Milk production of cows grazing pasture supplemented with grain mixes containing canola meal or corn grain or both over the first 100 days of lactation.

Grain mixes varying in proportions of wheat grain, barley grain, canola meal, and corn grain were fed to grazing dairy cows in early lactation to determine the contribution of canola meal and corn grain to milk yield, BW, BCS, eating behavior, and blood serum metabolite concentrations. The experiment used 80 multiparous, seasonally calving Holstein-Friesian dairy cows during the first 100 d of lactation, the treatment period, and over the subsequent carryover period of 100 d, during which all cows were fed a common diet. Cows were divided into 4 cohorts (blocks) based on calving date and within each cohort, 5 cows were randomly allocated to each of the 4 treatments. Dietary treatments included disc-milled grain mixes comprising (on a DM basis) (1) a control treatment of wheat (25%) and barley (75%); (2) wheat (25%), barley (50%), and canola meal (25%); (3) wheat (25%), barley (50%), and corn (25%), and (4) wheat (25%), barley (25%), canola meal (25%), and corn (25%). Treatment diets were introduced at 19 DIM ± 4.7 d, which included a 7-d adaptation period and were applied up until 100 DIM. Each grain mix was fed at 9 kg of DM/cow per day, offered twice daily, in equal proportions in the parlor at milking times. In addition to the grain mix, all cows grazed perennial ryegrass pasture at a daily allowance of ∼35 kg of DM/cow per day (measured to ground level). Results were analyzed in terms of corn and canola presence or absence in the diet. Including canola meal in grain mixes increased grain intake and pasture intake by 0.6 and 2.1 kg of DM/cow per day, respectively, resulting in an increased milk yield of 2.6 kg/cow per day during the first 100 d of lactation. Including canola meal also increased yields of milk fat and protein, and concentrations of milk fat, as well as increasing mean BW and BCS over the 100 d. The inclusion of canola meal in the grain mixes also resulted in greater blood serum BHB and urea concentrations, compared with feeding grain mixes that did not contain canola meal. The inclusion of corn grain provided no milk production benefits and did not change BW, BCS, or any feeding behavior variables. There were no carryover effects on milk production from either canola meal or corn grain after the treatment period. In summary, the results demonstrate that the provision of canola meal in grain mixes can improve milk production and increase mean BCS. Further, there are no benefits to milk yield when a proportion of barley is substituted for corn, in a wheat and barley grain mix fed to grazing dairy cows in early lactation. However, these results are dependent on the level of inclusion and the feeding system employed.

Influence of proportion of wheat in a pasture-based diet on milk yield, methane emissions, methane yield, and ruminal protozoa of dairy cows.

Wheat is the most common concentrate fed to grazing dairy cows in Australia, but no studies have examined the effects of wheat proportion in a pasture-based diet on milk production and methane emissions. In this 47-d experiment, 32 Holstein dairy cows were offered 1 of 4 diets during d 1 to 36. Cows in each of the dietary treatment groups were individually offered no wheat (W0) or wheat at 3 kg of dry matter (DM)/d (W3), 6 kg of DM/d (W6), or 9 kg of DM/d (W9). The remainder of the diet was 2.2 kg of DM of concentrate mix and freshly harvested perennial ryegrass (Lolium perenne) such that all individual cows were offered a total diet of approximately 20.2 kg of DM/d. From d 37 to 47 the diets of cows receiving treatments W0 and W3 remained unchanged, but cows in treatments W6 and W9 received the W3 diet. Individual cow feed intakes, milk yields, milk compositions, and methane emissions were measured for d 31 to 35 (period 1) and d 45 to 47 (period 2). During period 1, the mean intakes of cows offered the W0, W3, W6, and W9 diets were 19.2, 20.4, 20.2, and 19.8 kg of DM/d. Diet caused differences in energy-corrected milk, and means for W0, W3, W6, and W9 were 29.5, 32.4, 33.0, and 32.9 kg/d, respectively. Milk fat percentage differed with respective means of 3.93, 3.94, 3.69, and 3.17. Diets also caused differences in methane emissions, with means for W0, W3, W6, and W9 of 440, 431, 414, and 319 g/d. During period 1, the cows fed the W9 diet produced less methane and had lower methane yields (g/kg of DMI) and intensities (g/kg of energy-corrected milk) than cows fed the W3 diet. However, in period 2 when the wheat intake of cows in the W9 treatment was reduced to the same level as in the W3 treatment, their methane emissions, yields, and intensities were similar to those offered the W3 treatment, yet protozoa numbers in ruminal fluid were still much lower than those in cows offered the W3 treatment. Our research shows that for diets based on perennial ryegrass and crushed wheat, only the diet containing more than 30% crushed wheat resulted in substantially depressed milk fat concentration and reduced methane emissions, methane yield, and methane intensity. Thus, although feeding a diet with a high proportion of wheat can cause substantial methane mitigation, it can come at the cost of depression in milk fat concentration.

