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.

Hemoglobin Drop is Associated with Early Post-operative Stroke Following Revascularization Surgery for Moyamoya Disease.

BACKGROUND: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients. METHODS: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review. Logistic regression analysis was used to test for the association between hemoglobin drop and early postoperative stroke. RESULTS: In all, 106 revascularization surgeries were included in the study. A stroke occurred within 7 days after surgery in 9.4% of cases. There were no significant associations between the occurrence of an early postoperative stroke and patient age, gender, or race. Mean postoperative hemoglobin drop was greater in patients who suffered an early postoperative stroke compared with patients who did not (2.3±1.1 g/dL vs. 1.3±1.1 g/dL, respectively; P=0.034). Patients who experienced a hemoglobin drop post-operatively had 2.03 times greater odds (95% confidence interval, 1.06-4.23; P=0.040) of having a stroke than those whose hemoglobin levels were stable. Early postoperative stroke was also associated with an increase in length of hospital stay (P<0.001), discharge to a rehabilitation facility (P=0.014), and worse modified Rankin scale at 1 month (P=0.001). CONCLUSION: This study found a significant association between hemoglobin drop and early postoperative stroke following revascularization surgery in adult patients with Moyamoya disease. Based on our findings, it may be prudent to avoid hemoglobin drops in Moyamoya patients undergoing surgical revascularization.

Preoperative Opioid Use and Postoperative Outcomes in Patients Undergoing Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND AND OBJECTIVES: The prescription of opioid analgesics for trigeminal neuralgia (TN) is controversial, and their effect on postoperative outcomes for patients with TN undergoing microvascular decompression (MVD) has not been reported. We aimed to describe the relationship between preoperative opioid use and postoperative outcomes in patients with TN undergoing MVD. METHODS: We reviewed the records of 920 patients with TN at our institution who underwent an MVD between 2007 and 2020. Patients were sorted into 2 groups based on preoperative opioid usage. Demographic information, comorbidities, characteristics of TN, preoperative medications, pain and numbness outcomes, and recurrence data were recorded and compared between groups. Multivariate ordinal regression, Kaplan-Meier survival analysis, and Cox proportional hazards were used to assess differences in pain outcomes between groups. RESULTS: One hundred and forty-five (15.8%) patients in this study used opioids preoperatively. Patients who used opioids preoperatively were younger (P = .04), were more likely to have a smoking history (P < .001), experienced greater pain in modified Barrow Neurological Institute pain score at final follow-up (P = .001), and were more likely to experience pain recurrence (P = .01). In addition, patients who used opioids preoperatively were more likely to also have been prescribed TN medications including muscle relaxants and antidepressants preoperatively (P < .001 and P < .001, respectively). On multivariate regression, opioid use was an independent risk factor for greater postoperative pain at final follow-up (P = .006) after controlling for variables including female sex and age. Opioid use was associated with shorter time to pain recurrence on Kaplan-Meier analysis (P = .005) and was associated with increased risk for recurrence on Cox proportional hazards regression (P = .008). CONCLUSION: Preoperative opioid use in the setting of TN is associated with worse pain outcomes and increased risk for pain recurrence after MVD. These results indicate that opioids should be prescribed cautiously for TN and that worse post-MVD outcomes may occur in patients using opioids preoperatively.

Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.

INTRODUCTION: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages. METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition. RESULTS: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures. DISCUSSION: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. HIGHLIGHTS: Mutation position influences Aß burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aß burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.

The influence of prior percutaneous rhizotomy on outcomes following microvascular decompression for trigeminal neuralgia.

