Advances in Cranial Surgery.

The landscape of the cranial neurosurgery has changed tremendously in past couple of decades. The main frontiers including introduction of neuro-endoscopy, minimally invasive skull base approaches, SRS, laser interstitial thermal therapy and use of tubular retractors have revolutionized the management of intracerebral hemorrhages, deep seated tumors other intracranial pathologies. Introduction of these novel techniques is based on smaller incisions with maximal operative corridors, decreased blood loss, shorter hospital stays, decreased post-operative pain and cosmetically appealing scars that improves patient satisfaction and clinical outcomes. The sophisticated tools like neuroendoscopy have improved light source, and better visualization around the corners. Advanced navigated tools and channel-based retractors help us to target deeply seated lesions with increased precision and minimal disruption of the surrounding neurovascular tissues. Advent of stereotactic radiosurgery has provided us alternative feasible, safe and effective options for treatment of patients who are otherwise not medically stable to undergo complex cranial surgical interventions. This paper review advances in treatment of intracranial pathologies, and how the neurosurgeons and other medical providers at the University of Missouri-Columbia (UMC) are optimizing these treatments for their patients.

Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice.

OBJECTIVE: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression. DESIGN: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation. RESULTS: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001). CONCLUSIONS: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability.

Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models.

Approximately 10% of Cystic Fibrosis (CF) patients, particularly those with CF transmembrane conductance regulator (CFTR) gene nonsense mutations, lack effective treatments. The potential of gene correction therapy through delivery of the CRISPR/Cas system to CF-relevant organs/cells is hindered by the lack of efficient genome editor delivery carriers. Herein, we report improved Lung Selective Organ Targeting Lipid Nanoparticles (SORT LNPs) for efficient delivery of Cas9 mRNA, sgRNA, and donor ssDNA templates, enabling precise homology-directed repair-mediated gene correction in CF models. Optimized Lung SORT LNPs deliver mRNA to lung basal cells in Ai9 reporter mice. SORT LNP treatment successfully corrected the CFTR mutations in homozygous G542X mice and in patient-derived human bronchial epithelial cells with homozygous F508del mutations, leading to the restoration of CFTR protein expression and chloride transport function. This proof-of-concept study will contribute to accelerating the clinical development of mRNA LNPs for CF treatment through CRISPR/Cas gene correction.

The Risk of Adverse Events in Smokers Undergoing Spinal Fusion: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: Determine if tobacco use is associated with increased risk of postoperative adverse events within 90 days in patients undergoing spinal fusion surgery. METHODS: Databases were queried to identify cohort studies that directly compared smokers with non-smokers and provided the absolute number of adverse events and the population at risk. Data quality was evaluated using the Quality in Prognosis Studies tool. Risk ratios (RR) and 95% confidence intervals were calculated and compared between studies. The grading of recommendation, assessment, development and evaluation (GRADE) criteria were used to assess the strength of the evidence. RESULTS: Seventeen studies assessing 37 897 participants met the inclusion criteria. Of these, 10 031 (26.5%) were smokers and 27 866 (73.5%) were nonsmokers. The mean age for the study population was 58 years, and 45% were males. Smoking was not associated with increased risk of one or more major adverse events within 90 days following spine surgery (seven studies, pooled RR 1.13, 95% CI [.75-1.71], I2 = 41%). However, smoking was significantly associated with one or more major adverse events in ≤2 level fusion (three studies, pooled RR 2.46, 95% CI [1.18-5.12], I2 = 0%), but not in fusions of ≥3 levels (four studies, pooled RR .87, 95% CI [.70-1.08], I2 = 0%). Additionally, there was no statistically significant association between smoking and any adverse event, nor increased reoperation risk due to adverse events. CONCLUSIONS: In this meta-analysis, tobacco use was not associated with a statistically significant increased risk of adverse events within 90 days in patients undergoing spinal fusion surgery. Our results are limited by the variable reporting methodology for both complication rates as well as smoking incidence between the included individual studies.

