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Alois Ebner

Publications and source records attributed to Alois Ebner.

18 recordsLinked to original sources

Neocortical microenvironment in patients with intractable epilepsy: potassium and chloride concentrations.

PURPOSE: The regulation of extracellular ion concentrations plays an important role in neuronal function and epileptogenesis. Despite the many studies into the mechanisms of epileptogenesis in human experimental models, no data are available regarding the fluctuations of extracellular potassium ([K(+)](o)) and chloride ([Cl(-)](o)) concentrations, which could underlie seizure susceptibility in human chronically epileptic tissues in vivo. METHODS: By using cerebral microdialysis during surgical resection of epileptic foci, the basic [K(+)](o) and [Cl(-)](o) as well as their changes after epicortical electric stimulation were studied in samples of dialysates obtained from 11 patients by ion-selective microelectrodes. RESULTS: The mean basal values of [K(+)](o) and [Cl(-)](o) in all patients were 3.83 +/- 0.08 mM and 122.9 +/- 2.6 mM, respectively. However, significant differences were observed in the basal levels of both [K(+)](o) and [Cl(-)](o) between different patients. Statistically, no correlation was found between basal [K(+)](o) or [Cl(-)](o) and electrocorticogram (ECoG) spike activity, but in one patient, dramatically lowered baseline [Cl(-)](o) was accompanied by enhanced ECoG spike activity. Application of epicortical electrical stimulation increased [K(+)](o) but not [Cl(-)](o) in all cases. According to the velocity as well as spatial distribution of [K(+)](o) reduction to the prestimulation levels, three different types of responses were observed: slow decline, fast decline, and slow and fast declines at adjacent sites. CONCLUSIONS: These data may represent abnormalities in ion homeostasis of the epileptic brain.

Adolescent↗

Comparison of brain extracellular fluid, brain tissue, cerebrospinal fluid, and serum concentrations of antiepileptic drugs measured intraoperatively in patients with intractable epilepsy.

PURPOSE: The mechanisms of drug resistance in epilepsy are only incompletely understood. According to a current concept, overexpression of drug efflux transporters at the blood-brain barrier may reduce levels of antiepileptic drugs (AEDs) in epileptogenic brain tissue. Increased expression of drug efflux transporters such as P-glycoprotein has been found in brain tissue surgically resected from patients with medically intractable epilepsy, but it is not known whether this leads to decreased extracellular (interstitial) AED concentrations in affected brain regions. This prompted us to measure concentrations of AEDs in the extracellular space of human neocortical tissue by using intraoperative microdialysis (IOMD) in those parts of the brain that had to be removed for therapeutic reasons. For comparison, AED levels were determined in brain tissue, subarachnoid CSF, and serum. METHODS: Concentrations of carbamazepine (CBZ), 10-hydroxy-carbazepine (10-OH-CZ, metabolite of oxcarbazepine), lamotrigine (LTG), levetiracetam (LEV), topiramate, or phenytoin were determined by using one to four catheters during IOMD in the medial temporal gyrus. Furthermore, to calculate the individual recovery of every catheter, an in vitro microdialysis was performed with ultrafiltrate of serum concurrently obtained from the respective patient. In addition, AED levels were determined in the resected brain tissue, CSF, and serum of the same patients. Altogether 22 pharmacoresistant epilepsy patients (nine male, 13 female patients; age 15-54 years) with complex partial seizures or secondarily generalized seizures were involved. In a first series, IOMD samples 40 min after beginning of the microdialysis (flow rate, 1 microl/min), and in a second series, continuous measurements 25, 30, 35, and 40 min from the beginning were evaluated (flow rate, 2 microl/min). With in vitro recovery data of the individual catheters, the concentration in the extracellular space (ECS) was estimated. RESULTS: AED concentrations in the ECS of the cortex measured by catheters located at a distance of 0.6 cm differed markedly in some patients, whereas concentrations in the ultrafiltrate of the serum of the respective patients measured with the same catheters varied only slightly. Furthermore, ECS concentrations related to the ultrafiltrate of serum showed considerable interindividual variations. The high intra- and interindividual variation of ECS concentrations is demonstrated by the low correlation between concentrations in ECS and the ultrafiltrate of serum (CBZ, r= 0.41; 10-OH-CZ, r= 0.42; LTG, r= 0.27) in contrast to the high correlation between brain tissue concentration and the ultrafiltrate of serum (CBZ, r= 0.97; 10-OH-CZ, r= 0.88; LTG, r= 0.98) in the same group of patients. When comparing AED concentrations in the ECS with those in the CSF, ECS concentrations were significantly lower for CBZ, 10-OH-CZ, LTG, and LEV. CONCLUSIONS: The data demonstrate that AED concentrations show a considerable intraindividual and interindividual variation in the ECS of cortical regions. Furthermore, the ECS concentration of several AEDs is significantly lower than their CSF concentration in patients with intractable epilepsy. However, in the absence of data from nonepileptic tissues, it is not possible to judge whether the present findings relate to overexpression of multidrug transporters in the brain. Instead, the present study illustrates the methodologic difficulties involved in performing IOMD studies in patients and may thus be helpful for future approaches aimed at elucidating the role of multidrug transporters in epilepsy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Left-sided interictal epileptic activity induces shift of language lateralization in temporal lobe epilepsy: an fMRI study.

