Treatment of Pediatric Epilepsy: Expert Opinion, 2005

2005 ◽  
Vol 20 (1_suppl) ◽  
pp. S1-S56 ◽  
Author(s):  
James W. Wheless ◽  
Dave F. Clarke ◽  
Daniel Carpenter

Background. Childhood epilepsies are a heterogeneous group of conditions that differ in diagnostic criteria and management and have dramatically different outcomes. Despite increasing data on treatment of epilepsy, research findings on childhood epilepsy are more limited and many clinical questions remain unanswered, so that clinicians must often rely on clinical judgment. In such clinical situations, expert opinion can be especially helpful. Methods. A survey on pediatric epilepsy and seizures (33 questions and 645 treatment options) was sent to 41 U.S. physicians specializing in pediatric epilepsy, 39 (95%) of whom completed it. In some questions, the experts were asked to recommend overall treatment approaches for specific syndromes (the order in which they would use certain strategies). Most of the questions asked the experts to rate options using a modified version of the RAND 9-point scale for medical appropriateness. Consensus was defined as a non-random distribution of scores by chisquare test, with ratings used to assign a categorical rank (first line/usually appropriate, second line/equivocal, and third line/usually not appropriate) to each option. Results. Valproate was treatment of choice for symptomatic myoclonic and generalized tonic-clonic seizures except in the very young, with lamotrigine and topiramate also first line (usually appropriate). Zonisamide was first line only if the child also has myoclonic seizures. For initial monotherapy for complex partial seizures, oxcarbazepine and carbamazepine were treatments of choice, with lamotrigine and levetiracetam also first line. As initial therapy for infantile spasms caused by tuberous sclerosis, viagabatrin was treatment of choice, with adrenocorticotropic hormone (ACTH) also first line. As initial therapy for infantile spasms that are symptomatic in etiology, ACTH was treatment of choice, with topiramate also first line As initial therapy for Lennox-Gastaut syndrome, valproate was treatment of choice, with topiramate and lamotrigine also first line. For acute treatment of a prolonged febrile seizure or cluster of seizures, rectal diazepam was treatment of choice. For benign childhood epilepsy with centro-temporal spikes, oxcarbazepine and carbamazepine were treatments of choice, with gabapentin, lamotrigine, and levetiracetam also first line. For childhood absence epilepsy, ethosuximide was treatment of choice, with valproate and lamotrigine also first line. For juvenile absence epilepsy, valproate and lamotrigine were treatments of choice. For juvenile myoclonic epilepsy in adolescent males, valproate and lamotrigine were treatments of choice, with topiramate also first line; for juvenile myoclonic epilepsy in adolescent females, lamotrigine was treatment of choice, with topiramate and valproate other first-line options. As initial therapy for neonatal status epilepticus, intravenous phenobarbital was treatment of choice, with intravenous lorazepam or fosphenytoin also first line. As initial therapy for all types of pediatric status epilepticus, lorazepam was treatment of choice, with intravenous diazepam also first line. For generalized tonic-clonic status epilepticus, rectal diazepam and fosphenytoin were also first line; for complex partial status epilepticus, fosphenytoin was also first line; and for absence status epilepticus, intravenous valproate was also first line. Conclusion. The expert panel reached consensus on many treatment options. Within the limits of expert opinion and with the understanding that new research data may take precedence, the experts' recommendations provide helpful guidance in situations where the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings. (J Child Neurol 2005;20:Sl-S56)

2019 ◽  
Vol 34 (11) ◽  
pp. 646-652 ◽  
Author(s):  
Dallas Armstrong ◽  
Rana R. Said

Objective: We performed a retrospective chart review of patients with trisomy 21 and infantile spasms in our university-based pediatric epilepsy center between 2002 and 2016 in order to describe the clinical characteristics of children with these diagnoses as well as to evaluate their response to first-line treatments. Methods: Patients with infantile spasms were identified via the neurophysiology database. Charts were reviewed with attention to infantile spasms diagnosis, presence of trisomy 21, age of reported clinical onset, treatment lag, treatments used, response to treatment, imaging findings, electroencephalography (EEG) data, and developmental outcomes. Results: Of the 310 patients with infantile spasms, 24 also had trisomy 21. Three patients did not meet inclusion criteria. Ten of the 21 patients received nonstandard therapies first line; 2 of the 10 (20%) achieved spasm control, and 4 of the 8 who failed therapy (50%) progressed to Lennox-Gastaut syndrome. Eleven of the 21 patients received standard therapies as first-line treatments (10 with prednisolone according to the protocol in the United Kingdom Infantile Spasms Study [UKISS] and 1 with adrenocorticotrophic hormone [ACTH]). Nine of the 10 patients (90%) who received prednisolone achieved spasm resolution, 6 (60%) of these without relapse. The final patient (10%) failed prednisolone as well as ACTH. One patient received ACTH first line with success. Conclusion: This is the only series to follow children with trisomy 21 and infantile spasms in which a significant proportion received UKISS-protocol prednisolone. It adds to current knowledge about safety, tolerability, and effectiveness of prednisolone in this group.