Analysis of the efficacy, safety, and cost of alternative forms of creatine available for purchase on Amazon.com: are label claims supported by science?

Creatine monohydrate (CM) is an established and effective dietary supplement, but it is not the only form of creatine. We analyzed forms of creatine for sale on Amazon.com" title = "http://Amazon.com">Amazon.com and evaluated if the advertised claims are supported by the available scientific evidence. We also analyzed the cost per gram of the forms of creatine. A total of 175 creatine supplements were included and we reported the total creatine content per serving, form(s) of creatine in products, product claims, and prevalence of products third party certified. The identified products contained 16 forms of creatine other than CM. The prevalence of products containing functional ingredients with CM or forms of creatine was 29.7%, and the prevalence of products containing blends of different forms of creatine was 21.7%. Only 8% of products were third party certified. The products using only CM (n = 91) had a mean price per gram of $0.12 ± 0.08, whereas products using only other forms of creatine (n = 32) had a mean price per gram of $0.26 ± 0.17. Approximately 88% of alternative creatine products in this study are classified as having limited to no evidence to support bioavailability, efficacy, and safety.

Chordoma of the Skull Base: A National Cancer Database Analysis of Current Practice Patterns and Outcomes.

BACKGROUND: Chordomas of the skull base are aggressive locally destructive tumors that arise from the remnants of the fetal notochord. Current guidelines recommend maximal safe surgical resection followed by adjuvant radiation therapy. However, because of the rarity of these tumors, the optimal radiotherapeutic regimen regarding dose and modality is unclear. METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2016. Data from adult patients were extracted, including tumor characteristics, comorbidity indices, and details of treatment (surgery, radiation, and chemotherapy). The primary outcome of interest was overall survival (OS), which was evaluated for specific treatment cohorts using Cox univariate and multivariate regression constructs along with associated survival curves. RESULTS: We identified 798 patients with a diagnosis of skull base chordoma. Mean OS in this cohort was 9.57 years. Most patients received surgical resection (89.1%), with 53.9% receiving radiotherapy and 6.5% receiving chemotherapy. After adjusting for baseline characteristics using multivariate regression, advanced age and increased tumor size were associated with decreased OS. Surgical resection was associated with increased OS, whereas neither radiotherapy nor chemotherapy was associated with OS. However, in patients who did receive radiation, dosage >6000 cGy was associated with increased OS (hazard ratio, 0.51; P = 0.038); OS did not vary significantly between traditional and proton-based methods. CONCLUSIONS: Our multi-institutional analysis supports the use of partial and radical surgical resection to improve survival in patients with skull base chordomas. Among patients who receive radiotherapy, higher radiation dose is associated with improved survival.

Bifrontal Osteoplastic Flap: An Option to Decrease Infection in Bifrontal Craniotomies with Skull Base Osteotomies.

Infection can be a common complication following bifrontal craniotomy with skull base osteotomies given the potential violation of sinuses and entry into the nasal structures. Our objective was to examine our series of patients who underwent a bifrontal craniotomy with skull base osteotomies and describe the infection rate. We propose the bifrontal osteoplastic flap as an adjunct to infection prevention. A retrospective single-center study of a patient database was performed. Twenty patients were identified. Fifty-five percent were male. The mean age was 55.7 ± 13.9 years. The most common indications for surgery were esthesioneuroblastomas (35%) and anterior skull base meningiomas (30%). Six patients (30%) developed an infection, 1 patient (5%) developed a CSF leak, and no patients developed a mucocele. All 6 infected cases had nasal pathology with intracranial extension, they all received chemoradiation post-operatively and were all combined cases with otorhinolaryngology. Eighty-three percent of these patients required a craniectomy and all of them required long-term IV antibiotics. Infection is not uncommon after a bifrontal craniotomy with skull base osteotomies and the use of the bifrontal osteoplastic flap in cases where the risk of infection is high, i.e., esthesioneuroblastomas surgery, may help reduce said risk and lead to better patient outcomes.

