Citations

OBJECTIVE Preoperative differentiation of facial nerve schwannoma (FNS) from vestibular schwannoma (VS) can be challenging, and failure to differentiate between these two pathologies can result in potentially avoidable facial nerve injury. This study presents the combined experience of two high-volume centers in the management of intraoperatively diagnosed FNSs. The authors highlight clinical and imaging features that can distinguish FNS from VS and provide an algorithm to help manage intraoperatively diagnosed FNS. METHODS Operative records of 1484 presumed sporadic VS resections between January 2012 and December 2021 were reviewed, and patients with intraoperatively diagnosed FNSs were identified. Clinical data and preoperative imaging were retrospectively reviewed for features suggestive of FNS, and factors associated with good postoperative facial nerve function (House-Brackmann [HB] grade ≤ 2) were identified. A preoperative imaging protocol for suspected VS and recommendations for surgical decision-making following an intraoperative FNS diagnosis were created. RESULTS Nineteen patients (1.3%) with FNSs were identified. All patients had normal facial motor function preoperatively. In 12 patients (63%), preoperative imaging demonstrated no features suggestive of FNS, with the remainder showing subtle enhancement of the geniculate/labyrinthine facial segment, widening/erosion of the fallopian canal, or multiple tumor nodules in retrospect. Eleven (57.9%) of the 19 patients underwent a retrosigmoid craniotomy, and in the remaining patients, a translabyrinthine (n = 6) or transotic (n = 2) approach was used. Following FNS diagnosis, 6 (32%) of the tumors underwent gross-total resection (GTR) and cable nerve grafting, 6 (32%) underwent subtotal resection (STR) and bony decompression of the meatal facial nerve segment, and 7 (36%) underwent bony decompression only. All patients undergoing subtotal debulking or bony decompression exhibited normal postoperative facial function (HB grade I). At the last clinical follow-up, patients who underwent GTR with a facial nerve graft had HB grade III (3 of 6 patients) or IV facial function. Tumor recurrence/regrowth occurred in 3 patients (16%), all of whom had been treated with either bony decompression or STR. CONCLUSIONS Intraoperative diagnosis of an FNS during a presumed VS resection is rare, but its incidence can be reduced further by maintaining a high index of suspicion and undertaking further imaging in patients with atypical clinical or imaging features. If an intraoperative diagnosis does occur, conservative surgical management with bony decompression of the facial nerve only is recommended, unless there is significant mass effect on surrounding structures.

ObjectiveIdentifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR‐tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer's disease related neurofibrillary tau pathological changes. We examined the cerebrospinal fluid (CSF) MTBR‐tau species in dominantly inherited Alzheimer's disease (DIAD) mutation carriers to assess the association with Alzheimer's disease (AD) biomarkers and clinical symptoms.MethodsCross‐sectional and longitudinal CSF from 229 DIAD mutation carriers and 130 mutation non‐carriers had sequential characterization of N‐terminal/mid‐domain phosphorylated tau (p‐tau) followed by MTBR‐tau species and tau positron emission tomography (tau PET), other soluble tau and amyloid biomarkers, comprehensive clinical and cognitive assessments, and brain magnetic resonance imaging of atrophy.ResultsCSF MTBR‐tau species located within the putative “border” region and one species corresponding to the “core” region of aggregates in neurofibrillary tangles (NFTs) increased during the presymptomatic stage and decreased during the symptomatic stage. The “border” MTBR‐tau species were associated with amyloid pathology and CSF p‐tau; whereas the “core” MTBR‐tau species were associated stronger with tau PET and CSF measures of neurodegeneration. The ratio of the border to the core species provided a continuous measure of increasing amounts that tracked clinical progression and NFTs.InterpretationChanges in CSF soluble MTBR‐tau species preceded the onset of dementia, tau tangle increase, and atrophy in DIAD. The ratio of 4R‐specific MTBR‐tau (border) to the NFT (core) MTBR‐tau species corresponds to the pathology of NFTs in DIAD and change with disease progression. The dynamics between different MTBR‐tau species in the CSF may serve as a marker of tau‐related disease progression and target engagement of anti‐tau therapeutics. ANN NEUROL 2023;93:1158–1172

