Biomedical subjects

H Clusmann

Publications and source records attributed to H Clusmann.

At least 19 recordsLinked to original sources

PubMed2003

Down-regulation of mGluR8 in pilocarpine epileptic rats.

Activation of presynaptic metabotropic glutamate receptors (mGluRs) leads to a powerful inhibition of glutamate release from many synaptic terminals throughout the CNS. mGluRs as autoreceptors are believed to provide a negative feedback system that prevents potentially toxic accumulation of glutamate in the extracellular space during synchronous synaptic activity such as epileptic seizures. In this study we analyzed the function of presynaptic mGluR8 on terminals of the lateral perforant pathway in the pilocarpine model of limbic epilepsy. Field excitatory postsynaptic potentials (fEPSPs) recorded in hippocampal slices of rats that developed spontaneous recurrent seizures after pilocarpine-induced status epilepticus (SRS group) showed a significantly reduced sensitivity to Group III mGluR agonists and severe mossy fiber sprouting. The Group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 10 microM) depressed fEPSPs in the SRS group only by 26 +/- 21% compared to 50 +/- 18% in untreated rats. Similarly, the mGluR8 preferring agonist (R,S)-4-phosphonophenylglycine (PPG, 5 microM) was significantly less effective in slices from SRS rats (43 +/- 4% vs. 83 +/- 5%). Concentration-response curves for L-AP4 revealed that the EC(50) values were not different between the control and SRS group (13 +/- 7 microM vs. 9 +/- 9 microM), while the maximal depressing effect was significantly reduced. The remaining depressing effect of L-AP4 in the SRS group could be blocked by the Group III specific antagonists (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) and alpha-methyl-L-AP4 (MAP4). Rats that did not develop SRS following pilocarpine-induced status epilepticus were indistinguishable from control rats: fEPSPs were highly sensitive to L-AP4 and there was no mossy fiber sprouting. The results show that pilocarpine-induced status epilepticus can lead to a downregulation of mGluR8 and suggest that the condition of SRS is associated with a deteriorated autoregulation of glutamate release.

Animals↗

PubMed2003

Outcome of epilepsy surgery in focal cortical dysplasia.

OBJECTIVE: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. METHODS AND SUBJECTS: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). RESULTS: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. CONCLUSIONS: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies.

Adolescent↗

PubMed2002

Improved hybrid clamp: resolution of tail currents following single action potentials.

Hybrid clamp protocols, in which a discontinuous single electrode voltage clamp (dSEVC) amplifier is switched from current to voltage clamp during the recording, are frequently used to investigate conductance changes after high frequency trains of action potentials. This technique is advantageous because it combines physiological stimulation of the cell with the possibility of analyzing the consecutive conductance changes quantitatively. In this study an improved hybrid clamp protocol, called dynamic hybrid clamp, is developed that enables the experimenter to study tail currents after single action potentials. The protocol employs real time action potential detection to assure precise timing of the mode switch and utilizes an external sample and hold amplifier to avoid voltage steps during the switch to voltage clamp. With the use of whole-cell patch clamp recordings and high switching frequencies (> or =25 kHz), dSEVC can easily be started with a minimal delay (<1.5 ms) after single action potentials and tail currents underlying afterhyperpolarisations (AHPs) and afterdepolarisations ensuing single spikes are clearly resolved. The dynamic hybrid clamp should also be useful for analysis of spontaneously occurring events such as intrinsic or population bursts.

Action Potentials↗

PubMed2002

Neuropsychological Outcome in Children after Frontal Lobe Epilepsy Surgery.

We investigated the neuropsychological performance of children with frontal lobe epilepsy (FLE, n = 12) before and 1 year after surgery. Children with temporal lobe epilepsy (TLE, n = 12) were included as control group. Preoperatively, children with FLE had a significantly higher IQ than children with TLE, but were significantly more often impaired in manual motor coordination. Postoperatively, both groups improved in attention, short-term and long-term memory, and manual coordination, although the latter was not significant. Neuropsychological outcome in FLE patients was not better in seizure-free patients than in patients with continuing seizures. To avoid deterioration in language functions of patients in whom surgery involved left area 44, correspondence of results in cortical stimulation and intracarotid amytal test may be essential. All in all, our data indicate a favorable cognitive outcome in children 1 year after frontal lobe surgery.

Journal Article↗

PubMed2002

Presynaptic group II metabotropic glutamate receptors reduce stimulated and spontaneous transmitter release in human dentate gyrus.

