Utility of video-EEG monitoring in a tertiary care epilepsy center.

Our video-EEG monitoring (VEEG) unit is part of a typical metropolitan tertiary care center that services a diverse patient population. We aimed to determine if the specific clinical reason for inpatient VEEG was actually resolved. Our method was to retrospectively determine the stated goal of inpatient VEEG and to analyze the outcome of one hundred consecutive adult patients admitted for VEEG. The reason for admission fit into one of four categories: 1) to characterize paroxysmal events as either epileptic or nonepileptic, 2) to localize epileptic foci, 3) to characterize the epilepsy syndrome, and 4) to attempt safe antiepileptic drug adjustment. We found that VEEG was successful in accomplishing the goal of admission in 77% of cases. The remaining 23% failed primarily due to lack of typical events during monitoring. Furthermore, of the overall study cohort, VEEG outcomes altered medical management in 53% and surgery was pursued in 5%.

Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 82/83.

This study evaluated gabapentin monotherapy in 275 patients with medically refractory complex partial or secondarily generalized seizures who were taking one or two antiepileptic drugs (AEDs). Following an 8-week baseline, patients received randomized dosages of gabapentin (600, 1,200, or 2,400 mg/d) during a 26-week double-blind phase comprising 2 weeks gabapentin add-on therapy, an 8-week AED taper, and a 16-week gabapentin monotherapy period. Patients exited the study if they experienced a protocol-defined exit event. Results of outcome measures, including time to exit, completion rate, and mean time on monotherapy, showed no significant differences among dosage groups. Possible reasons for this lack of a dose-response relationship include withdrawal seizures and the limited range of gabapentin dosages studied. Overall, 20% of patients completed the study. Completion rates were higher among patients who had discontinued one AED (23%) than two AEDs (14%), and higher among patients who were not withdrawn from carbamazepine (27%) than among those who were (16%).

On the structure of water-alcohol and ammonia-alcohol protonated clusters.

Collision-induced dissociation (CID) of protonated ammonia-alcohol and water-alcohol heteroclusters was studied using a triple quadrupole mass spectrometer with a corona discharge atmospheric pressure ionization source. CID results suggested that the ammonia-alcohol clusters had NH: at the core of the cluster and that hydrogen-bonded alcohol molecules solvated this central ion. In contrast, CID results in water-alcohol clusters showed that water loss was strongly favored over alcohol loss and that there was a preference for the charge to reside on an alcohol molecule. The results also indicated that a loose chain of hydrogen-bonded molecules was formed in the water-alcohol clusters and that there appeared to be no rigid protonation site or a fixed central ion. (J Am Soc Mass.

No evidence for a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

Juvenile myoclonic epilepsy (JME) is a distinct epileptic syndrome with a complex mode of inheritance. Several studies found evidence for a locus involved in JME on chromosome 6 near the HLA region. Recently, Elmslie et al. [1997] reported evidence of linkage in JME to chromosome 15q14 assuming a recessive mode of inheritance with 50% penetrance and 65% linked families. The area on chromosome 15q14 encompasses the location of the gene for the alpha-7 subunit of the nicotinic acetylcholine receptor. This could fit the hypothesis that there are two interacting loci, one on chromosome 6 and on chromosome 15 or that there is genetic heterogeneity in JME. In an independent dataset of JME families, we tested for linkage to chromosome 15 but found little evidence for linkage. Moreover, families with more than one family member affected with JME provide a lodscore of 3.4 for the HLA-DR/DQ haplotype on chromosome 6. The lodscore for these same families on chromosome 15q14 is <-2 assuming homogeneity and the maximum lodscore is 0.2 assuming alpha =.25. Only one of these families has a negative lodscore on chromosome 6 and a positive lodscore of 0.5 on chromosome 15q14. Our results indicate that this possible gene on chromosome 15 plays at most a minor role in our JME families. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:49-52, 2000.

Effect of topiramate on attention.

Impaired attention is a frequently reported side effect of anti-epileptic medication, as well as a frequent general complaint of epilepsy. It is thus important to evaluate the effect of new medications on attention processes. Attention was assessed weekly in ten subjects receiving topiramate over a 3 month period. Attention was evaluated with digit span, a widely used index of attention. Different number sequences were constructed and randomized to allow for repeated use. Four of nine subjects showed significant correlations between topiramate dosage and forward digit span measured weekly, such that higher dosage was associated with poorer attention. The average topiramate dosage and seizure reduction did not differ between these subjects and those who did not show a significant relationship.