Delayed Presentation of Patients with Hip Fractures during the COVID-19 "Stay-at-Home" Order in the Southmost Region of the United States.

To evaluate the effects of COVID-19 and stay-at-home orders in traumatic hip fractures presentation, we conducted a retrospective chart review cohort study from March 13 to June 13 in 2020 compared to 2019 from a single-hospital Trauma Level 2 Center. Males and females, 18 years of age and older presenting with a diagnosis of displaced or nondisplaced, intracapsular, or extracapsular hip fracture, underwent standard of care-comparative analysis of the patient's characteristics and clinical outcomes. The primary study outcomes included age, sex, ethnicity, and body mass index, the onset of injury, date of arrival, payer, the primary type of injury and comorbidities, mechanism of injury, treatment received, postoperative complications, days in an intensive care unit (ICU), discharge disposition, pre- and postinjury functional status, and COVID-19 test. Age, sex, ethnicity, and body mass index were similar in the patients in 2019 compared to 2020. The patients' average age was 76 years old, 80% reported Hispanic ethnicity, and 63% of the patients were females. Most injuries (90%) occurred due to falls. On average, patients in 2020 presented 4.8 days after the injury onset as compared to 0.7 days in 2019 (p < 0.05). There was an increase in displaced fractures in 2019 compared to 2020 and an increase in patients' disposition into rehabilitation facilities compared to skilled nursing facilities. Despite the delay in presentation, length of stay, days in the ICU, or functional outcomes of the patients were not affected. Although the patients showed a delayed presentation after hip fracture, this does not appear to significantly interfere with the short-term or the 6-month mortality outcomes of the patients, suggesting the possibility of guided delayed care during times of national emergency and increased strain in hospital resources.

Brief Research Report: Prehospital Rapid Sequence Airway.

BACKGROUND: Rapid Sequence Airway (RSA) describes the administration of an induction agent and paralytic followed by the intended primary placement of an extraglottic airway device rather than an endotracheal tube. The purpose of this study was to determine the success rates for prehospital RSA. The secondary goal was to determine aspiration rates among patients managed with RSA. METHODS: Adult and pediatric prehospital RSA cases between 2005 and 2017 reported to an airway quality assurance registry from one ground and one air agency were reviewed. Success was defined as the ability to adequately ventilate patients after extraglottic device placement. Aspiration was defined as radiologic evidence (chest x-ray or CT scan) within 48 hours of hospital presentation. RESULTS: 68 patients underwent RSA with a King LTS-D (n = 24), LMA-Supreme (n = 28), Combitube (n = 2), LMA-Unique (n = 8) and iGel (n = 6). Age ranged from 1 year to 73 years with 10 patients less than 18. RSA was successful in 64 (94%) cases; 56 (88%) were successful on first pass and 63 (98%) within 2 attempts. The RSA procedure occurred in an aircraft in 14 (21%) of cases and 71% of patients were in cervical precautions. Duration of EGD insertion prior to hospital arrival ranged from 5 to 102 minutes with an average of 34.5 minutes. Aspiration data was available for 46 patients of whom 4 (8.7%) were found to have evidence of aspiration. CONCLUSION: Overall and first pass RSA success rates were high and aspiration rates were low in this quality assurance registry despite predictors of airway difficulty. RSA may be a reasonable alternative to RSI for prehospital airway management that merits further research.

Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes.

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.

Suicide and suicidality in somatic symptom and related disorders: A systematic review.

