Microbubble Contrast-Enhanced Transcutaneous Ultrasound Enables Real-Time Spinal Cord Perfusion Monitoring Following Posterior Cervical Decompression.

INTRODUCTION: Ultrasound imaging is inexpensive, portable, and widely available. The development of a real-time transcutaneous spinal cord perfusion monitoring system would allow more precise targeting of mean arterial pressure goals following acute spinal cord injury (SCI). There has been no prior demonstration of successful real-time cord perfusion monitoring in humans. METHODS: Four adult patients who had undergone posterior cervical decompression and instrumentation at a single center were enrolled into this prospective feasibility study. All participants had undergone cervical laminectomies spanning ≥2 contiguous levels ≥2 months prior to inclusion with no history of SCI. The first two underwent transcutaneous ultrasound without contrast and the second two underwent contrast-enhanced ultrasound (CEUS) with intravenously injected microbubble contrast. RESULTS: Using non-contrast ultrasound with or without Doppler (n=2), the dura, spinal cord, and vertebral bodies were apparent however ultrasonography was insufficient to discern intramedullary perfusion or clear white-gray matter differentiation. With application of microbubble contrast (n=2), it was possible to quantify differential spinal cord perfusion within and between cross-sectional regions of the cord. Further, it was possible to quantify spinal cord hemodynamic perfusion using CEUS by measuring peak signal intensity and the time to peak signal intensity after microbubble contrast injection. Time-intensity curves were generated and area under the curves were calculated as a marker of tissue perfusion. CONCLUSION: CEUS is a viable platform for monitoring real-time cord perfusion in patients who have undergone prior cervical laminectomies. Further development has the potential to change clinical management acute SCI by tailoring treatments to measured tissue perfusion parameters.

MRI-Based Prediction of Clinical Improvement Following Ventricular Shunt Placement for Normal Pressure Hydrocephalus (NPH): Development and Evaluation of an Integrated Multi-Sequence Machine Learning Algorithm.

BACKGROUND AND PURPOSE: Symptoms of normal pressure hydrocephalus (NPH) are sometimes refractory to shunt placement, with limited ability to predict improvement for individual patients. We evaluated an MRI-based artificial intelligence method to predict post-shunt NPH symptom improvement. MATERIALS AND METHODS: NPH patients who underwent magnetic resonance imaging (MRI) prior to shunt placement at a single center (2014-2021) were identified. Twelve-month post-shunt improvement in modified Rankin Scale (mRS), incontinence, gait, and cognition were retrospectively abstracted from clinical documentation. 3D deep residual neural networks were built on skull stripped T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Predictions based on both sequences were fused by additional network layers. Patients from 2014-2019 were used for parameter optimization, while those from 2020-2021 were used for testing. Models were validated on an external validation dataset from a second institution (n=33). RESULTS: Of 249 patients, n=201 and n=185 were included in the T2-based and FLAIR-based models according to imaging availability. The combination of T2-weighted and FLAIR sequences offered the best performance in mRS and gait improvement predictions relative to models trained on imaging acquired using only one sequence, with AUROC values of 0.7395 [0.5765-0.9024] for mRS and 0.8816 [0.8030-0.9602] for gait. For urinary incontinence and cognition, combined model performances on predicting outcomes were similar to FLAIR-only performance, with AUROC values of 0.7874 [0.6845-0.8903] and 0.7230 [0.5600-0.8859]. CONCLUSIONS: Application of a combined algorithm using both T2-weighted and FLAIR sequences offered the best image-based prediction of post-shunt symptom improvement, particularly for gait and overall function in terms of mRS. ABBREVIATIONS: NPH = normal pressure hydrocephalus; iNPH = idiopathic NPH; sNPH = secondary NPH; AI = artificial intelligence; ML = machine learning; CSF = cerebrospinal fluid; AUROC = area under the receiver operating characteristic; FLAIR = fluid attenuated inversion recovery; BMI = body mass index; CCI = Charlson Comorbidity Index; SD = standard deviation; IQR = interquartile range.

Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

Clinical criteria for filum terminale resection in occult tethered cord syndrome.

