Christoph Baumgartner

Health-related quality of life (HRQOL), activity of daily living (ADL) and depressive mood disorder in temporal lobe epilepsy patients

We determined the interrelations of chronological age, age at seizure onset, duration of seizure disorder, cognitive functioning (IQ), scales of activities of daily living, depressive mood disorder and measures of health-related quality of life (HRQOL). Furthermore, we investigated the association of the laterality of seizure onset zone and absence/presence of hippocampal atrophy and/or sclerosis (HA/HS) with measures of HRQOL, activities of daily living (ADL) and depressive mood disorder. In the setting of pre-surgical epilepsy evaluation, a sample of 56 patients with temporal lobe epilepsy (TLE) was studied using the Bonner Skalen für Epilepsie (BPSE) and the depression inventory D-S of von Zerssen. Patients reported high levels of dependency on others and poor coping capabilities. Our data also showed specific ADL-behaviour suggesting social withdrawal and isolation. Our results indicate emotional impairment as a major problem in TLE, because 45% of our patients scored in the depressive range of the D-S depression scale. Depression score was found to be a powerful predictor of self-reported quality of life after adjusting for seizure-related variables, demographic variables and cognitive functioning (IQ). The only scale showing a significant laterality effect was ADL-home. No relationship between the dependent measures of HRQOL, ADL-social, ADL-cultural, depressive mood disorder and laterality of the epileptogenic zone or absence/presence of HA/HS was found. HRQOL and depressive mood disorder are strongly interrelated indicating that patients with depressive symptoms report lower quality of life and specific patterns of ADL. HRQOL, ADL and depressive mood disorder are largely independent of biological markers such as laterality of seizure onset zone and absence/presence of HA/HS in TLE.

Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy

The multidrug transporter P-glycoprotein is suspected of contributing to pharmacoresistance in temporal lobe epilepsy (TLE). To assess the role of functional variations in its coding gene (ABCB1) the authors genotyped 210 patients with TLE who were stratified according to their degree of drug resistance. They identified a common haplotype that when present in the homozygous state significantly increased the risk for pharmacoresistance.

Longterm Prognosis of Analgesic Withdrawal in Patients with Drug‐Induced Headaches

SYNOPSIS

Long-Term Outcome of Patients with Headache and Drug Abuse after Inpatient Withdrawal: Five-Year Follow-Up

Thirty-eight patients with “chronic daily” headache and ergotamine and/or analgesics abuse according to the criteria proposed by the international Headache Society were re-investigated 5 years after inpatient drug withdrawal. At the end of the observation period, 19 patients (50.0%) had their headaches on only 8 days per month or less, 18 patients (47.4%) were free of symptoms or had only mild headaches. A close correlation was found between the frequency of headache and the duration of drug abuse, as well as between the intensity of headache and the number of tablets taken per month. Frequency and intensity of headache had changed within the first 2 years after withdrawal, but remained stable afterwards. Fifteen patients (39.5%) reported on recurrent drug abuse. Patients with migraine showed a tendency towards a better prognosis compared to patients with tension-type headache or with combined migraine and tension-type headache. The results of this study highlight the long-term efficacy of inpatient drug withdrawal in patients with headache and ergotamine and/or analgesics abuse.

Pharmacoresistance in epilepsy: A pilot PET study with the p-glycoprotein substrate R-[(11)C]verapamil

Summary:u2002 Purpose and Methods: Regional overexpression of the multidrug transporter P‐glycoprotein (P‐gp) in epileptic brain tissue may lower target site concentrations of antiepileptic drugs and thus contribute to pharmacoresistance in epilepsy. We used the P‐gp substrate R‐[11C]verapamil and positron emission tomography (PET) to test for differences in P‐gp activity between epileptogenic and nonepileptogenic brain regions of patients with drug‐resistant unilateral temporal lobe epilepsy (n = 7). We compared R‐[11C]verapamil kinetics in homologous brain volumes of interest (VOIs) located ipsilateral and contralateral to the seizure focus. Results: Among different VOIs, radioactivity was highest in the choroid plexus. The hippocampal VOI could not be used for data analysis because it was contaminated by spill‐in of radioactivity from the adjacent choroid plexus. In several other temporal lobe regions that are known to be involved in seizure generation and propagation ipsilateral influx rate constants K1 and efflux rate constants k2 of R‐[11C]verapamil were descriptively increased as compared to the contralateral side. Parameter asymmetries were most prominent in parahippocampal and ambient gyrus (K1, range: −3.8% to +22.3%; k2, range: −2.3% to +43.9%), amygdala (K1, range: −20.6% to +31.3%; k2, range: −18.0% to +38.9%), medial anterior temporal lobe (K1, range: −8.3% to +14.5%; k2, range: −14.5% to +31.0%) and lateral anterior temporal lobe (K1, range: −20.7% to +16.8%; k2, range: −24.4% to +22.6%). In contrast to temporal lobe VOIs, asymmetries were minimal in a region presumably not involved in epileptogenesis located outside the temporal lobe (superior parietal gyrus, K1, range: −3.7% to +4.5%; k2, range: −4.2% to +5.8%). In 5 of 7 patients, ipsilateral efflux (k2) increases were more pronounced than ipsilateral influx (K1) increases, which resulted in ipsilateral reductions (10%–26%) of R‐[11C]verapamil distribution volumes (DV). However, for none of the examined brain regions, any of the differences in K1, k2 and DV between the epileptogenic and the nonepileptogenic hemisphere reached statistical significance (p > 0.05, Wilcoxon matched pairs test). Conclusions: Even though we failed to detect statistically significant differences in R‐[11C]verapamil model parameters between epileptogenic and nonepileptogenic brain regions, it cannot be excluded from our pilot data in a small sample size of patients that regionally enhanced P‐gp activity might contribute to drug resistance in some patients with temporal lobe epilepsy.

