Outcomes of status epilepticus and their predictors in the elderly-A systematic review.

Status epilepticus (SE) is associated with high mortality and morbidity. Although SE is frequently seen in elderly patients, there is a lack of a cohesive report of outcome measures and associated factors within this population. Our aim was to systematically review studies reporting outcomes of SE among elderly patients and factors influencing these outcomes. A literature search was conducted in PubMed/MEDLINE, EMBASE, CINAHL Complete, and Cochrane Library from database conception to April 22, 2018. A total of 85 studies were included in this systematic review. The included studies show that mortality is higher in elderly patients than in adult patients. Lesional etiologies, higher number of comorbidities, NCSE, RSE, longer hospital and intensive care unit stays, and infection during hospitalization are associated with poor outcome. Future studies should consider measuring functional outcomes, comparative studies between elderly and adults and AED clinical trials specific for elderly with SE.

Racial variations in lacosamide serum concentrations in adult patients with epilepsy.

Lacosamide (LCM) is a third-generation anti-epileptic drug (AED) for partial-onset epilepsy with minimal hepatic metabolism and drug-drug interactions. The impact of individual patient variables such as race on drug metabolism have been under-reported in AEDs and LCM has not been specifically investigated. Our aim was to assess the role race plays on serum LCM levels in the management of epilepsy. Thus, we retrospectively reviewed patients with focal seizures who received LCM and had LCM levels as part of their routine clinical care in our Level IV Epilepsy Center. Variables including age, race, gender, LCM serum levels, LCM daily dose, and concomitant AEDs were collected and analyzed. A total of 93 patients with 1-3 clinic visits yielded 122 LCM serum levels. African Americans (AA) comprised 62.3% of our serum samples. Daily LCM doses averaged 350 mg/day (range 50-1000 mg/day). Eighty-nine percent of patients took 1-2 other AEDs. Overall, AA patients had lower LCM levels (mean 6.8 µg/mL) compared to White patients (mean of 7.1 µg/mL) (p = .017) even when considering for the daily dose effect (p = .007). Analysis of co-variables did not have significant effect on LCM levels. Overall, AA patients had a weaker relationship between LCM daily dose (adjusted for weight) and serum levels as compared to White patients and require a higher LCM dose per weight to achieve similar levels. Differences in pharmacogenetics may play an important role in these findings and focus on how these variations impact seizure burden.

Inadequate benzodiazepine dosing may result in progression to refractory and non-convulsive status epilepticus.

Status epilepticus (SE) is defined as ongoing seizures lasting longer than five minutes or multiple seizures without recovery. Benzodiazepines (BZDs) are first-line agents for the management of SE. Our objective was to evaluate BZD dosing in SE patients and its effects on clinical/electrographic outcomes. A retrospective analysis was conducted from a prospective database of SE patients admitted to a university-based neurocritical care unit. The initial presentation and progression to refractory SE (RSE) and non-convulsive SE (NCSE) with coma was evaluated. Outcome measures included length of stay (LOS), rates of intubation, ventilator-dependent days, and Glasgow outcome scale (GOS). The lorazepam equivalent (LE) dosage of BZDs administered was calculated and we analysed variations in progression if 4 mg or more of LE (adequate BZDs) was administered. Among 100 patients, the median dose of LE was 3 mg (IQR: 2-5 mg). Only 31% of patients received adequate BZDs. Only 18.9% of patients with NCSE without coma received adequate BZDs (p=0.04). Among patients progressing to RSE, 75.4% had not received adequate BZDs (p=0.04) and among patients developing NCSE with coma, 80.6% did not receive adequate BZDs (p=0.07). Escalating doses of BZDs were associated with a decrease in cumulative incidences of RSE (correlation coefficient r=-0.6; p=0.04) and NCSE with coma (correlation coefficient r=-0.7; p=0.003). Outcome measures were not influenced by BZD dosing. The majority of our patients were not adequately dosed with BZDs. Inadequate BZD dosing progressed to RSE and had a tendency to lead to NCSE with coma. Our study demonstrates the need to develop a hospital-wide protocol to guide first responders in the management of SE.

