Contraceptive vaginal ring reduces lamotrigine levels.

OBJECTIVE: The objective of the study was to describe the effect of the vaginal ring and transdermal patch on lamotrigine serum levels in women with epilepsy. BACKGROUND: Previous studies demonstrate that oral hormonal contraceptives containing synthetic estrogen increase lamotrigine clearance through induction of glucuronidation. This leads to variable lamotrigine serum concentrations throughout monthly cycles in women who are on combined oral contraceptives (COCs). The effects of estrogen-containing nonoral hormonal contraceptive methods, including the vaginal ring and transdermal patch, on lamotrigine pharmacokinetics are not well described. METHODS: Retrospective chart review was performed to identify serum lamotrigine levels drawn from women with epilepsy while on the active phase of vaginal ring or transdermal patch and while off contraception. Wilcoxon signed-rank tests for paired data were used to compare the difference in dose-corrected lamotrigine concentration in plasma between values while on hormonal contraception to those while off contraception in patients using a vaginal ring. RESULTS: Six patients were using the vaginal ring, and one patient was using the transdermal patch. Lamotrigine dose-corrected concentrations were decreased during the active phase of the vaginal ring compared with concentrations during the period off contraception (p = .04). There was one patient without a decrease in concentration, but the other five patients on the vaginal ring had a decrease in dose-corrected lamotrigine concentration ranging from 36 to 70% while on the vaginal ring. Similarly, one patient using the transdermal patch had a decrease of 37% in dose-corrected lamotrigine concentration while on the patch. CONCLUSIONS: The findings support that the vaginal ring contraceptive method decreases lamotrigine concentrations during the active phase of treatment. This has important implications for contraceptive counseling and maintaining therapeutic levels in women of childbearing age with epilepsy.

Counseling by epileptologists affects contraceptive choices of women with epilepsy.

INTRODUCTION: There are several important interactions between antiepileptic drugs (AEDs) and hormonal contraception that need to be carefully considered by women with epilepsy (WWE) and their practitioners. Many AEDs induce hepatic enzymes and decrease the efficacy of hormonal contraception. In addition, estrogen-containing hormonal contraception can increase the metabolism of lamotrigine, the most commonly prescribed AED in women of childbearing age. The intrauterine device (IUD) is a highly effective form of reversible contraception without AED drug interactions that is considered by many to be the contraceptive of choice for WWE. Women with epilepsy not planning pregnancy require effective contraceptive counseling that should include discussion of an IUD. There are no guidelines, however, on who should deliver these recommendations. The objective of this study was to explore the hypothesis that contraceptive counseling by a neurologist can influence the contraceptive choices of WWE. In particular, we explored the relationship between contraceptive counseling in the epilepsy clinic and the likelihood that patients would obtain an IUD. METHODS: We conducted a retrospective chart review of female patients age 18-45 seen at our institution for an initial visit between 2010 and 2014 to ascertain the type of contraceptive counseling each patient received as well as AED use and contraceptive methods. Patients who were pregnant or planning pregnancy at the first visit were excluded from further analyses as were patients with surgical sterilization. We also examined a subgroup of 95 patients with at least 4 follow-up visits to evaluate the efficacy of epileptologists' counseling. Specifically, we looked at the likelihood a patient obtained an IUD based on the type of counseling she had received. Fisher exact tests assessed associations between counseling type and whether patients had obtained an IUD. RESULTS: Three hundred and ninety-seven women met criteria for inclusion. Only 35% of female patients were counseled about contraception at the first visit. If women were not counseled at the first visit, they were unlikely to be counseled at subsequent visits; only 37% had ever received counseling by their fourth visit. Of the 95 patients who completed 4 visits, 28.4% were counseled about an IUD as an optimal contraceptive choice, 38.9% were generally counseled about contraceptive interactions, and 32.6% were not counseled about contraception. Women with epilepsy who received IUD-specific counseling were significantly more likely to switch to an IUD (44.4%) compared with women who received no contraceptive counseling (6.5%; p=0.0009). Women with epilepsy who received IUD-specific counseling also tended to switch to an IUD more often than those women receiving general counseling about AEDs and contraceptive interactions (18.9%; p=0.027). There was no significant difference in the likelihood of acquiring an IUD between the general counseling and no counseling groups. CONCLUSIONS: Contraceptive counseling by epileptologists and specific mention of an IUD is significantly associated with patient selection of an IUD as a contraceptive method. This suggests that neurologists can play an important role in patients' contraceptive choices.