2018 ◽  
Vol 14 (6) ◽  
pp. 359-366 ◽  
Author(s):  
Jun Gong ◽  
Ravi Salgia

Despite high response rates to initial therapy, relapses are common in patients with small-cell lung cancer (SCLC). Systemic therapy after first-line failure remains important in the treatment paradigm of SCLC. Reinitiation of a previously administered first-line chemotherapy regimen is recommended for relapse > 6 months from completion of initial therapy. For relapse ≤ 6 months of initial therapy, sequential therapy with single agents is recommended. Clinical trial enrollment should be considered at all stages of treatment of SCLC. This review highlights the available treatment options in relapsed SCLC. In particular, we focus on prospective clinical trials demonstrating activity for the most commonly used agents in this setting. We end with a discussion on future directions and emerging targets with potential to improve outcomes in relapsed SCLC.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1928-1928
Author(s):  
Christopher R. Cogle ◽  
Sudipto Mukherjee ◽  
Moira E. Lawrence ◽  
Thomas J. McKearn ◽  
Rita Percy ◽  
...  

Abstract Background: The choice of optimal salvage therapy in patients with MDS is challenging due to a current lack of therapeutic options and a lack of data in regard to the risks and benefits of existing disease management. We undertook this study with the aim of evaluating the clinical outcomes, economic impact, and cost effectiveness of currently available treatment options for MDS patients who failed first-line hypomethylating agent (HMA) therapy. Methods: We developed a Markov model to compare five second-line MDS treatment options: low- and high-intensity chemotherapy; switching HMA treatment; hematopoietic stem cell transplant (HSCT); and best supportive care (BSC). Hypothetical cohorts of patients who had failed a first-line HMA were simulated, and initiated each of these strategies. During each four-week cycle, patients could progress to acute myeloid leukemia (AML), experience a treatment- or disease-related adverse event (thrombocytopenia, anemia and neutropenia), discontinue treatment, or die (Figure 1). Costs were considered from the payer perspective and included those related to drug acquisition and administration, adverse event treatment, hospitalization, and supportive care. Inputs were based on published literature and expert opinion. Results were reported as lifetime costs (2013 USD), life expectancy in life years (LY), and incremental cost-effectiveness ratios (ICERs). Figure 1: Model Schematica Figure 1:. Model Schematica AML, acute myeloid leukemia; HMA, hypomethylating agent; MDS, myelodysplastic syndrome. a Green circles represent model health states. b MDS patients who have failed initial HMA therapy. c Second-line treatments considered for model strategies/comparators are: best supportive care (BSC), HMA, low or high intensity chemotherapy, or hematopoietic stem cell transplant. d Adverse events: thrombocytopenia, anemia, and neutropenia. Results: The model predicted that treating patients who had failed a first-line HMA with BSC was the least expensive option ($55,343 per person) but provided the shortest survival: 0.48 years. Switching patients to a second HMA increased costs to $84,625 and could extend survival modestly. Patients treated with low- and high-intensity chemotherapy had lifetime costs of $89,877 and $146,519 and life expectancy of 0.88 and 1.08 years, respectively. HSCT patients had the highest lifetime costs ($492,359) and survival (2.26 years). Compared with BSC, the ICER for low intensity chemotherapy was $87,343/LY gained, while high intensity chemo and transplant had ICERs of $284,303 and $291,375/LY, respectively. The strategy of switching patients to a second HMA was removed during the calculation of ICERs due to extended dominance, i.e., there was another strategy, namely low intensity chemotherapy, that provided greater clinical benefit and had a more attractive ICER. Conclusions: For MDS patients who had relapsed after, failed to respond, or progressed during administration of a first-line HMA, subsequent alternative active treatments provide some clinical benefit. However, such therapies substantially increase costs and a relatively small population of patients may be eligible due to functional status or matching donors. Although our results suggest that high intensity chemotherapy and transplant provide the greatest clinical benefits, they may cause substantial treatment-related morbidity. The increases in cost of care could thus be interpreted as an inefficient use of resources according to current societal standards, especially as the availability of these therapies is restricted to a limited number of patients. These findings suggest that there is an unmet need among MDS patients failing first-line HMA therapy; more research and treatment options would benefit clinical decision-making, patient outcomes, and healthcare resource allocation. Disclosures Cogle: Partnership for Health Analytic Research (PHAR): Consultancy, I was paid as a consultant for my expert opinion while developing the analyses Other. Mukherjee:Partnership for Health Analytic Research: Consultancy, I was paid as a consultant for my expert opinion while developing the analyses Other. Lawrence:Onconova Therapeutics, Inc. : Employment. McKearn:Onconova Therapeutics, Inc. : Employment. Percy:Onconova Therapeutics, Inc. : Employment. Petrone:Onconova Therapeutics, Inc. : Employment, Stock Options Other. Megaffin:Onconova Therapeutics, Inc. : Employment. Anene:Partnership for Health Analytic Research (PHAR): Employment, I am an employee of PHAR, LLC, which was paid by Onconova Therapeutics to conduct the analyses described in this abstract. Other. Ortendahl:Partnership for Health Analytic Research (PHAR): Employment, I am an employee of PHAR, LLC, which was paid by Onconova Therapeutics to conduct the analyses described in this abstract. Other. Romanus:Partnership for Health Analytic Research (PHAR): Employment, I am an employee of PHAR, LLC, which was paid by Onconova Therapeutics to conduct the analyses described in this abstract. Other. Bentley:Partnership for Health Analytic Research (PHAR): Employment, I am an employee of PHAR, LLC, which was paid by Onconova Therapeutics to conduct the analyses described in this abstract. Other.


