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J Zentner

Publications and source records attributed to J Zentner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Reconsideration of biallelic inactivation of the VHL tumour suppressor gene in hemangioblastomas of the central nervous system.

OBJECTIVES: Cerebellar haemangioblastoma occurs sporadically or as a component tumour of autosomal dominant von Hippel-Lindau disease. Biallelic inactivation of the VHL tumour suppressor gene, which is located on chromosome 3p, has been shown to be involved in the pathogenesis of both tumour entities. Mechanisms of VHL inactivation are intragenic mutations, mitotic recombination events, and hypermethylation of the promoter region. The systematic and complete examination of these genetic and epigenetic phenomena in large series of von Hippel-Lindau disease related and sporadic hemangioblastomas has, thus far, not been performed. METHODS: In the largest series to date, 29 von Hippel-Lindau disease associated and 13 sporadic haemangioblastomas were investigated for all suggested inactivating mechanisms of the VHL gene using single strand conformational polymorphism (SSCP), loss of heterozygosity (LOH), and methylation analyses. Additionally, corresponding blood samples of all patients were screened for VHL germline mutations by SSCP and Southern blotting. RESULTS: Germline mutations were identified in 94% of patients with von Hippel-Lindau disease and their tumours and 62% of these hemangioblastomas showed LOH of chromosome 3p. Of the 13 sporadic tumours, 23% showed a single somatic mutation of the VHL gene that was not present in the germline. 3p LOH was identified in 50% of informative sporadic tumours. No von Hippel-Lindau disease related or sporadic tumour demonstrated VHL promoter hypermethylation. CONCLUSIONS: For most von Hippel-Lindau disease related haemangioblastomas, the inactivation or loss of both alleles of the VHL gene, as predicted by the Knudson two hit theory, is required. However, in a subset of tumours including most sporadic haemangioblastomas, the genetic pathways involved in tumorigenesis have yet to be defined and may represent alterations of a different pathway or pathways.

Adolescent↗
PubMed2000

Cortical reorganization following multiple subpial transection in human brain - a study with positron emission tomography.

We investigated the cortical activation pattern in a 30-year-old woman 4 years after multiple subpial transection (MST) of the right fronto-parietal cortex and six healthy controls using positron emission tomography. Sequential finger-to-thumb opposition at the frequency of 1.5 Hertz contralateral to the operated hemisphere was used as the activation paradigm. We found preserved cortical activation in the transected fronto-parietal cortex and additional activation of the prefrontal cortex bilaterally and the inferior parietal cortex contralaterally when compared with the control group. This activation pattern indicates that MST induces a rather selective lesion leaving the cortical structures functionally intact. However, it necessitates the recruitment of additional motor areas.

Adult↗
PubMed2000

Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy.

PURPOSE: Electrocorticograms of 32 patients with medically intractable seizures, recorded through intracranial electrodes, were retrospectively analyzed. The objective was to assess whether quantitative analysis of interictal spikes may be used for delineation of the epileptogenic zone. METHODS: We used a newly developed computer program for automatic detection of interictal spikes and averaging procedures. This allowed determination of the earliest spike of each spike cluster, the maximal averaged spike amplitude, the highest spike frequency, and the shortest averaged spike duration at each recording site. RESULTS: The following results were obtained: (a) Within a zone </=2 cm from the site of seizure origin, we localized the averaged earliest spike of a spike cluster in 27 (84%) of 32 patients, the highest averaged spike amplitude in 24 (75%) of 32, the shortest averaged spike duration in 22 (69%) of 32, and the maximal spike frequency in 17 (53%) of 32; (b) No correlation was found between spike occurrence and histopathology; (c) No evidence was found for decreased postoperative seizure control in patients with several multilobar or bihemispheric occurrence of spike clusters. CONCLUSIONS: The zones of the earliest spike and seizure origin demonstrate a high correlation that favors a common epileptic generator. Removal of all brain areas demonstrating spike clusters is unnecessary to achieve seizure control. Quantification of interictal spike activity is a valuable tool for localization of the seizure generator.

