Biomedical subjects

Heinz-Gregor Wieser

Publications and source records attributed to Heinz-Gregor Wieser.

12 recordsLinked to original sources

PubMed2006

Magnetic iron compounds in the human brain: a comparison of tumour and hippocampal tissue.

Iron is a central element in the metabolism of normal and malignant cells. Abnormalities in iron and ferritin expression have been observed in many types of cancer. Interest in characterizing iron compounds in the human brain has increased due to advances in determining a relationship between excess iron accumulation and neurological and neurodegenerative diseases. In this work, four different magnetic methods have been employed to characterize the iron phases and magnetic properties of brain tumour (meningiomas) tissues and non-tumour hippocampal tissues. Four main magnetic components can be distinguished: the diamagnetic matrix, nearly paramagnetic blood, antiferromagnetic ferrihydrite cores of ferritin and ferrimagnetic magnetite and/or maghemite. For the first time, open hysteresis loops have been observed on human brain tissue at room temperature. The hysteresis properties indicate the presence of magnetite and/or maghemite particles that exhibit stable single-domain (SD) behaviour at room temperature. A significantly higher concentration of magnetically ordered magnetite and/or maghemite and a higher estimated concentration of heme iron was found in the meningioma samples. First-order reversal curve diagrams on meningioma tissue further show that the stable SD particles are magnetostatically interacting, implying high-local concentrations (clustering) of these particles in brain tumours. These findings suggest that brain tumour tissue contains an elevated amount of remanent iron oxide phases.

Brain Neoplasms↗

PubMed2006

Altered expression of alpha3-containing GABAA receptors in the neocortex of patients with focal epilepsy.

Impaired transmission in GABAergic circuits is thought to contribute to the pathogenesis of epilepsy. Although it is well established that major reorganization of GABA(A) receptor subtypes occurs in the hippocampus of patients with medically refractory temporal lobe epilepsy (TLE), it is unclear whether this disorder is also associated with alterations in GABA(A) receptor subtypes in the neocortex. Here we have investigated immunohistochemically the subunit composition and neocortical distribution of three major GABA(A) receptor subtypes using antibodies specifically recognizing the subunits alpha1, alpha2, alpha3, beta2/3 and gamma2. Cortical tissue was obtained at surgery from patients with TLE and hippocampal sclerosis (HS; n = 9), TLE associated with neocortical lesions (non-HS; n = 12) and frontal lobe epilepsy (FLE; n = 5), with post-mortem samples serving as controls (n = 4). A distinct laminar and neuronal expression pattern of the alpha-subunit variants was found across the neocortical regions examined in the temporal and frontal lobes in both control and patient tissue samples. In the five patients with FLE, GABA(A) receptor subunit staining was unchanged as compared to controls. In patients with TLE we observed a marked decrease in alpha3-subunit staining in the superficial neocortical layers (I-III), but no change in the deep layers (V and VI) or in the expression pattern of the alpha1 and alpha2-subunits. Reduced expression in alpha3-containing GABA(A) receptors was detected in six out of nine patients of the HS group and four out of twelve patients of the non-HS group. Histopathological changes were present in eight out of the ten patients with decreased alpha3-subunit staining. The selective reduction in alpha3-containing GABA(A) receptors was confirmed using semiquantitative measurements of optical density (OD). The specific changes unique to alpha3-subunit expression in the superficial neocortical layers of patients with TLE suggest that this subtype is of particular significance in the reorganization of cortical GABAergic systems in focal epilepsy.

Adolescent↗

PubMed2006

Beta activity in status epilepticus.

Focal beta activity on scalp EEG is a rare seizure pattern that has most extensively been studied in patients undergoing evaluation for epilepsy surgery. However, ictal beta activity is uncommon beyond this population and has not been reported in human status epilepticus. We observed ictal focal beta activity as the predominant seizure pattern in a patient with refractory status epilepticus. Continuous left temporal beta activity clinically correlated with complex partial semiology on video-EEG.

Anticonvulsants↗

PubMed2005

Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis.

Multidrug resistance protein, also referred as P-glycoprotein (P-gp, MDR1; ABCB1) and multidrug resistance-associated protein (MRP) 1 (ABCC1) and 2 (ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascular endothelial cells (HBMEC) from epileptic patients (HBMEC-EPI) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue, the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that MDR1, MRP1 as well as MRP5 (ABCC5) and MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood-brain barrier (BBB).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Levetiracetam in patients with refractory epilepsy: results of the SKATE trial in Austria, Germany and Switzerland.

