Lance Adams Syndrome in the Setting of COVID-19 Pneumonia.

Lance-Adams syndrome (LAS) is a rare clinical presentation of hypoxic-ischemic brain injury typically occurring in the setting of cardiac arrest. It is rare for it to be associated with respiratory failure. The advent of the COVID-19 pandemic heralded a new cause of respiratory failure, and not much is known about the occurrence of Lance-Adams syndrome in the context of COVID-19 pneumonia. A 23-year-old male was brought to the emergency department (ED) after being found unconscious at home. He had prominent generalized myoclonus in the context of COVID-19 pneumonia and a possible clonazepam overdose. Magnetic resonance imaging (MRI) of the brain with and without contrast revealed findings suggestive of hypoxic-ischemic brain injury. A diagnosis of LAS was made based on electroencephalography (EEG). As LAS typically carries a relatively favorable prognosis, aggressive treatment was pursued. This resulted in a fairly good outcome, although he had to be maintained on several antiseizure medications. Our case is a rare occurrence of Lance-Adams syndrome in the setting of respiratory failure and COVID-19 pneumonia in the absence of cardiac arrest. It is critical to distinguish myoclonic status epilepticus (MSE) from Lance-Adams syndrome due to the difference in prognosis. Our case can provide future direction for studies in a larger cohort of patients to see if LAS is frequently associated with respiratory failure secondary to COVID-19 pneumonia in the absence of cardiac arrest. It is important to consider Lance-Adams syndrome as one of the emerging neurological complications of COVID-19 pneumonia.

Long-term quality of life in patients with focal seizures treated with adjunctive eslicarbazepine acetate.

By controlling seizures, anti-seizure medications can improve health-related quality of life (HRQOL). Data from a post-hoc pooled analysis of adjunctive eslicarbazepine acetate (ESL) was used to describe HRQOL measures, including overall quality of life, seizure worry, emotional well-being, energy/fatigue, cognitive functioning, medication effects, social function, and overall score over a period of up to one year. Patients who completed a double-blind treatment phase (Part 1) of these trials were eligible to enter the open label extension (OLE; Part 2). Patients who continued into the OLE initiated adjunctive ESL at 800 mg/day for 1 month before investigators could titrate dosages based on efficacy and tolerability. HRQOL was measured at baseline and at the last assessment using the Quality of Life in Epilepsy Inventory (QOLIE-31) in all patients who entered the 1-year OLE and in patients who completed the 1-year OLE. The mean QOLIE-31 scores and mean change in scores were analyzed using paired t-tests. The percentage of patients with improvements in QOLIE-31 scores beyond the minimally important change (MIC) threshold from baseline to end of 1-year OLE is described. Of 1410 patients in the intent-to-treat population, 1120 patients continued to part 2, and 795 patients completed the OLE. In patients who entered the OLE, mean improvements in scores for seizure worry, overall quality of life, emotional well-being, medication side effects, social functioning, and total score were statistically significant. In patients who completed the OLE, the mean change to final assessment was statistically significantly improved for all QOLIE categories. In patients who entered the OLE with a final assessment, the percentage of patients meeting the MIC for social functioning was the highest (46.9%), followed by medication effects (44.9%), and seizure worry (42.9%). Patients who completed the OLE with a final assessment found a similar rank ordering in QOLIE scale improvements compared with those who entered the OLE with a final assessment. For both sets of patient groups, the least number of subjects met MIC criteria for the energy/fatigue QOLIE category. Treatment with therapeutic doses of adjunctive ESL in patients with focal seizures was associated with improvements in HRQOL for a period of up to one year.

Time to baseline seizure count in patients with focal seizures receiving adjunctive eslicarbazepine acetate in a phase IV clinical trial.

BACKGROUND: The efficacy and tolerability of eslicarbazepine acetate (ESL), a once-daily, orally-administered, anti-seizure medication (ASM), have primarily been established in treatment-resistant epilepsy patients, the population most often enrolled in clinical trials of anti-seizure medications. More recently, ESL was also shown to be effective and well-tolerated as first adjunctive therapy in non-treatment-resistant patients in an open-label, non-randomized, Phase IV, 24-week study of ESL using standard efficacy parameters in adults with focal seizures. OBJECTIVE: To determine the time required to reach baseline seizure count, as an alternative method of assessing the efficacy of adjunctive ESL in patients with relatively low baseline monthly seizure frequencies. This additional analysis was undertaken, as subtle changes and improvements are difficult to analyze using standard efficacy parameters, such as standardized seizure frequency reduction when the baseline frequency of seizures is particularly low. METHODS: This was a post-hoc analysis of the Phase IV study data, which investigated time to baseline seizure count in patients aged ≥ 18 years with focal seizures as an alternative measure of anti-seizure efficacy. In the Phase IV trial, patients had been enrolled into 2 groups: Arm 1: ESL as first adjunctive therapy to levetiracetam (LEV) or lamotrigine (LTG), the two most commonly-prescribed ASMs, in patients with inadequate response to treatment; Arm 2: ESL as a later adjunctive therapy, following prior use of 1-2 ASMs in patients who required an additional therapeutic option. RESULTS: The time to reach individual baseline seizure count was longer in patients with focal seizures receiving ESL as a first (Arm 1) versus later (Arm 2) adjunctive therapy (p = 0.005). Patients who received ESL as a first adjunctive therapy had a longer time to ESL discontinuation than patients who received ESL as a later adjunctive therapy (p = 0.04). In Arm 1, patients receiving concomitant LTG reported treatment-emergent adverse events (TEAEs) significantly earlier than those receiving LEV (p = 0.02). Compared to patients receiving concomitant LTG, a greater number of patients in Arm 1 who were taking concomitant LEV had a modal ESL dose > 1200 mg and completed the full maintenance period. A greater number of patients in Arm 1 who were receiving concomitant LEV and completed the 24-week maintenance period reached a maximum ESL dose of 1600 mg, compared to those taking LTG, who reached a maximum ESL dose of 1200 mg. CONCLUSIONS: This analysis of the Phase IV clinical trial data provides an alternative way of assessing efficacy beyond standardized seizure frequency reduction, in the context of relatively low monthly median seizure frequencies at baseline (SSF 2.0-2.4). These results provide further support for the use of ESL as an earlier or later adjunctive therapy to LEV or LTG.

Adult Presentation of Ornithine Transcarbamylase Deficiency: 2 Illustrative Cases of Phenotypic Variability and Literature Review.

Ornithine transcarbamylase (OTC) deficiency is an X-linked recessive disorder that usually presents in the neonatal period. Late-onset presentation of OTC can cause mild to severe symptoms. We describe laboratory and clinical findings of late-onset presentations of OTC deficiency. We conducted a literature search using search terms "ornithine transcarbamylase deficiency," "late onset presentation," and "hyperammonemia" from January 1, 1987, to December 31, 2016, was performed. Only papers published in English were included. We searched on PubMed, MEDLINE, and Google Scholar. We also present 2 OTC deficiency cases. A total of 30 adult cases had late-onset presentation of OTC deficiency reported. The majority were women (57%) with a median age of 37 years. The median level of ammonia was 308 mmol/L and the mortality rate was 30%. Our case 1 was a 40-year-old woman who succumbed to neurologic complications after a hyperammonemia crisis following an increased protein intake. Our case 2 was a 43-year-old woman with seizures associated with increased ammonia levels. Our 2 case reports show the wide phenotypic variability and severity in late-onset presentation of OTC ranging from seizures to cerebral herniation. Our literature review is the first to detail published laboratory and neurologic sequelae of late-onset OTC deficiency.