Adolescent↗
PubMed1999

Safety of single and repetitive focal transcranial magnetic stimuli as assessed by intracranial EEG recordings in patients with partial epilepsy.

The safety of single and repetitive (paired and quadruple) focal transcranial magnetic stimuli as possible inducers of epileptic discharges or clinically manifest seizures was investigated in 21 patients with intractable epilepsy during invasive presurgical monitoring. Subdural and/or intracerebral depth electrodes had been implanted in close proximity to the suspected epileptogenic zone, and the anticonvulsant medication had been reduced. Focal transcranial magnetic stimuli were applied by a Magstim QuadroPulse magnetic stimulator over the hand area of the motor cortex ipsilateral to the epileptogenic focus at intensities of 120% and 150% of motor threshold and additionally as close as possible to the suspected epileptogenic zone at 40-100% of maximal stimulator output. Stimulation did not induce any complex partial or secondary generalized tonic-clonic seizures. One patient with hippocampal sclerosis experienced an aura associated with rhythmic electroencephalographic discharges restricted to the ipsilateral intrahippocampal depth electrode after stimulation over his left temporal lobe. This patient, however, also had frequent spontaneously occurring auras with focal ictal discharges originating from this hippocampus. Interictal discharges were not influenced significantly by single or repetitive magnetic stimuli. In conclusion, from this study there is no evidence that single or serial focal transcranial magnetic stimuli activate epileptogenic foci. At least four high-frequency repetitive stimuli of high intensity may thus be applied with a low risk of seizure induction even in patients with low seizure threshold.

Adolescent↗
PubMed1999

Nosocomial infections in a neurosurgery intensive care unit.

In order to identify overall and site-specific nosocomial infection (NI) rates in patients receiving neurosurgical intensive care therapy, a prospective study was started in February 1997 in the eight-bed neurosurgical ICU of the University Hospital of Freiburg, Germany. Case records were reviewed twice a week, all microbiology reports were reviewed and ward staff was consulted. NI were defined according to the CDC-criteria and were categorised into specific infection sites. Within 20 months, 545 patients with a total of 5,117 patient days were investigated (mean length of stay: 9.4 days). 113 NI were identified in 90 patients (72 pts. with one, 13 with two and 5 with three infections, respectively). A moderate to high overall incidence (20.7/100 pts.) and a moderate incidence density (22.1/1,000 patient days) of NI in the neurosurgical ICU could be documented; these figures are well within the range of published data. Site specific incidence rates and incidence densities were: 1 bloodstream infection per 100 patients (0.9 central line-associated BSIs per 1,000 central line-days), 9 pneumonias per 100 patients (15.1 ventilator-associated pneumonias per 1,000 ventilator-days), 7.3 urinary tract infections per 100 patients (8.5 urinary catheter-associated UTIs per 1,000 urinary catheter-days). Additionally, 1.1 cases of meningitis, 0.7 brain abscesses/ventriculitis, and 1.7 other infections (surgical site infection, bronchitis, catheter related local infection, diarrhoea) were documented per 100 patients, respectively. 14.6% of isolated pathogens were E. coli, 10.2% enterococci, 9.6% S. aureus, 6.4% CNS, 6.4% Klebsiella spp., 5% Enterobacter spp. and 5% Pseudomonas spp. In 11 cases of NI no pathogen could be isolated.

Adolescent↗
PubMed1999

Minimally invasive stereotactically-guided extirpation of brain stem cavernoma with the aid of electrophysiological methods.

The surgical extirpation of brain stem cavernomas always includes a risk of neurological deficits. To minimize the risk of deficits and control the motor and sensory function intraoperative monitoring of SEP and MEP seems to be helpful. The high density of motor and sensory fibers within the brain stem makes bilateral intraoperative monitoring necessary. The following case demonstrates a stereotactically-guided supratentorial, transventricular approach for extirpation of a brain stem cavernoma. Sensory and motoric functions were observed by transcranial recording of SEP's and by transcranial stimulation of motor cortex.