OBJECTIVE: Tethered cord syndrome (TCS) comprises three symptom categories: back/leg pain, bowel/bladder, and neurological complaints. MRI typically reveals a low-lying conus medullaris, filum terminale (FT) pathology, or lumbosacral abnormalities. FT resection is established in TCS but not in radiologically occult TCS (OTCS). This study aims to identify patients with OTCS who are likely to benefit from FT resection. METHODS: The authors recruited 149 patients with OTCS (31 pediatric, 118 adult) treated with FT resection-including only cases with progressive TCS, negative spine MRI, and no concurrent neurological/urological conditions. A comprehensive questionnaire collected patient self-reported symptoms and clinical findings at the preoperative and at 3- and 12-month follow-up examinations. Based on questionnaire data, the authors extracted a 15-item symptoms and findings scale to represent the three TCS symptom categories, assigning 1 point for each item present. RESULTS: OTCS presents without radicular/segmental sensorimotor findings, but with leg/back pain and conus dysfunction, in addition to leg fatigue and spasticity; the latter indicating an upper motoneuron pathology. The 15-item scale showed clinical improvement in 89% of patients at the 3-month follow-up and 68% at the 12-month follow-up. Multivariate analysis of the scale revealed that it accurately predicts outcome of FT resection in 82% of cases. Patients with a preoperative score exceeding 6 points are most likely to benefit from surgery. CONCLUSIONS: By applying the study's inclusion criteria and incorporating the novel 15-item scale, surgeons can effectively select candidates for FT resection in patients with OTCS. The observed outcomes in these selected patients are comparable to those achieved in degenerative spine surgery.

Animal model considerations for chordoma research: reproducing the tumor microenvironment in vivo with humanized mice.

Animal models have been commonly used in immunotherapy research to study the cell response to external agents and to assess the effectiveness and safety of new therapies. Over the past few decades, immunocompromised (also called immunodeficient) mice allowed researchers to grow human tumor cells without the impact of the host's immune system. However, while this model is very valuable to understand the tumor biology and to understand the underlying mechanism of immunotherapy, the results may not always directly translate to humans. The tumor microenvironment has significant implications for tumor engraftment, growth, invasion, etc., and the immune system plays a critical role in shaping the tumor microenvironment. Human immunocompetent mice, also named humanized mice, are engineered mice that possess functional human immune cells. This in vivo model can be used to effectively study the effect of the human immune system to a human implanted tumor. Moreover, this can effectively mimic the response to treatment. This section is an overview of the current understanding of the different humanized mice that could be utilized to mimic the tumor microenvironment in chordoma.

Endoscopic Lateral Lumbar Interbody Fusion: Technical Note and Case Series.

BACKGROUND: Our objective is to describe a minimally invasive endoscopic surgical technique for performing lateral lumbar interbody fusion (LLIF). LLIF is a common approach to lumbar fusion in cases of degenerative lumbar disease; however, complications associated with psoas and lumbar plexus injury sometimes arise. The endoscopic modification presented here diminishes the requirement for sustained muscle retraction, minimizing complication risk while allowing for adequate decompression in select cases. METHODS: Endoscopic LLIF (ELLIF) was performed in 3 patients from 2019 to 2021. Surgeries were performed in the lateral position under general anesthesia with neurophysiological monitoring. Discectomy, endplate preparation, and harvesting of iliac crest bone were performed through a working channel endoscope. The introduction of an interbody cage (Joimax EndoLIF) was performed over a nitinol blunt-tip wire (Joimax). No expandable blade retractors were required. RESULTS: At 2-year follow-up of these 3 patients, the mean visual analog scale (VAS) score for leg pain improved from 9.3 to 1.7, and the mean Oswestry Disability Index (ODI) score improved from 40 to 8.3. There were no complications, readmissions, or recurrence of symptoms during the 2-year follow-up period. Patients spent an average of 36 hours in the hospital postoperatively and returned to normal daily activities after an average of 48 days. CONCLUSIONS: A minimally invasive modification to the LLIF procedure is presented that offers several potential advantages due to the application of endoscopic techniques: reduced muscle retraction, smaller incision, and the opportunity to perform both indirect decompression and endoscopically visualized discectomy in the same fusion procedure. CLINICAL RELEVANCE: The proposed endoscopic lateral lumbar interbody fusion and decompression is a minimally invasive technique that may provide patients with minimal complications, quick recovery, and good functional recovery.

