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Biomedical subjects

David M Labiner

Publications and source records attributed to David M Labiner.

8 recordsLinked to original sources
PubMed2007

Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings.

Vagus nerve stimulation (VNS) therapy is an effective adjunctive treatment for chronic or recurrent treatment-resistant depression in adults, and for pharmacoresistant epilepsy in adults and adolescents. VNS therapy is administered through an implanted pulse generator that delivers programmed electrical pulses through an implanted lead to the left vagus nerve. Programmable pulse parameters include output current, frequency, pulse width, and ON/OFF times. Within a range of typical values, individual patients respond best to different combinations of parameter settings. The physician must identify the optimum settings for each patient while balancing the goals of maximizing efficacy, minimizing side effects, and preserving battery life. Output current is gradually increased from 0.25 mA to the maximum tolerable level (maximum, 3.5 mA); typical therapeutic settings range from 1.0 to 1.5 mA. Greater output current is associated with increased side effects, including voice alteration, cough, a feeling of throat tightening, and dyspnea. Frequency is typically programmed at 20 Hz in depression and 30 Hz in epilepsy. Pulse width is typically 250 or 500 micros. The recommended initial ON time is 30 s, followed by 5 min OFF; OFF time > ON time is recommended. As with pharmacotherapy, VNS therapy must be adjusted in a gradual, systematic fashion to individualize therapy for each patient.

Depressive Disorder↗
PubMed2006

Correlation of electrocorticographic to clinical seizure onset and interhemispheric propagation times in temporal lobe epilepsy.

This study was performed to test the hypothesis that, in human temporal lobe epilepsy, electrocorticographic time factors involved in the ictal EEG to clinical ictal transition (electrocorticographic to clinical seizure onset time, ECOT) and the interhemispheric propagation of epileptic activity (interhemispheric propagation time, IHPT), which are independently correlated with temporal lobe epileptogenicity and predictive of seizure-free outcome following temporal lobectomy, are correlated with one another in a quantitative fashion. A series of 37 patients with medically intractable temporal lobe seizures was studied with long-term subdural videoelectroencephalographic monitoring. Temporal lobe seizure interhemispheric propagation time (IHPT) was found to be a negative, exponential function of electrocorticographic to clinical seizure onset time (ECOT) (f(x)=8.201x10(-0.016x), r=0.347, d.f.=35, t=2.19, p<0.05, where f(x)=IHPT and x=ECOT). A small increase in ECOT was associated with a substantial decrease in IHPT and vice versa. The results suggest the electrophysiological time factor, ECOT, involved in the transition from ictal EEG seizure onset to clinical seizure onset, may determine the speed of interhemispheric propagation of established epileptic activity. The results suggest the interesting hypothesis that, in human temporal lobe epilepsy and, perhaps, under non-pathological circumstances, the human temporal lobe might possess a "time-labeling" function amenable to quantitative analysis.

Journal Article↗
PubMed2004

Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients.

BACKGROUND: Vagus nerve stimulation (VNS) has shown promising antidepressant effects in treatment-resistant depression, but the mechanisms of action are not known. Cerebrospinal fluid (CSF) studies in epilepsy patients show that VNS alters concentrations of monamines and gamma-aminobutyric acid (GABA), neurotransmitter systems possibly involved in the pathogenesis of depression. METHODS: Twenty-one adults with treatment-resistant, recurrent, or chronic major depression underwent standardized lumbar puncture for collection of 12 mL CSF on three separate but identical procedure days during participation in the VNS D-02 clinical trial. All subjects remained on stable regimens of mood medications. Collections were made at baseline (2 weeks after surgical implantation but before device activation), week 12 (end of the acute-phase study), and week 24. Cerebrospinal fluid concentrations of norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined with high-performance liquid chromatography. Concentrations of GABA were assayed with mass spectrometry. RESULTS: Comparison of sham versus active VNS revealed a significant (mean 21%) VNS-associated increase in CSF HVA. Mean CSF concentrations of NE, 5-HIAA, MHPG, and GABA did not change significantly. Higher baseline HVA/5-HIAA ratio predicted worse clinical outcome. CONCLUSIONS: Although several of the CSF neurochemical effects we observed in this VNS study were similar to those described in the literature for antidepressants and electroconvulsive therapy, the results do not suggest a putative antidepressant mechanism of action for VNS.

Adult↗
PubMed2004

Bilateral hippocampal volume predicts verbal memory function in temporal lobe epilepsy.