"Ictal" lateralized periodic discharges.

OBJECTIVE: Whether lateralized periodic discharges (LPDs) represent ictal or interictal phenomena, and even the circumstances in which they may represent one or the other, remains highly controversial. Lateralized periodic discharges are, however, widely accepted as being ictal when they are time-locked to clinically apparent symptoms. We sought to investigate the characteristics of "ictal" lateralized periodic discharges (ILPDs) defined by time-locked clinical symptoms in order to explore the utility of using this definition to dichotomize LPDs into "ictal" and "nonictal" categories. METHODS: Our archive of all continuous EEG (cEEG) reports of adult inpatients undergoing prolonged EEG monitoring for nonelective indications between 2007 and 2011 was searched to identify all reports describing LPDs. Lateralized periodic discharges were considered ILPDs when they were reported as being consistently time-locked to clinical symptoms; LPDs lacking a clear time-locked correlate were considered to be "nonictal" lateralized periodic discharges (NILPDs). Patient charts and available neuroimaging studies were also reviewed. Neurophysiologic localization of LPDs, imaging findings, presence of seizures, discharge outcomes, and other demographic factors were compared between patients with ILPDs and those with NILPDs. p-Values were adjusted for false discovery rate (FDR). RESULTS: One thousand four hundred fifty-two patients underwent cEEG monitoring at our institution between 2007 and 2011. Lateralized periodic discharges were reported in 90 patients, 10 of whom met criteria for ILPDs. Nine of the patients with ILPDs demonstrated motor symptoms, and the remaining patient experienced stereotyped sensory symptoms. Ictal lateralized periodic discharges had significantly increased odds for involving central head regions (odds ratio [OR]=11; 95% confidence interval [CI]=2.16-62.6; p=0.018, FDR adjusted), with a trend towards higher proportion of lesions involving the primary sensorimotor cortex (p=0.09, FDR adjusted). CONCLUSIONS: When defined by the presence of a time-locked clinical correlate, ILPDs appear to be strongly associated with a central EEG localization. This is likely due to cortical irritability in central head regions having greater propensity to manifest with positive, clinically apparent, and time-locked symptoms. Thus, dichotomization of ILPDs and NILPDs on this basis principally reflects differences in underlying anatomical locations of the periodic discharges rather than providing a clinically salient categorization.

Assessment of a quasi-piezoelectric mattress monitor as a detection system for generalized convulsions.

The risk of sudden unexpected death in epilepsy (SUDEP) is highest with nocturnal, unattended generalized convulsions, and basic resuscitation may be able to prevent SUDEP. This study investigates an under-mattress device (ElectroMechanical Film - Emfit®) which is triggered by rhythmic motor activity of a specifiable duration, frequency, and intensity using a quasi-piezoelectric material sensitive to changes in mattress pressure. The device was tested during inpatient video-EEG monitoring. Eighteen GTCSs were recorded, 10 out of wakefulness and 8 out of sleep. Sixteen of the 18 seizures (89%) resulted in Emfit® activation with both false negative alarms occurring during wakefulness. On average, the device was activated within 9 s of onset of bilateral clonic motor movements (range: -37 to +39 s) and occurred, on average, 45 s before seizure end (range: 19 to 76 s). Only 21 false alarms were encountered, all occurring during wakefulness (PPV: 43%). The data suggest that the Emfit® detection device has a high predictive value for generalized convulsions, offers caregivers a reliable and early warning to assist the patient during convulsions, and may be a novel way to prevent SUDEP.

Auditory hallucinations as ictal phenomena in a patient with voltage-gated potassium channel antibody-associated limbic encephalitis.

Limbic encephalitis involving anti-voltage-gated potassium channel antibodies (VGKC-LE) has become increasingly recognised, with seizures and psychotic features, such as hallucinations being typical clinical manifestations. Though the literature supports auditory hallucinations as ictal phenomena, there are no reported cases of these hallucinations correlating with electrographic seizure for this disease entity. Early recognition of auditory hallucinations as seizures could alter treatment and subsequently affect short-term outcomes in these patients. We report the case of a patient with auditory hallucinations and progressive cognitive decline, as well as serological evidence of VGKC antibodies, in whom ictal hallucinations were identified by continuous video-EEG monitoring. This case highlights the subtlety of this entity, in both clinical and electrographic detection. [Published with video sequences].

