Assembly of FAP93 at the proximal axoneme in Chlamydomonas cilia.

To identify proteins specific to the proximal ciliary axoneme, we used iTRAQ to compare short (~2 µm) and full-length (~11 µm) axonemes of Chlamydomonas. Known compoents of the proximal axoneme such as minor dynein heavy chains and LF5 kinase as well as the ciliary tip proteins FAP256 (CEP104) and EB1 were enriched in short axonemes whereas proteins present along the length of the axoneme were of similar abundance in both samples. The iTRAQ analysis revealed that FAP93, a protein of unknown function, and protein phosphatase 2A (PP2A) are enriched in the short axonemes. Consistently, immunoblots show enrichment of FAP93 and PP2A in short axonemes and immunofluorescence confirms the localization of FAP93 and enrichment of PP2A at the proximal axoneme. Ciliary regeneration reveals that FAP93 assembles continuously but more slowly than other axonemal structures and terminates at 1.03 µm in steady-state axonemes. The length of FAP93 assembly correlates with ciliary length, demonstrating ciliary length-dependent assembly of FAP93. Dikaryon rescue experiments show that FAP93 can assemble independently of IFT transport. In addition, FRAP analysis of GFP-tagged FAP93 demonstrates that FAP93 is stably anchored in axoneme. FAP93 may function as a scaffold for assembly of other specific proteins at the proximal axoneme.

Postoperative Cerebrospinal Fluid-Related Complications After Posterior Fossa and Posterolateral Skull Base Surgeries: Development of a Predictive Model and Clinical Risk Score.

BACKGROUND: Postoperative pseudomeningocele (PMC) and cerebrospinal fluid (CSF) leak are common complications following posterior fossa and posterolateral skull base surgeries. We sought to 1) determine the rate of CSF-related complications and 2) develop a perioperative model and risk score to identify the highest risk patients for these events. METHODS: We performed a retrospective cohort of 450 patients undergoing posterior fossa and posterolateral skull base procedures from 2016 to 2020. Logistic regressions were performed for predictor selection for 3 prespecified models: 1) a priori variables, 2) predictors selected by large effect sizes, and 3) predictors with P ≤ 0.100 on univariable analysis. A final model was created by elimination of nonsignificant predictors, and the integer-based postoperative CSF-related complications (POCC) clinical risk score was derived. Internal validation was done using 10-fold cross-validation and bootstrapping with uniform shrinkage. RESULTS: A total of 115 patients (25.6%) developed PMC and/or CSF leakage. Age >55 years (odds ratio [OR], 0.560; 95% confidence interval [CI], 0.328-0.954), body mass index >30 kg/m2 (OR, 1.88; 95% CI, 1.14-3.10), and postoperative CSF diversion (OR, 2.85; 95% CI, 1.64-5.00) were associated with CSF leak and PMC. Model 2 was the most predictive (cross-validated area under the receiver operating characteristic curve, 0.690). The final risk score was devised using age, body mass index class, dural repair technique, use of bone substitute, and duration of postoperative CSF diversion. The POCC score performed well (cross-validated area under the receiver operating characteristic curve, 0.761) and was highly specific (96.1%). CONCLUSIONS: We created the first generalizable and predictive risk score to identify patients at risk of CSF-related complications. The POCC score could improve surveillance, inform doctor-patient discussions regarding the risks of surgery, and assist in perioperative management.

Transition Cow Nutrition and Management Strategies of Dairy Herds in the Northeastern United States: Associations of Nutritional Strategies with Analytes, Health, Milk Yield, and Reproduction.

The objective was to identify relationships between transition cow nutritional strategies and the prevalence of elevated analytes (nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), and haptoglobin (Hp)), disorder incidence (DI), milk yield, and reproductive performance. Multiparous and primiparous cows from 72 farms in the northeastern US were enrolled in a herd-level cohort study. Farms were dichotomized within parity into a nutritional strategy within each period; far-off: controlled energy (CE; <16.5% starch and ≥40% forage neutral detergent fiber (FNDF)) or not CE (NCE; ≥16.5% starch or <40% FNDF or both), close-up: high FNDF (HF; ≥40% FNDF) or low FNDF (LF; <40% FNDF), and fresh: low starch (LS; <25.5% starch) or high starch (HS; ≥25.5% starch). No evidence existed that transition cow nutritional strategies were associated with milk yield outcomes (p ≥ 0.20). In general, our results support feeding multiparous cows HF close-up and HS fresh to minimize excessive BHB and DI; however, multiparous cows fed LF close-up had a higher pregnancy rate, and lower prepartum NEFA and Hp. Similarly, our results support feeding primiparous cows CE far-off, HF close-up, and HS fresh to maximize reproductive performance, and minimize BHB and DI; however, herds fed HF close-up or HS fresh had higher Hp.

