Search

Purpose: Epilepsy patients consider driving issues to be one of their most serious concerns. Ideally, decisions regarding fitness to drive should be based upon thorough evaluations by specialists in epilepsy care. In 2009, an EU directive was published aiming to harmonize evaluation practices within European countries, but, despite these recommendations, whether all epileptologists use the same criteria is unclear. We therefore conducted this study to investigate routine practices on how epileptologists at European epilepsy centers evaluate fitness to drive.Methods: A questionnaire was sent to 63 contact persons identified through the European Epi-Care and the E-pilepsy network. The questionnaire addressed how fitness-to-drive evaluations were conducted, the involvement of different professionals, the use and interpretation of EEG, and opinions on existing regulations and guidelines.Results: The questionnaire was completed by 35 participants (56 % response rate). Results showed considerable variation regarding test routines and the emphasis placed on the occurrence and extent of epileptiform discharges revealed by EEG. 82 % of the responders agreed that there was a need for more research on how to better evaluate fitness-to-drive in people with epilepsy, and 89 % agreed that regulations on fitness to drive evaluations should be internationally coordinated.Conclusion: Our survey showed considerable variations among European epileptologists regarding use of EEG and how findings of EEG pathology should be assessed in fitness-to-drive evaluations. There is a clear need for more research on this issue and international guidelines on how such evaluations should be carried out would be of value.

Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p

Introduction: Prenatal exposure to antiepileptic drugs (AEDs) is associated with developmental compromises in verbal intelligence and social skills in childhood. Our aim was to evaluate whether a multifeature Mismatch Negativity (MMN) paradigm assessing semantic and emotional components of linguistic and emotional processing would be useful to detect possible alterations in early auditory processing of newborns with prenatal AED exposure. Material and methods: Data on AED exposure. pregnancy outcome, neuropsychological evaluation of the mothers, information on maternal epilepsy type, and a structured neurological examination of the newborn were collected prospectively. Blinded to AED exposure, we compared a cohort of 36 AED-exposed with 46 control newborns at the age of two weeks by measuring MMN with a multifeature paradigm with six linguistically relevant deviant sounds and three emotionally uttered sounds. Results: Frontal responses for the emotionally uttered stimulus Happy differed significantly in the exposed newborns compared with the control newborns. In addition, responses to sounds with or without emotional component differed in newborns exposed to multiple AEDs compared with control newborns or to newborns exposed to only one AED. Conclusions: These preliminary findings suggest that prenatal AED exposure may alter early processing of emotionally and linguistically relevant sound information. (C) 2019 Elsevier Inc. All rights reserved.

Background and Purpose— Seizures are a common complication of intracerebral hemorrhage (ICH). We developed a novel tool to quantify this risk in individual patients. Methods— Retrospective analysis of the observational Helsinki ICH Study (n=993; median follow-up, 2.7 years) and the Lille Prognosis of InTra-Cerebral Hemorrhage (n=325; 2.2 years) cohorts of consecutive ICH patients admitted between 2004 and 2010. Helsinki ICH Study patients’ province-wide electronic records were evaluated for early seizures occurring within 7 days of ICH and among 7-day survivors (n=764) for late seizures (LSs) occurring >7 days from ICH. A Cox regression model estimating risk of LSs was used to derive a prognostic score, validated in the Prognosis of InTra-Cerebral Hemorrhage cohort. Results— Of the Helsinki ICH Study patients, 109 (11.0%) had early seizures within 7 days of ICH. Among the 7-day survivors, 70 (9.2%) patients developed LSs. The cumulative risk of LSs was 7.1%, 10.0%, 10.2%, 11.0%, and 11.8% at 1 to 5 years after ICH, respectively. We created the CAVE score (0–4 points) to estimate the risk of LSs, with 1 point for each of cortical involvement, age 10 mL, and early seizures within 7 days of ICH. The risk of LSs was 0.6%, 3.6%, 9.8%, 34.8%, and 46.2% for CAVE scores 0 to 4, respectively. The c-statistic was 0.81 (0.76–0.86) and 0.69 (0.59–0.78) in the validation cohort. Conclusions— One in 10 patients will develop seizures after ICH. The risk of this adverse outcome can be estimated by a simple score based on baseline variables.