OBJECTIVE: Microvascular decompression (MVD) is an effective intervention in patients with trigeminal neuralgia (TN). How prior rhizotomy can impact long-term pain outcomes following MVD is not well understood. In this study, the authors sought to compare pain outcomes in patients who had undergone primary MVD versus those who had undergone secondary MVD after a single or multiple rhizotomies. METHODS: The authors retrospectively reviewed the data on all patients who had undergone MVD at their institution from 2007 to 2020. Patients were included in the study if they had undergone primary MVD or if their surgical history was notable for past rhizotomy. Barrow Neurological Institute (BNI) pain scores were assigned at preoperative and final follow-up appointments. Perioperative complications were noted for each patient, and evidence of pain recurrence was recorded as well. A history of rhizotomy as well as other variables that might influence TN pain recurrence were evaluated using a Cox proportional hazards model. The impact of prior rhizotomy on TN pain recurrence following MVD was further assessed using Kaplan-Meier survival analysis. RESULTS: Of 1044 patients reviewed, 947 met the study inclusion criteria. Of these, 796 patients had undergone primary MVD, 84 had a history of a single rhizotomy before MVD, and 67 had a history of ≥ 2 rhizotomies prior to MVD. Patients in the single rhizotomy and multiple rhizotomies cohorts exhibited a greater frequency of preoperative numbness (p < 0.001), higher preoperative BNI pain scores (p < 0.005), and higher rates of postoperative numbness (p = 0.04). However, final follow-up BNI pain scores were not significantly different between the primary MVD and prior rhizotomy groups (p = 0.34). Cox proportional hazards analysis revealed that younger age, multiple sclerosis, and female sex independently predicted an increased risk of pain recurrence following MVD. Neither a history of a single prior rhizotomy nor a history of multiple prior rhizotomies independently increased the risk of pain recurrence. Furthermore, Kaplan-Meier analysis of pain-free survival among the 3 groups revealed no relationship between a history of prior rhizotomy and pain recurrence following MVD (p = 0.57). CONCLUSIONS: Percutaneous rhizotomy does not complicate outcomes following subsequent MVD for TN pain. However, patients undergoing rhizotomy before MVD may have an increased risk of postoperative facial numbness compared to that in patients undergoing primary MVD.

Perioperative Infection After Aneurysmal Subarachnoid Hemorrhage: Risk Factors, Causative Pathogens, and Long-Term Outcomes.

BACKGROUND AND OBJECTIVES: Nosocomial infections are the most common complication among critically ill patients and contribute to poor long-term outcomes. Patients with aneurysmal subarachnoid hemorrhage (aSAH) are highly susceptible to perioperative infections, yet it is unclear what factors influence infection onset and functional recovery. The objective was to investigate risk factors for perioperative infections after aSAH and relate causative pathogens to patient outcomes. METHODS: Clinical records were obtained for 194 adult patients with aSAH treated at our institution from 2016 to 2020. Demographics, clinical course, complications, microbiological reports, and outcomes were collected. χ 2 , univariate, and multivariate logistic regression analyses were used to analyze risk factors. RESULTS: Nearly half of the patients developed nosocomial infections, most frequently pneumonia and urinary tract infection. Patients with infections had longer hospital stays, higher rates of delayed cerebral ischemia, and worse functional recovery up to 6 months after initial hemorrhage. Independent risk factors for pneumonia included male sex, comatose status at admission, mechanical ventilatory use, and longer admission, while those for urinary tract infection included older age and longer admission. Staphylococcus , Klebsiella , and Enterococcus spp. were associated with poor long-term outcome. Certain pathogenic organisms were associated with delayed cerebral ischemia. CONCLUSION: Perioperative infections are highly prevalent among patients with aSAH and are related to adverse outcomes. The risk profiles for nosocomial infections are distinct to each infection type and causative organism. Although strong infection control measures should be universally applied, patient management must be individualized in the context of specific infections.

