PURPOSE:To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS:Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS:The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS:The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

OBJECTIVE:To evaluate and identify the incidence of visual field defects (VFD) after anterior temporal lobectomy (ATL) versus amygdalohippocampectomy (AH). VFD occur frequently after ATL and are usually superotemporal quadrantanopias. Little is known about the incidence of VFD after AH and this surgical method offers the possibility of a seizure-free survival without visual loss.METHODS:Patients with similar characteristics were examined. All patients had intractable seizures and mesial temporal sclerosis, small tumors localized to only the uncus, amygdala, or hippocampus, or no known pathology. Postoperative kinetic field testing using the I4e isopter on a Goldmann perimeter was performed 30 days or more after surgery.RESULTS:Of 29 patients examined, 14 underwent AH and 15 had ATL. Four of 14 AH patients (28%) had a VFD at 10 degrees from center and 11/14 (78%) had VFD at 40 degrees. One of 15 ATL patients (7%) had a VFD at 10 degrees from center and 11/15 (73%) had VFD at 40 degrees. There was no significant difference between surgery types.CONCLUSIONS:AH in this study was associated with a significant number of VFD. No significant difference was found between the frequency of VFD produced from AH and ATL. The mechanism of injury is due to direct trauma to the optic radiations while accessing the mesial temporal structures. Because all patients in the study were asymptomatic for VFD, it remains to be determined whether these VFD are clinically significant.

Background: Chronic vagus nerve stimulation (VNS) continues to be evaluated as an adjunctive treatment for medically intractable seizures. A previous randomized controlled trial of 114 patients demonstrated a significant decrease in seizure frequency during 3 months of VNS at effective stimulation levels.Objective: To evaluate the efficacy of 1 year of VNS therapy for the treatment of medically refractory partial seizures and the relationship between initial and long-term response.Patients and Methods: All patients exiting the randomized controlled study of VNS for treatment of medically refractory partial seizures were offered indefinite treatment extension as part of an open-label trial. One hundred (88%) of 114 patients completed 12 months of VNS treatment at effective stimulation levels. Fourteen patients discontinued VNS treatment prior to 1 year, principally because of the treatment's lack of efficacy. These 14 patients were retained in the present analysis using an intent-to-treat approach. Antiepileptic drug use was monitored throughout the trial. Seizure frequency was analyzed in 4 sequential 3-month treatment periods.Results: Compared with pretreatment baseline, there was a significant decrease in seizure frequency during each of the 3-month treatment periods. Seizure frequency was reduced by a median of 20% during the first 3 months of VNS treatment and by 32% during stimulation months 10 through 12. Response during the first 3 months of VNS treatment was a statistically significant predictor of response at months 10 through 12. The observed reduction in seizure frequency was not explained by overall changes in antiepileptic drug use.Conclusions: The results indicate that VNS remains an effective adjunctive therapy for medically refractory partial seizures over a period of at least 1 year. Response during the first 3 months of treatment is predictive of long-term response.

Background: Two prospective observations of adults with symptomatic, localization-related (partial) epilepsy included 1,102 patients in VA multicenter studies (VA-118; and VA-264). Analyses assessed the likelihood of remaining seizure free for 12 and 24 months after initiating adequate antiepileptic drug therapy. Methods: Patients were grouped as having only secondarily generalized tonic-clonic seizures (GTC), only complex partial seizures (CPS), or both types (MIXED) at entry. The cumulative proportion of patients remaining seizure free with standard antiepileptic drug therapy was determined by actuarial life table methods. Results: At 12 months, 70% and 61% of GTC patients (VA-118 and VA-264, respectively) had no further GTC; 53% and 50% of MIXED, predominantly GTC patients had no further GTC, 21% and 28% of CPS patients had no further CPS and 98% and 91% were seizure free for GTC; 32% and 35% of MIXED, predominantly CPS patients had no further CPS, and 62% and 51% of patients with MIXED seizure types remained seizure free for CPS for 12 months after enrollment. Conclusions: The overall prognosis for control of seizures of any type for 12 months was best for those who had only GTC at entry (55% and 48%), worst for those who had only CPS at entry (23% and 26%), and intermediate for those with MIXED seizures at entry (32% and 25%) (all p < 0.0001). Prognosis can be based on the predominant seizure type in patients with multiple types.

