Low-frequency electrical stimulation of a fiber tract in temporal lobe epilepsy.

OBJECTIVE: Surgical resection of the temporal lobe is an effective treatment for medically intractable temporal lobe epilepsy, but can cause memory impairment. Deep brain stimulation in epilepsy has targeted gray matter structures using high frequencies, but achieved limited success. We tested the hypothesis that low-frequency stimulation of the fornix reduces interictal epileptiform discharges and seizures in patients with intractable mesial temporal lobe epilepsy, without affecting memory. METHODS: We implanted depth electrodes in 11 patients for surgical evaluation of intractable epilepsy. Low-frequency stimulation of the fornix occurred in 4-hour sessions in the video-electroencephalography unit. Mental status assessment was performed at baseline and during stimulation. We studied the effect of stimulation on hippocampal spikes and seizures. RESULTS: There were no complications, and the patients were unaware of the stimulation. Fornix stimulation elicited evoked responses in the hippocampus and the posterior cingulate gyrus. Hourly Mini-Mental Status Examination (MMSE) scores showed an increase during stimulation when compared to prestimulation MMSE, largely due to improvement in recall, possibly representing a practice effect. Hippocampal spikes were significantly reduced during and outlasting each stimulation session. Seizure odds (n = 7) were reduced by 92% in the 2 days that followed stimulation. INTERPRETATION: Low-frequency stimulation of the fornix activates the hippocampus and other areas of the declarative memory circuit. The results of this preliminary study suggest that low-frequency stimulation is tolerable and reduces epileptiform discharges and seizures in patients with intractable mesial temporal lobe epilepsy. A controlled clinical trial may be warranted.

Accuracy of frame-based stereotactic depth electrode implantation during craniotomy for subdural grid placement.

BACKGROUND: Frame-based stereotaxy and open craniotomy may seem mutually exclusive, but invasive electrophysiological monitoring can require broad sampling of the cortex and precise targeting of deeper structures. OBJECTIVES: The purpose of this study is to describe simultaneous frame-based insertion of depth electrodes and craniotomy for placement of subdural grids through a single surgical field and to determine the accuracy of depth electrodes placed using this technique. METHODS: A total of 6 patients with intractable epilepsy underwent placement of a stereotactic frame with the center of the planned cranial flap equidistant from the fixation posts. After volumetric imaging, craniotomy for placement of subdural grids was performed. Depth electrodes were placed using frame-based stereotaxy. Postoperative CT determined the accuracy of electrode placement. RESULTS: A total of 31 depth electrodes were placed. Mean distance of distal electrode contact from the target was 1.0 ± 0.15 mm. Error was correlated to distance to target, with an additional 0.35 mm error for each centimeter (r = 0.635, p < 0.001); when corrected, there was no difference in accuracy based on target structure or method of placement (prior to craniotomy vs. through grid, p = 0.23). CONCLUSION: The described technique for craniotomy through a stereotactic frame allows placement of subdural grids and depth electrodes without sacrificing the accuracy of a frame or requiring staged procedures.

Can semiology predict psychogenic nonepileptic seizures? A prospective study.

OBJECTIVE: Reducing health and economic burdens from diagnostic delay of psychogenic nonepileptic seizures (PNES) requires prompt referral for video electroencephalography (VEEG) monitoring, the diagnostic gold standard. Practitioners make VEEG referrals when semiology suggests PNES, although few semiological signs are supported by well-designed studies, and most VEEG studies neglect to concurrently measure how accurately seizure witnesses can ascertain semiology. In this study, we estimate the value of eyewitness-reported and video-documented semiology for predicting PNES, and we measure accuracy of eyewitness reports. METHODS: We prospectively interviewed eyewitnesses of seizures in patients referred for VEEG monitoring, to inquire about 48 putative PNES and ES signs. Multiple, EEG-blinded, epileptologists independently evaluated seizure videos and documented the presence/absence of signs. We used generalized estimating equations to identify reliable video-documented PNES and ES signs, and we compared eyewitness reports with video findings to assess how accurately signs are reported. We used logistic regression to determine whether eyewitness reports could predict VEEG-ascertained seizure type. RESULTS: We analyzed 120 seizures (36 PNES, 84 ES) from 35 consecutive subjects. Of 45 video-documented signs, only 3 PNES signs ("preserved awareness," "eye flutter," and "bystanders can intensify or alleviate") and 3 ES signs ("abrupt onset," "eye-opening/widening," and postictal "confusion/sleep") were significant and reliable indicators of seizure type. Eyewitness reports of these 6 signs were inaccurate and not statistically different from guessing. Consequentially, eyewitness reports of signs did not predict VEEG-ascertained diagnosis. We validated our findings in a second, prospective cohort of 36 consecutive subjects. INTERPRETATION: We identified 6 semiological signs that reliably distinguish PNES and ES, and found that eyewitness reports of these signs are unreliable. We offer suggestions to improve the accuracy of eyewitness reports.

