Coffee and cigarette smoking interactions with lamotrigine.

The objective of this analysis was to determine possible interactions between lamotrigine (LTG) and coffee or cigarette use. As part of the statistical analysis of factors influencing LTG pharmacokinetics (PK) in the Equigen chronic dose study, we collected prospective data from enrolled patients on their use of coffee and cigarettes. Subjects were part of a crossover replication study of generic LTG products with rigorous blood sampling and were instructed to not change their typical consumption of these products for the duration of the study.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

Objective: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin.

Methods: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline.

Qualitative analysis of double inversion recovery MRI in drug-resistant epilepsy.

Purpose: To determine whether Double Inversion Recovery (DIR) on 3T MRI can enhance detection of epileptogenic lesions Methods: 29 adult patients with DRE were enrolled in a prospective pilot study. Brain MRIs were obtained using a specialized protocol that included: (1) Fast-Spin EchoT2, (2) T2 fluid attenuated inversion recovery (FLAIR), and (3) DIR sequences. Two neuroradiologists blinded to clinical information independently reviewed each sequence in the order listed above for T2-hyperintense lesions.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography.

Objective: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.

Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design.

Benign MRI findings and their pathologic mimics.

Otherwise benign MRI findings (so-called "incidentalomas") are a frequent cause of worry on the part of both clinician and patient. Knowledge of the imaging characteristics of incidentalomas, their (typically slight) pathologic significance, and how to distinguish these from less benign pathologic mimics can help avoid unnecessary worry, expense, and workup.

Recent insights into cerebral cavernous malformations: animal models of CCM and the human phenotype.

Cerebral cavernous malformations are common vascular lesions of the central nervous system that predispose to seizures, focal neurologic deficits and potentially fatal hemorrhagic stroke. Human genetic studies have identified three genes associated with the disease and biochemical studies of these proteins have identified interaction partners and possible signaling pathways. A variety of animal models of CCM have been described to help translate the cellular and biochemical insights into a better understanding of disease mechanism.

IGF-1 partially restores chemotherapy-induced reductions in neural cell proliferation in adult C57BL/6 mice.

Chemotherapeutic agents produce persistent difficulties in memory through an unknown mechanism. We tested the hypothesis that chemotherapeutic agents readily able to cross the blood-brain barrier (cyclophosphamide and fluorouracil), as opposed to those not known to readily cross the barrier (paclitaxel and doxorubicin), reduce neural cell proliferation following chemotherapy. We found that 5-bromo-2-deoxyuridine labeling following chemotherapy given to C57BL/6 mice revealed a similar reduction in neural cell proliferation in the dentate gyrus for all four agents.

Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Angioma Alliance Scientific Advisory Board.

Background And Purpose: Cavernous malformations of the brain (CMs) cause intracranial hemorrhage, but its reported frequency varies, partly attributable to study design. To improve the validity of future research, we aimed to develop a robust definition of CM hemorrhage.

Methods: We systematically reviewed the published literature (Ovid Medline and Embase to June 1, 2007) for definitions of CM hemorrhage used in studies of the untreated clinical course of >or=20 participants with CM(s), to inform the development of a consensus statement on the clinical and imaging features of CM hemorrhage at a scientific workshop of the Angioma Alliance.

Generic substitution in the treatment of epilepsy: patient and physician perceptions.

Generic substitution of branded antiepileptic drugs (AEDs) has sparked recent debates. We sought to understand perceptions about generic AED substitution and how these guide prescribing. Surveys were conducted among 550 adult patients with self-reported epilepsy and 606 physicians who treat patients with epilepsy.

Stochastic kinematic modeling and feature extraction for gait analysis.

This research presents a new model-based approach toward the three-dimensional (3-D) tracking and extraction of gait and human motion. We suggest the use of a hierarchical, structural model of the human body that introduces the concept of soft kinematic constraints. These constraints take the form of a priori, stochastic distributions learned from previous configurations of the body exhibited during specific activities; they are used to supplement an existing motion model limited by hard kinematic constraints.

Deletions in CCM2 are a common cause of cerebral cavernous malformations.

Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in a variety of neurological disabilities, including hemorrhagic stroke and seizures. Mutations in the gene KRIT1 are responsible for CCM1, mutations in the gene MGC4607 are responsible for CCM2, and mutations in the gene PDCD10 are responsible for CCM3. DNA sequence analysis of the known CCM genes in a cohort of 63 CCM-affected families showed that a high proportion (40%) of these lacked any identifiable mutation.

Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus.

Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in a variety of neurological disabilities, including stroke and seizures. Linkage analyses using autosomal dominant families manifesting CCMs have identified three different causative loci on chromosomes 7q21.2 (CCM1), 7p13 (CCM2), and 3q25.

Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations.

Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. Mutations in the gene KRIT1 are responsible for type 1 CCM (CCM1). We report that a novel gene, MGC4607, exhibits eight different mutations in nine families with type 2 CCM (CCM2).