Weeping as a common element of pseudoseizures.

Weeping is an extremely rare ictal phenomenon. We report weeping during or at the very end of electrographically proved pseudoseizures in 10 patients. We conclude that weeping is a relatively common and specific clinical feature of pseudoepileptic seizures.

Vagus nerve stimulation for the treatment of medically intractable seizures. Results of a 1-year open-extension trial. Vagus Nerve Stimulation Study Group.

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.

Prevalence of psychologic disorders after surgical treatment of seizures.

To investigate whether surgical treatment of refractory epilepsy is associated with increased risk for serious psychopathology, 25 treated patients were compared with 25 current candidates for surgery matched on demographic and neuroepileptic characteristics. Diagnoses were made by the National Institute of Mental Health Diagnostic Interview Schedule. No differences between groups in lifetime or point prevalence rates were significant. The rate of psychosis in the postoperative group (8%) approximated the lower estimates in previous studies. Thus, surgical treatment of seizures did not increase the risk for psychopathology. However, patients with temporal lobe electroencephalogram foci or tumor as the epileptogenic lesion were more likely to have serious disorders than other patients. Also, anxiety disorders were more prevalent in our patient groups than in the general population.

Tailored anterior temporal lobectomy. Relation between extent of resection of mesial structures and postsurgical seizure outcome.

OBJECTIVE: The purpose of this study was to assess the relationship between the extent of resection of mesial temporal structures and postsurgical seizure outcome in a group of patients who had undergone a tailored anterior temporal lobectomy. METHODS: Twenty-four patients with unilateral interictal and ictal foci restricted to anterior/mesial temporal regions underwent resection of mesial and temporal lateral structures, the extent of which was tailored by intraoperative electrocorticographic findings and functional mapping of eloquent cortex. The extent of resection was determined with postoperative magnetic resonance imaging scans, using a semiquantitative method, based on a 20-compartment model of the temporal lobe. The magnetic resonance imaging scans were rated by three investigators blinded to seizure outcome. Follow-up period ranged between 18 months and 5 years. RESULTS: Amygdala and hippocampus were spared in six patients; nine patients had a partial to total resection of amygdala, eight patients had a resection of amygdala and the anterior third of the hippocampus, and one patient underwent resection of amygdala and anterior two thirds of hippocampus. Twenty-one of the 24 patients were seizure free (Engel's class I) and three had rare seizures (Engel's class II). Among these three patients, one had a resection of amygdala; one had resection of amygdala and anterior third of hippocampus; while in the third patient, mesial structures were spared. CONCLUSION: These data suggest that in patients with an anterotemporal seizure focus, the sparing or limited resection of amygdala and/or hippocampus is not necessarily associated with a poor seizure outcome, as had been previously suggested, provided that the decision not to resect is based on the absence of epileptiform activity during intraoperative electrocorticography or during recordings with depth electrodes.

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Vagus nerve stimulation therapy for epilepsy in older adults.

The authors assessed the efficacy, safety, and tolerability of vagus nerve stimulation (VNS) for refractory epilepsy in 45 adults 50 years of age and older. They determined seizure frequency, adverse effects, and quality of life. At 3 months, 12 patients had a >50% decrease in seizure frequency; at 1 year, 21 of 31 studied individuals had a >50% seizure decrease. Side effects were mild and transient. Quality of life scores improved significantly with time.

A comparative study of treatments for positional sleep apnea.

Sixty male patients all with apnea plus hypopnea indices (A + HI) above 12.5, who met a criterion of positionality by having two or more times the rate of these events during supine sleep in comparison to their lateral sleep rate, were randomly assigned to one of four treatments for 8 weeks. All were restudied for two nights, one with and one without treatment devices. On treatment more than half the patients in each group reduced their A + HI to within normal limits and a third remained WNL without the use of devices. Half of those trained to sleep in the lateral position with the help of an alarm maintained this learning without the alarm as did half of those who were encouraged to learn this sleep posture on their own. There is an additive effect for the positional patient from wearing a tongue retaining device (TRD) if they continue to sleep in the supine position. Factors associated with successful treatment include overall severity, severity in the lateral position, weight, weight change, nasal patency and motivation to help their condition.

Evaluation of the abuse liability of modafinil and other drugs for excessive daytime sleepiness associated with narcolepsy.

