Muybridge, Dercum, and the Early Use of Photography in the Study of Psychogenic Non-Epileptic Seizures.

The impact of the collaboration between photographer Eadweard Muybridge and neurologist Francis Dercum is detailed within the context of a photographic study of an artificially induced psychogenic non-epileptic seizure. Their contribution served as inspiration to other contemporary European neurologists and photographers to use motion photography to further understand psychogenic neurological disorders, such as seizures.

Portrait of My Father: Frida Kahlo's Intimate Relation to Epilepsy.

The painting Portrait of My Father (1951) by the Mexican painter, Frida Kahlo, is discussed by the author within the context of epilepsy and biographical events in the lives of both Frida and her father, the German Mexican photographer Guillermo Kahlo. The biographical accounts of the photographer's seizures are suggestive of juvenile absence epilepsy but cannot discount the possibility of posttraumatic epilepsy of mesial frontal origin.

Francisco de Goya and the Seizing Impenitent.

The painting, St. Francis and the Dying Impenitent (1788) by the Spanish Baroque painter, Francisco Goya, is discussed by the author within the context of epilepsy and biographical events in the lives of both the saint and the painter.

Dosing feasibility and tolerability of intranasal diazepam in adults with epilepsy.

OBJECTIVE: To determine the feasibility of administering a diazepam nasal spray formulation (diazepam-NS) to adults with epilepsy during a generalized tonic-clonic seizure or in the postictal period following a tonic-clonic or other seizure type, to assess pharmacokinetics and to assess tolerability. METHODS: An open-label study was conducted in patients admitted to the epilepsy monitoring unit. Eligible patients received a single dose of diazepam-NS approximating 0.2 mg/kg. Plasma diazepam concentrations were measured serially up to 12 h postdose, and maximum observed plasma concentration (Cmax ); time to maximum concentration (Tmax ); and the area under the plasma concentration-time curve for time zero to last sampling time (AUC0-12 ) were estimated and dose-normalized. Pharmacodynamic assessments included Kaplan-Meier analysis to determine the time-to-next seizure. Safety and tolerability were assessed. RESULTS: Of the 78 patients who consented, 30 had treatment and pharmacokinetic data. Ten patients were treated during a convulsive tonic-clonic seizure, seven within 5 min following the last clonic jerk, and 13 in the postictal period ≥ 5 min after a tonic-clonic or following other seizure-types. Diazepam median Tmax was 45 min. Dose-normalized mean Cmax and AUC0-12 values of diazepam were comparable among patients regardless of the timing of diazepam-NS administration in relation to seizure. Of those treated, 65% were seizure-free during the 12-h observation period and 35% had post-dose seizures. Treatment was well tolerated, with no unexpected safety findings: 74% had mild and 25% had moderate adverse events. Nasopharyngeal signs were resolved by 12 h postdose. SIGNIFICANCE: Diazepam can be delivered in effective therapeutic concentrations by a nasal spray device during the convulsive phase of tonic-clonic seizures or in the postictal periods following tonic-clonic or other seizure types.

The history of motion photography to video electroencephalography in the study of functional seizures and related seizure disorders: The first 100 years.

This historical note highlights pivotal events of technology progressing between the late 19th and the 20th century to capture functional seizures and other related seizure episodes. From Charcot's initial use of photography for his study of hysteria at the Salpêtrière to the development of cinematography by Muybridge and Marey to study motion to the initial use of video electroencephalography (vEEG) through a pairing of cinematography with EEG, and the advent of EEG telemetry to eventually the development of modern epilepsy monitoring unit through the adoption of cameras and an improved long-term monitoring vEEG system.

Late-onset, praxis-induced myoclonic epilepsy.

Praxis-induction of seizures is an interesting subset of reflex epilepsy in which seizures are induced by higher mental activities associated with the use of part of the body. Reflex traits have often been described in patients with juvenile myoclonic epilepsy. We report a patient presenting with praxis-induced myoclonic epilepsy at a late age. Ictal myoclonus was triggered by building a bird house and captured by video-polygraphic EEG recording. At 39 years old, the patient's age at onset of epilepsy was consistent with the syndrome of adult myoclonic epilepsy. Our case supports the notion of adult myoclonic epilepsy with possible occurrence of praxis-activation of seizures, as has been noted with the other idiopathic generalised epilepsies. [Published with videosequences].