2012 ◽  
Vol 6 ◽  
pp. CMPed.S8330 ◽  
Author(s):  
Ayşe Ülgey ◽  
Recep Aksu ◽  
Cihangir Bicer

Acute seizure and status epilepticus constitute major medical emergencies in children. Four to six percent of children will have at least one seizure in the first 16 years of life. Status epilepticus is a common neurological emergency in childhood and is associated with significant morbidity and mortality. The early application of antiepileptic treatment is very important. Because early treatment prevents the status epilepticus formation and shortens the duration of seizure activity. For this reason administration of anticonvulsant therapy in the prehospital setting is very important. Seizures generally begin outside the hospital, and thus parents and caregivers need simple, safe and effective treatment options to ensure early intervention. The only special preparation used for this purpose is rectal diazepam but has some disadvantages. Midazolam is a safe, short-acting benzodiazepin. It is suitable to use oral, buccal, nasal, im and iv routes. This provides a wide area for clinical applications. Recently there are many clinical studies about the usage of nasal and buccal midazolam for treatment of pediatric epileptic seizures. The nasal and buccal applications in pediatric seizures are very practical and effective. Parents and caregivers can apply easily outside the hospital.


2011 ◽  
Vol 3 ◽  
pp. JCNSD.S6371 ◽  
Author(s):  
Michele A. Faulkner ◽  
Justin A. Tolman

In 2009, vigabatrin became the first FDA approved medication for the treatment of infantile spasms in the United States. There are few well-designed prospective studies comparing the drug to placebo or other modalities used in the treatment of infantile spasms. The available data have demonstrated that vigabatrin is efficacious in the treatment of infantile spasms regardless of underlying etiology, but that it is particularly beneficial in patients with a diagnosis of tuberous sclerosis. Adrenocorticotropic hormone (ACTH), the only other medication with robust efficacy data, has been used as first line therapy for infantile spasms associated with other etiologies, and in general controls spasms sooner than vigabatrin, though relapse is common with both therapies. Vigabatrin is generally well tolerated. However, use has been associated with permanent loss of peripheral vision in some patients. In children with tuberous sclerosis, vigabatrin should be considered as initial therapy for infantile spasms. It is a viable alternative for patients with suboptimal response, contraindications or intolerance to ACTH.


Author(s):  
J. G. Burneo ◽  
R. S. McLachlan

Background:Choosing an antiepileptic medication to treat a patient with epilepsy can be a complicated process during which the treating physician must base her or his decision on efficacy and safety of each of many available drugs. The lack of comparative studies between medications is one of the reasons.Methods:We conducted a survey on the management of newly diagnosed epilepsy in adult patients. The surveyed were adult and pediatric neurologists with a subspecialty interest in epilepsy who were working in academic institutions or private practice across Canada. Scenarios presented were grouped in categories according to the epilepsy syndrome (absence epilepsy, juvenile myoclonic epilepsy, undetermined idiopathic generalized epilepsy, symptomatic or cryptogenic partial epilepsy, and unclassified epilepsy), the patient's gender and age. First and second step in medical treatment for status epilepticus were surveyed as well.Results:Forty one of 64 experts responded the survey (responder rate of 66%). The results revealed a consensus among Canadian epileptologists that the first choice of antiepileptic medication in generalized epilepsies was between valproate in men (chosen by 88% of respondents) and lamotrigine in women. In localization-related epilepsies, carbamazepine was the preferred drug of choice (chosen by 90% of respondents). In the treatment of status epilepticus, an initial intravenous dose of lorazepam (95% of respondents), followed by a second dose of lorazepam or intravenous phenytoin in case the initial dose of lorazepam failed, were the treatments preferred.


