smell Identification Tests (BSIT) (12 points maximum) and post-procedure surveys including parosmia severity scores on a scale of 1 (absent) to 10 (severe). Scores were compared from before treatment (pre-SGB) to after first (SGB1) or second (SGB2) treatments in overall, UL, and BL cohorts. RESULTS: Forty-seven patients with post-COVID OD underwent SGB, including 23 UL and 24 BL. Twenty patients completed pre- and post-SGB BSITs (eight UL and 12 BL). Twenty-eight patients completed postprocedure surveys (11 UL and 17 BL). There were no differences in BSIT scores from pre-SGB to post-SGB1 or post-SGB2 for the overall (p = 0.098), UL (p = 0.168), or BL (p = 0.230) cohorts. Parosmia severity for the overall cohort improved from pre-SGB (8.82 ± 1.28) to post-SGB1 (6.79 ± 2.38) and post-SGB2 (5.41 ± 2.35), with significant differences from pre-SGB to post-SGB1 (p < 0.001) and pre-SGB to post-SGB2 (p < 0.001), but not post-SGB1 to post-SGB2 (p = 0.130). Number of parosmia triggers decreased for overall (p = 0.002), UL (p = 0.030) and BL (p = 0.024) cohorts. Quality of life (QOL) improved for all cohorts regarding food enjoyment, meal preparation, and socialization (p < 0.05). CONCLUSION: SGB may improve subjective parosmia and QOL for patients with post-COVID OD, however it may not affect odor identification. Further placebo-controlled studies are warranted.

The role of the insula in chronic pain following spinal cord injury: A resting-state fMRI study.

BACKGROUND AND PURPOSE: Spinal cord injury (SCI) results in the loss of motor and sensory function from disconnections between efferent and afferent pathways. Most SCI patients are affected with chronic neuropathic pain, but there is a paucity of data concerning neuroplastic changes following SCI. Chronic pain disrupts default networks and is associated with abnormal insular connectivity. The posterior insula (PI) is associated with the degree of pain and intensity of pain. The anterior insula (AI) is related to signal changes. Comprehension of SCI pain mechanisms is essential to elucidate effective treatment options. METHODS: This study examines the insular gyri functional connectivity (FC) of seven (five male, two female) SCI participants with moderate-severe chronic pain compared to 10 (five male, five female) healthy controls (HC). All subjects had 3-Tesla MRI performed and resting-state functional MRI (fMRI) was acquired. FC metrics were obtained from the comparisons of resting-state fMRI among our various groups. A seed-to-voxel analysis was pursued, encompassing six gyri of the insula. For multiple comparisons, a correction was applied with a significance level of p < .05. RESULTS: There were significant differences in FC of the insula between SCI participants with chronic pain compared with HC. In the SCI participants, there was hyperconnectivity of the AI and PI to the frontal pole. In addition, there was increased FC noted between the PI and the anterior cingulate cortex. Hyperconnectivity was also observed between the AI and the occipital cortex. CONCLUSIONS: These findings illustrate that there is a complex hyperconnectivity and modulation of pain pathways after traumatic SCI.

Evaluation of eight registration algorithms applied to the insula and insular gyri.

BACKGROUND AND PURPOSE: Spatial registration is crucial in establishing correspondence between anatomic brain regions for research and clinical purposes. The insular cortex (IC) and gyri (IG) are implicated in various functions and pathologies including epilepsy. Optimizing registration of the insula to a common atlas can improve the accuracy of group-level analyses. Here, we compared six nonlinear, one linear, and one semiautomated registration algorithms (RAs) for registering the IC and IG to the Montreal Neurologic Institute standard space (MNI152). METHODS: 3T images acquired from 20 controls and 20 temporal lobe epilepsy patients with mesial temporal sclerosis underwent automated segmentation of the insula. This was followed by manual segmentation of the entire IC and six individual IGs. Consensus segmentations were created at 75% agreement for IC and IG before undergoing registration to MNI152 space with eight RAs. Dice similarity coefficients (DSCs) were calculated between segmentations after registration and the IC and IG in MNI152 space. Statistical analysis involved the Kruskal-Wallace test with Dunn's test for IC and two-way analysis of variance with Tukey's honest significant difference test for IG. RESULTS: DSCs were significantly different between RAs. Based on multiple pairwise comparisons, we report that certain RAs performed better than others across population groups. Additionally, registration performance differed according to specific IG. CONCLUSION: We compared different methods for registering the IC and IG to MNI152 space. We found differences in performance between RAs, which suggests that algorithm choice is important factor in analyses involving the insula.

The Impact of Responsive Neurostimulation on the Treatment of Epilepsy.

There is a considerable number of patients with epilepsy that have drug resistant epilepsy (DRE). An additional option for these patients is resective surgery of ictal onset zones. However, a significant portion of DRE patients have unidentified or unresectable ictal zones. For these patients, RNS is a potential treatment option. The RNS system is a closed loop system that delivers stimulation in response to ECoG changes at seizure foci. It is programmed with an algorithm capable of detecting specific patterns of epileptogenic activity and triggers focal stimulation to interrupt seizures. The long term monitoring potential of the RNS system allows for a better understanding of the circadian rhythms behind epilepsy.

Tip60 protects against amyloid-ß-induced transcriptomic alterations via different modes of action in early versus late stages of neurodegeneration.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder hallmarked by amyloid-ß (Aß) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between reduced histone acetyltransferases (HAT) Tip60 and increased histone deacetylase 2 (HDAC2) levels, can directly contribute to AD pathology. However, whether such AD-associated neuroepigenetic alterations occur in response to Aß peptide production and can be protected against by increasing Tip60 levels over the course of neurodegenerative progression remains unknown. Here we profile Tip60 HAT/HDAC2 dynamics and transcriptome-wide changes across early and late stage AD pathology in the Drosophila brain produced solely by human amyloid-ß42. We show that early Aß42 induction leads to disruption of Tip60 HAT/HDAC2 balance during early neurodegenerative stages preceding Aß plaque accumulation that persists into late AD stages. Correlative transcriptome-wide studies reveal alterations in biological processes we classified as transient (early-stage only), late-onset (late-stage only), and constant (both). Increasing Tip60 HAT levels in the Aß42 fly brain protects against AD functional pathologies that include Aß plaque accumulation, neural cell death, cognitive deficits, and shorter life-span. Strikingly, Tip60 protects against Aß42-induced transcriptomic alterations via distinct mechanisms during early and late stages of neurodegeneration. Our findings reveal distinct modes of neuroepigenetic gene changes and Tip60 neuroprotection in early versus late stages in AD that can serve as early biomarkers for AD, and support the therapeutic potential of Tip60 over the course of AD progression.