Decrease in mortality of adult epilepsy patients since 1980: lessons learned from a hospital-based cohort.

BACKGROUND AND PURPOSE: Data on mortality in patients with epilepsy have been available since the 1800s. They consistently show a 2-3-fold increase compared to the general population. Despite major advances in diagnostic tools and treatment options, there is no evidence for a decrease in premature deaths. The temporal trend of mortality in a hospital-based epilepsy cohort over three decades was assessed. METHODS: A hospital-based incidence cohort was recruited from a specialized epilepsy outpatient clinic at Innsbruck Medical University between 1980 and 2007, divided by decade into three cohorts and followed for 5 years after initial epilepsy diagnosis. Deaths and their primary causes were determined using probabilistic record linkage with the Austrian death registry. Age-, sex- and period-adjusted standardized mortality rates (SMRs) were computed in relation to the general population of the same area and grouped according to time of diagnosis. RESULTS: In all, 122 deaths in 4549.9 person-years (1954.5 women, 2595.2 men) were identified. The overall SMR was 2.2 [95% confidence interval (CI) 1.8-2.6] and decreased from 3.0 (95% CI 2.1-4.3) in 1980-1989, to 2.7 (95% CI 2.0-3.5) in 1990-1999 and to 1.4 (95% CI 1.0-2.0) in 2000-2007. CONCLUSIONS: This study indicates a decrease in mortality in newly diagnosed epilepsy patients over the last three decades. This may be due to advances in diagnosis and treatment over the past three decades, including early identification of drug resistance, introduction of new anti-epileptic drugs and establishment of a comprehensive epilepsy surgery programme in this region.

[Family planning in women with epilepsy]. / Familienplanung bei Epilepsiepatientinnen.

Epilepsy is a common neurological condition with gender-related management implications. Epilepsy and antiepileptic drug treatment affect aspects of contraception, fertility and pregnancy which are discussed in the article.

Idiopathic generalised epilepsy of late onset: a separate nosological entity?

AIM: Seizure onset in idiopathic generalised epilepsies (IGE) is considered to be rare after the second decade of life. The authors aimed to explore age of seizure onset in patients with IGE and compare 'classical' onset to late onset cases. METHODS: Patients with IGE, treated at the outpatient epilepsy clinic (Medical University of Innsbruck, Austria, 1985-2006, n=798) were retrospectively screened. The inclusion criteria were: diagnosis of IGE, more than two follow-up (FU) visits, duration of FU more than 1 year and normal brain imaging. The authors analysed demographic data, age of seizure onset, seizure types, syndromes, neuroimaging and EEG findings, seizure triggers and seizure freedom for 1 and 5 years at last FU. RESULTS: A total of 492 patients (mean age at seizure onset 14.6 years, range 0.1-55, SD 7.9) with IGE were identified: childhood absence epilepsy (n=113, range 1-55, SD 6.5), juvenile absence epilepsy (n=75, range 4-39, SD 5.1), juvenile myoclonic epilepsy (n=112, range 2-39, SD 5.7), and epilepsy with grand mal seizures on awakening (n=192 range 1-52, SD 17.3). Population was stratified into three groups: 28 patients with seizure onset at >30 years, 180 patients between 15 and 30 years and 284 patients <15 years. The distribution of seizure types and epilepsy syndromes differed significantly in a group comparison (p<0.001); seizure outcome and other clinical variables did not differ throughout the groups. CONCLUSION: Apart from age-related onset of seizure types and syndromes with a loose upper limit of onset age, patients with a late onset did not differ from their younger counterparts. These data do not support the view of IGE of late onset as a separate syndrome.

Oxcarbazepine treatment in male epilepsy patients improves pre-existing sexual dysfunction.

