Planum-Clival Angle Classification: A Novel Preoperative Evaluation for Sellar/Parasellar Surgery

Objective Endonasal approaches are increasingly used to treat sellar pathologies, leading to increased interest in achieving maximal safe resection. We propose a tool—the planum-clival angle (PCA)—and explore its surgical implications for sellar pathology resections. Design Retrospective analysis. Participants Consecutive patients with pituitary lesions between 2003 and 2013. Outcome Measures The PCA and suprasellar extension ratios; head position and extent of surgical resection. Results We enrolled 89 patients (ages 21–88 years). There were 15 type A patients (17%), 13 with suprasellar extension (89%) and ratios between 0.12 and 0.70. There were 61 type B patients (70%), 49 with suprasellar extension (81%) and ratios from 0.09 to 0.66. Finally, there were 13 type C patients (13%), 10 with suprasellar extension (73%) and ratios from 0.21 to 0.76. Type B was treated with a sphenoidectomy and neutral head positioning, type A with 10 to 20 degrees of flexion and an additional posterior ethmoidectomy with or without posterior planum resection, and type C with 10 to 20 degrees of extension and an additional superior clival resection. Conclusions Sellar anatomy and PCA influence the growth patterns of sellar lesions. Thus PCA should allow for better surgical planning and thereby improve surgical efficacy.     

Health Care Utilization After Ventricular Tachycardia Ablation: A Propensity Score-Matched Cohort Study

Background

Catheter ablation of ventricular tachycardia (VT) can reduce the burden of ventricular arrhythmia (VA) but its effect on health care utilization and costs after such therapy is poorly known. We sought to compare the rates of cardiovascular (CV)-related hospitalizations, survival, and health care costs in patients with recurrent VT treated either with VT ablation or with medical therapy.

Effect of sinapic acid on aripiprazole pharmacokinetics in rats: Possible food drug interaction

Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans.     

Pediatric intracranial hypertension: Experience from 2 Tertiary Centers

Objectives:To review the experience of 2 tertiary centers in Saudi Arabia with intracranial hypertension (IH) in the pediatric population.Methods:We retrospectively reviewed and analyzed pediatric patients diagnosed with IH from June 2002 to May 2017 in 2 institutes.Results:We identified 53 patients (30 females and 23 males) with a mean age of 7 years at the time of presentation. Among them, 41 patients were younger than 12 years, and 12 were older. Obese and overweight patients constituted 27.00% (n = 14) of all cases, 8 (66.7%) of whom were older than 12 years. The most common presenting feature was papilledema followed by headache. Vitamin D deficiency, which constituted the most common associated condition, was identified in 12 (22.6%) patients. Acetazolamide was the treatment option in 98.11% of patients, and only 5.7% underwent surgical interventions. The length of follow-up ranged from 6 months to 8 years.Conclusion:Intracranial hypertension is rare in children and commonly seen in overweight females older than 12 years similar to adults. Patients younger than 12 years tend to develop secondary IH. More studies are needed to characterize the clinical presentation and guide the management plan.

Intracranial hypertension (IH) is rarely reported in children. It is characterized by increased intracranial pressure (ICP) without any evidence of underlying brain pathology, structural abnormalities, hydrocephalus, or any abnormal meningeal enhancement.1 The incidence of IH differs from region to region due to variations in the prevalence of obesity and other secondary causes. The annual incidence of IH in children is 0.9 per 100,000 in the United States,2 0.5 per 100,000 in Germany,3 0.6 per 100,000 in Nova Scotia and Prince Edward Island in Eastern Canada,4 and 1.2 per 100,000 in Croatia.5 A study carried out in Oman estimated the incidence of IH to be 1.9 per 100,000 in children below 15 years of age; with it being higher in female children.6 The present study aimed to review the clinical presentation, possible aetiological factors, diagnosis, management, and outcomes in children with IH in 2 tertiary institutes in Saudi Arabia.     

Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Association between craniovertebral junction abnormalities and syringomyelia in patients with chiari malformation type-1

Objectives:To assess the correlation between craniovertebral junction (CVJ) abnormalities and syringomyelia in patients with Chiari malformation type-1 (CM1).Methods:This was a retrospective study including patients with CM1. Identification of cases was done by searching a radiology database at a university hospital from 2012 to 2017. Patients were divided into 2 groups based on whether CVJ abnormalities were present (CVJ+) or absent (CVJ-). The patients’ demographic and clinical data were reviewed. All magnetic resonance imaging studies were examined by a certified neuroradiologist.Results:Sixty-four consecutive patients with CM1 were included. The mean age was 24±17 years; 59% were females. The CVJ+ group had more female patients (p = 0.012). The most frequent CVJ abnormality was platybasia (71%), followed by short clivus (44%) and cervical kyphosis (33%). The CVJ abnormalities were more in Syringomyelia cases (p = 0.045). However, the results were not significant when hydrocephalus cases were excluded.Conclusion:Among CM1 patients, CVJ abnormalities were found more in patients with syringomyelia. Future studies with larger sample size are required to further study the correlation between CVJ abnormalities and both syringomyelia and hydrocephalus in CM1 patients.

