Clinical, microbiological profile and treatment response to intraventricular antibiotics in the Management of Post-Neurosurgical Meningitis: A single center experience.

Introduction Post-Neurosurgical Meningitis (PNM) is a serious medical condition with high mortality and morbidity caused by organisms like Staphylococcus aureus and Gram-negative organisms like Acinetobacter baumannii. Optimum concentration of antibiotics in the cerebrospinal fluid (CSF) to treat these infections are 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 post-neurosurgical meningitis and received intraventricular antibiotic therapy during the period of July 2017 to December 2022. Demographic and clinical data along with type of antibiotic, route, dose and duration of administration was collected. CSF parameters before and after intraventricular antibiotic administration were collected and analyzed. Results 26 patients with post-neurosurgical meningitis received intraventricular antibiotic therapy. Intracranial tumors were the most common underlying pathology followed by aneurysms. 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. 6 cases showed growth of organism in CSF before starting intraventricular antibiotics, 1 case remained culture positive despite treatment. 3/26 patients 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.

An Observational Comparative Study to Evaluate the Use of Image-Guided Surgery in the Management and Outcome of Supratentorial Intracranial Space-Occupying Lesions.

Objectives: The objective of this article is to study the effect of neuronavigation on the outcome of surgery for supratentorial tumors, such as the extent of resection, size of craniotomy, and overall morbidity and mortality by comparing with conventional excision. Methods: A total of 50 patients undergoing intracranial surgery for supratentorial space-occupying lesions from 2020 to 2022 were included in the study. One intervention group consisted of patients undergoing surgical resection of supratentorial tumors utilizing image guidance versus the control group, which consisted of patients undergoing surgical excision of supratentorial tumor excision without image guidance. Parameters used to compare the outcome were the extent of resection of the lesions, craniotomy size, and overall morbidity and mortality. Results and Conclusion: There was no significant reduction in craniotomy size or prolongation of operative duration with the use of neuronavigation. There was no significant difference in postoperative hospital stay between the two groups. Neuronavigation-assisted cases did not show any significant reduction in the occurrence of postoperative neurological deficits or any reduction of overall morbidity and mortality.

Primary diffuse large B-cell lymphoma of the prostate: Histopathological diagnosis of a rare entity in the prostate.

ABSTRACT: Lymphoma of the prostate is rare whether it is primary extranodal lymphoma or secondary involvement of the prostate by primary lymphoma elsewhere. Of all the lymphomas of the prostate, primary lymphomas of the prostrate are very rare. Although less frequent, it should be a differential diagnosis when evaluating prostate tumors. Here, we report a case of a 61-year-old man who presented with hematuria with clot retention. A cystoscopy with clot removal and transurethral resection of the prostate (TURP) was performed. This biopsy was sent for histopathological examination at an external center, where a diagnosis of benign prostatic hyperplasia was given. Fifteen days later, the patient presented with hematuria again. On examination, clots were present in the bladder. There was significant prostatomegaly. A re-resection of the prostate was performed and sent for another review to us. The biopsy was reported as high-grade round cell neoplasm, most likely lymphoma. Immunohistochemistry (IHC) was recommended for confirmation. Tumor cells showed immunoreactivity for CD20, B-cell Lymphoma (BCL)-2, BCL-6, Myelocytomatosis (c-Myc), and multiple myeloma 1 (MUM1). Cluster Differentiation (CD)10 was negative. Kiel-67 was high. A final diagnosis of double-expressor diffuse large B-cell lymphoma (DLBCL) of non-germinal center type was made. We share this case to emphasize the fact that primary lymphoma of the prostate is primarily a histopathological diagnosis as the clinical presentation is not unique. Owing to its rarity, the clinical and histopathological suspicion is low. Hence, keeping the differential in mind while evaluating prostate biopsy is beneficial in a timely diagnosis of the entity as the management of prostatic carcinoma and lymphoma is different.

Correlation Between Aneurysm Dome Direction and Patient Outcomes Following Surgery for Ruptured Anterior Communicating Artery Aneurysms.