OBJECTIVE: To collect data on sexual dysfunction in a larger population of male patients with epilepsy treated with oxcarbazepine in a naturalistic setting. PATIENTS AND METHODS: Six hundred seventy-three adult male patients with partial epilepsy in whom monotherapy with oxcarbazepine was indicated were evaluated at baseline and after approximately 12 weeks of treatment with regard to the number of seizures and occurrence of any adverse drug reactions. All patients were questioned regarding their sexual function. RESULTS: Out of 228 patients with pre-existing sexual function impairment at baseline, an improvement was observed in 181 (79.4%) patients, 23 (10.1%) patients experienced no impairment at the final visit. The improvements were more marked in those patients, who were pretreated with enzyme-inducing antiepileptic drugs. No worsening of the sexual dysfunction was observed. CONCLUSIONS: Oxcarbazepine was found to have beneficial effects on sexual dysfunction and to be effective and well tolerated in male patients with partial epilepsy.

Effect of valproic acid treatment on body composition, leptin and the soluble leptin receptor in epileptic children.

PURPOSE: The aim of the study was to determine the influence of valproic acid (VPA) treatment on leptin, the soluble leptin receptor (sOB-R), the sOB-R/leptin ratio, body composition and insulin resistance in epileptic children. METHODS: A cross-sectional cohort study was conducted at the Medical University Innsbruck, Austria. Children >6 years with idiopathic epilepsy and antiepileptic drug therapy since at least six months were eligible. Leptin concentration, the sOB-R, the sOB-R/leptin ratio, body composition and glucose homeostasis were determined. RESULTS: 87 children (median [range] age 12.8 years [6.0-18.6]) were on treatment with VPA, 55 (12.3 years [6.4-18.3]) on other AEDs, comprising the non-VPA group. VPA-treated children had higher leptin concentrations, body-mass-index standard-deviation score (SDS), body fat (each p<0.001), serum insulin concentrations (p=0.014) and homeostasis model assessment (HOMA) index (p=0.009), as well as a lower sOB-R/leptin ratio (p<0.001) when compared to the non-VPA group. Overweight VPA-treated children showed lower sOB-R concentrations and a lower sOB-R/leptin ratio (each p<0.001) as well as higher body fat and leptin levels (each p<0.001) compared to lean VPA-treated children. CONCLUSION: VPA monotherapy was associated with higher body weight, body fat and serum leptin concentrations as well as impaired glucose homeostasis. Low sOB-R concentrations and a low sOB-R/leptin ratio in overweight VPA-treated patients might contribute to disturbances in glucose homeostasis and to the development of the metabolic syndrome in these children later in life.

Unilateral polymicrogyria with ipsilateral cerebral hemiatrophy: a distinct syndrome?

INTRODUCTION: There are sporadic reports of unilateral polymicrogyria with ipsilateral hemiatrophic cerebri associated with epilepsy, focal neurological deficit and mental retardation. The mechanisms which cause this condition are not well understood. The aim of our study was to delineate further, clinical and neuroimaging features of this malformation of cortical development and to explore its possible etiological background. PATIENTS AND METHODS: Four patients (two males and two females), aged from 23 to 31 years (mean age range 27.5 years) were evaluated. Subjects underwent clinical, electrophysiological, neuropsychological and high resolution magnetic resonance imaging assessment. RESULTS: No significant perinatal event or exposure to intrauterine infection was noted. None suffered from birth asphyxia or ischemic injury. The parents of two patients were first cousins. Every subject had delayed developmental milestones, mental disability and congenital, non-progressive, spastic hemiparesis. They had epilepsy with seizure-onset ranging from three months to 17 years (mean 6.8 years); two had intractable seizures. In all patients, unilateral, right-sided polymicrogyria was associated with ipsilateral cerebral hemiatrophy. Polymicrogyria involved mainly anterior perisylvian areas; occipital regions were relatively spared. CONCLUSION: The evaluated patients showed homogenous clinical and neuroimaging characteristics. We support the idea that the disorder could constitute a clinical entity with an underlying genetic cause.

Relationship of high-density lipoprotein subfractions and cholesteryl ester transfer protein in plasma to carotid artery wall thickness.