Hypothermia is Associated with Improved Neurological Outcomes After Mechanical Thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) is the second leading cause of death globally. Mechanical thrombectomy (MT) has improved patient prognosis but expedient treatment is still necessary to minimize anoxic injury. Lower intraoperative body temperature decreases cerebral oxygen demand, but the role of hypothermia in treatment of AIS with MT is unclear. METHODS: We retrospectively reviewed patients undergoing MT for AIS from 2014 to 2020 at our institution. Patient demographics, comorbidities, intraoperative parameters, and outcomes were collected. Maximum body temperature was extracted from minute-by-minute anesthesia readings, and patients with maximal temperature below 36°C were considered hypothermic. Risk factors were assessed by χ2 and multivariate ordinal regression. RESULTS: Of 68 patients, 27 (40%) were hypothermic. There was no significant association of hypothermia with patient age, comorbidities, time since last known well, number of passes intraoperatively, favorable revascularization, tissue plasminogen activator use, and immediate postoperative complications. Hypothermic patients exhibited better neurologic outcome at 3-month follow-up (P = 0.02). On multivariate ordinal regression, lower maximum intraoperative body temperature was associated with improved 3-month outcomes (P < 0.001), when adjusting for other factors influencing neurological outcomes. Other significant protective factors included younger age (P = 0.03), better revascularization (P = 0.03), and conscious sedation (P = 0.02). CONCLUSIONS: Lower intraoperative body temperature during MT was independently associated with improved neurological outcome in this single center retrospective series. These results may help guide clinicians in employing therapeutic hypothermia during MT to improve long-term neurologic outcomes from AIS, although larger studies are needed.

Risk of Subdural Hematoma Expansion in Patients With End-Stage Renal Disease: Continuous Venovenous Hemodialysis Versus Intermittent Hemodialysis.

BACKGROUND AND OBJECTIVES: Subdural hematoma (SDH) patients with end-stage renal disease (ESRD) require renal replacement therapy in addition to neurological management. We sought to determine whether continuous venovenous hemodialysis (CVVHD) or intermittent hemodialysis (iHD) is associated with higher rates of SDH re-expansion as well as morbidity and mortality. METHODS: Hemodialysis-dependent patients with ESRD who were discovered to have an SDH were retrospectively identified from 2016 to 2022. Rates of SDH expansion during CVVHD vs iHD were compared. Hemodialysis mode was included in a multivariate logistic regression model to test for independent association with SDH expansion and mortality. RESULTS: A total of 123 hemodialysis-dependent patients with ESRD were discovered to have a concomitant SDH during the period of study. Patients who received CVVHD were on average 10.2 years younger ( P < .001), more likely to have traumatic SDH (47.7% vs 19.0%, P < .001), and more likely to have cirrhosis (25.0% vs 10.1%, P = .029). SDH expansion affecting neurological function occurred more frequently during iHD compared with CVVHD (29.7% vs 12.0%, P = .013). Multivariate logistic regression analysis found that CVVHD was independently associated with decreased risk of SDH affecting neurological function (odds ratio 0.25, 95% CI 0.08-0.65). Among patients who experienced in-hospital mortality or were discharged to hospice, 5% suffered a neurologically devastating SDH expansion while on CVVHD compared with 35% on iHD. CONCLUSION: CVVHD was independently associated with decreased risk of neurologically significant SDH expansion. Therefore, receiving renal replacement therapy through a course of CVVHD may increase SDH stability in patients with ESRD.

Neurovascular Compression in Patients With Trigeminal Neuralgia May Be Associated With Worse Outcomes After Primary Percutaneous Rhizotomy.

BACKGROUND AND OBJECTIVES: Percutaneous rhizotomy may be an effective primary intervention in patients with trigeminal neuralgia who are poor candidates for microvascular decompression or those who desire a less invasive approach. However, the influence of neurovascular compression on pain-free survival after primary percutaneous rhizotomy is not well understood. METHODS: We retrospectively reviewed all patients undergoing percutaneous rhizotomy at our institution from 1995 to 2022. Patients were included if they had no history of surgical intervention, available preoperative MRI imaging, and postoperative follow-up data. Barrow Neurological Institute pain scores were assigned at various time points. We collected baseline patient information, pain characteristics, and perioperative complications for each patient. In addition, we recorded evidence of pain recurrence. Patients were dichotomized into those with evidence of neurovascular compression on preoperative MRI vs those without. The effect of neurovascular compression on pain-free survival was assessed using Kaplan-Meier Cox proportional hazards analyses. RESULTS: Of the 2726 patients reviewed, 298 met our inclusion criteria. Our study comprised 261 patients with no evidence of neurovascular compression on preoperative MRI vs 37 patients with evidence of neurovascular compression on preoperative MRI. Patients in the compression group had a shorter median duration to recurrence compared with those in the no compression group, P = .01. Kaplan-Meier survival analysis revealed that patients with preoperative evidence of neurovascular compression on MRI imaging demonstrated shorter pain-free survival compared with those without such evidence [hazard ratio = 1.57 (1.03-2.4), P = .037]. Cox proportional hazards analysis demonstrated that evidence of neurovascular compression was associated with poor pain-free survival [hazard ratio = 1.64 (1.06-2.53), P = .03]. CONCLUSION: Patients with neurovascular compression on preoperative MRI may experience reduced time to recurrence compared with those without after percutaneous rhizotomy. These patients should be counseled on potential reduced efficacy of percutaneous rhizotomy as a primary intervention for their pain.