Effect of dietary fat supplementation on methane emissions from dairy cows fed wheat or corn.

Diets that contain high proportions of either wheat or supplementary fat have been individually reported to reduce enteric methane production. The objective of this research was to determine the effect of dietary fat supplementation on methane emissions and milk yield from cows fed diets containing either corn or wheat grains. It was hypothesized that cows fed a diet containing wheat would produce less methane and have lower methane yield (methane per kg of dry matter intake; MY) than cows fed a diet containing corn and that methane mitigation from fat supplementation would occur irrespective of the type of grain in the basal diet. The experiment involved 32 Holstein-Friesian dairy cows allocated to 1 of 4 treatment groups (n = 8) and individually fed different diets restricted to approximately 90% of their mean ad libitum intake measured during a covariate period. All animals were offered 11.5 kg of dry matter/d of alfalfa hay, 1.8 kg of dry matter/d of solvent-extracted canola meal, and 1 of 4 dietary supplements. Dietary supplements were 8 kg of dry matter/d of either corn or wheat, or these same treatments with the addition of 0.8 kg of canola oil. In this 5-wk experiment, d 1 to 7 served as the covariate period, d 8 to 14 as the transition period, d 15 to 28 as the adaptation period, and d 29 to 35 as the experimental period. Cows were fed their full treatment diets from d 15 to 35 during which time milk production and feed intake were measured daily. During d 29 to 35, methane production was measured for individual cows daily using the sulfur hexafluoride tracer method. The resulting averages for milk production and feed intake were analyzed by analysis of covariance with factorial grain by fat as treatment structure, animal as the unit within blocks, and the corresponding milk production or feed intake covariate averages as principal covariate. Data on milk fatty acids, ruminal fluid data on pH, ammonia, volatile fatty acids, protozoa, and methane were analyzed by ANOVA using the same treatment and blocking structures excluding the principal covariate. Cows fed a diet containing wheat had greater MY than cows fed a diet containing corn. Irrespective of the type of grain in the diet, increasing the fat concentration from 2 to 6% dry matter reduced MY. It is concluded that the grain component in the basal diet does not affect the mitigating effects of dietary fat supplements on MY.

Adaptation responses in milk fat yield and methane emissions of dairy cows when wheat was included in their diet for 16 weeks.

Short-term studies have shown that feeding dairy cows diets containing a high proportion (>40%) of wheat may result in reduced milk fat concentration and reduced CH4 emissions (g of CH4/cow per d), but no long-term studies have been done on these responses. This study compared the milk production and CH4 responses when 24 dairy cows were fed diets containing high proportions of either wheat or corn over 16 wk. Cows were assigned to 2 groups and offered a diet (CRN) containing 10.0 kg of dry matter/d of crushed corn grain, 1.8 kg of dry matter/d of canola meal, 0.2 kg of dry matter/d of minerals, and 11.0 kg of dry matter/d of chopped alfalfa hay or a similar diet (WHT) in which wheat replaced the corn. Dry matter intake and milk yields of individual cows were measured daily. Methane emissions from individual cows were measured using controlled climate respiration chambers over 2 consecutive days during each of wk 4, 10, and 16. Milk composition was measured on the 2 d when cows were in chambers during wk 4, 10, and 16. Over the 16-wk experimental period, total dry matter intake remained relatively constant and similar for the 2 dietary treatment groups. At wk 4, CH4 emission, CH4 yield (g of CH4/kg of dry matter intake), milk fat yield, and milk fat concentration were substantially less in cows fed the WHT diet compared with the same metrics in cows fed the CRN diet; but these differences were not apparent at wk 10 and 16. The responses over time in these metrics were not similar in all cows. In 4 cows fed the WHT diet, CH4 yield, milk fat concentration, and milk fat yield remained relatively constant from wk 4 to 16, whereas for 5 fed the WHT diet, their CH4 emissions, milk fat yields, and milk fat concentrations almost doubled between wk 4 and 16. In the short term (4 wk), the inclusion of approximately 45% wheat instead of corn in the diet of cows resulted in reductions of 39% in CH4 yield, 35% in milk fat concentration, and 40% in milk fat yield. However, these reductions did not persist to wk 10 or beyond. Our data indicate that cows do not all respond in the same way with some "adaptive" cows showing a marked increase in CH4 yield, milk fat concentration, and milk fat yield after wk 4, whereas in other "nonadaptive" cows, these metrics were persistently inhibited to 16 wk. This research shows that short-term studies on dietary interventions to mitigate enteric CH4 emissions may not always predict the long-term effects of such interventions.

