Role of Copeptin in Predicting Postoperative Hyponatremia and Hypernatremia in Patients Undergoing Endoscopic Pituitary Adenoma Surgery.

BACKGROUND AND OBJECTIVES: Arginine vasopressin (AVP) is an important hormone responsible for maintaining sodium homeostasis after pituitary surgery. The measurement of AVP levels is difficult because of its short half-life (t1/2). Copeptin is a preprohormone of AVP, and it is a more stable peptide, which can be used as surrogate marker for AVP. This study aims to assess the role of copeptin as a predictor of postoperative hyponatremia and hypernatremia in patients undergoing endoscopic pituitary adenoma surgery. METHODS: This prospective study included 50 patients who underwent endoscopic pituitary adenoma surgery. Serum copeptin levels of these patients were assessed (1) preoperatively (C1), (2) at extubation (C2), and (3) postoperative day 4 (C3). Perioperative data regarding fluid and sodium balance were collected from patients. Statistical analysis was done using the above data. RESULTS: The copeptin values were assessed against the sodium disturbances. 100% of patients who developed transient diabetes insipidus had a relative decrease in C2 from C1 (P - .0002). 88% of patients who developed early hyponatremia had a relative increase in C2 as compared with C1 (P < .01). 75% of patients who developed delayed hyponatremia had a relative increase in C3 as compared with C1 (P = .003). CONCLUSION: A relative increase or decrease in early change in copeptin (C2-C1) can predict development of early hyponatremia or transient central diabetes insipidus, respectively. A relative increase in delayed change in copeptin (C3-C1) can predict development of delayed hyponatremia.

Endoscopic Endonasal Transsphenoidal Transcavernous Transoculomotor Triangle Approach for Resection of an Invasive Pituitary Adenoma Extending Into the Parapeduncular Space Through the Cavernous Sinus.

BACKGROUND AND IMPORTANCE: A subset of invasive pituitary adenomas invade not only the medial wall of the cavernous sinus but can progress superiorly through the cavernous sinus roof at the oculomotor triangle and reach the subarachnoid parapeduncular space. We describe a series of 2 of 3 cases where an endoscopic endonasal approach was used to reach the parapeduncular space through the oculomotor triangle for tumor decompression. Images of the third case are presented. CLINICAL PRESENTATION: Case 1: We present a 2-dimensional surgical video of a recurrent corticotroph adenoma post gamma knife radiotherapy which was invading the left cavernous sinus and extending into the left parapeduncular space. Histopathological examination revealed densely granulated corticotrophin adenoma. The patient had reduction in the serum cortisol level postoperatively and was induced into remission medically. Postoperative third nerve palsy recovered partially, and sixth nerve palsy recovered completely at the 3-month follow-up. Case 2 : A case of recurrent silent corticotrophin adenoma invading the right parapeduncular space through the right cavernous sinus was operated through the same approach as case 1. Only a subtotal excision of the tumor in the cisternal space was possible. The patient developed a complete right third cranial palsy in the immediate postoperative period with near total recovery at the 6-month follow-up. CONCLUSION: Endoscopic endonasal approach to the parapeduncular space through a transcavernous transoculomotor route is reasonably safe and effective, as long as key anatomic landmarks and structures are identified and preserved while using natural tumor corridors to achieve tumor clearance.

Colloid Cyst: Revision of Third Ventricular Zones for Risk Stratification of Hydrocephalus.

OBJECTIVE: We sought to reclassify the "anatomic risk zones of colloid cysts" as proposed by Beaumont et al, by proposing newer landmarks, and to assess predictive value for the risk of occurrence of hydrocephalus with the new classification compared with the old. METHODS: A retrospective cohort of 122 cases of colloid cyst of third ventricle were categorized into zones 1, 2, or 3 based on Beaumont's classification (old zone) and our classification (new zone) based on radiologic images. We attempted to recategorize these zones by assigning new anatomic landmarks. The difference in zonal distribution of colloid cyst and association with hydrocephalus was studied using the 2 methods of zonal classification. RESULTS: Per the old zone classification, 3/122 patients were in zone 2, whereas 21/122 were in zone 2 per the new zone classification. The new zone method had a higher specificity (36.21% vs. 5.263 %) and positive predictive value (63.37% vs. 54.23%) for occurrence of hydrocephalus in patients with colloid cyst. The Spearman correlation showed better correlation with the new method for occurrence of hydrocephalus (rho = 0.4 [P < 0.00000] vs. 0.2 [P = 0.011]). CONCLUSIONS: Symptomatic colloid cysts are more likely to develop hydrocephalus and sudden acute deterioration. The colloid cyst risk score is a step towards objective decision making, with scope for modification such as the one that we have attempted with new zone classification to achieve superior prognostic ability.