Systematic Review of Prophylactic Plastic Surgery Closure to Prevent Postoperative Wound Complications Following Spine Surgery.

Spinal surgeries are increasingly performed in the United States, but complication rates can be unacceptably high at up to 26%. Consequently, plastic surgeons (PS) are sometimes recruited by spine surgeons (SS) for intraoperative assistance with soft tissue closures. An electronic multidatabase literature search was systematically conducted to determine whether spinal wound closure performed by PS minimizes postoperative wound healing complications when compared to closure by SS (neurosurgical or orthopedic), with the hypothesis that closures by PS minimizes incidence of complications. All published studies involving patients who underwent posterior spinal surgery with closure by PS or SS at index spine surgery were identified. Filtering by exclusion criteria identified 10 studies, 4 of which were comparative in nature and included both closures by PS and SS. Of these 4, none reported significant differences in postoperative outcomes between the groups. Across all studies, PS were involved in cases with higher baseline risk for wound complications and greater comorbidity burden. Closures by PS were significantly more likely to have had prior chemotherapy in 2 of the 4 (50%) studies (P = 0.014, P < 0.001) and radiation in 3 of the 4 (75%) studies (P < 0.001, P < 0.01, P < 0.001). In conclusion, closures by PS are frequently performed in higher risk cases, and use of PS in these closures may normalize the risk of wound complications to that of the normal risk cohort, though the overall level of evidence of the published literature is low.

Disparities in Primary Spinal Osseous Malignant Bone Tumor Survival by Medicaid Status: A National Population-Based Risk Analysis.

BACKGROUND: The impact of Medicaid status on survival outcomes of patients with spinal primary malignant bone tumors (sPMBT) has not been investigated. METHODS: Using the SEER-Medicaid database, adults diagnosed between 2006 and 2013 with sPMBT including chordoma, osteosarcoma, chondrosarcoma, Ewing sarcoma, or malignant giant cell tumor (GCT) were studied. Five-year survival analysis was performed using the Kaplan-Meier method. Adjusted survival analysis was performed using Cox proportional-hazards regression controlling for age, sex, marital status, cancer stage, poverty level, vertebral versus sacral location, geography, rurality, tumor diameter, tumor grade, tumor histology, and therapy. RESULTS: A total of 572 patients with sPMBT (Medicaid: 59, non-Medicaid: 513) were identified. Medicaid patients were more likely to be younger (P < 0.001), Black (P < 0.001), live in high poverty neighborhoods (P = 0.006), have distant metastases at diagnosis (P < 0.001), and less likely to receive surgery (P = 0.006). The 5-year survival rate was 65.7% (chondrosarcoma: 70.0%, chordoma: 91.5%, Ewing sarcoma: 44.6%, GCT: 90.0%, osteosarcoma: 34.2%). Medicaid patients had significantly worse 5-year survival than non-Medicaid patients (52.0% vs. 67.2%, P = 0.02). Minority individuals on Medicaid were associated with an increased risk of cancer-specific mortality compared with White non-Medicaid patients (adjusted hazard ratio [aHR] = 2.51, [95% CI 1.18-5.35], P = 0.017). Among Medicaid patients, those who received surgery had significantly better survival than those who did not (64.5% vs. 30.6%, P = 0.001). For all patients, not receiving surgery (aHR = 1.90 [1.23-2.95], P = 0.004) and tumor diameter >50 mm (aHR=1.89 [1.10-3.25], P = 0.023) were associated with an increased risk of mortality. CONCLUSIONS: Medicaid patients may be less likely to receive surgery and suffer from poorer survival. These disparities may be especially prominent among minorities.

Short-Term Pain Outcomes and Pain Medication Utilization Among Urine Toxicology-Identified Opioid and Marijuana Users After Elective Spine Surgery.