Adult↗
PubMed1999

Influence of fentanyl, alfentanil, and sufentanil on motor evoked potentials.

The effects of the opioids fentanyl, alfentanil, and sufentanil on motor pathways were studied in a total of 30 rabbits. Compound muscle action potentials (CMAP) were recorded from the extensor muscles of the upper extremity as well as evoked spinal cord potentials (ESCP) from the thoracic epidural space in response to electrical stimulation of the motor cortex. After establishing stable baseline values, an equipotent intravenous bolus of one of the three opioids was applied that abolished reflex motor response to noxious stimulation. Motor evoked potentials (MEP) were recorded from the time of bolus administration until recovery of MEP amplitudes and latencies. Afterwards, the opioids were administered continuously with cumulative dosage up to total absence of motor evoked response. Our results show a dose-dependent suppression of the CMAP: When reflex movement to noxious stimulation was extinguished, we found a significant (P < .001) reduction of the amplitudes to 34+/-18% (mean +/- SD) in the fentanyl group, to 43+/-24% in the alfentanil group, and to 53+/-20% of baseline values in the sufentanil group. Increasing opioid plasma levels were associated with complete extinction of the CMAP. We hypothesize that the descending volleys within motor pathways are mainly inhibited at a spinal level, because ESCP, particularly the number of spinal I-waves, are not severely affected even when CMAP are completely suppressed. In conclusion, intraoperative monitoring of descending pathways by means of MEP during anesthesia with opioids is feasible at anesthetic plasma concentrations maintaining a surgical level of analgesia. Even with high opioid plasma levels, a valid MEP monitoring could be performed evaluating neural activity of spinal MEP.

Action Potentials↗
PubMed1999

The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system.

OBJECTIVES: Haemangioblastoma of the CNS occurs as a sporadic entity and as a manifestation of the autosomal dominant von Hippel-Lindau disease with the major additional components retinal angioma, renal cancer, and pheochromocytoma. Genetic testing for germline mutations predisposing to von Hippel-Lindau disease has been available since identification of the VHL tumour suppressor gene. The impact of this testing was evaluated in patients with haemangioblastomas seen in this centre. METHODS: A register and database of patients with symptomatic haemangioblastomas for the last 15 years was evaluated. The VHL gene was analysed by the SSCP method for all exons and Southern blotting for mutations and deletions of the gene. RESULTS: 141 patients with haemangioblastoma of the CNS were registered. In 81 patients (57%) there was a disease predisposing germline mutation including eight novel mutations. Population related calculation of patients from the administrative district of Freiburg disclosed VHL germline mutations in 22% of the patients with haemangioblastoma. Analysis of mutation carriers for clinical information suggestive of the syndrome showed (1) a positive family history of a brain tumour in 50%, (2) a history for the patient of extracranial manifestations in 36% (retinal angioma 30%, pheochromocytoma 6%), and (3) 19% presenting with multiple brain tumours when first admitted. By genetic testing of haemangioblastoma patients without any indications of von Hippel-Lindau disease mutation carriers were identified in 14%. Sensitivity of VHL germline testing was 86%. CONCLUSIONS: DNA analysis for VHL germline mutations is clearly superior to clinical information in the diagnosis of von Hippel-Lindau disease. Although the percentage of von Hippel-Lindau disease associated haemangioblastoma decreases after the fourth decade of life and is infrequent in patients without other symptomatic lesions and a negative family history, it is recommended that every patient with CNS haemangioblastoma should be screened for von Hippel-Lindau disease germline mutations. This provides the key information and enables screening for extraneurological tumours of the patients and investigations of the patient's family to ameliorate management of von Hippel-Lindau disease.

Adolescent↗
PubMed1999

Clinical relevance of amygdala sclerosis in temporal lobe epilepsy.