OBJECTIVE: We sought to determine the frequency of and risk factors for suicide outcomes in somatic symptom and related disorders and whether any risk was independent of co-occurring mental disorders. METHODS: We conducted a systematic review of studies on suicide death, suicide attempts, and suicidal ideation in those with somatic symptom disorders published prior to September 22, 2020 and indexed in PubMED, MEDLINE, PsycARTICLES, PsycINFO, EMBASE, or SCOPUS according to PRISMA guidelines. RESULTS: Our search yielded 33 articles with significant heterogeneity in study design, sample selection, and assessment for suicide or risk factors. While suicide deaths have not been adequately studied, somatic symptom and related disorders are associated with increased risk for suicidal ideation and suicide attempts, with estimates ranging from 24 to 34% of participants who endorsed current active suicidal ideation and 13-67% of participants who endorsed a prior suicide attempt. The risk appeared independent of co-occurring mental disorders. Identified risk factors for suicide attempts in samples with somatic symptom and related disorders include scores on measures of anger, alexithymia, alcohol use, past hospitalizations, dissociation, and emotional abuse. CONCLUSION: Although the literature is sparse, there exists evidence for an association, even independent of other mental disorders, between somatic symptom and related disorders and suicide outcomes. Practice guidelines for the management of these disorders should incorporate recommendations for the assessment and management of suicide risk. Future study is necessary to more fully elucidate potential unique risk factors for those suffering from these complex disorders.

Temporal Evolution of Hypertrophic Olivary Degeneration in a Pediatric Patient: A Case Report and Review of Literature.

Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration seen after interruption of the dentato-rubro-olivary tract also known as the Guillain-Mollaret triangle (GMT). It is associated with hypertrophic changes of the inferior olive. Commonly reported in adults, this lesion presents with ataxia and oculopalatal myoclonus. Up to date, few cases have been published in the literature that refer to pediatric cases. This diagnosis is particularly important in the setting of brainstem tumor surgery as it should not be confused for tumor recurrence or metastasis, in turn avoiding unwarranted surgical intervention. We present the case of a 15-year-old male who underwent resection of a left superior cerebellar peduncle (SCP) pilocytic astrocytoma. On follow-up, magnetic resonance imaging (MRI) demonstrated evidence of mild residual tumor as well as progressive engorgement of the inferior olivary nucleus (ION). The patient was clinically asymptomatic and has since been observed expectantly without any issues. We were able to pinpoint the most probable location of injury in our patient's GMT. HOD remains a somewhat obscure entity. Its presentation may be early and not accompanied by significant neurologic findings, in contrast to what has been previously reported. Particularly in neoplastic cases, it may represent a diagnostic challenge and could be easily confused for tumor recurrence. A multidisciplinary approach for this entity, as with other pathologies, is of particular importance. Its proper recognition will result in the best outcomes for the patient.

Progressive Loss of Corneal Nerve Fibers and Sensitivity in Rats Modeling Obesity and Type 2 Diabetes Is Reversible with Omega-3 Fatty Acid Intervention: Supporting Cornea Analyses as a Marker for Peripheral Neuropathy and Treatment.

PURPOSE: To determine whether cornea nerve fiber density and/or corneal function are valid markers for early detection and treatment of peripheral neuropathy in rats modeling prediabetes and type 2 diabetes. METHODS: High-fat feeding combined without or with low-dose streptozotocin was used to create rat models for prediabetes and type 2 diabetes that were longitudinally studied for loss of structure and function of sensory nerves in the cornea and skin as well as nerve conduction velocity and vascular reactivity of epineurial arterioles. There were three time points examined in each of the three conditions with 12 rats per group. The latest time point (24 weeks of high-fat diet with or without 16 weeks of hyperglycemia) was used to examine reversibility of neuro and vascular pathology following 16 weeks of treatment with menhaden oil, a natural source of long-chain omega-3 polyunsaturated fatty acids. The number of rats in the intervention study ranged from 6 to 17. RESULTS: Our longitudinal study demonstrated that vascular and neural dysfunction associated with obesity or type 2 diabetes occur early and are progressive. Decrease in cornea nerve fiber length and function were valid markers of disease in both the pre-diabetic and diabetic rat models and were more sensitive than decrease in intraepidermal nerve fiber density of the skin and thermal nociception of the hindpaw. Late intervention with menhaden oil significantly reversed both vascular and peripheral nerve damage induced by chronic obesity or type 2 diabetes. CONCLUSION: These studies provide support for examination of corneal structure and function as an early marker of peripheral neuropathy in prediabetes and type 2 diabetes. Furthermore, we demonstrate that omega-3 polyunsaturated fatty acids derived from fish oil are an effective treatment for peripheral neuropathy that occurs with chronic obesity or type 2 diabetes.

