Favorable change of lipid profile after carbamazepine withdrawal.

OBJECTIVE: Patients treated with carbamazepine (CBZ) have increased serum levels of total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoproteins (LDL). We aimed to investigate whether these changes of serum lipids are reversible after CBZ withdrawal. MATERIAL AND METHODS: We used a prospective, randomized double-blinded design. A total of 160 patients who had been seizure free on anti-epileptic drug monotherapy for more than 2 years were included and randomized to withdrawal or not. The intervention was completed by 150 (80 females, 53%) patients. Serum samples from before and 4 months after completed withdrawal or no withdrawal were obtained from 130 patients (63 females, 48%). Of these, 84 were treated with CBZ, 28 with valproate, nine with phenytoin, four with phenobarbital, and five with lamotrigine. Of the patients who had been treated with CBZ, 47 were randomized to the withdrawal group, and 37 were randomized to the non-withdrawal group. RESULTS: Among the CBZ-treated patients, a significant decrease in serum levels of TC, LDL, and apolipoprotein B (ApoB) were found in the withdrawal group compared with the non-withdrawal group. Mean differences in change were as follows: TC 0.68 mmol/l (P = 0.005, CL - 1.15 to -0.21); LDL - 0.67 mmol/l (P = 0.001, CL - 1.03 to -0.29); ApoB - 0.13 g/l (P = 0.02, CL - 0.23 to -0.03). No significant changes in HDL, apolipoprotein A, and C-reactive protein were detected. CONCLUSION: Our results indicate that CBZ may have unfavorable effects on serum levels of TC, LDL, and ApoB. However, these changes seem to be reversible even after years of treatment.

Repeated neuropsychological assessment in well-controlled epilepsy.

BACKGROUND: The majority of patients with epilepsy are seizure-free, and repeated neuropsychological assessment may be highly relevant in this group. However, previous studies have not addressed the possible influence of important clinical variables on repeated neuropsychological assessment in this population. METHODS: Using data from a large antiepileptic drug (AED) withdrawal study, we calculated the neuropsychological practice effects for 139 seizure-free patients with epilepsy and analysed the influence of different epilepsy-related factors on improvement that were observable 7 months after the initial neuropsychological assessment. RESULTS: A clear and significant improvement in neuropsychological test performance was found for all the tests employed, regardless of AED withdrawal. Furthermore, patients characterized by evidence of brain pathology, such as known cerebral aetiology, pathological MRI and pathological EEG, showed less practice effects than patients not characterized by these variables. The differences were primarily evident for measures of verbal learning and memory. CONCLUSION: The data obtained from this study suggest that the development of general norms for change in the particular patient population, as well as specific norms for change related to important clinical variables, might be necessary to be able to determine whether genuine neuropsychological changes have occurred in individual patients in this group.

The Norwegian Brain Council ('Hjernerådet')--united efforts are necessary!

There is a strong tradition of neuroscience in Norway, and Norwegian neurologists have been actively involved in developing partnerships between all those who recognize the importance of the brain and of brain diseases. It was therefore unsurprising that Norwegian neurologists took the initiative in establishing the Norwegian Brain Council (NBC). NBC was founded in 2007 and now comprises 27 organizations and institutions. It includes all those who work with brain research and brain diseases in Norway, as well as all relevant user organizations. Industries and businesses that are related to brain disease may be partners, but do not have full membership. The main mission of NBC is to provide information about the brain and brain diseases for both lay people and public authorities, including politicians, and to promote better treatment for patients with brain diseases and more research in neuroscience. The council has firm ties to the European Brain Council (EBC). NBC plans to follow the initiative taken by EBC in organizing a 'Month of the Brain' in 2013 and a 'Year of the Brain' in 2014. These initiatives could provide an impetus for greater focus on brain diseases, which is essential in order to meet the considerable challenges that are posed by brain diseases in the years to come.

Partnership and cooperation is necessary to improve and expand neurology.