Transpetrosal Approach to a Ruptured Distal Basilar Perforating Artery Aneurysm.

Basilar perforating artery aneurysms are rare and underreported vascular anomalies in the cerebrovascular literature. Various open and endovascular treatment approaches can be employed to treat these aneurysms based on several patient- and aneurysm-specific factors. Some authors have even advocated for conservative, nonoperative management. Here, we report a case of a ruptured distal basilar perforating artery aneurysm secured by an open transpetrosal approach. A 67-year-old male presented to our institution with a Hunt-Hess grade 2, modified Fisher grade 3 subarachnoid hemorrhage (SAH). Initial cerebral digital subtraction angiography (DSA) did not identify an intracranial aneurysm or other vascular lesions. However, the patient had a re-rupture event several days after presentation. DSA at this time revealed a posteriorly projecting distal basilar perforating artery aneurysm. Initial attempts with endovascular coil embolization were unsuccessful. Thus, an open transpetrosal approach was taken to gain access to the middle and distal basilar trunk to secure the aneurysm. This case underscores the unpredictability of basilar perforating artery aneurysms and the challenges encountered when considering active treatment. We demonstrate an open surgical approach with an intraoperative video for definitive management after failed attempted endovascular treatment.

Incidence and management of postoperative pseudomeningocele and cerebrospinal fluid leak after Chiari malformation type I decompression.

OBJECTIVE: The optimal surgical management of Chiari malformation type I (CM-I) remains controversial and heterogeneous. The authors sought to investigate patient-specific, technical, and perioperative features that may affect the incidence of CSF-related complications including pseudomeningocele and CSF leak at their institution. METHODS: The authors performed a single-center, retrospective review of all adult patients with CM-I who underwent posterior fossa decompression. Patient demographics, operative details, and perioperative factors were collected via electronic medical record review. The authors performed Fisher's exact test and independent Student t-tests for categorical and continuous variables, respectively. Univariate regression analysis was performed to determine odds ratios. A multivariable regression analysis was performed for those factors with p < 0.10 or large effect sizes (OR ≥ 2.0 or ≤ 0.50) by univariate analysis. The STROBE guidelines for observational studies were followed. RESULTS: A total of 59 adult patients were included. Most patients were female (78.0%), and the mean body mass index was 32.2 (± 9.0). Almost one-third (30.5%) of patients had a syrinx on preoperative imaging. All patients underwent expansile duraplasty, of which 47 (79.7%) were from autologous pericranium. Arachnoid opening for fourth ventricular inspection was performed in 26 (44.1%) cases. CSF-related complications were identified in 18 (30.5%) of cases. Thirteen (22.0%) patients required readmission and 11 (18.6%) required intervention such as wound revision (n = 5), wound revision with CSF diversion (n = 4), CSF diversion alone (n = 1), or blood patch (n = 1). Three (5.1%) patients required permanent CSF diversion. Male sex (OR 3.495), diabetes mellitus (OR 0.249), tobacco use (OR 2.53), body mass index more than 30 (OR 2.45), preoperative syrinx (OR 1.733), autologous duraplasty (OR 0.331), and postoperative steroids (OR 2.825) were included in the multivariable analysis. No factors achieved significance by univariate or multivariable analysis (all p > 0.05). CONCLUSIONS: The authors report a single-center, retrospective experience of posterior fossa decompression for 59 adults with CM-I. No perioperative or technical features were found to affect the CSF-related complication rate. More standardized practices within centers are necessary to better delineate the true risk factors and potential protective factors against CSF-related complications.

Predictors and Outcomes of Subdural Hematomas Managed via Subdural Evacuation Port System.

Background: Subacute subdural hematoma (SDH) is a common pathology most frequently affecting older patients and may be treated operatively through burr holes versus craniotomy or minimally invasively with bedside twist drill craniostomy. Less invasive intervention is favored when possible given a frequently comorbid population. The subdural evacuation port system (SEPS) is a popular treatment option that warrants investigation and reporting of its use and outcomes. Methods: A retrospective review of consecutive patients undergoing SEPS drain placement for chronic or mixed density SDH between 2010 and 2021 was conducted. Outcomes of SDH recurrence, need for operating room procedure after SEPS placement, discharge disposition other than home, and modified Rankin Scale score <3 at discharge were modeled with logistic regression using multiple demographic, clinical, and radiographic features. Results: Ultimately, 86 patients (mean age 68) were included in the analysis with 66 (78%) presenting with mixed-density SDHs. Radiographic factors such as hematoma thickness and midline shift were not associated with the need for an operating room procedure after SEPS placement or discharge disposition. However, the presence of septations and mixed-density SDH versus chronic SDH was significantly associated with increased odds of requiring an operative intervention after SEPS placement. Conclusions: Subacute SDHs are a frequent neurosurgical issue in patient populations where less invasive measures are favored. SEPS drainage continues to be an effective treatment option. However, the presence of septations and mixed-density SDHs has a significantly increased odds of requiring surgical intervention that must be considered in the decision to pursue SEPS drainage.

