Pott's puffy tumor with intracranial extension in a child with incontinentia pigmenti: case based review of the eponymous disease.

BACKGROUND: Pott's puffy tumor (PPT) is an uncommon infection involving the frontal bone, first described by Sir Percival Pott more than 250 years ago. It can present with intracranial extension and serious neurological morbidity. Incontinentia pigmenti (IP) is a rare inherited genodermatosis that is lethal prenatally in males and manifests clinically in females. IP is associated with recurrent infections and immune dysfunction/suppression. METHODS: We report a case of Pott's puffy tumor presenting in a child with IP. We also performed a literature review of reported cases of PPT associated with immune dysfunction. We discuss the clinical presentation, diagnosis, and management of these lesions. RESULTS: We identified 12 cases of PPT associated with immune dysfunction/suppression. Diabetes was the most commonly identified cause followed by iatrogenic immunosuppression. Surgery is the standard treatment for managing PPT and the management of PPT with and without intracranial involvement, particularly in the context of underlying immune dysfunction/suppression, is discussed. CONCLUSION: PPT remains a rare but not infrequent diagnosis, often requiring neurosurgical intervention. Immune dysfunction/suppression is an additional risk factor that may predispose to PPT. Early and aggressive management should be instituted for optimal outcome.

Subdural hemorrhage in middle cranial fossa arachnoid cysts: a report of two cases at two ends of the spectrum.

Arachnoid cysts are usually asymptomatic, benign lesions commonly occurring in the middle cranial fossa. However, the cysts may rupture in rare cases causing intracystic or subdural hemorrhages with significant mass effect. We report two cases of middle cranial fossa arachnoid cyst with subdural hemorrhage with very different clinical course. The first case presented with significant mass effect with cerebral herniation and had significant neurological morbidity post-surgery. The second case had minimal symptoms and was managed conservatively with offer of elective surgery. The report underscores the importance of prompt diagnosis and appropriate surgical intervention in managing arachnoid cysts with hemorrhage, highlighting the potential for diverse clinical presentations and outcomes.

Can we do better supporting young adults with cerebral palsy as they navigate adulthood? A review of current and future transitional practices.

OBJECTIVE: Patients with cerebral palsy (CP) face lifelong consequences of their condition, and their healthcare needs evolve as they age. Transitional care for these patients is not universally available and various models have been described. In this article, the authors review the current literature surrounding transitional care for patients with CP, focusing predominantly on the neurosurgical aspects of transitional care, and they describe current approaches adopted by programs in North America. They further describe their own experience developing a transitional care clinic for patients with CP, as well as the integration of this program with a multidisciplinary clinic to address the specific challenges that growing patients face in our region. METHODS: The authors performed a literature review to identify models, barriers, and assessments of effective transitional care for CP patients. They also reviewed the recommendations of various professional societies regarding transitional care practices. They performed qualitative analysis of the relevant literature. RESULTS: Transitional care has been broadly categorized into transitional care clinics with multidisciplinary teams and facilitator-led transitional care. CP patients have to overcome a variety of barriers, including those from within the healthcare system as well as environmental and personal, during the period of their transition. These challenges are all interconnected, and navigation requires healthcare professionals to work closely with patients and their caregivers. Multiple instruments are described to measure successful transition, which is likely a reflection of the unique needs that a patient may require. Current guidelines recommend that neurosurgeons select a suitable model of care based on their own local practice and available services, develop a well-defined transition plan, and identify a primary transition facilitator or care coordinator. CONCLUSIONS: Providing effective transitional care to CP patients remains challenging given the different models of care and the barriers faced by them during the period of transition. In developing a transitional care program for these patients, attention must be given to the resources that are available regionally, with an effort to incorporate the best practices from successful transitional care programs.

Aggressive vertebral hemangiomas in children.

BACKGROUND: Aggressive vertebral hemangiomas are rare tumors in children, usually occurring in the thoracic spine that can cause significant neurological morbidity. They are technically difficult to treat with significant risk of blood loss during surgery. METHODS: We describe a case of aggressive vertebral hemangioma managed in our institution. We performed a literature review of reported cases of aggressive vertebral hemangiomas in pediatric age group. We discuss the clinical presentation, diagnosis, and management of these lesions. RESULTS: We identified 23 cases of aggressive vertebral reported in children. Neurodeficit was the most common presentation, and the most common location was the thoracic spine. Surgery was the most common modality of treatment. All the patients reported in literature had improvement in their symptoms after treatment. CONCLUSION: Although technically challenging, aggressive vertebral hemangiomas have a good outcome after treatment. Treatment should be tailored to the individual patient. Further studies are needed to determine the optimum treatment strategy.

