Cognitive dysfunction after generalized tonic-clonic status epilepticus in adults.

OBJECTIVES: Generalized tonic-clonic status epilepticus (GTC-SE) is considered a risk for cognitive impairment. Research with standardized tools is scarce and non-conclusive. We systematically assessed short-term and long-term cognitive function after GTC-SE. MATERIALS AND METHODS: Thirty-three patients were tested after the clinical post-ictal phase of GTC-SE (timepoint 1) and again after 1 year (timepoint 2). Twenty controls were examined with the same tests. Tests from Cambridge Neuropsychological Test Automated Battery were used. Motor screening test (MOT) assessed motor speed, delayed matching to sample (DMS) and paired associates learning (PAL) assessed memory, and Stockings of Cambridge (SOC) assessed executive function. Estimated premorbid IQ and radiologically visible brain lesions were controlled for in adjusted results. Outcome measures were z-scores, the number of standard deviations a score deviates from the mean of a norm population. RESULTS: At timepoint 1, unadjusted patient results were significantly below both norm and control group performances on all subtests. Patient mean was 1.9 z-scores below controls (P < .001) on PAL total errors. Results remained significant for PAL and DMS after adjustments. Patient results improved at timepoint 2, but memory tests remained lower than norms and for controls. An executive dysfunction emerged on the most complex SOC stage (z-score difference -0.83; P = .008, adjusted difference -0.94; P = .02). CONCLUSIONS: Memory and learning impairment in the early phase after SE and late developing executive dysfunction remained significant after adjusting for estimated premorbid IQ and pre-SE brain lesions. Results suggest that GTC-SE poses a risk for cognitive impairment.

Identifying patients at risk of acute symptomatic seizure after ischemic stroke.

BACKGROUND: Contributors to post-stroke seizure research have advocated the need for prospective studies of acute symptomatic seizures after stroke. Identification of the patient at risk of seizure and the impact of the event on outcome is a prerequisite for this kind of research. The aim of this study was to identify risk factors, make an outline for a risk score, and look at consequences of seizure on short-time clinical outcomes. METHODS: This registry-based study included patients with ischemic stroke admitted between 2007 and 2013. We identified variables associated with the presence of acute symptomatic seizures and made a risk score. Clinical outcome measures were modified Rankin scale, National Institute of Health Stroke Scale (NIHSS), and death at discharge or at day seven. RESULTS: A total of 2598 ischemic stroke patients were included, 66 experiencing seizure within seven days of stroke. We found diabetes mellitus, NIHSS on admission, and cortical lesion to be associated with the risk of seizure. The risk score had a sensitivity of 58%, specificity of 85%, and a positive predictive value of 9% with a three-point cutoff. We found a negative effect of seizure on survival in mild-to-moderate strokes after adjusting for infections and stroke severity. CONCLUSIONS: Because of low incidence and the lack of specific risk factors, acute symptomatic seizure after ischemic stroke is hard to predict. The negative effect of seizure on stroke outcome is uncertain, and more thorough studies are needed because of possible subtle or non-overt seizures.

Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations.

OBJECTIVE: To investigate three families and one sporadic case with a recessively inherited ataxic syndrome. METHODS: Clinical and genetic studies were performed in six individuals. Southern blotting and real time PCR were used to detect deletions of mtDNA and mutations in the POLG gene were identified using a combination of DHPLC and direct DNA sequencing. RESULTS: The patients have a distinctive, progressive disorder that starts with episodic symptoms such as migraine-like headache or epilepsy. Ataxia, which is a combination of central and peripheral disease, develops later as does ophthalmoplegia. The commonest form of epilepsy was focal and involved the occipital lobes. Myoclonus was common and patients have a high risk of status epilepticus. MRI typically shows signal changes in the central cerebellum, olivary nuclei, occipital cortex, and thalami. COX negative muscle fibers were found in four of six; in one patient these were rare and in another absent. Multiple mtDNA deletions were identified in all patients, although in two these were not apparent on Southern blotting and real time PCR was required to demonstrate the defect. Two families were homozygous for a previously described POLG mutation, G1399A (A467T). One family and the sporadic case had the same two new mutations, a G to C at position 1491 (Q497H) and a G to C at 2243 (W748S). CONCLUSIONS: Mutations in POLG cause a recessively inherited syndrome with episodic features and progressive ataxia. Characteristic changes on MRI are seen and although skeletal muscle may appear morphologically normal, multiple mtDNA deletions can be detected using real-time PCR.

The impact of affectivity dispositions, self-efficacy and locus of control on psychosocial adjustment in patients with epilepsy.