Background Anterior communicating (Acom) artery aneurysms are the most common type of intracranial aneurysms. Despite the enormous advancements in the field of endovascular surgery for intracranial aneurysms, open surgical clipping of aneurysms remains the most durable management of Acom aneurysms. There have been various studies based on the clinical-radiological profile and outcome of open clipping for intracranial aneurysms, but the correlation of the direction of the aneurysm with the surgical outcome remains incompletely defined. Aim To analyze the correlation between the direction of the aneurysm dome and patient outcomes after surgery for ruptured Acom artery aneurysms. Materials and methods  CT angiography of the brain was done in all patients pre-operatively as part of the standard treatment protocol. Retrospective data was collected from an inter-departmental computerized database, which included the patient's details, history, investigations, a course in the hospital from admission to discharge, and an operative note by the surgeon. Prospective data was collected from patients with ruptured Acom artery aneurysms. We analyzed the relationship between the direction of the dome of the Acom aneurysm and preoperative, intraoperative, and postoperative variables. Results Of the 48 patients who underwent surgery for ruptured aneurysms, 34 (70.8%) were female and 14 (29.2%) were male. Among the 27 cases with anteriorly projecting aneurysms, 11 (40.7%) experienced postoperative complications. Of the five cases with posteriorly projecting aneurysms, two (40%) experienced postoperative complications. One-third of cases of the inferior dome direction and 10% of cases of the superior direction of the dome of aneurysm were also found to have postoperative complications. However, using the chi-square test, the association between postoperative complications and the direction of the aneurysm was determined to be statistically non-significant (p-value = 0.93). Conclusion The findings of our investigation indicate that aneurysms with superior projection exhibit the lowest likelihood of experiencing intraoperative rupture. However, it was seen that the outcome was influenced by dome projection throughout the three-month follow-up. The findings of our study indicate that aneurysms with a superior orientation exhibit the least likelihood of experiencing intraoperative rupture.

Rare Case of Hemorrhagic Atypical Choroid Plexus Papilloma of Fourth Ventricle in Adult: A Diagnostic Dilemma.

Choroid plexus papillomas are highly vascular tumors, and such tumors causing subarachnoid hemorrhage have been reported in literature. Similarly, few articles have reported atypical fourth ventricular choroid plexus tumors in adults. However, such an atypical tumor presenting with grossly hemorrhagic transformation without any acute symptoms could not be found in the literature.

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.

Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.

Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin's neuroprotective role in Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.

Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants.

Understanding cannabis-drug interactions is critical given regulatory changes that have increased access to and use of cannabis. Cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (Δ9-THC), the most abundant phytocannabinoids, are in vitro reversible and time-dependent (CBD only) inhibitors of several cytochrome P450 (CYP) enzymes. Cannabis extracts were used to evaluate quantitatively potential pharmacokinetic cannabinoid-drug interactions in 18 healthy adults. Participant received, in a randomized cross-over manner (separated by ≥ 1 week), a brownie containing (i) no cannabis extract (ethanol/placebo), (ii) CBD-dominant cannabis extract (640 mg CBD + 20 mg Δ9-THC), or (iii) Δ9-THC-dominant cannabis extract (20 mg Δ9-THC and no CBD). After 30 minutes, participants consumed a cytochrome P450 (CYP) drug cocktail consisting of caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A). Plasma and urine samples were collected (0-24 hours). The CBD + Δ9-THC brownie inhibited CYP2C19 > CYP2C9 > CYP3A > CYP1A2 (but not CYP2D6) activity, as evidenced by an increase in the geometric mean ratio of probe drug area under the plasma concentration-time curve (AUC) relative to placebo (AUCGMR ) of omeprazole, losartan, midazolam, and caffeine by 207%, 77%, 56%, and 39%, respectively. In contrast, the Δ9-THC brownie did not inhibit any of the CYPs. The CBD + Δ9-THC brownie increased Δ9-THC AUCGMR by 161%, consistent with CBD inhibiting CYP2C9-mediated oral Δ9-THC clearance. Except for caffeine, these interactions were well-predicted by our physiologically-based pharmacokinetic model (within 26% of observed interactions). Results can be used to help guide dose adjustment of drugs co-consumed with cannabis products and the dose of CBD in cannabis products to reduce interaction risk with Δ9-THC.