PURPOSE: By using speech-activated functional MRI (fMRI), we investigated whether the frequency of left-sided interictal epileptic activity (IED: spikes or sharp waves on the EEG) is associated with atypical speech lateralization. METHODS: We investigated 28 patients (13 men, aged 17-59 years) with left-sided mesial temporal lobe epilepsy (MTLE) and 11 patients with right-sided MTLE as a control population. Only patients with unilateral hippocampal sclerosis with unilateral IED were included. For fMRI of individual patients, we contrasted images sampled during covert word generation with a low-level rest condition. With SPM99, an individual comparison for the contrast "word generation versus resting inactivity" was conducted. To characterize speech lateralization in individual patients, we calculated asymmetry indexes (AIs): the difference between activated left-sided and right-sided voxels was divided by all activated voxels. Analyzing long-term EEG, the first 2 min of each hour were evaluated for the frequency of IED. Univariate associations with AIs were assessed by Pearson's correlation and by t test. When testing the independent associations, multivariate linear regression was performed. RESULTS: The AIs in patients with left-sided MTLE were 0.40 +/- 0.53 on average (range, -0.83 to +1.0), whereas in right-sided MTLE, they were 0.78 +/- 0.15 (p = 0.029). For the further investigations, we included left-sided MTLE patients only. The median frequency of IED was six per hour (range, 0-240). Higher IED frequency was correlated with left-right shift of lateralization of speech fMRI activity (p = 0.002). CONCLUSIONS: Higher left-sided spike frequency in MTLE was associated with a left-right shift of speech representation, suggesting that chronic frequent interictal activity may induce a reorganization of speech lateralization.

Adolescent↗

Epilepsy surgery in professional musicians: subjective and objective reports of three cases.

We describe a small series of three professional musicians who had right (two patients) and left (one patient) temporal lobe epilepsy surgery with the histological diagnoses of hippocampal sclerosis (two patients) and benign tumor (one patient, xanthoastrocytoma). The musicians were asked to complete a questionnaire about their musical abilities before and after surgery with respect to special musical skills like melody processing, musical memory, rhythm, meter, harmony/dissonance, timbre, concentration and endurance, emotionality, and absolute pitch. In addition, the musicians submitted reports of their experiences. Surgical outcome was excellent with respect to seizures and professional skills. The two patients with right temporal lobe epilepsy reported improvements of specific musical abilities. Vocational development was very positive in all three patients. We conclude that epilepsy surgery can be safe and rewarding in professional musicians and propose initiating a database on epilepsy surgery in this special group of patients.

Adult↗

Postoperative routine EEG correlates with long-term seizure outcome after epilepsy surgery.