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.

A Case Series of Stereotactic Radiosurgery First for Trigeminal Neuralgia: A History of Stereotactic Radiosurgery Does Not Complicate Microvascular Decompression.

BACKGROUND AND OBJECTIVES: The influence of prior stereotactic radiosurgery (SRS) on outcomes of subsequent microvascular decompression (MVD) for patients with trigeminal neuralgia (TN) is not well understood. To directly compare pain outcomes in patients undergoing primary MVD vs those undergoing MVD with a history of 1 prior SRS procedure. METHODS: We retrospectively reviewed all patients undergoing MVD at our institution from 2007 to 2020. Patients were included if they underwent primary MVD or had a history of SRS alone before MVD. Barrow Neurological Institute (BNI) pain scores were assigned at preoperative and immediate postoperative time points and at every follow-up appointment. Evidence of pain recurrence was recorded and compared via Kaplan-Meier analysis. Multivariate Cox proportional hazards regression was used to identify factors associated with worse pain outcomes. RESULTS: Of patients reviewed, 833 met our inclusion criteria. Thirty-seven patients were in the SRS alone before MVD group, and 796 patients were in the primary MVD group. Both groups demonstrated similar preoperative and immediate postoperative BNI pain scores. There were no significant differences between average BNI at final follow-up between the groups. Multiple sclerosis (hazard ratio (HR) = 1.95), age (HR = 0.99), and female sex (HR = 1.43) independently predicted increased likelihood of pain recurrence on Cox proportional hazards analysis. SRS alone before MVD did not predict increased likelihood of pain recurrence. Furthermore, Kaplan-Meier survival analysis demonstrated no relationship between a history of SRS alone and pain recurrence after MVD ( P = .58). CONCLUSION: SRS is an effective intervention for TN that may not worsen outcomes for subsequent MVD in patients with TN.

Preoperative Characteristics and Postoperative Pain Outcomes in Trigeminal Neuralgia With Concomitant Autoimmune Disease.

BACKGROUND AND OBJECTIVES: Although the association between multiple sclerosis and trigeminal neuralgia (TN) is well established, little is known about TN pain characteristics and postoperative pain outcomes after microvascular decompression (MVD) in patients with TN and other autoimmune diseases. In this study, we aim to describe presenting characteristics and postoperative outcomes in patients with concomitant TN and autoimmune disease who underwent an MVD. METHODS: A retrospective review of all patients who underwent an MVD at our institution between 2007 and 2020 was conducted. The presence and type of autoimmune disease were recorded for each patient. Patient demographics, comorbidities, clinical characteristics, postoperative Barrow Neurological Institute (BNI) pain and numbness scores, and recurrence data were compared between groups. RESULTS: Of the 885 patients with TN identified, 32 (3.6%) were found to have concomitant autoimmune disease. Type 2 TN was more common in the autoimmune cohort ( P = .01). On multivariate analysis, concomitant autoimmune disease, younger age, and female sex were found to be significantly associated with higher postoperative BNI score ( P = .04, <0.001, and <0.001, respectively). In addition, patients with autoimmune disease were more likely to experience significant pain recurrence ( P = .009) and had shorter time to recurrence on Kaplan-Meier analysis ( P = .047), although this relationship was attenuated on multivariate Cox proportional hazards regression. CONCLUSION: Patients with concomitant TN and autoimmune disease were more likely to have Type 2 TN, had worse postoperative BNI pain scores at the final follow-up after MVD, and were more likely to experience recurrent pain than patients with TN alone. These findings may influence postoperative pain management decisions for these patients and support a possible role for neuroinflammation in TN pain.

