Beware of Neurotoxins in Common Plants: Water Hemlock Poisoning Presenting as Convulsive Status Epilepticus.

BACKGROUND: Pediatric status epilepticus occurs in about 44/100.000 children per year with an unknown cause in about a third of patients. One cause can be the ingestion of plants containing toxins that target the central nervous system. Here we describe an ingestion of water hemlock resulting in a status epilepticus. METHODS: We studied in detail the clinical, laboratory, electrophysiological, and radiological features of a patient with status epilepticus. RESULTS: A 9-year-old boy presented to the pediatric emergency department for sudden onset of nausea, vomiting, and status epilepticus approximately one hour after the patient had bitten into the root of a water plant in an inner-city park. Bilateral tonic-clonic seizures could only be terminated after administration of midazolam, lorazepam, and finally propofol. Cranial MRI, cerebrospinal fluid, and EEG findings were largely unremarkable. The ingested plant was identified as water hemlock through a detailed search with the help of a drawing issued by the patient with the help of the medical team. The specific toxicological analysis for water hemlock verified the presence of cicutoxin and cicudiol in the blood sample. The patient was discharged, levetiracetam was weaned off four weeks later, and he has remained seizure free since. CONCLUSIONS: Given the considerable percentage of cases of unknown etiology in new-onset pediatric status epilepticus, it is important to consider plant intoxication as a possible cause.

Hair analysis of antidepressants and antipsychotics-Overview of quantitative data.

Antidepressant and antipsychotic drugs are regularly encountered in different aspects of forensic toxicology, and some cases require the examination of hair samples. In this study, common antidepressant and antipsychotic drugs regarding hair concentrations over the past decades were reviewed. Although numerous publications around method validations, case reports, or controlled dose studies were found, apparently there is a lack of comprehensive data for many substances. Information on the hair length and dosage across the publications varied largely, and case numbers were generally low except for several retrospective controlled dose studies. Many substances were described only in method validations or case reports, and data were obtained from small case numbers. On the contrary, clozapine, haloperidol, amitriptyline, nortriptyline, risperidone and its metabolite, methylphenidate, citalopram, chlorpromazine, chlorprothixene, and quetiapine had a well-founded database as these substances were investigated in controlled dose studies with higher case numbers. Given the advancements made in analytical techniques over the past years, gas chromatography-mass spectrometry and liquid chromatography with tandem mass spectrometry techniques were the methods of choice and allowed the detection of chemical compounds at low concentrations. The controversy around a potential use of hair analysis to estimate the dosage remains as dose-concentration studies provided divergent results. A harmonization on the investigated hair length as well as on the extraction protocol would be of favor to achieve better comparability. Although hair analysis research focused mainly on drug abuse, availability of more data on antidepressants and antipsychotics would help to gain better knowledge and assist other forensic investigators.

Positive findings of ethyl glucuronide in hair of young children from families with addiction background.

AIMS: Small children are expected to be abstinent from alcohol, and children's hair is frequently used as the blank matrix for calibration of the alcohol consumption marker ethyl glucuronide (EtG). The basal EtG concentrations of total abstainers were described to be 0.3-2.1 pg/mg (Pirro et al. 2013). It is examined whether this assumption is valid for children from families with addiction background. METHODS: In a social support system for families with drug and/or alcohol addicted parents, 161 hair samples from 126 children (age 1-14 years, hair segment 0-3 cm) were analyzed for EtG by a validated LC-MS/MS method (LOD 0.56 pg/mg, LLOQ 2.3 pg/mg). For comparison, ethyl palmitate (EtPa) was measured and hair samples from parents were included. EtG ≥ 3 pg/mg was considered as an alarming result for children. RESULTS AND DISCUSSION: EtG concentrations between 3.0 and 42.6 pg/mg (mean 9.55 pg/mg, median 6.40 pg/mg) were measured for 25 samples (15.5%, age 22 × 1-5 years, 3 × 9-11 years). Elevated EtPa (0.15-0.46 ng/mg) was found in 6 samples and cocaethylene (0.02-0.07 ng/mg) was detected in 5 samples with high cocaine findings. Hair results of one or both parents indicated drug abuse in 12 from 14 cases (85.7%) if both parents were tested. CONCLUSION: Although accidental or voluntary intake of alcoholic beverages cannot be excluded, the external contamination of children's hair by EtG-containing wine and sweat or urine of the alcohol abusing parents is assumed to be the most probable explanation for the positive EtG results in hair of 1-5-year-old children.

Hair analysis of more than 140 families with drug consuming parents. Comparison between hair results from adults and their children.