We investigated the correlation of interictal epileptiform discharges (IED) in routine EEG 6 and 24 months after epilepsy surgery with regard to long-term seizure outcome. In 148 patients (74% temporal lobe epilepsy (TLE), 26% extratemporal epilepsy) EEG results (IED present or absent) were correlated with the postoperative outcome using the Engel classification 6 and 24 months after resection (PO6m and PO2y, respectively). Self-evaluation was conducted 3 and 5 years after resection (PO3y and PO5y, respectively). Ninety-one patients (62%) were seizure-free 5 years after resection; 88% of them showed no IED in PO6m. Twenty-eight patients (19%) displayed IED in routine EEG 6 months after resection; 61% of them had recurrent seizures at PO5y, whereas of 120 patients without IED only 33% had recurrent seizures at PO5y; p=0.01. Absence of IED in PO6m and PO2y correlated with good outcome: 71% without IED remained seizure-free, whereas only 25% with IED at PO6m and PO2y remained seizure-free; p=0.001. Seizure-free patients (Engel 1) and patients with less favourable outcome (Engel 3-4) at PO6m and PO2y rarely changed categories of outcome during the following years (p<0.001). Half of the patients with favourable seizure reduction (Engel 2) changed to seizure-free (Engel 1) or to a worse outcome category (Engel 3-4). Postoperative routine EEG is a good prognostic instrument for the prediction of long-term seizure outcome, especially for TLE. It predicts the running up and down of fits in patients with rare seizures (Engel 2).

Adolescent↗

Intrinsic excitability, synaptic potentials, and short-term plasticity in human epileptic neocortex.

Although studies of epileptic human hippocampus suggest changes of synaptic and intrinsic excitability, few changes, save the appearance of spontaneous field/synaptic potentials, are known in epileptic neocortical tissue. However, invasive EEG and histological studies suggest that neocortical tissue, even in mesial temporal lobe epilepsy, can play an important role as an irritative zone or extrahippocampal focus. We hypothesized that intrinsic neuronal and synaptic excitability, as well as short-term plasticity, are altered in neocortical areas, particularly with elevated K+ levels as occur during seizures. We analyzed neuronal firing properties, synaptic responses, and paired-pulse plasticity in human neocortical slices from tissue resected during epilepsy surgery, both under normal and under pathological conditions, i.e., after elevating K+ (4/8 mM), with rat neocortical slices as controls. Neuronal firing properties were not different. We did find, however, alterations of synaptic responsiveness in epileptic tissue, i.e., an elevated network excitability with K+ elevations, and reduction of paired-pulse depression.

Adult↗

Do antiepileptic drugs accelerate forgetting?

The majority of patients with epilepsy become seizure-free with antiepileptic drug therapy. However, seizures in approximately one-third of patients with epilepsy are difficult to treat with antiepileptic drugs and require high doses or polytherapy. High dosages increase the risk of cognitive side effects. We retrospectively investigated 162 patients with refractory temporal lobe epilepsy to determine whether the antiepileptic drugs carbamazepine, phenobarbital, and phenytoin affect the acquisition and retention of verbal and visual information. We found that patients with high serum levels of these antiepileptic drugs were selectively impaired in the retention but not acquisition of new information. Intelligence, age, duration of epilepsy, and seizure frequency were controlled for and were not factors in the observed results. There were no differences in favor of a certain drug with respect to memory functioning. Our results suggest that patients with refractory epilepsy with high serum levels of the antiepileptic drugs studied are at higher risk of accelerated forgetting.

Adult↗

Functional MRI predicts memory performance after right mesiotemporal epilepsy surgery.