BACKGROUND: Brain disorders have a large impact on society, representing one third of the total burden of disease. Neurology is more than before divided into fields of highly specialized branches. OBJECTIVE: To assess the need for co-operation in neuromedicine to achieve optimal results for patient treatment, diagnosis and care. DISCUSSION: Co-operation regarding patients with disorders in the brain and nervous system should involve medical specialists, general practitioners, other professionals, patients and carers. Optimal co-operation represents both an institutional and personal challenge. The principle of joint action between several subspecialists should also have consequences for educational systems and requirements. Formalised co-operation is well established in medical research, and principles for good practice in neuroscience have relevance also for clinical medicine. How to organise the optimal treatment is therefore not only a challenge for neurologists, but also for the total health system within hospitals and in society. CONCLUSION: Open-handedness and a willingness to co-operate should be a hallmark for neurologists.

Gender differences in risk-taking behaviour in youth with epilepsy: a Norwegian population-based study.

OBJECTIVES: It is well known that behavioural problems and psychiatric disorders occur with greater prevalence in children and adolescents with epilepsy. Youth with epilepsy (YWE) may also be more susceptible to risk-taking behaviour, but this has seldom been studied. The aim of this study was to explore risk-taking behaviour in YWE. MATERIAL AND METHODS: In this study, 19,995 young people (age range: 13-19 years) participated and completed an extensive questionnaire, including The Strengths and Difficulties Questionnaire self-report. A variable, risk-taking behaviour, was identified, including daily consumption of alcohol, substance abuse or having committed a criminal offence such as being in a fight with a weapon, committing a burglary or using threats to obtain money. RESULTS: Two hundred and forty-seven youths reported currently having, or having had, epilepsy (lifetime prevalence: 1.2%). Of these, 8.3% reported daily alcohol consumption (1.0% in controls; P<0.001), 12.4% had tried illegal substances (5.5% of controls; P<0.001), and 19.7% had committed criminal offences (8.5% in controls; P<0.001). A gender difference was found: girls with epilepsy did not exhibit risk-taking behaviour more frequently than controls, but having epilepsy was a risk factor for such behaviour in boys (OR: 3.2). CONCLUSION: Boys with epilepsy exhibit risk-taking behaviour more frequently than controls. Other risk factors for this behaviour were living with a single parent, low family income and psychiatric symptoms. This behavioural association should be addressed as it probably contributes to the negative social outcomes that frequently occur in the adult epilepsy population.

Haematological side effects of antiepileptic drug treatment in patients with epilepsy.

OBJECTIVES: Little is known about the haematological side effects of the newer antiepileptic drugs (AEDs), but recent case reports have raised concerns regarding the possibility of altered thrombocyte counts or function in some patients during levetiracetam (LEV) treatment. The aim of our study was to investigate haematological changes in patients treated with the newer AEDs, LEV and lamotrigine (LTG), compared with the older AEDs, valproate (VPA) and carbamazepine (CBZ). METHODS: This cross-sectional study included 251 patients with epilepsy of both genders, aged 18-45 years, using AED monotherapy: 52 patients on LEV (31 men, 21 women), 80 on LTG (37 men, 43 women), 90 on CBZ (61 men, 29 women), 29 on VPA (15 men, 14 women), and 79 healthy controls (36 men, 43 women). Haemoglobin (Hb), white blood cells (WBC) and platelet (thrombocyte) counts were estimated. The subjects were recruited from hospitals in south-eastern Norway and Innsbruck, Austria. RESULTS: Significantly lower platelet counts were recorded in both men and women on LEV monotherapy. In the LEV group, platelets were 14% lower (40.68 × 10(9) /l lower) than in the control group. There was no difference according to sex or age of the patients. Only minor changes in haematological parameters were observed for the other drugs investigated. CONCLUSIONS: Both men and women treated with LEV monotherapy have lower blood platelet counts than healthy controls, with no difference in Hb or WBC. Haematological changes observed with the other AEDs were minor.

Improvement in verbal memory after withdrawal of carbamazepine and valproate in patients with well-controlled epilepsy: a randomized, double-blind study.

