Biomedical subjects

Sandra L Helmers

Publications and source records attributed to Sandra L Helmers.

6 recordsLinked to original sources

PubMed2006

An epilepsy mutation in the sodium channel SCN1A that decreases channel excitability.

Mutations in three voltage-gated sodium channel genes, SCN1A, SCN2A, and SCN1B, and two GABAA receptor subunit genes, GABRG2 and GABRD, have been identified in families with generalized epilepsy with febrile seizures plus (GEFS+). A novel mutation, R859C, in the Nav1.1 sodium channel was identified in a four-generation, 33-member Caucasian family with a clinical presentation consistent with GEFS+. The mutation neutralizes a positively charged arginine in the domain 2 S4 voltage sensor of the Nav1.1 channel alpha subunit. This residue is conserved in mammalian sodium channels as well as in sodium channels from lower organisms. When the mutation was placed in the rat Nav1.1 channel and expressed in Xenopus oocytes, the mutant channel displayed a positive shift in the voltage dependence of sodium channel activation, slower recovery from slow inactivation, and lower levels of current compared with the wild-type channel. Computational analysis suggests that neurons expressing the mutant channel have higher thresholds for firing a single action potential and for firing multiple action potentials, along with decreased repetitive firing. Therefore, this mutation should lead to decreased neuronal excitability, in contrast to most previous GEFS+ sodium channel mutations, which have changes predicted to increase neuronal firing.

Action Potentials↗

PubMed2004

The new antiepileptic drugs: scientific review.

CONTEXT: The past decade has brought many advances to the treatment of epilepsy, including many new pharmacological agents. Primary care physicians often care for patients with epilepsy and therefore should be familiar with the new options available. OBJECTIVE: To review data regarding the efficacy and tolerability of antiepileptic drugs introduced in the past decade. DATA SOURCES: A search of the Cochrane Central Register of Controlled Trials was performed to identify all published human and English-language randomized controlled trials evaluating the efficacy and tolerability of the antiepileptic drugs that have been approved for use in the United States since 1990. Additional reports evaluating pharmacokinetic properties were identified through a MEDLINE search as well as review of article bibliographies. STUDY SELECTION AND DATA EXTRACTION: Search terms included felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, and zonisamide. Studies were selected if efficacy and tolerability were reported as major outcome measures. Included studies (n = 55) enrolled a minimum of 20 adult subjects and had a treatment period of at least 6 weeks. DATA SYNTHESIS: Eight new antiepileptic drugs have been approved for use in the United States in the past decade. Each new antiepileptic drug is well tolerated and demonstrates statistically significant reductions in seizure frequency over baseline. No randomized controlled trials have compared the new antiepileptic drugs with each other or against the traditional antiepileptic drugs. Although there is no evidence to suggest that the newer medications are more efficacious, several studies have demonstrated broader spectrum of activity, fewer drug interactions, and overall better tolerability of the new agents. CONCLUSIONS: New antiepileptic drugs offer many options in the treatment of epilepsy, each with unique mechanisms of action as well as adverse effect profiles. The new antiepileptic drugs are well tolerated with few adverse effects, minimal drug interactions, and a broad spectrum of activity.

Acetates↗

PubMed2004

The new antiepileptic drugs: clinical applications.

In the past decade, 8 new antiepileptic drugs have been approved for use in the United States, offering many new treatment options to patients with epilepsy. With expanding use of these newer agents, primary care clinicians are challenged with understanding the roles that each new agent plays in the treatment of patients with epilepsy as well as possible interactions with other pharmacological therapies. Each new medication provides a unique profile of pharmacokinetics, adverse effects, and mechanisms of action, making an appreciation of how these agents are best utilized even more difficult. Despite well-performed trials evaluating the safety and efficacy of specific antiepileptic drugs, the lack of head-to-head comparisons among them makes it difficult to endorse a single therapeutic regimen. Limited studies have compared the new antiepileptic drugs with more traditional medications and found similar efficacy but improved tolerability of the newer agents. There remains no well-established guidelines for choosing a particular antiepileptic drug or for choosing a newer agent over a traditional one. However, careful consideration of seizure type, patient comorbidities, and specific medication toxicities aids in prescribing the most appropriate medication. This article aims to familiarize the general practitioner with the appropriate roles and effective uses of the new antiepileptic drugs in specific clinical scenarios.

Adult↗

PubMed2003

Observations on the use of vagus nerve stimulation earlier in the course of pharmacoresistant epilepsy: patients with seizures for six years or less.

BACKGROUND: This study retrospectively compared the effectiveness of vagus nerve stimulation (VNS) therapy among a constant cohort of patients in the patient outcome registry, which systematically monitors outcomes of patients receiving VNS therapy. Patients in the study had pharmacoresistant seizures for 6 years or less (early treatment group) or more than 6 years (late treatment group) before initiation of VNS therapy, and results are provided after both 3 and 12 months. REVIEW SUMMARY: Of 405 patients, 51 were in the early and 354 in the late treatment groups. Median age at onset of seizures was 7 years in the early and 4.5 years in the late treatment group. Seizure reduction of 100% was reported in 7.8% (early) and 3.7% (late) patients at 3 months and 11.8% (early) and 4.5% (late) at 12 months (P = 0.033). Reductions in seizure frequency greater than or equal to 90% for early and late treatment groups were similar: 11.8% (early) and 11.0% (late) at 3 months and 23.5% (early) and 17.0% (late) at 12 months. CONCLUSIONS: Patients treated earlier with VNS therapy were twice as likely to report no seizures as patients who had seizures for more than 6 years before they received VNS therapy. The effectiveness of VNS therapy should be assessed among other patients with pharmacoresistant seizures and lesser cumulative seizure loads.

Adolescent↗

PubMed2003

Epilepsy in the elderly.

BACKGROUND: Epilepsy is one of the most common neurologic diseases that affect the elderly population. Underlying etiologies as well as diagnostic and treatment issues vary from that of younger adults and deserve special consideration. REVIEW SUMMARY: The substantially increased risk of seizures and epilepsy in the elderly is associated with medical conditions that affect this group such as stroke, dementia, and metabolic disturbances. In addition, there is an increased incidence and associated mortality of status epilepticus among seniors. Distinguishing epilepsy from paroxysmal nonepileptic events can be a particular challenge. As in the general adult population, EEG and MRI are the cornerstones of diagnostic assessment; however, the clinician must be aware of nonspecific changes associated with aging that do not necessarily indicate an underlying predisposition for epilepsy. Finally, there are unique challenges to the treatment of epilepsy in this population, but fortunately there are multiple treatment options available, including nonpharmacological therapies. CONCLUSIONS: Knowledge of the unique challenges in identifying and treating the elderly patient with epilepsy is important for effective management as well as maximizing quality of life. However, further studies in this area are still needed to establish optimal treatment strategies.

Aged↗

PubMed2002

Vagus nerve stimulation therapy, epilepsy, and device parameters: scientific basis and recommendations for use.

Our understanding of a precise dose-response relationship for vagus nerve stimulation (VNS) therapy in the treatment of seizures is still evolving. Because several parameters are involved in VNS therapy, the individual contribution of each is not well understood. This review discusses the efficacy of stimulation parameters used in the VNS clinical trials. The background, influence on safety and efficacy, and role in helping to achieve seizure control are discussed for each VNS device parameter: output current, pulse duration, frequency, and duty cycle. Finally, we provide an algorithm for the adjustment of VNS device settings (see Appendices).

Electric Stimulation Therapy↗