New antiepileptic drug (AED) options for generalised seizure types have been adopted for use as treatment for Unverricht-Lundborg disease. Whether this has led to improved seizure control or functional outcome in ULD patients remains obscure. We retrospectively identified all patients seen at Helsinki University Hospital due to Unverricht-Lundborg disease during 2003-2008 in order to determine which AED treatments had been retained for long-term use. The majority of the patients had severe functional disabilities. In the year preceding the last hospital visit, all patients (n=20) were receiving polytherapy and 14 patients had been free of tonic-clonic seizures. During follow-up, improvement in myoclonia had been recorded for the majority of patients with either add-on piracetam, topiramate, or levetiracetam, but valproate was still in use by all patients. Treatment with lamotrigine had been started and retained less often relative to other AEDs. Add-on AED treatment was often associated with significant adverse effects. Unverricht-Lundborg disease patients may benefit from add-on treatment with levetiracetam or topiramate for seizure control. Treatment of eventual comorbidities with other than AEDs is also discussed.

Introduction: Prenatal antiepileptic drug (AED) exposure is associated with an increased risk of cognitive impairment and autism spectrum disorders detected mainly at the age of two to six years. We examined whether the developitiental aberrations associated with prenatal AED exposure-could be-detected already in infancy and whether effects on visual attention can be observed at this early age. Material and methods: We compared a prospective cohort of infants with in utero exposure to AED (n = 56) with infants without drug exposures (n = 62). The assessments performed at the age of seven months included standardized neurodevelopmental scores (Griffiths Mental Developmental Scale and Hammersmith Infant Neurological Examination) as well as a novel eye-tracking-based test for visual attention and orienting to faces. Background information included prospective collection of AED exposure data, pregnancy outcome, neuropsychological evaluation of the mothers, and information on maternal epilepsy type. Results: Carbamazepine, oxcarbazepine, and valproate, but not lamotrigine or levetiracetam, were associated with impaired early language abilities at the age of seven months. The general speed of visuospatial orienting or attentional bias for faces measured by eye-tracker-based tests did not differ between AED-exposed and control infants. Discussion: Our findings support the idea that prenatal AED exposure may impair verbal abilities, and this effect may be detected already in infancy. In contrast, the early development of attention to faces was spared after in utero AED exposure. (C) 2016 Elsevier Inc. All rights reserved.

SUMMARY Purpose: Ictal video‐electroencephalography (EEG) is commonly used to establish ictal onset-zone location. Recently software development has enabled systematic studies of ictal magnetoencephalography (MEG). In this article, we evaluate the ability of ictal MEG signals tolocalize the seizure-onset zone. Methods: Twenty-six patients underwent ictal MEG and epilepsy surgery. Prediction of seizure-onset zone by ictal and interictal MEG was retrospectively compared with ictal-onset area found by intracranial EEG in 12 patients. The specificity and sensitivity of the prediction were calculated at hemisphere-lobe (HL) and at hemisphere-lobesurface (HLS) levels. Key Findings: The sensitivity of ictal MEG source localization was 0.958 on HL and 0.706 on HLS levels, and its specificity was 0.900 on HL and 0.731 on HLS levels. The interictal MEG dipole cluster, defined as >10 dipoles on one lobar surface, had sensitivity of 0.400 and specificity of 0.769. Ictal MEG was equally sensitive and specific on dorsolateral and nondorsolateral neocortical surfaces up to a depth of 4 cm from the scalp. Significance: Sources of ictal-onset MEG signals and interictal dipole clusters are essentially equally specific in estimation of the ictal-onset zone on lobar surface resolution, but ictal MEG is more sensitive. On the lobe resolution, ictal MEG estimates ictal-onset zone with high sensitivity

Cavernomas of the temporal lobe occur in 10–20% of patients with cerebral cavernomas. They frequently cause epileptic seizures, some of which tend to become refractory to medical therapy. Surgical removal of safely achievable symptomatic lesions has been frequently consistent with good long-term outcome. In the present study, a postoperative outcome is assessed. Of our 360 consecutive patients with cerebral cavernomas, 53 (15%) had a single cavernoma in the temporal lobe. Forty-nine patients were treated surgically and were included in the study. All data were analyzed retrospectively. The cavernomas were allocated into three groups based on the temporal lobe site: medial, anterolateral, and posterolateral. To collect follow-up data, all available patients were interviewed by phone. Seizure outcome was assessed using the Engel classification and general outcome using the Glasgow Outcome Scale (GOS). Patients’ median age at presentation was 37 (range, 7–64) years, with a female/male ratio of 2.5:1. Epileptic seizures occurred in 40 patients (82%). Median duration of seizures preoperatively was 3 (range, 0.1–23) years. In addition, four patients (10%) had memory disorder. Three patients without history of seizures (6%) complained of headache and two (4%) had memory problems. Three patients (6%) had an incidental cavernoma. Hemorrhage occurred in nine patients (18%) preoperatively. Median postoperative follow-up time was 6 (range, 0.2–26) years. Favorable seizure outcome (Engel class I and II) was registered in 35 patients (90%). Ten patients (25%) who had only a single seizure before surgery were seizure free during postoperative follow-up. Good general outcome (GOS, 4.5) was detected in 46 patients (96%). Two patients (4%) developed a new mild memory deficit after surgery, and in two patients existing memory deficits worsened. Microsurgical removal of temporal lobe cavernomas is a safe and effective method to improve seizure outcome in patients with medically intractable epilepsy and to prevent deterioration caused by hemorrhage.

