Cognition in adult patients with newly diagnosed non-lesional temporal lobe epilepsy.

OBJECTIVE: To evaluate whether cognitive performance is affected in newly diagnosed temporal lobe epilepsy (TLE) and to determine the most vulnerable cognitive domains. METHODS: In this baseline longitudinal study, differences in memory and non-memory cognitive functions were assessed using comprehensive neuropsychological test batteries in 21 adult patients with newly diagnosed non-lesional TLE and individually matched controls. In addition, the analyses included ratings of self-perceived emotional status. RESULTS: The patients performed more poorly than the control group regarding delayed visual memory (p = 0.013) and executive function tasks related to switching (Trail Making Test and verbal fluency shifting; p = 0.025 and p = 0.03, respectively). We found no differences in verbal learning and memory, attention/working memory/processing speed, and other executive functions. SIGNIFICANCE: Our results show that patients with TLE often have specific cognitive deficits at time of diagnosis, even in the absence of structural brain abnormalities. This supports the hypothesis that memory dysfunction is linked to an underlying pathology rather than to the effect of recurrent seizures, long-term use of anti-seizure medication, or other epilepsy-related factors. As certain executive functions are affected at an early stage, the pathology may involve brain regions beyond the temporal lobe and may comprise larger brain networks. These results indicate the need for greater awareness of cognition at the time of diagnosis of TLE and before initiation of treatment, and integration of neuropsychological assessment into early routine clinical care.

Psychiatric comorbidity in children and youth with epilepsy: An association with executive dysfunction?

OBJECTIVES: Psychopathology in children and youth with epilepsy has previously been related to executive dysfunction, but the nature of the association is uncertain. We sought to explore risk factors for psychiatric disorders in children and youth with epilepsy, with emphasis on executive dysfunction, along with seizure-related and psychosocial factors. METHODS: The cohort consisted of one hundred and one consecutive patients aged 10-19 years with focal (n=52) or genetic generalized (n=49) epilepsy. All were screened for psychiatric symptoms, using part of an extensive questionnaire, the Strengths and Difficulties Questionnaire (SDQ) for both patients and their parents. Participants scoring in the borderline or abnormal range on the SDQ received a psychiatric interview (Kiddie-SADS-PL). All participants underwent a neuropsychological examination, and those with general cognitive abilities (IQ)<70 were excluded. RESULTS: Forty-seven of 101 participants (46.5%) had a SDQ score in the borderline or abnormal range and underwent a psychiatric evaluation. Of these, 44 (93.6%) met the criteria for a psychiatric diagnosis, the most common being ADHD and anxiety. An executive deficit was identified in 26.8% of the participants with a psychiatric diagnosis, but in only 5.4% of those without such a diagnosis (p=0.003). Multivariate logistic regression analysis showed that executive dysfunction was an independent risk factor for having a psychiatric disorder (OR 8.2, CI 1.8-37.2, p=0.006), along with male gender (OR 2.9, CI 1.2-7.3, p=0.02), and early seizure onset (0.86-that is one year older equals risk of psychiatric disorder reduced by 14%-CI 0.77-0.96, p=0.01). Other epilepsy-related or psychosocial factors were not significantly associated with psychiatric disorders. CONCLUSIONS: Multiple factors are associated with psychiatric problems in children and youth with epilepsy. In this study, executive dysfunction, male gender, and early epilepsy onset were independent risk factors for having a psychiatric disorder. An evaluation of psychiatric and cognitive problems is important to enable a positive long-term outcome in childhood epilepsy.

Early sexual debut in Norwegian youth with epilepsy: A population-based study.

OBJECTIVES: In comparison with controls, youth with epilepsy (YWE) have greater psychosocial problems. However, information about their sexual behavior is sparse. We have performed a large, population-based questionnaire study to examine differences in sexual behavior between YWE and controls. METHODS: A randomly chosen cohort of youth (13-19 years) from Akershus county, Norway (n=19,995) was asked to complete a questionnaire anonymously with questions on epilepsy and sexual activity. RESULTS: The response rate was 85%. Two hundred forty-seven participants reported having or having had epilepsy, i.e., a lifetime epilepsy prevalence of 1.2%. Compared with controls, a higher proportion of YWE reported having had sexual intercourse (43.6% vs. 35.3%, p=0.009). The mean age at sexual debut was significantly lower in YWE than in controls (14.0 years vs. 15.0 years, p<0.001), and this was particularly marked among boys. A higher proportion of YWE reported not having used contraceptives at their last sexual intercourse compared with controls (31.6% vs. 22.3%, p=0.03). Ten percent of YWE, compared with 2% of the controls, reported that they had been forced into their first sexual intercourse. CONCLUSION: In YWE, some aspects of sexual behavior differ from those of their peers, with earlier sexual debut and less frequent use of contraceptives. More attention should be directed toward this subject, aiming at avoiding unwanted pregnancies and potential emotional traumas in this already vulnerable patient group.