Effects of Dalfampridine Extended-release Tablets on 6-minute Walk Distance in Patients With Multiple Sclerosis: A Post Hoc Analysis of a Double-blind, Placebo-controlled Trial.

PURPOSE: Dalfampridine extended-release (ER) tablets 10 mg BID have been approved for use in improving walking in people with multiple sclerosis (MS). This subgroup analysis evaluated the effects of dalfampridine ER 5 and 10 mg BID on distance walked, as assessed using the 6-minute walk (6MW) test. METHODS: This analysis of data from a randomized, placebo-controlled, double-blind study (N = 430) included only the 153 patients with 6MW data available. Participants (aged 18-70 years) were randomly assigned in a 1:1:1 ratio to receive dalfampridine ER 5 or 10 mg or placebo, BID for 4 weeks. The 6MW was used for assessing walking distance at baseline and 2 weeks after the start of treatment at the 26 study sites that were able to perform this test. Participants were administered the 12-item MS Walking Scale (MSWS-12), a patient-reported measure of the impact of MS on walking. Post hoc outcomes included the percentages of patients who achieved an increase from baseline in 6MW distance of ≥20% and who achieved a minimal clinically important difference (MCID) from baseline in 6MW distance, defined as ≥+55 m. Changes from baseline in walking speed (MSWS-12) were compared, stratified by subgroup that achieved ≥20% versus <20% improvement on the 6MW. The correlation between change in walking speed over time and subgroup (by change in distance walked) was evaluated. The tolerability of dalfampridine was assessed based on the prevalence of treatment-emergent adverse events (TEAEs). FINDINGS: In the post hoc analysis, the percentage of patients with an improvement in 6MW distance that met or exceeded the MCID was significantly greater with dalfampridine ER 10 mg BID relative to placebo (37.3% vs 12.2%; nominal P = 0.004). Similarly, the percentage with an improvement in 6MW distance of ≥20% was significantly greater with dalfampridine 10 mg BID relative to placebo (45.1% vs 14.3%; nominal P < 0.001). Regardless of treatment allocation, improvement in MSWS-12 was significantly greater in the subgroup that achieved a ≥20% improvement on the 6MW compared with the subgroup with <20% improvement (mean changes, -15.5 vs -7.2; nominal P = 0.041). The prevalences and types of TEAEs were consistent with those reported in previous studies. IMPLICATIONS: Based on the MCID for 6MW, the use of dalfampridine ER 10 mg BID but not 5 mg BID was associated with statistically significant and clinically meaningful improvements in walking relative to placebo. The correlation between improvement on MSWS-12 and the 20% increase in 6MW distance suggests that an improvement on MSWS-12 is clinically relevant. These results, although highlighting a lack of efficacy of dalfampridine ER 5 mg BID, suggest that the 10-mg BID dose is effective for improving walking speed, as observed on short timed-walk tests, and for increasing distance walked over longer timed-walk periods. ClinicalTrials.gov identifier: NCT01328379.

Evaluation of Dalfampridine Extended Release 5 and 10 mg in Multiple Sclerosis: A Randomized Controlled Trial.

BACKGROUND: Dalfampridine extended-release (ER) tablets, 10 mg twice daily, have been shown to improve walking in people with multiple sclerosis. We evaluated the safety and efficacy of dalfampridine-ER 5 mg compared with 10 mg. METHODS: Patients were randomized to double-blind treatment with twice-daily dalfampridine-ER tablets, 5 mg (n = 144) or 10 mg (n = 143), or placebo (n = 143) for 4 weeks. Primary efficacy endpoint was change from baseline walking speed by the Timed 25-Foot Walk 3 to 4 hours after the last dose. At 40% of sites, 2-week change from baseline walking distance was measured by the 6-Minute Walk test. RESULTS: At 4 weeks, walking speed changes from baseline were 0.363, 0.423, and 0.478 ft/s (placebo, dalfampridine-ER 5 mg, and dalfampridine-ER 10 mg, respectively [P = NS]). Post hoc analysis of average changes between pretreatment and on-treatment showed that relative to placebo, only dalfampridine-ER 10 mg demonstrated a significant increase in walking speed (mean ± SE): 0.443 ± 0.042 ft/s versus 0.303 ± 0.038 ft/s (P = .014). Improvement in 6-Minute Walk distance was significantly greater with dalfampridine-ER 10 mg (128.6 ft, P = .014) but not with 5 mg (76.8 ft, P = .308) relative to placebo (41.7 ft). Adverse events were consistent with previous studies. No seizures were reported. CONCLUSIONS: Dalfampridine-ER 5 and 10 mg twice daily did not demonstrate efficacy on the planned endpoint. Post hoc analyses demonstrated significant increases in walking speed relative to placebo with dalfampridine-ER 10 mg. No new safety signals were observed.

