Falk Oppel

Spreading depression in human neocortical slices

Cortical spreading depression (CSD) occurrence has been suggested to be associated with seizures, migraine aura, head injury and brain ischemia-infarction. Only few studies identified CSD in human neocortical slices and no comprehensive study so far evaluated this phenomenon in human. Using the neocortical tissue excised for treatment of intractable epilepsy, we aimed to investigate CSD in human. CSD was induced by KCl injection and by modulating T-type Ca(2+) currents in incubated human neocortical tissues in an interphase mode. The DC-fluctuations were recorded by inserting microelectrodes into different cortical layers. Local injection of KCl triggered single CSD that propagated at 3.1+/-0.1 mm/min. Repetitive CSD also occurred spontaneously during long lasting application (5 h) of the T-type Ca(2+) channel blockers amiloride (50 microM) or NiCl(2) (10 microM) which was concomitant with a reversible extracellular potassium increase up to 50 mM. CSD could be blocked by the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid in all cases. The results demonstrate that modulation of the Ca(2+) dynamics conditioned human neocortical slices and increased their susceptibility to generate CSD. Furthermore, these data indicate that glutamatergic pathway plays a role in CSD phenomenon in human.

Long-term outcome after temporal lobe epilepsy surgery in 434 consecutive adult patients

OBJECT The aim of this study was to evaluate the long-term efficacy of temporal lobe epilepsy (TLE) surgery and potential risk factors for seizure recurrence after surgery. METHODS This retrospective study included 434 consecutive adult patients who underwent TLE surgery at Bethel Epilepsy Centre between 1991 and 2002. RESULTS Hippocampal sclerosis was found in 62% of patients, gliosis in 17.3%, tumors in 20%, and focal cortical dysplasia (FCD) in 6.9%. Based on a Kaplan-Meier analysis, the probability of Engel Class I outcome for the patients overall was 76.2% (95% CI 71-81%) at 6 months, 72.3% (95% CI 68-76%) at 2 years, 71.1% (95% CI 67-75%) at 5 years, 70.8% (95% CI 65-75%) at 10 years, and 69.4% (95% CI 64-74%) at 16 years postoperatively. The likelihood of remaining seizure free after 2 years of freedom from seizures was 90% (95% CI 82-98%) for 16 years. Seizure relapse occurred in all subgroups. Patients with FCD had the highest risk of recurrence (hazard ratio 2.15, 95% CI 0.849-5.545). Predictors of remission were the presence of hippocampal atrophy on preoperative MR imaging and a family history of epilepsy. Predictors of relapse were the presence of bilateral interictal sharp waves and versive seizures. Six-month follow-up electroencephalography predicted relapse in patients with FCD. Short epilepsy duration was predictive of seizure remission in patients with tumors and gliosis; 28.1% of patients were able to discontinue antiepileptic medications without an increased risk of seizure recurrence (hazard ratio 1.05, 95% CI 0.933-1.20). CONCLUSIONS These findings highlight the role of etiology in prediction of long-term outcome after TLE surgery.

Long-term outcome of extratemporal epilepsy surgery among 154 adult patients

OBJECT The goal of this study was to evaluate the long-term outcome of patients who underwent extratemporal epilepsy surgery and to assess preoperative prognostic factors associated with seizure outcome. METHODS This retrospective study included 154 consecutive adult patients who underwent epilepsy surgery at Bethel Epilepsy Centre, Bielefeld, Germany between 1991 and 2001. Seizure outcome was categorized based on the modified Engel classification. Survival statistics were calculated using Kaplan-Meier curves, life tables, and Cox regression models to evaluate the risk factors associated with outcomes. RESULTS Sixty-one patients (39.6%) underwent frontal resections, 68 (44.1%) had posterior cortex resections, 15 (9.7%) multilobar resections, 6 (3.9%) parietal resections, and 4 (2.6%) occipital resections. The probability of an Engel Class I outcome for the overall patient group was 55.8% (95% confidence interval [CI] 52-58% at 0.5 years), 54.5% (95% CI 50-58%) at 1 year, and 51.1% (95% CI 48-54%) at 14 years. If a patient was in Class I at 2 years postoperatively, the probability of remaining in Class I for 14 years postoperatively was 88% (95% CI 78-98%). Factors predictive of poor long-term outcome after surgery were previous surgery (p = 0.04), tonic-clonic seizures (p = 0.02), and the presence of an auditory aura (p = 0.03). Factors predictive of good long-term outcome were surgery within 5 years after onset (p = 0.015) and preoperative invasive monitoring (p = 0.002). CONCLUSIONS Extratemporal epilepsy surgery is effective according to findings on long-term follow-up. The outcome at the first 2-year follow-up visit is a reliable predictor of long-term Engel Class I postoperative outcome.