Preliminary reports have suggested that chronic, intermittent stimulation of the vagus nerve (VNS) is an alternative treatment for patients with medically refractory seizures. We performed a multicenter, randomized, controlled trial to evaluate the efficacy and safety of adjunctive VNS in patients with poorly controlled partial seizures. An implanted, programmable pacemaker-like device was connected to two stimulating electrodes wrapped around the left vagus nerve. One hundred fourteen patients were randomized to receive 14 weeks of high-level stimulation (presumed therapeutic dose) or low-level stimulation (presumed subtherapeutic dose) using a blinded, parallel study design. Seizure frequency was compared with a 12-week baseline. Mean reduction in seizure frequency was 24.5% for the "high" stimulation group versus 6.1% for the "low" stimulation group (p = 0.01). Thirty-one percent of patients receiving high stimulation had a seizure frequency reduction of greater than or equal to 50%, versus 13% of patients in the low group (p = 0.02). Treatment emergent side effects were largely limited to a transient hoarseness occurring during the stimulation train. One patient with no previous history of cardiac disease experienced a myocardial infarction during the third month of vagal stimulation. VNS may be an effective alternative treatment for patients who have failed antiepileptic drug therapy and are not optimal candidates for epilepsy surgery.

Vagus nerve stimulation (VNS) was shown to reduce seizure frequency in refractory epilepsy patients in two pilot studies. Based on these results, a multicenter, prospectively randomized, parallel, double-blind study of patients with refractory partial seizures was initiated. After a 12-week baseline period, identical vagus nerve stimulators were implanted and patients randomized to either a high or low 14-week VNS treatment paradigm. The primary objective was to demonstrate that high VNS (therapeutic parameters) was more effective in reducing partial seizure frequency than was low VNS (less or noneffective parameters). Patients continued receiving antiepileptic drugs (AEDs) with plasma concentrations held constant throughout the study. We report results of the first 67 patients to exit the 14-week acute phase. After 14 weeks of VNS, 31 patients receiving high VNS experienced a mean seizure frequency percentage reduction of 30.9%, which was statistically significant as compared with the mean seizure frequency percentage reduction of 11.3% in 36 patients receiving low VNS (p = 0.029, t test; p = 0.036, Wilcoxon rank-sum test). In addition to the significant intragroup p-values, mean seizure frequency percentage change reached statistical significance for high VNS (p < 0.001) but not low VNS (p = 0.072) as compared with baseline. Twelve of 31 (38.7%) patients receiving high VNS achieved at least 50% reduction in seizure frequency whereas 7 of 36 (19.4%) patients receiving low VNS experienced at least 50% reduction after 14 weeks. The implant procedure and VNS therapy were well tolerated. Our study confirmed the effectiveness of VNS as treatment for epilepsy patients with refractory partial seizures.

Summary: Vagus nerve stimulation (VNS) significantly reduces the frequency of partial seizures in refractory epilepsy patients. We examined the serious adverse events, side effects, and tolerability as they relate to the surgical implant procedure and the stimulating device.We also reviewed potential drug interactions, device out‐put complications, and impact of the therapy on overallhealth status. We analyzed the first 67 patients to exit theacute phase of the EO3 VNS trial comparing high (therapeutic) VNS to low (less or noneffective) VNS. Datawere collected from case report forms used at each of thefour visits during the 12‐week baseline and at each of thefour visits during the 14‐week randomized phase of the trial. No significant complications were reported as a re‐sult of the implant procedure. Serious adverse events in‐cluded 1 patient who experienced direct current to thevagus nerve owing to generator malfunction resulting inleft vocal cord paralysis and withdrawal of the patientfrom the study. No clinically significant effects on vitalsigns, cardiac function, or gastric function were detected. Side effects associated with VNS in the high group werehoarseness (35.5%), coughing (13.9%), and throat pain(12.9%). In the low group, only hoarseness (13.9%) andthroat pain (13.9%) were associated with VNS. Theseeffects generally were not considered clinically significantand occurred primarily during the stimulation pulses. Nopatients discontinued VNS therapy during the acutephase because of side effects associated with normal stimulation. Except for the one instance of a short circuitin the system resulting in a direct current, stimulatingsystem complications were minor, limited to programming, unscheduled stimulation, and high lead impedance.Patients, investigators, and patient companions rated patients receiving high stimulation as more “improved” than those receiving low stimulation in regards to overallhealth status. Antiepileptic drug (AED) plasma concentrations were not affected by VNS. The implant procedure, stimulating system, and therapy proved safe andtolerable during the study. The high percentage (67 of 68)of patients completing the study reflects patient acceptance and tolerability of this mode of therapy.