Efficacy of oxcarbazepine in the treatment of painful diabetic neuropathy.

OBJECTIVES: To evaluate the safety, tolerability, and efficacy of oxcarbazepine in the treatment of painful diabetic neuropathy. METHODS: This was an open-label, 9-week trial, consisting of a 1-week prospective Screening Phase followed by an 8-week Treatment Phase. Treatment with oxcarbazepine was initiated at 150 mg/day, and the daily dose was doubled on a weekly basis and titrated to tolerability over 4 weeks, up to 1200 mg/day. This was followed by a 4-week fixed-dose Maintenance Phase, during which patients were maintained on oxcarbazepine at 1200 mg/day or highest tolerated dose. The primary efficacy variable was the change in the weekly pain rating assessed on the Visual Analog Scale (VAS) of the short-form McGill Pain Questionnaire between the Screening Phase and the Treatment Phase. All analyses were performed on the intent-to-treat population. RESULTS: Thirty patients were enrolled in the trial. The mean daily oxcarbazepine dose during the Maintenance Phase was 814 mg. The mean VAS score dropped from 66.3 during the Screening Phase to 34.3 at the end of the trial (P = 0.0001), for a mean reduction of 48.3%. In addition, there were significant improvements in the total pain score and present pain intensity. Oxcarbazepine was well tolerated, with the most common adverse events consisting of drowsiness and dizziness. DISCUSSION: The results suggest that oxcarbazepine administered as monotherapy is an efficacious and safe option for the symptomatic treatment of pain associated with symmetrical diabetic neuropathy. These results will need to be confirmed in large, double-blind, placebo-controlled, randomized clinical trials.

Mild cognitive impairment: new neuropsychological and pharmacological target.

Mild cognitive impairment (MCI) is increasingly being conceptualized in the literature as a cognitive disturbance representing a transitional phase between normal aging and dementia. The operational definitions of MCI provide an opportunity for neuropsychologists to detect subtle deficit and monitor cognitive status sequentially in order to determine rate and degree of progression. More importantly, clinical and neuropsychological studies are needed that can better characterize which MCI patients are at greatest risk for conversion to dementia. Preliminary data has also designated MCI as a potential indicator for initiation of pharmacotherapy, with the objective of decelerating rate of progression to dementia. Current criteria and clinical issues related to MCI are discussed, with the objective of better familiarizing clinicians with this syndrome and fostering ongoing investigations.

Assessment of pharmacokinetics and tolerability of intranasal diazepam relative to rectal gel in healthy adults.

Diazepam rectal gel (RG) is currently the only approved rescue therapy for outpatient management of seizure clusters in the United States. There is an unmet medical need for an alternative rescue therapy for seizure clusters that is effective, and more convenient to administer with a socially acceptable method of delivery. An intranasal diazepam formulation has been developed, and this study evaluates the tolerability and bioavailability of diazepam nasal spray (NS) relative to an equivalent dose of diazepam-RG in healthy adults. Twenty-four healthy adults were enrolled in a phase 1, open-label, 3-period crossover study. Plasma diazepam and metabolite concentrations were measured by serial sampling. Dose proportionality for 5- and 20-mg intranasal doses and the bioavailability of 20mg diazepam-NS relative to 20mg diazepam-RG were assessed by maximum plasma concentration (Cmax) and systemic exposure parameters (AUC0-∞ and AUC0-24). The mean Cmax values for 20mg diazepam-NS and 20mg diazepam-RG were 378 ± 106 and 328 ± 152 ng/mL, achieved at 1.0 and 1.5h, respectively. Subjects administered intranasal and rectal gel formulations experienced nasal and rectal leakage, respectively. Diazepam absorption following intranasal administration was consistent but 3 subjects with diazepam-RG had low plasma drug levels at the earliest assessment of 5 min, due to poor retention, and were excluded from analysis. Excluding them, the treatment ratios (20mg diazepam-NS:20mg diazepam-RG) and 90% confidence intervals for diazepam Cmax and AUC0-24 were 0.98 (0.85-1.14) and 0.89 (0.80-0.98), respectively, suggesting that the bioavailability was comparable between the two formulations. Dose proportionality was observed between the lowest and highest dose-strengths of intranasal formulation. Both intranasal and rectal treatments were well tolerated with mild to moderate adverse events. Results suggest that a single-dose of 20mg diazepam-NS is tolerable and comparable in bioavailability to that of diazepam-RG. The intranasal formulation may provide caregivers and patients with a more socially acceptable and convenient alternative rescue therapy in the acute treatment of seizure clusters.

