Pediatric Cervical Spine Trauma: Injury Patterns, Diagnosis, and Treatment.

Traumatic injuries to the cervical spine or spinal cord are uncommon pathologies in the pediatric population. Unlike adults, children possess unique features such as incomplete ossification of vertebrae, synchondroses, pseudo-subluxation, horizontal alignment of ligaments, and absence of lordosis, which results in greater mobility and flexibility in the pediatric spine. These features are prominent in the cervical spine, which accounts for the most common area of traumatic spinal injuries in children. In this review, we summarize injury patterns, diagnosis, and treatment of traumatic cervical spine injuries in the pediatric population.

Using Dimensionality Reduction to Visualize Phenotypic Changes in High-Throughput Microscopy.

High-throughput microscopy has enabled screening of cell phenotypes at unprecedented scale. Systematic identification of cell phenotype changes (such as cell morphology and protein localization changes) is a major analysis goal. Because cell phenotypes are high-dimensional, unbiased approaches to detect and visualize the changes in phenotypes are still needed. Here, we suggest that changes in cellular phenotype can be visualized in reduced dimensionality representations of the image feature space. We describe a freely available analysis pipeline to visualize changes in protein localization in feature spaces obtained from deep learning. As an example, we use the pipeline to identify changes in subcellular localization after the yeast GFP collection was treated with hydroxyurea.

Convolutions are competitive with transformers for protein sequence pretraining.

Pretrained protein sequence language models have been shown to improve the performance of many prediction tasks and are now routinely integrated into bioinformatics tools. However, these models largely rely on the transformer architecture, which scales quadratically with sequence length in both run-time and memory. Therefore, state-of-the-art models have limitations on sequence length. To address this limitation, we investigated whether convolutional neural network (CNN) architectures, which scale linearly with sequence length, could be as effective as transformers in protein language models. With masked language model pretraining, CNNs are competitive with, and occasionally superior to, transformers across downstream applications while maintaining strong performance on sequences longer than those allowed in the current state-of-the-art transformer models. Our work suggests that computational efficiency can be improved without sacrificing performance, simply by using a CNN architecture instead of a transformer, and emphasizes the importance of disentangling pretraining task and model architecture. A record of this paper's transparent peer review process is included in the supplemental information.

Protein structure generation via folding diffusion.

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction, directly generating diverse, novel protein structures from neural networks remains difficult. In this work, we present a diffusion-based generative model that generates protein backbone structures via a procedure inspired by the natural folding process. We describe a protein backbone structure as a sequence of angles capturing the relative orientation of the constituent backbone atoms, and generate structures by denoising from a random, unfolded state towards a stable folded structure. Not only does this mirror how proteins natively twist into energetically favorable conformations, the inherent shift and rotational invariance of this representation crucially alleviates the need for more complex equivariant networks. We train a denoising diffusion probabilistic model with a simple transformer backbone and demonstrate that our resulting model unconditionally generates highly realistic protein structures with complexity and structural patterns akin to those of naturally-occurring proteins. As a useful resource, we release an open-source codebase and trained models for protein structure diffusion.

Intraoperative cortical stimulation mapping with laryngeal electromyography for the localization of human laryngeal motor cortex.

OBJECTIVE: The objectives of this study were to describe the authors' clinical methodology and outcomes for mapping the laryngeal motor cortex (LMC) and define localization of the LMC in a cohort of neurosurgical patients undergoing intraoperative brain mapping. Because of mapping variability across patients, the authors aimed to define the probabilistic distribution of cortical sites that evoke laryngeal movement, as well as adjacent cortical somatotopic representations for the face (mouth), tongue, and hand. METHODS: Thirty-six patients underwent left (n = 18) or right (n = 18) craniotomy with asleep motor mapping. For each patient, electromyography (EMG) electrodes were placed in the face, tongue, and hand; a nerve integrity monitor (NIM) endotracheal tube with surface electrodes detected EMG activity from the bilateral vocal folds. After dense cortical stimulation was delivered throughout the sensorimotor cortex, motor responses were then mapped onto a three-dimensional reconstruction of the patient's cortical surfaces for location characterization of the evoked responses. Finally, stimulation sites were transformed into a two-dimensional coordinate system for probabilistic mapping of the stimulation site relative to the central sulcus and sylvian fissure. RESULTS: The authors found that the LMC was predominantly localized to a mid precentral gyrus region, dorsal to face representation and surrounding a transverse sulcus ventral to the hand knob. In 14 of 36 patients, the authors identified additional laryngeal responses located ventral to all orofacial representations, providing evidence for dual LMC representations. CONCLUSIONS: The authors determined the probabilistic distribution of the LMC. Cortical stimulation mapping with an NIM endotracheal tube is an easy and effective method for mapping the LMC and is simply integrated into the current neuromonitoring methods for brain mapping.