Influence of feeding supplements of almond hulls and ensiled citrus pulp on the milk production, milk composition, and methane emissions of dairy cows.

Almond hulls and citrus pulp have been fed to dairy cows with variable responses for milk production, but no information exists on their effect on enteric methane emissions. This experiment examined the effects of dietary supplementation with either almond hulls or ensiled citrus pulp on the milk yield, milk composition, and enteric methane emissions of dairy cows. Thirty-two Holstein dairy cows in mid lactation were offered 1 of 3 diets over a 28-d experiment. Twelve cows received a control (CON) diet, 10 cows a diet containing almond hulls (ALH), and 10 cows a diet containing ensiled citrus pulp (CIT). All cows were offered 6.0 kg of dry matter (DM)/d of crushed corn, 2.0 kg of DM/d of cold-pressed canola, and 0.2 kg of DM/d of a mineral mix. In addition, cows fed the CON diet were offered 14.5 kg of DM/d of alfalfa cubes; cows fed the ALH diet were offered 10.5 kg of DM/d of alfalfa cubes and 4.0 kg of DM/d of almond hulls; and cows on the CIT diet were offered 11.5 kg of DM/d of alfalfa cubes and 3.0 kg of DM/d of ensiled citrus pulp. Milk yield was measured daily and milk composition was measured on 4 d of each week. Individual cow methane emissions were measured by a sulfur hexafluoride tracer technique on d 24 to 28 of the experiment. The mean milk yield of cows fed the CON diet (27.4 kg/d) was greater than the mean milk yield of cows fed the ALH diet (24.6 kg/cow per day), whereas the mean milk yield of cows fed the CIT diet (26.2 kg/cow per day) was not different from the mean milk yield from cows fed the other 2 diets. Dietary treatment did not influence the concentrations of milk fat, protein, and lactose or fat yields, but the mean protein yield from cows fed the CON diet (0.87 kg/d) was greater than that from cows fed the ALH diet (0.78 kg/d) but not different to those fed the CIT diet (0.85 kg/d). In general, we found no differences in the proportion of individual fatty acids in milk. The mean pH of ruminal fluid from cows offered the CON diet was not different to the pH in the ruminal fluids of cows offered the ALH or the CIT diets. The mean methane emissions (g/d) and yields (g/kg of DM intake) were not influenced by dietary treatment. These findings indicate that, although almond hulls and ensiled citrus pulp can be used as a low-cost feed supplement, almond hulls did negatively affect milk production and neither inhibited enteric methane emissions.

Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery.

BACKGROUND: Left anterior temporal lobectomy (L-ATL) may be complicated by confrontation naming deficits. OBJECTIVE: To determine whether preoperative fMRI predicts such deficits in patients with epilepsy undergoing L-ATL. METHODS: Twenty-four patients with L-ATL underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language dominance, and pre- and postoperative neuropsychological testing. fMRI laterality indexes (LIs), reflecting the interhemispheric difference between activated volumes in left and right homologous regions of interest, were calculated for each patient. Relationships between the fMRI LI, Wada language dominance, and naming outcome were examined. RESULTS: Both the fMRI LI (p < 0.001) and the Wada test (p < 0.05) were predictive of naming outcome. fMRI showed 100% sensitivity and 73% specificity in predicting significant naming decline. Both fMRI and the Wada test were more predictive than age at seizure onset or preoperative naming performance. CONCLUSIONS: Preoperative fMRI predicted naming decline in patients undergoing left anterior temporal lobectomy surgery.