The main hypothesis of this study was that negative and positive affectivity, self-efficacy and health-related locus of control are important for psychosocial adjustment in patients with epilepsy. These dimensions are rarely examined directly in relation to the psychosocial adjustment in these patients. Correlations between measures of these constructs and measures of psychosocial adjustment in epilepsy were investigated. One hundred and one patients answered the Washington psychosocial seizure inventory (WPSI), the positive and negative affect schedule (PANAS-X), the multidimensional health locus of control scales (MHLC), the generalized self-efficacy scale and a scale measuring self-efficacy in epilepsy. Reliability analyses, correlational analyses and multiple stepwise regression analyses were performed. Negative affectivity (NA), positive affectivity (PA) and generalized self-efficacy showed high correlations with the WPSI scales emotional adjustment, overall psychosocial adjustment and quality of life. The epilepsy self-efficacy measures showed high, but lower correlations with the same WPSI scales. The MHLC scales showed low correlations with the WPSI scales. Multiple regression analyses showed that PA, NA and measures of self-efficacy explained more than 50% of the variances on emotional adjustment, overall psychosocial functioning and quality of life. In conclusion, positive and negative affectivity and self-efficacy are important predictors of perceived emotional adjustment, psychosocial adjustment and quality of life in patients with epilepsy. NA is the best predictor, but PA and self-efficacy measures give unique predictions independent of NA.

Juvenile myoclonic epilepsy: clinical characteristics, treatment and prognosis in a Norwegian population of patients.

Forty-three patients with juvenile myoclonic epilepsy (JME) is presented. The female to male ratio was 2.9:1. The patients answered a standardized questionnaire pertaining to social situation, medical history, onset of epilepsy, types and frequency of seizures, treatment, experienced control over seizures and consequences of having epilepsy. Myoclonic jerks, which are the hallmark of the condition, are often forgotten by the patients or not considered as epileptic seizures. This could be one reason why JME still seems underdiagnosed. JME may comprise absence, myoclonic and generalized tonic-clonic seizures (GTCS), proposed to occur in age-related sequence. We found that absence seizures may start after onset of other seizures. Our results confirm the need for medication since, during the last year, only 7% were seizure free without medication. Of patients on antiepileptic drugs (AEDs), 79.5% had no GTCS and 41% were seizure free during the last year, which confirms a relatively good response to appropriate treatment. Although most patients used AED daily and many still had one or more types of epileptic seizure, the epilepsy in general had very little impact on their lives.

Differential effect of carbamazepine and valproate monotherapy on plasma levels of oestrone sulphate and dehydroepiandrosterone sulphate in male epileptic patients.

Steroid sulphates such as oestrone sulphate (OE1S) and dehydroepiandrosterone sulphate (DHEAS) have been suggested to be of biological importance in different disease states such as breast cancer and atherosclerosis. Previous studies have shown that drugs such as aminoglutethimide and rifampicin that induce P450-dependent mixed-function oxygenases selectively suppress plasma OE1S levels. The aim of this study was to evaluate the influence of treatment with carbamazepine, an antiepileptic drug known to stimulate mixed-function oxygenases, on plasma levels of OE1S and DHEAS. We measured plasma OE1S and DHEAS together with other plasma oestrogens and androgens in male epileptic patients before and during carbamazepine monotherapy. Patients treated with valproate monotherapy acted as a control group. Treatment with carbamazepine decreased plasma OE1S levels from a mean value of 810.8 to 411.6 pmol/l (mean suppression to 50.7% of pretreatment levels, P < 0.001). Similarly, the ratio of OE1S to OE1 fell to 59.9% of pretreatment levels (P < 0.001)). DHEAS decreased from a mean level of 4.9 mumol/l before treatment to 3.0 mumol/l during carbamazepine therapy (mean reduction to 62.7% of pretreatment levels (P < 0.001), while the ratio of DHEAS to DHEA fell to 63.0% of pretreatment values (P < 0.01). No significant change in plasma levels of the other oestrogens or androgens measured was observed. Treatment with valproate caused a slight decrease in FSH levels (P < 0.05), but no change in any of the other hormones measured was observed. Studies are warranted to evaluate the possible effects of long-term treatment with carbamazepine on the risk of developing endocrine-sensitive tumours and cardiovascular disease and also the possible effects of alterations in plasma DHEAS on epileptic activity.

Epileptic seizures in patients with multiple sclerosis. Is the prognosis of epilepsy underestimated?

The exact prevalence of epileptic seizures in patients with multiple sclerosis (MS) is still a matter of some controversy. In a population-based, unselected group of 423 patients with MS we identified 17 (4.02%) with epileptic seizures. The mean age at onset of MS was 25.2 years and at onset of epilepsy 32.6 years. A prevalence of 'active epilepsy', i.e. seizures within the last 5 years, was estimated to 3.2%. The prevalence of epilepsy in our MS population is much higher than should be expected when compared to lifetime prevalence of epilepsy in corresponding age groups. The occurrence of convulsive status epilepticus is also higher than expected, and suggests a rather serious prognosis. Thus, drug treatment should be considered after the first epileptic seizure.

