Language impairment in children aged 5 and 8 years after antiepileptic drug exposure in utero - the Norwegian Mother and Child Cohort Study.

BACKGROUND AND PURPOSE: The purpose was to examine the consequences of antiepileptic drug (AED) exposure during pregnancy on language abilities in children aged 5 and 8 years of mothers with epilepsy. METHODS: The study population included children of mothers with and without epilepsy enrolled in the Norwegian Mother and Child Cohort Study 1999-2008. Mothers prospectively provided information on epilepsy diagnosis, AED use during pregnancy and the child's language abilities at age 5 and 8 years, in questionnaires with validated language screening tools. AED concentrations in gestation week 17-19 and in the umbilical cord were measured. RESULTS: The study population included 346 AED-exposed and 388 AED-unexposed children of mothers with epilepsy, and 113 674 children of mothers without epilepsy. Mothers of 117 and 121 AED-exposed children responded to the questionnaires at age 5 and 8 years, respectively. For AED-exposed children, the adjusted odds ratio for language impairment was 1.6 [confidence interval (CI) 1.1-2.5, P = 0.03] at age 5 years and 2.0 (CI 1.4-3.0, P < 0.001) at age 8 years, compared to children of mothers without epilepsy. Children exposed to carbamazepine monotherapy had a significantly increased risk of language impairment compared to control children at age 8 years (adjusted odds ratio 3.8, CI 1.6-9.0, P = 0.002). Higher maternal valproate concentrations correlated with language impairment at age 5 years. Periconceptional folic acid supplement use protected against AED-associated language impairment. CONCLUSION: Foetal AED exposure in utero is associated with an increased risk of language impairment in children aged 5 and 8 years of mothers with epilepsy. Periconceptional folic acid use had a protective effect on AED-associated language impairment.

Maternal myasthenia gravis represents a risk for the child through autoantibody transfer, immunosuppressive therapy and genetic influence.

Females with myasthenia gravis (MG) worry about their disease having negative consequences for their children. Autoimmune disease mechanisms, treatment and heredity could all have an impact on the child. This is a subject review where Web of Science was searched for relevant keywords and combinations. Controlled and prospective studies were included, and also results from selected and unselected patient cohorts, guidelines, consensus papers and reviews. Neonatal MG with temporary muscle weakness occurs in 10% of newborn babies where the mother has MG, due to transplacental transfer of antibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or lipoprotein receptor-related protein 4 (LRP4). Arthrogryposis and fetal AChR inactivation syndrome with contractures and permanent myopathy are rare events caused by mother's antibodies against fetal type AChR. The MG drugs pyridostigmine, prednisolone and azathioprine are regarded as safe during pregnancy and breastfeeding. Methotrexate, mycophenolate mofetil and cyclophosphamide are teratogenic. Mother's MG implies at least a 10-fold increased risk for MG and other autoimmune diseases in the child. MG females should receive specific information about pregnancy and giving birth. First-line MG treatments should usually be continued during pregnancy. Intravenous immunoglobulin and plasma exchange represent safe treatments for exacerbations. Neonatal MG risk means that MG women should give birth at hospitals experienced in neonatal intensive care. Neonatal MG needs supportive care, rarely also acetylcholine esterase inhibition or intravenous immunoglobulin. Women with MG should be supported in their wish to have children.

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.

HLA and MuSK-positive myasthenia gravis: A systemic review and meta-analysis.

OBJECTIVES: Myasthenia gravis (MG) represents a spectrum of clinical subtypes with differences in disease mechanisms and treatment response. MG with muscle-specific tyrosine kinase (MuSK) antibodies accounts for 1%-10% of all MG patients. We conducted a meta-analysis to evaluate the association between HLA genes and MuSK-MG susceptibility. SUBJECTS AND METHODS: Studies were searched in Pubmed, EMBASE database and other sources between 2001 and 2018. Genotype, allele and haplotype frequencies of HLA loci in MuSK-MG patients and healthy controls were extracted from each included study. RESULTS: The meta-analysis showed that HLA DQB1*05, DRB1*14 and DRB1*16 were strongly associated with an increased risk of MuSK-MG (P < .0001), whereas HLA DQB*03 was less frequent in MuSK patients compared with healthy controls (P < .05). Haplotype analysis showed that these DQB1 and DRB1 alleles were closely linked, forming both risk (DQ5-DR14, DQ5-DR16, P < .0001) and protective (DQ3-DR4, DQ3-DR11, P < .05) haplotypes. CONCLUSION: The distinct genetic patterns of MuSK-MG indicate that variation in HLA class II genes plays an important role in the pathogenesis of MuSK-MG patients.

