Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study.

PURPOSE: To determine the influence of epilepsy and its treatment on pregnancy and its outcome. DESIGN: Controlled, observational study. SETTING: National Health Service maternity hospitals in Liverpool and Manchester regions. POPULATION: 277 women with epilepsy (WWE) and 315 control women. METHODS: WWE were recruited from antenatal clinics. Controls were matched for age and parity but not gestational age. Information was obtained by interview and from clinical records. MAIN OUTCOME MEASURES: Obstetric complications, mode of delivery, condition of newborn. RESULTS: Distribution of epilepsy syndromes was similar to previous surveys. Most WWE (67%) received monotherapy with carbamazepine, sodium valproate or lamotrigine. Half WWE had no seizures during pregnancy but 34% had tonic clonic seizures. Seizure-related injuries were infrequent. Pregnancies with obstetric complications were increased in women with treated epilepsy (WWTE 45%, controls 33%; p=0.01). Most had normal vaginal delivery (WWTE 63%, controls 61%; p=0.65). Low birth weight was not increased (WWTE 6.2%, controls 5.2%; p=0.69). There were more major congenital malformations (MCM) (WWTE 6.6%, controls 2.1%; p=0.02) and fetal/infant deaths (WWTE 2.2%, controls 0.3%; p=0.09). Amongst monotherapies MCM prevalence was highest with valproate (11.3%; p=0.005). Lamotrigine (5.4%; p=0.23) and carbamazepine (3.0%; p=0.65) were closer to controls (2.1%). There was no association between MCM and dose of folic acid pre-conception. CONCLUSION: MCM were more prevalent in the babies of WWTE particularly amongst those receiving sodium valproate.

Forensic Botany: Evidence and Analysis.

Forensic botany is the use of plant evidence in matters of law. While plant fragments are often collected as trace evidence, they are only occasionally identified using microscopy and are still more rarely assessed using molecular biology techniques for individualization and sourcing of a sample. There are many different methods useful for DNA typing of plants; this review focuses on those techniques (DNA sequencing, STR, AFLP, RAPD) most relevant to the forensic science community and on those methods currently in practice. Plant evidence is commonly associated with homicides, with clandestine graves, as trace pollen on clothing, vehicles, or packaging, or in the transport of illicit drugs. DNA can be especially useful for the identification of minute quantity of samples, for differentiation of plants that lack distinguishing morphological features, and for generating a unique identifier for associative forensic evidence.

The longer term outcome of children born to mothers with epilepsy.

OBJECTIVES: To determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero. DESIGN: Retrospective study of children born to mothers with epilepsy. SETTING: Regional epilepsy clinics in Liverpool and Manchester, UK. PARTICIPANTS: Children aged between 6 months and 16 years born to mothers with epilepsy. MAIN OUTCOME MEASURES: Structured interviews, hospital records, clinical examination, and psychometric tests (Wechsler) were used to assess exposure and intelligence quotient (IQ). Blinded assessment of photographs was used to score children with characteristic dysmorphic features. RESULTS: A total of 249 children aged 6 and over were studied: 41 were exposed to sodium valproate, 52 to carbamazepine, 21 to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the valproate group compared to unexposed and other monotherapy groups. Multiple regression analysis showed that both valproate exposure and frequent tonic-clonic seizures in pregnancy were significantly associated with a lower verbal IQ despite adjusting for other confounding factors. There was a significant negative correlation between dysmorphic features and verbal IQ in children exposed to valproate. CONCLUSIONS: This study identifies valproate as a drug carrying potential risks for developmental delay and cognitive impairment and is the first to suggest that frequent tonic-clonic seizures have a similar effect. Our results need to be interpreted with caution given their retrospective nature. Women with epilepsy need careful counselling about individual risk benefit of AED treatment before pregnancy.

The Green Revolution: botanical contributions to forensics and drug enforcement.

Forensic botany encompasses many sub-disciplines, including plant anatomy, plant ecology, plant systematics, plant molecular biology, palynology, and limnology. Although the field of forensic botany has been recognized since the mid-1900's, the use of trace plant material as physical evidence in criminal casework is still novel. A review of published forensic casework that used plant evidence is presented here. Cases include the analysis of wood evidence in the Charles Lindbergh baby kidnapping, the use of pollen in establishing the location of a sexual assault, and pollen analysis to determine the time of year for burial in a mass grave. Additional cases discuss the use of plant growth rates to determine the time of a body deposit in a field, the use of diatoms to link individuals to a crime scene, and plant DNA typing to match seedpods to a tree under which a body was discovered. New DNA methods in development for plant species identification and individualization for forensic applications are also discussed. These DNA methods may be useful for linking an individual to a crime scene or physical evidence to a geographic location, or tracking marijuana distribution patterns.

