Electromyography-based seizure detector: Preliminary results comparing a generalized tonic-clonic seizure detection algorithm to video-EEG recordings.

OBJECTIVE: Automatic detection of generalized tonic-clonic seizures (GTCS) will facilitate patient monitoring and early intervention to prevent comorbidities, recurrent seizures, or death. Brain Sentinel (San Antonio, Texas, USA) developed a seizure-detection algorithm evaluating surface electromyography (sEMG) signals during GTCS. This study aims to validate the seizure-detection algorithm using inpatient video-electroencephalography (EEG) monitoring. METHODS: sEMG was recorded unilaterally from the biceps/triceps muscles in 33 patients (17white/16 male) with a mean age of 40 (range 14-64) years who were admitted for video-EEG monitoring. Maximum voluntary biceps contraction was measured in each patient to set up the baseline physiologic muscle threshold. The raw EMG signal was recorded using conventional amplifiers, sampling at 1,024 Hz and filtered with a 60 Hz noise detection algorithm before it was processed with three band-pass filters at pass frequencies of 3-40, 130-240, and 300-400 Hz. A seizure-detection algorithm utilizing Hotelling's T-squared power analysis of compound muscle action potentials was used to identify GTCS and correlated with video-EEG recordings. RESULTS: In 1,399 h of continuous recording, there were 196 epileptic seizures (21 GTCS, 96 myoclonic, 28 tonic, 12 absence, and 42 focal seizures with or without loss of awareness) and 4 nonepileptic spells. During retrospective, offline evaluation of sEMG from the biceps alone, the algorithm detected 20 GTCS (95%) in 11 patients, averaging within 20 s of electroclinical onset of generalized tonic activity, as identified by video-EEG monitoring. Only one false-positive detection occurred during the postictal period following a GTCS, but false alarms were not triggered by other seizure types or spells. SIGNIFICANCE: Brain Sentinel's seizure detection algorithm demonstrated excellent sensitivity and specificity for identifying GTCS recorded in an epilepsy monitoring unit. Further studies are needed in larger patient groups, including children, especially in the outpatient setting.

A mutation in the pericentrin gene causes abnormal interneuron migration to the olfactory bulb in mice.

Precise control of neuronal migration is essential for proper function of the brain. Taking a forward genetic screen, we isolated a mutant mouse with defects in interneuron migration. By genetic mapping, we identified a frame shift mutation in the pericentrin (Pcnt) gene. The Pcnt gene encodes a large centrosomal coiled-coil protein that has been implicated in schizophrenia. Recently, frame shift and premature termination mutations in the pericentrin (PCNT) gene were identified in individuals with Seckel syndrome and microcephalic osteodysplastic primordial dwarfism (MOPD II), both of which are characterized by greatly reduced body and brain sizes. The mouse Pcnt mutant shares features with the human syndromes in its overall growth retardation and reduced brain size. We found that dorsal lateral ganglionic eminence (dLGE)-derived olfactory bulb interneurons are severely affected and distributed abnormally in the rostral forebrain in the mutant. Furthermore, mutant interneurons exhibit abnormal migration behavior and RNA interference knockdown of Pcnt impairs cell migration along the rostal migratory stream (RMS) into the olfactory bulb. These findings indicate that pericentrin is required for proper migration of olfactory bulb interneurons and provide a developmental basis for association of pericentrin function with interneuron defects in human schizophrenia.

Absence status induced by lacosamide adjunctive therapy.

Since lacosamide was approved as an adjuvant agent for the treatment of medically refractory focal epilepsy over ten years ago, it is becoming more widely used for the treatment of idiopathic (genetic) generalized epilepsies. Several studies have demonstrated efficacy in reducing primary generalized tonic-clonic seizures (GTCS), but efficacy is less well-characterized for myoclonic and absence seizures. A 29-year-old man with juvenile myoclonic epilepsy and medically refractory GTCS on a combination of levetiracetam and topiramate was started on lacosamide adjunctive therapy with the plan to replace topiramate. While his GTCS became controlled, he was witnessed to have confusional episodes, with waxing and waning responsiveness, lasting a few days, several times a month. After eight months of adjunctive lacosamide therapy, he was admitted to the epilepsy monitoring unit, where paroxysms of generalized spike-and-wave complexes, lasting for 30-90 minutes, were recorded, interrupted only by sleep. During these periods, he demonstrated psychomotor slowing and disorientation on examination. The absence status was successfully broken by lorazepam, and lacosamide was discontinued. The patient had no further confusional episodes at the most recent follow-up visit, four months after discharge.

Cortical inhibition modified by embryonic neural precursors grafted into the postnatal brain.