Chiari malformation type-1 (CM1) was first described in 1891 by Austrian pathologist Hans Chiari.1,2 The CM1 is defined as caudal displacement of the cerebellar tonsils below the foramen magnum by 5 mm or more.3,4 This definition is merely a radiological definition. In the literature, the degree of cerebellar tonsil displacement varies from 3 mm to 5 mm.4 CM1 affects approximately 1% of the population and may involve a spectrum of neurologic involvement.2 Syringomyelia is reported in 25% of CM1 cases and may cause irreversible damage to the spinal cord with subsequent neurological deficits.5The pathophysiology of syringomyelia development in patients with CM1 has been extensively studied.6-9 Majority of publications indicated a block to the cerebrospinal fluid (CSF) circulation at the level of the craniovertebral junction (CVJ).8,9 Subsequently, the cerebrospinal fluid (CSF) accumulates and forms syringomyelia.8,9 The source of the CSF forming the syringomyelia can be from the fourth ventricle, the subarachnoid space (SAS), or from an extracellular source.8,9 From the 1950s to the 1970s, syringomyelia was believed to result from a difference in CSF pressure between the fourth ventricle and the central canal of the spinal canal.7 Theories to explain this mechanism include James Gardner’s water-hammer theory, Bernard Williams’ cranio-spinal pressure dissociation theory, and Ball and Dayan’s theory of tonsillar obstruction to the CSF pathway.10-12 In the 1990s, Oldfield believed that the mechanism of the development of syringomyelia involved abnormal CSF flow at the level of the foramen magnum.6,7 The descent of the cerebellar tonsils with each cardiac cycle produces a pressure wave in the spinal SAS, and thereby compresses the spinal cord from the outside and propagates a syrinx.7,9Several intradural and extradural factors have been implicated in the pathophysiology of CM1. Among the intradural factors identified during surgery for CM1, the presence of an arachnoid membrane obstructing the foramen of Magendie (i.e., an arachnoid veil) was significantly more frequent in patients with an associated syringomyelia.6 Other studies have examined whether the degree of tonsillar descent below foramen magnum in the CM1 patients is a contributing factor to the development of syringomyelia; however, the impact of tonsillar descent is controversial.6,9,13 Some studies have reported that the rate of syringomyelia increases as the degree of tonsillar herniation increases.6,9 As a possible explanation for syringomyelia development, other studies14,15 have addressed crowding of the SAS at the foramen magnum caused by tonsillar decent. In a study by Doruk et al15, the measured cervicomedullary compression ratio, defined as the ratio of the area occupied by the cerebellar tonsils to the area of the foramen magnum, was significantly correlated with the development of syringomyelia. This ratio could reflect the severity of blockage of the SAS at the CVJ and further supports the previously described mechanisms of syringomyelia development.9Extradural abnormalities at the CVJ are associated with CM1.15 Such pathologies include a small posterior cranial fossa, platybasia, basilar invagination, and short clivus.3,6,8,9 Several studies have examined the presence of CVJ abnormities in CM1 patients with and without syringomyelia.13,16-21 However, the presence of associated syringomyelia within the context of CM1 with and without CVJ abnormalities was inadequately highlighted. For instance, in one study,13 syringomyelia existed in 64% of CM1 patients with a short clivus, compared to 36% of CM1 patients without a short clivus. In order to further understand the relationship between the presence of one or more CVJ abnormalities and syringomyelia in CM1, the current study was conducted. Such knowledge will likely enhance the understanding of CVJ relationship with CM1 and may aid in the management of syringomyelia in such patients.     

Role of the vulnerable elders survey-13 screening tool in predicting treatment plan modification for older adults with cancer

Background: The Vulnerable Elders Survey (VES-13) is commonly used to identify older patients who may benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cut point of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive VES-13 scores (7–10)have a higher likelihood of a change in treatment compared to low positive scores (3–6).Methods: Retrospective review of a customized database of all patients seen for pre-treatment assessment in an academic geriatric oncology clinic from June 2015 to June 2019. Various VES-13 cut points were analyzed to identify those individuals whose treatment was modified after CGA. Area under the curve (AUC) was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by treatment modality.Results: We included 386 patients with mean age 81, 58% males. Gastrointestinal cancer was the most common site (31%) and 60% were planned to receive curative treatment. The final treatment plan was modified in 59% overall, with 52.7% modified with VES-13 scores 7–10, 50.8% with scores 3–6 and 28.1% with scores <3 (P = 0.002). VES-13 performance in predicting treatment modification was similar for cut points 3 (AUC 0.58), 4 (0.59), 5 (0.59), and 6 (0.59) and in those considering local treatment vs. chemotherapy.Conclusions: A positive VES-13 score was associated with final oncologic treatment plan modification. A high positive score was not superior to the conventional cut point of ≥3.