Multiple antibody detection in 'seronegative' myasthenia gravis patients.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disease caused by antibody mediated impairment in the neuromuscular junction. Seronegative MG (SNMG) without antibodies against acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) by routine assays accounts for about 20% of all MG patients. METHODS: Plasma from 81 Chinese MG patients previously found to be seronegative was tested by routine assays for AChR and MuSK antibodies. These samples were screened by (i) a novel, highly sensitive radioimmunoassay for AChR antibodies; (ii) cell-based assays for clustered AChR, MuSK and lipoprotein receptor-related protein 4 (LRP4) antibodies; (iii) a radioimmunoassay for titin antibodies. RESULTS: Antibodies to AChR, MuSK, LRP4 and titin were found in 25% (20/81), 4% (3/81), 7% (6/81) and 6% (5/78) of SNMG patients, respectively. In total, 37% of SNMG patients were found to be positive for at least one of the tested antibodies. AChR antibody positive patients had more severe disease (P = 0.008) and a trend towards fewer remissions/minimal manifestations than AChR antibody negative patients. The four patients with coexistence of antibodies had more severe disease, whilst the seronegative patients had milder MG (P = 0.015). CONCLUSIONS: Detection of multiple muscle antibodies by more sensitive assays provides additional information in diagnosing and subgrouping of MG and may guide MG treatment.

Myasthenia gravis and risks for comorbidity.

Myasthenia gravis (MG) is an autoimmune disorder leading to skeletal muscle weakness and fatigability. MG subgroups are defined according to pathogenetic autoantibody (against acetylcholine receptor, muscle-specific tyrosine kinase or lipoprotein receptor-related protein 4), thymus pathology and clinical manifestations. MG patients have an increased risk for concordant autoimmune disease, in particular with early onset MG. Most common comorbidities are thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. Cardiomyositis and subclinical heart dysfunction have been described in patients with thymoma MG and late onset MG but represent no major threat. A thymic lymphoepithelioma implies an increased risk for another cancer. Autoimmune MG represents no distinct cancer risk factor, although lymphomas and a few other cancer types have been reported with slightly increased frequency. Severe MG-related muscle weakness means a risk for respiratory failure and respiratory tract infection. Drug MG treatment can lead to side-effects. Thymectomy is regarded as a safe procedure both short and long term. Non-MG-related comorbidity represents a diagnostic and therapeutic challenge, especially in elderly patients. Diagnostic accuracy and optimal follow-up is necessary to identify and treat all types of coexisting disease in MG.

EFNS/ENS Guidelines for the treatment of ocular myasthenia.

BACKGROUND AND PURPOSE: The symptoms of acquired autoimmune ocular myasthenia are restricted to the extrinsic eye muscles, causing double vision and drooping eyelids. These guidelines are designed to provide advice about best clinical practice based on the current state of clinical and scientific knowledge and the consensus of an expert panel. SEARCH STRATEGY: Evidence for these guidelines was collected by searches in the MEDLINE and Cochrane databases. The task force working group reviewed evidence from original articles and systematic reviews. The evidence was classified (I, II, III, IV) and consensus recommendation graded (A, B or C) according to the EFNS guidance. Where there was a lack of evidence but clear consensus, good practice points are provided. CONCLUSIONS: The treatment of ocular myasthenia should initially be started with pyridostigmine (good practice point). If this is not successful in relieving symptoms, oral corticosteroids should be used on an alternate-day regimen (recommendation level C). If steroid treatment does not result in good control of the symptoms or if it is necessary to use high steroid doses, steroid-sparing treatment with azathioprine should be started (recommendation level C). If ocular myasthenia gravis is associated with thymoma, thymectomy is indicated. Otherwise, the role of thymectomy in ocular myasthenia is controversial. Steroids and thymectomy may modify the course of ocular myasthenia and prevent myasthenia gravis generalization (good practice point).

Total drug treatment and comorbidity in myasthenia gravis: a population-based cohort study.