Predictive Factors for Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery: A Single-Center Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is particularly useful for treatment of deep arteriovenous malformations (AVMs) in eloquent territory with a high associated surgical risk. Prior studies have demonstrated high rates of AVM obliteration with SRS (60%-80%) in a latency period of 2-4 years for complete obliteration. Studies have identified several factors associated with successful obliteration of the AVM nidus; however, these present inconsistent and conflicting data. The aim of this single-center study was to examine factors associated with successful obliteration of AVMs treated with SRS. METHODS: A retrospective review was performed of 210 consecutive patients undergoing SRS for brain AVMs between 2010 and 2019. The χ2 test and logistic regression analysis were used to identify patient and AVM factors associated with successful obliteration. RESULTS: Younger age (P = 0.034) and prior embolization (P = 0.012) were associated with complete obliteration. The presence of coronary artery disease was associated with incomplete obliteration (P = 0.04). No AVM characteristics were statistically associated with complete obliteration, although superficial venous drainage (P = 0.08) and frontal location (P = 0.06) trended toward significance. CONCLUSIONS: Successful obliteration of the AVM nidus was significantly associated with younger age and prior embolization. The presence of coronary artery disease negatively affected obliteration rates. These results add to the mixed results seen in the literature and emphasize the need for continued studies to delineate more specific patient and AVM factors that contribute to successful obliteration.

Seizure Rates After Stereotactic Radiosurgery for Cerebral AVMs: A Single Center Study.

OBJECTIVES: Seizure control after stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is an area of growing interest, with previous studies reporting up to 70% seizure freedom after treatment. The goals of this study were to identify specific patient and AVM characteristics associated with seizure presentation and seizure outcomes after SRS treatment. METHODS: A retrospective review of consecutive patients undergoing SRS for brain AVMs between 2009 and 2019 at our institution was conducted. Chi-squared and logistic regression analyses were utilized to identify patient and AVM factors associated with preoperative seizure presentation and development of new onset seizures after SRS. RESULTS: Two hundred ten consecutive patients presenting with AVMs treated with SRS were reviewed. Factors associated with seizure presentation included larger AVM size (P = 0.02), superficial venous drainage (P < 0.05), and parietal location (P = 0.04). Of 188 patients with follow-up (90%), 30 patients presented with seizures and 14 (47%) were seizure-free post-SRS. Of 158 patients presenting without seizure, 29 (18%) developed de novo seizures during follow-up. De novo post-SRS seizures were associated with prior craniotomy for resection of AVM (P = 0.04), post-treatment hemorrhage (P = 0.02), parietal location (P = 0.05), adverse effect requiring steroids (P < 0.01), and adverse effect requiring surgery (P < 0.01). CONCLUSIONS: Seizures are a common presentation of brain AVMs and can be treated effectively with SRS. However, seizures can also be a complication of SRS and are associated with post-treatment hemorrhage, edema, and need for future open surgery.

Hannover Classification of Vestibular Schwannomas: A Reliability Study.

BACKGROUND: The Hannover classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem. We have previously reported the reliability of the Koos system, but to date, no study has assessed the reliability of the similar Hannover classification. OBJECTIVE: We present an assessment of the intrarater and interrater reliability of the Hannover classification system. METHODS: After institutional review board approval was obtained, a cross-sectional group of the magnetic resonance imaging of 40 patients with vestibular schwannomas varying in size comprised the study sample. Four raters were selected to assign a Hannover grade to 50 total scans. Interrater and intrarater reliability was calculated and reported using Fleiss's kappa, Kendall's W, and intraclass correlation coefficient (ICC). RESULTS: Interrater observer reliability was found to be moderate when measured using Fleiss' kappa (0.49), extremely strong using Kendall's W (0.93), and excellent as calculated by ICC (0.88). The results were all statistically significant (P < 0.05). Intrarater reliability for Hannover grade ranged from 0.77 to 1.00 (substantial to perfect). By Kendall's W and ICC, all raters had near perfect or excellent agreement. The results were all statistically significant (P < 0.05). CONCLUSIONS: The Hannover classification is a reliable system for grading the size of vestibular schwannomas. This supports its continued use and previously published results of the literature in studies relying on this classification. Further studies are needed to evaluate its validity and determine its role in preoperative counseling and determining microsurgery and radiosurgery outcomes.