Ictal sensory periodic lateralized epileptiform discharges.

We describe the case of a 74-year-old man with left parietal arteriovenous malformation (AVM) and cerebral white matter radiation necrosis who developed persistent subjective right-sided groin pulsations. The EEG revealed left parietal periodic lateralized epileptiform discharges (PLEDs) time-locked to these sensations, confirming that the patient's symptoms represented sensory seizures with ictal PLEDs as the electrographic correlate. To our knowledge, this is the first reported case of ictal PLEDs manifesting as sensory seizures.

Anticonvulsant use and outcomes after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There are few data on the effectiveness and side effects of antiepileptic drug therapy after intracerebral hemorrhage. We tested the hypothesis that antiepileptic drug use is associated with more complications and worse outcome after intracerebral hemorrhage. METHODS: We prospectively enrolled 98 patients with intracerebral hemorrhage and recorded antiepileptic drug use as either prophylactic or therapeutic along with clinical characteristics. Antiepileptic drug administration and free phenytoin serum levels were retrieved from the electronic medical records. Patients with depressed mental status underwent continuous electroencephalographic monitoring. Outcomes were measured with the National Institutes of Health Stroke Scale and modified Rankin Scale at 14 days or discharge and the modified Rankin Scale at 28 days and 3 months. We constructed logistic regression models for poor outcome at 3 months with a forward conditional model. RESULTS: Seven (7%) patients had a clinical seizure, 5 on the day of intracerebral hemorrhage. Phenytoin was associated with more fever (P=0.03), worse National Institutes of Health Stroke Scale at 14 days (23 [9 to 42] versus 11 [4 to 23], P=0.003), and worse modified Rankin Scale at 14 days, 28 days, and 3 months. In a forward conditional logistic regression model, phenytoin prophylaxis was associated with an increased risk of poor outcome (OR, 9.8; 1.4 to 68.6; P=0.02), entering after admission National Institutes of Health Stroke Scale and age. Excluding patients with a seizure did not change the results. Levetiracetam was not associated with demographics, seizures, complications, or outcomes. CONCLUSIONS: Phenytoin was associated with more fever and worse outcomes after intracerebral hemorrhage.

Facial nerve electromyographic monitoring to predict movement in patients titrated to a standard anesthetic depth.

BACKGROUND: Facial nerve (FN) monitoring has been accepted as a standard of care in craniofacial, middle ear, and skull-based surgeries as a means of reducing iatrogenic injury, localizing the FN, and predicting postoperative neurologic function. Past studies have also shown that FN electromyographic monitoring (FNEMG) may have some clinical utility as a monitor of anesthetic depth and predicting patient movement. In this study, we evaluated Bispectral Index (BIS) and FNEMG using two different anesthetic techniques to determine whether these monitors can be used to predict movement in patients undergoing skull-based surgical procedures. METHODS: Using a single-blinded, randomized, controlled clinical trial, the relationship between FNEMG monitoring and BIS to predict movement during specific craniofacial and skull-based surgeries performed under general anesthesia was evaluated. In addition, a total IV anesthetic (TIVA) technique, using propofol and remifentanil, was compared with an inhaled anesthetic technique, using desflurane (DES), to determine which regimen provides the best conditions of adequate anesthesia and prevents movement in nonparalyzed patients undergoing a surgical procedure requiring FNEMG monitoring. RESULTS: The TIVA technique produced better hemodynamic conditions compared with DES. No significant differences were noted in BIS values between the two groups. However, FNEMG activity was lower in the TIVA group during emergence from the effects of anesthesia. More patients moved during anesthesia with DES compared with TIVA, and of the 10 patients who moved, eight had significant FNEMG activity. The positive predictive value of the FNEMG for movement was found to be 38%, and the negative predictive value was 95%. There was no significant change from baseline values in hemodynamics or BIS value for patients who experienced movement compared with those who did not move with FNEMG activity. CONCLUSION: This study shows that FNEMG may be an effective monitor for predicting patient movement when undergoing craniofacial and skull-based surgeries. BIS monitoring, however, was not an adequate monitor to predict movement in this patient population. The DES group had more hemodynamic variability and FNEMG activity, whereas TIVA proved to be a more effective anesthetic in preventing patient movement when clinically titrated to produce stable operation conditions. FNEMG was a useful clinical tool to help predict and prevent movement in these patients.