High plasma concentrations of high-density lipoprotein (HDL) cholesterol are a powerful indicator of low vascular risk. By decreasing HDL cholesterol, cholesteryl ester transfer protein (CETP) could perhaps constitute an atherogenic protein. We measured HDL cholesterol and HDL subfractions and quantified CETP mass in fasting plasma in 21 asymptomatic probands, and related these variables to the mean intima media thickness of the extracranial carotid arteries. HDL2 cholesterol, the less dense HDL subfraction, was inversely related to carotid wall thickness (r = -0.378; P < 0.05), and CETP was directly related to carotid wall thickness (r = 0.436; P < 0.05). In plasma CETP is associated mostly with the HDL3 subfraction. We therefore calculated from our measurements the relative CETP content of HDL3, i.e., CETP/HDL3 cholesterol. This ratio was correlated with carotid wall thickness stronger than any other variable measured (r = 0.718, P < 0.001). We conclude that variation in HDL subfractions and CETP may be more closely associated with carotid intima media thickness than the accepted strong risk factor of HDL cholesterol.

Asymmetric termination of secondarily generalized tonic-clonic seizures in temporal lobe epilepsy.

In patients with secondarily generalized tonic-clonic seizures (sGTCS) an asymmetric termination of the clonic phase can be observed. The authors systematically analyzed this phenomenon in patients with temporal lobe epilepsy (TLE). Thirty-nine sGTCS from 29 patients with TLE who underwent successful epilepsy surgery were analyzed, in addition to a prospectively collected group of 28 patients with TLE who had 35 sGTCS. The clonic phase of sGTCS did not end synchronously in 65.7% of all patients and in 59.4% of all seizures. In 79.3% to 80% this was ipsilateral to the hemisphere of seizure onset, and there was excellent interobserver agreement.

1-H-localized magnetic resonance spectroscopy: preliminary observations in transient ischemic attacks.

Water-suppressed proton magnetic resonance spectroscopy which has recently shown diagnostic potential in human stroke victims was performed in two patients who had suffered a hemispheric transient ischemic attack. Localized spectra were targeted from routine MR images. In one patient lactate could be observed 8 weeks after a transient ischemic attack. Lactate concentration was low compared with that of a patient who had suffered acute stroke. The other TIA patient did not show evidence of lactate production. Although these observations are preliminary, we demonstrated that localized in vivo proton spectroscopy can detect persistent biochemical alterations after transient ischemic attacks. We suggest that non-invasive in vivo proton spectroscopy will become a useful method in diagnosis and management of TIA in the future.

Idiopathic generalized epilepsies with pure grand mal: clinical data and genetics.

OBJECTIVE: To analyze the clinical features and family history of patients with idiopathic generalized epilepsy (IGE), with pure grand mal (GM), divided into epilepsies with GM occurring exclusively on awakening (GMA) and random GM (RGM). METHODS: We studied retrospectively 98 patients from a large epilepsy outpatient clinic. All patients had a full clinical examination and computed cerebral tomography scans (CCT) or magnetic resonance imaging (MRI) when feasible. We analyzed seizure type, seizure frequency, provocative factors, prognosis, electroencephalography (EEG) findings and family history. RESULTS: Sixty-eight patients had GMA and 30 had RGM. The mean age at seizure onset was 16.6 years (+/-6.3 S.D., range: 5-41) and 16.7 years in those with RGM (+/-7.5 S.D., range: 4-42, NSD). Patients with GMA had a longer course of active epilepsy (median 8.5 years) compared to RGM (median 2 years). Seizure-provoking factors, especially sleep deprivation, were significantly (P=0.001) more common in patients with GMA (52/68, 77%) than in the group with RGM (13/30, 43%). Of all patients, 23% (23/98) reported first degree relatives with seizures or epilepsy. Pure GM was found in 41% (12/29) of affected first degree relatives, other idiopathic generalized epilepsy syndromes were less frequently observed (4/29, 14%). The concordance rate was high within the syndrome - none of the patients with RGM had an affected relative with GMA and vice versa only two of affected relatives of GMA patients had RGM. CONCLUSION: GMA seems to be associated with a longer duration of active epilepsy, a higher relapse rate and a stronger tendency to be precipitated by seizure provoking factors. The different concordance rates between the syndromes suggest a genetically different background.