Massive Pulmonary Hemorrhage from Bronchial Varix.

Bronchial varix is a rare pulmonary disorder which may lead to life-threatening hemorrhage. Diagnosis is difficult because of the subtle abnormalities on radiographic and bronchoscopic examination. We present a case of massive hemoptysis from a bleeding bronchial varix. In the absence of immediate complex endobronchial therapy in the island of Guam, this case was initially managed with nebulized and intravenous tranexamic acid. This was followed by endobronchial blockade of the bleeding airway with endobronchial epinephrine instillation. Selective bronchial artery embolization alleviated the acute-phase bleeding. Prone positioning was initiated due to severe hypoxia after blood clots compromised the patency of bilateral bronchial airways. Prone ventilation was employed for 17 hours for 2 consecutive days with intermittent bronchoscopic forceps extraction of airway blood clots while in the prone position. These maneuvers resulted to improved lung ventilation and oxygenation. The patient underwent bronchial sleeve resection surgery for definitive management.

Retrospective Data Analysis and Literature Review for a Development of Enhanced Recovery after Surgery Pathway for Anterior Cervical Discectomy and Fusion.

Objective While enhanced recovery after surgery (ERAS) protocols are associated with shorter length of stay and improved outcomes in multiple surgical specialties, its application to spine surgery has been limited. Anterior cervical discectomy and fusion (ACDF) is a common spinal procedure with a relative efficacy and safety profile that makes it suitable for the application of ERAS principles. Reviewing our outcomes and practice and incorporating evidence-based clinical studies, we propose the development of an ERAS pathway for ACDF. Methods This is a retrospective review of ACDF cases performed at a single institution by a single surgeon from 2014 to 2017. Primary outcome measures included length of stay, complications, and 30-day readmission rates. The 1- and 2-level and the 3- and 4-level groups were also each consolidated into a single cohort for comparison. A comprehensive review of evidence-based literature pertaining to ACDF was then performed. Best-practice recommendations derived from the literature were incorporated into the proposed ERAS protocol. Results In this series of 75 1-level, 77 2-level, 44 3-level and 20 4-level ACDF procedures, the average surgical time (minutes) was 68, 90, 118 and 141; length of stay (days) was 1, 1, 1.4, and 1.7; drain usage (%) was 1.3, 2.6, 13.6 and 10; and 30-day readmission rates (%) were 2.7, 3.9, 4.5, and 15, respectively. Combining the 1- and 2-level as a single group and 3- and 4-level as another cohort, the 3- and 4-level cohort had a significantly higher rate of drain usage and estimated blood loss (EBL) but there was not a difference in length-of-stay, complications or 30-day readmission rates. Conclusions Given the relative equivalent safety profile between 1- and 2-level as compared to 3- and 4-level ACDF, the proposed ERAS pathway can be applied to all patients, and not just restricted to 1-level or 2-level ACDF. Taking into account feasibility parameters as deduced from a review of institutional outcomes, this pathway can streamline same-day discharge and improve the patient experience. Its success will be predicated on an iterative improvement process deriving from optimal prospective outcome measurements.

Minority Gene Expression Profiling: Probing the Genetic Signatures of Pathogenesis Using Ribosome Profiling.