Vagus nerve stimulation (VNS) has demonstrated a significant anticonvulsant effect in preclinical studies, in pilot studies in humans, and in the acute phase of a multicenter, double-blinded, randomized study. After completion of a 14-week, blinded, randomized study, with 31 receiving high (therapeutic) VNS and 36 receiving low (less or noneffective) VNS, 67 patients elected to continue in an open extension phase. During the extension phase, all 67 patients received high VNS. Seizure frequency during the 3-month treatment blocks was compared with a 12-week baseline. For both groups, all periods of high VNS demonstrated a significant decrease in seizure frequency (p < 0.01 level) as compared with baseline. For the 16-18-month period of VNS, data were available for 26 of the 31 patients randomized to high VNS. This group achieved a 52.0% mean seizure frequency percentage reduction as compared with baseline. For those converted from low to high VNS, data were available for 24 of the 36 patients at the 16-18-month time period. This group reported a mean seizure frequency percentage reduction of 38.1% as compared with baseline. No significant change in the safety/side effect profile was reported during long-term follow-up. The previously reported side effects of hoarseness/voice change, coughing, and paresthesia (sensation in neck and jaw) continued to occur during VNS. These side effects were well tolerated. During the follow-up period, 1 patient died of thrombotic thrombocytopenic purpura (TTP) and 5 patients discontinued treatment because of unsatisfactory efficacy.

There has been much research in the electrophysiologic correlates of alertness and attention, but it is fragmented into many subfields. This article integrates current knowledge across multiple disciplines and methodologies to provide a broad overview of alertness and attention. First, terms that are related to alertness and attention are clarified. Then, there is a discussion of basic neuroscience, human neurophysiology, and clinical fields that impact on alertness and attention. Areas discussed include thalamic and neurotransmitter-specific ascending pathways, EEG, event-related potentials, and both physiologic and pathologic states of decreased alertness or attention.

Phasic event-related desynchronization (ERD) of alpha activity briefly follows many types of stimulation. In order to define EEG changes resulting from longer stimulation. EEG records were made before and during hand immersion into cool and painfully cold water (cold pressor). Five minutes of 13-lead EEG records were obtained from 14 subjects for each condition. EEG frequency analysis was performed on artifact-free epochs from 60 to 240 sec following immersion. Following an initial phasic decrease in alpha power during cold water immersion, there was an augmentation of alpha power (8-12 Hz) in bilateral frontal and posterior electrodes. This augmentation was largely the result of an increase in the low alpha band (8-10 Hz). Alpha power at both central electrodes C3 and C4 changed little during cold water immersion. Cool water immersion produced less alpha power augmentation than cold water immersion. These observed changes were primarily in the high alpha band (10-12 Hz) and were larger in electrodes ipsilateral rather than contralateral to the stimulation. There was also an increase of beta bilaterally in frontal and posterior regions with cold water immersion. Our data demonstrate sustained topographic EEG responses during tonic stimulation from hand immersion in painfully cold water. These changes differ from those produced by stimulation with cool water immersion.

We performed computerized EEG frequency analysis (C-EEGFA) in 69 controls and 20 patients with focal brain lesions and focally abnormal conventional EEGs. Individual channel EEG frequency analysis variables that were helpful in differentiating the 2 groups were absolute delta and theta band power, relative delta, theta, and alpha band powers, and median-power frequency. High-frequency beta band power (20 to 32 Hz) was not useful. Changes in EEG with age were seen only after age 50 and generally consisted of an increase in anterior alpha power, with no significant increase in slowing. Correlations of C-EEGFA variables with posterior alpha power were more significant than correlations with age. Calculating normative C-EEGFA data for 5 subsets of controls, each with a different amount of posterior alpha power, increased the sensitivity of the EEG frequency analysis test without altering the specificity. Even with this correction, 2 of 20 patients with focal lesions and focally abnormal conventional EEGs had normal C-EEGFA studies. If these obvious focal lesions produced normal results, more subtle diseases might not be detected. A significant clinical utility of C-EEGFA remains to be proven.

Color Density Spectral Array (CDSA) is a new technique that uses the fast Fourier transform and color graphics to provide a display of frequency, power, and time. CDSA sleep records provide an overview of sleep architecture as well as quantitative+ EEG data. To validate this technique, overnight sleep records from five patients were independently staged from polygraph recordings and overnight CDSA records. Observed agreement between the two techniques was 85-92% for approximately 1,100 epochs per night.