OBJECT: The goal of this study was to define the incidence and clinical significance of amygdala sclerosis (AS) in patients with temporal lobe epilepsy (TLE). METHODS: Surgical specimens of the lateral amygdaloid nucleus and the hippocampus excised from 71 patients who were treated for medically intractable TLE were quantitatively evaluated using a computer-assisted image-analysis system and compared with 10 normal autopsy specimens. Densities of neurons and reactive astrocytes in the patients with TLE were correlated with clinical, neuropsychological, and depth-electroencephalography data. The neuron counts of the lateral amygdaloid nucleus did not correlate with various presumed etiological factors of TLE including hereditary seizures, birth complications, febrile convulsions, traumatic brain injury, infections, seizure semiology, and epileptological outcome. However, patient age at surgery was significantly higher (mean difference 10 years) when AS was present, as compared with patients without AS (p < 0.01). Seizure origin, as determined by using amygdalohippocampal depth electrodes, did not correlate with the presence or absence of AS. Neuropsychologically, there was a significant correlation between the neuronal densities of the lateral amygdaloid nucleus and both preoperative visual recognition and postoperative deterioration of short-term verbal memory performance (p < 0.05). CONCLUSIONS: Except for the relatively long history of epilepsy, the presence of AS is not associated with specific clinical or electrocorticographic features of mesial TLE. However, patients without AS are particularly at risk for deterioration of short-term verbal memory following amygdalohippocampectomy.

Adolescent↗
PubMed1999

[Motor evoked potentials during embolization of arteriovenous malformations for the detection of ischemic complications].

Motor evoked potentials (MEP) recorded from the distal extremity muscles in response to transcranial magnetoelectrical stimulation were analyzed in a total of 10 patients during embolization of arteriovenous malformations (AVM) localized in frontal and parietal lobe (N = 5), in the temporal lobe (N = 2), in the the brain stem (N = 1), in the medulla oblongata (N = 1), and in the cerebellum (N = 1). The objective of this study was to clarify whether MEP allow reliable detection of ischemic complications during these procedures. Stable potentials as observed in 8 of 10 patients coincided in every case with an uneventful neurological outcome. Temporary significant prolongation of the central motor conduction time (CMCT) was observed in 2 patients. Both patients demonstrated a transient hemiparesis after the procedure, probably caused by ischemia. Our results clearly indicate that MEP are able to detect ischemic events during embolization of AVMs. Therefore, the use of MEP as a monitor of pyramidal function during endovascular therapeutic procedures seems to be promising.

Adolescent↗
PubMed1999

Calcium channels involved in K+- and veratridine-induced increase of cytosolic calcium concentration in human cerebral cortical synaptosomes.

Human cerebral cortical synaptosomes were used to study voltage-dependent Ca(2+) channels mediating calcium influx in human axon terminals. Synaptosomes were depolarized by elevation of the extracellular K(+) concentration by 30 mM or by the addition of veratridine (10 microM). Increase in cytosolic concentration of calcium [Ca(2+)](i) induced by either stimulus was abolished in the absence of extracellular Ca(2+) ions. omega-Agatoxin IVA inhibited the K(+)-induced [Ca(2+)](i) increase concentration-dependently (IC(50): 113 nM). omega-Conotoxin GVIA (0.1 microM) inhibited K(+)-induced [Ca(2+)](i) increase by 20%. omega-Conotoxin MVIIC (0.2 microM) caused an inhibition by 85%. Nifedipine (1 microM) had no effect on K(+)-induced [Ca(2+)](i) increase. Veratridine-induced increase in [Ca(2+)](i) was inhibited by omega-conotoxin GVIA (0.1 microM) and omega-Agatoxin IVA (0.2 microM; by about 25 and 45%, respectively). Nifedipine inhibited the veratridine-evoked [Ca(2+)](i) increase concentration-dependently (IC(50): 4.9 nM); Bay K 8644 (3 microM) shifted the nifedipine concentration-response curve to the right. Mibefradil (10 microM) abolished the increase in [Ca(2+)](i) evoked by K(+) and reduced the increase evoked by veratridine by almost 90%. KB-R7943 (3 microM) an inhibitor of the Na(+)/Ca(2+) exchanger NCX1, decreased the increase in [Ca(2+)](i) evoked by veratridine by approximately 20%. It is concluded that the increase in [Ca(2+)](i) after K(+) depolarization caused by Ca(2+) influx predominantly via P/Q-type Ca(2+) channels and after veratridine depolarization via N- and P/Q-type, but also by L-type Ca(2+) channels. The toxin- and nifedipine-resistant fraction of the veratridine response may result both from influx via R-type Ca(2+) channels and by Ca(2+) inward transport via Na(+)/Ca(2+) exchanger.