PURPOSE: Anterior temporal lobe resection (ATR) is a treatment option in drug-resistant epilepsy. An important risk of ATR is loss of memory because mesiotemporal structures contribute substantially to memory function. We investigated whether memory-activated functional MRI (fMRI) can predict postoperative memory loss after anterior temporal lobectomy in right-sided medial temporal lobe epilepsy (MTLE). METHODS: We included 16 patients (10 women) aged 16-54 years. The mean age at epilepsy onset was 12.5 years (range, 1-26 years). The patients' mean Wechsler IQ score was 95.2 (range, 62-125). The activation condition of fMRI consisted of retrieval from long-term memory induced by self-paced performance of an imaginative walk. All but one patient had left-sided speech dominance according to speech-activated fMRI. Outside the scanner, we evaluated the pre- and postoperative visual memory retention by using Rey Visual Design Learning Test. RESULTS: We found a correlation between the preoperative asymmetry index of memory-fMRI and the change between pre- and postsurgical measures of memory retention. Reduced activation of the mesiotemporal region ipsilateral to the epileptogenic region correlated with a favorable memory outcome after right-sided ATR. CONCLUSIONS: In light of the postoperative results, the theoretical implication of our study is that fMRI based on a simple introspective retrieval task measures memory functions. The main clinical implication of our study is that memory-fMRI might replace the invasive Wada test in MTLE by using a simple fMRI paradigm. Predictive power, however, will be studied in larger patient samples. Other studies are required for left-sided MTLE and neocortical epilepsies to assess the clinical usefulness of memory-fMRI.

Adolescent↗

Hyperorality in epileptic seizures: periictal incomplete Klüver-Bucy syndrome.

PURPOSE: To analyze systematically hyperorality associated with epileptic seizures and its relation to the localization of epileptic activity. METHODS: To identify patients with periictal hyperorality, we reviewed video-recordings of 269 patients (aged 6-59 years) who had consecutively undergone presurgical evaluations including ictal video-EEG recordings and high-resolution magnetic resonance imaging (MRI) and had had epilepsy surgery because of intractable frontal (FLE) or temporal lobe epilepsy (TLE). Periictal hyperorality was defined if patients put or unambiguously intended to put nonfood items into their mouths during or after at least one of the reviewed seizures. For the further analysis, we included only patients with periictal hyperorality. We reviewed their medical records and reexamined their ictal video-EEG recordings. RESULTS: We identified eight patients (six women) aged 8-59 years who had hyperorality during or after seizures. Seven patients had TLE, and one patient had frontal lobe epilepsy (FLE). Three of these patients underwent right-sided surgery, whereas five patients had surgery on the left. Three patients exhibited ictal and five showed postictal hyperorality. Interictal EEG suggested bilateral interictal epileptiform discharges (IEDs) in three patients; in two other patients, no IEDs were detected. Ictal EEG suggested bilateral involvement in six cases. Patients with unilateral epileptiform activity had left TLE. CONCLUSIONS: Periictal hyperorality is a rare phenomenon occurring in 3% of the investigated epilepsy population. We suggest that periictal hyperorality is an ictal-postictal mental disturbance, an incomplete Klüver-Bucy syndrome. In most patients, bilateral seizure activity plays an important role in the pathomechanism, but it would appear that left-sided epileptic activity without contralateral involvement also can cause periictal hyperorality.

Adolescent↗

Ring chromosome 20 with nonconvulsive status epilepticus: electroclinical correlation of a rare epileptic syndrome.

The electroclinical features of two Thai women with ring chromosome 20 and nonconvulsive status epilepticus (NCSE) were studied. Both have also had generalized tonic-clonic seizures and complex partial seizures of varying frequencies since adolescence. Their intellectual functions were normal. Twenty-four-hour video/EEG telemetry recorded during the NCSE showed fluctuating consciousness between overt unresponsiveness and normal awareness. The EEG consisted of long-lasting generalized rhythmic 3-5 Hz sharp or slow waves with a few spikes, lasting several days. Despite the continuous discharges, the patients had relatively subtle clinical episodes of seizures, during which they were sometimes responsive to verbal stimuli. Intravenous antiepileptic drugs (AED) had little effect on the rhythmic EEG. No lesion in their MRIs contributed to NCSE. Ring chromosome 20 was found in 20% of female karyotype in both patients [46,XX,r(20) (p13 q13)/46,XX] but were negative in four healthy siblings. Oral AEDs decreased more than 75% of the overt CPS episodes in both patients at 22 and 26 months of follow-up but had no effect on the natural history of electrical NCSE. The patients' daily activities were minimally affected by the ongoing electrical discharges. These are the first two cases reported of ring chromosome 20 with NCSE in Thailand. Our patients present a rather benign and pharmacologically responsive course probably because of the low percentage of r(20) mosaicism. The electroclinical correlations in our cases raise the possibility that the mechanism of continuous rhythmic waves in this syndrome may be unrelated to epilepsy. Assessing the severity of this syndrome using both clinical seizures and EEG is crucial.