Cluster Analysis of Clinical Seizure Semiology of Psychogenic Nonepileptic Seizures

Summary: Purpose: To develop an objective classification of psychogenic nonepileptic seizures (NES) based on cluster analysis of clinical seizure semiology.

A functional polymorphism in the prodynorphin gene promotor is associated with temporal lobe epilepsy

The prodynorphin gene (PDYN) encoding the anticonvulsant peptide dynorphin is a strong candidate for a seizure suppressor gene and thus a possible modulator of susceptibility to temporal lobe epilepsy. We performed a case control association study in 155 patients with nonlesional temporal lobe epilepsy and 202 controls and found that PDYN promotor low‐expression L‐alleles confer an increased risk for temporal lobe epilepsy in patients with a family history for seizures. Irrespective of the familial background, L‐homozygotes display a higher risk for secondarily generalized seizures and status epilepticus.

Angiocentric glioma: report of clinico-pathologic and genetic findings in 8 cases.

Angiocentric glioma has recently been described as a novel epilepsy associated tumor with distinct clinico-pathologic features. We report the clinical and pathologic findings in 8 additional cases of this rare tumor type and extend its characterization by genomic profiling. Almost all patients had a history of long-standing drug-resistant epilepsy. Cortico-subcortical tumors were located in the temporal and parietal lobes. Seizures began at 3 to 14 years of age and surgery was performed at 6 to 70 years. Histologically, the tumors were characterized by diffuse growth and prominent perivascular tumor cell arrangements with features of astrocytic/ependymal differentiation, but lacking neoplastic neuronal features. Necrosis and vascular proliferation were not observed and mitoses were sparse or absent. MIB-1 proliferation indices ranged from <1% to 5%. Immunohistochemically, all cases stained positively for glial fibrillary acidic protein, vimentin, protein S100B, variably for podoplanin, and showed epithelial membrane antigen-positive cytoplasmic dots. Electron microscopy showed ependymal characteristics in 2 of 3 cases investigated. An analysis of genomic imbalances by chromosomal comparative genomic hybridization revealed loss of chromosomal bands 6q24 to q25 as the only alteration in 1 of 8 cases. In 1 of 3 cases, a high-resolution screen by array-comparative genomic hybridization identified a copy number gain of 2 adjacent clones from chromosomal band 11p11.2 containing the protein-tyrosine phosphatase receptor type J (PTPRJ) gene. All patients are seizure free and without evidence of tumor recurrence at follow-up times ranging from 1/2 to 6.9 years. Our findings support 2 previous reports proposing that angiocentric glioma is a novel glial tumor entity of low-grade malignancy.

Is Refractory Epilepsy Preventable

Summary: About a third of the patients diagnosed with epilepsy will not be fully controlled with antiepileptic drugs (AEDs), and many of them will have frequent and disabling seizures. These patients will undergo multiple drug trials, most often without complete seizure remission. Moreover, refractory epilepsy is associated with increased morbidity (from seizures and medications), social isolation, unemployment, and overall reduced quality of life. There is evidence that refractory epilepsy can be a progressive disorder, which, if controlled early, might never develop into a full syndrome with all of its associated sequelae. The difficulty lies in identifying at an early stage patients who are likely to progress to intractability. No currently known markers enable clinicians to make this identification with confidence. Advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy may change this situation. Even now, we are able to identify many patients with a poor prognosis earlier than before, particularly in the pediatric population, in which syndromic classification may provide an approach to predict intractability. The early initiation of aggressive therapy may improve outcome and overall quality of life.

Spontaneous body sway as a function of sex, age, and vision: posturographic study in 30 healthy adults.

Detailed neurological examinations and body sway measurements with a stable force measuring platform were carried out on 30 healthy adults between 21 and 63 years of age. The results were analyzed for sex- and age-associated changes with regard to three different sway components (total sway, anterio-posterior sway, lateral sway) and two different conditions (eyes open, eyes closed). Sex-associated differences were highly significant for all sway components in the oldest age group (51-65 years) in which men exhibited more spontaneous postural sway than women in the condition eyes open. With eyes closed these differences increased. Middle-aged men (36-50 years) also exhibited significantly more postural sway than women of the same age. In the condition eyes open especially total sway and anterioposterior sway were increased, whereas in the condition eyes closed total sway and lateral sway were predominantly higher in men than in women. In the youngest age group (21-35 years) no sex-related differences in postural sway were found. Age-associated differences were significant for anterioposterior sway (eyes open) in men, increasing continuously from the young to the middle-aged, and again from the middle-aged to the older age group. Anterioposterior sway in women, on the contrary, did not change with age. Age-associated differences in women were found for total sway (eyes open) and lateral sway (eyes closed). However, the highest values for total sway and lateral sway within the female group were obtained from young women in both conditions eyes open and eyes closed.(ABSTRACT TRUNCATED AT 250 WORDS)