Author(s):  
B. González Astorga ◽  
F. Salvà Ballabrera ◽  
E. Aranda Aguilar ◽  
E. Élez Fernández ◽  
P. García-Alfonso ◽  
...  

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.


2021 ◽  
Vol 13 ◽  
pp. 175883592110311
Author(s):  
Chiun Hsu ◽  
Lorenza Rimassa ◽  
Hui-Chuan Sun ◽  
Arndt Vogel ◽  
Ahmed O. Kaseb

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii186
Author(s):  
O’Dell Patrick ◽  
H Nickols ◽  
R LaRocca ◽  
K Sinicrope ◽  
D Sun ◽  
...  

Abstract BACKGROUND Patients who have recurrent glioblastoma have limited treatment options. We conducted a retrospective review of patients with recurrent glioblastoma treated with standard initial radiation and temozolomide with tumor treating fields to investigate whether reirradiation using radiosurgery would be associated with improved outcomes. METHODS We reviewed the records of 54 consecutively treated patients with recurrent glioblastoma with ECOG 0 or 1 at recurrence and conducted Kaplan-Meier analysis with Log-rank testing to determine significance between groups. RESULTS We identified 24 patients who were treated without radiation therapy (control) while 30 patients underwent re-irradiation using radiosurgery (ReSRS) with a median total dose of 25Gy in five fractions. All patients had completed standard initial therapy, and there was no difference in the time to recurrence between the two groups (10 months for control, 15 months for ReSRS, [P = 0.17, HR for progression 0.65 (95% CI 0.38-1.13)]. A larger proportion of patients in the control arm (54%) had subtotal or gross total resection of the recurrence compared with the ReSRS group (44%, P < 0.05). The majority of patients had recurrence confirmed with biopsy (18/22 in control group, 25/31 in the ReSRS group). MGMT methylation status did not differ between control vs ReSRS (29% vs. 27%). ReSRS was associated with improved median survival from the time of first recurrence of 11.6 months versus 3.8 months in the control arm [P< 0.0001, HR for death 0.33 (95% CI 0.18-0.6)]. CONCLUSIONS In a group of patients with high performance status diagnosed with recurrent glioblastoma, reirradiation with stereotactic radiosurgery was associated with nearly one year median survival after recurrence. Additional analyses are warranted to determine the impact of concurrent systemic therapies with irradiation and underlying tumor or patient factors to predict outcomes.


2021 ◽  
pp. 088307382110195
Author(s):  
Sabrina Pan ◽  
Alan Wu ◽  
Mark Weiner ◽  
Zachary M Grinspan

Introduction: Computable phenotypes allow identification of well-defined patient cohorts from electronic health record data. Little is known about the accuracy of diagnostic codes for important clinical concepts in pediatric epilepsy, such as (1) risk factors like neonatal hypoxic-ischemic encephalopathy; (2) clinical concepts like treatment resistance; (3) and syndromes like juvenile myoclonic epilepsy. We developed and evaluated the performance of computable phenotypes for these examples using electronic health record data at one center. Methods: We identified gold standard cohorts for neonatal hypoxic-ischemic encephalopathy, pediatric treatment-resistant epilepsy, and juvenile myoclonic epilepsy via existing registries and review of clinical notes. From the electronic health record, we extracted diagnostic and procedure codes for all children with a diagnosis of epilepsy and seizures. We used these codes to develop computable phenotypes and evaluated by sensitivity, positive predictive value, and the F-measure. Results: For neonatal hypoxic-ischemic encephalopathy, the best-performing computable phenotype (HIE ICD-9 /10 and [brain magnetic resonance imaging (MRI) or electroencephalography (EEG) within 120 days of life] and absence of commonly miscoded conditions) had high sensitivity (95.7%, 95% confidence interval [CI] 85-99), positive predictive value (100%, 95% CI 95-100), and F measure (0.98). For treatment-resistant epilepsy, the best-performing computable phenotype (3 or more antiseizure medicines in the last 2 years or treatment-resistant ICD-10) had a sensitivity of 86.9% (95% CI 79-93), positive predictive value of 69.6% (95% CI 60-79), and F-measure of 0.77. For juvenile myoclonic epilepsy, the best performing computable phenotype (JME ICD-10) had poor sensitivity (52%, 95% CI 43-60) but high positive predictive value (90.4%, 95% CI 81-96); the F measure was 0.66. Conclusion: The variable accuracy of our computable phenotypes (hypoxic-ischemic encephalopathy high, treatment resistance medium, and juvenile myoclonic epilepsy low) demonstrates the heterogeneity of success using administrative data to identify cohorts important for pediatric epilepsy research.


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