Markers of bone and lipid metabolism with eslicarbazepine acetate monotherapy.

OBJECTIVE: To evaluate the impact of eslicarbazepine acetate (ESL) monotherapy on markers of bone and lipid metabolism. METHODS: We conducted a post-hoc analysis of data pooled from two Phase III, dose-blind, conversion-to-ESL (1600 mg and 1200 mg) monotherapy studies in patients with focal seizures. Laboratory measurements included lipids (total cholesterol [TC]; high-density lipoprotein cholesterol [HDL-C]; low-density lipoprotein cholesterol; and triglycerides) and markers of bone metabolism (alkaline phosphatase; 25-hydroxyvitamin D; osteocalcin; and parathyroid hormone [PTH]); measurements were taken at baseline, Week 18, and Month 12, and analyzed according to enzyme-inducing antiepileptic drugs (EIAEDs) use at baseline (+EIAED and -EIAED subgroups). RESULTS: Data from 337 treatment-compliant patients were used for the Week 18 analyses (+EIAED subgroup, n = 119; -EIAED subgroup, n = 218); data from 161 treatment-compliant patients were used for the Month 12 analyses (+EIAED subgroup, n = 53; -EIAED subgroup, n = 108). At baseline, alkaline phosphatase and PTH concentrations were higher in the + EIAED versus -EIAED subgroup. Changes from baseline in markers of bone turnover were generally insignificant, except for some elevation in alkaline phosphatase in the -EIAED subgroup (18 weeks and 12 months) and osteocalcin in both subgroups (18 weeks only). Regarding lipids, TC and HDL-C concentrations were higher in the + EIAED versus -EIAED subgroup at baseline. Concentrations of markers of lipid metabolism fell in the + EIAED group and rose in the -EIAED group, reaching very similar values that were intermediate between the -EIAED and + EIAED baseline values. CONCLUSIONS: Based on this retrospective analysis, ESL seems to have had only a modest and primarily clinically insignificant impact on plasma lipids. More prospective data are needed to definitively ascertain the effects of ESL on bone metabolism.

Magnetoencephalographic Infraslow Activity: A Feasibility Study.

PURPOSE: To explore if background infraslow activity (ISA) can be retrieved from archived magnetoencephalographic (MEG) recordings and its potential clinical relevance. METHODS: Archived recordings of 15 patients with epilepsy and 10 normal subjects were evaluated for MEG/EEG delta (0.5-3 Hz) and ISA (0.01-0.1 Hz). The data were obtained on a Neuromag/Elekta system with 204 planar gradiometers and 102 magnetometer sensors and also 60 EEG channels. To remove artifacts, all MEG files were temporal signal space separation filtered. The data were then analyzed with the BESA Research software. RESULTS: Infraslow activity was present in all files for MEG and EEG. Good concordance between EEG and MEG ISA was seen with delta for laterality and with clinical features. Delta frequencies were always less than 2 Hz. During sleep, an inverse relationship between delta and ISA occurred. With increasing depth of sleep, delta activity increased while ISA decreased and vice versa. Intermittent higher amplitude transients, arising from background, were also seen but their nature is at present unknown. Clinically relevant ictal onset baseline shifts were likewise observed. CONCLUSION: Infraslow activity is a normal segment of the cerebral electromagnetic frequency spectrum. It follows physiologic rules and can be related to areas of pathology. This is in accord with previously published EEG observations and further studies of this segment of the electromagnetic frequency spectrum for its origin and changes in health and disease are indicated.

Peri-ictal and interictal, intracranial infraslow activity.

It is widely assumed that the recording of EEG infraslow activity (ISA) requires direct current amplifiers. Yet, it has been shown during the past decade that conventional EEG systems can record activity between 0.01 and 0.1 Hz and that this frequency band contains additional information, especially in regard to seizure onset. To delineate the characteristics of background ISA, 24-hour scalp and intracranial recordings obtained from 5 patients during long-term monitoring were investigated. Scalp recordings had been sampled but intracranial tracings were continuous over periods of up to 3 days. Although scalp recordings were subject to artifact, intermittent genuine ISA increase could occur episodically in the interictal state not only distant from the ictal onset zone but also in the contralateral hemisphere. Intracranial recordings were limited, in this study, to portions of one hemisphere but likewise revealed that distant areas could show ISA increase lasting minutes or hours. This was at times not detectable when only the conventional frequency band was viewed. It is concluded that ISA information is contained in the clinical setting of intensive video-monitoring studies for the detection of the epileptogenic zone and can provide additional information above and beyond what is seen in the conventional frequencies.