BACKGROUND: For most major antiepileptic drugs, neuropsychological side effects have been reported. Healthy volunteer studies have found that both carbamazepine and valproate impair aspects of verbal memory. OBJECTIVE: The aim of this study was to assess the effects of carbamazepine and valproate on verbal memory, in a well-controlled epilepsy population. METHODS: This was carried out with a randomized, double-blind and placebo-controlled study of anticonvulsant withdrawal in patients receiving monotherapy. RESULTS: In the carbamazepine group (n=92), withdrawal significantly improved recall after 30 min (P=0.03). In the valproate group (n=32), withdrawal significantly improved performance of immediate word span (P=0.04). CONCLUSIONS: Withdrawal was randomized to placebo, but the choice of medication was not randomized to placebo. This means that the shown differences in neuropsychological outcome cannot with full certainty be attributed to either antiepileptic drug. The improvement of memory, after both carbamazepine and valproate withdrawal, was slight, and the impact on daily life function is uncertain.

Cost of disorders of the brain in Norway.

BACKGROUND: Little is known about the cost of neurological disorders in Norway. OBJECTIVES: To estimate the cost of disorders of the brain, including the main psychiatric, neurological and neurosurgical conditions in Norway. METHODS: Most of the data are extrapolations from a large European cost study that collected the best available epidemiological and health economical evidence for the year 2004. Some epidemiological data are available from Norway, but very little on costs. RESULTS: Brain disorders seemed to affect 1.5 million Norwegians in 2004, and the total cost amounted to 5.8 billion Euros. The most prevalent disorders are anxiety disorders and migraine, and the most costly are affective disorders, addiction and dementia. Migraine is the most costly of the purely neurological conditions, followed by stroke, epilepsy and Parkinson's disease. The indirect costs account for more than half of the total costs. DISCUSSION: Although the different brain disorders are very dissimilar in appearance, from health economic and public health perspectives, it is relevant to view them as a whole, since many of them share important pathophysiological mechanisms. This means that new insights into one disorder can have relevance for many other disorders. CONCLUSION: As a result of the high impact on individuals and society, more resources should be allocated to treatment and research into brain disorders.

Cardiovascular risk factors in epilepsy patients taking levetiracetam, carbamazepine or lamotrigine.

OBJECTIVES: The aim of the study was to investigate risk factors for cardiovascular disease in patients with epilepsy using the new antiepileptic drug levetiracetam (LEV), compared with patients taking carbamazepine (CBZ) or lamotrigine (LTG). METHODS: Two hundred and twelve patients and 80 controls (age: 18-45 years) of both genders were included. The patients had been treated with either LEV (n = 52), CBZ (n = 87) or LTG (n = 73) monotherapy for at least 6 months. Total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured. Smoking, drinking habits and physical activity were recorded and body mass index (BMI) was calculated. RESULTS: Neither LEV nor LTG altered TC, LDL or HDL. Both men and women using CBZ had higher TC, HDL and LDL than controls. LDL/HDL and TC/HDL ratios were unchanged. Women on CBZ and LTG had a greater BMI when compared with the control group. Patients with epilepsy recorded less physical activity and lower alcohol use than the controls. CONCLUSIONS: Neither LEV nor LTG affected blood lipid levels, while patients treated with CBZ have higher cholesterol, HDL and LDL than controls. The patients were less physically active, and women on CBZ and LTG had higher BMI.

Norwegian neurology: present status and future trends.

Diseases of the nervous system constitute a major cause of morbidity and mortality. The chronic nature of many neurological diseases demands long-term follow-up and good communicative skills. Financial conditions and compensation is closely linked to modern health care and may limit the availability of new therapeutic options. An ageing population and modern lifestyle represent challenges for neurology in the future. The participation in public debate and strategic planning of health services are crucial to improve neurological services on a national and global level. Our focus should be the promotion of special needs of patients with neurological disease.

Phenotypic characteristics of temporal lobe epilepsy: the impact of hippocampal sclerosis.

