Ekokobe Fonkem

Clinical Pharmacology and Pharmacokinetics of Levetiracetam

Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam (IV LEV), a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of IV LEV and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.

Selection of Antiepileptic Drugs in Older People

Opinion statementElderly people are one of the fastest-growing populations in the United States, and the incidence of epilepsy in older people is much higher than in other population subgroups. This age group is the most vulnerable because of the increased incidence of multiple medical comorbidities, including stroke. The diagnosis of epilepsy is extremely challenging and often delayed in this age group because of an atypical presentation. Seizures are manifest through extremely vague complaints, such as episodes of altered mental status or memory lapses. Once the diagnosis is established by careful history taking and diagnostic testing, anticonvulsants are the mainstay of treatment. The choice of anticonvulsants in elderly patients requires careful evaluation of medical comorbidities, which vary on an individual basis. This subgroup also is more susceptible to adverse effects because of the physiologic changes in the body due to older age, which affect the pharmacokinetics of most anticonvulsants. The ideal drug in this age group should have linear pharmacokinetics, fewer adverse effects, minimal or no drug–drug interactions, no enzyme induction/inhibition, a long half-life, and minimal protein binding, and should be cost-effective. As such, there is no ideal drug for this patient population, although both older- and newer-generation anticonvulsants are used for long-term treatment. Most newer anticonvulsants have the advantage of a favorable pharmacokinetic profile, minimal or no drug–drug interactions, and fewer adverse events, as well as being well tolerated. The older anticonvulsants still are widely used, because the newer anticonvulsants are much more expensive.

Efficacy and tolerability of intravenous levetiracetam in children

Intractable epilepsy in children poses a serious medical challenge. Acute repetitive seizures and status epilepticus leads to frequent emergency room visits and hospital admissions. Delay of treatment may lead to resistance to the first-line anticonvulsant therapies. It has been shown that these children continue to remain intractable even after acute seizure management with approved Food and Drug Administration (FDA) agents. Intravenous levetiracetam, a second-generation anticonvulsant was approved by the FDA in 2006 in patients 16 years and older as an alternative when oral treatment is not an option. Data have been published showing that intravenous levetiracetam is safe and efficacious, and can be used in an acute inpatient setting. This current review will discuss the recent data about the safety and tolerability of intravenous levetiracetam in children and neonates, and emphasize the need for a larger prospective multicenter trial to prove the efficacy of this agent in acute seizure management.

A retrospective analysis of meningioma in Central Texas

Documented meningioma cases in Central Texas (USA) from 1976 to 2013 were studied utilizing the Scott & White Brain Tumor Registry. All the cases examined were histologically diagnosed as meningiomas. Of the 372 cases, most were benign tumors (p < 0.05). A majority of the patients were females (p < 0.05). Elderly individuals (>45 years of age) superseded the younger patients in meningioma incidence (p < 0.05). Previous data regarding meningioma epidemiology in Texas showed a higher incidence in black patients when compared to white patients. By contrast, this study’s findings of Central Texas meningioma demographics show increased incidence of meningiomas in white patients (p < 0.05). This interesting find in meningioma prevalence warrants further investigation with a larger sample size, in order to establish validity and further parse out possible causes of meningioma development among white individuals.

Incidence trends, rates, and ethnic variations of primary CNS tumors in Texas from 1995 to 2013

Abstract Background Although rare, primary central nervous system (CNS) tumors are associated with significant morbidity and mortality. Texas is a representative sample of the United States population given its large population, ethnic disparities, geographic variations, and socio-economic differences. This study used Texas data to determine if variations in incidence trends and rates exist among different ethnicities in Texas. Methods Data from the Texas Cancer Registry from 1995 to 2013 were examined. Joinpoint Regression Program software was used to obtain the incidence trends and SEER*Stat software was used to produce average annual age-adjusted incidence rates for both nonmalignant and malignant tumors in Texas from 2009 to 2013. Results The incidence trend of malignant primary CNS tumors in whites was stable from 1995 to 2002, after which the annual percent change decreased by 0.99% through 2013 (95% CI, -1.4, -0.5; P = .04). Blacks and Asian/Pacific Islanders showed unchanged incidence trends from 1995 to 2013. Hispanics had an annual percent change of -0.83 (95% CI, -1.4, -0.2; P = .009) per year from 1995 through 2013. From 2009 to 2013, the incidence rates of nonmalignant and malignant primary CNS tumors were highest among blacks, followed by whites, Hispanics, Asians, and American Indians/Alaskan Natives. Conclusions Consistent with the 2016 Central Brain Tumor Registry of the United States report, the black population in Texas showed the highest total incidence of CNS tumors of any other race studied. Many factors have been proposed to account for the observed differences in incidence rate including geography, socioeconomic factors, and poverty factors, although the evidence for these external factors is lacking.

Abstract 465: CD44 as a potential therapeutic target and prognosis marker for glioblastoma

Glioblastoma (GBM) is a common and very aggressive primary brain tumor with no cure. The current diagnosis relying on magnetic resonance imagining, computed tomography, and biopsy is a very expensive and aggressive process. More effective therapeutic strategies such as target therapies and simplified early diagnosis tools are urgently needed for GBM management and prognosis. As recent reports suggest that GBM expresses CD44, a type-I transmembrane glycoprotein, is a marker of cancer stem cell and therapy resistance, with a goal of identifying a therapeutic target and a prognosis maker for GBM, we analyzed several data sets previously detected by microarrays using an online R2 Genomics analysis and visualization platform (http://r2.amc.nl). Through examining of the expression levels of CD44 in the tissues of normal cerebellum (without brain tumor) and in GBM tissues, we find that the expression level of CD44 in GBM is higher than that in non-brain tumor tissues. Comparing the expression levels of CD44 in Primary and recurrent GBMs, GBM cell lines, neuron stem cell lines, and normal cortex tissues, we observe that the expression levels of CD44 in recurrent GBMs are higher than primary GBMs; the CD44 levels in GBM cell lines are similar to neuron stem cell lines which are significantly higher than that in the normal cortex tissues. We further evaluated the correlation of CD44 levels with patients’ overall survival in 4 available complete data sets in the R2 database, including 2 from The Cancer Genome Atlas (TCGA) database. We show that an elevated level of CD44 in GBM is associated with a short overall survival time although variations exist from cohort to cohort. In addition, we studied the effect of p53 status on CD44 expression, we reveal that CD44 level is higher in the GBMs carrying p53 mutation compared to those with wild-type p53. Taken together, these results indicate that CD44 could be a potential therapeutic target of GBM and the expression level of CD44 in the GBM may be an indicator of poor outcome for patients with GBM. Citation Format: Fengfei Wang, Xin Shen, Jessica Pruszynski, Jason Huang, Batool Kirmani, Erxi Wu, Ekokobe Fonkem. CD44 as a potential therapeutic target and prognosis marker for glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 465.