[Sudden unexpected death in epilepsy (SUDEP)]. / Plutselig, uventet epilepsirelatert død.

Sudden unexpected death is the most frequent cause of seizure-related death in cases of epilepsy. Those primarily affected are young adults with a long disease duration and regular seizures. The deaths are often related to a nocturnal generalised tonic-clonic seizure attack. In Norway around 30 persons are thought to be affected each year. Optimisation of epilepsy treatment will probably prevent some of these deaths.

Uptake and metabolism of fructose by rat neocortical cells in vivo and by isolated nerve terminals in vitro.

Fructose reacts spontaneously with proteins in the brain to form advanced glycation end products (AGE) that may elicit neuroinflammation and cause brain pathology, including Alzheimer's disease. We investigated whether fructose is eliminated by oxidative metabolism in neocortex. Injection of [(14) C]fructose or its AGE-prone metabolite [(14) C]glyceraldehyde into rat neocortex in vivo led to formation of (14) C-labeled alanine, glutamate, aspartate, GABA, and glutamine. In isolated neocortical nerve terminals, [(14) C]fructose-labeled glutamate, GABA, and aspartate, indicating uptake of fructose into nerve terminals and oxidative fructose metabolism in these structures. This was supported by high expression of hexokinase 1, which channels fructose into glycolysis, and whose activity was similar with fructose or glucose as substrates. By contrast, the fructose-specific ketohexokinase was weakly expressed. The fructose transporter Glut5 was expressed at only 4% of the level of neuronal glucose transporter Glut3, suggesting transport across plasma membranes of brain cells as the limiting factor in removal of extracellular fructose. The genes encoding aldose reductase and sorbitol dehydrogenase, enzymes of the polyol pathway that forms glucose from fructose, were expressed in rat neocortex. These results point to fructose being transported into neocortical cells, including nerve terminals, and that it is metabolized and thereby detoxified primarily through hexokinase activity. We asked how the brain handles fructose, which may react spontaneously with proteins to form 'advanced glycation end products' and trigger inflammation. Neocortical cells took up and metabolized extracellular fructose oxidatively in vivo, and isolated nerve terminals did so in vitro. The low expression of fructose transporter Glut5 limited uptake of extracellular fructose. Hexokinase was a main pathway for fructose metabolism, but ketohexokinase (which leads to glyceraldehyde formation) was expressed too. Neocortical cells also took up and metabolized glyceraldehyde oxidatively.

Correction of partial volume effect in (18)F-FDG PET brain studies using coregistered MR volumes: voxel based analysis of tracer uptake in the white matter.

A voxel-based algorithm to correct for partial volume effect in PET brain volumes is presented. This method (named LoReAn) is based on MRI based segmentation of anatomical regions and accurate measurements of the effective point spread function of the PET imaging process. The objective is to correct for the spill-out of activity from high-uptake anatomical structures (e.g. grey matter) into low-uptake anatomical structures (e.g. white matter) in order to quantify physiological uptake in the white matter. The new algorithm is presented and validated against the state of the art region-based geometric transfer matrix (GTM) method with synthetic and clinical data. Using synthetic data, both bias and coefficient of variation were improved in the white matter region using LoReAn compared to GTM. An increased number of anatomical regions doesn't affect the bias (<5%) and misregistration affects equally LoReAn and GTM algorithms. The LoReAn algorithm appears to be a simple and promising voxel-based algorithm for studying metabolism in white matter regions.

Mild cognitive impairment: cerebrospinal fluid tau biomarker pathologic levels and longitudinal changes in white matter integrity.

