Pharmacologic treatment and SUDEP risk: A nationwide, population-based, case-control study.

OBJECTIVE: We conducted a nationwide case-control study in Sweden to test the hypothesis that antiepileptic drugs (AEDs) mono- or polytherapy, adherence, antidepressants, neuroleptics, ß-blockers, and statins are associated with sudden unexpected death in epilepsy (SUDEP) risk. METHODS: Included were 255 SUDEP cases and 1,148 matched controls. Information on clinical factors and medications came from medical records and the National Patient and Prescription Registers. The association between SUDEP and medications was assessed by odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for potential risk factors including type of epilepsy, living conditions, comorbidity, and frequency of generalized tonic-clonic seizures (GTCS). RESULTS: Polytherapy, especially taking 3 or more AEDs, was associated with a substantially reduced risk of SUDEP (OR 0.31, 95% CI 0.14-0.67). Combinations including lamotrigine (OR 0.55, 95% CI 0.31-0.97), valproic acid (OR 0.53, 95% CI 0.29-0.98), and levetiracetam (OR 0.49, 95% CI 0.27-0.90) were associated with reduced risk. No specific AED was associated with increased risk. Regarding monotherapy, although numbers were limited, the lowest SUDEP risk was seen in users of levetiracetam (0.10, 95% CI 0.02-0.61). Having nonadherence mentioned in the medical record was associated with an OR of 2.75 (95% CI 1.58-4.78). Statin use was associated with a reduced SUDEP risk (OR 0.34, 95% CI 0.11-0.99) but selective serotonin reuptake inhibitor use was not. CONCLUSION: These results provide support for the importance of medication adherence and intensified AED treatment for patients with poorly controlled GTCS in the effort to reduce SUDEP risk and suggest that comedication with statins may reduce risk.

Swedish emergency hospital surgical surge capacity to mass casualty incidents.

BACKGROUND: In Sweden the surgical surge capacity for mass casualty incidents (MCI) is managed by county councils within their dedicated budget. It is unclear whether healthcare budget constraints have affected the regional MCI preparedness. This study was designed to investigate the current surgical MCI preparedness at Swedish emergency hospitals. METHODS: Surveys were distributed in 2015 to department heads of intensive care units (ICU) and surgery at 54 Swedish emergency hospitals. The survey contained quantitative measures as the number of (1) surgical trauma teams in hospital and available after activating the disaster plan, (2) surgical theatres suitable for multi-trauma care, and (3) surgical ICU beds. The survey was also distributed to the Armed Forces Centre for Defence Medicine. RESULTS: 53 hospitals responded to the survey (98%). Included were 10 university hospitals (19%), 42 county hospitals (79%), and 1 private hospital (2%). Within 8 h the surgical capacity could be increased from 105 to 399 surgical teams, while 433 surgical theatres and 480 ICU beds were made available. The surgical surge capacity differed between university hospitals and county hospitals, and regional differences were identified regarding the availability of surgical theatres and ICU beds. CONCLUSIONS: The MCI preparedness of Swedish emergency care hospitals needs further attention. To improve Swedish surgical MCI preparedness a national strategy for trauma care in disaster management is necessary.

Clinical risk factors in SUDEP: A nationwide population-based case-control study.

OBJECTIVE: We conducted a nationwide case-control study in Sweden to test the hypothesis that specific clinical characteristics are associated with increased risk of sudden unexpected death in epilepsy (SUDEP). METHODS: The study included 255 SUDEP cases (definite and probable) and 1,148 matched controls. Clinical information was obtained from medical records and the National Patient Register. The association between SUDEP and potential risk factors was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) and interaction assessed by attributable proportion due to interaction (AP). RESULTS: Experiencing generalized tonic-clonic seizures (GTCS) during the preceding year was associated with a 27-fold increased risk (OR 26.81, 95% CI 14.86-48.38), whereas no excess risk was seen in those with exclusively non-GTCS seizures (OR 1.15, 95% CI 0.54-48.38). The presence of nocturnal GTCS during the last year of observation was associated with a 15-fold risk (OR 15.31, 95% CI 9.57-24.47). Living alone was associated with a 5-fold increased risk of SUDEP (OR 5.01, 95% CI 2.93-8.57) and interaction analysis showed that the combination of not sharing a bedroom and having GTCS conferred an OR of 67.10 (95% CI 29.66-151.88), with AP estimated at 0.69 (CI 0.53-0.85). Among comorbid diseases, a previous diagnosis of substance abuse or alcohol dependence was associated with excess risk of SUDEP. CONCLUSIONS: Individuals with GTCS who sleep alone have a dramatically increased SUDEP risk. Our results indicate that 69% of SUDEP cases in patients who have GTCS and live alone could be prevented if the patients were not unattended at night or were free from GTCS.