Minority Gene Expression Profiling (MGEP) refers to a scenario where the expression profiles of specific genes of interest are concentrated in a small cellular pool that is embedded within a larger, non-expressive pool. An example of this is the analysis of disease-related genes within sub-populations of blood or biopsied tissues. These systems are characterized by low signal-to-noise ratios that make it difficult, if not impossible, to uncover the desired signatures of pathogenesis in the absence of lengthy, and often problematic, technical manipulations. We have adapted ribosome profiling (RP) workflows from the Illumina to the Ion Proton platform and used them to analyze signatures of pathogenesis in an MGEP model system consisting of human cells eliciting <3% productive dengue infection. We find that RP is powerful enough to identify relevant responses of differentially expressed genes, even in the presence of significant noise. We discuss how to deal with sources of unwanted variation, and propose ways to further improve this powerful approach to the study of pathogenic signatures within MGEP systems.

Spontaneous Chylothorax following Septic Pulmonary Embolization.

Chylothorax is the occurrence of chyle (lymph) in the pleural cavity secondary to damage of the thoracic duct. It is a rare form of pleural effusion which appears as a milky white turbid fluid. Malignancy is the leading cause of nontraumatic chylothorax while inadvertent surgical injury to the thoracic duct is the major cause of traumatic chylothorax. We report a case of spontaneous left-side chylothorax following septic pulmonary embolization (SPE) with Methicillin-Resistant Staphylococcus aureus (MRSA). This is a rare case of a nonmalignant, nontraumatic, and nontuberculous spontaneous chylothorax which was conservatively treated with fibrinolysis and diet modification.

Economic and technical assessment of rooftop solar photovoltaic potential in Brownsville, Texas, U.S.A.

Localized assessment of solar energy economic feasibility will benefit the structuring of residential solar energy deployment globally. In the U.S. growing interest in rooftop residential solar among city managers has spurred the development of photovoltaic (PV) feasibility maps of the technical and economic solar potential within cities. The City of Brownsville, Texas was interested in evaluating solar feasibility for their city but lacked information to make informed policy decisions on PV development. This paper presents novel and systems approaches for determining the technical and economic feasibility of solar development for homes in the Brownsville using LiDAR and local information. Residential technical and economic potential was assessed by optimizing the internal rate of return (IRR) and an average residential building demand profile to determine ideal size and placement of solar arrays. Results showed that residential structures in Brownsville have the technical potential to generate approximately 11% of the total energy provided by the local utility; however, average IRR was only 2.9% with a payback period of over 15 years. Five neighborhoods in the City of Brownsville were identified with spatially clustered homes that had relatively higher IRRs compared with other areas in the city. Despite the high technical potential, modeled results indicate that perspective home owners interested in solar development may require additional incentives to improve the economic feasibility of PV in Brownsville. This study provides a demonstration of an interdisciplinary systems approach and methodology that can be adopted internationally to evaluate the feasibility of solar development in other areas.

Intra-Arterial Dantrolene for Refractory Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Dantrolene has a safe side-effect profile and a mechanism of action that makes it attractive as an option for treatment of cerebral vasospasm. The authors report 2 cases of refractory cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage that were successfully treated with intra-arterial (IA) dantrolene. CASE DESCRIPTION: Two patients, a 63-year-old woman and 36-year-old woman, developed severe vasospasm refractory to IA vasodilators after rupture of anterior communicating artery aneurysms. IA dantrolene was injected in doses of 15-30 mg in the affected distributions and mean arterial pressure, intracranial pressure, and heart rate were monitored. There was immediate improvement in lumen diameter of the affected vessels following dantrolene injection. No significant differences in mean arterial pressure or intracranial pressure before and after IA dantrolene were observed. Both patients demonstrated clinical improvement within 24 hours without any further deterioration during the rest of their admission. Follow-up angiography 48 hours after IA dantrolene treatment demonstrated continued resolution of cerebral vasospasm. CONCLUSIONS: This evidence suggests IA dantrolene as a safe and effective novel alternative for the treatment of cerebral vasospasm.