The effects of verapamil and flunarizine on epileptiform activity induced by bicuculline and low Mg2+ in neocortical tissue of epileptic and primary non-epileptic patients

In human neocortical slices the specific L-type calcium channel blocker verapamil had been shown to be antiepileptic in the low Mg(2+)-model of epilepsy. The present investigation demonstrated: (1) verapamil exerted also an antiepileptic effect on epileptiform field potentials (EFP) induced by the GABAA-antagonist bicuculline. (2) The unspecific calcium channel modulator flunarizine, which in contrast to verapamil penetrates the blood-brain barrier, depressed EFP in the low Mg(2+)-model and in the bicuculline model. (3) There was no significant difference in the antiepileptic efficacy of verapamil and flunarizine in epileptic (epilepsy surgery) and primary non-epileptic (tumor surgery) neocortical slices.

EVALUATION WITH SUBDURAL PLATES IN CHILDREN AND ADOLESCENTS

Noninvasive EEG examination is not always adequate for the determination of the epileptogenic area. In such cases invasive methods are required. The authors report on their experience with the implantation of subdural plates for the precise ictal and inter-ictal determination of the epileptogenic areal and the stimulation of the eloquent cortex. From December 1992 to December 1997, 97 patients were evaluated in the Bethel epilepsy center using subdural plates. Of these patients, 44 were children or adolescents, who underwent 45 resections. In order to be able to draw differentiated conclusions on the use of subdural plates in children and adolescents, these patients were divided into three age groups: Group 1, 0-5 years (n = 12); Group 2, 6-11 years (n = 13 + 1 repeat evaluation and resection); Group 3, 12-18 years (n = 19). In the groups of children and adolescents examined there were no complications or progress impediments which might give reason to assume that the application of these techniques involves risks or hazards. This has been verified by the results, in which 75% of age Groups 1 and 3 were categorized as 1 a/b or 2d according to the Engel classification.

Anoxic terminal negative DC-shift in human neocortical slices in vitro

In animal models, the hallmark of a hypoxic condition is a strong negative shift of the DC potential (anoxic terminal negativity, ATN). This DC-shift is interpreted to be primarily due to a breakdown of the membrane potential of neurons. Such massive neuronal depolarizations have not been reported for all human neocortical neurons in vitro even during prolonged hypoxic periods. This poses the question whether ATN develop also in human neocortical slices made hypoxic. ATN could be observed when human brain slice preparations (n = 15, 13 patients) were subjected to periods of hypoxia (10 to 120 min). These ATN were usually monophasic and appeared with a latency of 16 +/- 4 min (mean +/- S.E.M.). Separating the ATN according to their slopes of rise, steep (> 10 mV/min) and flat (< 10 mV/min) ATN could be distinguished. Steep and flat ATN may be regarded as two different entities of reactions since steep ATN had also greater amplitudes and slopes of decay as compared a flat ATN. With repetitive hypoxias, the latency of both the steep and flat ATN was reduced for the following hypoxic episodes. During hypoxic DC-shifts, evoked potentials were suppressed. With the 1st through 4th hypoxia, they recovered fully within 30 min after reoxygenation when hypoxia was terminated at the plateau of ATN; with extension of hypoxia, recovery was only partial. From the 5th hypoxia onwards, recovery usually did not take place or was not complete.