Metabotropic glutamate receptors (mGluRs) control excitatory neurotransmission as inhibitory autoreceptors at many synapses throughout the CNS. Since pharmacological activation of mGluRs potently depresses excitatory transmission, anticonvulsive effects were found in a number of experimental epilepsies. However, although native rodent mGluRs and heterologously expressed human mGluRs have so far been investigated in great detail, our knowledge about native human mGluRs in situ is limited. Here we used acute human hippocampal slices prepared from hippocampi surgically removed for the treatment of temporal lobe epilepsy in order to investigate the modulation of glutamatergic transmission by human mGluRs at the perforant path-granule cell synapse. The broad spectrum mGluR agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) profoundly and reversibly reduced field EPSPs (fEPSPs) with an EC(50) of 30+/-7.4 microM. Paired-pulse depression of fEPSPs was converted into strong facilitation. The inhibition of fEPSPs by ACPD was mimicked by the specific group II mGluR agonist (2S, 2'R, 3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), while the specific group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) was ineffective. The effect of ACPD was blocked by group II antagonist (2S,3S,4S)-2methyl-2-(carboxycyclopropyl)glycine (MCCG) but was not changed by coapplication of the specific group III antagonist (S)2 amino2methyl4phosphonobutanoic acid (MAP4). ACPD reduced pharmacologically isolated intracellular EPSPs in granule cells to the same extent as fEPSPs, whereas a specific group III agonist had no effect on EPSPs. Whole-cell recordings from morphologically identified granule cells revealed that DCG-IV significantly reduced the frequency of miniature EPSCs (mEPSCs) in granule cells while the mean amplitude of mEPSCs was not affected. We conclude that in human dentate gyrus mGluR2/3 can almost completely depress glutamate release by a presynaptic mechanism which acts downstream of presynaptic voltage gated calcium-entry and most likely involves a direct modulation of the release machinery.

Action Potentials↗

PubMed2002

Pre- and postoperative verbal memory in pediatric patients with temporal lobe epilepsy.

Outcome studies concerning memory after pediatric temporal lobe surgery in the treatment of epilepsy are rare and have not yielded consistent results. In the present study, 55 children and adolescents with temporal lobe epilepsy (TLE; 26 left, 29 right, 6-17 years) performed a verbal memory test before and 3 as well as 12 months after different types of temporal lobe resections (anterior lobectomy, amygdalo-hippocampectomy (AH), lesionectomy (LX)). Groups did not significantly differ before surgery. Three months after surgery, the left resected group showed a decline in learning and delayed recall, and performed significantly lower than the right resected group. Recoveries were evident 1 year after surgery. The postoperative memory declines were associated with a left-sided resection and a higher preoperative performance. Comparisons on the different resection types suggest a special risk in patients undergoing a left-sided AH. In summary, our results indicate a functional association of verbal memory functions with the left temporal lobe similar to findings in adult patients. Declines after left-sided temporal resections seem to be reversible at least for part of the children, perhaps due to the greater plasticity of the immature brain.

Adolescent↗

PubMed2002

Preoperative evaluation for epilepsy surgery (Bonn Algorithm).

SUMMARY: Epilepsy surgery has been established as a successful treatment in patients with drug-resistant focal epilepsies. Different standardized surgical approaches were developed for resective or functional treatment. Successful surgical treatment, however, necessitates a careful presurgical evaluation. Although there are international standards for non invasive and invasive presurgical procedures most centers differ in their diagnostic strategy. This article gives a survey of the Bonn Epilepsy surgery program within which more than 1300 patients have been treated. After the method of patient selection different we describe tools of non invasive and invasive evaluation. This article serves only as a description of current practice in one center with a relatively large volume of cases. It presents just one opinion of a specific group within a wide spectrum of possible algorithms for presurgical evaluation that have briefly been outlined for 33 centers in Engels book [4].

Electroencephalography↗

PubMed2001

Messenger RNA of steroid 21-hydroxylase (CYP21) is expressed in the human hippocampus.

21-hydroxylase converts progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol, the substrates which are required for the production of the main adrenal steroids, corticosterone, aldosterone, and cortisol. As 21-hydroxylase activity has been detected in rodent and fetal human brain, we studied whether and to what extent 21-hydroxylase mRNA is expressed in hippocampal tissue specimens from patients undergoing epilepsy surgery (n=42). 21-hydroxylase mRNA was detected in the hippocampus with an expression 10 000 times lower than in adrenal gland tissue. There was no significant difference in expression levels between women (9.5+/-2.7 arbitrary units (aU); mean+/-SEM) and men (8.0+/-2.2 aU); however, mRNA concentrations in the hippocampus of children (n=4, 1.8+/-0.5 aU) were considerably lower than in adults (n=38, 8.6+/-1.7 aU). The expression of 21-hydroxylase mRNA in the hippocampus suggests that this human brain area has the enzymatic capability to convert progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol.