BACKGROUND AND OBJECTIVES: Postoperative pain outcomes may be influenced by preoperative substance use, which is often underreported due to associated stigma. This study examined the impact of urine toxicology-identified preoperative opioid and marijuana use on pain outcomes after elective spinal surgery. METHODS: Patients undergoing elective spinal surgery between September 2020 and May 2022 were recruited for this prospective cohort study. Detailed chart review was completed to collect demographic, urine toxicology, Visual Analog Scale (VAS), and pain medication data. Comparisons between self-reported and urine toxicology-identified substance use, preoperative/postoperative VAS ratings, and postoperative pain medication use were made using χ 2 tests, Student t -tests, and logistic regression, respectively. Models were adjusted for age, sex, and race. RESULTS: Among 111 participants (mean age 58 years, 59% female, 95% with ≥1 comorbidity), urine toxicology overestimated drug use (47% vs 16%, P < .001) and underestimated alcohol use (16% vs 56%, P < .001) at preoperative baseline relative to patient reports. Two weeks postoperatively, participants with preoperative opioid metabolites reported no significant improvements in pain from baseline (6.67 preoperative vs 5.92 postoperative, P = .288) unlike nonusers (6.56 preoperative vs 4.61 postoperative, P < .001). They also had worse postoperative VAS (5.92 vs 4.61, P = .030) and heavier reliance on opioid medications (odds ratio = 3.09, 95% CI = 1.21-7.89, P = .019). Conversely, participants with preoperative marijuana reported similar improvements in pain from baseline (users: 6.88 preoperative vs 4.36 postoperative, P = .001; nonusers: 6.49 preoperative vs 5.07 postoperative, P = .001), similar postoperative pain (4.36 vs 5.07, P = .238), and similar postoperative reliance on opioid medications (odds ratio = 0.96, 95% CI = 0.38-2.44, P = .928). Trends were maintained among the 83 patients who returned for the 3-month follow-up. CONCLUSION: Although urine toxicology-identified preoperative opioid use was associated with poor postoperative pain relief and reliance on postoperative opioids for pain management after elective spinal surgery, preoperative marijuana use was not. Preoperative marijuana use, hence, should not delay or be a contraindication to elective spinal surgery.

Trends in engagement with cognitive-behavioral therapy for chronic pain conditions after referral.

Cognitive-behavioral therapy for chronic pain (CBT-CP) is an important evidence-based non-pharmacologic treatment for chronic back and neck pain that is frequently recommended as a component of multidisciplinary treatment. However, the success of CBP-CP's implementation in clinical settings is affected by a variety of poorly understood obstacles to patient engagement with CBT-CP. Expanding upon the limited prior research conducted in heterogeneous practice settings, this study examines patterns of treatment initiation for CBT-CP at an interdisciplinary, hospital-based chronic pain practice and conducts exploratory comparisons between groups of patients who did and did not engage in CBT-CP after receiving a referral. Patients' descriptive data, including pain severity, work status, prior therapy, and behavioral health questionnaire scores at intake visit, were obtained through a retrospective chart review of electronic medical records. Data were then analyzed using inter-group comparisons and logistic regression modeling to determine factors that predicted treatment initiation for CBT-CP. On multivariate analysis, we found that patient's depression level as measured by their Patient Health Questionnaire 9 (PHQ-9) score was solely predictive of treatment initiation, as chronic pain patients with a higher level of depression were found to be more likely to attend their recommended appointments of CBT-CP. Anxiety score as measured by GAD-7, work status, pain scores, and prior therapy engagement were not independently predictive. No single "profile" of patient-level factors was found to delineate patients who did and did not initiate CBT-CP, demonstrating the limitations of clinical variables as predictors of uptake.

Cognitive-behavioral therapy (CBT) is a frequently used therapy option, and can be helpful for patients with chronic low back and/or neck pain. However, patients do not always choose to engage in CBT when offered in the context of chronic pain. Reasons patients choose not to pursue CBT, when recommended, are not well understood. This study used data from a hospital-based chronic pain practice in order to identify reasons that patients choose to begin CBT and those who do not. Data about these patients was collected from electronic medical records (EMRs) and was used to conduct statistical analyses, with the goal of determining what factors were significantly different between the two groups of patients. We identified that patients who have more severe depression symptoms based on a specific mental health questionnaire (the Patient Health Questionnaire 9, or PHQ-9) were more likely to engage with CBT. Study results imply that patients without comorbid depression may benefit from additional counseling on the potential benefits of CBT in the management of chronic pain. These results also suggest that reasons other than clinical factors are impacting whether or not patients engage with CBT.

