Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes.

In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

OBJECTIVES: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. METHODS: We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. RESULTS: Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). SIGNIFICANCE: These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Patient-specific structural connectivity informs outcomes of responsive neurostimulation for temporal lobe epilepsy.

OBJECTIVE: Responsive neurostimulation is an effective therapy for patients with refractory mesial temporal lobe epilepsy. However, clinical outcomes are variable, few patients become seizure-free, and the optimal stimulation location is currently undefined. The aim of this study was to quantify responsive neurostimulation in the mesial temporal lobe, identify stimulation-dependent networks associated with seizure reduction, and determine if stimulation location or stimulation-dependent networks inform outcomes. METHODS: We modeled patient-specific volumes of tissue activated and created probabilistic stimulation maps of local regions of stimulation across a retrospective cohort of 22 patients with mesial temporal lobe epilepsy. We then mapped the network stimulation effects by seeding tractography from the volume of tissue activated with both patient-specific and normative diffusion-weighted imaging. We identified networks associated with seizure reduction across patients using the patient-specific tractography maps and then predicted seizure reduction across the cohort. RESULTS: Patient-specific stimulation-dependent connectivity was correlated with responsive neurostimulation effectiveness after cross-validation (p = .03); however, normative connectivity derived from healthy subjects was not (p = .44). Increased connectivity from the volume of tissue activated to the medial prefrontal cortex, cingulate cortex, and precuneus was associated with greater seizure reduction. SIGNIFICANCE: Overall, our results suggest that the therapeutic effect of responsive neurostimulation may be mediated by specific networks connected to the volume of tissue activated. In addition, patient-specific tractography was required to identify structural networks correlated with outcomes. It is therefore likely that altered connectivity in patients with epilepsy may be associated with the therapeutic effect and that utilizing patient-specific imaging could be important for future studies. The structural networks identified here may be utilized to target stimulation in the mesial temporal lobe and to improve seizure reduction for patients treated with responsive neurostimulation.

Generalized paroxysmal fast activity in EEG: An unrecognized finding in genetic generalized epilepsy.

OBJECTIVE: To study generalized paroxysmal fast activity (GPFA) in patients with genetic generalized epilepsy (GGE). INTRODUCTION: GPFA is an electroencephalographic (EEG) finding in patients with symptomatic generalized epilepsy consisting of 15-25Hz bifrontally predominant generalized fast activity seen predominantly in sleep. Historically GPFA is linked to epileptic encephalopathy with drug resistant epilepsy and intellectual disability. However, GPFA has been rarely described as an atypical finding in patients with GGE without negative prognostic implication. We report cognitive profile and seizure characteristics in seven patients with GGE and GPFA. METHODS: The Vanderbilt EMU and EEG reports were searched for the keywords "idiopathic generalized epilepsy", "GPFA"and "generalized spike and wave discharges (GSWD)". We reviewed the EEG tracings and the electronic medical records of patients thus identified. The seizure type, frequency, neurological work-up, clinical profile and imaging data were recorded. RESULTS: Awake and sleep states were captured on EEGs of all patients. On EEG tracing review six patients were confirmed to have GSWD and GPFA; one patient had GPFA but no GSWD. All patients had normal cognitive function. Four had a normal brain MRI and one a normal head CT (two were never imaged). None of the patients had tonic seizures. The main seizure type was generalized tonic-clonic seizures (GTCS) in five patients, absence in two. Age at onset of epilepsy ranged from 4 to 24years. The mean GTC seizure frequency at the time of EEG was 3; two patients were seizure free on two antiepileptic drugs (AEDs). CONCLUSIONS: GPFA can be an unrecognized electrographic finding in patients with genetic generalized epilepsy. While GPFA remains an important diagnostic EEG feature for epileptic encephalopathy (Lennox-Gastaut syndrome) it is not specific for this diagnosis. Thus, GPFA may have a spectrum of variable phenotypic expression. The finding of GPFA is not necessarily indicative of unfavorable outcome.

Temporal lobe origin is common in patients who have undergone epilepsy surgery for hypermotor seizures.