Interictal Epileptiform Discharge Detection in EEG in Different Practice Settings.

OBJECTIVE: The goal of the study was to measure the performance of academic and private practice (PP) neurologists in detecting interictal epileptiform discharges in routine scalp EEG recordings. METHODS: Thirty-five EEG scorers (EEGers) participated (19 academic and 16 PP) and marked the location of ETs in 200 30-second EEG segments using a web-based EEG annotation system. All participants provided board certification status, years of Epilepsy Fellowship Training (EFT), and years in practice. The Persyst P13 automated IED detection algorithm was also run on the EEG segments for comparison. RESULTS: Academic EEGers had an average of 1.66 years of EFT versus 0.50 years of EFT for PP EEGers (P < 0.0001) and had higher rates of board certification. Inter-rater agreement for the 35 EEGers was fair. There was higher performance for EEGers in academics, with at least 1.5 years of EFT, and with American Board of Clinical Neurophysiology and American Board of Psychiatry and Neurology-E specialty board certification. The Persyst P13 algorithm at its default setting (perception value = 0.4) did not perform as well at the EEGers, but at substantially higher perception value settings, the algorithm performed almost as well human experts. CONCLUSIONS: Inter-rater agreement among EEGers in both academic and PP settings varies considerably. Practice location, years of EFT, and board certification are associated with significantly higher performance for IED detection in routine scalp EEG. Continued medical education of PP neurologists and neurologists without EFT is needed to improve routine scalp EEG interpretation skills. The performance of automated detection algorithms is approaching that of human experts.

Clinical classification of post anoxic myoclonic status.

INTRODUCTION: Despite decades of research into the prognostic significance of post anoxic myoclonic status (MS), no consistent definition has been used to describe its clinical appearance. We set out to characterize the clinical features of MS and hypothesized that there are distinct clinical subtypes that may have prognostic implications. METHODS: Video EEG reports from 2008 to 2016 were searched to identify adult patients with post anoxic MS defined as persistent myoclonus for >30min beginning within 3days of cardiac arrest in a comatose patient. Forty-three patients met inclusion and exclusion criteria. To generate definitions of the clinical features of MS, we reviewed videos of 23 cases and characterized 3 distinct clinical semiologies. An additional 20 cases were independently reviewed and categorized by 3 raters to evaluate inter-rater agreement (IRA). All 43 patients were assigned to a group based on consensus review for the first 23 patients and majority agreement for IRA patients. We also examined the relationship between semiology and outcome. RESULTS: Three distinct clinical semiologies of MS were identified: Type 1: distal, asynchronous, variable; type 2: axial or axial and distal, asynchronous, variable; and type 3: axial, synchronous, stereotyped. For IRA, Gwet's kappa was 0.64 indicating substantial agreement. Two of 3 type 1 patients (66.6%) and 7.4% of type 2 followed commands whereas none of type 3 followed commands (p=0.03). CONCLUSION: We defined and validated a classification system of post anoxic MS based on clinical semiology. This classification may be a useful bedside prognostication tool.

SUNCT syndrome: Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing.

The SUNCT syndrome refers to Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing. It is characterized by brief attacks of severe unilateral pain in the orbitotemporal region, associated with ipsilateral cranial autonomic disturbances. All SUNCT patients experience ipsilateral conjunctival injection and lacrimation. Mean age of onset is 50 years with a male predominance. The syndrome is often misdiagnosed as trigeminal neuralgia or cluster headache. Primary and secondary forms exist, the secondary form is most commonly associated with lesions of the posterior fossa or pituitary adenoma. The SUNCT syndrome is refractory to most commonly employed therapies. Lamotrigine has recently been reported as an effective first line therapy.

Topiramate, pseudotumor cerebri, weight-loss and glaucoma: an ophthalmologic perspective.

Approved for the treatment of epilepsy and migraine prophylaxis, topiramate also acts as a carbonic anhydrase inhibitor implying a potential role in the treatment of pseudotumor cerebri (PTC). Topiramate has a propensity to cause anorexia with consequent weight loss, which alone may be curative in PTC. Prescribers must be aware of several reported cases of acute secondary angle-closure glaucoma reported in patients treated with topiramate.