OBJECTIVES: Whether mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a condition with a unique biological background that can be delineated from other TLE, is unresolved. Here we performed a comparative analysis of two TLE patient cohorts - one cohort with HS and one without HS - in order to identify phenotypic characteristics specifically associated with MTLE-HS. METHODS: Epidemiological data and clinical and diagnostic features were compared between patients with MTLE-HS and TLE patients without HS. When appropriate, data were compared with healthy controls. RESULTS: Fifty-six (26%) patients were diagnosed with MTLE-HS and 162 (74%) with other TLE. Age at epilepsy onset was lower in patients with MTLE-HS (P = 0.003) than in TLE patients without HS. Incidence of simple partial seizures was higher in the MTLE-HS group (P = 0.006), as were complex partial seizures (P = 0.001), ictal psychiatric symptoms (P = 0.015), and autonomic symptoms (P < 0.001). Interictal psychiatric symptoms, including depression, were less frequent in MTLE-HS (P = 0.043). MTLE-HS patients had a higher incidence of childhood febrile seizures (FS; P = 0.043) than TLE patients without HS. In contrast, the former group had the lower frequency of first-grade family members with childhood FS (P = 0.019). CONCLUSIONS: We identified phenotypic characteristics that distinguish MTLE-HS from other types of TLE. These characteristics will be important in diagnostics, treatment, and determination of prognosis, and provide a basis for future phenotype-genotype studies.

Antiepileptic monotherapy significantly impairs normative scores on common tests of executive functions.

BACKGROUND: Understanding how antiepileptic (AED) monotherapy influences normative test scores is of importance in the clinic for correct interpretation of neuropsychological profiles. Previous studies have primarily reported minor influence on neuropsychological raw scores, and the clinical relevance of these findings is unclear. AIM OF THE STUDY: To obtain a clinical valid answer to this question, we analysed changes in T-scores after AED withdrawal in a large group of well-controlled epilepsy patients, for tests previously shown to be sensitive to AED withdrawal. METHODS: We report outcomes on measures of choice reaction time from the California Computerized Assessment Package, on the Controlled Oral Word Association Test and on the Stroop Color-Word Interference Test. RESULTS: Significantly improved T-scores were revealed after AED withdrawal on five of the six tests of executive functions with mean improvement of 5 T-scores. Comparable results were achieved in the subgroup taking carbamazepine, with a mean improvement of 6.2 T-scores. CONCLUSION: The present results suggest that T-scores for computerized tests of choice reaction time and tests of verbal fluency and response inhibition may be significantly impaired as a consequence of AED monotherapy, and that careful interpretation of these scores is required in diagnostic assessment of patients receiving AED monotherapy.

Multimodal imaging in mild cognitive impairment: Metabolism, morphometry and diffusion of the temporal-parietal memory network.

This study compared sensitivity of FDG-PET, MR morphometry, and diffusion tensor imaging (DTI) derived fractional anisotropy (FA) measures to diagnosis and memory function in mild cognitive impairment (MCI). Patients (n=44) and normal controls (NC, n=22) underwent FDG-PET and MRI scanning yielding measures of metabolism, morphometry and FA in nine temporal and parietal areas affected by Alzheimer's disease and involved in the episodic memory network. Patients also underwent memory testing (RAVLT). Logistic regression analysis yielded 100% diagnostic accuracy when all methods and ROIs were combined, but none of the variables then served as unique predictors. Within separate ROIs, diagnostic accuracy for the methods combined ranged from 65.6% (parahippocampal gyrus) to 73.4 (inferior parietal cortex). Morphometry predicted diagnostic group for most ROIs. PET and FA did not uniquely predict group, but a trend was seen for the precuneus metabolism. For the MCI group, stepwise regression analyses predicting memory scores were performed with the same methods and ROIs. Hippocampal volume and FA of the retrosplenial WM predicted learning, and hippocampal metabolism and parahippocampal cortical thickness predicted 5 minute recall. No variable predicted 30 minute recall independently of learning. In conclusion, higher diagnostic accuracy was achieved when multiple methods and ROIs were combined, but morphometry showed superior diagnostic sensitivity. Metabolism, morphometry and FA all uniquely explained memory performance, making a multi-modal approach superior. Memory variation in MCI is likely related to conversion risk, and the results indicate potential for improved predictive power by the use of multimodal imaging.