Updates in Refractory Status Epilepticus.

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status.

Response Rates to Anticonvulsant Trials in Patients with Triphasic-Wave EEG Patterns of Uncertain Significance.

BACKGROUND: Generalized triphasic waves (TPWs) occur in both metabolic encephalopathies and non-convulsive status epilepticus (NCSE). Empiric trials of benzodiazepines (BZDs) or non-sedating AED (NSAEDs) are commonly used to differentiate the two, but the utility of such trials is debated. The goal of this study was to assess response rates of such trials and investigate whether metabolic profile differences affect the likelihood of a response. METHODS: Three institutions within the Critical Care EEG Monitoring Research Consortium retrospectively identified patients with unexplained encephalopathy and TPWs who had undergone a trial of BZD and/or NSAEDs to differentiate between ictal and non-ictal patterns. We assessed responder rates and compared metabolic profiles of responders and non-responders. Response was defined as resolution of the EEG pattern and either unequivocal improvement in encephalopathy or appearance of previously absent normal EEG patterns, and further categorized as immediate (within <2 h of trial initiation) or delayed (>2 h from trial initiation). RESULTS: We identified 64 patients with TPWs who had an empiric trial of BZD and/or NSAED. Most patients (71.9%) were admitted with metabolic derangements and/or infection. Positive clinical responses occurred in 10/53 (18.9%) treated with BZDs. Responses to NSAEDs occurred in 19/45 (42.2%), being immediate in 6.7%, delayed but definite in 20.0%, and delayed but equivocal in 15.6%. Overall, 22/64 (34.4%) showed a definite response to either BZDs or NSAEDs, and 7/64 (10.9%) showed a possible response. Metabolic differences of responders versus non-responders were statistically insignificant, except that the 48-h low value of albumin in the BZD responder group was lower than in the non-responder group. CONCLUSIONS: Similar metabolic profiles in patients with encephalopathy and TPWs between responders and non-responders to anticonvulsants suggest that predicting responders a priori is difficult. The high responder rate suggests that empiric trials of anticonvulsants indeed provide useful clinical information. The more than twofold higher response rate to NSAEDs suggests that this strategy may be preferable to BZDs. Further prospective investigation is warranted.

Generalized periodic discharges and 'triphasic waves': A blinded evaluation of inter-rater agreement and clinical significance.

OBJECTIVES: Generalized periodic discharges (GPDs) are associated with nonconvulsive seizures. Triphasic waves (TWs), a subtype of GPDs, have been described in relation to metabolic encephalopathy and not felt to be associated with seizures. We sought to establish the consistency of use of this descriptive term and its association with seizures. METHODS: 11 experts in continuous EEG monitoring scored 20 cEEG samples containing GPDs using Standardized Critical Care EEG Terminology. In the absence of patient information, the inter-rater agreement (IRA) for EEG descriptors including TWs was assessed along with raters' clinical EEG interpretation and compared with actual patient information. RESULTS: The IRA for 'generalized' and 'periodic' was near-perfect (kappa=0.81), but fair for 'triphasic' (kappa=0.33). Patients with TWs were as likely to develop seizures as those without (25% vs 26%, N.S.) and surprisingly, patients with TWs were less likely to have toxic-metabolic encephalopathy than those without TWs (55% vs 79%, p<0.01). CONCLUSIONS: While IRA for the terms "generalized" and "periodic" is high, it is only fair for TWs. EEG interpreted as TWs presents similar risk for seizures as GPDs without triphasic appearance. GPDs are commonly associated with metabolic encephalopathy, but 'triphasic' appearance is not predictive. SIGNIFICANCE: Conventional association of 'triphasic waves' with specific clinical conditions may lead to inaccurate EEG interpretation.