BACKGROUND AND PURPOSE: Comorbidity in myasthenia gravis (MG) is important for diagnosis, treatment and prognosis. Disease complexity was assessed by examining total drug treatment, immune therapy and comorbidity in a complete national MG cohort. METHODS: All recipients of the MG-specific drug pyridostigmine 2004-2010 registered in the compulsory Norwegian Prescription Database who met the inclusion criteria were included. The pyridostigmine group was compared with the general Norwegian population. RESULTS: Myasthenia gravis patients received co-medication more often than the controls for nearly all groups of medication, including insulins (95% confidence interval 2.0-3.7), thyroid therapy (1.7-2.5), antidepressants (1.3-1.7), anti-infectives (1.2-1.4), lipid-modifying agents (1.1-1.4) and immunomodulating agents (6.8-8.8). CONCLUSIONS: Myasthenia gravis patients are more often treated with non-MG prescription drugs than controls, reflecting frequent co-medication and comorbidity.

Antititin antibody in early- and late-onset myasthenia gravis.

OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease caused by antibodies against neuromuscular junction proteins, 85% of patients have antibodies against acetylcholine receptor (AChR-MG). Antititin antibodies are present in a subset of patients with MG. We aimed to determine the value of antititin antibodies as severity markers and thymoma predictors in early- and late-onset MG. MATERIALS & METHODS: Two-hundred and ninety-five consecutive MG patients (188 F and 107 M) aged 12-89 years (mean 50y) were included. 164 patients had early-onset (EOMG, ≤50 years of age), 131 had late-onset MG (LOMG). Twenty-six patients had thymoma. symptoms, severity graded with MGFA scale, thymus histology, medications, and treatment results were analyzed. RESULTS: Antititin antibodies were present in 81 (27%) of all patients: 54% of thymoma MG, 0.6% of non-thymomatous EOMG, and 55% of LOMG, with proportion of titin-positive patients increasing linearly from 40% in the 6th to 88% in the 9th decade of life. Titin-positive patients had more bulbar symptoms (P = 0.003). Severity of MG, need for immunosuppression, myasthenic crisis risk or treatment results were not related to its presence. Antititin antibodies had 56% sensitivity, 99% specificity, 90% positive predictive value (PPV), and 95% negative predictive value (NPV) for thymoma diagnosis in EOMG, and 50% sensitivity, 75% specificity, 71% PPV and 55% NPV in LOMG. CONCLUSIONS: Antititin antibodies have high PPV and NPV for thymoma in EOMG. In MG without thymoma, antititin antibodies can be considered as markers of LOMG, but not of a severe course in our MG cohort.

Screening for tumours in paraneoplastic syndromes: report of an EFNS task force.

BACKGROUND: paraneoplastic neurological syndromes (PNS) almost invariably predate detection of the malignancy. Screening for tumours is important in PNS as the tumour directly affects prognosis and treatment and should be performed as soon as possible. OBJECTIVES: an overview of the screening of tumours related to classical PNS is given. Small cell lung cancer, thymoma, breast cancer, ovarian carcinoma and teratoma and testicular tumours are described in relation to paraneoplastic limbic encephalitis, subacute sensory neuronopathy, subacute autonomic neuropathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome (LEMS), myasthenia gravis and paraneoplastic peripheral nerve hyperexcitability. METHODS: many studies with class IV evidence were available; one study reached level III evidence. No evidence-based recommendations grade A-C were possible, but good practice points were agreed by consensus. RECOMMENDATIONS: the nature of antibody, and to a lesser extent the clinical syndrome, determines the risk and type of an underlying malignancy. For screening of the thoracic region, a CT-thorax is recommended, which if negative is followed by fluorodeoxyglucose-positron emission tomography (FDG-PET). Breast cancer is screened for by mammography, followed by MRI. For the pelvic region, ultrasound (US) is the investigation of first choice followed by CT. Dermatomyositis patients should have CT-thorax/abdomen, US of the pelvic region and mammography in women, US of testes in men under 50 years and colonoscopy in men and women over 50. If primary screening is negative, repeat screening after 3-6 months and screen every 6 months up till 4 years. In LEMS, screening for 2 years is sufficient. In syndromes where only a subgroup of patients have a malignancy, tumour markers have additional value to predict a probable malignancy.

Obstetric outcome in women with epilepsy: a hospital-based, retrospective study.