Summary: The initial evaluation of patients with seizure disorders frequently includes cerebrospinal fluid (CSF) examination in order to identify an underlying cerebral lesion. With increasing use of computed tomography (CT) scanning to detect cerebral neoplasms, the value of CSF examination has become less certain. The significance of mild CSF abnormalities in patients with a normal CT scan remains unknown. We reviewed the records of 95 patients with adult onset partial epilepsy whose initial evaluation included CSF examination and CT scan. A CSF abnormality not temporally related to convulsive seizure was seen in 24 patients (25%). The CSF study confirmed a clinically suspect subarachnoid hemorrhage in 4 patients. Isolated mild (49–106 mg/dl) increases in CSF protein were seen in 19 patients. Of these 19 patients, 8 had a structural lesion on CT scan. Clinical follow‐up of the other 11 patients (mean 5 years) has revealed no evidence of a focal lesion or increasing seizure frequency. This suggests that in an adult population with partial epilepsy routine CSF examination may not be necessary and should be reserved for situations in which there is particular clinical indication. RÉSUMÉ Ľévaluation initiale des patients épileptiques comprend souvent ľexamen du liquide céphalo‐rachidien (LCR) qui est pratiquéà la recherche ľune lesion cérébrale sous‐jacente. Ľutilisation fréquente de la tomodensitométrie cérébrale (TDM) dans la recherche des néoplasmes cerébraux, la valeur de la ponction lombaire a été mise en doute. La signification ľanomalies modérées ľun LCR chez les patients avec TDM normale n'est pas connue. Nous avons revus les dossiers de 95 patients présentant une épilepsie partielle ayant débutéàľâge adulte, chez lesquels ľévaluation initiale avait comporté une TDM et un examen du LCR. Une anomalie du LCR sans relation temporelle avec une crise convulsive a été retrouvée chez 24 patients (25%), Ľexamen du LCR a confirméľexistence ľune hémorragie meningée suspectée cliniquement chez 4 patients. Une augmentation modérée, isolée de ľalbuminorachie (0.49‐1.06 g/l) a été constatée chez 19 patients, parmi lesquels 8 présentaient une lésion anatomique à la TDM. La surveillance clinique des 11 patients restants (en moyenne pendant 5 ans) n'a pas révélé de lésion focale ou ľaugmentation de fréquence des crises. Ceci suggère que dans une population adulte ľépilepsies focales, ľexamen de routine du LCR ne semble pas nécessaire, et devrait être réservéà des indications cliniques particulières. RESUMEN La evaluación inicial de pacientes con trastornos convulsivos incluye, fracuentemente, el examen del líquido céfalo raquídeo (LCR) con el fin de identificar una lesión cerebral subyacente. Con el incremento de la utilización de la Tomografia Computarizada (TC) para detectar tumores cerebrales el valor del estudio adicional del LCR resulta menos cierto. El significado de moderadas anormalidades del LCR en pacientes con una TC normal permanece desconocido. Hemos revisado las historias clínicas de 95 enfermos con comienzo adulto de epilepsía parcial, en los que la evaluación incial incluía un examen del LCR y una TC. Una anomalia en el LCR no relacionada temporalente con un ataque convulsive fue detectada en 24 pacientes (25%). El estudio del LCR confirmó la sospecha clínica de una hemorragia subaracnoidea en 4 enfermos. Ligeras elevaciones de las proteinas en el LCR (45–106 mg/dl.) fueron observadas en 19 pacientes, 9 de los cuales tenían una lesión estructural en la TC. El seguimiento clínico de los otros 11 enfermos (promedio de 5 años) no reveló ninguna evidencia de lesión focal o incremento de la frecuencia de ataques. Estos datos sugieren que, en la población adulta con epilepsía parcial, el examen rutinario del LCR puede no ser necesario y debe ser reservado para situaciones en las que existe una indicación clínica particular.

Multiple-channel color density spectral array (CDSA) was used to graphically represent sleep stages. This technique uses color coding of Fast Fourier Transforms to provide a compact display of frequency, power, and real time. Distinct CDSA patterns correlate to the awake, non-REM, and REM sleep states. The graphic compression of sleep data could considerably shorten the time required to stage overnight sleep recordings.

Interictal epileptiform activity (IIEA) on EEG may be useful in the diagnosis and characterization of epilepsy. A single scalp EEG may fail to detect this abnormality, which is then discovered on repeat recordings. Since many people with epilepsy have persistently normal EEGs, a practical question arises concerning the yield of multiple EEGs. To determine the probability of finding IIEA with serial EEGs (the operational curve), we reviewed data from 1,201 EEGs on 429 adult patients, most with definite epilepsy presenting in adulthood. The diagnosis was made either clinically or with the support of the EEG. In 50% of our patients with IIEA, the abnormality is present on the first record, in 84% by the third EEG, and in 92% by the fourth. There is relatively little yield to serial EEGs beyond this point.