Holocord metastasis from supratentorial glioblastoma multiforme: an uncommon manifestation of a common tumor.

Intramedullary metastasis from primary glioblastoma multiforme (GBM) is a rare phenomenon with a poor prognosis. The rate of spinal metastasis from intracranial GBM has been variably reported to be 0.4-2%. According to a review by Lawton in 2012, there were only 42 documented cases of primary intracranial GBM with spinal metastasis. We present a unique case of early-onset symptomatic holocord metastasis of GBM in a patient approximately 2 months of detection of primary GBM.

PatientExploreR: an extensible application for dynamic visualization of patient clinical history from electronic health records in the OMOP common data model.

MOTIVATION: Electronic health records (EHRs) are quickly becoming omnipresent in healthcare, but interoperability issues and technical demands limit their use for biomedical and clinical research. Interactive and flexible software that interfaces directly with EHR data structured around a common data model (CDM) could accelerate more EHR-based research by making the data more accessible to researchers who lack computational expertise and/or domain knowledge. RESULTS: We present PatientExploreR, an extensible application built on the R/Shiny framework that interfaces with a relational database of EHR data in the Observational Medical Outcomes Partnership CDM format. PatientExploreR produces patient-level interactive and dynamic reports and facilitates visualization of clinical data without any programming required. It allows researchers to easily construct and export patient cohorts from the EHR for analysis with other software. This application could enable easier exploration of patient-level data for physicians and researchers. PatientExploreR can incorporate EHR data from any institution that employs the CDM for users with approved access. The software code is free and open source under the MIT license, enabling institutions to install and users to expand and modify the application for their own purposes. AVAILABILITY AND IMPLEMENTATION: PatientExploreR can be freely obtained from GitHub: https://github.com/BenGlicksberg/PatientExploreR. We provide instructions for how researchers with approved access to their institutional EHR can use this package. We also release an open sandbox server of synthesized patient data for users without EHR access to explore: http://patientexplorer.ucsf.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein α-synuclein.

The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well.

Substrate and inhibitor-induced dimerization and cooperativity in caspase-1 but not caspase-3.

Caspases are intracellular cysteine-class proteases with aspartate specificity that is critical for driving processes as diverse as the innate immune response and apoptosis, exemplified by caspase-1 and caspase-3, respectively. Interestingly, caspase-1 cleaves far fewer cellular substrates than caspase-3 and also shows strong positive cooperativity between the two active sites of the homodimer, unlike caspase-3. Biophysical and kinetic studies here present a molecular basis for this difference. Analytical ultracentrifugation experiments show that mature caspase-1 exists predominantly as a monomer under physiological concentrations that undergoes dimerization in the presence of substrate; specifically, substrate binding shifts the KD for dimerization by 20-fold. We have created a hemi-active site-labeled dimer of caspase-1, where one site is blocked with the covalent active site inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. This hemi-labeled enzyme is about 9-fold more active than the apo-dimer of caspase-1. These studies suggest that substrate not only drives dimerization but also, once bound to one site in the dimer, promotes an active conformation in the other monomer. Steady-state kinetic analysis and modeling independently support this model, where binding of one substrate molecule not only increases substrate binding in preformed dimers but also drives the formation of heterodimers. Thus, the cooperativity in caspase-1 is driven both by substrate-induced dimerization as well as substrate-induced activation. Substrate-induced dimerization and activation seen in caspase-1 and not in caspase-3 may reflect their biological roles. Whereas caspase-1 cleaves a dramatically smaller number of cellular substrates that need to be concentrated near inflammasomes, caspase-3 is a constitutively active dimer that cleaves many more substrates located diffusely throughout the cell.

Intramedullary Spinal Epidermoid Cyst-A Rare Cause of Spastic Paraparesis.

Spinal intramedullary epidermoids are rare intramedullary lesions of the spinal cord. They may be congenital or acquired with the congenital type often associated with spinal dysraphism and other spinal anomalies. The clinical presentation depends on the level of the involvement of the spinal cord. Management of these lesions is surgical excision. We report a case of intramedullary spinal epidermoid who presented with spastic paraparesis.

Clinical, Microbiological Profile, and Treatment Response to Intraventricular Antibiotics in the Management of Postneurosurgical Meningitis: A Single-Center Experience.