The present study used quantitative volume estimates of the hippocampus based on structural magnetic resonance imaging (MRI) to predict memory performance of individuals with epilepsy of temporal lobe origin (TLE). Twenty individuals with TLE completed standardized neuropsychological tests and a quality of life inventory, and participated in a brain MRI protocol designed to obtain high-resolution images of the hippocampus. The combined volume of the left and right hippocampi was found to be the best predictor of objective verbal memory performance. This finding is consistent with the functional adequacy model of hippocampal function. In contrast, the asymmetry between right and left hippocampal volume was the best predictor of subjective ratings of cognitive functioning, which is consistent with the functional reserve model. The collective and complementary functions of the left and right hippocampi merit further exploration in prospective studies of memory function and TLE.

Adult↗
PubMed2002

Prognostic value of concordant seizure focus localizing data in the selection of temporal lobectomy candidates.

This study was performed to test the hypotheses that (a) resection of the temporal lobe epileptic focus, amenable to noninvasive as opposed to invasive localization, is associated with superior seizure outcome and (b) that quadruple (versus lesser degrees of) concordance of seizure focus localizing data predicts superior seizure-free outcome. Eighty-three patients underwent invasive (subdural-EEG) and/or noninvasive (video/scalp-EEG, SPECT, PET, MRI, neuropsychological testing) evaluation. All patients underwent anterior temporal lobectomy and amygdalohippocampectomy (ATL/AH) and seizure outcome was assessed at minimum one-year follow-up. At 34.8 +/- 2.5 months following ATL/AH, outcome was superior for patients in whom the seizure focus was amenable to noninvasive compared to invasive localization (80% versus 40% seizure-free, X2 = 14.03, p < 0.05). Seizure outcome was superior for patients with quadruple, compared to all lesser degrees of, concordance of seizure focus localizing data (85% versus 51% seizure-free, X2 = 7.34, p < 0.05). Post-ATL/AH, seizure outcome is superior in patients (1) harboring an epileptic focus amenable to noninvasive localization and (2) with quadruple concordance of seizure focus localizing data. These findings support the development of temporal lobectomy selection criteria including up to four invasive and/or noninvasive concordant seizure focus localizing techniques.

Adolescent↗
PubMed2002

Neurologic consultation for seizures. When, why, and how to pursue.

Primary care physicians can successfully manage seizure in many patients who respond well to initial antiepileptic drug therapy. However, management of recurrent seizures is often complex and best accomplished by consultation with a neurologist or epilepsy specialist. In this article, Drs Labiner and Ahern discuss the issues involved in evaluation and treatment of seizure and offer a model for working with general neurologists and specialized epilepsy centers.

Algorithms↗
PubMed2002

DP-VPA D-Pharm.

Shire is developing DP-VPA, a prodrug of valproic acid (VPA) licensed from D-Pharm, for the potential treatment of severe forms of epilepsy, including status epilepticus, acute repetitive seizures in children and possibly manic depression and migraine [242649], [385958]; the drug is also being developed for bipolar disorder and migraine prophylaxis [385862]. By March 2000, phase I trials had been completed [359581], [373232] and in October 2000, the compound entered phase II trials for the treatment of epilepsy, bipolar disorder and migraine [385862]; these trials were ongoing in November 2001 [429470]. In October 2001, Shire initiated multicenter, multinational phase II trials of SPD-421 as add-on therapy in the treatment of complex partial seizures [425660]. In February 2002, Shire reported that it planned to make a decision regarding the future of the compound by the second half of 2002 [441819]. DP-VPA is based on D-Pharm's regulation activation of prodrugs (RAP) technology, which designs drugs to be internalized within cells and to be activated only when the tissue becomes diseased. In the case of DP-VPA, the pathological epilepsy process activates it on demand [342433]. RAP-prodrugs are composed of the active drug moiety attached via a chemical linkage to a hydrophobic molecule which allows the agent to penetrate into the cell [182806]. In October 2000, D-Pharrm received patent US-06077837 from the USPTO covering novel 'Prodrugs with enhanced penetration into cells'. This patent claims prodrugs, comprising a pharmacologically active compound covalently linked to an intracellular transporter by a bond which is preferentially cleaved by disease-associated supranormal enzyme activity [385507]. In April 2000, Lehman Brothers predicted the launch of DP-VPA during 2003 [365103]. In December 2001, Lehman Brothers suggested that the product would be approved in 2004. The analysts estimated a 25% probability of the drug reaching the market, and envisaged peak sales of $200 million [434768]. Analysts at Schroder Salomon Smith Barney predicted in March 2002, that sales for Shire of DP-VPA would reach US $9.5 million in 2005, rising to US $31 million in 2006 [449087].

Animals↗