Adolescent↗
PubMed1998

The need for repeat angiography in subarachnoid haemorrhage.

This study was designed to assess the necessity for a second angiogram study in patients in whom initial angiography after primary subarachnoid haemorrhage (SAH) was negative. During a 12-year period, 122 of 694 patients (17.5%) had negative initial angiograms. CT, available for 98 patients, showed a preponderance of subarachnoid blood in the perimesencephalic cisterns in 50 of 73 patients (68.5%) in whom blood was visible on CT. Angiography, repeated in 67 patients, revealed an aneurysm in 4 (6%): 2 had an aneurysm of the anterior communicating artery, 1 of the posterior inferior cerebellar artery, and 1 of the P2 segment of the posterior cerebral artery. CT showed subarachnoid blood in the interpeduncular and ambient cisterns in this last case, and a preponderance of subarachnoid blood outside the perimesencephalic cisterns in the remaining 3 patients.

Adolescent↗
PubMed1998

Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy.

The present study investigated the effect of frontal lobe surgery on "cognitive functions", which have previously been shown to be discriminative in the evaluation of non-resected patients with frontal lobe epilepsy (FLE). The cognitive outcome was evaluated with particular consideration of the side (left/right), the site (lateral, orbital, mesial, premotor/SMA), the type of surgery (resections vs. resections plus multiple subpial transections; MST), and seizure outcome. The evaluation is based on 33 patients with left (n = 17) or right (n = 16) frontal surgery. Forty-five patients who underwent successful left (n = 21) or right (n = 24) temporal lobectomy served as controls. The neuropsychological examination covered speed/attention, motor sequencing/coordination, response maintenance/inhibition, short-term memory, and language. With the exception of short-term memory, the chosen tests were discriminative in determining preoperative frontal lobe dysfunctions but they did not differentiate patients with a different lateralization or localization of the frontal focus. At the 3 month follow-up examination, patients with temporal lobectomy had improved frontal functions, whereas patients with frontal lobe surgery showed a mild deterioration. Within the frontally resected group, completely seizure-free patients had significantly improved short-term memory. Further consideration of the side, site and the type of the frontal resection indicated that patients with premotor/SMA surgery and patients with precentral/central MST had additional impairment after surgery. Premotor/SMA resections led to a deterioration in response maintenance/inhibition and if performed left sided also to deteriorated language functions. The latter impairment could be clearly related to transient aphasia directly after surgery. Irrespective of pareses observed immediately after surgery, patients with MSTs of the precentral/central areas displayed additional problems in motor coordination at the follow-up examination. In this group the seizure outcome was also less favourable. In summing up, frontal lobe surgery does not cause any considerable additional impairment in the short-term follow-up. However, caution is recommended when surgery or MST affect functional relevant cortex (here the prefrontal/SMA and precentral/central area). Finally, a release of functions associated with frontal areas not affected by surgery is suggested, when seizures are successfully controlled by surgery.

Adult↗
PubMed1998

Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy.

