Electroencephalographic and Electrocardiographic Effect of Intravenous Lacosamide in Refractory Focal Epilepsy.

PURPOSE: Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels to achieve seizure reduction. We studied the effect of intravenous lacosamide given as one of three single doses on EEG and electrocardiogram, as well as its tolerability in patients with drug-resistant epilepsy. METHODS: This Canadian, investigator-initiated, multicenter, double-blind study recruited patients with refractory focal epilepsy admitted to a seizure monitoring unit. Participants received a loading dose of 100, 200, or 400 mg lacosamide over 30 minutes during continuous monitoring by video-EEG and 12-lead electrocardiogram. The number of interictal spikes, frequency and quantity of background EEG rhythms, corrected QT interval (QTc), PR interval, heart rate (HR), blood pressure, and respiration rate during 60 minutes before the administration were compared with 60 minutes after the infusion. We documented any adverse event during and after the infusion. RESULTS: Seventy-one patients completed the study. There was a significant decrease in interictal spikes (P = 0.039) and decreased frequency of the alpha rhythm (P = 0.003). No significant difference in beta, theta, and delta frequency or amount was noted. There were significant increases in PR interval (153.4-155.8 ms, P = 0.031) and HR (73.4-75.5 bpm, P = 0.022), but QTc, blood pressure, and respiration rate were not affected. Twelve patients (16.9%) experienced transient and mild adverse events, mainly dizziness and leg tingling. More adverse events occurred with 400 mg lacosamide than with the lower doses (P = 0.048). CONCLUSIONS: Intravenous lacosamide is effective in decreasing interictal spikes. Despite a small effect on EEG and electrocardiogram rhythms, it is well tolerated with no serious adverse events.

Epileptogenic Source Imaging Using Cross-Frequency Coupled Signals From Scalp EEG.

OBJECTIVE: The epileptogenic zone (EZ) is a brain region containing the sources of seizure genesis. Removal of the EZ is associated with cessation of seizures after resective surgical procedures, as measured by Engel Class I score. This study describes a novel EEG (electroencephalography) source imaging (ESI) method which uses cross-frequency coupled potential signals (SCFC) derived from scalp EEG. METHODS: Scalp EEG were recorded from ten patients (20 seizures) suffering from epilepsy. The S CFC were constructed from the phase and amplitude of the lower and higher frequency rhythms at electrographic seizure onset. ESI was then performed using the SCFC. Validation of the technique was facilitated by forward and inverse computer modeling of known cortical sources, and the correspondence of the ESI with EZ in resected regions of patients. RESULTS: For ten seizures sampled at or above 500 Hz from four patients, all estimated sources lay within the resected region, emphasizing the clinical importance of higher sampling rates. The SCFC demonstrated significant advantages over the "raw" scalp EEG, indicating its robust noise performance. Modeling investigations indicated that a signal-to-noise ratio above 0.2 was sufficient to achieve successful localization regarding EMG artifacts. CONCLUSION: The association of the estimated sources to the EZ suggests that cross-frequency coupling is a feature of the brain's neural networks, not of artifactual activity. The SCFC can effectively extract brain signals from a noisy background. SIGNIFICANCE: We propose this approach to enhance the placement of intracranial electrode for surgical intervention.

Hepatotoxicidad inducida por paroxetina / Hepatotoxicity due to paroxetine

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