The effects of brain lesions on the course of chronic epilepsies.

The effect of intercurrent brain lesions on the characteristics of chronic epilepsies has not yet been the subject of detailed investigation. We therefore retrospectively examined this issue for idiopathic, cryptogenic as well as symptomatic chronic epilepsies in patients documented in routine investigations at our outpatient seizure unit between the occurrence of epilepsy and commencement of the study. The clinical criteria for inclusion in this study were brain injury by trauma, stroke or intracerebral hemorrhage, documented by CT scan, and the occurrence of this so-called index event in patients with established chronic epilepsy. These requirements were met by 63 patients (40 male, mean age 44.8 years, SD 14.7 a; 23 female, mean age 43.1 years, SD 16.4 a). Seizure characteristics, EEG recordings as well as seizure frequencies before and after the index event were compared. Patients and controls were observed for a mean time of 22.12 years (SD 7.33 a) and 22.01 years (SD 11.31 a), respectively. Two patients presenting with generalized seizures prior to brain injury underwent a change in seizure characteristics. One control (without intercurrent brain lesion; matched for age, sex, age at onset of seizure disorder and classification of seizure disorder) primarily presenting with partial seizures evolving to generalized seizures showed changed seizure characteristics. These changes are statistically insignificant (McNemar test for the significance of changes). Seizure frequencies decreased significantly after brain injury. EEG recordings mirrored clinical findings with additional focal aspects according to brain lesion. These findings are discussed mainly with respect to the cofactorial etiology of epilepsies.(ABSTRACT TRUNCATED AT 250 WORDS)

Childhood febrile convulsions--which factors determine the subsequent epilepsy syndrome? A retrospective study.

To analyze the spectrum of epilepsy syndromes which follow childhood febrile convulsions (FC) and to examine whether retrospective analysis of clinical features of the FC enables discrimination of patients who develop temporal lobe epilepsy (TLE) from those who develop generalized epilepsy (GE). One hundred and thirteen patients with epilepsy and antecedent FC were retrospectively analyzed. We inquired in detail about the clinical characteristics of FC (age, duration, number, focal symptoms) as well as family history, birth history, neurological status, and psychomotor development before onset of FC. Forty five (39.8%) patients had TLE, 41 (36.6%) GE, and 27 (23.9%) had extratemporal epilepsy (ETE). Patients with TLE had a significantly longer duration of FC (P< or =0.001), more often focal features (P< or =0.001), and febrile status epilepticus (P< or =0.001) than patients with GE. Age at FC, Number of FC, family history, birth history and neurological status at FC did not differ between groups. A stepwise discriminant model allowed correct assignment after cross validation in 84.2% to TLE and in 100% to GE. A broad spectrum of epilepsy syndromes follow FC. We found a strong association of prolonged and focal FC with later development of TLE. Short generalized FC were associated with GE.

Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate.

Among a sample of 43 women with epilepsy treated for at least 2 years with valproate (n=22) or other antiepileptic drugs (AEDs) (n=21), polycystic ovary syndrome (PCOS) was diagnosed in three women, two of them were treated with valproate. Although the rate of PCOS and of menstrual disturbances, weight body mass index (BMI) and waist to hip ratio as well as fasting blood glucose levels, fasting insulin, proinsulin and C-peptide values was similar in this small sample of women treated with valproate and other AEDs, valproate exposure was associated with higher androgen levels, higher postprandial (pp) insulin and proinsulin levels, as well as lower cholesterol and low density lipoprotein (LDL) cholesterol levels. The pronounced increase in pp insulin levels during VPA treatment may indicate an effect of the fatty acid derivate VPA on pancreatic islet cells.

Successful treatment of spinal sarcoidosis by high-dose intravenous methylprednisolone.