Analysis of Evolution of Hydrocephalus in Posterior Fossa Tumors and Validation Study of the Modified Canadian Preoperative Prediction Rule for Hydrocephalus in Children and Frankfurt Grading System for Prediction of Cerebrospinal Fluid Diversion in Adults with Posterior Fossa Tumors.

OBJECTIVE: We sought to analyze the evolution of hydrocephalus and enumerate its predictive factors in posterior fossa tumors in children and adults. We also validated the modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) and Frankfurt grading systems as tools to predict cerebrospinal fluid (CSF) diversion in children and adults, respectively. METHODS: A retrospective review of patients with posterior fossa tumors operated between 2012 and 2019 was performed. Clinical, radiologic, and operative data were obtained. Validation was performed for both scores via receiver operating characteristic (ROC) curves and evaluation of the area under the curve (AUC). RESULTS: We included 116 children and 343 adults in the study. Of the adults, 141 patients had intraaxial tumors and 172 had extraaxial tumors. The insertion of external ventricular drain (EVD), its duration, papilledema was noted to have significant influence on the need for permanent CSF diversion (P < 0.05) in children. The ROC for mCPPRH score was 0.659 (0.501-0.816), Age- 0.496 (0.334-0.658) and Evans index- 0.788 (0.654-0.922). In adults- Intraaxial tumours Age, Frankfurt score, duration of EVD, Diagnosis, Extent of resection and periventricular capping significant predictors and ROC age AUC 0.300 (0.193-0.407), Evans index 0.939 (0.888-0.990), and Frankfurt score 0.908 (0.853-0.964) (P < 0.05), whereas in extraaxial tumors Frankfurt grading, sex, duration of EVD, presence of perilesional edema and extent of resection (P < 0.05) ROC age AUC 0.439 (0.344-0.534), Evans index 0.941 (0.906-0.977), and Frankfurt score 0.847 (0.782-0.912). CONCLUSIONS: This is the first external validation study for the 2 predictive systems in use. mCPPRH demonstrated poor predictive accuracy, and Frankfurt grading system demonstrated good accuracy. EVD insertion and its duration was significantly predictive of the need for permanent CSF diversion.

Design and evaluation of propranolol hydrochloride loaded thiolated Zein/PEO electrospun fibrous matrix for transmucosal drug delivery.

Thiolated polymers have garnered wide attention from researchers on mucoadhesive drug delivery. This work explores the thiolation of zein protein using cysteine amino acid via the EDC crosslinker. The optimization of thiolation and purification have been done and confirmed using Ellman's assay and Raman spectra. The thiolated Zein/PEO polymer blend has been appraised for electrospinning to fabricate fibrous matrices. The extent of thiol modification augmented the mechanical properties and adhesion in rabbit intestinal mucosa. In vitro cytotoxicity evaluations such as direct contact assay, MTT assay, and live dead assay performed in RPMI 2650 cells corroborated the non-cytotoxicity of the fabricated matrices with and without propranolol hydrochloride (PL). Detailed drug release studies were conducted in PBS. Drug release in PBS followed the Korsmeyer Peppas model of release. On treating RPMI 2650 cells with the matrix, F-actin and adherens junctional proteins retained integrity, and consequently, drug permeation would proceed through the transcellular transport mechanism. Transepithelial electrical resistance (TEER) measurement of the RPMI 2650 cell monolayer also supported the transcellular transport mechanism. Ex vivo permeation study through porcine buccal mucosa showed 41.26 ± 0.56% PL permeation within 24 h of study. It validated the competence of the electrospun thiolated Zein/PEO matrix for transmucosal drug delivery.

Clinical Reasoning: A Teenager With Chronic Meningitis-Does Occam's Razor Apply?