ATG14 plays a critical role in hepatic lipid droplet homeostasis.

BACKGROUND & AIMS: Autophagy-related 14 (ATG14) is a key regulator of autophagy. ATG14 is also localized to lipid droplet; however, the function of ATG14 on lipid droplet remains unclear. In this study, we aimed to elucidate the role of ATG14 in lipid droplet homeostasis. METHODS: ATG14 loss-of-function and gain-of-function in lipid droplet metabolism were analyzed by fluorescence imaging in ATG14 knockdown or overexpression hepatocytes. Specific domains involved in the ATG14 targeting to lipid droplets were analyzed by deletion or site-specific mutagenesis. ATG14-interacting proteins were analyzed by co-immunoprecipitation. The effect of ATG14 on lipolysis was analyzed in human hepatocytes and mouse livers that were deficient in ATG14, comparative gene identification-58 (CGI-58), or both. RESULTS: Our data show that ATG14 is enriched on lipid droplets in hepatocytes. Mutagenesis analysis reveals that the Barkor/ATG14 autophagosome targeting sequence (BATS) domain of ATG14 is responsible for the ATG14 localization to lipid droplets. Co-immunoprecipitation analysis illustrates that ATG14 interacts with adipose triglyceride lipase (ATGL) and CGI-58. Moreover, ATG14 also enhances the interaction between ATGL and CGI-58. In vitro lipolysis analysis demonstrates that ATG14 deficiency remarkably decreases triglyceride hydrolysis. CONCLUSIONS: Our data suggest that ATG14 can directly enhance lipid droplet breakdown through interactions with ATGL and CGI-58.

Flux estimation analysis systematically characterizes the metabolic shifts of the central metabolism pathway in human cancer.

Introduction: Glucose and glutamine are major carbon and energy sources that promote the rapid proliferation of cancer cells. Metabolic shifts observed on cell lines or mouse models may not reflect the general metabolic shifts in real human cancer tissue. Method: In this study, we conducted a computational characterization of the flux distribution and variations of the central energy metabolism and key branches in a pan-cancer analysis, including the glycolytic pathway, production of lactate, tricarboxylic acid (TCA) cycle, nucleic acid synthesis, glutaminolysis, glutamate, glutamine, and glutathione metabolism, and amino acid synthesis, in 11 cancer subtypes and nine matched adjacent normal tissue types using TCGA transcriptomics data. Result: Our analysis confirms the increased influx in glucose uptake and glycolysis and decreased upper part of the TCA cycle, i.e., the Warburg effect, in almost all the analyzed cancer. However, increased lactate production and the second half of the TCA cycle were only seen in certain cancer types. More interestingly, we failed to detect significantly altered glutaminolysis in cancer tissues compared to their adjacent normal tissues. A systems biology model of metabolic shifts through cancer and tissue types is further developed and analyzed. We observed that (1) normal tissues have distinct metabolic phenotypes; (2) cancer types have drastically different metabolic shifts compared to their adjacent normal controls; and (3) the different shifts in tissue-specific metabolic phenotypes result in a converged metabolic phenotype through cancer types and cancer progression. Discussion: This study strongly suggests the possibility of having a unified framework for studies of cancer-inducing stressors, adaptive metabolic reprogramming, and cancerous behaviors.

FLUXestimator: a webserver for predicting metabolic flux and variations using transcriptomics data.