BACKGROUND: Hair samples from children are frequently analyzed in order to characterize their endangerment in a drug using environment. However, the interpretation of the results remains difficult because of lacking data for comparison. In this study, hair samples from families with drug consuming parents were analyzed for illegal and selected medical drugs and the results were evaluated concerning a relationship between findings of parents and children depending on kind of drug, age and gender of children as well as maternal or paternal drug concentrations in hair. METHODS: In an ongoing social supporting project for families with underage children and drug consuming parents, hair samples were analyzed since 2011 for methadone, opiates and opioid analgesics, cocaine, amphetamines, ecstasy, cannabinoids and benzodiazepines by LC-MS/MS with LOQs ≈ 0.01 ng/mg. From the data pool of more than 1300 individuals, 100 families with results for one or both parents and one to five children, 30 families with results only for both parents, and 11 families with results only for 2-4 children were selected. Fifty eight of these 141 families were repeatedly tested (altogether 251 family tests). RESULTS: One to 5 drugs were detected in 239 (95.2%) of the family tests with highest occurrence of cocaine (79.7%) and THC (50.2%). According to the concentrations of the tested persons, the most probable drug users were the mother (25%), the father (24%), both parents (16%), or were not tested (30%). Within the families, there was an agreement of the detected drugs between parents and children of 47.8%, between both parents of 36.1%, and between children of 42.3%. For parents with hair concentrations in the typical range of regular drug use, the drug was detected in children hair with the following frequency: methadone 65.5%, heroin (6-AM) 63.6%, cocaine 92.1%, amphetamine 80%, MDMA 42.9% and THC 67.4% with higher percentage for younger children. The agreement for medical drugs (benzodiazepines 7.7%, synthetic opioids 8.7%, diphenhydramine 7.1%) was much lower suggesting voluntary administration or intake. Despite the strong variation of the data, clear trends were found that the child/parent drug concentration ratio decreases with increasing children age and is higher for boys than for girls. CONCLUSION: The comparison of hair results within families gives a deeper insight in the drug situation, often enables the identification of the drug user and is helpful for social and legal decisions to improve the conditions of the children.

Toxicological findings in suicides - frequency of antidepressant and antipsychotic substances.

The role of psychoactive substances in the treatment of mental disorders and the risk of suicide are major public health issues. This cross-sectional study examined the prevalence of antidepressants and antipsychotics detected in toxicological screenings in suicides. Cases from the Institute of Legal Medicine of the Charité-University Medicine Berlin were reviewed over a 4-year-period. All cases (n = 477) with positive toxicology for antidepressants and antipsychotics in blood or organ tissue were included. Frequencies of the detected substances in non-suicide cases (n = 212; male n = 177, 55.2%; female n = 95, 52.5%) and suicide cases (n = 235; male n = 149, 63.4%; female n = 86, 36.6%) were examined. Tricyclic antidepressants (48.1%) were found most frequently in suicides, followed by atypical neuroleptics (37.0%), selective serotonin reuptake inhibitors (28.1%), typical neuroleptics (17.4%), tetracyclic antidepressants (16.2%) and other substances (8.9%). Alcohol was detected in 37.2% of suicides. The leading cause of death was drug poisoning (35.6%) followed by polytrauma (26.8%) and death by hanging (18.5%). A mental disorder (depression, schizophrenia, bipolar disorder, suicidality) was known in 22.9% of suicides. The most common location of death was the person's own house (63.8%) followed by public places (28.1%) and hospitals (8.1%) The five most common substances in the suicide group were doxepin (20%) citalopram (15.3%), mirtazapine (14.9%), quetiapine (13.6%) and amitriptyline (12.3%). Toxicological findings from cross-sectional studies provide insight into how often certain types of antidepressants and antipsychotics are associated with suicide. A complementary approach is valuable for assessing the risk of suicide during medical treatment because the various available approaches (analysis of suicidal behavior/ideation, toxicity of drugs) each have strengths and limitations.

The use of nails as an alternative matrix for the long-term detection of previous drug intake: validation of sensitive UHPLC-MS/MS methods for the quantification of 76 substances and comparison of analytical results for drugs in nail and hair samples.

PURPOSE: This article describes the validation of multi-target methods for the determination of 76 different analytes in hair and nail samples. Segmented hair and nail samples taken from autopsy cases were included in this study. METHOD: Drugs of abuse, psychotropic drugs, and other drugs were included for the validation of this method. Hair and nail samples were ground using a ball mill and extracted for 18 h. Extracts were measured using a UHPLC-triple quadrupole-mass analyzer. Analytes were separated on a RP 18 column under gradient elution of the mobile phases, water with 0.1 % formic acid and acetonitrile. Whole nail and hair samples from seven autopsy cases were split into segments and analyzed. RESULTS: The entire method was validated according to the German Society of Forensic Toxicology guidelines. In addition, the concentration ratios of selected substances and their metabolites were calculated. Similar concentration ratios in hair and nails were detected for 3,4-methylendioxyamphetamine (MDA)/3,4-methylenedioxy-N-methylamphetamine (MDMA), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)/methadone, and bisnortilidine/nortilidine in some of the cases. Reduced 6-monoacetylmorphine (6-MAM) and cocaine concentrations were observed as a result of sample preparation using the ball mill. Previous heroin intake could be assumed from the detection of 6-MAM and morphine in only one nail segment in one case. CONCLUSIONS: Nail samples may serve as an alternative matrix for the detection of long-term consumption of a wide range of drugs. Based on our results, drug concentrations in nails are not comparable to those in hair. The main mechanisms for drug incorporation into the nails may be during the formation of the nail plate by the germinal matrix. However, external contamination can also affect the analysis of nail clippings.