A 14-year-old girl presented with subacute onset headache, fever, and vomiting and was managed initially with antibiotics for suspected bacterial meningitis. Her symptoms further evolved over the next few weeks with systemic signs and symptoms favoring chronic meningitis with raised intracranial pressure. After the etiologic workup was unrevealing, she was started on empirical antituberculous therapy. After a period of partial improvement, symptoms recurred with a new-onset focal seizure. Her imaging findings evolved from features suggestive of focal leptomeningitis to multifocal heterogeneous enhancing cortical and subcortical lesions with hemorrhagic foci, leading to brain biopsy that confirmed diagnosis. Our case highlights the utility of diagnostic biopsy in patients with "chronic meningitis" in uncertain cases rather than confining the approach to the law of parsimony. The decision to initiate empirical therapy in chronic meningitis should be considered on a case-by-case basis and take into account factors, such as clinical examination findings, immune status, recent exposures, and potential risks of treatment. Atypical MRI features should lower the threshold for meningocortical biopsy when indicated.

Electrospun Mucoadhesive Zein/PVP Fibroporous Membrane for Transepithelial Delivery of Propranolol Hydrochloride.

Mucoadhesive drug delivery systems have been extensively studied to effectively reduce the limitations of conventional drug delivery systems. Zein and polyvinyl pyrrolidone (PVP) are appraised for mucoadhesive properties. This study focuses on developing a mechanically stable zein/PVP electrospun membrane for propranolol hydrochloride (PL) transport. Fourier transform infrared, Raman spectra, and swelling studies gave evidence for PVP crosslinking, whereas circular dichroism spectroscopy revealed crosslinking of zein owing to the conformational change from α-helix to ß-sheet. A 10 h thermal treatment of zein/PVP imparted 3.92 ± 0.13 MPa tensile strength to the matrix. Thermally crosslinked electrospun zein/PVP matrix showed 22.1 ± 0.1 g mm work of adhesion in porcine buccal mucosa tissue. Qualitative and quantitative evaluation of cytotoxicity in RPMI 2650 has been carried out. The in vitro drug release profile of PL from thermally crosslinked zein/PVP best fitted with the Korsmeyer-Peppas model. Immunostaining of ß-catenin adherens junctional protein confirmed the absence of paracellular transport through the junctional opening. Still, drug permeation was observed through the porcine buccal mucosa, attributed to the transcellular transport of PL owing to its lipophilicity. The ex vivo permeation of PL through porcine buccal mucosa was also evaluated.

Rapid malignant transformation of an intracranial epidermoid cyst: Report of a case.

Intracranial epidermoid cysts (ECs) occur at various locations along the neuraxis and account for nearly 2% of all intracranial tumors. Considering the frequency of ECs, transformation of ECs into squamous cell carcinomas is a rare occurrence. Here, we report the case of a 39-year-old man who presented with a lesion in the left cerebellopontine angle and underwent gross total resection for the same. Histopathological examination revealed a benign EC with mild chronic inflammation. Five months later, the patient presented with another lesion at the same location with evidence of brainstem bleed. Histopathological examination revealed a moderately differentiated squamous cell carcinoma and remnants of the previous cyst in the form of lamellated keratin, indicating malignant transformation of the EC.

Endoscopic Transpterygoid Corridor for Petroclival Tumors: Case Series and Technical Nuances.

Background: The petroclival area is a technically challenging region to operate owing to the proximity of the internal carotid artery (ICA) and the need to obtain gross total excision of tumors in this area as they are often resistant to radiotherapy. Objective: We present our experience with the endonasal endoscopic transpterygoid approach in managing tumors of the petroclival region and discuss various operative nuances for safer resection. Materials and Methods: A retrospective study of all consecutive cases of lesions occupying the petroclival region that were operated via endonasal endoscopic transpterygoid approach at our center between January 2016 and December 2021 was performed. Results: The study included 14 cases of lesions occupying the petroclival region. Gross total resection by intraoperative observation was achieved in 10 patients, near total decompression was performed in two patients, and the remaining two patients underwent marsupialization of lesion. Postoperatively, one patient had right Lower motor neuron (LMN) facial nerve palsy and one patient required surgery for Cerebrospinal fluid (CSF) rhinorrhea on postoperative day 8. The mean duration of follow-up was 13.8 ± 16.6 months (range: 2-59 months). Four of six patients with visual symptoms on presentation reported improvement in vision, and the other two patients had a stable vision on follow-up. Two patients received radiotherapy postsurgery. No mortality was noted. Conclusion: The extended endonasal endoscopic transpterygoid approach can be safely and efficiently used for petroclival lesions. Very sound knowledge of anatomical relationship, use of intraoperative image guidance to avoid injury to ICA, and multilayer reconstruction with a vascularized nasoseptal flap are required to optimize the clinical outcome.