Postmarketing experience with topiramate and cognition.

Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited central nervous system (CNS) side effects. However, CNS-related treatment-emergent adverse events (TEAEs) often occur in patients receiving AEDs. Topiramate (TPM) is an AED proven to be safe and effective as adjunctive treatment for epilepsy patients with partial seizures. Double-blind, placebo-controlled, multicenter trials demonstrated potential effects on cognition. The P.A.D.S. (post-marketing antiepileptic drug survey) group, a cooperative group of 14 epilepsy centers that collaborate on obtaining data about new AEDs and devices, prospectively collected standardized data forms before and during treatment with TPM for epilepsy, and analyzed the postmarketing experience of CNS TEAEs with TPM. Our results from 701 treated patients show that cognitive complaints were the most common reason to discontinue TPM. The presence of complaints did have predictive value if the patient would discontinue TPM, although was not specific as to when discontinuation would occur. The spectrum of complaints in our open-label prospective multicenter postmarketing study was similar to those observed in controlled clinical trials. We were unable to demonstrate a specific population, dose titration, or concomitant AED that was at risk to discontinue treatment. We conclude that most patients treated with TPM will continue therapy beyond 6 months. Cognitive complaints and not efficacy reflect the primary reason for discontinuing therapy. Psychomotor slowing was the most common complaint, yet most patients elect to continue treatment, with "better" or "much better" ratings of both seizure and global improvement during treatment.

Magnetic resonance analysis of postsurgical temporal lobectomy.

BACKGROUND AND PURPOSE: The effect of temporal lobe transection area, volume of postoperative gliosis, and surgical technique on patients' seizure-free outcome is unknown. The authors studied the effects of these variables on patients' seizure-free outcome. METHODS: A retrospective review of magnetic resonance imaging examinations acquired 3 to 18 months after temporal lobe resection was carried out for 18 patients with intractable temporal lobe seizures and known postsurgical outcomes for more than 2 years. The total volume of radiologically probable gliosis evident on axial proton-density-weighted images was calculated for each patient using software on an independent console. The total area of temporal lobe surface transected by the scalpel was calculated as well, using sagittal T1-weighted images. The total volume of gliosis, the total area of transected temporal lobe, and the specific type of surgery (sparing vs no sparing of the superior temporal gyrus) were then correlated with the postsurgical outcome of the patients. An examiner with no prior knowledge of the patients' postsurgical outcomes carried out the above calculations and measurements. The patients' postoperative outcome was defined using Engel classifications, and patients were divided into 2 groups: group A with Engel class 1 (n = 9) and group B with Engel classes 2-4 (n = 9). RESULTS: The mean volumes of postoperative gliosis were not significantly different between group A (3592.3 mm3) and group B (4270 mm3). The mean area of transected temporal lobe was also similar between group A (1865.2 mm2) and group B (1930 mm2). With regard to surgical technique, there were 5 patients who had the superior temporal gyrus resected and 13 who did not. Eighty percent of patients with the superior temporal gyrus resected were Engel class 1 or 2, whereas only 20% were of Engel class 3 or 4. CONCLUSIONS: The authors found no clear association between postoperative outcome and residual temporal lobe gliosis, the surgical technique, or the total area of temporal lobe transected by the scalpel.

Prognostic value of the consistency of lateralizing ictal features and ictal EEG in patients undergoing temporal lobectomy for refractory complex partial seizures.

PURPOSE: Ictal and postictal clinical manifestations have lateralizing value in the presurgical evaluation of intractable seizures. The consistency and frequency of these signs during seizures and the associated implications for postoperative seizure outcome are unknown. METHODS: The videotaped complex partial seizures of 49 patients with known postoperative outcomes greater than 2 years after temporal lobectomy were blindly reviewed for: (1) unilateral hand posturing (UHP), (2) unilateral hand automatism (UHA), (3) forced and nonforced head turning (HT), and (4) postictal dysphasia (PID). The presence and laterality of each assessable sign were recorded. Data were analyzed as follows: (1) the prevalence of each sign in patients with Engel class 1 and Engel class 2-4, and (2) the postsurgical outcome when the sign was present in more than or less than 50% of the seizures for each patient. We reviewed patients' presurgical work-up, specifically ictal EEG and MRI. RESULTS: The prevalence of UHP, UHA, HT, and PID was similar for Engel class 1 and Engel class 2-4 patients. Engel class 1 outcome when UHP, UHA, HT, and PID were present for greater than 50% of seizures was no different compared to when these signs were present for less than 50% of seizures. Patients who had concordant ictal EEG and MRI abnormalities had the best postsurgical outcome. CONCLUSIONS: The consistency and frequency of ictal manifestations in the presurgical evaluation of complex partial seizures does not predict seizure outcome. The presence of any specific lateralizing sign need not be present in every complex partial seizure for the sign to hold predictive value. Concordant ictal EEG and MRI abnormalities are still the best predictors of outcome.