SummaryObjective Prenatal exposure to antiepileptic drugs (AEDs) is associated with an increased risk of cognitive dysfunction at early school age. Our aim was to investigate whether signs of adverse drug effects on brain function could be detected already during the first 2 weeks of life. Methods We studied prospectively 56 full-term newborns with prenatal exposure to AEDs and 67 unexposed newborns for the following characteristics: Background information, AED exposure data, pregnancy outcome, neuropsychological evaluation of the mothers, clinical neurologic status with Hammersmith Neonatal Neurological Examination and early cortical activity using electroencephalography (EEG). For EEG assessment, we developed and provide automated quantitation algorithms of several earlier described features: oscillatory bouts at theta and alpha frequencies, frequency spectra, interhemispheric synchrony, and interburst intervals (IBIs). Results The AED-exposed newborns had lower limb and axial tone and were less irritable than the unexposed newborns. EEG assessment disclosed significant differences in alpha bouts, in the frequency spectra, as well as in the spatial distributions of interhemispheric synchrony and IBIs. Significance The results indicate that fetal AED exposure may affect early neonatal neurologic status and several features of early cortical activity. The findings suggest that interference of activity-dependent network development may be a possible mechanism to explain the link from fetal AED exposure to later neurocognitive sequelae.

Summary For about 30% of patients with epilepsy the cause is unknown. Even in patients with a known risk factor for epilepsy, such as ischaemic stroke, only a subpopulation of patients develops epilepsy. Factors that contribute to the risk for epileptogenesis in a given individual generally remain unknown. Studies in the past decade on epilepsy in patients with ischaemic stroke suggest that, in addition to the primary ischaemic injury, existing difficult-to-detect microscale changes in blood vessels and white matter present as epileptogenic pathologies. Injury severity, location and type of pathological changes, genetic factors, and pre-injury and post-injury exposure to non-genetic factors (ie, the exposome) can divide patients with ischaemic stroke into different endophenotypes with a variable risk for epileptogenesis. These data provide guidance for animal modelling of post-stroke epilepsy, and for laboratory experiments to explore with increased specificity the molecular 'mechanisms, biomarkers, and treatment targets of post-stroke epilepsy in different circumstances, with the aim of modifying epileptogenesis after ischaemic stroke in individual patients without compromising recovery.

Boucherit, Soraya/0000-0002-8819-7594; Lorenzo, Lazaro/0000-0001-6648-8684; Jouanguy, Emmanuelle/0000-0002-7358-9157; Zhang, Shen-Ying/0000-0002-9449-3672; Abel, Laurent/0000-0001-7016-6493; Seppanen, Mikko/0000-0001-9733-3650; Ciancanelli, Michael/0000-0002-4623-852X; Hautala, Timo/0000-0001-7889-1614; Casanova, Jean-Laurent/0000-0002-7782-4169; Byun, Minji/0000-0002-2830-4079 WOS: 000345301000005 PubMed: 25339207 Objective: To determine the proportion of children with herpes simplex encephalitis (HSE) displaying TLR3 deficiency, the extent of TLR3 allelic heterogeneity, and the specific clinical features of TLR3 deficiency. Methods: We determined the sequence of all exons of TLR3 in 110 of the 120 patients with HSE enrolled in our study who do not carry any of the previously described HSE-predisposing mutations of TLR3 pathway genes (TLR3, UNC93B1, TRIF, TRAF3, and TBK1). All the new mutant TLR3 alleles detected were characterized experimentally in-depth to establish the causal relationship between the genotype and phenotype. Results: In addition to the 3 previously reported TLR3-deficient patients from the same cohort, 6 other children or young adults with HSE carry 1 of 5 unique or extremely rare (minor allele frequency