Association between sociodemographic status and antiepileptic drug prescriptions in children with epilepsy.

PURPOSE: We investigated whether in Sweden sociodemographic differences are associated with access to expert health care and antiepileptic drug (AED) prescriptions in children with epilepsy. METHODS: Data on epilepsy, prescription of AEDs, and sociodemographic variables were obtained from several national administrative registers. We linked individual data to examine whether access by pediatric epilepsy patients to neuropediatricians and the prescription of individual AEDs differed according to gender, age, parental education, place of residence, parental region of birth, and household income. We also assessed whether AEDs are prescribed differently to patients with epilepsy by neuropediatricians as compared to other physicians. KEY FINDINGS: Of 1,788,382 children aged 1-17 years in 2006, living in the country by the end of 2006, 9,935 had a diagnosis of epilepsy (0.56%). Patients with epilepsy on AED treatment (n = 3,631) comprised 0.24% of the total Swedish population aged 1-17 years. Out of 3631 patients with epilepsy on AED treatment, 2301 (63.4%) received prescriptions from a neuropediatrician. Children with epilepsy aged 1-5 years old--as opposed to older children and adolescents--and children with epilepsy residing in large cities--as opposed to children living in smaller cities and rural areas--were more likely to be treated by a neuropediatrician. Children living in large cities received oxcarbazepine to a greater extent than children living in rural areas. Levetiracetam was prescribed more extensively to children whose parents had higher incomes. Of the five most frequently used AEDs, three (lamotrigine, oxcarbazepine, and levetiracetam) were prescribed to a larger extent by a neuropediatrician rather than by other specialists, and one AED (carbamazepine) was prescribed to a lesser extent. SIGNIFICANCE: The results of this nationwide cross-sectional study of children with epilepsy are important because they show that universal coverage for medical care does not eliminate inequalities of access to health care services among children and adolescents. No data are available that can guide us as to whether the density of child neurologists is of importance to access to expert health care, but this seems likely. Prescription patterns of AEDs differ between child neurologists and other specialists.

Physical fitness, but not muscle strength, is a risk factor for death in amyotrophic lateral sclerosis at an early age.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder mainly characterised by motor symptoms. Extensive physical activity has been implicated in the aetiology of ALS. Differences in anthropometrics, physical fitness and isometric strength measured at 18-19 years were assessed to determine if they are associated with subsequent death in ALS. METHOD: Data on body weight and height, physical fitness, resting heart rate and isometric strength measured at conscription were linked with data on death certificates in men born in 1951-1965 in Sweden (n=809 789). Physical fitness was assessed as a maximal test on an electrically braked bicycle ergometer. Muscle strength was measured as the maximal isometric strength in handgrip, elbow flexion and knee extension in standardised positions, using a dynamometer. Analyses were based on 684 459 (84.5%) men because of missing data. A matched case control study within this sample was performed. The population was followed until 31 December 2006, and 85 men died from ALS during this period. RESULTS: Weight adjusted physical fitness (W/kg), but not physical fitness per se, was a risk factor for ALS (OR 1.98, 95% CI 1.32 to 2.97), whereas resting pulse rate, muscle strength and other variables were not. CONCLUSIONS: Physical fitness, but not muscle strength, is a risk factor for death at early age in ALS. This may indicate that a common factor underlies both fitness (W/kg) and risk of ALS.