The Validity of the Koos Classification System With Respect to Facial Nerve Function.

BACKGROUND: The Koos classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem. Our prior study demonstrated excellent reliability. No study has yet assessed its validity. OBJECTIVE: To present a retrospective study designed to assess the validity of the Koos grading system with respect to facial nerve function following treatment of 81 acoustic schwannomas. METHODS: We collected data retrospectively from 81 patients with acoustic schwannomas of various Koos grades who were treated with microsurgical resection or stereotactic radiosurgery. House-Brackmann (HB) scores were used to assess facial nerve function and obtained at various time points following treatment. We generated Spearman's rho and Kendall's tau correlation coefficients along with a logistic regression curve. RESULTS: We found no significant difference in the presence or absence of facial dysfunction by Koos classification when looking at all patients. There was a positive but fairly weak correlation between HB score and Koos classification, which was only significant at the first postoperative clinic appointment. There was a statistically significant difference in the presence or absence of facial dysfunction between patients treated with surgery vs radiation, which we expected. We found no statistically significant difference when comparing surgical approaches. Logistic regression modeling demonstrated a poor ability of the Koos grading system to predict facial nerve dysfunction following treatment. CONCLUSION: The Koos grading system did not predict the presence of absence of facial nerve dysfunction in our study population. There were trends within subgroups that require further exploration.

Composition and function of ciliary inner-dynein-arm subunits studied in Chlamydomonas reinhardtii.

Motile cilia (also interchangeably called "flagella") are conserved organelles extending from the surface of many animal cells and play essential functions in eukaryotes, including cell motility and environmental sensing. Large motor complexes, the ciliary dyneins, are present on ciliary outer-doublet microtubules and drive movement of cilia. Ciliary dyneins are classified into two general types: the outer dynein arms (ODAs) and the inner dynein arms (IDAs). While ODAs are important for generation of force and regulation of ciliary beat frequency, IDAs are essential for control of the size and shape of the bend, features collectively referred to as waveform. Also, recent studies have revealed unexpected links between IDA components and human diseases. In spite of their importance, studies on IDAs have been difficult since they are very complex and composed for several types of IDA motors, each unique in composition and location in the axoneme. Thanks in part to genetic, biochemical, and structural analysis of Chlamydomonas reinhardtii, we are beginning to understand the organization and function of the ciliary IDAs. In this review, we summarize the composition of Chlamydomonas IDAs particularly focusing on each subunit, and discuss the assembly, conservation, and functional role(s) of these IDA subunits. Furthermore, we raise several additional questions/challenges regarding IDAs, and discuss future perspectives of IDA studies.

Cerebellar talcosis following posterior reversible encephalopathy syndrome in an intravenous methamphetamine abuser.

BACKGROUND: Intravenous (IV) methamphetamine abuse is associated with a variety of short- and long-term effects on the nervous system, some of which have yet to be fully elucidated. One known systemic complication that has not been described in nervous system tissues is the deposition of substrate crystals contained in injectable drugs. CASE DESCRIPTION: An unusual case is presented of a 35-year-old active IV methamphetamine abuser with posterior reversible encephalopathy syndrome (PRES) who subsequently developed multifocal bilateral cerebellar enhancing lesions and leptomeningeal enhancement due to biopsy-proven crystalline deposits. CONCLUSION: Although large crystalline substances will not normally penetrate the blood-brain barrier (BBB), during a state of BBB compromise such as with PRES, talc deposition may occur in the central nervous system.

Upward transtentorial herniation.

While subfalcine, transtentorial, and transmagnal herniation are most often thought of as downward phenomena, brain herniation can also occur in the upward direction with similarly disastrous clinical consequences.

Mutations in PIH proteins MOT48, TWI1 and PF13 define common and unique steps for preassembly of each, different ciliary dynein.

Ciliary dyneins are preassembled in the cytoplasm before being transported into cilia, and a family of proteins containing the PIH1 domain, PIH proteins, are involved in the assembly process. However, the functional differences and relationships between members of this family of proteins remain largely unknown. Using Chlamydomonas reinhardtii as a model, we isolated and characterized two novel Chlamydomonas PIH preassembly mutants, mot48-2 and twi1-1. A new allele of mot48 (ida10), mot48-2, shows large defects in ciliary dynein assembly in the axoneme and altered motility. A second mutant, twi1-1, shows comparatively smaller defects in motility and dynein assembly. A double mutant mot48-2; twi1-1 displays greater reduction in motility and in dynein assembly compared to each single mutant. Similarly, a double mutant twi1-1; pf13 also shows a significantly greater defect in motility and dynein assembly than either parent mutant. Thus, MOT48 (IDA10), TWI1 and PF13 may define different steps, and have partially overlapping functions, in a pathway required for ciliary dynein preassembly. Together, our data suggest the three PIH proteins function in preassembly steps that are both common and unique for different ciliary dyneins.