PURPOSE: To further evaluate the safety, efficacy and optimal dose of levetiracetam (LEV) in daily clinical practice among patients with uncontrolled partial epilepsy with or without secondary generalization. METHODS: In this phase IV, open-label, 16-week community-based study, 178 at least 16-year-old patients with refractory focal epilepsy were treated with 1000, 2000 or 3000 mg levetiracetam as adjunctive therapy. All patients started with 500 mg LEV b.i.d. (1000 mg/day); the dose was adjusted in 2-week intervals up to 1500 b.i.d. (3000 mg/day) depending on seizure control and tolerability. The main objectives were the adverse events, the percentage reduction in partial and total seizure frequency per week from baseline and the retention rate, defined as the percentage of patients taking LEV at the end of the 16-week treatment period. RESULTS: Of the 178 patients who took at least one dose of LEV 151 completed the study. Thus, the retention rate (number of patients taking LEV at the end of the 16-week treatment period) was 84.8%. Most frequently reported adverse events were asthenia, dizziness, headache, nausea, somnolence and hostility; the majority of these events were of mild to moderate intensity. The seizure-free rate of the ITT population with focal seizures was 16.7%, for all seizures 16.6%; the median reduction of focal seizure frequency was 47.6%, and 46.5% for all seizures. The 50% responder rate was 46.6% for focal seizures and 45.1% for all seizures. CONCLUSION: Add-on treatment with LEV in patients with refractory partial epilepsy was safe and effective in this study.

Adolescent↗

PubMed2005

Characterization of iron compounds in tumour tissue from temporal lobe epilepsy patients using low temperature magnetic methods.

Excess iron accumulation in the brain has been shown to be related to a variety of neurodegenerative diseases. However, identification and characterization of iron compounds in human tissue is difficult because concentrations are very low. For the first time, a combination of low temperature magnetic methods was used to characterize iron compounds in tumour tissue from patients with mesial temporal lobe epilepsy (MTLE). Induced magnetization as a function of temperature was measured between 2 and 140 K after cooling in zero-field and after cooling in a 50 mT field. These curves reveal an average blocking temperature for ferritin of 10 K and an anomaly due to magnetite at 48 K. Hysteresis measurements at 5 K show a high coercivity phase that is unsaturated at 7 T, which is typical for ferritin. Magnetite concentration was determined from the saturation remanent magnetization at 77 K. Hysteresis measurements at various temperatures were used to examine the magnetic blocking of magnetite and ferritin. Our results demonstrate that low temperature magnetic measurements provide a useful and sensitive tool for the characterisation of magnetic iron compounds in human tissue.

Astrocytoma↗

PubMed2005

Awake surgery for glioma resection in eloquent areas--Zurich's experience and review--.

Awake surgery was performed in a series of 21 patients with gliomas in eloquent areas with the use of intraoperative electrical mapping. Gross total removal was performed in 18 patients. There was no operative mortality. Postoperative findings included no change in symptoms and signs in 10 patients, improvement of the preoperative deficit in 11 patients. Four patients had improved Karnofsky performance status (KPS) scores after surgery, 17 patients were stable, and no patient had lower KPS score. Extensive radical resection of gliomas prolongs the overall survival and improves the patient's quality of life. However, surgical resection of gliomas located within the sensorimotor or language areas remains a neurosurgical challenge in reducing eloquent neurological sequelae. Awake surgery with intraoperative functional mapping is a safe approach to maximize the extent of tumor removal and to minimize the resultant neurological deficits in the treatment of glioma involving the eloquent cortex.

Adult↗

PubMed2004

Can memories kindle nonconvulsive behavioral seizures in humans? Case report exemplifying the "limbic psychotic trigger reaction".

We present three hypotheses-(1) the limbic psychotic trigger reaction (LPTR) is a form of nonconvulsive behavioral seizures (NCBS), (2) kindling may occur in the LPTR, and (3) kindling may occur with memory stimuli-and report a case that may exemplify a LPTR kindled by memory and triggered by light and smell. The LPTR has a primate model, in which NCBS are kindled by intermittent exposure to actual subthreshold stimuli. In humans, we propose that such triggering stimuli can be revived by memory alone. Thus, individualized stimuli can trigger partial limbic seizures or seizure-like bizarre episodes with a transient loss of frontal control functions. We present a case of paroxysmal episodes of out-of-character, bizarre, unplanned nonvoluntary acts that occurred with flat affect and without drive motivation (e.g., "fire setting"). Implicated is a transient state of limbic "paleo-consciousness" with preserved memory, autonomic arousal, and first-time brief psychosis (e.g., olfactory, visual hallucinations and depersonalization with olfactory attributes). As in kindled primates, LPTR patients do not show a consistent pattern of morphological brain abnormality; half have had an abnormal electroencephalogram, computed tomography scan, or magnetic resonance image at some time during their lives, and half (including the new patient) have had closed head injuries.