Memory outcome after left anterior temporal lobectomy in patients with expected and reversed Wada memory asymmetry scores.

PURPOSE: The ideal candidate for anterior temporal lobectomy surgery shows a Wada memory asymmetry (WMA) score characterized by better memory performance in the hemisphere contralateral to the seizure focus relative to the ipsilateral (surgical) hemisphere. However, some surgical candidates show a reversed WMA or better Wada memory performance in the hemisphere of surgical interest relative to the hemisphere contralateral to the seizure focus. To date, no data are available contrasting memory and seizure outcome for these two Wada groups. The present study compared memory and seizure outcome after left anterior temporal lobectomy (L-ATL) in patients showing expected and reversed WMA scores, and also examined the relationship of the individual hemisphere Wada memory scores for predicting verbal memory outcome after L-ATL. METHODS: We compared 6-month postoperative verbal memory change scores and seizure outcome in L-ATL patients with either an expected (n=12) or reversed WMA (n=9) pattern on Wada memory testing. RESULTS: L-ATL patients showing a reversed WMA score had a poorer verbal memory outcome and poorer seizure control after surgery compared with patients showing a WMA score in the expected direction. CONCLUSIONS: L-ATL patients with a reversed WMA score have a greater risk for memory morbidity and poorer seizure outcome than do patients with a WMA score in the expected direction. The WMA score was the best predictor of memory outcome after L-ATL. When the WMA score is not considered, both individual Wada hemisphere scores (contralateral and ipsilateral) provided significant and independent contribution to predicting postoperative verbal memory functioning. These findings are discussed in the context of the functional reserve and hippocampal adequacy models of memory change after temporal lobectomy.

Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.

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.

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.

Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05.

OBJECTIVE: To perform an open-label, long-term efficacy and safety/tolerability study of vagus nerve stimulation (VNS) of 454 patients with refractory epilepsy. METHODS: Subjects were enrolled from five clinical trials of VNS between 1988 and 1995 after undergoing an implantation of a pulse generator in the chest and a left cervical vagus nerve-stimulating lead coil. Patients were assessed at 6-month intervals until device approval. Seizure frequencies, medication treatment, and adverse events (AEs) were recorded and entered into a database. RESULTS: A total of 454 patients were implanted, and 440 patients yielded assessable data. A > or =50% seizure reduction postimplantation occurred in 36.8% of patients at 1 year, in 43.2% at 2 years, and in 42.7% at 3 years. Median seizure reductions compared with baseline were 35% at 1 year, 44.3% at 2 years, and 44.1% at 3 years. Most common AEs postimplantation at 1 year were hoarseness (28%) and paraesthesias (12%), at 2 years were hoarseness (19.8%) and headache (4.5%), and at 3 years was shortness of breath (3.2%). Continuation rates were 96.7% at 1 year, 84.7% at 2 years, and 72.1% at 3 years. CONCLUSION: Long-term, open-label vagus nerve stimulation (VNS) provided seizure reduction similar to or greater than acute studies, for median reductions and for those reaching a > or =50% seizure reduction. VNS remained safe and well tolerated, with nearly three-quarters of the patients choosing to continue therapy.

Language dominance in neurologically normal and epilepsy subjects: a functional MRI study.

Language dominance and factors that influence language lateralization were investigated in right-handed, neurologically normal subjects (n = 100) and right-handed epilepsy patients (n = 50) using functional MRI. Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic, auditory discrimination task provided an index of language system lateralization. As expected, the majority of both groups showed left hemisphere dominance, although a continuum of activation asymmetry was evident, with nearly all subjects showing some degree of right hemisphere activation. Using a categorical dominance classification, 94% of the normal subjects were considered left hemisphere dominant and 6% had bilateral, roughly symmetric language representation. None of the normal subjects had rightward dominance. There was greater variability of language dominance in the epilepsy group, with 78% showing left hemisphere dominance, 16% showing a symmetric pattern and 6% showing right hemisphere dominance. Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right hand dominance. Language lateralization in the normal group was weakly related to age, but was not significantly related to sex, education, task performance or familial left-handedness.