Long-term outcome of lesional posterior cortical epilepsy surgery in adults

Objective: The aim of this study was to evaluate the short- and long-term seizure outcome and to find predictors of outcome after epilepsy surgery in lesional posterior cortical epilepsies (PCEs). Methods: The operative outcome in 80 consecutive adult patients with lesional PCEs who underwent resective surgery for intractable partial epilepsy between 1991 and 2006 was retrospectively studied. Results: The probability of remaining in Engel Class I was 66.3% (95% CI 60 to 72) at 6 months, 52.5% (95% CI 47 to 57) at 2 years, 52.9% (CI 45 to 59) at 5 years and 47.1% (CI 42 to 52) at 10 years. Factors predicting poor outcome were the presence of a somatosensory aura, extraregional spikes, incomplete resection, interictal epileptiform discharge (IED) in EEG 6 months and 2 years postsurgery, history of generalised tonic-clonic seizure (GT-CS) and the presence of focal cortical dysplasia in the resected specimen. Factors predicting good outcome were childhood onset of epilepsy, short epilepsy duration, ipsilateral spikes, visual aura, presence of well-circumscribed lesion in preoperative MRI and a pathologically defined tumour. In the multivariate analysis, predictors were different in the long and short term as follows: incomplete resection as proven by postoperative MRI (hazard ratio (HR) 2.059 (CI 1.19 to 3.67)) predicts seizure relapse in short-term follow-up. The presence of IED in the EEG performed 6 months after surgery (HR 2.3 (CI 1.128 to 4.734)) predicts seizure relapse in the long-term fellow-up. However, the absence of a history of GT-CS independently predicts seizure remission in short- and long-term follow-up. Conclusions: Surgery in PCEs proved to be effective in short- and long-term follow-up. Lesional posterior cortical epilepsy may be a progressive process in a substantial number of cases.

Vigabatrin reduces epileptiform activity in brain slices from pharmacoresistant epilepsy patients.

Human neocortical temporal lobe tissue resected for treatment of pharmacoresistant epilepsy was investigated. In slices prepared from this tissue, epileptiform field potentials (EFP) were induced by omission of magnesium from the artificial cerebrospinal fluid (ACSF). The effects of the gamma-aminobutyric acid transaminase inhibitor vigabatrin on EFP were tested. Vigabatrin exerted a dose-dependent reduction of the repetition rate of EFP: after 3 h of administration of vigabatrin in concentrations of 100 and 200 micromol/l, the repetition rate of EFP was reduced to 35% and 18% of the initial values, respectively. This effect was not reversible. In control experiments with neocortical slices from rats, vigabatrin reduced EFP in a comparable range. The results demonstrate a strong antiepileptic effect of vigabatrin on EFP in tissues from pharmacoresistant epilepsy patients.

Flat and steep terminal negativity in the DC-potential after deprivation of oxygen and glucose in human neocortical slices

The so-called terminal negativity (TN) of the DC-potential is a characteristic reaction of neuronal tissue to hypoxia or ischemia. In a previous study on human neocortical slices, two types of TN with flat and steep slopes of rise (< or >10 mV/min) were found with hypoxia. The aim of the present study was to further investigate causes underlying the occurrence of flat and steep TN. Experiments were performed on 23 human neocortical slices (500 micron) resected from 13 patients (epilepsy and tumour surgery). DC-potential and evoked potentials (white matter stimulation) were recorded in layer III. The extracellular potassium concentration ([K+]o) was measured by K+-sensitive microelectrodes. In an interface type chamber, ischemic episodes were induced by oxygen and glucose deprivation. They were terminated when TN had peaked. Both flat and steep TN also existed with ischemic conditions. There was a linear correlation between the slope of rise of TN and the associated slope of rise in [K+]o, respectively, but none regarding latencies of TN or recovery of evoked potentials. Peak levels in [K+]o were 13.9+/-0.9 mmol/l. Compared to control, the slope of rise and latency of TN were clearly increased by addition of dimethyl sulfoxide (DMSO, 0.4%) to the bath solution, whereas nimodipine (40 micromol/l) in 0.4% DMSO had neither an effect on slope of rise of TN nor on latency of TN. As a whole, our observations suggest, that the actual metabolic state determines the occurrence of flat or steep TN.

Diastematomyelia combined with disc herniation at T 6/7 in an adult. Case report.

A case of thoracic diastematomyelia associated with acute disc herniation is reported. The female patient noted sensory and motor symptoms at 49 years of age, four months before hospitalization. Myelography, myelo-computerized tomography and nuclear resonance tomography of the thoracic spine and cord showed the region of diastematomyelia with an additional disc herniation at T 6/7. The bone spur and the disc was successfully excised. Post-operatively, the patients deficits improved.