Person:

Cole, Andrew

Aim. Caregiver burden (CB) in epilepsy constitutes an understudied area. Here we attempt to identify the magnitude of this burden, the factors associated with it, and its impact to caregiver quality of life (QOL). Methods:. 48 persons with epilepsy (PWE) underwent video-EEG monitoring and their caregivers completed questionnaires providing demographic, disease-related, psychiatric, cognitive, sleep, QOL, and burden information. Results:. On regression analysis, higher number of antiepileptic drugs, poorer patient neuropsychological performance, lower patient QOL score, and lower caregiver education level were associated with higher CB. Time allocated to patient care approximated but did not attain statistical significance. A moderate inverse correlation between CB and caregiver QOL physical component summary score and a stronger inverse correlation between CB and caregiver QOL mental component summary score were seen. Conclusion:. In a selected cohort of PWE undergoing video-EEG monitoring, we identified modest degree of CB, comparable to that reported in the literature for other chronic neurological conditions. It is associated with specific patient and caregiver characteristics and has a negative effect on caregiver QOL.

The elderly population faces an increasing number of cases of chronic neurological conditions, such as epilepsy and Alzheimer’s disease. Because the elderly with epilepsy are commonly excluded from randomized controlled clinical trials, there are few rigorous studies to guide clinical practice. When the elderly are eligible for trials, they either rarely participate or frequently have poor adherence to therapy, thus limiting both generalizability and validity. In contrast, large observational data sets are increasingly available, but are susceptible to bias when using common analytic approaches. Recent developments in causal inference-analytic approaches also introduce the possibility of emulating randomized controlled trials to yield valid estimates. We provide a practical example of the application of the principles of causal inference to a large observational data set of patients with epilepsy. This review also provides a framework for comparative-effectiveness research in chronic neurological conditions.

Aim

As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy.

Method

The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood-onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype.

Results

A total of 180 SRS questionnaires were filled out in the TSC, NF1, and EUC outpatient clinics at the Massachusetts General Hospital (90 females, 90 males; mean age 21y, range 4–63y), and SRS data from 210 patients with ASD recruited from an autism research collaboration (167 males, 43 females; mean age 9y range 4–22y) and 130 unaffected siblings were available. Regression models showed a significant association between SRS scores and intelligence outcomes (p<0.001) and various seizure variables (p<0.02), but not with a specific underlying disorder or genotype. The level of autistic features was strongly associated with intelligence outcomes in patients with TSC and epilepsy (p<0.01); in patients with NF1 these relationships were weaker (p=0.25). For all study groups, autistic trait subdomains covaried with neurocognitive comorbidity, with endophenotypes similar to that of idiopathic autism.

Interpretation

Our data show that in TSC and childhood-onset epilepsy, the severity and phenotype of autistic features are inextricably linked with intelligence and epilepsy outcomes. Such relationships were weaker for individuals with NF1. Findings suggest that ASDs are not specific for these conditions.

Objective: Brain connectivity at rest is altered in temporal lobe epilepsy (TLE), particularly in “hub” areas such as the posterior default mode network (DMN). Although both functional and anatomical connectivity are disturbed in TLE, the relationships between measures as well as to seizure frequency remain unclear. We aim to clarify these associations using connectivity measures specifically sensitive to hubs. Methods: Connectivity between 1000 cortical surface parcels was determined in 49 TLE patients and 23 controls with diffusion and resting-state functional magnetic resonance imaging. Two types of hub connectivity were investigated across multiple brain modules (the DMN, motor system, etcetera): (1) within-module connectivity (a measure of local importance that assesses a parcel's communication level within its own subnetwork) and (2) between-module connectivity (a measure that assesses connections across multiple modules). Results: In TLE patients, there was lower overall functional integrity of the DMN as well as an increase in posterior hub connections with other modules. Anatomical between-module connectivity was globally decreased. Higher DMN disintegration (DD) coincided with higher anatomical between-module connectivity, whereas both were associated with increased seizure frequency. DD related to seizure frequency through mediating effects of anatomical connectivity, but seizure frequency also correlated with anatomical connectivity through DD, indicating a complex interaction between multimodal networks and symptoms. Interpretation We provide evidence for dissociated anatomical and functional hub connectivity in TLE. Moreover, shifts in functional hub connections from within to outside the DMN, an overall loss of integrative anatomical communication, and the interaction between the two increase seizure frequency.

Seizures are known to occur in Creutzfeldt–Jakob disease (CJD). In the setting of a rapidly progressive condition with no effective therapy, determining appropriate treatment for seizures can be difficult if clinical morbidity is not obvious yet the electroencephalogram (EEG) demonstrates a worrisome pattern such as status epilepticus. Herein, we present the case of a 39-year-old man with CJD and electrographic seizures, discuss how this case challenges conventional definitions of seizures, and discuss a rational approach toward treatment. Coincidentally, our case is the first report of CJD in a patient with Stickler syndrome.