Psychogenic nonepileptic seizures.

This review by three established clinicians/researchers and two 'rising stars' in the field of psychogenic nonepileptic seizures (PNES) describes recent progress in this area and highlights priorities for future research. Empirically testable models of PNES are emerging but many questions about the aetiology of PNES remain unanswered at present. Video-EEG has made it possible for doctors to make secured diagnoses of PNES in more cases. However, unacceptable diagnostic delays and misdiagnoses are still common. Non-specific EEG changes are often misinterpreted as evidence of epilepsy. A better understanding of the symptomatology of PNES may allow earlier and more accurate diagnoses using self-report questionnaires. The communication of the diagnosis and the engagement of patient in psychological treatment can be difficult. A recent pilot RCT has demonstrated the effectiveness of a psychological treatment in reducing seizures in the short term, but longer-term effectiveness is yet to be demonstrated.

Transection of CA3 does not affect memory performance in rats.

Longitudinal hippocampal pathways are needed for seizure synchronization, and there is evidence that their transection may abolish seizures. However, the effect of such transection on memory is unknown. In this study, we investigated the effect of transverse CA3 transections on memory function in Sprague-Dawley rats. With a stereotactic knife, a single CA3 transection was made unilaterally (n=5) or bilaterally (n=5). Sham surgery was done in another group (n=4). Morris water maze and novel object recognition tests were started 18 days later and revealed no significant differences between transected animals and controls. Cresyl-violet brain staining confirmed the locations of transections in the CA3 region. We conclude that normal performances in Morris water maze and novel object recognition tests do not appear to require intact transmission throughout the whole length of CA3, supporting the hypothesis that CA3 transections may be used in temporal lobe epilepsy to interrupt seizure circuitry while preserving memory.

National Institutes of Health stroke scale assists in predicting the need for percutaneous endoscopic gastrostomy tube placement in acute ischemic stroke.

Percutaneous endoscopic gastrostomy (PEG) tubes are commonly needed for early nutrition in patients with acute ischemic stroke. We evaluated the relationship between the NIH Stroke Scale (NIHSS) score and the need for PEG tube placement. Patients with acute ischemic stroke were included in this study. We collected information on patient demographics, stroke severity as indicated by the NIHSS, and risk factors for vascular disease. We ascertained the swallowing evaluation and PEG tube placement during the same hospitalization. A hierarchical optimal classification tree was determined for the best predictors. A total of 187 patients (mean age, 67.2 years) were included, only 33 (17.6%) of whom had a PEG tube placed during the course of hospitalization. Those who had the PEG were slightly older (73.8 vs 65.8 years), had severe stroke (median NIHSS score, 18 vs 4), and a longer hospital stay (median 12 vs 4 days). Independent predictors for PEG placement included bulbar symptoms at onset, higher NIHSS score, stroke in the middle cerebral artery distribution, and aspiration pneumonia. Hierarchical analysis showed that patients with aspiration pneumonia and NIHSS score >or=12 had the highest likelihood (relative risk [RR] = 4.67; P < .0001) of requiring a PEG tube. In the absence of pneumonia, NIHSS score >or=16 yielded a moderate likelihood of requiring PEG (RR = 1.80; P < .0001). Our findings indicate that the presence of pneumonia and high NIHSS score are the best predictors for requiring PEG tube insertion in patients with ischemic stroke. These findings may have benefits in terms of early decision making, shorter hospitalization, and possible cost savings.

Seizure symptoms and ambulatory EEG findings: incidence of epileptiform discharges.