BACKGROUND: Postneurosurgical meningitis (PNM) is a serious medical condition with high mortality and morbidity caused by Gram positive organisms like Staphylococcus aureus and Gram-negative organisms like Acinetobacter baumannii. Optimum concentration of antibiotics in the cerebrospinal fluid (CSF) to treat these infections is difficult to achieve. Intraventricular antibiotic administration bypasses the blood-brain barrier and can achieve high CSF concentration without causing systemic toxicity. METHODS: Retrospective review of all patient records were done to identify patients who developed postneurosurgical meningitis and received intraventricular antibiotic therapy during the period of July 2017 to December 2022. Demographic and clinical data along with the type of antibiotic, route, dose, and duration of administration were collected. CSF parameters before and after intraventricular antibiotic administration were collected and analyzed. RESULTS: Twenty-six patients with postneurosurgical meningitis received intraventricular antibiotic therapy. Intracranial tumors were the most common underlying pathology followed by aneurysms. In all, 17/26 patients had received vancomycin and 9/26 patients had received colistin. External ventricular drain was used in 17/26 cases and Ommaya reservoir was used in 9/26 cases. Six patients showed growth of organism in CSF before starting intraventricular antibiotics, while one patient remained culture positive despite treatment. Of the 26 patients, 3 died despite treatment. There were significant changes in the CSF parameters after intraventricular antibiotic therapy. CONCLUSION: Intraventricular administration of antibiotic provides an alternative therapeutic option in the management of patients who are not responding or poorly responding to systemic antibiotics.

Lingual Abscess after Posterior Fossa Surgery: An Unusual Complication of the Concorde Position.

Posterior fossa tumors are one of the most common tumors occurring in children. These tumors are often operated in the Concorde or prone position. Venous congestion can occur due to neck flexion during the positioning causing macroglossia. We report a case of a lingual abscess in a child after surgery in the Concorde position. There was no preoperative evidence of any lingual and dental complaints or injury during intubation. We hypothesize that the lingual abscess in the immediate postoperative period was secondary to venous stasis during the positioning for surgery.

Circular Configuration of Torcular Herophili Presenting as Childhood Headache: 2D Computational Fluid Dynamic Analysis with a Proposed Mechanism.

This case report presents a rare anatomical variant of the torcular Herophili, characterized by a circular configuration and the absence of the left transverse sinus. A 12-year-old child presented with intermittent holocranial headaches, and imaging revealed the circular torcular Herophili along with mild ventricular enlargement. The straight sinus drained into the left side of the circular torcular Herophili. Following lumbar puncture and cerebrospinal fluid (CSF) drainage, the child experienced symptom improvement. During a 6-month follow-up, the patient remained asymptomatic, without further headaches or academic disruptions. Similar to a previously reported case, the circular torcular Herophili with unilateral absent transverse sinus may be associated with impaired CSF absorption due to altered blood flow through abnormal venous anatomy. We performed two-dimensional computational fluid dynamic analysis of simulated flow through a synthetic model and showed that this circular configuration is associated with venous stasis. The venous stasis in the sinus may impair CSF absorption through the arachnoid granulations causing hydrocephalus and explaining the headache. Close monitoring and follow-up are recommended for patients with this variant. Further investigation is needed to better understand the clinical implications and underlying mechanisms of such torcular Herophili variations.

Intracranial peripheral primitive neuroectodermal tumor presenting as neurosurgical emergency: A report of two cases.

Ewing's sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) belongs to the family of malignant small and blue round cell tumors. It usually occurs in children and young adults with 3/4th of the cases arising from bone and 1/4 from soft tissue. Here, we present two cases of intracranial ES/pPNET who presented with mass effect. Management consists of surgical excision followed by adjuvant chemotherapy. Intracranial ES/pPNETs are highly aggressive and rare malignancies, reported to comprise of 0.03% of all intracranial tumors. The most common genetic aberration associated with ES/pPNET is chromosomal translocation t (11,12) (q24;q12). Patients with intracranial ES/pPNETs may present in acute or delayed manner. The presenting symptoms and signs depend on the location of the tumor. Intracranial pPNET although slow growing, they are highly vascular and may present as neurosurgical emergencies due to mass effect. We have presented the acute presentation of this tumor and its management.

Oral Midodrine as an Adjunct in Rapid Weaning of Intravenous Vasopressor Support in Spinal Cord Injury.