Vagus nerve stimulation treatment for Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome is a severe age-specific epilepsy syndrome that presents with medication-resistant seizures in childhood. Antiepileptic drugs are the mainstay of treatment. Nonpharmacologic treatments include corpus callosum section and the ketogenic diet. However, no single treatment is safe and effective. We treated 13 patients with Lennox-Gastaut syndrome between the ages of 4 and 44 years (mean, 16.7 years) with vagus nerve stimulation. During the first 6 months of treatment, vagus nerve stimulation produced a median seizure rate reduction of 52% (range, 0% to 93%; P = .04). At 6 months of follow-up, three patients had a greater than 90% reduction in seizures, two had a greater than 75% reduction, one had a greater than 50% reduction, and six had at least a 25% reduction. One patient did not improve. No patient worsened after initial improvement. Side effects, including hoarseness, coughing, and pain in the throat, were transient and tolerable. No patient discontinued vagus nerve stimulation. Our results suggest that vagus nerve stimulation could be an effective and safe adjunct therapy for the treatment of Lennox-Gastaut syndrome.

Infantile spasms in COFS syndrome.

Cerebro-oculo-facial-skeletal (COFS) syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia and/or cataracts, neurogenic arthrogryposis, and multiple congenital anomalies. A term female infant with COFS syndrome who developed infantile spasms at the age of 3 months is reported. The patient had a good response to intramuscular ACTH with disappearance of infantile spasms and resolution of the hypsarrhythmic pattern on electroencephalography succeeded by a slow, synchronous pattern. Modified hypsarrhythmia returned after ACTH therapy was discontinued. Infantile spasms have not previously been reported in association with COFS syndrome and are a potentially treatable aspect of the disease. This patient may add to the clinical spectrum of COFS syndrome or may have a variant.

Pseudoseizures and dissociative disorders: a common mechanism involving traumatic experiences.

Patients with psychogenic non-epileptic seizures (pseudoseizures) have been diagnosed as having conversion disorder or dissociative disorder. Pseudoseizure patients frequently report a history of physical and sexual abuse, and traumatic experience is considered part of the mechanism for producing dissociation. Pseudoseizures may be a manifestation of dissociative disorder, especially when a history of sexual or physical abuse is documented. A common mechanism involving traumatic experience may be present in both pseudoseizures and dissociative disorders. A complete neurodiagnostic evaluation along with an awareness of this relationship is needed to provide appropriate care for this patient population.

Epileptogenesis: left or right hemisphere dominance? Preliminary findings in a hospital-based population.

The aim of this study was to determine if there is cerebral cortical hemispheral asymmetry in human epileptogenesis. We studied 75 epilepsy patients using electroencephalograms, neuroimaging, ictal semiology and physical examination to determine if epilepsy originates more frequently from the left or the right hemisphere. We considered epilepsy to be definitely-lateralized if one or more of these was abnormal unilaterally and there were no contradictory findings. Twenty-seven of the patients had lateralized epilepsy: 20 from the left hemisphere and seven from the right hemisphere (P< 0.05). These findings from our hospital-based ambulatory patient population suggest that the left hemisphere is more epileptogenic than the right. Further study of lateralization of epileptogenesis in a community population-based sample of incident new-onset cases seems warranted.

Accurate and reproducible ion mobility measurements for chemical standard evaluation.

Chemical standards are used to calibrate ion mobility spectrometers (IMS) for accurate and precise identification of target compounds. Research over the past 30 years has identified several positive and negative mode compounds that have been used as IMS standards. However, the IMS research community has not come to a consensus on any chemical compound(s) for use as a reference standard. Also, the reported K(0) values for the same compound analyzed on several IMS systems can be inconsistent. In many cases, mobility has not been correlated with a mass identification of an ion. The primary goal of this work was to provide mass-identified mobility (K(0)) values for standards. The results of this work were mass-identified K(0) values for positive and negative mode IMS chemical standards. The negative mode results of this study showed that TNT is a viable negative mode reference standard. New temperature-dependent K(0) values were found by characterizing drift gas temperature and water content; several examples were found of temperature-dependent changes for the ion species of several standards. The overall recommendation of this study is that proposed IMS standards should have temperature-dependent K(0) values quoted in the literature instead of using a single K(0) value for a compound.

Progesterone vs placebo therapy for women with epilepsy: A randomized clinical trial.