AIMS: Ambulatory video-EEG monitoring has been utilized as a cost-effective alternative to inpatient video-EEG monitoring for non-surgical diagnostic evaluation of symptoms suggestive of epileptic seizures. We aimed to assess incidence of epileptiform discharges in ambulatory video-EEG recordings according to seizure symptom history obtained during clinical evaluation. METHODS: This was a retrospective cohort study. We queried seizure symptoms from 9,221 consecutive ambulatory video-EEG studies in 35 states over one calendar year. We assessed incidence of epileptiform discharges for each symptom, including symptoms that conformed to a category heading, even if not included in the ILAE 2017 symptom list. We report incidences, odds ratios, and corresponding p values using Fisher's exact test and univariate logistic regression. We applied multivariable logistic regression to generate odds ratios for the six symptom categories that are controlled for the presence of other symptoms. RESULTS: History that included motor symptoms (OR=1.53) or automatisms (OR=1.42) was associated with increased occurrence of epileptiform discharges, whereas history of sensory symptoms (OR=0.76) predicted lack of epileptiform discharges. Patient-reported symptoms that were associated with increased occurrence of epileptiform discharges included lip-smacking, moaning, verbal automatism, aggression, eye-blinking, déjà vu, muscle pain, urinary incontinence, choking and jerking. On the other hand, auditory hallucination memory deficits, lightheadedness, syncope, giddiness, fibromyalgia and chronic pain predicted absence of epileptiform discharges. The majority of epileptiform discharges consisted only of interictal sharp waves or spikes. CONCLUSIONS: Our study shows that the use of ILAE 2017 symptom categories may help guide ambulatory video-EEG studies.

Outcome of ambulatory video-EEG monitoring in a ˜10,000 patient nationwide cohort.

PURPOSE: We evaluate outcome of in-home diagnostic ambulatory video-EEG monitoring (AVEM) performed on a nationwide cohort of patients over one calendar year, and we compare our findings with outcomes of inpatient adult and pediatric VEM performed during the same year at two academic epilepsy centers. METHODS: This is a retrospective cohort study. We obtained AVEM outcome data from an independent ambulatory-EEG testing facility. Inpatient VEM data from a 4-bed adult epilepsy center and an 8-bed pediatric epilepsy center were also included. Primary outcome measure was composite percentage of VEM records with epileptiform activity on EEG tracings or at least one video-recorded pushbutton event. We assessed patient-reported symptoms documented in AVEM event diaries. RESULTS: Of 9221 AVEM recordings performed across 28 states, 62.5% attained primary outcome. At least one patient-activated pushbutton event was captured on video in 54% of AVEM recordings (53.6% in adults, 56.1% in children). Epileptiform activity was reported in 1657 (18.0%) AVEM recordings (1473 [88.9%] only interictal, 9 [0.5%] only ictal, 175 [10.6%] both interictal and ictal). Most common patient-reported symptomatology during AVEM pushbutton events was behavioral/autonomic/emotional in adults and children. Compared to AVEM, inpatient VEM captured more confirmed representative events in adult and pediatric samples. CONCLUSIONS: AVEM is useful for non-urgent diagnostic evaluation of events.

Visual evoked potentials.

Pattern reversal evoked potentials (PVEPs) are a noninvasive procedure that are useful for detecting lesions of the visual pathways. This article reviews anatomy of the visual pathway and the testing protocols for fullfield and hemifield PVEP and flash (goggle) visual evoked potentials (FVEP). Criteria for evaluation of normal and abnormal responses and clinical correlates are discussed. We conclude with a brief discussion of recording visual evoked potentials (VEPs) from subdural or depth electrodes to localize primary visual cortex in patients, with a parieto-occipital seizure focus, who are undergoing evaluation for epilepsy surgery.

Risk factors associated with death in in-hospital pediatric convulsive status epilepticus.

OBJECTIVE: To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort. PATIENTS AND METHODS: We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant. RESULTS: We identified 12,365 (5,541 female) patients with convulsive SE aged 0-20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years) among 14,965,571 pediatric inpatients (0.08%). Of these, 117 died while in the hospital (0.9%). The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure. Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4-426.8), hemorrhagic shock (OR 17.83; CI 6.5-49.1), sepsis (OR 10.14; CI 4.0-25.6), massive aspiration (OR 9.1; CI 1.8-47), mechanical ventilation >96 hours (OR9; 5.6-14.6), transfusion (OR 8.25; CI 4.3-15.8), structural brain lesion (OR7.0; CI 3.1-16), hypoglycemia (OR5.8; CI 1.75-19.2), sepsis with liver failure (OR 14.4; CI 5-41.9), and admission in December (OR3.4; CI 1.6-4.1). African American ethnicity (OR 0.4; CI 0.2-0.8) was associated with a decreased risk of death in SE. CONCLUSION: Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management.