Quantitative assessment of single cell fluxome is critical for understanding the metabolic heterogeneity in diseases. Unfortunately, laboratory-based single cell fluxomics is currently impractical, and the current computational tools for flux estimation are not designed for single cell-level prediction. Given the well-established link between transcriptomic and metabolomic profiles, leveraging single cell transcriptomics data to predict single cell fluxome is not only feasible but also an urgent task. In this study, we present FLUXestimator, an online platform for predicting metabolic fluxome and variations using single cell or general transcriptomics data of large sample-size. The FLUXestimator webserver implements a recently developed unsupervised approach called single cell flux estimation analysis (scFEA), which uses a new neural network architecture to estimate reaction rates from transcriptomics data. To the best of our knowledge, FLUXestimator is the first web-based tool dedicated to predicting cell-/sample-wise metabolic flux and metabolite variations using transcriptomics data of human, mouse and 15 other common experimental organisms. The FLUXestimator webserver is available at http://scFLUX.org/, and stand-alone tools for local use are available at https://github.com/changwn/scFEA. Our tool provides a new avenue for studying metabolic heterogeneity in diseases and has the potential to facilitate the development of new therapeutic strategies.

A comparison of incidental and symptomatic unruptured brain arteriovenous malformations in children.

OBJECTIVE: Patients with unruptured brain arteriovenous malformations (AVMs) may present with headaches, seizures, and/or neurological deficits. A smaller number of cases may be discovered incidentally. These lesions remain incompletely understood due to their sparse reporting. Herein, the authors describe the largest series to date comparing the presentation, angioarchitecture, and management of incidental versus symptomatic unruptured AVMs in children. METHODS: The authors performed a retrospective analysis of patients who presented with brain AVMs from 1998 to 2022 at the University of California, San Francisco. Inclusion criteria were age ≤ 18 years at the time of presentation and an angiographically proven unruptured AVM that had been diagnosed postnatally. RESULTS: Of 76 children with unruptured AVMs, 66 (86.8%) presented with headaches, seizures, and/or neurological deficit. Ten AVMs (13.1%) were incidentally discovered through unrelated disease workup (50%), cranial trauma (40%), or research study participation (10%). Compared with patients with symptomatic unruptured AVMs, patients with incidental unruptured AVMs had a smaller mean ± SD maximum nidus diameter (2.82 ± 1.1 vs 3.98 ± 1.52 cm, p = 0.025) and fewer had deep venous drainage (20% of patients vs 61%, p = 0.036). They also presented at an earlier age (10 ± 5.2 vs 13.5 ± 4 years, p = 0.043) and with longer duration to first treatment (541 ± 922 vs 196 ± 448 days, p = 0.005). During the observation period, 1 patient developed recurring headaches and demonstrated AVM nidus growth. Four AVMs greater than 3 cm in size or in a deep location were treated with radiosurgery. Six other AVMs were treated with resection, with 2 receiving preoperative embolization. Eight AVMs (80%) were obliterated on last follow-up. Postprocedural complications included 2 transient neurological deficits after resection and 1 case of delayed seizure development after radiosurgery. The mean follow-up period was 5.7 ± 5.7 years without any hemorrhage episodes. CONCLUSIONS: A substantial proportion of pediatric patients with unruptured AVMs are discovered incidentally. With earlier presentation and more elementary angioarchitecture than symptomatic unruptured AVMs, these incidental lesions provide a snapshot into the natural history of AVM before symptom development or rupture.

Interdisciplinary care of children with diffuse midline glioma.

Diffuse Midline Glioma (DMG) which includes Diffuse Intrinsic Pontine Glioma (DIPG) is an infiltrative tumor of the midline structures of the central nervous system that demonstrates an aggressive pattern of growth and has no known curative treatment. As these tumors progress, children experience ongoing neurological decline including inability to ambulate, swallow and communicate effectively. We propose that optimal care for patients with DMG should involve a specialized team experienced in caring for the multifaceted needs of these patients and their families. Herein we review the roles and evidence to support early involvement of a specialized interdisciplinary team and outline our views on best practices for these challenging tumors.

Discovering molecular features of intrinsically disordered regions by using evolution for contrastive learning.

A major challenge to the characterization of intrinsically disordered regions (IDRs), which are widespread in the proteome, but relatively poorly understood, is the identification of molecular features that mediate functions of these regions, such as short motifs, amino acid repeats and physicochemical properties. Here, we introduce a proteome-scale feature discovery approach for IDRs. Our approach, which we call "reverse homology", exploits the principle that important functional features are conserved over evolution. We use this as a contrastive learning signal for deep learning: given a set of homologous IDRs, the neural network has to correctly choose a held-out homolog from another set of IDRs sampled randomly from the proteome. We pair reverse homology with a simple architecture and standard interpretation techniques, and show that the network learns conserved features of IDRs that can be interpreted as motifs, repeats, or bulk features like charge or amino acid propensities. We also show that our model can be used to produce visualizations of what residues and regions are most important to IDR function, generating hypotheses for uncharacterized IDRs. Our results suggest that feature discovery using unsupervised neural networks is a promising avenue to gain systematic insight into poorly understood protein sequences.