Venous thromboembolism in aneurysmal subarachnoid hemorrhage: Risk factors and timing of chemoprophylaxis.

INTRODUCTION: Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality among patients recovering from aneurysmal subarachnoid hemorrhage (aSAH). Prophylactic heparin reduces the risk of VTE, but the optimal timing for its initiation among aSAH patients remains unclear. OBJECTIVE: To conduct a retrospective study assessing risk factors for VTE and optimal timing of chemoprophylaxis in patients treated for aSAH. METHODS: From 2016-2020, 194 adult patients were treated for aSAH at our institution. Patient demographics, clinical diagnoses, complications, pharmacologic interventions, and outcomes were recorded. Risk factors for symptomatic VTE (sVTE) were analyzed via Chi-squared, univariate, and multivariate regression. RESULTS: In total 33 patients presented with sVTE (25 DVT, 14 PE). Patients with sVTE had longer hospital stays (p < 0.01) and worse outcomes at one-month (p < 0.01) and three-month follow-up (p = 0.02). Univariate predictors of sVTE included male sex (p = 0.03), Hunt Hess score (p = 0.01), Glasgow Coma scale (p = 0.02), intracranial hemorrhage (p = 0.03), hydrocephalus requiring external ventricular drain (EVD) placement (p < 0.01), and mechanical ventilation (p < 0.01). Only hydrocephalus requiring EVD (p = 0.01) and ventilator use (p = 0.02) remained significant upon multivariate analysis. Patients with delayed heparin introduction were significantly more likely to sustain sVTE on univariate analysis (p = 0.02) with a trend-level significance on multivariate analysis (p = 0.07). CONCLUSIONS: Patients with aSAH are more likely to develop sVTE following use of perioperative EVD or mechanical ventilation. sVTE leads to longer hospital stays and worse outcomes among patients treated for aSAH. Delayed heparin initiation increases the risk of sVTE. Our results may help guide surgical decision-making during recovery from aSAH and improve VTE-related postoperative outcomes.

Outcomes After Microvascular Decompression for Sole Arterial Versus Venous Compression in Trigeminal Neuralgia.

OBJECTIVE: In most cases of trigeminal neuralgia (TN), the trigeminal nerve is compressed by the arterial vasculature. We sought to address the gap in understanding of pain outcomes in patients with sole arterial versus sole venous compression. METHODS: We retrospectively reviewed all patients undergoing microvascular decompression at our institution, identifying patients with either sole arterial or venous compression. We dichotomized patients into arterial or venous groups and obtained demographics and postoperative complications for each case. Barrow Neurological Index (BNI) pain scores were collected preoperatively, postoperatively, and at final follow-up, as well as recurrence of pain. Differences were calculated via χ2 tests t tests, and Mann-Whitney U Tests. Ordinal regression was used to account for variables known to influence TN pain. Kaplan-Meier analysis was used to determine recurrence-free survival. RESULTS: Of 1044 patients, 642 (61.5%) had either sole arterial or venous compression. Of these cases, 472 showed arterial compression and 170 showed sole venous compression. Patients in the venous compression group were significantly younger (P < 0.001). Patients with sole venous compression showed worse preoperative (P = 0.04) and final follow-up (P < 0.001) pain scores. Patients with sole venous compression had significantly higher rate of pain recurrence (P = 0.02) and BNI score at pain recurrence (P = 0.04). On ordinal regression, venous compression was found to independently predict worse BNI pain scores (odds ratio, 1.66; P = 0.003). Kaplan-Meier analysis showed a significant relationship between sole venous compression and increased risk of pain recurrence (P = 0.03). CONCLUSIONS: Patients with TN with sole venous compression show worse pain outcomes after microvascular decompression compared with those with only arterial compression.