Sleep-wake patterns of seizures in children with lesional epilepsy.

This study examined diurnal patterns of seizures and their occurrence during wakefulness and sleep in children with lesional focal epilepsy. We reviewed 332 consecutive children with lesional focal epilepsy and video-electroencephalogram monitoring during a 3-year period. Data were analyzed in relationship to clock time, wakefulness/sleep, and seizure localization. The distribution of lesions in 66 children (259 seizures) included mesial temporal, 29%; neocortical temporal, 18%; frontal, 29%; parietal, 13.5%; and occipital, 12%. Seizures in patients with frontal lesions occurred mostly during sleep (72%). Seizures in mesial temporal (64%), neocortical temporal (71%), and occipital (66%) lesional epilepsy occurred mostly during wakefulness. Temporal lobe seizures occurred more frequently during wakefulness (66%), compared with extratemporal seizures (32%) (odds ratio, 2.67; 95% confidence interval, 1.61-4.42). Temporal lobe seizures peaked between 9:00 am and noon and 3:00-6:00 pm, whereas extratemporal seizures peaked between 6:00-9:00 am. Sleep, not clock time, provides a more robust stimulus for seizure onset, especially for frontal lobe seizures. Temporal lobe seizures are more frequent during wakefulness than are extratemporal seizures. Circadian patterns of seizures may provide additional diagnostic and treatment options, such as differential medication dosing and sleep-schedule adjustments.

Extended-release lamotrigine in the treatment of patients with epilepsy.

IMPORTANCE TO THE FIELD: Epilepsy is a neurological disorder primarily characterized by recurrent, unprovoked seizures resulting from excessive or synchronous neuronal activity in the brain. Depending on the case definition and population studied, the lifetime prevalence of epilepsy in the USA is estimated to be 1.2 - 2.9%. In general, epilepsy is related to a significant increased risk of mortality and injury. A cornerstone of epilepsy management is use of antiepileptic drugs (AEDs). This review focuses on the AED lamotrigine, with particular emphasis on the extended-release formulation, in the management of patients with epilepsy, and the significant clinical issues that may be relevant with once-daily AED therapy. AREAS COVERED IN THIS REVIEW: An introductory section overviews the prevalence of epilepsy, current treatment recommendations for patients with epilepsy, and unmet needs in epilepsy management. This is followed by an overview of the AED market with currently available and developing compounds, a summary of lamotrigine and extended-release lamotrigine, clinical efficacy and tolerability studies with extended-release lamotrigine, and regulatory issues. The review concludes with an expert opinion summary on the important issue of treatment adherence, the possible role of extended-release lamotrigine in adherence enhancement, and additional research and areas which need further focus for optimal epilepsy outcomes. WHAT THE READER WILL GAIN: The reader will gain familiarity with extended-release (once-daily) lamotrigine and clinical issues that may be relevant to once-daily use. Once-daily AED use might be one way to simplify the epilepsy treatment regimen and can pave the way for other approaches that can maximize adherence, such as a frank discussion of risks, benefits, and attitudes towards treatment - all critical components of a strong and positive doctor-patient relationship. TAKE HOME MESSAGE: The AED lamotrigine is widely used in clinical settings and has become available in a once-daily extended-release version, which may minimize serum concentration fluctuation and presumably would both reduce patient burden and maximize treatment adherence as opposed to the immediate-release version of the compound. Adverse effects and safety concerns between the immediate- and extended-release versions of lamotrigine seem similar based upon interpretation of the limited literature.

Triple pathology in epilepsy: coexistence of cavernous angiomas and cortical dysplasias with other lesions.

Coexistence of cortical dysplasias (CD) with cavernomas has rarely been reported. We reviewed our surgical specimens from patients who underwent surgery for pharmacoresistant epilepsy between 2003 and 2008, and identified seven cases with cavernoma, of whom two had overlying CD. In addition, each of these patients had a third form of a potentially epileptogenic lesion: hippocampal sclerosis in one, and venous angioma in the other. We conclude that CD is heterogeneous, with milder forms appearing to co-exist with other pathologies, including vascular abnormalities and hippocampal sclerosis.

Hemispherectomy-associated complications from the Kids' Inpatient Database.