A prospective-randomized placebo-controlled trial comparing the effects of nebulized dexmedetomidine v/s dexmedetomidine-lignocaine mixture on intraoperative hemodynamics and surgical field quality in patients undergoing endoscopic transnasal transsphenoidal pituitary tumor surgery.

Background: During transnasal transsphenoidal pituitary surgery (TNTSS), the primary objective is to maintain stable hemodynamics while ensuring ideal surgical conditions. This study aimed to investigate the effect of nebulized dexmedetomidine on hemodynamic parameters and the quality of the surgical field during TNTSS. Methods: Seventy-five patients scheduled for TNTSS were randomized into three groups of 25 each and received preoperative nebulization with 5 mL of nebulizing fluid consisting of 1.5 µg/kg of dexmedetomidine with saline in dexmedetomidine (D) group; 1.5 µg/kg of dexmedetomidine with 2% lignocaine in dexmedetomidine-lignocaine (DL) group and normal saline in the control (S) group. Heart rate (HR), mean blood pressure, Formmers score, anesthetic requirement, and emergence were evaluated for each group. Results: Group S had significantly higher HR and mean arterial pressure than the other two groups across various time points during surgery (P < 0.01). The total requirements for fentanyl, propofol, sevoflurane, and labetalol and the incidence of delayed emergence were significantly higher in the S group compared to the other two groups (P < 0.01). The D and DL groups exhibited significantly better surgical field conditions than the S group. In all the parameters assessed, patients in the D group outperformed those in the DL group. Conclusion: The administration of nebulized dexmedetomidine, both alone and in combination with lignocaine, resulted in stable hemodynamics, favorable operative conditions, reduced anesthetic requirement, and facilitated prompt emergence during TNTSS. Nebulized dexmedetomidine proved superior to its combination with lignocaine across all evaluated parameters.

Large Pituitary Adenoma: Strategies to Maximize Volumetric Resection Using Endoscopic Endonasal Approaches and an Analysis of Factors Limiting Resection.

BACKGROUND: Large pituitary adenomas (LPAs), which constitute ∼5%-14% of all pituitary adenomas, are considered challenging tumors owing to their locally aggressive behavior, low gross total resection rate, and high prevalence of visual deficits and hypopituitarism. We evaluated the utility of various extended endoscopic endonasal approaches in maximizing the resection of LPAs and studied the factors affecting the extent of surgical resection. METHODS: A retrospective study of all LPAs (defined as a minimum diameter >3 cm and tumor volume >10 cm3) treated via an endoscopic endonasal approach between January 2015 and December 2020 was performed. The volumetric extent of resection (3-dimensional volumetric analysis software) was correlated with various demographic, tumor-related, pathologic, and immunohistochemical factors and its effects on the clinical outcomes studied. RESULTS: The present study included 106 patients with LPAs. The mean extent of the resection volume was 79.18 ± 21.75 cm3. The factors that affected the extent of resection included the preoperative tumor volume (P = 0.03) and Knosp grade (P = 0.03). The percentage increase in the extent of resection with the use of 2 endonasal corridors was 10.6% and with 3 corridors was 14%. Visual improvement occurred in 82% of patients, and new-onset persistent hormonal insufficiency occurred in 2.9% of patients. Mortality directly related to surgery occurred in 1.8% of cases. CONCLUSIONS: Extended endoscopic endonasal approaches can safely and effectively be used for gross total resection of LPAs. However, we found that the preoperative tumor volume and Knosp grade were significant factors affecting the extent of tumor resection. The use of multiple endoscopic endonasal corridors can increase the volumetric extent of resection for LPAs.

Endoscopic Endonasal Excision of a Meckel's Cave Dermoid Cyst.

Background: Meckel's cave dermoid cyst is an extremely rare and a technically challenging lesion. The objective of the study is to show that endoscopic endonasal approach (EEA) has recently emerged as a better alternative to transcranial approach for this formidable tumor, owing to minimal retraction-related morbidity. Method: A 52-year-old male presented with numbness over the right side of the face and temporal area for the last 3 years. On examination, there was decreased sensation to touch, pain, and temperature over the right V1, V2, and V3 areas with an absent right corneal reflex. Imaging revealed a heterogenous extra-axial lesion in the right Meckel's cave. The tumor was resected by an extended endonasal transpterygoid approach. Results: The patient had improvement in his symptoms with no endocrine complication. Conclusion: This case demonstrates the surgical techniquenof endoscopic endonasal transpterygoid resection of a Meckel's cave dermoid cyst.