Morphometric changes in the episodic memory network and tau pathologic features correlate with memory performance in patients with mild cognitive impairment.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) may affect several cognitive domains, including attention and reasoning, but is often first characterized by memory deficits. The purpose of this study was to ask these 2 questions: 1) Can levels of CSF tau proteins and amyloid beta 42 peptide explain thinning of the cerebral cortex in patients with MCI? 2) How are brain morphometry, CSF biomarkers, and apolipoprotein E (APOE) allelic variation related to episodic memory function in MCI? MATERIALS AND METHODS: Hippocampal volume and cortical thickness were estimated by MR imaging and compared for patients with MCI (n = 18) and healthy controls (n = 18). In addition, regions of interest (ROIs) were selected in areas where the MCI group had atrophy and which overlapped with the episodic memory network (temporal, entorhinal, inferior parietal, precuneus/posterior cingulate, and frontal). Relationships among morphometry, CSF biomarkers, APOE, and memory were tested. The analyses were repeated with an independent sample of patients with MCI (n = 19). RESULTS: Patients with MCI and pathologic CSF values had hippocampal atrophy. However, both patients with pathologic and patients with nonpathologic CSF had a thinner cortex outside the hippocampal area. CSF pathology was related to hippocampal volume, whereas relationships with cortical thickness were found mainly in one of the samples. Morphometry correlated robustly with memory performance across MCI samples, whereas less stable results were found for tau protein. CONCLUSION: The differences in hippocampal volume between the MCI and the healthy control groups were only found in patients with pathologic CSF biomarkers, whereas differences in cortical thickness were also found for patients without such pathologic features. Morphometry in areas in the episodic memory network was robustly correlated with memory performance. It is speculated that atrophy in these areas may be associated with the memory problems seen in MCI.

A retrospective view on research in neuroscience in Norway.

This brief historical review on neuroscience in Norway shows a comparatively high research activity with many important results. The Norwegian zoologist Fridtjof Nansen, who later became a famous Arctic explorer, was the first to formulate the neuron doctrine. 'The Oslo School of Neuroanatomy' contributed enormously to the understanding of the detailed anatomy and chemistry of the central nervous system. Norwegian neurophysiologists made important findings from studies of hippocampus including the inhibitory basket cell, the LTP phenomenon and the 'hippocampal-slice-technique'. In clinical neuroscience the description of Refsum's disease and studies of myasthenia gravis and multiple sclerosis have been of particular importance. Two of 13 centres of excellence in Norway selected in 2003 were from neuroscience, and The Norwegian Research Council has its own programme for neuroscience. The Norwegian Neurological Association arranges annual meetings to promote interest in neurological research.

G protein beta3 subunit C825T polymorphism modifies the presentation of temporal lobe epilepsy.

PURPOSE: Experimental studies suggest a role of G protein-mediated signaling pathways in epileptogenesis. A genetic variation affecting the G protein subunit Gbeta3 denoted the C825T polymorphism has been reported to increase the signaling efficiency through G(i) proteins and to modify responses to certain drugs. The C825T polymorphism has also been associated with several diseases including hypertension, diabetes type II, obesity, and major depressive disorder. In this study, we have explored whether the G protein polymorphism C825T is associated with or influences temporal lobe epilepsy (TLE). METHODS: The study included 227 TLE patients, 186 controls, and 106 family members of TLE patients. DNA was extracted from blood samples and typing of the polymorphism was performed. Case record forms were analyzed for all the homozygote TLE patients and homozygote controls, i.e., carrying the TT genotype as well as for 28 matched TLE patients (16 females, 12 males) without the polymorphism (CC genotype). RESULTS: Typing of the C825T polymorphism showed that 6.0% of the TLE patients, 7.0% of the controls, and 7.5% of the family members were homozygote for the polymorphism; i.e., carrying the TT genotype. TLE patients carrying the TT genotype had higher severity score on eight out of nine predefined parameters compared with the TLE patients without polymorphism, i.e., carrying CC genotype. TT genotype TLE patients also had increased body mass index, body weight, and waist circumference compared with the TLE patients carrying the CC genotype. There was no increased frequency of hypertension or diabetes. CONCLUSIONS: There was no increased frequency of TLE between the carriers of the TT genotype compared with the healthy controls and/or family members without epilepsy. However, the TLE patients with the TT genotype showed tendencies of a more severe disease phenotype.