PURPOSE: To evaluate the relationship between (a) pathologic levels of cerebrospinal fluid (CSF) total tau as an index of the intensity of ongoing neuronal degeneration and (b) longitudinal changes in white matter (WM) integrity in patients with mild cognitive impairment (MCI). MATERIALS AND METHODS: Participants gave written informed consent, and the Norwegian committee for medical research ethics approved the study. Thirty patients with MCI and nonpathologic CSF total tau levels, nine patients with MCI and pathologic CSF total tau levels, and 16 age-matched healthy control subjects underwent diffusion-tensor imaging at baseline and after a mean follow-up of 2.6 years ± 0.54 (standard deviation), with range of 1.58-3.98 years. The effect of diagnosis (MCI vs no MCI) at baseline and CSF tau levels at fractional anisotropy (FA), mean diffusivity, radial diffusivity (D(R)), and axial diffusivity were tested with tract-based spatial statistics. Differences in WM integrity at baseline and follow-up and change over time were compared among patients with pathologic CSF total tau levels (MCI high tau), patients with normal CSF total tau levels (MCI low tau), and healthy control subjects. Linear mixed-model between-group within-subject analyses were conducted to examine differences in rate of change over time in FA and D(R). RESULTS: Longitudinal analysis of regional WM change revealed significant decrease in FA (P = .038) and increase in D(R) (P = .018) in the MCI high-tau group relative to control subjects. For D(R), the changes were regionally specific to the right cingulum and the right superior and inferior longitudinal fasciculi. CONCLUSION: Reduction in WM integrity was greater in patients with MCI who had the most intense neuronal degeneration as indexed by using CSF total tau, suggesting that these patients might represent a subgroup of MCI with more intense WM degeneration who are possibly at greater risk of developing Alzheimer disease.

Biological rhythms and epilepsy treatment.

Approximately one-third of patients with epilepsy are drug-refractory, necessitating novel treatment approaches. Chronopharmacology, which adjusts pharmacological treatment to physiological variations in seizure susceptibility and drug responsiveness, offers a promising strategy to enhance efficacy and tolerance. This narrative review provides an overview of the biological foundations for rhythms in seizure activity, clinical implications of seizure patterns through case reports, and the potential of chronopharmacological strategies to improve treatment. Biological rhythms, including circadian and infradian rhythms, play an important role in epilepsy. Understanding seizure patterns may help individualize treatment decisions and optimize therapeutic outcomes. Altering drug concentrations based on seizure risk periods, adjusting administration times, and exploring hormone therapy are potential strategies. Large-scale randomized controlled trials are needed to evaluate the efficacy and safety of differential and intermittent treatment approaches. By tailoring treatment to individual seizure patterns and pharmacological properties, chronopharmacology offers a personalized approach to improve outcomes in patients with epilepsy.

Increased risk of sudden unexpected death in epilepsy in females using lamotrigine: a nested, case-control study.

PURPOSE: To estimate the incidence of sudden unexpected death in epilepsy (SUDEP) in Rogaland County, Norway, in the period August 1 1995-July 31 2005, and to investigate whether use of lamotrigine (LTG) was associated with increased risk in female patients or other subgroups. METHODS: SUDEP victims were identified from autopsy reports and data from the Norwegian Cause of Death Registry. In all cases where SUDEP was considered as a possible cause of death, the hospital records were also reviewed. For each deceased, at least three living patients with epilepsy were randomly selected as controls. The market share in defined daily doses was collected for each year to estimate the number of patient-years at risk on each antiepileptic drug. KEY FINDINGS: We identified 26 cases of SUDEP: 16 definite, 3 probable, and 7 possible; 15 patients were female and 11 were male. Of these, 10 patients (38.5%) were treated with LTG: 9 of these patients were female. The incidence of SUDEP was estimated as 1.0 per 1,000 patient-years when all cases were included, and 0.7 per 1,000 patient-years for definite and probable SUDEP. Seven of 12 (58.3%) of female patients with definite and probable SUDEP and 10 of 41 (24.4%) of controls matched on age and gender were on LTG (p = 0.038). The incidence of definite and probable SUDEP in women on LTG, was estimated as 2.5 per 1,000 patient-years and 0.5 per 1,000 patient-years in female who were not taking LTG (p = 0.007). SIGNIFICANCE: The incidence of SUDEP was significantly higher among female patients with epilepsy who were being treated with LTG than among female patients with epilepsy who were not taking LTG, and a significantly higher proportion of female SUDEP cases than controls were taking LTG. Our findings may have implications for treatment of epilepsy in female patients.