Prospective Study of Sinonasal Outcome Following Endoscopic Skull Base Surgery.

Background: Endoscopic endonasal surgery (EES) requires wide sinonasal dissection to achieve adequate visualisation of anatomical landmarks. This can also result in nasal sequelae like crusting, nasal discharge, and anosmia. Aim: To use the sinonasal outcome test (SNOT) 22 questionnaire to study the postoperative sinonasal morbidity and its recovery in patients who have undergone EES. Materials and Method: Prospective study conducted from November 2017 to May 2018. SNOT-22 questionnaire was administered on patients operated between before EES and then re-administered during outpatient visits at 1 month, 3 months, and 6-12 months following surgery. Results: Results of 46 patients were analyzed. The mean duration of follow-up was 11.8 months. The mean preoperative SNOT-22 score was 2.69 ± 4.95. SNOT-22 score at 1 month was 5.52 ± 6.77, at 3 months follow-up was 0.39 ± 1.02, and after 6 months was 0.30 ± 1.00. In 32 patients with a nasoseptal flap, mean preoperative score was 3.34 ± 5.68 (P = 0.18), one month following surgery it was 6.68 ± 6.88 and at 3 and 6 months following surgery it was 0.56 ± 1.19 and 0.38 ± 1.15. The mean preoperative nasal domain score was 1.022 (±2.13), the postoperative 1 month score was 2.3 ± 3.7, at 3 months following surgery was 0.22 ± 0.82 and after 6 months of surgery was 0.28 ± 0.96. Conclusion: Patients undergoing EES experienced transient worsening of SNOT 22 scores in the first month following surgery and recovered within 3 months of surgery. The improvement was sustained in follow-up visits beyond 6 months of surgery.

Endoscopic Endonasal Excision of a Complex Craniopharyngioma Operated Multiple Times by Transcranial Route.

Background: Complex craniopharyngiomas pose a significant surgical challenge owing to its proximity to critical structures and its intrinsic nature to resist radical excision. Objective: To show that endoscopic endonasal approach (EEA) is potentially a better alternative to transcranial approach in tumors that have been operated multiple times by transcranial route for achieving radical excision with minimal morbidity. Materials and Methods: A 32-year-old male previously operated twice through interhemispheric approach for craniopharyngioma presented with blurring of vision accompanied by headache and intermittent diplopia. Imaging revealed a large lobulated suprasellar recurrence with a large calcified part adjacent to left internal carotid artery. The tumor was resected by an extended endonasal approach. The patient experienced improvement in his vision with no significant endocrine complication. Results and Conclusion: This case demonstrates the surgical technique and various operative nuances of endoscopic endonasal resection of a complex craniopharyngioma.

UV-Crosslinked Electrospun Zein/PEO Fibroporous Membranes for Wound Dressing.

Electrospun zein membranes are suitable for various biomedical applications. A UV-crosslinked electrospun membrane of a zein/PEO blend for wound healing application was explored in this work. The improvement in mechanical properties of the membrane after UV crosslinking was attributed to the change in protein conformation from an α-helix to a ß-sheet. The circular dichroism (CD) spectra and FTIR spectra confirmed this conformational change. XRD analysis was shown to prove the amorphous nature of polymer blends with specific broad peaks at 2θ = 9° and 20°. The water vapor transmission rate (WVTR) of the membrane was found to be in the range of 1500-2000 g m-2 day-1, which was well suited with that of commercially available wound dressing material. Enough number of available functional groups like thiol, amino, and hydroxyl groups supplement a blood clotting index (BCI) to the matrix, causing 99% BCI within 4 min. A 91% cell viability result in the MTT assay with human dermal fibroblast cells confirmed the noncytotoxicity of the membrane. Tripeptides produced after the thermolysin-based hydrolysis of zein caused inhibition of TGF ß1 expression and thus increased fibroblast and collagen production. The membrane stimulated 54% more collagen production compared to control cells at day 2 and caused 84% wound closure in human dermal fibroblast cells, which were desirable index markers of a potential wound care material.