Background Majority of acute cervical spinal cord injury end up requiring long-term stay in intensive care unit (ICU). During the initial few days after spinal cord injury, most patients are hemodynamically unstable requiring intravenous vasopressors. However, many studies have noted that long-term intravenous vasopressors remain the main reason for prolongation of ICU stay. In this series, we report the effect of using oral midodrine in reducing the amount and duration of intravenous vasopressors in patients with acute cervical spinal cord injury. Materials and Methods Five adult patients with cervical spinal cord injury after initial evaluation and surgical stabilization are assessed for the need for intravenous vasopressors. If patients continue to need intravenous vasopressors for more than 24 hours, they were started on oral midodrine. Its effect on weaning of intravenous vasopressors was assessed. Results Patients with systemic and intracranial injury were excluded from the study. Midodrine helped in weaning of intravenous vasopressors in the first 24 to 48 hours and helped in complete weaning of intravenous vasopressors. The rate of reduction was between 0.5 and 2.0 µg/min. Conclusion Oral midodrine does have an effect in reduction of intravenous vasopressors for patients needing prolonged support after cervical spine injury. The real extent of this effect needs to be studied with collaboration of multiple centers dealing with spinal injuries. The approach seems to be a viable alternative to rapidly wean intravenous vasopressors and reduce duration of ICU stay.

ALK Inhibitor Treatment Patterns and Outcomes in Real-World Patients with ALK-Positive Non-Small-Cell Lung Cancer: A Retrospective Cohort Study.

BACKGROUND: Randomized trials have demonstrated that anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) can be safe and efficacious treatments for patients with ALK-positive advanced non-small-cell lung cancer (aNSCLC). However, their safety, tolerability, effectiveness, and patterns of use in real-world patients remain understudied. OBJECTIVE: We sought to assess the overall treatment pattern characteristics, safety, and effectiveness outcomes of real-world patients with ALK-positive aNSCLC receiving ALK TKIs. PATIENTS AND METHODS: This retrospective cohort study using electronic health record data included adult patients with ALK-positive aNSCLC receiving ALK TKIs between January 2012 and November 2021 at a large tertiary medical center, University of California, San Francisco (UCSF), with alectinib or crizotinib as the initial ALK TKI therapy. Our primary endpoints included the incidence of treatment changes (treatment dose adjustments, interruptions, and discontinuations) during the initial ALK TKI treatment, the count and type of subsequent treatments, rates of serious adverse events (sAEs), and major adverse events (mAEs) leading to any ALK TKI treatment changes. Secondary endpoints included the hazard ratios (HRs) for median mAE-free survival (mAEFS), real-world progression-free survival (rwPFS), and overall survival (OS) when comparing alectinib with crizotinib. RESULTS: The cohort consisted of 117 adult patients (70 alectinib and 47 crizotinib) with ALK-positive aNSCLC, with 24.8%, 17.9%, and 6.0% experiencing treatment dose adjustments, interruptions, and discontinuation, respectively. Of the 73 patients whose ALK TKI treatments were discontinued, 68 received subsequent treatments including newer generations of ALK TKIs, immune checkpoint inhibitors, and chemotherapies. The most common mAEs were rash (9.9%) and bradycardia (7.0%) for alectinib and liver toxicity (19.1%) for crizotinib. The most common sAEs were pericardial effusion (5.6%) and pleural effusion (5.6%) for alectinib and pulmonary embolism (6.4%) for crizotinib. Patients receiving alectinib versus crizotinib as their first ALK TKI treatment experienced significantly prolonged median rwPFS (29.3 versus 10.4 months) with an HR of 0.38 (95% CI 0.21-0.67), while prolonged median mAEFS (not reached versus 91.3 months) and OS (54.1 versus 45.8 months) were observed in patients receiving alectinib versus crizotinib but did not reach statistical significance. Yet, it is worth noting that there was a high degree of cross-over post-progression, which could significantly confound the overall survival measures. CONCLUSIONS: We found that ALK TKIs were highly tolerable, and alectinib was associated with favorable survival outcomes with longer time to adverse events (AE) requiring medical interventions, disease progression, and death, in the context of real-world use. Proactive monitoring for adverse events such as rash, bradycardia, and hepatotoxicity may help further promote the safe and optimal use of ALK TKIs in the treatment of patients with aNSCLC.

Cerebral abscess as a neurosurgical emergency in Eisenmenger syndrome: illustrative case.