C2 translaminar screw fixation in pediatric occipitocervical fusion.

PURPOSE: Rigid occipitocervical (O-C) instrumentation can reduce the anterior pathology and has a high fusion rate in children with craniovertebral instability. Typically, axis (C2) screw fixation utilizes C1-C2 transarticular screws or C2 pars screws. However, anatomic variation may preclude these screw types due to the size of fixation elements or by placing the vertebral artery at risk for injury. Pediatric C2 translaminar screw fixation has low risk of vertebral artery injury and may be used when the anatomy is otherwise unsuitable for C1-C2 transarticular screws or C2 pars screws. METHODS: We retrospectively reviewed a neurosurgical database at UCSF Benioff Children's Hospital Oakland for patients who had undergone a cervical spinal fusion that utilized translaminar screws for occipitocervical instrumentation between 2002 and 2020. We then reviewed the operative records to determine the parameters of C2 screw fixations performed. Demographic and all other relevant clinical data were then recorded. RESULTS: Twenty-five patients ranging from 2 to 18 years of age underwent O-C fusion, with a total of 43 translaminar screws at C2 placed. Twenty-three patients were fused (92%) after initial surgery with a mean follow-up of 43 months. Two patients, both with Down syndrome, had a nonunion. Another 2 patients had a superficial wound dehiscence that required wound revision. One patient died of unknown cause 7 months after surgery. One patient developed an adjacent-level kyphosis. CONCLUSION: When performing occipitocervical instrumentation in the pediatric population, C2 translaminar screw fixation is an effective option to other methods of C2 screw fixation dependent on anatomic feasibility.

Advanced Functions Embedded in the Second Version of Database, Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2.

The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2 (GESS v2 https://shiny.ph.iu.edu/GESS_v2/) is an updated version of GESS, which has offered a handy query platform to analyze single-nucleotide variants (SNVs) on millions of high coverages and high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complete genomes provided by the Global Initiative on Sharing Avian Influenza Data (GISAID). Including the tools in the first version, the GESS v2 is embedded with new functions, which allow users to search SNVs, given the viral nucleotide or amino acid sequence. The GESS v2 helps users to identify SNVs or SARS-CoV-2 lineages enriched in countries of user's interest and show the migration path of a selected lineage on a world map during specific time periods chosen by the users. In addition, the GESS v2 can recognize the dynamic variations of newly emerging SNVs in each month to help users monitor SNVs, which will potentially become dominant soon. More importantly, multiple sets of analyzed results about SNVs can be downloaded directly from the GESS v2 by which users can conduct their own independent research. With these significant updates, the GESS v2 will continue to serve as a public open platform for researchers to explore SARS-CoV-2 evolutionary patterns from the perspectives of the prevalence and impact of SNVs.

Validation of the Ruptured Arteriovenous Malformation Grading Scale in a pediatric cohort.

OBJECTIVE: Pediatric brain arteriovenous malformations (AVMs) are the leading cause of spontaneous intracranial hemorrhage (SICH) in children. Although the incidence of SICH is low in pediatric populations, such events cause substantial morbidity. The recently created Ruptured Arteriovenous Malformation Grading Scale (RAGS) is proposed as a reliable and novel grading system to specifically serve as a predictor of clinical outcomes in patients following AVM rupture, similar to the Hunt and Hess (HH) grade for ruptured aneurysms. While these data are promising, pediatric patients were notably absent from the original study validating the RAGS. Therefore, correlation of the RAGS score with clinical outcomes following AVM rupture in individuals younger than 18 years of age using the RAGS score is needed. The objective of this study was to validate the RAGS in a cohort of pediatric patients with AVMs who presented with hemorrhage, thereby demonstrating the score's generalizability, and expanding its external validity. METHODS: A cohort of children with ruptured AVMs were retrospectively reviewed. Using disability, measured by the modified Rankin Scale (mRS), as the response variable, the area under the receiver operating characteristic curve (AUROC) was calculated for patients based on their RAGS scores for three time periods. The AUROC values were then compared with those generated by two commonly used clinical grading systems, the HH classification and Glasgow Coma Scale. RESULTS: A total of 81 children who presented with ruptured AVMs were included in the study, with a mean follow-up duration of 4 years. The RAGS score outperformed other clinical grading scales in predicting mRS scores, with AUROC values of 0.81, 0.82, and 0.81 at three distinct follow-up periods. CONCLUSIONS: The RAGS score correlated well with the clinical outcome after AVM rupture in pediatric patients. Additional validation studies across multiple treatment centers are needed to further demonstrate the generalizability of the scoring system.