Adult↗

PubMed2001

Expression of the 17beta-hydroxysteroid dehydrogenase type 5 mRNA in the human brain.

An enzyme-mediated metabolism of androgens and estrogens including 17beta-HSD activity in the brain of vertebrates was discovered approximately 30 years ago. Mainly 5alpha-reductase and aromatase have been studied in detail. Recently we could demonstrate reductive and oxidative 17beta-HSD activity as well as considerable mRNA expression of the 17beta-HSD types 3 and 4 in the human brain. In the present study, we report on 17beta-HSD type 5 mRNA expression in brain tissue of women and men. Data analysis did not reveal sex specific differences, but we determined a significantly higher mRNA concentration in the subcortical white matter (SC) than in the cerebral cortex (CX). Investigation of reductive 17beta-HSD in vitro activity with 2 microM androstenedione as the substrate revealed no sex specific differences. Testosterone formation was significantly higher in SC than in CX. Moreover, enzyme activity was significantly higher in brain tissue of adults compared to that of children.

17-Hydroxysteroid Dehydrogenases↗

PubMed2001

Postsurgical outcome of children and adolescents with medically refractory frontal lobe epilepsies.

OBJECTS: In the adult population surgical treatment is generally less favorable for refractory frontal lobe epilepsy (FLE) than for temporal lobe epilepsy (TLE). Predictive factors and outcome of FLE surgery had not previously been described for the pediatric and adolescent population. Therefore, 32 children and adolescents who underwent FLE surgery were analyzed in this study. METHODS: Medical records were reviewed for demographic data, presurgical evaluation procedures, surgical procedures, pathological findings and follow-up. RESULTS: Mean age at operation was 10.8 years, with seizure onset at 4.6 years. Excellent outcomes were observed in 21 of the 32 patients following evaluation a mean of 34.5 months after surgery. Nineteen of 22 patients became seizure free after tailored resections, versus 2 out of 10 after lobectomy. Transient neurological and surgical complications occurred in 4 patients. Focal neoplastic lesions detectable by MRI were associated with a favorable outcome. CONCLUSIONS: As seen in adult FLE series, the detection of a resectable ictal neoplastic lesion on preoperative MRI is associated with an excellent outcome comparable to that of TLE surgery.

Adolescent↗

PubMed2001

Transsylvian keyhole functional hemispherectomy.

OBJECTIVE: To describe the technical steps, advantages, and limitations of a quicker, minimal-exposure, functional hemispherectomy procedure developed from a hemispherical deafferentation technique previously described. METHODS: The surgical approach using the transsylvian/transsulcal passage to the ventricular system, with the anatomic orientation points and key features for planning of the small trepanation, is described. Through a linear incision, a craniotomy (4 x 4 to 4 x 5 cm) is placed over the sylvian fissure. Transsylvian exposure of the circular sulcus allows transcortical exposure of the entire ventricular system, from the frontal horn to the temporal horn encircling the insular cortex. The frontobasal and mesial white matter is disconnected via the intraventricular approach, with a callosotomy. An amygdalohippocampectomy completes the dissection. The experience with 20 patients who were treated using the transsylvian keyhole hemispherectomy technique is summarized. RESULTS: The operation time was significantly shorter (mean, 3.6 h) than with the Rasmussen technique (mean, 6.3 h) and 25% shorter than with the transcortical perisylvian technique (mean, 4.9 h). The proportion of patients requiring blood replacements was lower (15 versus 58%), as was the mean amount of transfused blood. The mean follow-up period was 46 months; 88% of patients were in Engel Outcome Class I, 6% in Class III, and 6% in Class IV. CONCLUSION: The transsylvian keyhole procedure has been demonstrated to further reduce operation time and the need for blood replacement. It is most easily performed in cases with enlarged ventricles or perinatal ischemic cysts and is not recommended for hemimegalencephaly. The immediate seizure relief was satisfying. This minimal-exposure approach seems to be a satisfying alternative among possible functional hemispherectomy procedures.

Adolescent↗

PubMed2001

Fixed and dilated pupils after trauma, stroke, and previous intracranial surgery: management and outcome.