RATIONALE: Hypermotor seizures are most often reported from the frontal lobe but may also have temporal, parietal, or insular origin. We noted a higher proportion of patients with temporal lobe epilepsy in our surgical cohort who had hypermotor seizures. We evaluated the anatomic localization and surgical outcome in patient with refractory hypermotor seizures who had epilepsy surgery in our center. METHODS: We identified twenty three patients with refractory hypermotor seizures from our epilepsy surgery database. We analyzed demographics, presurgical evaluation including semiology, MRI, PET scan, interictal/ictal scalp video-EEG, intracranial recording, and surgical outcomes. We evaluated preoperative variables as predictors of outcome. RESULTS: Most patients (65%) had normal brain MRI. Intracranial EEG was required in 20 patients (86.9%). Based on the presurgical evaluation, the resection was anterior temporal in fourteen patients, orbitofrontal in four patients, cingulate in four patients, and temporoparietal in one patient. The median duration of follow-up after surgery was 76.4months. Fourteen patients (60%) had been seizure free at the last follow up while 3 patients had rare disabling seizures. CONCLUSIONS: Hypermotor seizures often originated from the temporal lobe in this series of patients who had epilepsy surgery. This large proportion of temporal lobe epilepsy may be the result of a selection bias, due to easier localization and expected better outcome in temporal lobe epilepsy. With extensive presurgical evaluation, including intracranial EEG when needed, seizure freedom can be expected in the majority of patients.

Does adherence to epilepsy quality measures correlate with reduced epilepsy-related adverse hospitalizations? A retrospective experience.

In 2011, the American Academy of Neurology (AAN) established eight epilepsy quality measures (EQMs) for chronic epilepsy treatment to address deficits in quality of care. This study assesses the relationship between adherence to these EQMs and epilepsy-related adverse hospitalizations (ERAHs). A retrospective chart review of 475 new epilepsy clinic patients with an ICD-9 code 345.1-9 between 2010 and 2012 was conducted. Patient demographics, adherence to AAN guidelines, and annual number of ERAHs were assessed. Fisher's exact test was used to assess the relationship between adherence to guidelines (as well as socioeconomic variables) and the presence of one or more ERAH per year. Of the eight measures, only documentation of seizure frequency, but not seizure type, correlated with ERAH (relative risk [RR] 0.343, 95% confidence interval [CI] 0.176-0.673, p = 0.010). Among patients in the intellectually disabled population (n = 70), only review/request of neuroimaging correlated with ERAH (RR 0.128, 95% CI 0.016-1.009, p = 0.004). ERAHs were more likely in African American patients (RR 2.451, 95% CI 1.377-4.348, p = 0.008), Hispanic/Latino patients (RR 4.016, 95% CI 1.721-9.346, p = 0.016), Medicaid patients (RR 2.217, 95% CI 1.258-3.712, p = 0.009), and uninsured patients (RR 2.667, 95% CI 1.332-5.348, p = 0.013). In this retrospective series, adherence to the eight AAN quality measures did not strongly correlate with annual ERAH.

Interictal discharge traveling waves recorded from stereoelectroencephalography electrodes.

OBJECTIVE: Interictal epileptiform discharges (IEDs) are intermittent high-amplitude electrical signals that occur between seizures. They have been shown to propagate through the brain as traveling waves when recorded with epicortical grid-type electrodes and small penetrating microelectrode arrays. However, little work has been done to translate experimental IED analyses to more clinically relevant platforms such as stereoelectroencephalography (SEEG). In this pilot study, the authors aimed to define a computational method to identify and characterize IEDs recorded from clinical SEEG electrodes and leverage the directionality of IED traveling waves to localize the seizure onset zone (SOZ). METHODS: Continuous SEEG recordings from 15 patients with medically refractory epilepsy were collected, and IEDs were detected by identifying overlapping peaks of a minimum prominence. IED pathways of propagation were defined and compared to the SOZ location determined by a clinical neurologist based on the ictal recordings. For further analysis of the IED pathways of propagation, IED detections were divided into triplets, defined as a set of 3 consecutive contacts within the same IED detection. Univariate and multivariate linear regression models were employed to associate IED characteristics with colocalization to the SOZ. RESULTS: A median (range) of 22.6 (4.4-183.9) IEDs were detected per hour from 15 patients over a mean of 23.2 hours of recording. Depending on the definition of the SOZ, a median (range) of 20.8% (0.0%-54.5%) to 62.1% (19.2%-99.4%) of IEDs per patient traversed the SOZ. IEDs passing through the SOZ followed discrete pathways that had little overlap with those of the IEDs passing outside the SOZ. Contact triplets that occurred more than once were significantly more likely to be detected in an IED passing through the SOZ (p < 0.001). Per our multivariate model, patients with a greater proportion of IED traveling waves had a significantly greater proportion of IEDs that localized to the SOZ (ß = 0.64, 95% CI 0.01-1.27, p = 0.045). CONCLUSIONS: By using computational methods, IEDs can be meaningfully detected from clinical-grade SEEG recordings of patients with epilepsy. In some patients, a high proportion of IEDs are traveling waves according to multiple metrics that colocalize to the SOZ, offering hope that IED detection, with further refinement, could serve as an alternative method for SOZ localization.