Single versus dual operative spine fractures in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis, the most common spondyloarthritis, fuses individual spinal vertebrae into long segments. The unique biomechanics of the ankylosed spine places patients at unusually high risk for unstable fractures secondary to low-impact mechanisms. These injuries are unique within the spine trauma population and necessitate thoughtful management. Therefore, the authors aimed to present a richly annotated data set of operative AS spine fractures with a significant portion of patients with simultaneous dual noncontiguous fractures. METHODS: Patients with ankylosing spondylitis with acute fractures who received operative management between 2012 and 2020 were reviewed. Demographic, admission, surgical, and outcome parameters were retrospectively collected and reviewed. RESULTS: In total, 29 patients were identified across 30 different admissions. At admission, the mean age was 71.7 ± 11.8 years. The mechanism of injury in 77% of the admissions was a ground-level fall; 30% also presented with polytrauma. Of admissions, 50% were patient transfers from outside hospitals, whereas the other half presented primarily to our emergency departments. Fifty percent of patients sustained a spinal cord injury, and 35 operative fractures were identified and treated in 32 surgeries. The majority of fractures clustered around the cervicothoracic (C4-T1, 48.6%) and thoracolumbar (T8-L3, 37.11%) junctions. Five patients (17.2%) had simultaneous dual noncontiguous operative fractures; these patients were more likely to have presented with a higher-energy mechanism of injury such as a bicycle or motor vehicle accident compared with patients with a single operative fracture (60% vs 8%, p = 0.024). On preoperative MRI, 56.3% of the fractures had epidural hematomas (EDHs); 25% were compressive of the underlying neural elements, which dictated the number of laminectomy levels performed (no EDH, 2.1 ± 2.36; noncompressive EDH, 2.1 ± 1.85; and compressive EDH, 7.4 ± 4 [p = 0.003]). The mean difference in instrumented levels was 8.7 ± 2.6 with a mean estimated blood loss (EBL) of 1183 ± 1779.5 mL. Patients on a regimen of antiplatelet therapy had a significantly higher EBL (2635.7 mL vs 759.4 mL, p = 0.015). Overall, patients had a mean hospital length of stay of 15.2 ± 18.5 days; 5 patients died during the same admission or after transfer to an outside hospital. Nine of 29 patients (31%) had died by the last follow-up (the mean follow-up was 596.3 ± 878.9 days). CONCLUSIONS: Patients with AS who have been found to have unstable spine fractures warrant a thorough diagnostic evaluation to identify secondary fractures as well as compressive EDHs. These patients experienced prolonged inpatient hospitalizations with significant morbidity and mortality.

Factors associated with seizures at initial presentation in pediatric patients with cerebral arteriovenous malformations.

OBJECTIVE: Children with cerebral arteriovenous malformations (AVMs) can present with seizures, potentially increasing morbidity and impacting clinical management. However, the factors that lead to seizures as a presenting sign are not well defined. While AVM-related seizures have been described in case series, most studies have focused on adults and have included patients who developed seizures after an AVM rupture. To address this, the authors sought to analyze demographic and morphological characteristics of AVMs in a large cohort of children. METHODS: The demographic, clinical, and AVM morphological characteristics of 189 pediatric patients from a single-center database were studied. Univariate and multivariate logistic regression models were used to test the effect of these characteristics on seizures as an initial presenting symptom in patients with unruptured brain AVMs. RESULTS: Overall, 28 of 189 patients initially presented with seizures (14.8%). By univariate comparison, frontal lobe location (p = 0.02), larger AVM size (p = 0.003), older patient age (p = 0.04), and the Supplemented Spetzler-Martin (Supp-SM) grade (0.0006) were associated with seizure presentation. Multivariate analysis confirmed an independent effect of frontal lobe AVM location and higher Supp-SM grade. All patients presenting with seizures had AVMs in the cortex or subcortical white matter. CONCLUSIONS: While children and adults share some risk factors for seizure presentation, their risk factor profiles do not entirely overlap. Pediatric patients with cortical AVMs in the frontal lobe were more likely to present with seizures. Additionally, the Supp-SM grade was highly associated with seizure presentation. Future clinical research should focus on the effect of therapeutic interventions targeting AVMs on seizure control in these patients.