Gabapentin.

Gabapentin (GBP) is a antiepileptic drug (AED) indicated as adjunct therapy for treatment of partial seizures, with and without secondary generalization, in patients 12 and older with epilepsy. GBP (1-(aminomethyl) cyclohexaneacetic acid) is structurally related to gamma-aminobutyric acid (GABA), which readily crosses the blood-brain barrier. Radiolabeled GBP binds throughout the central nervous system in anatomic areas important in treatment of seizures. Its precise mechanism of action is unknown. An open-label, dose-ranging study of doses up to 1,800 mg produced > or =50% seizure reductions [responder rate (RR)] in 29% of patients with partial seizures. Three double-blind, placebo-controlled, parallel add-on trials at doses of 300-1,800 mg have produced RR of up to 28%, with a placebo RR of 8-10%. An active controlled, parallel group comparison of 600 mg to 2,400 mg in monotherapy conversion design showed no significant difference among the 600 mg, 1,200 mg, and 2,400 mg groups compared to a placebo group. An inpatient, active-controlled comparison of 300 mg and 3,600 mg in a parallel-design monotherapy trial showed that time to exit from the study was significantly longer for the 3,600-mg group and the completion rate significantly higher (53% vs. 17%) for patients receiving 3,600 mg/day vs. 300 mg/day of GBP. Successful double-blind, placebo-controlled trials in refractory childhood partial seizures and benign childhood epilepsy with centrotemporal spikes have been recently concluded. Absence was not successfully treated in one small double-blind trial. Open-label reports emphasize adjustments of patients to higher doses than those indicated in the package labeling. An open-label trial of GBP therapy in patients with partial seizures (n = 2,216) produced progressively greater seizure freedom rates as patients were titrated from > or =900 mg daily to > or = 1,800 mg daily (15.1% vs. 33.4%), with a similar effect on RR (18.1% vs. 44.9%). An add-on, open-label study treating partial seizures (n = 141) reported an RR of 71%, with 46% seizure-free in the last 8 weeks of treatment and doses up to 2,400 mg daily. A comparison trial of three doses of GBP to 600 mg of carbamazepine showed similar retention rates for 1,800 mg of GBP and 600 mg of CBZ. Another study reported 48% of patients experiencing 50% reduction, nine of whom had doses greater than 2,400 mg. Treatment in children has reported a 34.4% RR in 32 children with refractory partial seizures. A French open-label adjunctive trial documented a 33.9% RR; 13.4% were seizure-free during the evaluation period. Adverse experiences most commonly noted included somnolence, dizziness, and ataxia. Weight gain was sometimes reported with higher doses of GBP, and pediatric reports cite prominent behavioral changes, including hyperactivity, irritability, and agitation. GBP appears best used at doses at and potentially above those suggested in its package labeling. Although efficacy occurs at lower levels, increased GBP doses are associated with additional efficacy. Reports suggest that initiation at 2,400 mg or 3,600 mg may not be associated with increased adverse experiences. Titration to 900 or 1,200 mg on the first day of GBP therapy appear to be well tolerated.

Oxcarbazepine: double-blind, randomized, placebo-control, monotherapy trial for partial seizures.

OBJECTIVE: To evaluate the efficacy and safety of oxcarbazepine in a placebo-control trial. METHODS: A multicenter, double-blind, randomized, placebo-control, two-arm parallel group, monotherapy design was used to compare oxcarbazepine administered 1,200 mg twice daily to placebo in hospitalized patients with refractory partial seizures, including simple and complex partial seizures and partial seizures evolving to secondarily generalized seizures. Patients exited the trial after completing the 10-day double-blind treatment phase or after experiencing four partial seizures, two new-onset secondarily generalized seizures, serial seizures, or status epilepticus, whichever came first. RESULTS: Analysis of the primary efficacy variable--time to meeting one of the exit criteria--showed a statistically significant effect in favor of oxcarbazepine (p = 0.0001). The secondary efficacy variables--percentage of patients who met one of the exit criteria (p = 0.0001) and total partial seizure frequency per 9 days during the double-blind treatment (p = 0.0001)--were also statistically significant in favor of oxcarbazepine. CONCLUSION: These results demonstrate that oxcarbazepine given as monotherapy is effective and safe for the treatment of partial seizures in this paradigm.