The present study investigated the effect of frontal lobe surgery on "cognitive functions", which have previously been shown to be discriminative in the evaluation of non-resected patients with frontal lobe epilepsy (FLE). The cognitive outcome was evaluated with particular consideration of the side (left/right), the site (lateral, orbital, mesial, premotor/SMA), the type of surgery (resections vs resections plus Multiple Subpial Transections), and seizure outcome. The evaluation is based on 33 patients with left (n = 17) or right (n = 16) frontal surgery. Forty-five patients who underwent successful left (n = 21) or right (n = 24) temporal lobectomy served as controls. The neuropsychological examination covered speed/attention, motor sequencing/coordination, response maintenance/inhibition, short-term memory, and language. With the exception of short term memory, the chosen tests were discriminative in determining preoperative frontal lobe dysfunctions but they did not differentiate patients with a different lateralization or localization of the frontal focus. At the three month follow-up examination, patients with temporal lobectomy had improved frontal functions, while patients with frontal lobe surgery showed a mild deterioration. Within the frontally resected group, completely seizure free patients had significantly improved short-term memory. Further consideration of the side, site and the type of the frontal resection indicated that patients with premotor/SMA surgery and patients with precentral/central MST had additional impairment after surgery. Premotor/SMA resections led to a deterioration in response maintenance/inhibition and if performed left sided also to deteriorated language functions. The latter impairment could be clearly related to transient aphasia directly after surgery. Irrespective of pareses observed immediately after surgery, patients with MST's of precentral/central areas displayed additional problems in motor coordination at the follow-up examination. In this group the seizure outcome was also less favorable. In summing up, frontal lobe surgery does not cause any considerable additional impairment in the short term follow-up. However, caution is recommended when surgery or MST affect functional relevant cortex (here the prefrontal/SMA and precentral/central area). Finally, a release of functions associated to frontal areas not affected by surgery is suggested, when seizures are successfully controlled by surgery.

Adolescent↗
PubMed1998

Vasospastic reactions in response to the transsylvian approach.

BACKGROUND: Cerebral vasospasm may occur with various neurosurgical procedures such as the treatment of intracranial aneurysms or of skull base tumors. This study was designed to provide more insight into the nature of vasospastic reactions in response to surgical manipulation alone. METHODS: Twenty patients who underwent selective amygdalohippocampectomy for medically intractable epilepsy using the transsylvian approach were studied prospectively. Transcranial Doppler ultrasound (TCD) was used for examination of blood flow velocities within the basal cerebral arteries before and after the operation. RESULTS: Three types of vascular reactions were observed: 1) No or only minimal reaction with increase of the blood flow velocities less than 50% as compared with the preoperative baseline values (N = 4); 2) Ipsilateral/bilateral increase of the blood flow velocities more than 50% of the baselines (N = 14); 3) Paradoxic reactions such as early postoperative resistance flow and contralateral rise of the blood flow velocities (N = 2). There was no morbidity or mortality in this series. CONCLUSIONS: The transsylvian approach is associated with significant changes in hemodynamics--partially caused by mechanical manipulation and partially by the degradation of blood--although the risk of neurological deterioration seems to be low.

Adolescent↗
PubMed1998

Continuous external CSF drainage--a perpetual problem in neurosurgery.

BACKGROUND: Continuous external CSF drainage represents a well established procedure which has been improved by many technical contributions. We present our experience in a prospective study of 212 needle trephinations in 165 consecutive patients with a new screw fixation device. METHODS: The entire procedure is performed at the bedside under local anesthesia with a twist drill. The trephination needle is inserted into the self-tapping cannulated screw fixed to the skull. RESULTS: The mean operation time was 6 min, and the duration of ventricular drainage ranged from 2 h to 44 days. Ninety-one percent (N = 193) of ventricular needles in our series were placed at the first targeting attempt. ICP-monitoring and -therapy (88%) were the main indications for needle trephination in our study. During the study period we observed needle associated complications, such as intracerebral hemorrhages (N = 2, 1%) and infections (N = 17, 8%). CONCLUSIONS: Concerning infection, primary insufficient fixation, and general surgical handling, we found a clear learning curve during the course of our study. In spite of the initial problems at the time of introduction we have to emphasize the outstanding advantages of the new ventriculostomy device: It is a time-saving bedside procedure equipped with an optimum fixation device and it enables uncomplicated exchange of the needle in case of obstruction.

Adolescent↗