A man with known pulmonary sarcoidosis presented with paraplegia and a rod-shaped increase in T2 signal intensity in his cervical and upper thoracic spine. Initial treatment efforts using oral doses of 40 mg of methyl-prednisolone were futile, but intravenous bolus therapy (500 mg of methyl-prednisolone daily for 1 week) led to long-lasting improvement of his neurological status and to normalization of MRI findings.

[Neurologic symptoms within the scope of endocrine emergencies]. / Neurologische Symptome im Rahmen endokriner Notfälle.

Functional disturbances of the central and peripheral nervous system can be seen in various internal diseases and it is not unusual that neurological symptoms are the first kind of presentation. The tight anatomical and functional junction between neurology and endocrinology predisposes to the development of neurological derangements such as somnolence, coma, seizures, and focal signs following endocrinological emergencies. In spite of modern imaging and laboratory methods, history and clinical examination are still of great importance to establish the correct diagnosis.

[Neurologic manifestations of diabetes mellitus: an overview]. / Neurologische Manifestationen des Diabetes mellitus: ein Uberblick.

Neurological manifestations of diabetes mellitus comprise structural changes in both central and peripheral nervous system, as well as functional cerebral disturbances. Macro- and microangiopathy are responsible for the development of cerebrovascular diseases; microangiopathic and metabolic disturbances are considered in the discussion to be responsible for the development of the various forms of diabetic polyneuropathy. Acute metabolic episodes with progressive impairment of consciousness have to be differentiated from structural neurological disorders. As a further point of interest the association between diabetes mellitus and special neurological diseases is mentioned.

[Course and management of tetanus]. / Verlauf und Management des Tetanus.

Within a span of 18 months 4 patients (2 men, 2 women) were admitted with generalized tetanus to our neurological intensive care unit. The "period of onset" ranged from 2 to 14 days. All patients needed artificial ventilation over 17 to 38 days. The clinical course was complicated by gram-negative pneumonia in 3 of the 4 patients. Time of hospitalization ranged between 35 and 60 days. One patient had never been immunized against tetanus. The other 3 had not received a booster dose for over 10 years. All 4 patients survived, 3 of them without sequelae.

[Determination of tuberculostearic acid--progress in early diagnosis of tuberculous meningitis]. / Tuberkulostearinsäurebestimmung--ein Fortschritt in der Frühdiagnostik der tuberkulösen Meningitis.

Rapid diagnosis of cerebral tuberculous meningitis is of the greatest importance in determining the outcome of therapy. Since tubercle bacilli are often not seen on microscopy of the cerebrospinal fluid, and culture of Mycobacterium tuberculosis takes many weeks, there is a need for more rapid and sensitive confirmatory tests. The importance of the detection of tuberculostearic acid in the cerebrospinal fluid in combination with magnet resonance imaging will be shown in this case report.

Laminar heterotopic grey matter (double cortex) in a patient with late onset Lennox-Gastaut syndrome.

The Lennox-Gastaut syndrome (LGS) is a severe epileptic disorder, characterized by developmental delay, typical electroencephalographic pattern and poor control of seizures. This epileptic syndrome generally presents in early childhood but exceptionally starts at the age of 5 years or later. We describe a patient who was classified as late-onset LGS, with evidence of mild hydrocephalus on CT. MRI added new diagnostic information by demonstrating laminar heterotopic grey matter.

Diagnosis of tuberculous meningitis by detection of tuberculostearic acid in cerebrospinal fluid.

Tuberculous meningitis still poses a major diagnostic problem. Recently, several new techniques for rapid diagnosis of tuberculous meningitis have been developed. One of these newer techniques is the detection of mycobacterial fatty acids, using gas chromatography--mass spectroscopy. In this study we evaluated the sensitivity and specificity of this recently reported method in a blind trial. The sensitivity was found to be 100%, specificity only 91%. The number of false positive results limits the value of this test in the primary diagnosis of tuberculous meningitis. Nonetheless, we consider this method to be a valuable tool for establishing the diagnosis in culture-negative patients presenting with signs and symptoms suggestive of tuberculous meningitis.