Neurophysiological investigation of idiopathic acquired auditory-visual synesthesia.

We present a case of acquired auditory-visual synesthesia and its neurophysiological investigation in a healthy 42-year-old woman. She started experiencing persistent positive and intermittent negative visual phenomena at age 37 followed by auditory-visual synesthesia. Her neurophysiological investigation included video-EEG, fMRI, and MEG. Auditory stimuli (700 Hz, 50 ms duration, 0.5 s ISI) were presented binaurally at 60 db above the hearing threshold in a dark room. The patient had bilateral symmetrical auditory-evoked neuromagnetic responses followed by an occipital-evoked field 16.3 ms later. The activation of occipital cortex following auditory stimuli may represent recruitment of existing cross-modal sensory pathways.

Seizure onset determination.

Digital electroencephalography has greatly expanded the opportunities for data analysis. Although commercial software packages are available they seem not to be used as widely in the preoperative work-up of epilepsy patients as might be warranted. This review will demonstrate that seizure onset can be better defined by judicious use of post hoc filter settings, expanded electrode coverage, and special electrode montages. In scalp recordings, ictal baseline shifts and infraslow activity (ISA) can be evaluated with conventional EEG systems by opening the high-pass filter to 0.01 Hz; in intracranial recordings high-frequency activity (>60 Hz; HFA) can be observed in addition. Inasmuch as ISA and HFA have considerably smaller electrical fields than the conventional frequencies they may better define seizure onset than might be possible otherwise. It is recommended that to determine the clinical value of ISA and HFA for epilepsy surgery, retrospective analyses of seizure data, which include assessment of ISA and HFA, be performed from patients who have undergone surgical resections of epileptogenic tissue. These may yield information as to whether or not the epileptogenic areas of ISA and HFA had been included in the resected tissue and their relationship to surgical outcome can then be determined.

Magnetoencephalographically directed review of high-spatial-resolution surface-coil MR images improves lesion detection in patients with extratemporal epilepsy.

PURPOSE: To determine whether (a) interictal magnetoencephalographic (MEG) epileptiform activity corresponds to anatomic abnormalities at magnetic resonance (MR) imaging, (b) high-spatial-resolution MR imaging depicts lesions in regions without MEG spike activity, (c) MEG-directed review of high-spatial-resolution MR images enables detection of abnormalities not apparent on conventional MR images, and (d) MEG information results in a greater number of diagnosed lesions at re-review of conventional MR images. MATERIALS AND METHODS: Twenty patients with neocortical epilepsy were evaluated with MEG, conventional brain MR imaging with a head coil, and high-spatial-resolution MR imaging with either a surface coil (n = 17) or a high-spatial-resolution birdcage coil (n = 3). Abnormal MEG foci were compared with corresponding anatomic areas on conventional and high-spatial-resolution MR images to determine the presence (concordance) or absence (discordance) of anatomic lesions corresponding to foci of abnormal MEG activity. RESULTS: Forty-four epileptiform MEG foci were identified. Twelve foci (27%) were concordant with an anatomic abnormality at high-spatial-resolution MR imaging, and 32 foci (73%) were discordant. Results of high-spatial-resolution MR imaging were normal in eight patients, and 23 lesions were detected in the remaining 12 patients. Twelve lesions (52%) were concordant with abnormal MEG epileptiform activity, and 11 (48%) were discordant (ie, there was normal MEG activity in the region of the anatomic abnormality). At retrospective reevaluation of conventional MR images with MEG guidance, four occult gray matter migration lesions that had initially been missed were observed. An additional patient with MEG-concordant postoperative gliosis was readily identified with high-spatial-resolution MR images but not with conventional MR images. CONCLUSION: Review of MEG-localized epileptiform areas on high-spatial-resolution MR images enables detection of epileptogenic neocortical lesions, some of which are occult on conventional MR images.