Nocturnal frontal lobe epilepsy presenting as excessive daytime sleepiness.

Excessive daytime sleepiness (EDS) is common in the general population. Etiologies include insufficient sleep and primary sleep disorders. Due to its high prevalence, physicians often overlook EDS as a significant problem. However, EDS may also be the presenting symptom of seizures, in particular Nocturnal Frontal Lobe Epilepsy (NFLE). Due to the clinical similarity between the nocturnal behaviors of NFLE and parasomnias, and poor patient-related history, NFLE remains a challenging diagnosis. We report the case of a patient with NFLE who presented with a primary complaint of EDS, and discuss the differential diagnosis and evaluation of patients with EDS associated with nocturnal behaviors. In the context of a patient presenting with EDS and stereotyped nocturnal events, clinical suspicion should be high for NFLE.

The Landau-Kleffner Syndrome.

Landau-Kleffner syndrome (LKS), or acquired epileptiform aphasia, is an epilepsy syndrome involving progressive neuropsychological impairment related to the appearance of paroxysmal electroencephalograph (EEG) activity. LKS appears to share a common pathophysiologic mechanism with continuous spike-wave of sleep (CSWS), acquired epileptic opercular syndrome (AEOS), and even benign childhood epilepsy with centrotemporal spikes (BECTS), with differentiating factors including age of onset, area of primary epileptogenicity, and severity of clinical presentation. This article covers the clinical, diagnostic, therapeutic, and prognostic features of LKS. In a child with autistic spectrum disorder, the presence of a fluctuating clinical course or regression should raise suspicion for the presence of associated epilepsy.

Estudio abierto, multicéntrico de gabapentina para el tratamiento preventivo de migraña / Open, multicentric study of gabapentin as preventive treatment for migraine

El objetivo de este estudio fue describir la respuesta de gabapentina como tratamiento profiláctico para migraña en varios centros de Latinoamérica y Miami. Se estudió un total de 101 pacientes con migraña, que recibieron gabapentina a diferentes dosis, iniciando con 300 mg/día hasta reducción de la frecuencia de migraña o hasta dosis tolerable. Despúes de un mes de tratamiento con dosis de mantenimiento, se determinó la respuesta de cada paciente de acuerdo a la reducción de la frecuencia de las crisis de la migraña (excelente: >75 por ciento, buena: 50-75 por ciento, regular: 25-50 por ciento y pobre: 25 por ciento). La mayoría de los pacientes (84 por ciento) tuvo una respuesta excelente (53 por ciento) o buena (32 por ciento). En estos pacientes, la mayoría recibió una dosis de 600 mg/día. Cincuenta y cinco por ciento de los pacientes no describieron eventos adversos. Los eventos adversos más frecuentes fueron somnolencia y fatiga. Aproximadamente la mitad de estos eventos fueron leves y sólo 9 pacientes (8.9 por ciento) los describieron como severos. Se puede concluir que la gabapentina puede ser útil en el tratamiento preventivo de la migraña, y se amerita un futuro estudio para demostrar la eficacia y seguridad de gabapentina a dosis bajas (600 mg/día) y dosis altas, contra placebo. Palabras claves: gabapentina, migraña, profilaxis de migraña, tratamiento.

Gabapentina / Gabapentin

Discute aspectos relevantes à compreensão dos mecanismos por meio dos quais os anticonvulsivantes de segunda geração podem atuar no controle da dor de origem neurópatica.(AU)

Gabapentina / Gabapentin

Discute aspectos relevantes à compreensão dos mecanismos por meio dos quais os anticonvulsivantes de segunda geração podem atuar no controle da dor de origem neurópatica.