Long-Term Intracranial EEG Lateralization of Epileptogenicity in Patients With Confirmed or Suspected Bilateral Mesial Temporal Lobe Onsets During Epilepsy Surgical Evaluation.

PURPOSE: The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah. METHODS: Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records. RESULTS: Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes (>1 year), and 25 patients had enough recorded data (>6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG. CONCLUSIONS: Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.

Long term video/EEG prevents unnecessary vagus nerve stimulator implantation in patients with psychogenic nonepileptic seizures.

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are common paroxysmal events that mimic and can often be misdiagnosed as epileptic seizures. PNES account for 10 to 40% of patients referred to epilepsy centers. Patients with uncontrolled PNES are at times subjected to vagus nerve stimulator (VNS) implantation. We report a series of such referred patients studied with video/EEG monitoring at our institution. METHODS: We evaluated patients who were implanted with a VNS by their primary neurologist for refractory seizures and who were referred to the Vanderbilt University epilepsy monitoring unit for a second opinion. The presumed diagnosis of epilepsy was based on abnormal routine EEG studies obtained by their primary neurologist. We evaluated these patients and recorded their typical spells between 2005 and 2009. We describe the results of 13 patients with VNS who were found to have PNES. The total number of patients with a VNS studied during this time was 60. RESULTS: None of the patients had undergone prior long-term video/EEG monitoring to document the nature of their events. A total of 13 patients with an implanted VNS had exclusive PNES, 9 women and 4 men with a mean age of 38.2±10.4 years. Mean age at seizure onset was 28.5±15.4 years. Patients were taking two to four antiepileptic medications in addition to VNS at the time of video/EEG monitoring. The average latency from the time of VNS implantation to the confirmatory diagnosis was 2.8 years. One to ten (median=3) of these patients' typical seizures were recorded during video/EEG monitoring. All patients were subsequently discharged off antiepileptic medications, and five of these patients were discharged home with the VNS turned off. CONCLUSION: A VNS may be implanted inappropriately in patients with PNES. As video/EEG monitoring may help in excluding the diagnosis of PNES and preventing unnecessary VNS implants, it should be a requirement before VNS implantation.

Wearable Reduced-Channel EEG System for Remote Seizure Monitoring.

Epitel has developed Epilog, a miniature, wireless, wearable electroencephalography (EEG) sensor. Four Epilog sensors are combined as part of Epitel's Remote EEG Monitoring platform (REMI) to create 10 channels of EEG for remote patient monitoring. REMI is designed to provide comprehensive spatial EEG recordings that can be administered by non-specialized medical personnel in any medical center. The purpose of this study was to determine how accurate epileptologists are at remotely reviewing Epilog sensor EEG in the 10-channel "REMI montage," with and without seizure detection support software. Three board certified epileptologists reviewed the REMI montage from 20 subjects who wore four Epilog sensors for up to 5 days alongside traditional video-EEG in the EMU, 10 of whom experienced a total of 24 focal-onset electrographic seizures and 10 of whom experienced no seizures or epileptiform activity. Epileptologists randomly reviewed the same datasets with and without clinical decision support annotations from an automated seizure detection algorithm tuned to be highly sensitive. Blinded consensus review of unannotated Epilog EEG in the REMI montage detected people who were experiencing electrographic seizure activity with 90% sensitivity and 90% specificity. Consensus detection of individual focal onset seizures resulted in a mean sensitivity of 61%, precision of 80%, and false detection rate (FDR) of 0.002 false positives per hour (FP/h) of data. With algorithm seizure detection annotations, the consensus review mean sensitivity improved to 68% with a slight increase in FDR (0.005 FP/h). As seizure detection software, the automated algorithm detected people who were experiencing electrographic seizure activity with 100% sensitivity and 70% specificity, and detected individual focal onset seizures with a mean sensitivity of 90% and mean false alarm rate of 0.087 FP/h. This is the first study showing epileptologists' ability to blindly review EEG from four Epilog sensors in the REMI montage, and the results demonstrate the clinical potential to accurately identify patients experiencing electrographic seizures. Additionally, the automated algorithm shows promise as clinical decision support software to detect discrete electrographic seizures in individual records as accurately as FDA-cleared predicates.