Psychostimulants have been used routinely for the treatment of the disabling daytime sleepiness associated with narcolepsy. However, the perceived and real potential for abuse of amphetamine and amphetaminelike stimulants prompted a search for new wake-promoting compounds with lower dependency and abuse liabilities. Modafinil is a novel wake-promoting agent with a mechanism of action that differs markedly from that of amphetamine and amphetamine-like stimulants. In controlled clinical trials, modafinil has been shown to be an effective and well-tolerated treatment for excessive daytime sleepiness (EDS) in patients with narcolepsy. With a benzhydrylsulfinylacetamide structure, modafinil has a low level of solubility in water (< 1 mg/mL) and is unstable at temperatures > or = 180 degrees C, physicochemical properties that reduce the potential for its abuse via intravenous injection and smoking, respectively. Available preclinical and clinical data on the abuse liability of modafinil suggest a much lower potential for abuse and dependency than amphetaminelike stimulants commonly used for treating EDS in patients with narcolepsy. Therefore, modafinil represents a valuable therapeutic option for the treatment of EDS associated with narcolepsy.

Weight loss in patients taking felbamate.

Felbamate is a new antiepileptic drug (AED) with a good safety profile. Anorexia has been reported in patients taking felbamate, but the incidence and severity of this side effect have not been adequately investigated. We studied 65 patients with intractable seizures who received adjunctive felbamate therapy as part of clinical research trials or in a compassionate-use program. Mean treatment time on felbamate was 23 weeks (+/- SD 16; range, 6-116 weeks). Forty-nine patients (75%) lost weight during the trials. For subjects older than 15 years, there was a mean weight loss of 3.17 kg or 4.11% of body weight (T = 191.5, z = 4.18, p < 0.001). For subjects 15 years or younger there was a mean weight loss 0.20 kg or a loss of 1.77% of body weight (T = 52.5, NS). Twenty-two patients (34%) lost > 4 kg, and seven patients (11%) lost > 8 kg. Adjunctive treatment of adults with severe epilepsy with felbamate may be associated with clinically significant weight loss.

The effect of vagal nerve stimulation on voice.

OBJECTIVE: Vagal nerve stimulation therapy through implanted vagal nerve stimulators is an accepted therapy for refractory seizure disorders. One significant side effect of vagal nerve stimulation is voice change. This study evaluates the impact that these voice changes have on patients' lives, and the physiological effects that vagal nerve stimulation has on the larynx. METHODS: Patients were selected from the pool of patients at Rush-Presbyterian-St. Luke's Medical Center who underwent implantation of vagal nerve stimulator devices. Three methods were used to evaluate the impact the devices had on patients and on their vocal cords. First, a questionnaire was sent to the patients to ascertain the degree of vocal and social impairment that occurs as a result of the implant. Second, videostroboscopy was used to analyze the effect that vagal nerve stimulation had on the larynx. Third, computerized voice analysis objectively analyzed the patients' voices both during and in between vagal nerve stimulations. RESULTS: Although patients noted significant voice changes during stimulation of the implant, the impairment is well tolerated and less debilitating than the underlying seizure disorder. Hyperstimulation of the affected vocal cord was observed during vagal stimulation with paramedian positioning, vocal fold tensing, and loss of mucosal wave. Increase in jitter and shimmer was consistent. CONCLUSION: Vagal nerve implantation devices create significant but well-tolerated vocal side effects. Investigation of these devices increases our understanding of laryngeal physiology and may give insight into future laryngeal pacing. Preimplantation laryngeal examination should be performed routinely to rule out laryngeal pathology that could lead to significant complications.

Polysomnographic sleep measures in Parkinson's disease patients with treatment-induced hallucinations.

Prior studies of sleep in Parkinson's disease (PD) have been compromised by inadequate comparison groups, mixed medication regimens, and absence of quantitative data collection. This is the first study to compare polysomnographic sleep measures in PD patients on only dopaminergic medications with and without hallucinations. We performed two consecutive nights of polysomnography in 10 nondepressed, nondemented PD patients, 5 with and 5 without hallucinations. All patients were being treated with carbidopa/levodopa and a dopaminergic agonist only. Hallucinators and nonhallucinators were group-matched for age, PD duration, severity, and medication doses. Both groups had abnormal sleep records. In particular, there was a reduction in K-complexes and spindle formation, and the frequent occurrence of motor activation during rapid eye movement (REM) sleep consistent with REM behavior disorder. The hallucinator group had a significantly lower sleep efficiency (0.25 in hallucinators vs 0.61 in nonhallucinators, p = 0.006), a reduced total REM sleep time (mean total REM sleep time, 3 minutes in hallucinators vs 50 in nonhallucinators; p = 0.005), and a reduced REM percentage (mean, 5% in hallucinators vs 20% in nonhallucinators; p = 0.011). This study demonstrates that advanced PD patients treated with dopaminergic agents have abnormal sleep patterns and that those with dopaminergic-induced hallucinations have significantly greater REM aberrations than nonhallucinating PD patients.