Attitudes towards epilepsy surgery: A nationwide survey among Swedish neurologists.

PURPOSE: Epilepsy surgery is safe and effective for epilepsy that is refractory to medical treatment. However, only a minority of candidates for epilepsy surgery are referred for surgical evaluation. We investigated Swedish neurologists' views on and criteria for referral for epilepsy surgery. MATERIALS AND METHODS: A survey was sent out to neurologists who treat patients with epilepsy. We received responses from 81% of referring hospitals and 57% of private practices. RESULTS: Sixty-one percent of respondents considered that epilepsy surgery reduced seizure frequency and 53% that it improved quality of life. Surgical treatment was thought to be cost-effective by 90% of respondents. Referral for surgery was considered if three or more antiepileptic drugs had failed. Seizure frequency and severity and, the patient's own wishes were regarded as the most important criteria for surgical referral. MRI and EEG findings were also important whereas duration of illness was considered less important. Age below 65 years and lack of mental retardation were important for considering referral. CONCLUSION: In general Swedish neurologists have a cautious but positive attitude towards epilepsy surgery. Uncertainties about eligibility criteria among referring clinicians may contribute to the underutilization of epilepsy surgery.

Metabolite concentrations in supraventricular white matter from teenage to early old age: A short echo time 1H magnetic resonance spectroscopy (MRS) study.

BACKGROUND: Age- and sex-related changes of metabolites in healthy adult brains have been examined with different (1)H magnetic resonance spectroscopy (MRS) methods in varying populations, and with differing results. A long repetition time and short echo time technique reduces quantification errors due to T(1) and T(2) relaxation effects and makes it possible to measure metabolites with short T(2) relaxation times. PURPOSE: To examine the effect of age on the metabolite concentrations measured by (1)H MRS in normal supraventricular white matter using a long repetition time (TR) and a short echo time (TE). MATERIAL AND METHODS: Supraventricular white matter of 57 healthy subjects (25 women, 32 men), aged 13 to 72 years, was examined with a single-voxel MRS at 1.5T using a TR of 6000 ms and a TE of 22 ms. Tissue water was used as a reference in quantification. RESULTS: Myoinositol increased slightly and total N-acetyl aspartate (NAA) decreased slightly with increasing age. Glutamine/glutamate complex (Glx) showed U-shaped age dependence, with highest concentrations in the youngest and oldest subjects. No significant age dependence was found in total choline and total creatine. No gender differences were found. Macromolecule/ lipid (ML) fractions were reliably measurable only in 36/57 or even fewer subjects and showed very large deviations. CONCLUSION: The concentrations of several metabolites in cerebral supraventricular white matter are age dependent on (1)H MRS, even in young and middle-aged people, and age dependency can be nonlinear. Each (1)H MRS study of the brain should therefore take age into account, whereas sex does not appear to be so important. The use of macromolecule and lipid evaluations is compromised by less successful quantification and large variations in healthy people.

Incomplete hippocampal inversion-is there a relation to epilepsy?

Incomplete hippocampal inversion (IHI) has been described in patients with epilepsy or severe midline malformations but also in nonepileptic subjects without obvious developmental anomalies. We studied the frequency of IHI in different epilepsy syndromes to evaluate their relationship. Three hundred patients were drawn from the regional epilepsy register. Of these, 99 were excluded because of a disease or condition affecting the temporal lobes or incomplete data. Controls were 150 subjects without epilepsy or obvious intracranial developmental anomalies. The coronal MR images were analysed without knowledge of the clinical data. Among epilepsy patients, 30% had IHI (40 left-sided, 4 right-sided, 16 bilateral). Of controls, 18% had IHI (20 left-sided, 8 bilateral). The difference was statistically significant (P < 0.05). Of temporal lobe epilepsy (TLE) patients, 25% had IHI, which was not a significantly higher frequency than in controls (P = 0.34). There was no correlation between EEG and IHI laterality. A total of 44% of Rolandic epilepsy patients and 57% of cryptogenic generalised epilepsy patients had IHI. The IHI frequency was very high in some epileptic syndromes, but not significantly higher in TLE compared to controls. No causality between TLE and IHI could be found. IHI can be a sign of disturbed cerebral development affecting other parts of the brain, maybe leading to epilepsy.