Probabilistic comparison of gray and white matter coverage between depth and surface intracranial electrodes in epilepsy.

In this study, we quantified the coverage of gray and white matter during intracranial electroencephalography in a cohort of epilepsy patients with surface and depth electrodes. We included 65 patients with strip electrodes (n = 12), strip and grid electrodes (n = 24), strip, grid, and depth electrodes (n = 7), or depth electrodes only (n = 22). Patient-specific imaging was used to generate probabilistic gray and white matter maps and atlas segmentations. Gray and white matter coverage was quantified using spherical volumes centered on electrode centroids, with radii ranging from 1 to 15 mm, along with detailed finite element models of local electric fields. Gray matter coverage was highly dependent on the chosen radius of influence (RoI). Using a 2.5 mm RoI, depth electrodes covered more gray matter than surface electrodes; however, surface electrodes covered more gray matter at RoI larger than 4 mm. White matter coverage and amygdala and hippocampal coverage was greatest for depth electrodes at all RoIs. This study provides the first probabilistic analysis to quantify coverage for different intracranial recording configurations. Depth electrodes offer increased coverage of gray matter over other recording strategies if the desired signals are local, while subdural grids and strips sample more gray matter if the desired signals are diffuse.

Aphasic or amnesic status epilepticus detected on PET but not EEG.

PURPOSE: To describe five patients with ictal aphasia and one patient with ictal amnesia, who had focal positron emission tomography (PET) hypermetabolism but no clear ictal activity on electroencephalography (EEG). METHODS: (18)F-Fluorodeoxyglucose (FDG)-PET scans with concomitant EEG were obtained in five patients with suspected ictal aphasia or ictal amnesia without ictal activity on EEG. We reviewed medical history, EEG, imaging data, and treatment outcome. RESULTS: Brain magnetic resonance imaging (MRI) showed no structural abnormalities in any of the patients. EEG showed left temporal irregular delta activity in three patients, with aphasia and nonspecific abnormalities in two other patients, all without clear ictal pattern. All patients demonstrated focal hypermetabolism on PET scan. The hypermetabolism was in the left frontotemporal region in patients with ictal aphasia and in the bilateral hippocampal region in the patient with amnesia. Three patients who received intravenous benzodiazepines during their episodes had transient clinical improvement. With antiepileptic drug (AED) treatment, symptoms gradually resolved in all patients. Concomitant resolution of PET hypermetabolism was documented in three patients who had follow up scans. One patient with ictal aphasia later developed recurrent episodes, each with recurrent PET hypermetabolism. This patient and one other patient required immune-modulating therapy in addition to AEDs. DISCUSSION: FDG-PET imaging should be considered as a diagnostic tool in patients with suspected ictal aphasia or amnesia, who fail to show clear evidence of ictal activity on EEG.

Localization value of ictal turning prone.

