Clinical utility of EEG in diagnosing and monitoring epilepsy in adults.

Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE.

Imaging of Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma is fatal if unresectable. However, improved survival has been reported after gross total resection and multimodality therapy. In this report, we describe the contrast-enhanced high-resolution CT characteristics of anaplastic thyroid carcinoma in 57 patients. Anaplastic thyroid carcinoma presented as a large neck mass with necrosis in 82% of cases. The tumors demonstrated common extrathyroidal extension (91%). Sixty-two percent of tumors demonstrated calcification. Visceral space invasion involved the esophagus (62%), trachea (57%), and larynx (29%). Carotid artery encasement was present in 42%, and 43% involved the internal jugular vein. Sixty-three percent had lateral compartment lymphadenopathy; 58% of these nodes were necrotic, and 11% were cystic. No metastatic nodes had calcification. Central compartment lymphadenopathy was seen in 56% of cases, and lateral retropharyngeal lymphadenopathy was detected in 12%. Knowledge of these imaging features aids in guiding the approach to the initial tissue diagnosis with either fine-needle aspiration or core biopsy, assessing the feasibility of surgical resection, and determining prognosis.

mild(®) Lumbar Decompression for the Treatment of Lumbar Spinal Stenosis.

More than 1.2 million people are undergoing treatment for lumbar spinal stenosis (LSS) in the United States. Yet, therapeutic options for these patients are limited to either conservative treatments or highly invasive surgeries. A new image-guided interlaminar decompression procedure, mild(®), offers significant relief for many of these patients by debulking dorsal element hypertrophy while preserving structural stability. mild can be performed without general anesthesia and offers a short recovery period. A meta-analysis of four clinical patient series from multiple institutions in the United States evaluated over 250 patients for safety and clinical efficacy of the mild procedure. Clinical efficacy was evaluated at baseline and at three-month follow-up using validated patient reported outcomes (PRO) instruments including the ten-point Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). Acute safety and patient outcomes was compared to the Spine Patient Outcomes Research Trial (SPORT). No device or procedure-related serious adverse events (SAEs) have been recorded with the mild procedure. Outcome metrics for patients treated with mild demonstrated statistically significant symptomatic improvement over baseline. When compared to open surgery, mild efficacy results compare favorably, and complication rates are much lower. mild is a safe and effective procedure that decompresses LSS in a minimally invasive manner while preserving the structural stability of the spine.

The value of multichannel MEG and EEG in the presurgical evaluation of 70 epilepsy patients.

OBJECTIVE: To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery. METHODS: Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers. RESULTS: MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients). CONCLUSION: Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.

Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy.

OBJECTIVE: To compare sexual function and reproductive hormone levels among men with epilepsy who took various antiepileptic drugs (AEDs), untreated men with epilepsy, and normal controls. METHODS: Subjects were 85 men with localization-related epilepsy (25 on carbamazepine [CBZ], 25 on phenytoin [PHT], 25 on lamotrigine [LTG], and 10 untreated for at least 6 months [no AED]) and 25 controls. Sexual function scores (S-scores), hormone levels (bioactive testosterone, estradiol), hormone ratios (bioactive testosterone/bioactive estradiol), and gonadal efficiency (bioactive testosterone/luteinizing hormone) were compared among the five groups. RESULTS: S-scores, bioactive testosterone levels, bioactive testosterone/bioactive estradiol, and bioactive testosterone/luteinizing hormone were significantly greater in the control and LTG groups than in the CBZ and PHT groups. Sex hormone binding globulin was significantly higher in the CBZ and PHT groups than in all other groups. S-scores were below the control range in 20% of the men with epilepsy, including 32.0% on CBZ, 24% on PHT, 20% on no AEDs, and 4% on LTG (chi2: p = 0.08 for all four groups; chi2: p = 0.02 for the three AED groups). Bioactive testosterone was below the control range in 28.2%, including 48% on CBZ, 28% on PHT, 20% on no AEDs, and 12% on LTG (chi2: p = 0.02). Among men with epilepsy who had low S-scores, 70.6% had bioactive testosterone levels below the control range as compared to 17.6% among men with normal S-scores (chi2: p < 0.0001). Among men with epilepsy who had abnormally low bioactive testosterone, 50.0% had low S-scores; among men with normal bioactive testosterone, 8.2% had low S-scores (chi2: p < 0.0001). Bioactive testosterone decline with age was significantly greater among men with epilepsy than among controls and notably greater in the CBZ and PHT groups than in the LTG and untreated groups. CONCLUSIONS: Sexual function, bioavailable testosterone levels, and gonadal efficiency in men with epilepsy who took lamotrigine were comparable to control and untreated values and significantly greater than with carbamazepine or phenytoin treatment.