Repetitive spreading depression (SD) waves, involving depolarization of neurons and astrocytes and up-regulation of glucose consumption, is thought to lower the threshold of neuronal death during and immediately after ischemia. Using rat models for SD and focal ischemia we investigated the expression of cyclooxygenase-1 (COX-1), the constitutive form, and cyclooxygenase-2 (COX-2), the inducible form of a key enzyme in prostaglandin biosynthesis and the target enzymes for nonsteroidal anti-inflammatory drugs. Whereas COX-1 mRNA levels were undetectable and uninducible, COX-2 mRNA and protein levels were rapidly increased in the cortex, especially in layers 2 and 3 after SD and transient focal ischemia. The cortical induction was reduced by MK-801, an N -methyl- d -aspartic acid-receptor antagonist, and by dexamethasone and quinacrine, phospholipase A 2 (PLA 2 ) inhibiting compounds. MK-801 acted by blocking SD whereas treatment with PLA 2 inhibitors preserved the wave propagation. NBQX, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-receptor antagonist, did not affect the SD-induced COX-2 expression, whereas COX-inhibitors indomethacin and diclofenac, as well as a NO synthase-inhibitor, N G -nitro- l -arginine methyl ester, tended to enhance the COX-2 mRNA expression. In addition, ischemia induced COX-2 expression in the hippocampal and perifocal striatal neurons and in endothelial cells. Thus, COX-2 is transiently induced after SD and focal ischemia by activation of N -methyl- d -aspartic acid-receptors and PLA 2 , most prominently in cortical neurons that are at a high risk to die after focal brain ischemia.

Haem oxygenase-1 (HO-1) is a stress protein and a rate-limiting enzyme in haem degradation, generating ferrous iron, carbon monoxide and bile pigments. HO-1 has been suggested to be protective against oxidative stress. In the normal rodent brain the enzyme is localized in selected neuron populations, but heat shock, glutathione depletion in vivo and oxidative stress in vitro induce HO-1 predominantly in glial cells. We studied HO-1 expression in the brain following transient occlusion of the middle cerebral artery, and found increased mRNA levels in the ischaemic region from 4 h to 7 days after 90 min of ischaemia. The mRNA levels peaked at 12 h, and were localized perifocally. HO-1-immunoreactive astrocytes and microglial cells were seen in the perifocal area, in the ipsilateral and occasionally in the contralateral hippocampus. Some perifocal neurons were also HO-1-immunoreactive. In the infarcted area HO-1-positive microglia/macrophages were detected in double-labelling experiments. A microassay measuring the conversion of [14C]haem to [14C]bilirubin showed a two-fold increase in haem oxygenase activity in the infarcted core. These observations show a long-term induction of HO-1 protein and its activity following ischaemia-reperfusion brain injury, and indicate increased capacity for haem degradation and the generation of biologically active bile products, carbon monoxide and iron in astrocytes and some microglia/macrophages during focal brain ischaemia.

Protein kinase C (PKC) consists of a family of closely related Ca2+/phospholipid-dependent phosphotransferase isozymes, most of which are present in the brain and are differentially activated by second messengers. Calcium-dependent PKC activity may cause neuronal degeneration after ischemic insult. PKC is also involved in trophic-factor signaling, indicating that activity of some PKC subspecies may be beneficial to the injured brain. Therefore, we screened long-term changes in the expression of multiple PKC subspecies after focal brain ischemia. Middle cerebral artery occlusion was produced by using an intraluminal suture for 30 min or 90 min. Inin situhybridization experiments, mRNA levels of PKCα, -β, -γ, -δ, -ε and -ζ were decreased in the infarct core 4 hr after ischemia and were lost completely 12 hr after ischemia. In areas surrounding the core, PKCδ mRNA was specifically induced 4, 12, and 24 hr after ischemia in the cortex. At 3 and 7 d, the core and a rim around it showed increased mRNA levels of PKCδ. No other subspecies were induced. At 2 d, immunoblotting demonstrated increased levels of PKCδ protein in the perifocal tissue, and immunocytochemistry revealed an increased number of PKCδ-positive neurons in the perifocal cortex. In the core, PKCδ-positive macrophages and endothelial cells were seen. Pretreatment with MK-801, an NMDA antagonist, inhibited cortical PKCδ mRNA induction. The data show that focal brain ischemia induces PKCδ mRNA and protein but not other PKC subspecies through the activation of NMDA receptors and that the upregulation lasts for several days in neurons of the perifocal zone.

Background and purpose After first-ever ischaemic stroke, to assess the risk and baseline factors associated with acute symptomatic seizure (ASS) (occurring within 7 days) and late post-stroke seizure (LPS) (>7 days). Methods All consecutive patients aged 15–49 with first-ever ischaemic stroke between 1994 and 2007 treated at the Helsinki University Central Hospital were included, using Cox proportional hazard models to identify factors associated with seizures. Adjustment was for age, gender, vascular risk factors, admission hyperglycemia (>6.1 mm) and hyponatremia (