Sex-Specific Pain Outcomes Following Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is more prevalent among women. However, while microvascular decompression (MVD) is the most effective long-term surgical treatment for TN, it is unclear whether it is equally efficacious for men and women. We sought to characterize the relationship between sex and pain outcomes following MVD for TN. METHODS: From 2007 to 2020, 938 unilateral TN patients were treated with MVD at our institution. Patient demographics, clinical characteristics, operative features, and pain outcomes were recorded. Differences between men and women were analyzed via t-test and chi-squared analyses. A multivariate ordinal regression was used to establish significant predictors of pain outcome. Differences in time to pain recurrence were assessed via Cox proportional hazards and Kaplan-Meier nonparametric survival analysis. RESULTS: A majority (67%) of the 938 patients analyzed were female. Men and women presented with similar preoperative pain severity (P = 0.17). Female sex (P = 0.048) and younger age (P = 0.03) were independently associated with worsened Barrow Neurological Institute pain scores at 3-month follow-up on multivariate analysis. Women were also more likely to experience recurrence than men (P = 0.01), and time to recurrence was shorter among women (P = 0.02). Only female sex was independently associated with increased risk of postoperative pain recurrence on multivariate Cox proportional hazards regression (P = 0.01). CONCLUSIONS: Female TN patients undergoing MVD had worse pain outcomes, more frequent pain recurrence, and shorter time to recurrence. Our results indicate a sex-specific dimorphism in response to MVD among TN patients.

The Structural and Functional Correlates of Frailty in Persons With Human Immunodeficiency Virus.

BACKGROUND: Persons with HIV (PWH) are at increased risk of frailty, a clinically recognizable state of increased vulnerability resulting from aging-associated decline in multiple physiologic systems. Frailty is often defined by the Fried criteria, which includes subjective and objective standards concerning health resiliency. However, these frailty metrics do not incorporate cognitive performance or neuroimaging measures. METHODS: We compared structural (diffusion tensor imaging [DTI]) and functional (cerebral blood flow [CBF]) neuroimaging markers in PWH with frailty and cognitive performance. Virologically controlled PWH were dichotomized as either frail (≥3) or nonfrail (<3) using the Fried criteria. Cognitive Z-scores, both domain (executive, psychomotor speed, language, and memory) and global, were derived from a battery of tests. We identified three regions of reduced CBF, based on a voxel-wise comparison of frail PWH compared with nonfrail PWH. These clusters (bilateral frontal and posterior cingulate) were subsequently used as seed regions of interest (ROIs) for DTI probabilistic white matter tractography. RESULTS: White matter integrity connecting the ROIs was significantly decreased in frail compared with nonfrail PWH. No differences in cognition were observed between frail and nonfrail PWH. However, reductions in white matter integrity among these ROIs was significantly associated with worse psychomotor speed and executive function across the entire cohort. CONCLUSIONS: We conclude that frailty in PWH can lead to structural and functional brain changes, including subtle changes that are not detectable by standard neuropsychological tests. Multimodal neuroimaging in conjunction with frailty assessment could identify pathological brain changes observed in PWH.

CSF Tau phosphorylation at Thr205 is associated with loss of white matter integrity in autosomal dominant Alzheimer disease.

BACKGROUND: Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer's disease (AD). However, it remains unknown whether white matter (WM) decline due to AD is associated with specific Tau phosphorylation site(s). METHODS: In autosomal dominant AD (ADAD) mutation carriers (MC) and non-carriers (NC) we compared cerebrospinal fluid (CSF) phosphorylation at tau sites (pT217, pT181, pS202, and pT205) and total tau with WM measures, as derived from diffusion tensor imaging (DTI), and cognition. A WM composite metric, derived from a principal component analysis, was used to identify spatial decline seen in ADAD. RESULTS: The WM composite explained over 70% of the variance in MC. WM regions that strongly contributed to the spatial topography were located in callosal and cingulate regions. Loss of integrity within the WM composite was strongly associated with AD progression in MC as defined by the estimated years to onset (EYO) and cognitive decline. A linear regression demonstrated that amyloid, gray matter atrophy and phosphorylation at CSF tau site pT205 each uniquely explained a reduction in the WM composite within MC that was independent of vascular changes (white matter hyperintensities), and age. Hyperphosphorylation of CSF tau at other sites and total tau did not significantly predict WM composite loss. CONCLUSIONS: We identified a site-specific relationship between CSF phosphorylated tau and WM decline within MC. The presence of both amyloid deposition and Tau phosphorylation at pT205 were associated with WM composite loss. These findings highlight a primary AD-specific mechanism for WM dysfunction that is tightly coupled to symptom manifestation and cognitive decline.