Adult↗

PubMed2004

ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis.

Experts discussed the definition, natural history, pathologic features, pathogenesis, electroclinical, neurophysiological, neuropsychological, structural and functional imaging findings, as well as surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). After a long-lasting consensus process the ILAE Commission Neurosurgery of epilepsy accepted the resulting conclusions as state-of-the art report on MTLE-HS. The majority of contributors considered MTLE-HS to represent a sufficient cluster of signs and symptoms to make up a syndromic diagnostic entity.

Cognition Disorders↗

PubMed2003

Amino acid composition of brain cysts: levels of excitatory amino acids in cyst fluid fail to predict seizures.

A recent study describing two epileptic patients with brain cysts has suggested that elevated concentrations of excitatory amino acids in cysts may play a role in induction and maintenance of epileptogenesis [Epilepsy Res. 28 (1997) 245]. Here, we report that only in 3 out of 22 patients with brain cysts undergoing brain surgery cyst fluids displayed highly increased amounts of the excitatory amino acids aspartate and/or glutamate. Two of these patients experienced epileptic seizures prior to neurosurgical intervention. Thus, highly increased excitatory amino acid levels are present only in a subset of patients with brain cysts. Our observation that one patient with highly increased glutamate and aspartate concentrations in the cyst did not display seizures or typical epileptiform potentials in the EEG questions that these excitatory amino acids in the cyst fluid are directly involved in epileptogenicity. This patient displayed an increased level of adenosine in the cyst fluid, which is known to have anticonvulsant properties and might provide protection from seizures. In summary, there is no evidence for a close correlation between excitatory amino acids in brain cysts and the occurrence of seizures.

Adenosine↗

PubMed2003

Antiepileptic drug treatment before and after selective amygdalohippocampectomy.

Retrospectively, we analyzed pre and postoperative (po) AED treatment in relation to long-term annual seizure outcome in the Zurich selective amygdalohippocampectomy (AHE) series. In 376 patients (hippocampal sclerosis ("HS"), n:185; other lesions ("lesional"), n:191) with a follow-up of more than 1 year, in the last available outcome (lao), 60% were seizure- and aura-free (ILAE Class 1). During the year prior to surgery, in the "HS" group a mean of 2.3 +/- 0.8 AEDs were taken. The percentage of patients without AEDs increases to 36.1% in the po years 1-5 (po year 5: "HS" (n:133) 27.8%; "lesional" (n:111) 45.9%). In po years 7-11 this percentage is between 40 and 43% (po year 10: "HS" (n:75) 29.3%; "lesional" (n:65) 55.4%). In the ILAE Class 1a, at po year 5 63/85 (74.1%) patients have discontinued AED intake. At lao 36.2% of patients were off AEDs and additional 18.9% had a "substantial" reduction (i.e. from polytherapy to monotherapy, or a reduction of the existing monotherapy by at least 66% compared to the year before AHE). The relapse rate is similar for patients who were free of disabling seizures (a) for > or =1 year and without AEDs (17.1%), (b) immediately after surgery with or without AEDs (18.4%), and (c) had a "substantial" AED reduction over the entire follow-up period (18.9%). The rate of re-gained full seizure control, however, is significantly better for group (b) compared to (c) (77% versus 53%). 10.9% of patients showed the "running down phenomenon," i.e. had seizures during the first po year, but then became seizure-free for 1 or more years. The percentage of patients free of "disabling" seizures, who did not follow the medical advice to discontinue/reduce AEDs, is about 30% after the 10th po year. In the 15th po year this figure is 4.2 times higher for "HS" versus "lesional" patients. We conclude that the time of discontinuation of AEDs after AHE should be tailored based on the results of the presurgical evaluation, the early po seizure outcome, the histopathological findings, the intraoperative ECoG findings and the po EEG. In an optimal constellation, "substantial" AED reduction with the goal of a monotherapy can be advised 1 year and discontinuation 2 years after surgery.

Amygdala↗

PubMed2002

Epilepsy with severe abdominal pain.

We describe a patient who experienced recurrent episodes of abdominal pain as a prominent feature of his seizure disorder. Treatment with carbamazepine could not prevent these painful sensations, but a selective amygdalohippocampectomy completely controlled the episodic pain and the seizures associated with loss or alteration of consciousness. During the presurgical evaluation, the episodes of abdominal pain correlated with amygdalar seizure discharges.

Abdominal Pain↗