BACKGROUND: Eisenmenger syndrome caused by severe pulmonary arterial hypertension in congenital heart disease can cause multisystemic involvement and is a risk factor for development of cerebral abscess. Cerebral abscess, if not detected and treated in a timely manner, can present as acute neurosurgical emergency. OBSERVATIONS: The authors reported a case of cerebral abscess in a patient with Eisenmenger syndrome. The patient presented with acute neurological deterioration with mass effect and cerebral infarcts and received emergency neurosurgical intervention. A further literature search was done to identify prior reported cases of cerebral abscess with Eisenmenger syndrome. LESSONS: Patients with Eisenmenger syndrome have compromised cardiorespiratory status, and decision for neurosurgical intervention should be given careful consideration. Multidisciplinary team management along with preoperative optimization of the patient should be used.

Trans-cranial Doppler Flow Characteristics of a Child with Paroxysmal Sympathetic Hyper-activity: A Preliminary Report.

Background: Paroxysmal sympathetic hyper-activity (PSH) is a syndrome characterized by excessive activity of the sympathetic nervous system. The cerebrovascular flow dynamics during the episodes of paroxysmal hyper-activity has also not been clearly examined in the literature. Case History: A 12-year-old boy with operated exophytic brain stem pilocytic astrocytoma was diagnosed with paroxysmal sympathetic hyper-activity. The trans-cranial Doppler flow characteristics of the bilateral middle cerebral artery and anterior cerebral artery are described in this report. Conclusion: The diagnosis of PSH requires an index of suspicion on the part of the clinician. The episodes of sympathetic hyper-activity are associated with significant changes in physiologic parameters in the patients including changes in cerebrovascular flow dynamics.

Shunt Migration in Children: A Patient Level Systematic Review of Risk Factors and Outcome.

Ventriculoperitoneal shunt insertion is one of the most common pediatric neurosurgical procedures performed. Shunt migration is one of the infrequent complications of shunt insertion and often requires a change of the shunt system. The objective of the study is to systematically review the sites of shunt migration and factors associated with mortality in children. Comprehensive search and review of the literature were done according to the PRISMA guidelines. Citations were selected using the following inclusion criteria: 1. Shunt migration in ventriculoperitoneal shunts was the primary inclusion criteria, 2. Age of the study participants <18 years, and 3. Patient-level data available in the study. Exclusion criteria were 1. Age >18 years, 2. Patient-level data not available, 3. Full text of the article not available, and 4. Article not in the English language. Sites of migration and risk factors for mortality were assessed. In total, 111 studies out of 161 studies were included in the final analysis. The scrotum was the most common site of shunt migration (30.67%), followed by anal migration, migration into the bowel, chest wall/thoracic migration, and intracranial/subgaleal migration. Univariate analysis showed the presence of infection and site of migration to be significantly associated with mortality. Multivariate analysis showed the presence of infection and age at presentation to be significant predictors of mortality. This study highlights that presence of infection is a significant predictor of mortality in cases of shunt migration. Infection should be managed expeditiously for optimum management of shunt migration.

Use of a Mobile Health Intervention by Older Versus Younger People with HIV: Analysis of Usage, Social Support, and Network Interactions.

Background: People with HIV in the United States are aging, with risk for negative health outcomes from social isolation. PositiveLinks is a mobile health (mHealth) intervention that includes an anonymous Community Message Board (CMB) for peer-to-peer conversations. We investigated differences in CMB usage and social support between younger (<50 years) and older (≥50) members. Methods: We assessed the relationship between age groups and app use using chi-square tests. CMB posts were analyzed qualitatively to categorize forms of social support. To have a visual understanding of this relationship, we created a network diagram to display interactions among PL members. Results: Among 87 participants, 31 (42.5%) were in the older age group. Older members launched the app more often at 6 months (445.5 vs. 240.5 mean launches per participant, p ≤ 0.001) and 12 months (712.3 vs. 292.6 launches, p ≤ 0.001) compared with younger members. Older members also demonstrated more CMB posts at 6 months (47.4 vs. 7.6 mean posts per participant, p = 0.02) and 12 months (77.5 vs. 10.6 posts, p = 0.04). Of 1861 CMB posts, 7% sought support and 72% provided support. In addition, the network visualization showed that four participants, who were in the older age group, had more post generation than others and most of their posts provided support. Conclusions: Older PL members demonstrated significantly more app use than younger members, including CMB posts for social support. This durable app engagement indicates that mHealth can enable social connection among people living with chronic disease across the lifespan.