A decade of diversity: using statistical indices to compare neurosurgery to other surgical specialties.

OBJECTIVE: Studies have demonstrated the benefits of diversity in neurosurgery. However, recruitment of minoritized groups within the neurosurgical workforce consistently lags other surgical specialties. While racial and gender demographics of neurosurgical residents are well documented, there has been minimal exploration into the multidimensional nature of diversity. The current study will evaluate the longitudinal diversity changes in neurosurgery residency programs compared with other surgical fields with validated diversity indices. METHODS: Nationwide reports including data about resident physicians were obtained from the American Medical Association and the Association of American Medical Colleges for the academic years 2008-2021. Self-reported race, biological sex, and medical school affiliation were recorded for surgical residents in the 10 commonly recognized surgical fields. The Gini-Simpson Diversity Index was used to calculate the effective counts (ECs) of races, sexes, and medical school types for each field. A Composite Diversity Index (CDI) comprising the aforementioned diversity traits was used to calculate the percentage of characteristics upon which two randomly selected residents within each specialty would differ. CDIs were calculated for each field in every year from 2008 to 2021. Median CDIs were compared between fields using Kruskal-Wallis testing, and p values < 0.05 were deemed statistically significant. RESULTS: Plastic surgery had the highest median sex EC (1.92, interquartile range [IQR] 1.78-1.95), indicating greater diversity, while neurosurgery had the third lowest sex EC (1.40, IQR 1.35-1.41). All surgical fields examined had fewer than 3 races effectively represented among their residents, despite there being 8 races present. Neurosurgery ranked among the top fields in effective racial diversity (EC 2.17, IQR 2.09-2.21) and medical school type diversity (EC 1.25, IQR 1.21-1.26). There were statistically significant differences in the sex, race, and school ECs between surgical specialties. While neurosurgery had a relatively low median overall diversity (CDI = 32.7, IQR 32.0-34.6), there was a consistent longitudinal increase in CDI from 2015 to 2021. CONCLUSIONS: Neurosurgery resident physicians have become increasingly diverse in the past decade but are more homogenous than residents in other surgical fields. The continued use of diversity indices to more accurately track diversity progress over time may better inform leaders in the field of how they may best focus their equity and inclusion efforts.

Optimizing surgical management of facet cysts of the lumbar spine: systematic review, meta-analysis, and local case series of 1251 patients.

OBJECTIVE: Lumbar facet cysts (LFCs) can cause neurological dysfunction and intractable pain. Surgery is the current standard of care for patients in whom conservative therapy fails, those with neurological deficits, and those with evidence of spinal instability. No study to date has comprehensively examined surgical outcomes comparing the multiple surgical treatment options for LFCs. Therefore, the authors aimed to perform a combined analysis of cases both in the literature and of patients at a single institution to compare the outcomes of various surgical treatment options for LFC. METHODS: The authors performed a literature review in accordance with PRISMA guidelines and meta-analysis of the PubMed, Embase, and Cochrane Library databases and reviewed all studies from database inception published until February 3, 2023. Studies that did not contain 3 or more cases, clearly specify follow-up durations longer than 6 months, or present new cases were excluded. Bias was evaluated using Cochrane Collaboration's Risk of Bias in Nonrandomised Studies-of Interventions (ROBINS-I). The authors also reviewed their own local institutional case series from 2015 to 2020. Primary outcomes were same-level cyst recurrence, same-level revision surgery, and perioperative complications. ANOVA, common and random-effects modeling, and Wald testing were used to compare treatment groups. RESULTS: A total of 1251 patients were identified from both the published literature (29 articles, n = 1143) and the authors' institution (n = 108). Patients were sorted into 5 treatment groups: open cyst resection (OCR; n = 720), tubular cyst resection (TCR; n = 166), cyst resection with arthrodesis (CRA; n = 165), endoscopic cyst resection (ECR; n = 113), and percutaneous cyst rupture (PCR; n = 87), with OCR being the analysis reference group. The PCR group had significantly lower complication rates (p = 0.004), higher recurrence rates (p < 0.001), and higher revision surgery rates (p = 0.001) compared with the OCR group. Patients receiving TCR (3.01%, p = 0.021) and CRA (0.0%, p < 0.001) had significantly lower recurrence rates compared with those undergoing OCR (6.36%). The CRA group (6.67%) also had significantly lower rates of revision surgery compared with the OCR group (11.3%, p = 0.037). CONCLUSIONS: While PCR is less invasive, it may have high rates of same-level recurrence and revision surgery. Recurrence and revision rates for modalities such as ECR were not significantly different from those of OCR. While concomitant arthrodesis is more invasive, it might lead to lower recurrence rates and lower rates of subsequent revision surgery. Given the limitations of our case series and literature review, prospective, randomized studies are needed.