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.

A Physiologically-Based Pharmacokinetic Model for Cannabidiol in Healthy Adults, Hepatically-Impaired Adults, and Children.

Cannabidiol (CBD) is available as a prescription oral drug that is indicated for the treatment of some types of epilepsy in children and adults. CBD is also available over-the-counter and is used to self-treat a variety of other ailments, including pain, anxiety, and insomnia. Accordingly, CBD may be consumed with other medications, resulting in possible CBD-drug interactions. Such interactions can be predicted in healthy and hepatically-impaired (HI) adults and in children through physiologically based pharmacokinetic (PBPK) modeling and simulation. These PBPK models must be populated with CBD-specific parameters, including the enzymes that metabolize CBD in adults. In vitro reaction phenotyping experiments showed that UDP-glucuronosyltransferases (UGTs, 80%), particularly UGT2B7 (64%), were the major contributors to CBD metabolism in adult human liver microsomes. Among the cytochrome P450s (CYPs) tested, CYP2C19 (5.7%) and CYP3A (6.5%) were the major CYPs responsible for CBD metabolism. Using these and other physicochemical parameters, a CBD PBPK model was developed and validated for healthy adults. This model was then extended to predict CBD systemic exposure in HI adults and children. Our PBPK model successfully predicted CBD systemic exposure in both populations within 0.5- to 2-fold of the observed values. In conclusion, we developed and validated a PBPK model to predict CBD systemic exposure in healthy and HI adults and children. This model can be used to predict CBD-drug or CBD-drug-disease interactions in these populations. SIGNIFICANCE STATEMENT: Our PBPK model successfully predicted CBD systemic exposure in healthy and hepatically-impaired adults, as well as children with epilepsy. This model could be used in the future to predict CBD-drug or CBD-drug-disease interactions in these special populations.

Assessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial.

Importance: Controlled clinical laboratory studies have shown that cannabidiol (CBD) can sometimes attenuate or exacerbate the effects of Δ9-tetrahydrocannabinol (Δ9-THC). No studies have evaluated differences in pharmacokinetics (PK) of Δ9-THC and pharmacodynamics (PD) between orally administered cannabis extracts that vary with respect to Δ9-THC and CBD concentrations. Objective: To compare the PK and PD of orally administered Δ9-THC-dominant and CBD-dominant cannabis extracts that contained the same Δ9-THC dose (20 mg). Design, Setting, and Participants: This randomized clinical trial was a within-participant, double-blind, crossover study conducted from January 2021 to March 2022 at the Johns Hopkins University Behavioral Pharmacology Research Unit, Baltimore, MD. Eighteen healthy adults completed 3 randomized outpatient experimental test sessions that were each separated by at least 1 week. Interventions: Brownies containing (1) no cannabis extract (ie, placebo); (2) Δ9-THC-dominant extract (20 mg Δ9-THC with no CBD); and (3) CBD-dominant extract (20 mg Δ9-THC + 640 mg CBD) were administered to participants 30 minutes prior to administering a cytochrome P450 (CYP) probe drug cocktail, which consisted of 100 mg caffeine, 20 mg omeprazole, 25 mg losartan, 30 mg dextromethorphan, and 2 mg midazolam. Main Outcomes and Measures: Change-from-baseline plasma concentrations for Δ9-THC or Δ9-THC metabolites and scores for subjective drug effects, cognitive and psychomotor performance, and vital signs. The area under the plasma vs concentration vs time curve (AUC) and maximum plasma concentration (Cmax) were determined. Results: The participant cohort of 18 adults included 11 males (61.1%) and 7 females (38.9%) with a mean (SD) age of 30 (7) years who had not used cannabis for at least 30 days prior to initiation of the study (mean [SD] day since last cannabis use, 86 [66] days). The CYP cocktail + placebo brownie and the CYP cocktail did not affect any PD assessments. Relative to CYP cocktail + Δ9-THC, CYP cocktail + Δ9-THC + CBD produced a higher Cmax and area under the plasma concentration vs time curve for Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH. The CYP cocktail + Δ9-THC + CBD increased self-reported anxiety, sedation, and memory difficulty, increased heart rate, and produced a more pronounced impairment of cognitive and psychomotor performance compared with both CYP cocktail + Δ9-THC and CYP cocktail + placebo. Conclusions and Relevance: In this randomized clinical trial of oral Δ9-THC and CBD, stronger adverse effects were elicited from a CBD-dominant cannabis extract compared with a Δ9-THC-dominant cannabis extract at the same Δ9-THC dose, which contradicts common claims that CBD attenuates the adverse effects of Δ9-THC. CBD inhibition of Δ9-THC and 11-OH-Δ9-THC metabolism is the likely mechanism for the differences observed. An improved understanding of cannabinoid-cannabinoid and cannabinoid-drug interactions are needed to inform clinical and regulatory decision-making regarding the therapeutic and nontherapeutic use of cannabis products. Trial Registration: clinicaltrials.gov Identifier: NCT04201197.