Cardiorespiratory Fitness Is Associated With Better White Matter Integrity in Persons Living With HIV.

BACKGROUND: Despite improved survival rates, neurocognitive impairment persists in persons living with HIV (PLWH). An active lifestyle is linked to improved cognition among PLWH, yet the neural substrates remain unclear. Diffusion tensor imaging and diffusion basis spectrum imaging measure HIV-related changes in brain white matter integrity. We used these measures of structural brain integrity to assess white matter changes, physical fitness, and cognition in a cross-sectional study of PLWH. METHODS: Forty-four virologically well-controlled PLWH were recruited (average age of 56 years, a median recent CD4+ count of 682 cells/mm3). Diffusion tensor imaging -derived fractional anisotropy (FA) and diffusion basis spectrum imaging-derived axonal density were calculated. Cardiorespiratory fitness [maximal volume of oxygen consumption (VO2 max)] was measured by performing indirect calorimetry during exercise to volitional exhaustion. Cardiovascular risk was assessed by the Framingham risk score. Neuropsychological performance (NP) testing evaluated learning, memory, psychomotor/processing speed, and executive function. Partial correlations assessed the relationships among cardiorespiratory fitness, neuroimaging, NP, and HIV clinical metrics (CD4+ count and time since diagnosis). RESULTS: Higher VO2 max was associated with higher FA and higher axonal density in multiple white matter tracts, including the corticospinal tract and superior longitudinal fasciculus. Better NP in the motor/psychomotor domain was positively associated with FA and axonal density in diverse tracts including those associated with motor and visuospatial processing. However, higher VO2 max was not associated with NP or HIV clinical metrics. CONCLUSIONS: An active lifestyle promoting cardiorespiratory fitness may lead to better white matter integrity and decreased susceptibility to cognitive decline in virologically well-controlled PLWH.

Effects of anticholinergic medication use on brain integrity in persons living with HIV and persons without HIV.

OBJECTIVE: This study examined relationships between anticholinergic medication burden and brain integrity in people living with HIV (PLWH) and people without HIV (HIV-). METHODS: Neuropsychological performance z-scores (learning, retention, executive function, motor/psychomotor speed, language domains, and global cognition), and neuroimaging measures (brain volumetrics and white matter fractional anisotropy) were analyzed in PLWH (n = 209) and HIV- (n = 95) grouped according to the Anticholinergic Cognitive Burden (ACB) scale (0 = no burden, 1-3 = low burden, >3 = high burden). Neuropsychological performance and neuroimaging outcomes were compared between HIV- and PLWH with high anticholinergic burden. Within a cohort of PLWH (n = 90), longitudinal change in ACB score over ∼2 years was correlated to the rate of change per month of study interval in neuropsychological performance and neuroimaging measures. RESULTS: A higher number of anticholinergic medications and ACB was observed in PLWH compared with HIV- (P < 0.05). A higher ACB was associated with worse motor/psychomotor performance, smaller occipital lobe, putamen, subcortical gray matter and total gray matter volumes in HIV-; and poorer executive function, retention and global cognition, smaller brain volumes (frontal, parietal and temporal lobes, hippocampus, amygdala, cortex, subcortical gray matter and total gray matter), and reduced fractional anisotropy (posterior corpus callosum, perforant pathway) in PLWH. PLWH with high anticholinergic burden performed worse on tests of learning and executive function compared with HIV- with high anticholinergic burden. Longitudinally, PLWH who reduced their ACB over time had better neuropsychological performance and neuroimaging measures. CONCLUSION: Anticholinergic medications were associated with worse neuropsychological performance and reduced structural brain integrity, and these effects were more widespread in PLWH. Use of anticholinergic medications should be carefully monitored in older adults with deprescription considered whenever possible.