Eight years after emigrating from Brazil, an otherwise healthy man developed rabies. An exposure prior to immigration was reported. Genetic analysis revealed a canine rabies virus variant found only in the patient’s home country, and the patient had not traveled internationally since immigrating to the United States. We describe how epidemiological, phylogenetic, and viral sequencing data provided confirmation that rabies encephalomyelitis may present after a long, multiyear incubation period, a consideration that previously has been hypothesized without the ability to exclude a more recent exposure. Accordingly, rabies should be considered in the diagnosis of any acute encephalitis, myelitis, or encephalomyelitis.

Objective: To characterize the risk for seizures over time in relation to EEG findings in hospitalized adults undergoing continuous EEG monitoring (cEEG).

Methods: Retrospective analysis of cEEG data and medical records from 625 consecutive adult inpatients monitored at a tertiary medical center. Using survival analysis methods, we estimated the time-dependent probability that a seizure will occur within the next 72-h, if no seizure has occurred yet, as a function of EEG abnormalities detected so far.

Results: Seizures occurred in 27% (168/625). The first seizure occurred early (<30 min of monitoring) in 58% (98/168). In 527 patients without early seizures, 159 (30%) had early epileptiform abnormalities, versus 368 (70%) without. Seizures were eventually detected in 25% of patients with early epileptiform discharges, versus 8% without early discharges. The 72-h risk of seizures declined below 5% if no epileptiform abnormalities were present in the first two hours, whereas 16 h of monitoring were required when epileptiform discharges were present. 20% (74/388) of patients without early epileptiform abnormalities later developed them; 23% (17/74) of these ultimately had seizures. Only 4% (12/294) experienced a seizure without preceding epileptiform abnormalities.

Conclusions: Seizure risk in acute neurological illness decays rapidly, at a rate dependent on abnormalities detected early during monitoring. This study demonstrates that substantial risk stratification is possible based on early EEG abnormalities.

Significance: These findings have implications for patient-specific determination of the required duration of cEEG monitoring in hospitalized patients.

Abstract Super‐refractory status epilepticus (SRSE) is associated with high morbidity and mortality. Treatment of SRSE is complicated by progressive cortical hyperexcitability believed to result in part from synaptic GABA receptor internalization and desensitization. Allopregnanolone, a neurosteroid that positively modulates synaptic and extrasynaptic GABAA receptors, has been proposed as a novel treatment. We describe the first two patients with SRSE who were each successfully treated with a 120‐h continuous infusion of allopregnanolone. Both patients recovered from prolonged SRSE with good cognitive outcomes.

Background. The optimal surgery in lesional neocortical temporal lobe epilepsy is unknown. Hippocampal electrocorticography maximizes seizure freedom by identifying normal-appearing epileptogenic tissue for resection and minimizes neuropsychological deficit by limiting resection to demonstrably epileptogenic tissue. We examined whether standardized hippocampal electrocorticography (hippocampography) guides resection for more consistent hippocampectomy than unguided resection in conventional electrocorticography focused on the lesion. Methods. Retrospective chart reviews any kind of electrocorticography (including hippocampography) as part of combined lesionectomy, anterolateral temporal lobectomy, and hippocampectomy over 8 years . Patients were divided into mesial (i.e., hippocampography) and lateral electrocorticography groups. Primary outcome was deviation from mean hippocampectomy length. Results. Of 26 patients, fourteen underwent hippocampography-guided mesial temporal resection. Hippocampography was associated with 2.6 times more consistent resection. The range of hippocampal resection was 0.7 cm in the mesial group and 1.8 cm in the lateral group (p = 0.01). 86% of mesial group versus 42% of lateral group patients achieved seizure freedom (p = 0.02). Conclusions. By rationally tailoring excision to demonstrably epileptogenic tissue, hippocampography significantly reduces resection variability for more consistent hippocampectomy than unguided resection in conventional electrocorticography. More consistent hippocampal resection may avoid overresection, which poses greater neuropsychological risk, and underresection, which jeopardizes postoperative seizure freedom.

Purpose: Persistent uncertainty over the clinical significance of various pathological continuous electroencephalography (cEEG) findings in the intensive care unit (ICU) has prompted efforts to standardize ICU cEEG terminology and an ensuing debate. We set out to understand the reasons for, and a satisfactory resolution to, this debate.

Method: We review the positions for and against standardization, and examine their deeper philosophical basis.

Results: We find that the positions for and against standardization are not fundamentally irreconcilable. Rather, both positions stem from conflating the three cardinal steps in the classic approach to EEG, which we term “description”, “interpretation”, and “prescription”. Using real-world examples we show how this conflation yields muddled clinical reasoning and unproductive debate among electroencephalographers that is translated into confusion among treating clinicians. We propose a middle way that judiciously uses both standardized terminology and clinical reasoning to disentangle these critical steps and apply them in proper sequence.

Conclusion: The systematic approach to ICU cEEG findings presented herein not only resolves the standardization debate but also clarifies clinical reasoning by helping electroencephalographers assign appropriate weights to cEEG findings in the face of uncertainty.