Kaarkuzhali B. Krishnamurthy

Depth of EEG Suppression and Outcome in Barbiturate Anesthetic Treatment for Refractory Status Epilepticus

Summary: Purpose: Barbiturate anesthetic treatment of patients with refractory status epilepticus (RSE) is often titrated to a burst‐suppression record on the EEG. We sought to determine whether the depth of EEG suppression correlated with persistent seizure control in such patients.

Relapse and Survival After Barbiturate Anesthetic Treatment of Refractory Status Epilepticus

Summary: Purpose: Pentobarbital is standard treatment for refractory status epilepticus (SE) and is almost uniformly effective, but the morbidity of treatment and the mortality of refractory SE are high. Recurrence of SE after pentobarbital discontinuation may predict a worsened outcome. We sought to determine the optimal use of barbiturate anesthetic treatment of refractory SE.

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

Summary: Purpose: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal‐associated hypoxemia.

Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use

Objective: To determine whether 1) combined oral contraceptive (COC) use affects serum levels of valproate (VPA) as well as lamotrigine (LTG) and 2) the naturally occurring high (mid-luteal) and low (early-mid follicular) reproductive steroid level phases of the menstrual cycle might affect antiepileptic drug levels as well. Methods: This investigation compared serum antiepileptic drug levels at two timepoints during a single menstrual cycle in four groups of women with epilepsy: 12 on VPA, 12 on VPA plus COC (VPA-COC), 12 on LTG, and 12 on LTG plus COC (LTG-COC). Results: Both VPA and LTG levels were lower (p < 0.01) on active COC than on inactive pill with median declines of 23.4% for the VPA-COC group and 32.6% for the LTG-COC group. Serum LTG levels showed a notable but not significant 31.3% median decline during the mid-luteal phase compared to the early-mid follicular phase in the non-COC group. The non-COC valproate group showed the least change of any group between the two measured timepoints with a decline of 8.3% (p = NS). Conclusions: The findings suggest that valproate (VPA), like lamotrigine (LTG), has substantially and significantly lower serum levels while women take active combined oral contraceptives as compared to inactive pills. Larger sample sizes will be required to determine whether LTG levels may drop significantly also during the luteal (high steroid) phase of natural menstrual cycles and whether VPA levels may show greater stability in levels across the phases of the menstrual cycle. AED = antiepileptic drug; BMI = basal metabolic index; COC = combined oral contraceptive; EIAED = enzyme-inducing antiepileptic drug; IGE = idiopathic generalized epilepsy; LRE = localization-related epilepsy; LTG = lamotrigine; VPA = valproate.

Postictal heart rate oscillations in partial epilepsy

We report postictal heart rate oscillations in a heterogeneous group of patients with partial epilepsy. This pattern is marked by the appearance of transient but prominent low-frequency heart rate oscillations (0.01 to 0.1 Hz) immediately after 5 of 11 seizures recorded in 5 patients. This finding may be a marker of neuroautonomic instability and, therefore, may have implications for understanding perturbations of heart rate control associated with partial seizures.

Managing Epilepsy During Pregnancy: Assessing Risk and Optimizing Care

Opinion statementEpilepsy is the most common neurologic condition found in pregnancy. As such, all neurologists, internists, and obstetricians should know how to counsel women with epilepsy as they are considering pregnancy. While all of the usual recommendations for women of childbearing potential apply, including preconceptual and ongoing use of folic acid, calcium, and vitamin D, additional consideration must be given to the need for adjustment or change of anticonvulsant therapy. Monotherapy with the lowest dose of medication needed to control seizures should be prescribed prior to conception. Most anticonvulsants have a favorable profile when used in pregnancy; older anticonvulsants such as valproate and carbamazepine should be avoided, as they are associated with higher rates of fetal malformation, and in the case of valproate, with proven cognitive deficits in children exposed to this medication in utero. With use of any anticonvulsant medication, dosing throughout pregnancy will need to be adjusted to maintain an appropriate serum concentration. Dosing of anticonvulsants needs to be decreased after delivery to avoid medication-related toxicity, although sleep deprivation and hormonal fluctuation can increase the risk of seizures in postpartum women. With proper management, the majority of women with epilepsy can have uneventful pregnancies and healthy babies.

Technical implementation and clinical findings/results of monitoring oxygen saturation in patients referred for long term EEG monitoring

Recent technical developments allow the recording of a patients oxygen saturation (SpO2) simultaneously with intensive long-term EEG monitoring (LTM). Clinically significant information from this enhanced multi-system physiological monitoring device can contribute to more accurate diagnoses in patients referred for LTM. This report covers the technical usage of combined SpO2/EEG recordings in a small group of patients. Clinically, the findings on the SpO2 monitor helped to define the diagnosis in many of these patients. In a few, the SpO2 changes were diagnostic in their own right and prompted referral to our Sleep Disorders Laboratory. From a research aspect, the details of the morphology and timing of the oxygen desaturations and EEG show several interesting relationships with respect to the dynamics of seizure semiology and respiratory physiology.

Sleep spindle alterations in patients with malformations of cortical development

Malformations of cortical development are disorders of altered brain anatomy and architecture that arise from abnormalities in the usual processes of cerebral cortical development. Although they often lead to epilepsy, cognitive delay, and motor impairment, little is known about their effect on sleep. Since malformations may anatomically or functionally disrupt the cerebral circuits that mediate sleep spindles, we hypothesized that these disorders would be associated with abnormal spindle characteristics. We analyzed the density, maximum frequency, laterality and distribution of sleep spindles seen in routine and long-term electroencephalographic recordings performed in ten brain malformation subjects and ten matched controls. There were no significant differences in spindle density or maximum frequency between the two groups, but malformation subjects had a significantly lower proportion of bilateral spindles and a significantly higher proportion of anterior and diffuse spindles compared to controls. In addition, unilateral malformations appeared to be associated with a skewing of unilateral spindles toward the contralateral side. Our findings suggest that brain malformations disrupt the thalamocortical circuits responsible for sleep spindle generation, and support the need for further studies on the relationships between cortical maldevelopment and sleep.

Phenobarbital and benzodiazepine assisted withdrawal of prolonged pentobarbital treatment for refractory status epilepticus

Status epilepticus (SE) usually responds to standard therapy, including phenytoin, benzodiazepines, and phenobarbital, but some patients require more prolonged treatment with benzodiazepine infusions or pentobarbital. Relapse of seizures and SE can occur when those drugs are discontinued, and tapering a patient from those treatments can be difficult. We report the successful control of refractory SE requiring over 7 weeks of pentobarbital therapy in which high doses of lorazepam, along with maintenance of phenytoin and phenobarbital, were helpful in tapering the pentobarbital without relapse. Some patients can make an excellent recovery after prolonged pentobarbital treatment, but several other anticonvulsants may be necessary in tapering the pentobarbital.

Folic Acid Supplementation

A 26-year-old woman is taking valproic acid for her stable Juvenile Myoclonic Epilepsy. There has been no other seizure medication which controlled her convulsive seizures except for valproic acid. She is taking prenatal vitamins since she is sexually active. Would you recommend higher dose of folic acid to her? How would you counsel her regarding the evidence for the dose you are recommending? Would it change your management if she was taking lamotrigine, topiramate, or levetiracetam?