UNLABELLED: Carefully selected pediatric patients undergo hemispherectomy (HS) for treatment of refractory epilepsy. HS is associated with a mortality rate of 0-6.6% across studies, mostly due to acute hemorrhage. The purpose of this study was to evaluate in-hospital mortality and predictors of the need for blood transfusion during HS in a large, nationwide cohort in recent years. METHODS: We identified our cohort from the Kids' Inpatient Database for the years 1997, 2000, and 2003. We queried the database for HS, and for associated diagnoses, including infections, congenital brain anomalies, and blood transfusion, among others. Predictors of blood transfusion were determined using a stepwise conditional logistic regression analysis. RESULTS: We identified 153 (74 female) patients with HS. Mean age was 6.4+/-5.6 years (range 2 months to 19 years). None of the socioeconomic factors examined were significant risk factors for blood transfusion. Admission diagnoses were epilepsy (88.3%), congenital brain anomalies (5.2%), and encephalitis (4.6%), among others. One patient died (0.7%) and 56 patients (36.6%) received blood transfusion. Independent risk factors for blood transfusion included congenital brain anomalies, geographic location of the hospitals (Midwest and Southern regions), medium and large hospital bed-sizes, and discharge months from July through September. Younger age was not a risk factor for blood transfusion. CONCLUSION: In-hospital mortality of HS is low, and blood transfusion was performed in over one third of patients. There appear to be several risk factors that can predict the likelihood of transfusion and may warrant close observation before hemispherectomy.

Phrenic nerve conduction studies in spinal cord injury: applications for diaphragmatic pacing.

The diaphragm pacing system (DPS) is a minimally invasive alternative to mechanical ventilation in patients with quadriplegia due to cervical myelopathy primarily caused by high cervical spinal cord injury. We evaluated 36 patients, 29 of whom had traumatic spinal cord injury, two who had a history of remote meningitis and demyelinating disease, and five who had cervical myelopathies of unknown etiology. Phrenic nerve conduction studies were performed with simultaneous fluoroscopic observation of diaphragm excursion to assess diaphragm viability. In the preoperative evaluation, diaphragm compound muscle action potentials (CMAPs) were recorded only when the diaphragm moved on fluoroscopy with ipsilateral stimulation. Twenty-six patients who were determined to have a viable diaphragm underwent DPS. Following DPS the primary outcome was the time (hours per day) that patients were able to pace and stay off the ventilator. Of 26 implanted patients, 96% (25 patients) were able to pace and tolerate being off the ventilator for more than 4 h per day. This study demonstrates that the presence of a diaphragm CMAP is associated with diaphragm movement observed by fluoroscopy in cervical myelopathy. In addition, DPS can help patients with cervical spinal cord injury to breathe unassisted by a ventilator.

Do observer and self-reports of ictal eye closure predict psychogenic nonepileptic seizures?

PURPOSE: Diagnostic delay in distinguishing psychogenic nonepileptic seizures (PNES) from epileptic seizures may result in unnecessary therapeutic interventions and higher health care costs. Previous studies demonstrated that video-recorded eye closure is associated with PNES. The present study prospectively assessed whether observer or self-report of eye closure could predict PNES, prior to video-EEG monitoring. METHODS: Adults referred to an epilepsy monitoring unit (EMU) were prospectively enrolled into the study. At baseline, self-report of eye closure was assessed by questionnaire, and observer report was obtained by interview. Physicians viewed video clips independent of EEG tracings and determined the duration of eye closure during PNES and epileptic seizures. We evaluated whether video-recorded eye closure identified an episode as PNES using random effects models that accounted for episode clustering by subject. The utility of observer and self-report of eye closure in predicting a diagnosis of PNES was tested using logistic regression. RESULTS: Of 132 enrolled subjects, 112 met study criteria during EMU stay for either PNES (n = 43, 38.4%) or epilepsy (n = 84, 75.0%). Fifteen of the 43 PNES subjects (34.9%) had coexisting epilepsy. Self and observer reports of eye closure were neither sensitive nor specific for the diagnosis of PNES. Self-report of eye closure more accurately predicted actual video-recorded eye closure than observer report. Video-recorded eye closure was 92% specific, but only 64% sensitive for PNES identification. DISCUSSION: Neither observer nor self-report of eye closure, prior to VEEG monitoring, predicts PNES. Video-recorded eye closure may not be as sensitive an indicator of PNES as previously reported.