Embryonic medial ganglionic eminence (MGE) cells transplanted into the adult brain can disperse, migrate, and differentiate to neurons expressing GABA, the primary inhibitory neurotransmitter. It has been hypothesized that grafted MGE precursors could have important therapeutic applications increasing local inhibition, but there is no evidence that MGE cells can modify neural circuits when grafted into the postnatal brain. Here we demonstrate that MGE cells grafted into one location of the neonatal rodent brain migrate widely into cortex. Grafted MGE-derived cells differentiate into mature cortical interneurons; the majority of these new interneurons express GABA. Based on their morphology and expression of somatostatin, neuropeptide Y, parvalbumin, or calretinin, we infer that graft-derived cells integrate into local circuits and function as GABA-producing inhibitory cells. Whole-cell current-clamp recordings obtained from MGE-derived cells indicate firing properties typical of mature interneurons. Moreover, patch-clamp recordings of IPSCs on pyramidal neurons in the host brain, 30 and 60 d after transplantation, indicated a significant increase in GABA-mediated synaptic inhibition in regions containing transplanted MGE cells. In contrast, synaptic excitation is not altered in the host brain. Grafted MGE cells, therefore, can be used to modify neural circuits and selectively increase local inhibition. These findings could have important implications for reparative cell therapies for brain disorders.

Magnetoencephalography source localization and surgical outcome in temporal lobe epilepsy.

OBJECTIVE: We prospectively investigated the role of magnetoencephalography (MEG) in localizing the seizure focus and in predicting outcome to surgical resections for intractable temporal lobe epilepsy (TLE). METHODS: We performed simultaneous interictal EEG and MEG recording (two 37-channel system) in 26 TLE patients followed by MEG source localization. We correlated early modeling dipoles with intracranial EEG, temporal surgical resection and surgical outcome. RESULTS: There were 12 patients who had anterior temporal horizontal or tangential dipoles to the anterior infero-lateral temporal tip cortex. Two patients underwent selective amygdalo-hippocampectomy (SAH) and nine patients had antero-medial temporal lobectomy (AMTL). All patients had successful outcome except for one patient who initially failed SAH, but became seizure-free after AMTL. There were 11 patients who demonstrated anterior temporal vertical or tangential oblique dipoles. Five patients had AMTL and three had SAH; all became seizure free. Five of above 23 patients had invasive EEG and demonstrated mesial seizure onset. Three TLE patients had lateral vertical dipoles that were concordant with intracranial EEG and these became seizure free after temporal neocortical resections. CONCLUSIONS: MEG source analysis produces distinct source patterns that provide useful localizing information, predict surgical outcome, and may aid in planning limited surgical resection in TLE.

Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons.

Although potentiation of the inhibitory glycine receptor (GlyR) may contribute to the mechanism of action of antiepileptic drugs (AEDs), the effects of AEDs on GlyRs have not been investigated in detail in forebrain neurons. We examined the effects of seven clinically important AEDs on GlyR-mediated currents using whole-cell patch clamp recordings from cultured embryonic mouse hippocampal neurons. At high therapeutic concentrations, topiramate (in 24% of neurons) and pentobarbital reversibly decreased glycine currents to 89+/-6 % and 81+/-7 % of control, respectively. At or below therapeutic concentrations, carbamazepine, felbamate, gabapentin, phenytoin, and valproate had no effect on glycine currents, while at supratherapeutic concentrations these agents produced modest reversible inhibition. We conclude that GlyR potentiation does not contribute to the antiepileptic action of the seven AEDs examined.

Focal cooling suppresses spontaneous epileptiform activity without changing the cortical motor threshold.

PURPOSE: Focal cerebral cooling has been shown to reduce epileptiform activity in animals. There are, however, few reports of this phenomenon in humans. METHODS: Electrocorticography was performed before resection of a right frontal tumor in a patient with partial seizures. Cold saline was applied to the interictal spike focus, and its effect on the epileptiform discharges was observed. RESULTS: Application of cold saline to the spike focus resulted in a transient, complete cessation of spiking. This effect was reproduced with a second application of cold saline. The motor threshold for electrical stimulation remained unchanged during the application of saline. CONCLUSIONS: In this patient with tumor-related epilepsy, focal cooling of the cortex reproducibly abolished interictal epileptiform discharges without changing the motor threshold to electrical stimulation.

Ictal magnetoencephalography in temporal and extratemporal lobe epilepsy.

PURPOSE: We evaluated visual patterns and source localization of ictal magnetoencephalography (MEG) in patients with intractable temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETE). METHODS: We performed spike and seizure recording simultaneously with EEG and MEG on two patients with TLE and five patients with ETE. Scalp EEG was recorded from 21 channels (10-20 international system), whereas MEG was recorded from two 37-channel sensors. We compared ictal EEG and MEG onset, frequency, and evolution and performed MEG dipole source localization of interictal spikes and early ictal discharges and co-registered dipoles to brain magnetic resonance imaging (MRI). We correlated dipole characteristics with intracranial EEG, surgical resection, and outcome. RESULTS: Ictal MEG lateralized seizure onset in both TLE patients and demonstrated ictal onset, frequency, and evolution in accordance with EEG. Ictal MEG source analysis revealed tangential vertical dipoles in the anterolateral angle in one patient, and anterior dipoles with anteroposterior orientation in the other. Intracranial EEG revealed regional entorhinal seizure onset in the first patient. Both patients became seizure free after temporal lobectomy. In ETE, ictal MEG demonstrated visual patterns similar to ictal EEG and had concordant localization with interictal MEG in all five patients. Two patients underwent surgery. Ictal MEG localization was concordant with intracranial EEG in both cases. One patient had successful outcome after surgery. The second patient did not improve after limited resection and multiple subpial transections. CONCLUSIONS: Ictal MEG can demonstrate ictal onset frequency and evolution and provide useful localizing information before epilepsy surgery.