Adult↗

A semiological classification of status epilepticus.

The classification of status epilepticus (SE) has been a subject of discussion for many years, yet no satisfactory agreement has been reached. Due to their complexity, status episodes often defy classification according to the current international classification scheme. The semiological seizure classification (SSC) has been in use in several epilepsy centers for more than a decade, and has proven to be a valid approach to the classification of epileptic seizures. Based on the detailed analysis of more than 100 episodes of SE documented with video-EEG recordings, the authors now present a proposal for a semiological classification of status epilepticus (SCSE). The SCSE reflects the assumption implied by all modern definitions of SE that "there are as many types of status as there are types of seizures" and relies on the same principles as the SSC, focusing on the main clinical manifestations and the evolution of the status episode. The clinical manifestations of SE are subdivided into semiological components and classified along three axes: the type of brain function predominantly compromised by the seizure activity, the body part involved, and the evolution over time. Each axis contains several subcategories, so that many different levels of accuracy are possible. The SCSE, just like the SSC, is meant to be part of a comprehensive epilepsy classification which classifies as independent variables (epileptogenic zone, ictal semiology, etiology, related medical conditions) the main features of the patient's epilepsy, allowing for each variable maximum flexibility.

Autonomic Nervous System↗

Paroxysmal alien limb phenomena due to epileptic seizures and electrical cortical stimulation.

Alien limb phenomena (ALPs) are characterized by limb movements, which are subjectively experienced as involuntary or alien induced. ALPs regularly remain unchanged and occur as a consequence of frontal, callosal, or posterior cerebral lesions. The authors present two patients with paroxysmal ALP proved to be focal seizures by using video-EEG monitoring. In another two patients, ALP could experimentally be induced by electrical cortical stimulation. Based on the stimulation results, the authors suspect a functional disconnection of 1) sensory cortical areas providing information about the extrapersonal space; and 2) areas of the frontal and/or limbic cortex that are regularly involved in the processing and executing of intentional motor activity as a pathophysiologic substrate for ictal ALP.

Adolescent↗

Age at onset in mesial temporal lobe epilepsy with a history of febrile seizures.

The authors demonstrated that temporal lobe epilepsy with hippocampal sclerosis preceded by febrile seizures can be divided into different groups according to age at epilepsy onset (AEO). AEO was found to be trimodal with a peak at ages 5.5, 15.3, and 26.7. In the adolescent AEO group, a family history of epilepsy occurred more frequently and the age at febrile convulsions was earlier than in the childhood group.

Adolescent↗

Functional organization of the brain with malformations of cortical development.

We examined the localization of cerebral functions in 28 patients with focal epilepsy and malformations of cortical development (MCDs). Polymicrogyria occurred in nine, hemimegalencephaly in four, heterotopia in eight, and focal cortical dysplasia (FCD) in nine cases. We used simple (sensomotor, visual) or complex (language, memory) functional magnetic resonance imaging (fMRI) paradigms. Two thirds of MCDs were activated by simple fMRI paradigms, whereas they less frequently showed activity during complex cognitive fMRI paradigms. During simple paradigms, all disturbances of cortical organization (polymicrogyria, schizencephaly, and mild-type FCD) showed activity, whereas other MCDs (disturbances of earlier steps of cortical development: hemimegalencephaly, Taylor-type FCD, and heterotopia) showed activity in only 44% (p < 0.01). The association between the pathophysiology and morphology of MCDs confirms the recently proposed classification system. Both focal neurological signs (p < 0.05) and focal electroencephalogram slowing (p < 0.05) independently correlated with MCD inactivity, confirming that fMRI showed neuronal functions of MCDs. Conclusively, fMRI visualizes the MCD functions and their relationship to the eloquent cortex, providing useful information before epilepsy surgery. Surgery of cortical organization disturbances should be cautiously performed because these malformations may participate to some degree in brain functions.

Adolescent↗

Gender-specific differences of hypometabolism in mTLE: implication for cognitive impairments.