Multiple Tumor-Associated Intracranial Aneurysms Adjacent to a Suprasellar Germ Cell Tumor: Case Report and Review of Literature.

INTRODUCTION: Tumor-associated intracranial aneurysms are rare and not well understood. CASE PRESENTATION: We describe a 4-year-old female with multiple intracranial aneurysms intimately associated with a suprasellar germ cell tumor (GCT). We provide the clinical history, medical, and surgical treatment course, as well as a comprehensive and concise synthesis of the literature on tumor-associated aneurysms. DISCUSSION: We discuss mechanisms for aneurysm formation with relevance to the current case, including cellular and paracrine signaling pertinent to suprasellar GCTs and possible molecular pathways involved. We review the complex multidisciplinary treatment required for complex tumor and cerebrovascular interactions.

Updated SARS-CoV-2 single nucleotide variants and mortality association.

By analyzing newly collected SARS-CoV-2 genomes and comparing them with our previous study about SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found that the SNV clustering had changed remarkably since June 2020. Apart from that the group of SNVs became dominant, which is represented by two nonsynonymous mutations A23403G (S:D614G) and C14408T (ORF1ab:P4715L), a few emerging groups of SNVs were recognized with sharply increased monthly incidence ratios of up to 70% in November 2020. Further investigation revealed sets of SNVs specific to patients' ages and/or gender, or strongly associated with mortality. Our logistic regression model explored features contributing to mortality status, including three critical SNVs, G25088T(S:V1176F), T27484C (ORF7a:L31L), and T25A (upstream of ORF1ab), ages above 40 years old, and the male gender. The protein structure analysis indicated that the emerging subgroups of nonsynonymous SNVs and the mortality-related ones were located on the protein surface area. The clashes in protein structure introduced by these mutations might in turn affect the viral pathogenesis through the alteration of protein conformation, leading to a difference in transmission and virulence. Particularly, we explored the fact that nonsynonymous SNVs tended to occur in intrinsic disordered regions of Spike and ORF1ab to significantly increase hydrophobicity, suggesting a potential role in the change of protein folding related to immune evasion.

Cerebrovascular complications of coccidioidomycosis meningitis: Case report and systematic review.

Coccidioidomycosis exposure is common in the southwest United States and northern Mexico. Dissemination to the meninges is the most severe form of progression. Although ischemic strokes are well-reported in these patients, other cerebrovascular complications of coccidioidomycosis meningitis (CM), as well as their treatment options and outcomes, have not been systematically studied. We present a uniquely severe case of CM with several cerebrovascular complications. We also systematically queried PubMed and EMBASE databases, including articles published before April 2020 reporting human patients with CM-induced cerebrovascular pathology other than ischemic infarcts. Sixteen articles met inclusion criteria, which describe 6 patients with aneurysmal hemorrhage, 10 with non-aneurysmal hemorrhage, one with vasospasm, and one with transient ischemic attacks. CM-associated aneurysms invariably presented with hemorrhage. These were universally fatal until the past decade, when advances in surgical clipping and/or combined surgical and endovascular treatment have improved outcomes. We found that non-aneurysmal intracranial hemorrhages were limited to male patients, involved a diverse set of intracranial vasculature, and had a mortality rate surpassing 80%. Vasospasm was reported once, and was treated with percutaneous transluminal angioplasty. Transient ischemic attacks were reported once, and were successfully treated with fluconazole and dexamethasone. This review suggests that CM can present with a wide array of cerebrovascular complications, including ischemic infarcts, aneurysmogenesis, non-aneurysmal intracranial hemorrhage, vasospasm, and transient ischemic attacks. Mortality has improved over time due to advances in surgical and endovascular treatment modalities. The exception is non-aneurysmal intracranial hemorrhage, which remains associated with high mortality rates and few targeted therapeutic options.