Effects of single-pulse transcranial magnetic stimulation (TMS) on functional brain activity: a combined event-related TMS and evoked potential study.

OBJECTIVE: To further evaluate the potential of slew-rate limiting amplifiers to record electrophysiological signals in spite of concurrent transcranial magnetic stimulation (TMS), and to explore the effects of single-pulse TMS on electroencephalographic (EEG) correlates of functional brain activity. METHODS: Visual-evoked potentials (VEPs) to checkerboards were recorded in 7 right-handed subjects, while single-pulse TMS was applied to the occipital pole either at visual stimulus onset, during the build-up or at the expected peak of the early VEP component P1 (VIS&TMS). Timing of TMS was individually adjusted based on each subject's VEP-latency. A condition of TMS without concurrent visual stimulation (TMS(alone)) served for subtraction purposes (VIS&TMS minus TMS(alone)) to partial out TMS-related contaminations of the EEG signal. RESULTS: When TMS was applied at visual stimulus onset, VEPs (as calculated by subtraction) perfectly matched control VEPs to visual stimulation alone. TMS at around P1, in contrast, modified the targeted (P1) and the subsequent VEP component (N1), independently of whether TMS was given at build-up or peak. CONCLUSIONS: The retrieval of regular VEPs with concomitant TMS at visual stimulus onset suggests that the employed EEG system and subtraction procedure are suited for combined EEG-TMS studies. The VEP changes following TMS at around P1 provide direct clues on the temporal dynamics of TMS pulse effects on functional activity in the human brain. Our data suggest effects of relatively long duration (approximately 100 ms) when TMS is applied while functional neuronal activity evolves.

Experimental tests of EEG source localization accuracy in realistically shaped head models.

OBJECTIVES: To determine the accuracy with which electrical sources in the human brain can be located using realistically shaped boundary element models of the head and to compare this accuracy with that using spherical head models. METHODS: In a previous study, electroencephalographs (EEGs) produced by sources at known locations in the brains of human subjects were recorded. The sources were created by injecting current into implanted depth electrodes. The locations of the implanted depth and scalp EEG electrodes and head shape were determined from computerized tomography images. The EEGs were used to calculate source locations in spherical head models and localization accuracy was determined by comparing the calculated and actual locations. In this study, these same EEGs are used to determine localization accuracy in realistically shaped head models. RESULTS: An average localization error of 10.5 (SD=5.4) mm was obtained in the realistically shaped models for all 176 sources in 13 subjects. This compares with 10.6 (5.5) mm in the spherical models. The average localization error for 105 sources at superior locations in the brain is 9.1 (4.2) mm. The average error for 71 inferior location sources is 12.4 (6.4) mm. The corresponding values for the spherical models are 9.2 (4.4) and 12.8 (6.2) mm. CONCLUSIONS: The realistically shaped head boundary element models used in this study produced very nearly the same localization accuracy as spherical models.

Mutations in the X-linked filamin 1 gene cause periventricular nodular heterotopia in males as well as in females.

Periventricular heterotopia (PH) is a human neuronal migration disorder in which many neurons destined for the cerebral cortex fail to migrate. Previous analysis showed heterozygous mutations in the X-linked gene filamin 1 (FLN1), but examined only the first six (of 48) coding exons of the gene and hence did not assess the incidence and functional consequences of FLN1 mutations. Here we perform single-strand conformation polymorphism (SSCP) analysis of FLN1 throughout its entire coding region in six PH pedigrees, 31 sporadic female PH patients and 24 sporadic male PH patients. We detected FLN1 mutations by SSCP in 83% of PH pedigrees and 19% of sporadic females with PH. Moreover, no PH females (0/7 tested) with atypical radiographic features showed FLN1 mutations, suggesting that other genes may cause atypical PH. Surprisingly, 2/24 males analyzed with PH (9%) also carried FLN1 mutations. Whereas FLN1 mutations in PH pedigrees caused severe predicted loss of FLN1 protein function, both male FLN1 mutations were consistent with partial loss of function of the protein. Moreover, sporadic female FLN1 mutations associated with PH appear to cause either severe or partial loss of function. Neither male could be shown to be mosaic for the FLN1 mutation in peripheral blood lymphocytes, suggesting that some neurons in the intact cortex of PH males may be mutant for FLN1 but migrate adequately. These results demonstrate the sensitivity and specificity of DNA testing for FLN1 mutations and have important functional implications for models of FLN1 protein function in neuronal migration.

Capecitabine for 5-fluorouracil-resistant brain metastases from breast cancer.

We report a case in which brain metastases originating from breast cancer responded to treatment with oral capecitabine. The metastases had progressed and Karnofsky performance status deteriorated despite whole brain irradiation, hormonal treatment, and systemic chemotherapy that included 5-fluorouracil (5-FU). In contrast, 2 months of treatment with oral capecitabine produced a partial response, documented by lesion size on magnetic resonance imaging and an improvement in performance status; both measures continued to improve during 11 months of capecitabine treatment.