OBJECTIVES: To clarify whether different causative events (trauma, stroke, intracranial surgery), time of intervention, and treatment mode influence outcome, patients with fixed and dilated pupils (FDPs) in a prospective neurosurgical series were evaluated. METHODS: Ninety nine consecutive patients who presented with or developed one or two FDPs, were split into three groups according to the respective aetiology: 46 patients had a trauma, 41 patients a stroke (subarachnoid or intracerebral haemorrhage), and 12 patients had undergone previous elective intracranial surgery. Appropriate therapy was performed depending on the CT findings. Outcome was classified according to the Glasgow outcome scale (GOS). RESULTS: Overall mortality was 75%. In 15% outcome was unfavourable (GOS 2 and 3), and in 10% favourable (GOS 4, 5) at 24 month follow up. No differences in outcome were found between trauma, stroke, and postelective surgery groups. Unilaterally FDP was associated with a better chance of survival (46% v 13%; p<0.01). Age did not correlate with survival, but younger survivors had a significantly better outcome. Patients in whom an intracranial mass was removed surgically had a 42% survival rate, compared with 8% with conservative treatment (p<0.01). Patients with a shorter delay from FDPs to intervention had a better chance of recovery after trauma and previous intracranial surgery (p<0.05). No patient survived better than a vegetative state, if previous FDPs did not become reactive shortly after therapy. If both pupils became reactive on therapy, the chance of survival was 62%. Of these survivors 42% had a favourable outcome. CONCLUSION: Bilateral restoration of pupillary reactivity shortly after therapy is crucial for survival. Surgical evacuation of an intracranial mass, unilateral FDPs, early intervention, and younger age are related to better chances of survival or recovery. The prognosis of patients with FDPs after trauma, stroke, and previous elective intracranial surgery is similar.

Adolescent↗

PubMed2000

Androgen receptor mRNA expression in the human hippocampus.

The androgen receptor (AR) plays a central role in mediating androgen action. Since the hippocampus is a target of steroid modulation, we studied the expression of AR mRNAs in hippocampal tissue specimens from patients undergoing epilepsy surgery (n=42). AR mRNA expression was in the same order of magnitude than in prostate tissue, known for its high expression of AR. AR mRNA concentrations showed no significant difference in AR mRNA expression between men (49.3+/-8.0 arbitrary units (aU); mean+/-SEM) and women (54.3+/-11.2 aU) and no sex-specific hippocampal lateralization pattern was observed. No relationship could be detected between duration of epilepsy, individual seizure frequency, age of the patients and the expression levels of AR. The high expression of AR in the hippocampus suggests that this human brain area is an important target for androgen action.

Adult↗

PubMed2000

Corticosteroid receptor mRNA expression in the brains of patients with epilepsy.

The effects of corticosteroids in the brain are mediated through the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). We used a sensitive competitive RT-PCR assay to quantify the amounts of GR and MR mRNA in human brain tissue specimens from patients with focal epilepsies. GR and MR mRNAs were expressed at approximately the same levels in the temporal lobe, frontal lobe, and hippocampus as compared to tissues with high glucocorticoid/mineralocorticoid receptor expression (liver/kidney). GR and MR mRNA concentrations in the temporal lobe increased markedly during childhood and reached adult levels at puberty. GR and MR mRNA expression was significantly higher in the temporal lobe and frontal lobe cortex of women than in those of men. In women, MR and GR mRNA concentrations were markedly lower in hippocampal tissue than in frontal and temporal lobe cortex tissue. In conclusion, our data demonstrate sex- and site-dependent expression of corticosteroid receptor mRNA in the human brain.

Adolescent↗

PubMed1999

Analysing metabotropic glutamate group III receptor mediated modulation of synaptic transmission in the amygdala-kindled dentate gyrus of the rat.

Metabotropic glutamate receptors (mGluRs) provide a powerful control of synaptic transmission in the hippocampus and may serve as a target for drug development in human temporal lobe epilepsies. Agonists and antagonists at these receptors influence the development and propagation of seizures in some animal models of epilepsy. Experimental seizures can change the level of expression of mGluRs in the rat hippocampus. In the human dentate gyrus of patients suffering from temporal lobe epilepsy (TLE), group III mGluR mediated inhibition of synaptic transmission is almost lost in the sub-group with Ammon's horn sclerosis. We tested the modulation of synaptic transmission by the group III mGluR specific agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) in the dentate gyrus outer molecular layer in control and amygdala-kindled rats, a common model for TLE. Extracellular field potential recordings upon subthreshold stimulation of lateral perforant path fibers were measured simultaneously in the outer molecular layer and granule cell layer. Analysis of 'paired-pulse' characteristics in the absence and presence of L-AP4 and group III mGluR mediated inhibition of synaptic transmission in the lateral perforant path revealed no significant alterations in fully kindled rats. Since there is no evidence of altered L-AP4 responses, a loss of group III mGluR function, particularly that of subtype mGluR8, seems not necessary for the kindling epilepsy.

