Data on the relationship between lamotrigine and levetiracetam serum/plasma levels and toxicity: Experience at an academic medical center.

Lamotrigine and levetiracetam are second-generation anti-epileptic drugs used for the management of seizure disorders and some other medical conditions. In the related research article using retrospective data from an academic medical center, we analyzed 5046 samples originating from 1930 unique patients that had lamotrigine drug levels performed on serum/plasma and 4359 samples from 2451 patients that had levetiracetam drug levels performed. The data in this article provides the patient demographic, clinical location at time of drug level, and specific lamotrigine or levetiracetam serum/plasma drug level for all patients. For those instances with lamotrigine drug level greater than 14.0 mg/L or levetiracetam drug level of 80 mg/L or higher, additional data from chart review includes: indication for ordering the drug level, two main presenting signs or symptoms at time of drug level, timing of drug level (random, trough, peak, or unknown), changes in drug dosing following the drug level, concomitant therapy with valproic acid (lamotrigine only), and details related to drug overdose (if applicable). The analyzed data is provided in the supplementary tables included in this article. Volumes of test ordering by year is included in a figure. The dataset reported is related to the research article entitled "Correlation of Elevated Lamotrigine and Levetiracetam Serum/Plasma Levels with Toxicity: A Long-Term Retrospective Review at an Academic Medical Center" [K. E. Wood, K. L. Palmer, M.D. Krasowski, Correlation of elevated lamotrigine and levetiracetam serum/plasma levels with toxicity: A long-term retrospective review at an academic medical center, Toxicol. Rep. (2021) 8:1592-1598].

Correlation of elevated lamotrigine and levetiracetam serum/plasma levels with toxicity: A long-term retrospective review at an academic medical center.

Lamotrigine and levetiracetam are widely used second-generation anti-epileptic drugs. Existing literature indicates that overdose of either drug is typically benign, but neurologic and cardiac toxicity can occur in some cases. In this retrospective study, we analyzed a large dataset of serum/plasma drug levels for lamotrigine and levetiracetam. The data covered 1,930 unique patients (5,046 levels) for lamotrigine and 2,451 patients (4,359 levels) for levetiracetam. We performed detailed chart review on all patients with one or more lamotrigine levels greater than 14.0 mg/L (293 unique patients) and all patients with one or more levetiracetam levels of 80 mg/L or higher (106 unique patients). No deaths directly attributable to lamotrigine or levetiracetam toxicity were reported. For cases with lamotrigine levels greater than 14.0 mg/L, the majority of patients were asymptomatic (55.3 %, n = 162). The most common presenting symptoms were ataxia (14.3 %, n = 42), seizures (14.0 %, n = 41), dizziness (11.9 %, n = 35), and altered mental status (11.6 %, n = 34). There were 12 overdoses (11 intentional) involving lamotrigine, all of which presented with either altered mental status (n = 8) or seizures (n = 4). The highest estimated dose reportedly ingested was 20 g. Cardiac toxicity was observed in two cases involving intentional overdose of lamotrigine. For patients with levetiracetam serum/plasma levels of 80 mg/L or higher, 48 patients (45.3 %) were asymptomatic. Symptomatic patients most commonly presented with seizures (31.1 %, n = 33) and altered mental status (15.1 %, n = 16), and none showed cardiac symptoms. There were only two cases involving intentional levetiracetam overdose, one of which presented with altered mental status after ingestion of 45 g and the other asymptomatic after ingestion of 6 g. Overall, our data is consistent with previous investigations that lamotrigine and levetiracetam toxicity most typically presents with neurologic symptoms and rarely cardiac arrhythmias. Approximately half of the patients with elevated lamotrigine or levetiracetam drug levels are asymptomatic.

Alternate Matrices: Meconium, Cord Tissue, Hair, and Oral Fluid.

Drug testing commonly involves serum, blood, or urine. More recently, alternative specimens for drug testing have been increasingly used for clinical and forensic toxicology. Examples include oral fluid (saliva), hair, meconium, and umbilical cord tissue. Each of these matrices has unique properties that provide advantages for certain applications. Oral fluid has easier and less invasive collection requirements than urine, the most common specimen for drug screening. Oral fluid drug testing is common in Europe and steadily gaining popularity in the United States. Hair accumulates drugs and drug metabolites and provides a much longer window of detection than blood or urine. Meconium and umbilical cord tissue each allow for assessment of prenatal drug exposure over the course of months. Limitations of these alternative matrices include need for laboratory-developed tests (exception being some oral fluid immunoassays), challenges with the specimen matrix, and incomplete understanding of drug incorporation and kinetics. This chapter briefly describes each of the above alternative specimens in terms of their utility, advantages, and limitations.

A Fatal Case of Herpes Simplex Encephalitis with Two False-Negative Polymerase Chain Reactions.

