Postictal psychosis: presymptomatic risk factors and the need for further investigation of genetics and pharmacotherapy

BACKGROUND: Postictal psychosis (PIP), an episode of psychosis occurring after a cluster of seizures, is common and may be associated with profound morbidity, including chronic psychosis. Symptoms are often pleomorphic, involving a range of psychotic symptoms, including hallucinations and disorders of thought. PIP is treatable and may be averted if presymptomatic risk factors are considered in susceptible patients and treatment is initiated. CASE PRESENTATION: In this report, we present an illustrative case of PIP. The patient, Mr. R, presented to our emergency room with delusions and disordered thought process following a cluster of seizures. He recovered after admission, sedation and treatment with antipsychotic medication. DISCUSSION: A list of presymptomatic risk factors is established based on review of current literature. Identification of such risk factors may potentially help with prophylactic treatment; however, little empirical research exists in this area and treatment guidelines are thus far largely based on expert opinion. Further, while the neurobiology of schizophrenia is advancing at a rapid pace, largely due to advances in genetics, the pathophysiology of PIP remains largely unknown. Considering the progress in schizophrenia research in the context of the clinical features of PIP and existing studies, potential neurobiological mechanisms for PIP are herein proposed, and further genetic analyses, which may help identify those susceptible, are warranted. CONCLUSION: While PIP is an important problem that may present first to general hospital psychiatrists, as in the case presented, this topic is under-represented in the medical psychiatry literature. As discussed in this article, further research is needed to develop presymptomatic screens and treatment pathways to help prevent morbidity

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Complex inheritance and parent-of-origin effect in juvenile myoclonic epilepsy

BACKGROUND: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy (IGE) with complex inheritance. Previous studies have suggested maternal inheritance and female excess in IGEs but have not been specific for JME. We investigated evidence for maternal inheritance, female excess and patterns of familial seizure risk in a well-characterized sample of JME families. METHODS: We ascertained 89 families through a JME proband and 50 families through a non-JME IGE proband. JME families were divided into those with and without evidence of linkage to the EJM1 susceptibility locus on chromosome 6. We analyzed transmission in 43 multigenerational families, calculated the adjusted sex ratio for JME, and looked for evidence of seizure specific risk in 806 family members. RESULTS: We found evidence for preferential maternal transmission in both EJM1-linked and unlinked families (2.7:1), evidence even more marked when potential selection factors were excluded. The adjusted female: male risk ratio was very high in JME (RR=12.5; 95% CI: 1.9–83.7). Absence seizures in JME probands increased the overall risk of seizures in first degree relatives (15.8% vs. 7.0%, P=0.011), as well as first-degree relatives' specific risk of absence seizures (6% vs. 1.6%, P=0.01), but not myoclonic seizures. CONCLUSIONS: We have confirmed the finding of maternal inheritance in JME, which is not restricted to JME families linked to the EJM1 locus. The striking female excess in JME may relate to anatomical and/or endocrine sexual dimorphism in the brain. Evidence for independent inheritance of absence and myoclonic seizures in JME families reinforces a model in which combinations of loci confer susceptibility to the component seizure types of IGE

Morphological Characteristics of Brain Tumors Causing Seizures

Objective: To quantify size and localization differences between tumors presenting with seizures vs nonseizure neurological symptoms. Design: Retrospective imaging survey. We performed magnetic resonance imaging–based morphometric analysis and nonparametric mapping in patients with brain tumors. Setting: University-affiliated teaching hospital. Patients or Other Participants: One hundred twenty-four patients with newly diagnosed supratentorial glial tumors. Main Outcome Measures: Volumetric and mapping methods were used to evaluate differences in size and location of the tumors in patients who presented with seizures as compared with patients who presented with other symptoms. Results: In high-grade gliomas, tumors presenting with seizures were smaller than tumors presenting with other neurological symptoms, whereas in low-grade gliomas, tumors presenting with seizures were larger. Tumor location maps revealed that in high-grade gliomas, deep-seated tumors in the pericallosal regions were more likely to present with nonseizure neurological symptoms. In low-grade gliomas, tumors of the temporal lobe as well as the insular region were more likely to present with seizures. Conclusions: The influence of size and location of the tumors on their propensity to cause seizures varies with the grade of the tumor. In high-grade gliomas, rapidly growing tumors, particularly those situated in deeper structures, present with non–seizure-related symptoms. In low-grade gliomas, lesions in the temporal lobe or the insula grow large without other symptoms and eventually cause seizures. Quantitative image analysis allows for the mapping of regions in each group that are more or less susceptible to seizures. Seizures are encountered in a majority of patients with primary brain tumors and are a major cause of morbidity in these patients.1,2 Thirty percent to 50% of patients experience a seizure by the time their tumors are diagnosed, and an additional 6% to 45% of patients who do not initially present with seizures eventually develop them.3- 5 Characteristics of brain tumors and their mechanism in causing seizures in patients are incompletely understood.4,6 Low-grade, well-differentiated gliomas,1,6- 9 cortically located tumors,3,10- 14 and location in the temporal/frontal and motor/sensory cortices6,8,15- 17 are more frequently associated with seizures. Although there is a high incidence of seizures in these patients, treatment strategies remain poorly defined. Prophylactic anticonvulsant therapy, shown to be ineffective in preventing seizures in patients with brain tumors in multiple large-scale studies,12,18- 20 is not recommended by the American Academy of Neurology.5 Nonetheless, prophylaxis remains a widespread practice21 because of difficulty in determining which patients are at greatest risk for seizures. Determination of morphometric factors influencing seizures would help in identifying patients at greatest risk for early, targeted treatment and prevent potentially toxic, unnecessary treatment in patients at minimal risk. Although studies examining brain tumors in relationship to epilepsy have localized tumors to a particular lobe,10 few studies have performed quantitative volumetric or spatial mapping analysis of tumors in relation to their epileptogenic potential. Regions within a particular lobe are likely to exhibit different epileptogenic potential to tumor invasion and tumors frequently affect multiple contiguous lobes.6 Modern imaging techniques allow for analysis of lesions over a large group of subjects through registration and mapping techniques. In this study, we used these techniques to examine the size and location of primary supratentorial glial brain tumors and characterized their propensity to cause seizures at presentation