OBJECTIVE: To report the complications during pregnancy and delivery in women with epilepsy, compared with a control group without epilepsy, with special focus on potential risk factors, such as epilepsy severity and dosage of antiepileptic drugs. DESIGN: Hospital-based retrospective study. SETTING: Data from pregnancy notification forms and hospital case records. POPULATION: Women with a past or present history of epilepsy (n = 205) delivered in Bergen, Norway, in the period 1999-2006, and a matched control group of women (n = 205) without epilepsy. METHODS: Data were compared and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by multiple logistic regression models. MAIN OUTCOME MEASURES: Pre-eclampsia (mild and severe), gestational hypertension, vaginal bleeding (early and late), caesarean section, vaginal operative delivery, postpartum haemorrhage and major malformations. RESULTS: Women with epilepsy using antiepileptic drugs had an increased risk of severe pre-eclampsia (OR, 5.0; 95% CI, 1.3-19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7-15.2), induction (OR, 2.3; 95% CI, 1.2-4.3) and caesarean section (OR, 2.5; 95% CI, 1.4-4.7) adjusted for maternal age, parity, education, smoking, medical conditions and body mass index ≥30 kg/m(2) . There was also an increased risk of malformations in the offspring (OR, 7.1; 95% CI, 1.4-36.6). Women without antiepileptic drug use had increased risks of forceps delivery and preterm birth. Active epilepsy (seizures during the last 5 years) versus nonactive epilepsy did not discriminate for any of these complications; 84.5% of women with epilepsy and antiepileptic drug use were using folate. CONCLUSION: Women with epilepsy using antiepileptic drugs had an increased risk of pregnancy and delivery complications, whereas women not using antiepileptic drugs had few complications. Seizures, high doses of antiepileptic drugs, obesity and lack of folate could not explain these increased risks.

Publishing affects funding in neurology.

BACKGROUND AND PURPOSE: A new national system for funding research in universities and hospitals in Norway based on publication output is described. METHODS: All scientific publications were counted and weighted according to the quality of the publication channel. Author addresses were credited. This led to a number of publication points for each institution/department. RESULTS: The number of publication points for neurology had increased from 75.0 in 2005 to 98.3 in 2007. Publishing and the quality of publications were given more attention than before, and there was a stronger focus on facilitating research at the institutions. Research was regarded as not only an institutional but also as an individual responsibility. CONCLUSIONS: The principle of performance-based funding in addition to funding based on project applications has been well received, and it stimulates more and better research. Scientific publications represent a useful marker, whereas the way of counting author addresses and determining quality is still debated.

Myasthenia gravis requiring pyridostigmine treatment in a national population cohort.

BACKGROUND: Pyridostigmine is the first drug of choice for patients with myasthenia gravis (MG). The drug is not prescribed regularly to any other patient groups. We aimed to determine the prevalence, incidence and gender-specific characteristics of patients with MG needing drug treatment in a well-defined population cohort. METHODS: Data were retrieved from the Norwegian Prescription Database (NorPD) 2004-2007, containing information on all dispensed drugs in Norway. The study population comprised 677 recipients of pyridostigmine who met the following inclusion criteria (one or more): (i) More than one prescription 1 January 2004-31 December 2007, (ii) prescription from a specialist in neurology, (iii) prescription for MG being specified in NorPD. RESULTS: A total of 435 (64%) women and 242 men were included; female:male ratio 1.8:1. Point prevalence (1 January 2008) of symptomatic MG was 131 per million; 92 for men, 170 for women. Seventy-four new users of pyridostigmine were registered in 2007 (42 women, 32 men), i.e. the incidence rate for 2007 being 16 per million; 14 for men, 18 for women. Mean age of incident cases was 59 years; 64 and 55 years, respectively. Prevalence and incidence were significantly higher in the age group ≥ 50 years than < 50 years (P < 0.001), and highest at 70-79 years. Prevalence and incidence did not differ in the five geographical health regions in Norway. CONCLUSIONS: Reported prevalence and incidence are amongst the highest found in similar studies. This may be explained by optimal case identification, higher incidence of drug requiring MG amongst the elderly, and recurrences of previous MG.

Guidelines for treatment of autoimmune neuromuscular transmission disorders.