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.

Assessment of Hearing Loss in Minor Head Injury: A Prospective Study.

Introduction Hearing loss following a head injury is common and well known. The numbers of road traffic accidents have increased recently, with minor head injuries being very common, and usually go unreported. Hearing loss after a minor head injury is often unnoticed. Available literature is limited in this regard. Objective This study was done to assess hearing loss in patients with minor head injuries and to define its natural history and progression/regression by a serial assessment of hearing. Methods This prospective study was done in the Department of Neurosurgery, AIIMS, Bhubaneshwar, Odisha, India, for a period of 24 months to look at the profile of hearing levels of patients presenting with history suggestive of minor head injury. Results This study has shown that some form of hearing loss is common after a minor head injury and should be evaluated in all patients to detect subclinical hearing loss. A significant number of patients having minimal or a mild degree of hearing loss, if managed properly, improve to preinjury status. Distortion product oto-acoustic emission testing should be used as the screening and follow-up tool. Conclusion This study highlights the importance of hearing assessment in minor-head-injury patients and the prognosis of recovery as per the severity of hearing loss and head injury.

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.

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.

Study of Arterial Blood Gas Analysis in Moderate-to-Severe COVID-19 Patients.

Background The high prevalence of pneumonia and renal involvement in coronavirus disease 2019 (COVID-19) leads to frequent acid-base abnormalities in serious patients and affects prognosis. In this study, we aimed to assess the arterial blood gas (ABG) and acid-base patterns in COVID-19 patients admitted to a tertiary care hospital. Methodology A retrospective observational study was conducted in a designated COVID-19 hospital involving 267 reverse transcription-polymerasechain reaction-positive COVID-19 patients. Demographic and laboratory data including ABG data within the first day after admission and in patients with multiple ABG analyses, only the first measurement was collected and analyzed statistically, including its association with comorbidities. Results The most common age group of the patients was 51-60 years (30.8%), with a male predominance (male:female = 2.7:1). The most common comorbidities were hypertension, diabetes mellitus, and chronic obstructive pulmonary disease found in 147 (55%) COVID-19 patients. Alkalosis and acidosis were observed in 145 (54.3%) and 50 (18.7%) patients, respectively. The most common ABG abnormality observed was primary respiratory alkalosis with secondary metabolic acidosis in 67 (25.1%) patients, followed by primary respiratory alkalosis with secondary metabolic alkalosis in 54 (20.2%) patients. Statistically significant negative correlation was found with PaCO2 and pH (r = -0.530, p < 0.0001), statistically significant positive correlation was found between pH and base (r = 0.533, p < 0.0001), pH and TCO2 (r = 0.260, p < 0.0001), and pH and HCO3 (r = 0.354, p < 0.0001). Conclusions Acid-base abnormalities are commonly encountered in COVID-19 patients. Respiratory alkalosis as a part of a single or mixed pattern on ABG was the most common pattern found in critically ill COVID-19 patients. ABG on admission in moderate-to-severe COVID-19 patients can help in the early correction of metabolic abnormalities leading to improved patient outcomes.