PURPOSE: Ictal semiology complements ictal EEG in identifying the likely epileptogenic zone. Ictal turning prone (ITP) with body turning of 90 ° or more can be seen with frontal lobe epilepsies. The aim of our study was to evaluate the localizing value of ITP in a general population of patients undergoing long term video-EEG monitoring. METHODS: We reviewed our epilepsy monitoring unit database for adult patients with recorded habitual seizures with ITP. All 16 patients identified had continuous video-EEG monitoring using standard scalp electrodes; eight patients also had intracranial EEG monitoring. We only included focal seizures without evolution to bilateral tonic-clonic activity. RESULTS: We identified 16 patients with ITP, mean age of 32.5 years (range 18-50). ITP was consistently seen in at least one focal impaired awareness seizure of all patients. Ictal onset zone on scalp EEG was left temporal in five, right temporal in three, left frontal convexity in two, right frontal convexity in two, probable right medial frontal in three and probable left medial frontal in one patient. Direction of ITP was uni-directional in 12 patients while 4 patients had ITP in opposite direction in different seizures. Nine patients underwent epilepsy surgery; five patients had Engel class I outcome and four patients had Engel class III outcome. CONCLUSIONS: Ictal turning prone does not have a consistent single localizing or lateralizing value and can be seen with various epileptogenic zones including medial frontal, lateral frontal or temporal. ITP direction can vary even with a single epileptogenic zone.

Revisiting the laterality of wicket spikes with continuous EEG.

PURPOSE: Wicket spikes (WS) are a benign EEG variant classically defined to be bilateral independent temporal in localization. The authors observed that the majority of WS are exclusively unilateral temporal. The aim was to identify the laterality and clinical significance of the WS. METHODS: Epilepsy monitoring unit reports of adult patients were searched for keywords "wicket" or "wickets" and examined for WS lateralization dividing it into three groups: bilateral, left, and right temporal. The age, sex, hand dominance, admission duration, epilepsy risk factors, cerebral microvascular disease, and final diagnosis were also collected. RESULTS: Wicket spikes were present in 133 studies and were significantly more prevalent in the left temporal region (69%, P < 0.05). Cerebral microvascular disease was more prevalent in patients with left temporal WS (64%, P < 0.05). There were no differences in the remaining studied variables among the three groups. Wicket spikes were not associated with epilepsy. CONCLUSIONS: The authors' findings demonstrate that the majority of WS are strictly left temporal. Despite their predominant unilaterality, WS are not associated with epilepsy but may be associated with cerebral microvascular disease. The authors propose redefining the WS lateralization to be mostly unilateral rather than bilateral. This may prevent misinterpretation of this challenging yet benign EEG variant.

Temporal Lobe Encephaloceles: A Potentially Curable Cause of Seizures.

OBJECTIVE: Temporal lobe encephaloceles are characterized by protrusion of brain parenchyma through a structural defect in the floor of the middle fossa. They have been reported to cause cerebrospinal fluid (CSF) leaks, conductive hearing loss, meningitis, and seizures. The association between temporal encephaloceles and epileptiform activity is particularly rare. PATIENTS: All patients who presented to a single tertiary referral center between 2011 and 2014 with intractable seizures and radiographic evidence of a middle cranial fossa encephalocele were evaluated. Five patients from this subset who underwent surgical repair of their encephalocele are presented. INTERVENTION(S): Middle cranial fossa approach for encephalocele repair. MAIN OUTCOME MEASURE(S): Postoperative epileptiform activity. RESULTS: Five patients underwent a craniotomy for resection of a temporal lobe encephalocele with repair of a middle fossa floor defect. After surgery, CSF rhinorrhea resolved, when present, and all patients remained seizure-free through their last available follow-up. Range of follow-up time was 3.5 months to 4 years. Average follow-up time was 19.7 months. CONCLUSION: Temporal lobe encephaloceles are an infrequent cause of seizures. Given that these lesions can be missed with standard imaging modalities, they are likely underdiagnosed upon initial medical evaluation. This diagnosis should be considered in patients with intractable seizures. If an encephalocele is found, focused resection of epileptogenic tissue associated with herniation and repair of the temporal floor defect can provide definitive treatment.

Psychogenic pseudosyncope: diagnosis and management.