BACKGROUND: Important progress has been made in our understanding of the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia (Isaacs' syndrome). METHODS: To prepare consensus guidelines for the treatment of the autoimmune NMT disorders, references retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts. CONCLUSIONS: Anticholinesterase drugs should be given first in the management of MG, but with some caution in patients with MuSK antibodies (good practice point). Plasma exchange is recommended in severe cases to induce remission and in preparation for surgery (recommendation level B). IvIg and plasma exchange are effective for the treatment of MG exacerbations (recommendation level A). For patients with non-thymomatous MG, thymectomy is recommended as an option to increase the probability of remission or improvement (recommendation level B). Once thymoma is diagnosed, thymectomy is indicated irrespective of MG severity (recommendation level A). Oral corticosteroids are first choice drugs when immunosuppressive drugs are necessary (good practice point). When long-term immunosuppression is necessary, azathioprine is recommended to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (recommendation level A). 3,4-Diaminopyridine is recommended as symptomatic treatment and IvIG has a positive short-term effect in LEMS (good practice point). Neuromyotonia patients should be treated with an antiepileptic drug that reduces peripheral nerve hyperexcitability (good practice point). For paraneoplastic LEMS and neuromyotonia optimal treatment of the underlying tumour is essential (good practice point). Immunosuppressive treatment of LEMS and neuromyotonia should be similar to MG (good practice point).

Delivery outcome of women with epilepsy: a population-based cohort study.

OBJECTIVE: To investigate whether women with epilepsy have increased risks of complications during labour, and to explore the impact of antiepileptic drug use. DESIGN: Population-based cohort study. SETTING: Data from the Medical Birth Registry of Norway 1999-2005. POPULATION: All births (n=372,128) delivered in Norway, ensured through linkage with the National Population Registry run by Statistics Norway. All singleton births and the first child in multiple pregnancies were included, leaving 365,107 pregnancies for analysis. METHODS: Data from the Medical Birth Registry of Norway 1999-2005 were analysed. MAIN OUTCOME MEASURES: Induction, caesarean section, use of forceps and vacuum, abnormal presentation, placental abruption, mechanical disproportion, postpartum haemorrhage, atony and Apgar score <7 after 5 minutes. RESULTS: We compared 2805 pregnancies in women with a current or past history of epilepsy (0.8%) and 362,302 pregnancies in women without a history of epilepsy. Antiepileptic drugs were used in 33.6% (n=942) of pregnant women with epilepsy. Women with epilepsy had an increased risk of induction [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.1-1.4], caesarean section (OR, 1.4; 95% CI, 1.3-1.6) and postpartum haemorrhage (OR, 1.2; 95% CI, 1.1-1.4) compared with women without epilepsy. These rates were even higher for women with epilepsy and antiepileptic drug use, with ORs (95% CIs) of 1.6 (1.4-1.9), 1.6 (1.4-1.9) and 1.5 (1.3-1.9), respectively. In addition, the risk of an Apgar score <7 was higher (OR, 1.6; 95% CI, 1.1-2.4). For women with epilepsy without antiepileptic drug use, only a slightly increased risk of caesarean delivery was observed and no increased risk for any other complications studied. CONCLUSIONS: Pregnant women with epilepsy have a low complication rate; however, they have a slightly increased risk of induction, caesarean section and postpartum haemorrhage. It is not possible to ascertain on the basis of this study whether this is a result of more severe epilepsy or antiepileptic drug use.

A 50-year follow-up of the incidence of traumatic spinal cord injuries in Western Norway.

STUDY DESIGN: Retrospective population-based epidemiological study. OBJECTIVE: To assess the prevalence and temporal trends in the incidence of traumatic spinal cord injuries (TSCI), and demographic and clinical characteristics of an unselected, geographically defined cohort in the period 1952-2001. METHODS: The patients were identified from hospital records. Crude rates and age-adjusted rates were calculated for each year. The multivariate relationship between cause of injury, age at injury, decade of injury and gender was examined using a Poisson regression model. RESULTS: Of 336 patients, 199 patients were alive on 1 January 2002, giving a total prevalence of 36.5 per 100,000 inhabitants. The average annual incidence increased from 5.9 per million in the first decade to 21.2 per million in the last. Mean age at injury was 42.9 years and the male to female ratio 4.7:1. Fall was the most common cause of injury (45.5%), followed by motor vehicle accidents (MVA) (34.2%). The incidence of MVA-related injuries increased during the observation period, especially among men <30 years. The lesion level was cervical in 52.4%, thoracic in 29.5% and lumbar/sacral in 18.2%. The lesion was clinically incomplete in 58.6% and complete in 41.4%. The incidence of fall-related injuries and the proportion of incomplete cervical lesions increased during the observation period, especially among men >60 years. CONCLUSIONS: The incidence of TSCI has increased during the past 50 years. Falls and MVA are potentially preventable causes. The increasing proportion of older patients with cervical lesions poses a challenge to the health system.