An Observational Study Investigating the Need for Decompressive Hemicraniectomy after Thrombectomy in Acute Ischemic Stroke of the Middle Cerebral Artery Territory.

OBJECTIVE: The frequency incidence of decompressive hemicraniectomy following intra-arterial thrombectomy (IAT) in acute ischemic stroke (AIS) involving the middle cerebral artery (MCA) territory was assessed as a surrogate for morbidity. METHODS: A single-institution retrospective chart review was conducted involving 209 consecutive patients between September 2014 and May 2017 with infarctions affecting the MCA territory and who subsequently underwent IAT. The outcomes of interest included the frequency of hemicraniectomy following IAT and the effects of intravenous tissue plasminogen activator (IV tPA) use and primary occlusion site on the Thrombolysis in Cerebral Infarction (TICI) score. RESULTS: Thirty-one patients were excluded for infarctions not involving the MCA territory. A total of 178 patients were included in the study. Sixty-eight patients (38.6%) had infarctions of less than one-third of the MCA territory, 50 (28.4%) had infarctions between one-third and two-thirds, and 58 (33%) had infarctions involving greater than two-thirds with 54.3% suffering infarctions of the left side. Only four patients (2.2%) required a hemicraniectomy with no statistically significant association found between TICI score and hemicraniectomy (p=0.41) or between administration of IV tPA and hemicraniectomy (p=0.36). The primary occlusion site was found to influence TICI score (p=0.045). CONCLUSION: A very small number of patients required hemicraniectomy after IAT as compared to previously published rates in the literature. However, several factors may prevent the patient from being an appropriate hemicraniectomy candidate in the first place and the small number of these patients in this study limits statistical analysis. The variables that determine a patient's candidacy for decompressive hemicraniectomy remains multi-factorial.

Loss of consciousness at onset of aneurysmal subarachnoid hemorrhage in good-grade patients.

Loss of consciousness (LOC) at presentation with aneurysmal subarachnoid hemorrhage (aSAH) has been associated with early brain injury and poor functional outcome. The impact of LOC on the clinical course after aSAH deserves further exploration. A retrospective analysis of 149 aSAH patients who were prospectively enrolled in the Cerebral Aneurysm Renin Angiotensin Study (CARAS) between 2012 and 2015 was performed. The impact of LOC was analyzed with emphasis on patients presenting in excellent or good neurological condition (Hunt and Hess 1 and 2). A total of 50/149 aSAH patients (33.6%) experienced LOC at presentation. Loss of consciousness was associated with severity of neurological condition upon admission (Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), Glasgow Coma Scale (GCS) grade), hemorrhage burden on initial head CT (Fisher CT grade), acute hydrocephalus, cardiac instability, and nosocomial infection. Of Hunt and Hess grade 1 and 2 patients, 21/84 (25.0%) suffered LOC at presentation. Cardiac instability and nosocomial infection were significantly more frequent in these patients. In multivariable analysis, LOC was the predominant predictor of cardiac instability and nosocomial infection. Loss of consciousness at presentation with aSAH is associated with an increased rate of complications, even in good-grade patients. The presence of LOC may identify good-grade patients at risk for complications such as cardiac instability and nosocomial infection.

Cerebellar Arteriovenous Malformation Rupture Despite Apparent Angiographic Obliteration.

BACKGROUND: Arteriovenous malformations (AVMs) can occur in all regions of the brain and spinal cord, with clinical consequences and risks varying by location. Delayed AVM rupture despite digital subtraction angiography-confirmed obliteration post-radiation is exceedingly rare. CASE DESCRIPTION: To our knowledge, we present the first documented case of delayed hemorrhage associated with a cerebellar AVM 5 years after linear accelerator-based radiation in a man aged 31 years despite apparent angiographic obliteration. CONCLUSIONS: Intracranial hemorrhage after radiosurgery in digital subtraction angiography-confirmed obliterated AVMs is rare, with limited understanding of risk factors, appropriate preventative management, and mechanisms of occurrence. This case serves to demonstrate the need for greater awareness of this rare complication, as well as the need for appropriate surveillance and management strategies.