Effects of restricted sleep with different exercise loads upon subsequent sleep.

Seven male cats were adapted to different schedules of restricted sleep. The cat was permitted to go to sleep either 2, 4 or 8 hours per day with the balance to 24-h periode spent in wakefulness enforced by means of a treadmill. Two experiments were run and the same cats served in both runs. The experiments and schedules were separated by at least two weeks during which time cats were maintained under ordinary laboratory conditions. Our experiment used treadmill speed of 2.6 m/min which was easily tolerated and effective in eliminating sleep. Another experiment used treadmill speed of 4.6 m/min which produced more physical exercise. As available sleep time become progressively shorter, REM sleep increased while SWS decreased. If restriction in sleep time was associated with more physical exercise then the composition of the subsequent sleep was different : SWS increased while REM sleep decreased. The functional significance of these opposite effects are presumably different. The immediate SWS response to the prior muscular exercise is suggestive of its recovery function.

Nonpharmacologic treatment of periodic leg movements in sleep.

The effects of a 30-minute stimulation of the dorsiflexors of the feet and toes before bedtime were investigated in eight patients with periodic leg movements in sleep (PLMS). None were taking medications at the time of the investigation. All subjects were treated with the EMS-250 Neuromuscular Stimulator, which has a maximum output per channel of 1.5mA and a frequency of 47Hz. Stimuli were delivered via a pulse train (on for 1.5sec and off for 1.8sec). A single all-night polysomnogram after this stimulation showed that all patients responded to stimulation, with reduction of leg movements from an average pretreatment PLMS index of 44.6 per hour to a posttreatment PLMS index of 14 per hour (p less than .01). Nocturnal leg movements were primarily reduced during the non-REM sleep. Multiple indices of sleep continuity did not change significantly, although there was a trend toward better sleep consolidation.

Magnetic resonance imaging as a sensitive and specific predictor of neoplasms removed for intractable epilepsy.

Twenty-three patients had magnetic resonance imaging (MRI) and computed tomography (CT) of the head prior to surgery for medically intractable epilepsy. Eleven patients had neoplasms, mostly astrocytomas. Six of the 11 tumors were seen on CT. In five of the six cases, the MRI showed a focal area of increased signal on T2-weighted images. All 11 tumors were detected by MRI. None of the non-neoplastic lesions produced an abnormal T2-weighted signal area on MRI. Only one of the non-neoplastic lesions was seen on both CT and on MRI. MRI allowed clear discrimination between tumors and non-neoplastic lesions in patients coming to surgery for intractable epilepsy.

Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group.

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.

Landau-Kleffner syndrome. Treatment with subpial intracortical transection.

Landau-Kleffner syndrome (LKS) is an acquired epileptic aphasia occurring in childhood and associated with a generally poor prognosis for recovery of speech. It is thought to be the result of an epileptogenic lesion arising in speech cortex during a critical period of development. Utilizing a new surgical technique designed to eliminate the capacity of cortical tissue to generate seizures while preserving the normal cortical physiological function, we have treated 14 children with aphasia, seizures and a severely abnormal EEG by multiple subpial transection of the epileptogenic cortex. Seven of the 14 patients (50%) have recovered age-appropriate speech, are in regular classes in school and no longer require speech therapy. Four of the 14 (29%) have shown marked improvement, are speaking and understanding verbal instruction but are still receiving speech therapy. Thus, 11 of the 14 (79%), none of whom had used language to communicate for at least 2 years, are now speaking--a rate of sustained improvement considered unusual in this disorder. This study documents the value of a treatment modality not previously used in LKS. Success depends on selection of cases having severe epileptogenic abnormality that can be demonstrated to be unilateral in origin despite a bilateral electrographic manifestation.