Complications during pregnancy in women with epilepsy: population-based cohort study.

OBJECTIVE: To investigate whether women with epilepsy have an increased risk of complications during pregnancy and to explore the impact of antiepileptic drug (AED) use. DESIGN: Population-based cohort study. SETTING: Data from Medical Birth Registry of Norway based on all births in Norway 1999-2005. POPULATION: All births (n=372,128) delivered in Norway, ensured through linkage with the National Population Registry run by Statistics Norway. All singleton births and the first child in multiple pregnancies were included, leaving 365,107 pregnancies for analyses. MAIN OUTCOME MEASURES: Pre-eclampsia (mild and severe), gestational hypertension, eclampsia, vaginal bleeding (early and late) and preterm birth. RESULTS: We compared 2805 pregnancies in women with a current or past history of epilepsy (0.8%) and 362 302 pregnancies in women without a history of epilepsy. Women with epilepsy had an increased risk of mild pre-eclampsia, [odds ratio 1.3: 95% confidence interval (1.1-1.5)] and delivery before week 34 [1.2: (1.0-1.5)]. Antiepileptic drugs were used in 33.6% (n=942) of the pregnant women with epilepsy. Compared to women without epilepsy, women with epilepsy and AED use had an increased risk of mild pre-eclampsia [1.8: (1.3-2.4)], gestational hypertension [1.5: (1.0-2.2)], vaginal bleeding late in pregnancy [1.9: (1.1-3.2)], and delivery before 34 weeks of gestation [1.5: (1.1-2.0)]. No significant increase in the risk of these complications was observed in women with epilepsy not using AED. These results remained unchanged after exclusion of multiple pregnancies. CONCLUSION: Women with epilepsy have a low complication rate, but special attention should be paid to those using AED during pregnancy.

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.

EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases.

Despite high-dose intravenous immunoglobulin (IVIG) is widely used in treatment of a number of immune-mediated neurological diseases, the consensus on its optimal use is insufficient. To define the evidence-based optimal use of IVIG in neurology, the recent papers of high relevance were reviewed and consensus recommendations are given according to EFNS guidance regulations. The efficacy of IVIG has been proven in Guillain-Barré syndrome (level A), chronic inflammatory demyelinating polyradiculoneuropathy (level A), multifocal mononeuropathy (level A), acute exacerbations of myasthenia gravis (MG) and short-term treatment of severe MG (level A recommendation), and some paraneoplastic neuropathies (level B). IVIG is recommended as a second-line treatment in combination with prednisone in dermatomyositis (level B) and treatment option in polymyositis (level C). IVIG should be considered as a second or third-line therapy in relapsing-remitting multiple sclerosis, if conventional immunomodulatory therapies are not tolerated (level B), and in relapses during pregnancy or post-partum period (good clinical practice point). IVIG seems to have a favourable effect also in paraneoplastic neurological diseases (good practice point) [corrected],stiff-person syndrome (level A), some acute-demyelinating diseases and childhood refractory epilepsy (good practice point).

Report of the Task Force on pre-graduate education in Europe of the education committee of the European Federation of Neurological Societies Composition of the task force of the education committee on pre-graduate education.

BACKGROUND AND PURPOSE: The demographical evolution and the technological revolution seen in the last decades, in developed countries, have dramatically changed the practice of Neurology. However, the academic curriculum in many medical schools has not been updated accordingly over many of the European Countries. The Education Committee of the European Federation of Neurological Societies (EFNS) implemented in 2000 a Task Force on pre-graduate education trying to give guidelines to adequate pre-graduate education to the present status. METHODS AND DISCUSSION: Based on the results of two questionnaires, the first sent to the delegates of the EFNS and to the delegates of the European Board of Neurology, and the second answered by the Task Force members themselves, this paper describes the Task Force recommendations aimed to improve Neurology Education in the Medical Schools. These recommendations are also discussed with the analyses of the current bibliography available.