OBJECTIVE: To assess progesterone treatment of intractable seizures in women with partial epilepsy. METHODS: This randomized, double-blind, placebo-controlled, phase III, multicenter, clinical trial compared the efficacy and safety of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects randomized 2:1 to progesterone or placebo, stratified by catamenial and noncatamenial status. It compared treatments on proportions of ≥50% responders and changes in seizure frequency from 3 baseline to 3 treated menstrual cycles. RESULTS: There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation (C1 level) was a significant predictor of responders for progesterone but not placebo. With increasing C1 levels, responders increased from 21% to 57% with progesterone vs 19% to 20% with placebo. Reductions in seizure frequency correlated with increasing C1 levels for progesterone but not placebo, progressing from 26% to 71% for progesterone vs 25% to 26% for placebo. A prespecified clinically important separation between progesterone and placebo responders (37.8% vs 11.1%; p = 0.037) was realized among 21.4% of women who had C1 level ≥3. CONCLUSION: There was no difference in the primary outcome of ≥50% responder rates between progesterone vs placebo for catamenial or noncatamenial groups. Post hoc findings suggest that the level of perimenstrual seizure exacerbation is a significant predictor of responder rate with progesterone and that progesterone may provide clinically important benefit for a subset of women with perimenstrually exacerbated seizures. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that cyclic progesterone is ineffective in women with intractable partial epilepsy. Post hoc analysis identified a subset of women with higher levels of perimenstrual seizure exacerbation that were responsive to treatment.

Evidence-based guideline update: intraoperative spinal monitoring with somatosensory and transcranial electrical motor evoked potentials: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Clinical Neurophysiology Society.

OBJECTIVE: To evaluate whether spinal cord intraoperative monitoring (IOM) with somatosensory and transcranial electrical motor evoked potentials (EPs) predicts adverse surgical outcomes. METHODS: A panel of experts reviewed the results of a comprehensive literature search and identified published studies relevant to the clinical question. These studies were classified according to the evidence-based methodology of the American Academy of Neurology. Objective outcomes of postoperative onset of paraparesis, paraplegia, and quadriplegia were used because no randomized or masked studies were available. RESULTS AND RECOMMENDATIONS: Four Class I and 8 Class II studies met inclusion criteria for analysis. The 4 Class I studies and 7 of the 8 Class II studies reached significance in showing that paraparesis, paraplegia, and quadriplegia occurred in the IOM patients with EP changes compared with the IOM group without EP changes. All studies were consistent in showing all occurrences of paraparesis, paraplegia, and quadriplegia in the IOM patients with EP changes, with no occurrences of paraparesis, paraplegia, and quadriplegia in patients without EP changes. In the Class I studies, 16%-40% of the IOM patients with EP changes developed postoperative-onset paraparesis, paraplegia, or quadriplegia. IOM is established as effective to predict an increased risk of the adverse outcomes of paraparesis, paraplegia, and quadriplegia in spinal surgery (4 Class I and 7 Class II studies). Surgeons and other members of the operating team should be alerted to the increased risk of severe adverse neurologic outcomes in patients with important IOM changes (Level A).

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. METHODS: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. RESULTS: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. RECOMMENDATIONS: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. METHODS: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008. RESULTS: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%-92%) of remaining seizure-free during pregnancy. RECOMMENDATIONS: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C).

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. METHODS: Systematic review of relevant articles published between January 1985 and June 2007. RESULTS: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. RECOMMENDATIONS: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).

Pregnancy registries in epilepsy: a consensus statement on health outcomes.

Most pregnant women with epilepsy require antiepileptic drug (AED) therapy. Present guidelines recommend optimizing treatment prior to conception, choosing the most effective AED for seizure type and syndrome, using monotherapy and lowest effective dose, and supplementing with folate. The Epilepsy Therapy Project established the international Health Outcomes in Pregnancy and Epilepsy (HOPE) forum to learn more about the impact of AEDs on the developing fetus, particularly the role of pregnancy registries in studying AED teratogenicity. The primary outcome of interest in these registries is the occurrence of major congenital malformations, with some data collected on minor malformations. Cognitive and behavioral outcomes are often beyond the timeframe for follow-up of these registries and require independent study. The HOPE consensus report describes the current state of knowledge and the limitations to interpretations of information from the various sources. Data regarding specific risks for both older and newer AEDs need to be analyzed carefully, considering study designs and confounding factors. There is a critical need for investigations to delineate the underlying mechanisms and explain the variance seen in outcomes across AEDs and within a single AED.