Current dipole orientation and distribution of epileptiform activity correlates with cortical thinning in left mesiotemporal epilepsy

To evaluate cortical architecture in mesial temporal lobe epilepsy (MTLE) with respect to electrophysiology, we analyze both magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 19 patients with left MTLE. We divide the patients into two groups: 9 patients (Group A) have vertically oriented antero-medial equivalent current dipoles (ECDs). 10 patients (Group B) have ECDs that are diversely oriented and widely distributed. Group analysis of MRI data shows widespread cortical thinning in Group B compared with Group A, in the left hemisphere involving the cingulate, supramarginal, occipitotemporal and parahippocampal gyri, precuneus and parietal lobule, and in the right hemisphere involving the fronto-medial, -central and -basal gyri and the precuneus. These results suggest that regardless of the presence of hippocampal sclerosis, in a subgroup of patients with MTLE a large cortical network is affected. This finding may, in part, explain the unfavorable outcome in some MTLE patients after epilepsy surgery

Malic Enzyme 2 May Underlie Susceptibility to Adolescent-Onset Idiopathic Generalized Epilepsy

Idiopathic generalized epilepsy (IGE) is a class of genetically determined, phenotypically related epilepsy syndromes. Linkage analysis identified a chromosome 18 locus predisposing to a number of adolescent-onset IGEs. We report a single-nucleotide polymorphism (SNP) association analysis of the region around the marker locus with the high LOD score. This analysis, which used both case-control and family-based association methods, yielded strong evidence that malic enzyme 2 (ME2) is the gene predisposing to IGE. We also observed association among subgroups of IGE syndromes. An ME2-centered nine-SNP haplotype, when present homozygously, increases the risk for IGE (odds ratio 6.1; 95% confidence interval 2.9–12.7) compared with any other genotype. Both the linkage analysis and the association analysis support recessive inheritance for the locus, which is compatible with the fact that ME2 is an enzyme. ME2 is a genome-coded mitochondrial enzyme that converts malate to pyruvate and is involved in neuronal synthesis of the neurotransmitter γ-aminobutyric acid (GABA). The results suggest that GABA synthesis disruption predisposes to common IGE and that clinical seizures are triggered when mutations at other genes, or perhaps other insults, are present

Antiepileptic drug use in women of childbearing age

Research on antiepileptic drug (AED) teratogenesis has demonstrated an increased risk for valproate. The impact of these findings on current AED prescribing patterns for women of childbearing age with epilepsy is uncertain. The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study is an ongoing prospective multicenter observational investigation that enrolled pregnant women with epilepsy on the most common AED monotherapies from October 1999 to February 2004 (carbamazepine, lamotrigine, valproate, and phenytoin). A 2007 survey of AED use in women of childbearing age at eight NEAD centers found a total of 932 women of childbearing age with epilepsy (6% taking no AED, 53% monotherapy, 41% polytherapy). The most common monotherapies were lamotrigine or levetiracetam. Since 2004, prescriptions of carbamazepine, phenytoin, and valproate have decreased, whereas those for levetiracetam have increased. Except for the top two AED monotherapies, there were marked differences in other monotherapies and in polytherapies between U.S. and UK centers. Future investigations are needed to examine reasons for drug choice