Experimental tests of EEG source localization accuracy in spherical head models.

OBJECTIVES: The locations of electrical sources in the brain can be calculated using EEG data. However, the accuracy of these calculations is not well known because it is usually not possible to compare calculated source locations with actual locations since little accurate location information is available about most sources in the brain. METHODS: In this study, sources at known locations are created by injecting current into electrodes implanted in the brains of human subjects. The locations of the implanted and scalp EEG electrodes are determined from CTs. The EEG signals produced by these dipolar sources are used to calculate source locations in spherical head models containing brain, skull, and scalp layers. The brain and scalp layers have the same electrical conductivity while 3 different skull conductivity ratios of 1/80th, 1/40th, and 1/20th of brain and scalp conductivity are used. Localization errors have been determined for 177 sources in 13 subjects. RESULTS: An average localization error of 10.6 (SD=5.5) mm for all 177 source was obtained for a skull conductivity ratio of 1/40. The average errors for the other ratios are only a few millimeters larger. The average localization error for 108 sources at superior locations in the brain is 9.2 (4.4) mm. The average error for 69 inferior location sources is 12.8 (6.2) mm. There are no significant differences in localization accuracy for deep and superficial sources. CONCLUSIONS: These results indicate that the best average localization that can be achieved using a spherical head model is approximately 10 mm. More realistic head models will be required for greater localization accuracy.

Intracranial Neurophysiological Correlates Related to the Processing of Faces.

Face perception and recognition is an intriguing ability, already present in neonates. Numerous studies in patients with brain lesions identified the temporo-occipital cortex as the crucial structure for this capacity. Analysis of electrical signals (EEG) inside the brain of patients implanted with intracranial electrodes for diagnostic purposes allows researchers to describe the temporal and spatial organization of responses to various aspects of face processing in human subjects. Several findings have emerged and appear relevant for cerebral organization in general: (1) Selective face responses were obtained from the basal temporo-occipital cortex at around 200 ms (N200); however, other structures such as the lateral temporal lobe and frontal cortex also participate in face recognition and perception tasks. (2) Each structure has a distinct "response profile"; that is, with respect to a given task certain structures respond strongly, others less or not at all. This profile might change with a different task, although the physical parameters of the stimuli remain the same. (3) The right hemispheric predominance of face processing, as suggested by patient data and studies in healthy volunteers, seemed to be restricted to its early stages (i.e., before 100-150 ms). (4) Recognition of faces might be associated with differential intracranial responses, despite an incorrect overt response, reflecting neurophysiological correlates of implicit memory. (5) The more the stimulus resembled a complete human face, the earlier and larger the N200 response was found, in particular over the basal temporobasal cortex. Analysis of electrical signals from intracranial electrodes might help to improve our understanding of the underlying physiological and anatomical constraints of cognitive processes.

Increased susceptibility to generalized seizures after immunolesions of the basal forebrain cholinergic neurons in rats.

We investigated whether basal forebrain cholinergic neurons influence the expression of generalized seizures. Animals received intracerebroventricular injections of saporin (lesioned) or saline (controls) and were tested for susceptibility to flurothyl- or pentylenetetrazole-induced seizures. Lesioned rats had significantly shorter latencies to onset of generalized tonic-clonic seizures than controls. Our findings suggest that basal forebrain cholinergic neurons may participate in the modulation of generalized seizures.

Reappraisal of filter effects on P300 voltage and latency.

The selection of which high-pass filter cutoff to use in P300 studies continues to be a serious methodological consideration. To determine whether there was an optimal range of bandpass widths-a range in which P300 voltage and latency would not show statistically significant differences-the authors recorded P300 responses to the auditory "oddball" paradigm from Cz and Pz electrodes in a group of eight healthy males. The authors used high-pass filter cutoffs of 0.01, 0.1, 0.3, and 1.0 Hz with low-pass filter cutoffs of 30 and 100 Hz and measured both P300 peak voltages and P300 integrated mean voltages at 12 bandpass settings. There were statistically significant differences in 7 out of 12 bandpass comparisons for P300 peak voltages and in 7 out of 12 bandwidth comparisons for P300 integrated mean voltages. For P300 latencies, there were statistically significant differences in 9 out of 12 bandwidth comparisons. Based on these results, the best recommendation, therefore, is that the high-pass filter be set no higher than 0.3 Hz.