Seizure and anatomical outcomes of repeat laser amygdalohippocampotomy for temporal lobe epilepsy: A single-institution case series.

OBJECTIVE: In patients with treatment-refractory temporal lobe epilepsy (TLE), a single stereotactic laser interstitial thermotherapy (LITT) procedure is sometimes insufficient to ablate epileptogenic tissue, particularly the medial structures often implicated in TLE. In patients with seizure recurrence after initial ablation, the extent to which a second ablation may achieve improved seizure outcomes is uncertain. The objective of this study was to investigate the feasibility and potential efficacy of repeat LITT amygdalohippocampotomy as a worthwhile strategy for intractable temporal lobe epilepsy by quantifying changes to targeted mesial temporal lobe structures and seizure outcomes. METHODS: Patients who underwent two LITT procedures for drug-resistant mesial TLE at our institution were included in the study. Lesion volumes for both procedures were calculated by comparing post-ablation intraoperative sequences to preoperative anatomy. Clinical outcomes after the initial procedure and repeat procedure were classified according to Engel scores. RESULTS: Five consecutive patients were included in this retrospective case series: 3 with right- and 2 with left-sided TLE. The median interval between LITT procedures was 294 days (range: 227-1918). After the first LITT, 3 patients experienced class III outcomes, 1 experienced a class IV, and 1 experienced a class IB outcome. All patients achieved increased seizure freedom after a second procedure, with class I outcomes (3 IA, 2 IB). CONCLUSIONS: Repeat LITT may be sufficient to achieve satisfactory seizure outcomes in some individuals who might otherwise be considered for more aggressive resection or palliative neuromodulation. A larger study to establish the potential value of repeat LITT amygdalohippocampotomy vs. other re-operation strategies for persistent, intractable temporal lobe epilepsy is worth pursuing.

Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus.

Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.

Early Signs of Elevated Intracranial Pressure on Computed Tomography Correlate With Measured Intracranial Pressure in the Intensive Care Unit and Six-Month Outcome After Moderate to Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Early triage and treatment after TBI have been shown to improve outcome. Identifying patients at risk for increased intracranial pressure (ICP) via baseline computed tomography (CT) , however, has not been validated previously in a prospective dataset. We hypothesized that acute CT findings of elevated ICP, combined with direct ICP measurement, hold prognostic value in terms of six-month patient outcome after TBI. Data were obtained from the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECTIII) multi-center clinical trial. Baseline CT scans for 881 participants were individually reviewed by a blinded central neuroradiologist. Five signs of elevated ICP were measured (sulcal obliteration, lateral ventricle compression, third ventricle compression, midline shift, and herniation). Associations between signs of increased ICP and outcomes (six-month functional outcome and death) were assessed. Secondary analyses of 354 patients with recorded ICP monitoring data available explored the relationships between hemorrhage phenotype/anatomic location, sustained ICP ≥20 mm Hg, and surgical intervention(s). Univariate and multi-variate logistic/linear regressions were performed; p < 0.05 is defined as statistically significant. Imaging characteristics associated with ICP in this cohort include sulcal obliteration (p = 0.029) and third ventricular compression (p = 0.039). Univariate regression analyses indicated that increasing combinations of the five defined signs of elevated ICP were associated with death, poor functional outcome, and time to death. There was also an increased likelihood of death if patients required craniotomy (odds ratio [OR] = 4.318, 95% confidence interval [1.330-16.030]) or hemicraniectomy (OR = 2.993 [1.109-8.482]). On multi-variate regression analyses, hemorrhage location was associated with death (posterior fossa, OR = 3.208 [1.120-9.188] and basal ganglia, OR = 3.079 [1.178-8.077]). Volume of hemorrhage >30 cc was also associated with increased death, OR = 3.702 [1.575-8.956]). The proportion of patient hours with sustained ICP ≥20 mm Hg, and maximum ICP ≥20 mm Hg were also directly correlated with increased death (OR = 6 4.99 [7.731-635.51]; and OR = 1.025 [1.004-1.047]), but not with functional outcome. Poor functional outcome was predicted by concurrent presence of all five radiographic signs of elevated ICP (OR = 4.44 [1.514-14.183]) and presence of frontal lobe (OR = 2.951 [1.265-7.067]), subarachnoid (OR = 2.231 [1.067-4.717]), or intraventricular (OR = 2.249 [1.159-4.508]) hemorrhage. Time to death was modulated by total patient days of elevated ICP ≥20 mm Hg (effect size = 3.424 [1.500, 5.439]) in the first two weeks of hospitalization. Sulcal obliteration and third ventricular compression, radiographic signs of elevated ICP, were significantly associated with measurements of ICP ≥20 mm Hg. These radiographic biomarkers were significantly associated with patient outcome. There is potential utility of ICP-related imaging variables in triage and prognostication for patients after moderate-severe TBI.