Intraoperative electrocochleography (ECOG) is performed using a single low-frequency acoustic stimulus (e.g., 500 Hz) to monitor cochlear microphonics (CM) during cochlear implant (CI) electrode insertion. A decrease in CM amplitude is commonly associated with cochlear trauma and is used to guide electrode placement. However, advancement of the recording electrode beyond the sites of CM generation can also lead to a decrease in CM amplitude and is sometimes interpreted as cochlear trauma, resulting in unnecessary electrode manipulation and increased risk of cochlear trauma during CI electrode placement. In the present study, multi-frequency ECOG was used to monitor CM during CI electrode placement. The intraoperative CM tracings were compared with electrode scan measurements, where CM was measured for each of the intracochlear electrodes. Comparison between the peak CM amplitude measured during electrode placement and electrode scan measurements was used to differentiate between different mechanisms for decrease in CM amplitude during CI electrode insertion. Analysis of the data shows that both multi-frequency electrocochleography and electrode scan could potentially be used to differentiate between different mechanisms for decreasing CM amplitude and providing appropriate feedback to the surgeon during CI electrode placement.

Abstract Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and CSF and is predictive of cognitive function in individuals with Alzheimer’s disease. There has been limited prior work linking neurofilament light and functional connectivity, and no prior work has investigated neurofilament light associations with functional connectivity in autosomal dominant Alzheimer’s disease. Here, we assessed relationships between blood neurofilament light, cognition, and functional connectivity in a cross-sectional sample of 106 autosomal dominant Alzheimer’s disease mutation carriers and 76 non-carriers. We employed an innovative network-level enrichment analysis approach to assess connectome-wide associations with neurofilament light. Neurofilament light was positively correlated with deterioration of functional connectivity within the default mode network and negatively correlated with connectivity between default mode network and executive control networks, including the cingulo-opercular, salience, and dorsal attention networks. Further, reduced connectivity within the default mode network and between the default mode network and executive control networks was associated with reduced cognitive function. Hierarchical regression analysis revealed that neurofilament levels and functional connectivity within the default mode network and between the default mode network and the dorsal attention network explained significant variance in cognitive composite scores when controlling for age, sex, and education. A mediation analysis demonstrated that functional connectivity within the default mode network and between the default mode network and dorsal attention network partially mediated the relationship between blood neurofilament light levels and cognitive function. Our novel results indicate that blood estimates of neurofilament levels correspond to direct measurements of brain dysfunction, shedding new light on the underlying biological processes of Alzheimer’s disease. Further, we demonstrate how variation within key brain systems can partially mediate the negative effects of heightened total serum neurofilament levels, suggesting potential regions for targeted interventions. Finally, our results lend further evidence that low-cost and minimally invasive blood measurements of neurofilament may be a useful marker of brain functional connectivity and cognitive decline in Alzheimer’s disease.

Objective To characterize the effect of the COVID-19 pandemic on national cochlear implantation utilization by age using inclusive cochlear implantation data from two manufacturers between 2015 and 2020. Study Design Analysis of prospectively registered consecutive patient data from two major cochlear implant (CI) manufacturers in the United States. Patients Children or adults who received CIs. Interventions Cochlear implantation. Main Outcome Measures Annual implantation utilization by age. Results A total of 46,804 patients received CIs from the two participating manufacturers between 2015 and 2020. The annual number of implant recipients increased significantly during the first 5 years of the study period for both children and adults, from a total of 6,203 in 2015 to 9,213 in 2019 (p < 0.001). During 2020, there was a 13.1% drop in national cochlear implantation utilization across all ages compared with 2019, including a drop of 2.2% for those ≤3 years old, 3.8% for those 4–17 years old, 10.1% for those 18–64 years old, 16.6% for those 65–79 years old, and 22.5% for those ≥80 years old. In a multivariable linear regression model, the percent drop in CIs differed significantly by age-group (p = 0.005). Conclusions Especially in light of the prepandemic projected CI counts for 2020, the COVID-19 pandemic reduced national cochlear implantation utilization by over 15% among Medicare-aged patients and by almost 25% among those ≥80 years old, resulting in more than a 3-year setback in total annual CIs. Children were less affected, with those ≤3 years old experiencing minimal interruption during 2020.