Progressive multifocal leukoencephalopathy with concurrent Richter's syndrome.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating infectious disease caused by the JC virus. It was originally described in patients with chronic lymphocytic leukemia (CLL). Richter's syndrome, or transformation to large cell Lymphoma, occurs in approximately 3% of patients with CLL, and carries a poor prognosis. We report a patient with documented PML and concurrent Richter's transformation outside the central nervous system. Before establishing a definitive diagnosis of PML, radiation therapy to the presumed lymphomatous brain lesion had been considered, raising the issue of whether stereotactic brain biopsy should be considered in every patient in a similar situation. Although this is likely a rare occurrence, patients with Richter's transformation documented at an extra-neural site and a brain lesion may benefit from the establishment of an infectious diagnosis which would influence therapy.

Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy.

PURPOSE: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal-associated hypoxemia. METHODS: During long-term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity. RESULTS: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (+/-SD) was 73 +/- 18 s. Mean Spo2 desaturation duration was 76 +/- 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 +/- 16 s. Mean (+/-SD) Spo2 nadir was 83 +/- 5% (range, 77-91%), occurring an average of 35 +/- 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations. CONCLUSIONS: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.

Performance analysis of a new semiorthogonal spline wavelet compression algorithm for tonal medical images.

Lossy image compression is thought to be a necessity as radiology moves toward a filmless environment. Compression algorithms based on the discrete cosine transform (DCT) are limited due to the infinite support of the cosine basis function. Wavelets, basis functions that have compact or nearly compact support, are mathematically better suited for decorrelating medical image data. A lossy compression algorithm based on semiorthogonal cubic spline wavelets has been implemented and tested on six different image modalities (magnetic resonance, x-ray computed tomography, single photon emission tomography, digital fluoroscopy, computed radiography, and ultrasound). The fidelity of the reconstructed wavelet images was compared to images compressed with a DCT algorithm for compression ratios of up to 40:1. The wavelet algorithm was found to have generally lower average error metrics and higher peak-signal-to-noise ratios than the DCT algorithm.

EEG-Linked functional magnetic resonance imaging in epilepsy and cognitive neurophysiology.

The ability to trigger functional magnetic resonance imaging (fMRI) acquisitions related to the occurrence of EEG-based physiologic transients has changed the field of fMRI into a more dynamically based technique. By knowing the temporal relationship between focal increases in neuronal firing rates and the provoked focal increase in blood flow, investigators are able to maximize the fMR-linked images that show where the activity originates. Our mastery of recording EEG inside the bore of a MR scanner has also allowed us to develop cognitive paradigms that record not only the fMR BOLD images, but also the evoked potentials (EPs). The EPs can subsequently be subjected to localization paradigms that can be compared to the localization seen on the BOLD images. These two techniques will most probably be complimentary. BOLD responses are dependent on a focal increase in metabolic demand while the EPs may or may not be related to energy demand increases. Additionally, recording EPs require that the source or sources of that potential come from an area that is able to generate far-field potentials. These potentials are related to the laminar organization of the neuronal population generating that potential. As best we know the BOLD response does not depend on any inherent laminar neuronal organization. Therefore, by merging these two recording methods, it is likely that we will gain a more detailed understanding of not only the areas involved in certain physiologic events, e.g. focal epilepsy or cognitive processing, but also on the sequencing of the activation of the various participating regions.

Flurothyl-induced seizures in rats activate Fos in brainstem catecholaminergic neurons.

Autonomic changes accompany seizures in both animals and humans. While ictal autonomic dysfunction can be life-threatening, the participating neural networks involved are poorly understood. In this study we examined the activation of Fos following generalized seizures in brainstem structures known to mediate autonomic function. Adult female rats were sacrificed 2 h after flurothyl-induced seizures. Double-immunostaining for c-Fos and dopamine-beta-hydroxylase (DBH), and c-Fos and phenylethanol-N-methyl-transferase (PNMT) were performed in brainstem slices. Numbers of DBH-labeled neurons expressing Fos-like immunoreactivity (FLI) (DBH/Fos) and PNMT labeled neurons expressing FLI (PNMT/Fos) were counted in the noradrenergic (A1, A2, A5, A7) and adrenergic (C1, C2) cell groups localized in pons and medulla oblongata. Among the experimental animals, the highest degree of co-localization of DBH/Fos neurons was observed in the locus coeruleus (A6; 87.7%), and in the A1(72.8%) cell group located in the caudal ventrolateral medulla (VLM). No co-localization of DBH/Fos neurons was observed in control animals. The highest degree of co-localization of PNMT/Fos neurons was observed in the C1 adrenergic cell group (84.2%) located in the rostral VLM. Control animals showed very few (5.5%) PNMT/Fos co-localized neurons in the C1 adrenergic cell group. Our results indicate that flurothyl-induced generalized seizures in rats activate catecholaminergic neurons in the pons and medulla oblongata. Further studies are necessary to determine whether activation of brainstem catecholaminergic neurons contribute to the autonomic manifestations that frequently accompany epileptic seizures.