Signal-averaged and standard electrocardiography in patients with newly diagnosed epilepsy.

Antiepileptic drugs (AEDs) have been associated with cardiac conduction abnormalities and arrhythmias, predominantly in patients with predisposing cardiac conditions. Ventricular late potentials (VLPs) detected in the signal-averaged electrocardiogram (SAECG) may imply an increased risk of ventricular tachycardia or fibrillation. Twenty-six AED-naïve patients with newly diagnosed epilepsy and no clinical evidence of heart disease were examined with SAECG and standard ECG. Fifteen patients were treated with lamotrigine and ten with carbamazepine. No significant abnormality was found in the standard ECG or SAECG three to nine months after initiation of AED therapy. In one patient, a VLP was detected at baseline and subsequent MRI demonstrated significant right ventricular pathology; therefore, this patient was excluded from the rest of the study. This exclusion along with only newly diagnosed patients with a low total seizure count being included in the study may explain the lack of AED-induced electrocardiographic abnormalities in this patient cohort.

White matter imaging changes in subjective and mild cognitive impairment.

BACKGROUND: To determine whether white matter (WM) memory network changes accompany early cognitive impairment and whether these changes represent early, pathologically independent axonal affection, we combined WM diffusion tensor imaging and cortical morphometric measurements of normal control subjects, patients with only subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). METHODS: We included 66 patients with SCI or MCI and 21 control subjects from a university-hospital-based memory clinic in a cross-sectional study. Morphometric analysis was performed in FreeSurfer, and Tract-Based Spatial Statistics was used for analysis of diffusion tensor imaging-derived WM fractional anisotropy, radial diffusivity (DR), and mean diffusivity (MD). Relationships between WM measures and stage were assessed with whole-brain voxelwise statistics and on a region-of-interest basis, with subsequent correction for cortical atrophy. RESULTS: In SCI patients, as compared with control subjects, there were widespread changes in DR and MD. No significant differences in thickness could be demonstrated. In MCI patients, as compared with control subjects, there were widespread changes in DR, MD, and fractional anisotropy; the precuneal and inferior parietal cortices were thinner; and the hippocampus was smaller. Multiple logistic regression analysis eliminated morphometry as an explanatory variable in favor of DR/MD for all regions of interest, except in the precuneus, where both thickness and DR/MD were significant explanatory variables. CONCLUSIONS: WM tract degeneration is prominent in SCI and MCI patients, and is at least in part independent of overlying gray matter atrophy.

Psychiatric symptoms in Norwegian children with epilepsy aged 8-13 years: effects of age and gender?

PURPOSE: In this population-based study we wanted to assess the prevalence and impact of psychiatric symptoms in children with epilepsy compared to controls, and investigate possible age and gender differences. METHODS: Data were collected using the Strengths and Difficulties Questionnaire-Parent report (SDQ-P) as part of a more extensive questionnaire. A total of 14,699 parents of children aged 8-13 years (response rate 78%) participated. Associations between SDQ scores and epilepsy, other chronic disease, age, gender, and socioeconomic factors were explored using logistic regression analysis. KEY FINDINGS: Children with epilepsy (CWE) (n=110) had a significantly higher frequency of psychiatric symptoms (37.8% vs. 17.0% in controls, p<0.001). Gender differences were found in several subscales of the SDQ; girls had more emotional problems, whereas boys had higher scores regarding peer relationship and hyperactivity/inattention problems. Male gender, low socioeconomic status (family income below poverty limit and living in a single parent home), and other chronic disease (asthma/diabetes) were independent risk factors of developing psychiatric symptoms, along with epilepsy. Having or having had epilepsy was, however, a much stronger risk factor for developing psychiatric symptoms in girls than in boys [odds ratio (OR) 4.2 vs. OR 2.3]. A minor effect of age was seen only in girls with epilepsy, with an increased risk of psychiatric symptoms in age group 10-13 years (OR 1.28 for scoring borderline/abnormal on SDQ-total difficulties). Borderline/abnormal impact scores were found in 31.8% of CWE compared with 13.0% of controls (p<0.001). SIGNIFICANCE: Multiple risk factors contribute to the high prevalence of psychiatric symptoms in CWE, perhaps differently in boys and girls. Awareness of this complex interaction may help target intervention toward high risk groups and thus prevent more serious problems from arising.

Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study.

Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio<1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.

Region-specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin.

PURPOSE: It is commonly assumed that antiepileptic drugs (AEDs) act similarly in the various parts of the brain as long as their molecular targets are present. A few experimental studies on metabolic effects of vigabatrin, levetiracetam, valproate, and lamotrigine have shown that these drugs may act differently in different brain regions. We examined effects of chronic treatment with levetiracetam or phenytoin on mRNA levels to detect regional drug effects in a broad, nonbiased manner. METHODS: mRNA levels were monitored in three brain regions with oligonucleotide-based microarrays. RESULTS: Levetiracetam (150 mg/kg for 90 days) changed the expression of 65 genes in pons/medulla oblongata, two in hippocampus, and one in frontal cortex. Phenytoin (75 mg/kg), in contrast, changed the expression of only three genes in pons/medulla oblongata, but 64 genes in hippocampus, and 327 genes in frontal cortex. Very little overlap between regions or drug treatments was observed with respect to effects on gene expression. DISCUSSION: We conclude that chronic treatment with levetiracetam or phenytoin causes region-specific and highly differential effects on gene expression in the brain. Regional effects on gene expression could reflect regional differences in molecular targets of AEDs, and they could influence the clinical profiles of AEDs.

Antiepileptic drugs and quality of life in the elderly: results from a randomized double-blind trial of carbamazepine and lamotrigine in patients with onset of epilepsy in old age.

During an international double-blind trial evaluating the efficacy and tolerability of lamotrigine and carbamazepine in patients aged >or=65 with newly diagnosed epilepsy, the comparative effects of the drugs on health-related quality of life were investigated based on screening and 12-, 28-, and 40-week data, using the modified Side Effect and Life Satisfaction (SEALS) Inventory and the Liverpool Adverse Event Profile. Of 167 patients, 29 discontinued before first follow-up, and data were incomplete for 13. In 125 eligible subjects (62 taking carbamazepine, 63 taking lamotrigine), comparable baseline data did not change significantly during medication, within or across treatments. A borderline difference in the SEALS Dysphoria subscores favored lamotrigine. No difference between completers and noncompleters was identified. Twelve-week data for noncompleters were comparable across treatments. Changes in the inventories up to 40 weeks correlated moderately. Neither lamotrigine nor carbamazepine seems likely to cause significant changes in health-related quality of life measures after 40 weeks at therapeutic doses.

Cardiac function and antiepileptic drug treatment in the elderly: a comparison between lamotrigine and sustained-release carbamazepine.

PURPOSE: To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy. METHODS: The study was conducted in the Norwegian subcohort (n = 108) of an international randomized double-blind 40-week trial, which compared the efficacy and tolerability of LTG and sustained-release CBZ in patients aged 65 and older with newly diagnosed epilepsy. Target maintenance doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on clinical response. Patients with significant unpaced atrioventricular (AV) conduction defect were excluded. Resting 12-lead ECG recordings were made under standardized conditions at pretreatment (baseline) and at the 40-week study visit (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR), PQ, and QTc (HR-corrected QT) intervals were assessed and compared between groups. RESULTS: Of the 108 patients randomized, 33 discontinued prematurely because of adverse events (n = 24, none of which was cardiac) or other reasons (n = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed ECG parameters differed significantly between groups at baseline. No significant ECG changes were recorded between baseline and treatment visit for QRS duration and QTc intervals, whereas HR fell and PQ intervals increased slightly on both treatments. However, there were no differences between groups in changes from baseline to treatment visit. There were no significant relationships between individual ECG changes and serum drug concentrations, except for QTc intervals, which decreased slightly with increasing CBZ concentrations. The proportion of patients with ECG parameters outside the normal range at treatment visit was similar to that recorded at baseline. DISCUSSION: Clinically significant ECG changes are not common during treatment with CBZ or LTG in elderly patients with no preexisting significant AV conduction defects.

Reversible effects of antiepileptic drugs on thyroid hormones in men and women with epilepsy: a prospective randomized double-blind withdrawal study.

Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This prospective, randomized study evaluated thyroid function in men and women with epilepsy both before and after double-blinded withdrawal of AED monotherapy, and assessed whether any changes were reversible. One hundred sixty patients were randomized to withdrawal and nonwithdrawal groups; 150 patients completed the intervention and were included in the 12-month study. Serum samples were obtained from 130 patients, from before and 4 months after intervention. Following AED withdrawal, significant increases in free thyroxine (FT(4)) serum concentrations were measured in men and women treated with carbamazepine. In women treated with valproate, serum concentrations of free triiodothyronine (FT(3)) decreased significantly in the withdrawal group. Thus, for both men and women with epilepsy, carbamazepine treatment reduces serum FT(4) concentrations, but valproate treatment of women with epilepsy increases serum FT(3.) Our study demonstrated that these changes can be reversed by treatment withdrawal, even after years of treatment.

Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults.

Animal studies have shown endocrine changes after levetiracetam treatment. The present study investigated reproductive and sexual function in patients with epilepsy (aged 18-45) treated with levetiracetam (LEV: 30 men/26 women), carbamazepine (CBZ: 63 men/30 women), or lamotrigine (LTG: 37 men/40 women) monotherapy and in healthy controls (36 men/44 women). In women, no endocrine changes were observed during LEV treatment, whereas steroid hormone-binding globulin levels were greater and progesterone levels lower in women using CBZ. Dehydroepiandrosterone sulfate levels were higher and androstenedione levels lower in LTG-treated women. Arizona Sexual Experience Scale scores, which were significantly lower in females using LTG or LEV, suggesting they have better sexual function than CBZ users and controls. In men, no drug-specific hormonal pattern was observed after LEV treatment. Male patients in all treatment groups had lower androstenedione and free testosterone. Those using CBZ had lower free androgen indices and dehydroepiandrosterone sulfate levels, and higher steroid hormone-binding globulin, follicle-stimulating hormone, and luteinizing hormone levels. Arizona Sexual Experience Scale scores for men were similar in all groups. In conclusion, LEV treatment apparently has no drug-specific sexual or endocrine side effects in men or women in this age group.

New SCN5A mutation in a SUDEP victim with idiopathic epilepsy.

Many idiopathic epilepsies have been shown to be caused by ion channel dysfunction. Channelopathies also cause the long QT syndrome (LQTS) which is associated with syncopes and sudden cardiac death. It has been postulated that the same channelopathy may be associated with both epilepsy and LQTS. We report a patient with idiopathic epilepsy who died in sudden unexpected death in epilepsy (SUDEP) at the age of 25. A post mortem DNA sequencing of the LQTS-associated genes revealed a novel missense mutation in the SCN5A gene coding for the cardiac sodium channel, voltage gated, type V, alpha subunit. The possibility that the mutation may explain both the epilepsy and the sudden death is discussed. However, the patient was treated with lamotrigine which may interfere with cardiac ion channels and may also have played a part in inducing a terminal cardiac arrhythmia.

White matter lesion subtypes and cognitive deficits in patients with memory impairment.

AIM: To analyze the relationship between periventricular (PV) and subcortical (SC) white matter lesions (WML) and cognitive function in patients with memory impairment. METHODS: In total, 253 patients with Global Deterioration Scale scores >or=3 who had been referred to a university-based memory unit due to memory complaints were included (mean age 69.7 years, 124 females). Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat), and full test results were available for 217 patients. PV and SC WML loads (semi-quantitative rating on axial T(2)-weighted MRI scans) were used in linear regression as predictors of cognition. RESULTS: MMSE was significantly correlated with SC WML (p = 0.005), but not with PV WML (p = 0.19). Cognistat tests for orientation, comprehension, visuoconstruction, calculation, similarities, and judgment were negatively correlated with SC WML (p < 0.01), as was verbal memory with parieto-occipital SC WML (p < 0.05). Visuoconstruction and calculation were negatively correlated with PV WML (p < 0.05). Parieto-occipital WML were more strongly related to cognition than fronto-temporal WML. Only SC WML were significantly correlated with cognition when PV and SC WML were entered simultaneously in the regression model. CONCLUSION: In patients with cognitive impairment, SC WML, in particular in parieto-occipital regions, were associated with reduced cognitive function.