Charlson comorbidity index applied to shunted idiopathic normal pressure hydrocephalus.

A series of epidemiological studies have shown the limited life expectancy of patients suffering from idiopathic normal pressure hydrocephalus (iNPH). In most cases, comorbid medical conditions are the cause of death, rather than iNPH. Though it has also been shown that shunting improves both life quality and lifetime. We sought to investigate the utility of the Charlson comorbidity index (CCI) for improved preoperative risk-benefit assessment of shunt surgery in individual iNPH cases. 208 shunted iNPH cases were prospectively investigated. Two in-person follow up visits at 3 and 12 months assessed postoperative clinical status. The correlation of the age adjusted CCI with survival was investigated over the median observation time of 2.37 years (IQR 1.16-4.15). Kaplan Meier statistics revealed that patients with a CCI score of 0-5 have a 5-year survival rate of 87%, compared to only 55% in patients with CCI > 5. Cox multivariate statistics revealed that the CCI was an independent predictor of survival, while common preoperative iNPH scores (modified Rankin Scale (mRS), gait score, and continence score) are not. As expected, mRS, gait, and continence scores improved during the postoperative follow up period, though relative improvement on any of these was not predicted by baseline CCI. The CCI is an easily applicable preoperative predictor of survival time in shunted iNPH patients. The lack of a correlation between the CCI and functional outcome means that even patients with multiple comorbidities and limited remaining lifetime may appreciate benefit from shunt surgery.

Reappraisal of intradural findings in Chiari malformation type I.