Payer costs of patients diagnosed with epilepsy.

PURPOSE: To identify the annual cost to a third-party payer of inpatient and outpatient services and prescription drugs for patients diagnosed with epilepsy or convulsions. METHODS: Retrospective study using administrative and claims data from a private insurer in the Northeast United States with >1.8 million covered lives. Health plan members were included if they had a claim for epilepsy or convulsions and a claim for an antiepileptic drug (AED) between January 1992 and December 1996. Annual costs and frequencies of all medical services, and of services related to epilepsy, were compared among five groups of patients defined by the most intensive procedure they received: invasive therapeutic procedure (group 1); invasive diagnostic procedure without an invasive therapeutic procedure (group 2); noninvasive diagnostic procedure without an invasive procedure (group 3); neurologist or neurosurgeon visit without an invasive procedure or noninvasive diagnostic procedure (group 4); or none of the preceding services (group 5). RESULTS: In the cohort of 9,090 patients meeting the inclusion criteria, mean age was 38 years, 53% were female, 30% had malignant disease, and 25% had cardiac disease. The mean annual cost of all medical services was $9,617. Mean annual costs of all services were $43,333, $29,847, $11,300, $4,362, and $5,855, and annual costs of inpatient and outpatient encounters coded as epilepsy plus AEDs were $24,369, $10,330, $3,127, $1,079, and $1,086, in groups 1-5, respectively. Services used to stratify patients into the groups accounted for 37% of the total costs. CONCLUSIONS: The annual costs of medical services for patients with epilepsy are high and vary considerably because of treatment of epilepsy and management of comorbidities.

Clinical utility of sleep-deprived versus computer-assisted ambulatory 16-channel EEG in epilepsy patients: a multi-center study.

PURPOSE: The objective of this prospective study was to compare the usefulness of a sleep-deprived electroencephalogram (EEG) versus a computer-assisted 16-channel ambulatory EEG in patients with historical information consistent with epilepsy but with a normal or non-diagnostic initial routine EEG. METHODS: A total of 46 patients had both a 30-60 min sleep-deprived EEG and a computer-assisted ambulatory 24 h EEG. Each EEG was assigned a number and reviewed independently by two board-certified electroencephalographers for the presence of interictal epileptiform discharges and seizures. RESULTS: Both the sleep-deprived EEG and ambulatory EEG improved detection of epileptiform discharges by a similar amount (24% versus 33%); however, the ambulatory EEG detected seizures in 7/46 (15%) patients, and in three patients the seizures were solely detected by the computer. CONCLUSIONS: we conclude that the computer-assisted ambulatory EEG offers greater benefit than a sleep-deprived recording because in addition to detecting interictal epileptiform discharges, it may also capture seizures. The discovery of unsuspected seizures can significantly impact clinical management.

Is speech arrest during wada testing a valid method for determining hemispheric representation of language?

BACKGROUND AND OBJECTIVE: The intracarotid amobarbital procedure, or Wada test, is the method of choice to determine hemispheric representation of language, and is routinely used in the presurgical evaluation for intractable epilepsy. Some investigators perform comprehensive language assessments, but others base language lateralization solely on speech arrest. This study sought to determine whether speech arrest alone during Wada testing provides valid data regarding language lateralization. METHODS: The subjects (previously reported) were 21 patients evaluated for intractable epilepsy, who underwent language lateralization by Wada testing and functional MRI (FMRI). For each patient, language representation was determined by calculating: (1) a Wada laterality index based exclusively on speech arrest; (2) a Wada laterality index based on comprehensive language assessment; and (3) an FMRI laterality quotient. Correlation coefficients and categorical classifications were analyzed. RESULTS: There was no significant correlation between the Wada laterality quotient derived from duration of speech arrest and either the comprehensive Wada language laterality score (r =.35, p =.12) or FMRI language laterality score (r =.32, p =.16). Categorical classification as left, right or bilateral language also showed marked discordance between speech arrest and the other two methods. CONCLUSION: Duration of speech arrest during Wada testing is not a valid measure of language dominance.