Cerebrospinal fluid proteins and free amino acids in patients with solvent induced chronic toxic encephalopathy and healthy controls.

The concentrations of protein, albumin, IgG, and free amino acids in the cerebrospinal fluid of 16 patients with chronic toxic encephalopathy due to organic solvents were measured. The patient group consisted of all patients with this diagnosis in a neurological department in 1985. The diagnosis was based on neuraesthenic symptoms, pathological psychometric performance, and verified exposure to neurotoxic organic solvents. A control group of 16 patients with myalgias or backache, or both, and no signs of disease was used for comparison. The purpose was to study possible changes in the cerebrospinal fluid that might contribute to understanding the aetiology of solvent induced chronic toxic encephalopathy. A rise in protein, albumin, and IgG was found in the patient group compared with the control group, as well as reduced concentrations of phosphoethanolamine, taurine, homocarnosine, ethanolamine, alpha-aminobutyric acid, and leucine. Using a stepwise multiple regression analysis, taurine was negatively correlated to exposure to solvents. These findings may indicate membrane alterations in the central nervous system related to exposure to organic solvents.

Penicillin-induced convulsions have preferential effects on transmitter glutamate pools in rat neostriatum.

Convulsant doses of penicillin and elevated ambient pressure of 41 bar enhance the excitability of neurons. Their effects have been studied in neostriatal tissue with methods allowing differentiation between transmitter and metabolic glutamate pools. Levels of glutamate (Glu), glutamine (Gln), aspartate (Asp); gamma-aminobutyric acid and taurine were measured in the intact and decorticated neostriatum and parieto-occipital cortex of rats with a unilateral frontal cortex ablation. Intravenous infusion of penicillin at 1 bar decreased the neostriatal Glu content in the intact but not in the decorticated hemisphere. Pressure of 41 bar significantly decreased the level of Asp in the decorticated side only. Infusion of penicillin at 41 bar reduced the levels of Glu by 20.1% and Gln by 21.0% in the intact neostriatum only, whereas it decreased the Asp level in both sides as compared to control. The cortical Glu content was decreased only after infusion of penicillin at 41 bar. The results suggest that intravenous penicillin has a more pronounced effect on transmitter than on metabolic Glu pools in rat brain.

Taurine treatment of dyskinesias: an attempt.

Taurine is a sulfonic amino acid with inhibitory effects in the central nervous system. The clinical effect of taurine on dyskinesias was tested in an open trial with 14 patients. Taurine (3 g/day) was given orally in divided doses. Six patients showed an initial improvement which, however, did not persist to the end of the 6-week treatment period. No side effects were observed. It seems unlikely that taurine administration will prove effective in the symptomatic treatment of dyskinesias.

The acute effect of ammonium acetate on levels of amino acids in the intact and decorticated rat neostriatum.

Unilateral frontal cortex ablations were performed in rats so that the glutamate terminals in the ipsilateral rostral neostriatum were removed. At 1 or 7 days later, intraperitoneal injections of ammonium acetate induced different changes in amino acid concentrations in the intact and deafferentated neostriatum. After 1 day, the level of glutamate decreased only in the intact side, whereas that of glutamine increased and that of aspartate decreased to the same extent on both sides following ammonia injection. After 7 days, the glutamate level decreased more in the intact than the decorticated side in both nonconvulsing and convulsing rats. The concentration of alanine increased most in the intact neostriatum, whereas glutamine levels increased and aspartate levels decreased to the same extent on both sides in nonconvulsing and convulsing rats. The results indicate that ammonia has a more pronounced effect on neuronal than glial glutamate pools.

Elevated concentrations of glutamate and aspartate in human ventricular cerebrospinal fluid (vCSF) during episodes of increased CSF pressure and clinical signs of impaired brain circulation.

In the ventricular cerebrospinal fluid (vCSF) of 10 hydrocephalic patients the mean (+/- S.D.) concentrations of glutamate and asparate were 2.9 +/- 0.2 and 0.2 +/- 0.2 microM, respectively. Significantly higher concentrations of these amino acids were found in two patients (glutamate 37.8 and 22.4 microM, aspartate 2.2 and 0.6 microM) with symptoms of impaired brain tissue perfusion, i.e. relative ischemia due to severely increased intraventricular CSF pressure. Our results are consistent with recent experiments in rats showing increased extracellular concentrations of glutamate and aspartate during transient cerebral ischemia.