An 88-year-old man presented with a 1-month history of altered mental status and seizures. His electrographic and imaging findings were suggestive of herpes simplex encephalitis (HSE), for which he was empirically treated with acyclovir. He underwent two lumbar punctures 3 days apart; both cerebrospinal fluid analyses tested negative for herpes simplex virus (HSV) by polymerase chain reaction (PCR). These negative results and his continued deterioration after 9 days of acyclovir therapy prompted treatment with steroids for possible autoimmune encephalitis. Shortly after the change in management, the patient died from cardiac arrest. At autopsy, his brain showed both gross and microscopic evidence of encephalitis and was positive for HSV by immunohistochemistry. This fatal case of HSE emphasizes the limitations of HSV PCR and the importance of clinical suspicion in the diagnosis and management of this disease.

Evaluating a switch from meconium to umbilical cord tissue for newborn drug testing: A retrospective study at an academic medical center.

BACKGROUND: The objective of this study was to compare detection rates of newborn drug exposure at an academic medical center transitioning from meconium to umbilical cord tissue toxicology testing. METHODS: We performed an Institutional Review Board-approved retrospective chart review on all newborns (n=2072) for whom newborn drug testing was ordered at our academic medical center between June 2012 and August 2015 (in August 2013, umbilical cord tissue became the preferred specimen). RESULTS: Meconium toxicology testing was positive for at least one compound in 221 cases (21.3% of 1037 total specimens), with non-medical drug use identified in 85 cases (8.2%). Umbilical cord tissue toxicology testing was positive for at least one compound in 302 cases (29.2%), with non-medical drug use identified in 107 cases (10.3%). Of the cases involving non-medical drug use, the most common compounds detected were tetrahydrocannabinol and amphetamines. Non-medical drug use did not differ significantly between meconium and umbilical cord tissue, either as a total or for classes of drugs such as amphetamines, cannabinoids, and opiates. Maternal non-medical use of tramadol (not tested for in meconium) was identified in 5 cases (0.4%). There were significant differences in rate of detection of iatrogenic medications. Specifically, morphine, lorazepam, phenobarbital, and codeine were more commonly detected in meconium, while oxycodone was more commonly detected in umbilical cord tissue. CONCLUSIONS: Umbilical cord tissue toxicology testing yielded a similar detection rate compared to meconium testing. The use of umbilical cord tissue avoids detection of medications given to the neonate prior to meconium collection.

A comparative genomics approach to understanding the biosynthesis of the sunscreen scytonemin in cyanobacteria.

BACKGROUND: The extracellular sunscreen scytonemin is the most common and widespread indole-alkaloid among cyanobacteria. Previous research using the cyanobacterium Nostoc punctiforme ATCC 29133 revealed a unique 18-gene cluster (NpR1276 to NpR1259 in the N. punctiforme genome) involved in the biosynthesis of scytonemin. We provide further genomic characterization of these genes in N. punctiforme and extend it to homologous regions in other cyanobacteria. RESULTS: Six putative genes in the scytonemin gene cluster (NpR1276 to NpR1271 in the N. punctiforme genome), with no previously known protein function and annotated in this study as scyA to scyF, are likely involved in the assembly of scytonemin from central metabolites, based on genetic, biochemical, and sequence similarity evidence. Also in this cluster are redundant copies of genes encoding for aromatic amino acid biosynthetic enzymes. These can theoretically lead to tryptophan and the tyrosine precursor, p-hydroxyphenylpyruvate, (expected biosynthetic precursors of scytonemin) from end products of the shikimic acid pathway. Redundant copies of the genes coding for the key regulatory and rate-limiting enzymes of the shikimic acid pathway are found there as well. We identified four other cyanobacterial strains containing orthologues of all of these genes, three of them by database searches (Lyngbya PCC 8106, Anabaena PCC 7120, and Nodularia CCY 9414) and one by targeted sequencing (Chlorogloeopsis sp. strain Cgs-089; CCMEE 5094). Genomic comparisons revealed that most scytonemin-related genes were highly conserved among strains and that two additional conserved clusters, NpF5232 to NpF5236 and a putative two-component regulatory system (NpF1278 and NpF1277), are likely involved in scytonemin biosynthesis and regulation, respectively, on the basis of conservation and location. Since many of the protein product sequences for the newly described genes, including ScyD, ScyE, and ScyF, have export signal domains, while others have putative transmembrane domains, it can be inferred that scytonemin biosynthesis is compartmentalized within the cell. Basic structural monomer synthesis and initial condensation are most likely cytoplasmic, while later reactions are predicted to be periplasmic. CONCLUSION: We show that scytonemin biosynthetic genes are highly conserved among evolutionarily diverse strains, likely include more genes than previously determined, and are predicted to involve compartmentalization of the biosynthetic pathway in the cell, an unusual trait for prokaryotes.