PURPOSE: To determine gender differences of hypometabolism and their implications for cognitive impairment in patients with medically refractory mesial temporal lobe epilepsy (mTLE). METHODS: Regional cerebral glucose metabolism (rCMRGlu) was studied in 42 patients (21 male, 21 female) with either left- or right-sided mTLE (22 left, 20 right) and in 12 gender- and age-matched healthy controls during resting wakefulness and in 12 sex- and age-matched healthy controls. Clinical characteristics were balanced across the patient subgroups. All patients were subjected to neuropsychological assessment: 41 patients had histologic changes of definite or probable hippocampal sclerosis. RESULTS: Data analysis based on pixel-by-pixel comparisons and on a laterality index of regions of interest (ROIs) showed significant depressions of the mean rCMRGlu extending beyond the mesiotemporal region and temporolateral cortex to extratemporal regions including the frontoorbital and insular cortex in mTLE patients. Extramesiotemporal hypometabolism prevailed in the male patients. Metabolic asymmetry in temporal and frontal regions was related to performance in the Trail-Making Test and WAIS-R subitems. CONCLUSIONS: Our data showed a gender-specific predominance of extramesiotemporal hypometabolism in male patients with mTLE related to abnormalities of temporal and frontal lobe functions.

Adult↗

Effects of chronic epilepsy on intellectual functions.

Intractable epilepsy is related to various transient and chronic brain electric and neurochemical disturbances. There is increasing evidence that long-lasting chronic epilepsy may induce secondary neuronal loss and metabolic dysfunctions. Still a matter of controversy is, however, whether cognitive abilities of patients deteriorate with increasing duration of intractable epilepsy. We present results from two independent cross-sectional studies dealing with measures of global cognitive performance in two different ways. The first study investigated in 78 patients with refractory temporal lobe epilepsy (TLE) the influence of duration of epilepsy on the difference between an estimated measure of former or pre-morbid intelligence and the current performance in an intelligence test. The second study aimed at duration of epilepsy-dependent effects on current IQ measures of 209 patients with refractory TLE. Both studies showed that the duration of epilepsy contributes to the explanation of interindividual variability in IQ measures of adult TLE patients to a higher degree than age and age of epilepsy onset. Similar to several studies on hippocampal neuronal density, hippocampal volume, and glucose metabolism, the presented cross-sectional data demonstrate that a duration of chronic epilepsy exceeding two decades is associated with worse cognitive abilities. Consequently, refractory TLE seems to induce a very slow but ongoing cognitive deterioration. It is assumed that epilepsy-related noxious events and agents exhaust the compensatory capacity of brain functions. A high cognitive reserve capacity, however, might delay the onset of deterioration.

Adult↗

Effect of levetiracetam on epileptiform discharges in human neocortical slices.

PURPOSE: The anticonvulsant effects of the novel antiepileptic drug (AED) levetiracetam (LEV) were tested in neocortical slice preparations from 23 patients who underwent surgery for the treatment of refractory epilepsy. METHODS: Slices were used to evaluate the effects of LEV on two different models of epilepsy: low-Mg2+-induced untriggered and bicuculline-evoked stimulus-triggered epileptiform burst discharges and spontaneously appearing rhythmic sharp waves. RESULTS: LEV (0.1-1 mM) did not influence spontaneously appearing rhythmic sharp waves or Mg2+-free aCSF-induced epileptiform field potentials. LEV affected neither the amplitudes or duration nor the repetition rates of burst discharges in these epilepsy models. However, LEV (100-500 microM) significantly suppressed the ictal-like discharges elicited by the gamma-aminobutyric acid subtype A (GABAA)-receptor antagonist bicuculline. A marked reduction of the amplitude and duration of bicuculline-evoked field response in the presence of LEV was observed. CONCLUSIONS: The results indicate the potential for LEV to inhibit epileptiform burst discharges in human neocortical tissue, which is consistent with its effects in animal models of epilepsy. These results also support the seizure reduction observed in clinical trials and support that this may, in part, be related to the ability of LEV to inhibit epileptiform discharges.

Adolescent↗