White matter lesion severity is associated with reduced cognitive performances in patients with normal CSF Abeta42 levels.

OBJECTIVE: To identify possible associations between white matter lesions (WML) and cognition in patients with memory complaints, stratified in groups with normal and low cerebrospinal fluid (CSF) Abeta42 values. MATERIAL AND METHODS: 215 consecutive patients with subjective memory complaints were retrospectively included. Patients were stratified into two groups with normal (n = 127) or low (n = 88) CSF Abeta42 levels (cut-off is 450 ng/l). Cognitive scores from the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat) were used as continuous dependent variables in linear regression. WML load was used as a continuous independent variable and was scored with a visual rating scale. The regression model was corrected for possible confounding factors. RESULTS: WML were significantly associated with MMSE and all Cognistat subscores except language (repetition and naming) and attention in patients with normal CSF Abeta42 levels. No significant associations were observed in patients with low CSF Abeta42. CONCLUSIONS: WML were associated with affection of multiple cognitive domains, including delayed recall and executive functions, in patients with normal CSF Abeta42 levels. The lack of such associations for patients with low CSF Abeta42 (i.e. with evidence for amyloid deposition), suggests that amyloid pathology may obscure cognitive effects of WML.

Changes in autonomic cardiac control in patients with epilepsy after discontinuation of antiepileptic drugs: a randomized controlled withdrawal study.

The aim of this study was to assess cardiac autonomic control in patients with epilepsy before and after withdrawal of antiepileptic drugs (AEDs). The study was prospective, randomized and double blinded. Spectral analysis of heart rate variability (HRV) in 24 h ECG-registration before and after withdrawal of AEDs was used to assess autonomic cardiac control. The assessment of HRV with spectral analysis was based on sinus rhythm and normal heart beats [normal to normal beat (NN)]. Thirty-nine patients had 24 h rhythms free from any ectopic beats both before and after intervention, and were included in the analysis. Significant differences were found in the withdrawal group: filtered RR intervals for all 5 min segments of the analysis; percentage of differences between adjacent filtered RR intervals that are greater than 50 ms for the whole analysis; very low frequency power; low frequency power and high frequency power. The results demonstrate that slow withdrawal of AEDs in seizure-free patients with epilepsy on drug mono-therapy resulted in an increase in both parasympathetic and sympathetic functions, indicative of increased power amongst patients following cessation of AED treatment. As low HRV has been associated with increased mortality in patients with other diseases, this increased HRV may be beneficial.

Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults.

OBJECTIVE: Status epilepticus (SE) and serial attacks (SA) represent neurological emergencies, and mortality rate for SE/SA is high, ranging from 3% to 25%, depending on cause and co-morbidity. As SE/SA become more refractory to treatment over time, rapid, appropriate treatment is extremely important. Here, we report a prospective registration of the effect of intravenous (IV) valproate (VPA) on SE/SA in a group of Norwegian patients. PATIENTS AND METHODS: Forty-one adult patients (18 males, 23 females) were included in the study. All had previously been unsuccessfully treated with diazepam. For 19, the main SE/SA seizure type was generalized tonic-clonic, while 16 had complex-partial seizures. Six had seizures that were difficult to classify. The treatment protocol recommended 25 mg/kg of VPA loading dose over 30 min, followed by continuous infusion of 100 mg/h for at least 24 h, then per oral administration. If seizures persisted after the loading dose, general anaesthesia (barbiturates/propofol/midazolam) was administered. RESULTS: No serious side effects were reported. In 76% of the cases (31 of 41), SE/SA stopped and anaesthesia was not required. Of the patients treated within 3 h, only 5% needed anaesthesia, whereas of those treated after 3-24 h, 38% needed anaesthesia. Of those who waited for more than 24 h before treatment, 60% required anaesthesia. Furthermore, 60% of the patients who needed anaesthesia were given loading doses below 2100 mg. CONCLUSIONS: VPA seems to be a safe, effective treatment of SE/SA, but efficacy is dependent on time lapse between symptoms and VPA treatment, and administration of a sufficiently high loading dose.