Epilepsy, the law and the media.

It is generally accepted that the media exerts a powerful influence over what the general public feels and believes. This study examined references to epilepsy and the law found in general media communications from January 1993 to December 1994 in the UK. These articles were extracted from general audience material mainly newspapers and magazines. Any article which referred to the legal aspects of epilepsy were then selected. These included those relating to legislation e.g. driving, state benefits and those relating to criminal law e.g. convictions. The reports were analyzed in terms of type of communication, space allotted, circulation and terminology used both in the title and the general text. An attempt was also made to classify the general image which the article portrayed. It is accepted that content analysis itself provides no direct data about the nature of the communicator, the audience or its effects and this method has cautiously been used to classify and describe the manifest content of the method of communication. The study concludes that although it is encouraging that legal aspects of epilepsy are receiving media attention, this attention could be used in a more positive manner in promoting awareness, rather than many of the cases examined which appeared to use negative images in order to pander to popular audience appeal.

Coroners' autopsy reporting of sudden unexplained death in epilepsy (SUDEP) in the UK.

Sudden Unexplained Death due to Epilepsy (SUDEP) is not uncommon. The incidence may be difficult to ascertain due to variations in reporting the cause of death investigated by coroners. To study this, we used a cuttings service to identify all cases of SUDEP reported in the UK press during 1992. These cases had been investigated by a number of different pathologists and coroners. Post-mortem reports, witness statements and other relevant information were examined in 40 cases. Inconsistencies were observed both in investigations performed and observations made at time of death. Varying degrees of detail concerning 'type' and history of epilepsy were found. In 70% of cases, type of epilepsy was either not known or not referred to. Similar inconsistencies were found with details of medication, position of body, toxicology reporting and detailed examination of organs, particularly the brain. Attributed cause of death varied considerably, with epilepsy stated as primary cause of death in less than half of the sample. Disparity was noted also in coroner's verdicts, with no distinct pattern emerging in relation to attributed cause of death. The wide variation in practice of individual coroners and pathologists in the investigation and registering of sudden deaths raises issues of quality assurance. As the majority of these deaths are unwitnessed, we rely on these investigations and the statements of officials in the process of registering deaths. If we are to build a profile of people who are at risk of SUDEP, epilepsy must be stated on the death certificate. Until this happens, many more of these deaths will go unrecorded.

Chimeric gamma-delta signal joints. Implications for the mechanism and regulation of T cell receptor gene rearrangement.

Rearrangement of Ag receptor genes requires recognition by the lymphocyte recombinase of heptamer-nonamer signal sequences followed by two endonucleolytic cleavages and two DNA ligations to form the coding and signal joints. The phenomenon of trans-rearrangement, in which Ag receptor gene segments located on different chromosomes recombine to yield chimeric products, provides an in vivo system in which to investigate the ability of the recombinase to carry out each of these functions in trans. Trans-rearrangements between TCRG and TCRD loci, similar in structure and frequency to those observed previously in human lymphoid tissues, were demonstrated in normal mouse thymus by PCR with crossed V gamma/J delta and V delta/J gamma primer pairs. A simple mechanistic model for trans-rearrangement was then tested. This model posits an ability of the recombinase to catalyze the formation of both coding and signal joints in trans and therefore predicts that trans-rearrangements will generate chimeric signal joints. In adult thymus, chimeric D delta 2-J gamma 1 and D delta 2-J gamma 2 signal joints, containing fused heptamer-nonamer sequences, could be detected by PCR and were each present at frequencies sufficient to account for a large proportion of the corresponding TCRG/TCRD trans-rearrangements. In agreement with the predictions of the model, chimeric signal joints were found as both linear chromosomal and circular episomal DNA. The results provide a framework for understanding the formation of chromosomal translocations in normal and neoplastic lymphoid cells and support the possibility of a looping mechanism for standard gene rearrangement. To test the form of regulation of TCRG rearrangement, the frequencies of specific signal joints from standard and trans-rearrangements were compared. Although J gamma 1 and J gamma 2 segments participated with equal frequency in trans-rearrangement with D delta 2, only the J gamma 1 segment participated in standard rearrangement with V gamma 5. The results suggest that V-J recombination in the TCRG locus is regulated directly at the DNA level by cis-acting constraints which do not affect the accessibility of individual TCRG gene segments to recombination in trans.

Eosinophilic fasciitis (Shulman syndrome) in association with morphoea and systemic sclerosis.

A case of Shulman syndrome or diffuse fasciitis with eosinophilia is reported. Both superficial scleroderma (morphoea) and systemic sclerosis accompanied the subcutaneous changes.