Psychogenic pseudosyncope (PPS) is the appearance of transient loss of consciousness (TLOC) in the absence of true loss of consciousness. Psychiatrically, most cases are classified as conversion disorder, which is hypothesized to represent the physical manifestation of internal stressors. The incidence of PPS is likely under-recognized and the disorder is under investigated in the unexplained syncope population, yet it can be diagnosed accurately with a focused history and confirmed with investigations including head-up tilt testing (HUTT), electroencephalogram (EEG; sometimes combined with video) or, in some centers, transcranial Doppler (TCD). Patients are more likely to be young females with an increased number of episodes over the past 6months. They frequently experience symptoms prior to their episodes including light-headedness, shortness of breath and tingling. Conversion disorder is associated with symptomatic chronicity, increased psychiatric and physical impairment, and diminished quality of life. Understanding the epidemiology, biological underpinnings and approach to diagnosis of PPS is important to improve the recognition of this disorder so that patients may be managed appropriately. The general treatment approach involves limiting unnecessary interventions, providing the patient with needed structure, and encouraging functionality. While there are no treatment data available for patients with PPS, studies in related conversion disorder populations support the utility of psychotherapy. Psychotropic medications should be considered in patients with comorbid psychiatric disorders.

Similar response to anti-epileptic medications among epileptic siblings.

BACKGROUND: When epilepsy does not respond to the initial anti-epileptic drug (AED) the subsequent search for an effective AED is predominantly a matter of trial and error, as only limited criteria exist for rational AED selection. Since epilepsy in siblings is likely to be relatively homogeneous, we hypothesized that an AED effective in one sibling would also be effective in the other. METHODS: We reviewed the antiepileptic medication response among nine sets of epileptic siblings (19 patients) in our practice. All but one patient were drug-resistant at one point during their treatment course. RESULTS: Eight sets of siblings (17 individuals) became seizure-free or almost seizure-free with treatment modification and using a medication proven effective for one sibling in the other siblings. The medication change that produced seizure freedom was lamotrigine monotherapy in two families, valproate monotherapy in one, lamotrigine adjunctive therapy in two, lamotrigine-levetiracetam combination in two, and lamotrigine-valproate combination in one family. In one remaining family with generalized epilepsy, one sibling was seizure-free on phenobarbital while the other had persistent seizures despite polytherapy. CONCLUSIONS: Our results indicated that siblings with epilepsy tend to respond to the same AED monotherapy or AED combination.

Pregabalin in the management of partial epilepsy.

Pregabalin is a new antiepileptic medication that works by binding to alpha 2 delta subunit of the voltage-dependent calcium channels present in presynaptic neurons. Its pharmacokinetic advantages include rapid and almost complete absorption, lack of protein binding, linear kinetics, absence of enzyme induction, and absence of interactions with other drugs. Pregabalin was found effective as adjunctive therapy for refractory partial-onset seizures, with up to 51% responder at a dose of 600 mg/day. The lowest effective dose was 150 mg/day. Pregabalin is also approved for treatment of painful diabetic polyneuropathy, postherpetic neuralgia and pain with fibromyalgia. Studies also suggest a beneficial effect on sleep and generalized anxiety disorders. Its main adverse effects in randomized adjunctive trials in adults have been mild to moderate. Most common side effects were dizziness, ataxia, somnolence and diplopia. Weight gain was not prominent in pivotal pregabalin trials, but was more problematic in long-term postmarketing analyses in epilepsy patients. Pregabalin, with its potent antiseizure effect, favorable pharmacokinetic profile, and effectiveness in common co-morbidities is an important addition to the treatment of epilepsy.

Management of new-onset epilepsy in the elderly.

The incidence of new-onset epilepsy is high among elderly patients. Seizures can present differently to and with more subtle semiology than those in younger adults. This difference in presentation frequently poses a diagnostic challenge. Elderly patients also often have comorbidities, are usually on multiple medications that can interact, have altered medication pharmacokinetics, and tend to be particularly sensitive to adverse effects of medication. Seizures in the elderly tend, however, to respond better to antiepileptic drugs than those in younger individuals, and can often be appropriately controlled with monotherapy. After the diagnosis of epilepsy is confirmed, treatment should be started with a single medication at a low dose, with subsequent gradual upward titration until seizures are controlled. First-generation antiepileptic drugs should be avoided in the elderly in view of poor tolerability. A large trial has shown that lamotrigine and gabapentin are better tolerated than carbamazepine. In elderly patients whose seizures remain uncontrolled on antiepileptic medications, surgery can be considered if excellent results are predicted and the risks are low.