OBJECTIVE: Management of Chiari malformation type I (CM-I) requires the functional restoration of an obstructed cisterna magna. In posterior fossa decompression with duraplasty (PFDD), various intradural pathologies are suggested to alter CSF flow at the craniocervical junction and require surgical correction. However, reports of the spectrum of intraoperative intradural findings and their nuances are scarce, especially those characterizing rarer findings pertaining to the vascular structures and vascular compression. METHODS: The authors conducted a retrospective cohort analysis of adults and children who underwent first-time PFDD for CM-I (2011-2021), with and without syringomyelia. The surgical reports and intraoperative videos were reviewed, and the frequency and nature of the intradural observations in regard to the tonsils, arachnoid, and vasculature were analyzed along with the clinical findings and surgical outcomes. RESULTS: All 180 patients (age range 1-72 years; median [interquartile range] 24 (14-38) years; 37% of patients were children < 21 years of age) exhibited multiple intradural findings, with a median of 7 distinct concurrent observations in each patient. Novel findings not previously reported included posterior inferior communicating artery (PICA) branches compressing the neural elements at the cervicomedullary junction (26.7%). Other common findings included arachnoid adhesions (92.8%), thickening (90.6%), webs at the obex (52.2%), tonsillar gliosis (57.2%), tonsillar hypertrophy (18.3%), adhesions obstructing the foramen of Magendie (FoM) (62.2%), PICA obstruction of the FoM (17.2%), and dural scarring (87.8%). Tonsillar gliosis and intertonsillar adhesions obstructing the FoM were more common in children than adults. Tonsillar gliosis and arachnoid webs were more common among syringomyelia patients. After multivariable adjustment, none of the observed findings were independently associated with syringomyelia, preoperative symptoms, or postoperative improvement. The vast majority of patients improved postoperatively. The complication rate was low: 1.2% of patients required revision PFDD at > 3 years postoperatively, 3.6% experienced other operative complications, and 0% had CSF leaks. CONCLUSIONS: The diversity of intradural findings and observations revealed in this study suggests that obstructive and compressive structural anomalies may be more common than previously reported among CM-I patients, both those patients with and those without syringomyelia and especially those with obstructive and compressive PICA branches. Although the authors cannot conclude that all these findings are necessarily pathological, further study may determine how they contribute to CM-I pathology and symptomatology in the setting of a compromised cisterna magna.

Right Ventricular Architectural Remodeling and Functional Adaptation in Pulmonary Hypertension.

BACKGROUND: Global indices of right ventricle (RV) function provide limited insights into mechanisms underlying RV remodeling in pulmonary hypertension (PH). While RV myocardial architectural remodeling has been observed in PH, its effect on RV adaptation is poorly understood. METHODS: Hemodynamic assessments were performed in 2 rodent models of PH. RV free wall myoarchitecture was quantified using generalized Q-space imaging and tractography analyses. Computational models were developed to predict RV wall strains. Data from animal studies were analyzed to determine the correlations between hemodynamic measurements, RV strains, and structural measures. RESULTS: In contrast to the PH rats with severe RV maladaptation, PH rats with mild RV maladaptation showed a decrease in helical range of fiber orientation in the RV free wall (139º versus 97º; P=0.029), preserved global circumferential strain, and exhibited less reduction in right ventricular-pulmonary arterial coupling (0.029 versus 0.017 mm/mm Hg; P=0.037). Helical range correlated positively with coupling (P=0.036) and stroke volume index (P<0.01). Coupling correlated with global circumferential strain (P<0.01) and global radial strain (P<0.01) but not global longitudinal strain. CONCLUSIONS: Data analysis suggests that adaptive RV architectural remodeling could improve RV function in PH. Our findings suggest the need to assess RV architecture within routine screenings of PH patients to improve our understanding of its prognostic and therapeutic significance in PH.

Antibiotic prophylaxis in penetrating traumatic brain injury: analysis of a single-center series and systematic review of the literature.

PURPOSE: Penetrating traumatic brain injury (pTBI) is an acute medical emergency with a high rate of mortality. Patients with survivable injuries face a risk of infection stemming from foreign body transgression into the central nervous system (CNS). There is controversy regarding the utility of antimicrobial prophylaxis in managing such patients, and if so, which antimicrobial agent(s) to use. METHODS: We reviewed patients with pTBI at our institution and performed a PRISMA systematic review to assess the impact of prophylactic antibiotics on reducing risk of CNS infection. RESULTS: We identified 21 local patients and 327 cases in the literature. In our local series, 17 local patients received prophylactic antibiotics; four did not. Overall, five of these patients (24%) developed a CNS infection (four and one case of intraparenchymal brain abscess and meningitis, respectively). All four patients who did not receive prophylactic antibiotics developed an infection (three with CNS infections; one superficial wound infection) compared to two of 17 (12%) patients who did receive prophylactic antibiotics. Of the 327 pTBI cases reported in the literature, 216 (66%) received prophylactic antibiotics. Thirty-eight (17%) patients who received antibiotics developed a CNS infection compared to 21 (19%) who did not receive antibiotics (p = 0.76). CONCLUSIONS: Although our review of the literature did not reveal any benefit, our institutional series suggested that patients with pTBI may benefit from prophylactic antibiotics. We propose a short antibiotic course with a regimen specific to cases with and without the presence of organic debris.