Incomplete inversion of the hippocampus--a common developmental anomaly.

Incomplete inversion of the hippocampus, an imperfect fetal development, has been described in patients with epilepsy or severe midline malformations. We studied this condition in a nonepileptic population without obvious developmental anomalies. We analyzed the coronal MR images of 50 women and 50 men who did not have epilepsy. Twenty of them were healthy volunteers and 80 were patients without obvious intracranial developmental anomalies, intracranial masses, hydrocephalus or any condition affecting the temporal lobes. If the entire hippocampus (the head could not be evaluated) were affected, the incomplete inversion was classified as total, otherwise as partial. Incomplete inversion of the hippocampus was found in 19/100 subjects (9 women, 10 men). It was unilateral, always on the left side, in 13 subjects (4 women, 9 men): 9 were of the total type, 4 were partial. It was bilateral in six subjects (five women, one man): four subjects had total types bilaterally, two had a combination of total and partial types. The collateral sulcus was vertically oriented in all subjects with a deviating hippocampal shape. We conclude that incomplete inversion of the hippocampus is not an unusual morphologic variety in a nonepileptic population without other obvious intracranial developmental anomalies.

A prospective study of anxiety with respect to seizure outcome after epilepsy surgery.

PURPOSE: To evaluate if degree of anxiety proneness is affected by seizure outcome after epilepsy surgery. METHODS: Five scales related to anxiety, which are part of the Karolinska Scales of Personality (KSP), were administered pre-operatively and 2-8 years post-operatively to 31 female and 26 male patients. High scores indicate a high degree of anxiety. Seizure outcome was either Engel I or Engel II-IV. RESULTS: Mean age of the patients was 39 years (S.D. 10). Forty-seven patients had temporal surgery and 10 patients had extra-temporal surgery. The outcome in 34 patients was classified as Engel I and in 23 patients as Engel II-IV. There were statistically significant decreases (paired t test) in t scores for the Somatic Anxiety scale (expected mean 50, from 55.4 to 50.2, P = 0.001) and the Psychic Anxiety scale (expected mean 50, from 56.2 to 51.6, P = 0.006) in patients in Engel I. No other significant differences were observed. After taking baseline imbalances into account (ANCOVA), there were no statistically significant differences in the change in degree of anxiety proneness between patients in the two outcome groups. CONCLUSION: Patients undergoing successful epilepsy surgery experienced small decreases in somatic anxiety and psychic anxiety. Since there were important pre-operative imbalances between the two outcome groups, these differences could not be attributed to the effect of seizure freedom after epilepsy surgery.

[A national curriculum in neurology for medical education]. / Nationellt core curriculum i neurologi för läkarutbildningen.

The knowledge within medicine is growing rapidly. It has become more and more difficult to decide what knowledge that has to be taught to medical students during their University Medical Degree (MD) education and what has to be omitted from their study plans. As help for teachers and students, a core curriculum of the education defines what is of importance for all students. However, there is a risk of "curriculum overload" with too much information being put into a short time interval. To avoid this and to define what is really the "core" of a course, a national consensus decision may be useful. As an example of this approach, we here report a new joint Swedish core curriculum in neurology for medical students. Teachers responsible for neurological education at all six universities giving University MD education in Sweden have in January 2003 agreed upon the core curriculum that we present. It is our hope that this method can be useful also for other clinical specialities.

Hormonal factors in migraine: a population-based study of women aged 40 to 74 years.

