Late-onset ornithine transcarbamylase deficiency mimicking a focal opercular syndrome.

A previously healthy 27-year-old man was brought to hospital after been found late at night confused, agitated and talking incoherently. He represented 12 days later with focal seizures, progressing to anarthria and encephalopathy. MR scan of brain showed diffuse cerebral oedema and his plasma ammonia was >2000 µmol/L (12-55 µmol/L).

Incidence of first seizures, epilepsy, and seizure mimics in a geographically defined area.

Objective: To determine the incidence of first seizures, epilepsy, and seizure mimics in a geographically defined area using the updated 2014 International League Against Epilepsy (ILAE) definition, which allows an epilepsy diagnosis after a single seizure when the risk of further seizures over the next 10 years is ≈60% or greater. This replaced the 1993 definition by which epilepsy was diagnosed when a person had ≥2 seizures separated by 24 hours.

Methods: Using multiple overlapping methods of case ascertainment followed by individual case classification by an epileptologist, we identified all first seizures, new diagnosis of epilepsy, and seizure mimics occurring in a defined geographic area (population 542,868) from January 1, 2017, to December 31, 2017.

Application of Recent International Epidemiological Guidelines to a Prospective Study of the Incidence of First Seizures, Newly-Diagnosed Epilepsy and Seizure Mimics in a Defined Geographic Region in Ireland.

Studies adherent to international guidelines and epilepsy classification are needed to accurately record the incidence of isolated seizures, epilepsy and seizure-mimics within a population. Because the diagnosis of epilepsy is largely made through clinical assessment by experienced physicians, seizures and epilepsy are susceptible to misdiagnosis. Previous epidemiological studies in epilepsy have not captured "seizure mimics".

Giant Cell Arteritis Presenting with Bilateral Subdural Haematomas of Arterial Origin.

Unlabelled: Giant cell arteritis or temporal arteritis is an inflammatory condition affecting medium to large sized vessels, particularly the cranial arteries. A 76-year-old man with no significant past medical history presented to the emergency department with a 3-week history of diffuse headaches associated with fever, loss of appetite, weight loss and general malaise. A CT scan of the brain showed bilateral shallow chronic low density subdural haematomas.

TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function.

Topoisomerase II (TOP2) removes torsional stress from DNA and facilitates gene transcription by introducing transient DNA double-strand breaks (DSBs). Such DSBs are normally rejoined by TOP2 but on occasion can become abortive and remain unsealed. Here we identify homozygous mutations in the TDP2 gene encoding tyrosyl DNA phosphodiesterase-2, an enzyme that repairs 'abortive' TOP2-induced DSBs, in individuals with intellectual disability, seizures and ataxia.

Heritability of subcortical volumetric traits in mesial temporal lobe epilepsy.

Objectives: We aimed to 1) determine if subcortical volume deficits are common to mesial temporal lobe epilepsy (MTLE) patients and their unaffected siblings 2) assess the suitability of subcortical volumetric traits as endophenotypes for MTLE.

Methods: MRI-based volume measurements of the hippocampus, amygdala, thalamus, caudate, putamen and pallidium were generated using an automated brain reconstruction method (FreeSurfer) for 101 unrelated 'sporadic' MTLE patients [70 with hippocampal sclerosis (MTLE+HS), 31 with MRI-negative TLE], 83 unaffected full siblings of patients and 86 healthy control subjects. Changes in the volume of subcortical structures in patients and their unaffected siblings were determined by comparison with healthy controls.

MRI-based brain structure volumes in temporal lobe epilepsy patients and their unaffected siblings: a preliminary study.

Introduction: Investigating the heritability of brain structure may be useful in simplifying complicated genetic studies in temporal lobe epilepsy (TLE). A preliminary study is presented to determine if volume deficits of candidate brain structures present at a higher rate in unaffected siblings than controls subjects.

Methods: T1-weighted MR images was acquired for 28 TLE patients, a same-sex unaffected sibling of 12 of these and 28 normal controls.

Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.

Aims: An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin.

Materials & Methods: We recruited patients with lamotrigine-induced cADRs (n = 46) and patients with phenytoin-cADRs (n = 44) and the 1958 British birth cohort was used as a control (n = 1296).

Pharmacogenomics and epilepsy: the road ahead.

Epilepsy is one of the most common, serious neurological disorders, affecting an estimated 50 million people worldwide. The condition is typically treated using antiepileptic drugs of which there are 16 in widespread use. However, there are many different syndrome and seizure types within epilepsy and information guiding clinicians on the most effective drug and dose for individual patients is lacking.

Using atypical symptoms and red flags to identify non-demyelinating disease.

Background: Red flags and atypical symptoms have been described as being useful in suggesting alternative diagnoses to multiple sclerosis (MS) and clinically isolated syndrome (CIS); however, their diagnostic utility has not been assessed. The aim of this study was to establish the predictive value of red flags and the typicality/atypicality of symptoms at presentation in relation to the final diagnosis of patients referred with suspected MS.

Methods: All patients referred with suspected MS over a 3-year period were assessed by the typicality of the clinical presentation and the occurrence of red flags in relation to the eventual diagnosis.

Genomic microdeletions associated with epilepsy: not a contraindication to resective surgery.

Purpose: Several recent reports of genomic microdeletions in epilepsy will generate further research; discovery of more microdeletions and other important classes of variants may follow. Detection of such genetic abnormalities in patients being evaluated for surgical treatment might raise concern that a genetic defect, possibly widely expressed in the brain, will affect surgical outcome.

Methods: A reevaluation was undertaken of clinical presurgical data, histopathology of surgical specimen, and postsurgical outcome in patients with mesial temporal lobe epilepsy (MTLE) who have had surgical treatment for their drug-resistant seizures, and who have been found to have particular genomic microdeletions.

HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.

Background: Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.

Methods: We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent.

Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients.

Ataxia Telangiectasia (A-T) patients have biallelic inactivation of the ATM gene and exhibit a 200-fold-increased frequency of lymphoid tumours. ATM mutations have been found in a number of adult lymphoid malignancies but there is no data on the occurrence of ATM mutations in multiple myeloma tumours. The purpose of our work was to investigate the occurrence of ATM mutations in multiple myeloma and to this end we screened 45 sporadic cases for ATM mutations using denaturing high-performance liquid chromatography analysis and DNA sequencing.

Broadening the phenotype of childhood-onset dopa-responsive dystonia.

Background: Dopa-responsive dystonia (DRD) may cause early-onset dystonia, with extrapyramidal or pyramidal tract dysfunction.

Objective: To broaden the phenotype of DRD.

Setting: Tertiary referral university hospital.