Amygdala↗

PubMed1999

Two electrophysiologically distinct types of granule cells in epileptic human hippocampus.

We investigated the electrophysiology of morphologically identified human granule cells with conventional current-clamp recordings. Slices were prepared from 14 human epileptic sclerotic hippocampi. Granule cells appeared to have a diverse electrophysiology. Each cell was distinguished by the shape of the afterhyperpolarization following single action potentials. Two types could be discerned: type I afterhyperpolarizations were monophasic and brief (typically 10-40 ms), whilst type II afterhyperpolarizations were biphasic and long (typically 50-100 ms). The two types also differed in their repetitive firing behaviour and action potential morphology: type I cells had significantly weaker spike frequency adaptation, lower action potential amplitude and smaller action potential upstroke/downstroke ratio. Thus, the firing pattern of type I cells resembled that of rodent dentate interneurons. In contrast, the corresponding parameters of type II cells were comparable to rodent dentate granule cells. Despite the distinct firing patterns, membrane properties were not different. The two types of cells also differed in their synaptic responses to stimulation of the perforant path. At strong suprathreshold stimulation intensity, type I cells always generated multiple action potentials, whereas type II cells usually spiked once only. Slow inhibitory postsynaptic potentials were not detected in type I neurons, but were easily identified in type II neurons. Extracellular recordings of perforant path-evoked field potentials in the cell layer confirmed that the majority of granule cells showed multiple discharges even when we recorded simultaneously from a type II cell that generated one action potential only. The morphology of both types of cells was characteristic of what has been described for primate dentate granule cells. Based on comparisons with previous studies on rodent and human granule cells, we tentatively hypothesize that: (i) the majority of granule cells from sclerotic hippocampus display an hyperexcitable epileptogenic electrophysiology; (ii) there is a subset of granule cells whose electrophysiology is preserved and is more comparable to granule cells from non-epileptic hippocampus.

Adult↗

PubMed1999

Reduced function of L-AP4-sensitive metabotropic glutamate receptors in human epileptic sclerotic hippocampus.

Human temporal lobe epilepsy is characterized by strong synaptic reorganization that leads to abnormal recurrent excitatory synaptic connections among hippocampal neurons. In addition, electrophysiological studies show that synaptic activity of the main afferent input to the hippocampus, the perforant path, is prolonged and amplified by changes in postsynaptic glutamate receptors. The current view is that these morphological and physiological abnormalities contribute significantly to the hyperexcitability seen in the hippocampus of temporal lobe epilepsy. Recently, it was found that presynaptic inhibitory metabotropic glutamate receptors are an important negative feedback mechanism that controls synaptic release of glutamate in the hippocampus. In this study, we assessed the functionality of this feedback system by investigating the metabotropic glutamate receptor mediated depression of excitatory synaptic transmission in surgically removed hippocampi from patients with marked synaptic reorganization (Ammon's horn sclerosis group) and from patients without detectable reorganization (lesion group). We report here that this control of synaptic transmission is lost in hippocampi from the Ammon's horn sclerosis group whereas this control is preserved in hippocampi from the lesion group. The data presented here suggest that the loss of feedback inhibition mediated by metabotropic glutamate receptors could be a further, previously not recognized, mechanism in the pathophysiology of temporal lobe epilepsy.

Action Potentials↗

PubMed1998

Treatment of accidental high dose intraventricular mezlocillin application by cerebrospinal fluid exchange.

An accidental high dose of intraventricular mezlocillin was given during antibiotic treatment for pneumonia in a patient admitted because of severe traumatic brain injury and occlusive hydrocephalus. Because of serial epileptic seizures not responsive to antiepileptic drug treatment, CSF exchange was performed. The CSF was drained through a ventricular catheter, while mock CSF was infused into the lumbar subarachnoid space. The patient soon recovered to her clinical status previous to intraventricular mezlocillin application. Side effects of CSF exchange were not seen. Under continued antiepileptic medication no more seizures occurred. It is concluded that high doses of intraventricular mezlocillin have proconvulsive effects. In this patient CSF exchange was a suitable means of preventing putatively permanent impairment of brain function caused by serial epileptic seizures due to intraventricular mezlocillin application.

Adult↗