OBJECTIVE: This study investigated some of the relationships between migraine and hormonal factors. METHODS: A neurologist clinically assessed 728 women aged 40 to 74 years attending a population-based mammography screening program. Headache criteria proposed by the International Headache Society were used. Data on hormonal factors were obtained by interview and questionnaire. RESULTS: Twenty-one percent of women with migraine without aura and 4% of women with migraine with aura reported that they experienced >/=75% of their attacks within -2 to +3 days of the menstrual cycle. During pregnancy, women experienced less frequent or less intense attacks of migraine without aura and migraine with aura. A small but significant proportion (12%, P =.04) of women with migraine without aura also had premenstrual disorder. Associations between migraine and menarche, pregnancy, pregnancy-related complications, and menopausal complaints were generally weak and insignificant. Migraine with aura was not related to menopause. A crude odds ratio of 0.47 (95% confidence interval [CI] 0.24-0.86) indicated a decrease in risk for migraine without aura in postmenopausal women. However, after adjusting for differences in age and the use of hormonal replacement therapy, this association was not statistically significant. Time since menopause was a significant factor for migraine without aura in postmenopausal women. CONCLUSION: Although many women with migraine reported a close relationship between their attacks and menses, and relief during pregnancy, the cross-sectional associations between migraine and menopause and menopausal complaints were insignificant.

Serum levels of androgens and migraine in postmenopausal women.

Female hormones are thought to be of importance in the aetiology of migraine, which is more common in women than in men. Little attention has been paid to androgens. This study investigates the associations between migraine and serum levels of androgens in postmenopausal women not taking oestrogens. A case-control study was carried out among women participating in a mammography screening program. A neurologist clinically assessed the participants. Headache criteria proposed by the International Headache Society were used. Each of the 15 women with migraine was matched to three controls by time since menopause and by body mass index. Serum levels of androstenedione and total testosterone were measured by radioimmunoassays. Free testosterone was calculated from total testosterone, immunoassayed sex hormone-binding globulin and albumin. The mean+/-S.D. serum level of androstenedione was 2.7+/-1.1 nmol/l and 3.4+/-1.9 nmol/l in cases and controls respectively. The mean serum level of testosterone was 0.8+/-0.4 nmol/l and 1.0+/-0.5 nmol/l in cases and controls respectively. The mean serum level of free testosterone was 12.5+/-8.5 pmol/l and 14.0+/-7.9 pmol/l in cases and controls respectively. Conditional logistic regression analysis was used to test for differences in serum levels of androstenedione, total testosterone and free testosterone between cases and controls. No statistically significant differences were found. To conclude, there was no evidence in this study that differences within normal levels of androgens play an important role in the aetiology of migraine in postmenopausal women not taking oestrogens.

Prostaglandin F(2alpha) metabolite and F(2)-isoprostane excretion rates in migraine.

The pathophysiology theory of migraine postulates a local, neurogenic inflammation and the possible involvement of oxidative stress. We analysed the levels of 15-oxo-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha)) and 8-iso-prostaglandin F(2alpha) (a major isoprostane), which are biomarkers for inflammation and oxidative stress respectively, in urine from 21 patients with migraine, with and without aura. Urine samples from migraine patients were collected during a migraine attack, and control samples were collected from the same subjects on a migraine-free morning. The mean basal levels of 15-oxo-dihydro-prostaglandin F(2alpha) and 8-iso-prostaglandin F(2alpha) in the morning control urine samples were 0.54+/-0.11 and 0.31+/-0.13 nmol/mmol of creatinine respectively. The mean levels of 15-oxo-dihydro-prostaglandin F(2alpha) and 8-iso-prostaglandin F(2alpha) in the urine samples collected during the migraine attack in the 21 patients were 0.53+/-0.13 and 0.32+/-0.11 nmol/mmol of creatinine respectively. Thus there were no differences in the 15-oxo-dihydro-prostaglandin F(2alpha) and 8-iso-prostaglandin F(2alpha) excretion rates during the migraine attack compared with on the migraine-free day. However, the basal 8-iso-prostaglandin F(2alpha) excretion levels on the migraine-free day were significantly lower in pre-menopausal women (0.24+/-0.08 nmol/mmol of creatinine, n=11) compared with post-menopausal women (0.39+/-0.14 nmol/mmol of creatinine; n=7; P=0.009). In conclusion, in this study we found no support for the involvement of inflammation and oxidative stress in migraine pathophysiology. Our results indicate, however, a lower level of oxidative stress in pre-menopausal compared with post-menopausal women.