Biomedical subjects

Carlo Schaller

Publications and source records attributed to Carlo Schaller.

At least 19 recordsLinked to original sources

PubMed2006

Cerebrospinal fluid obstruction and malabsorption in human neonatal hydrocephaly.

INTRODUCTION: The pathophysiology involved in human neonatal high-pressure hydrocephalus (HC) includes both cerebrospinal fluid (CSF) malabsorption and obstruction. OBJECTIVE: The aim was to estimate the relative contribution between CSF malabsorption and obstruction in three different etiological groups of neonatal high-pressure HC by assessment of specific CSF biomarkers indicative of growth factor- and fibrosis-related CSF malabsorption (transforming growth factor beta-1 (TGF beta-1), aminoterminal propeptide of type 1 collagen (PC1NP)]. MATERIALS AND METHODS: Patients were subdivided into three groups. Group A: spina bifida HC (n=12); group B: non-haemorrhagic triventricular HC (n=4); and group C: posthaemorrhagic HC (n=6). To exclude for confounding differences in pro-inflammatory state between the three groups, interleukin-6 (IL-6) CSF concentrations were assessed. Consecutively, the CSF concentrations of TGF beta-1 and PC1NP were compared between the different groups. RESULTS: Median CSF concentrations of IL-6 were low and did not differ between groups. Median CSF concentrations of PC1NP were significantly lower in group A (median: 180 ng/ml, range 90-808) than in group C (median: 1,060, range 396-1194; p=0.002). TGF beta-1 concentrations were significantly higher in group C (median 355 pg/ml, range 129-843) than in groups A (median 103, range 78-675 pg/ml) and B (median 120 pg/ml, range 91-188; p=0.01 and 0.03, respectively). CONCLUSIONS: In neonatal posthaemorrhagic HC, high concentrations of malabsorption-related biomarkers contrast with lower concentrations in SB and non-haemorrhagic triventricular HC. During the early development of high pressure HC in SB neonates, CSF biomarkers strongly indicate that CSF obstruction contributes more to the development of HC than malabsorption.

Collagen Type I↗

PubMed2006

Hippocampus proper distinguishes between identified and unidentified real-life visual objects: an intracranial ERP study.

Converging evidence indicates that the medial temporal lobe participates not only in memory but also in visual object processing. We investigated hippocampal contributions to visual object identification by recording event-related potentials directly from within the hippocampus during a visual object identification task with spatially filtered pictures of real objects presented at different levels of filtering. Hippocampal responses differentiated between identified and unidentified visual objects within a time window of 200-900 ms after stimulus presentation: identified objects elicited a small negative component peaking around 300 ms (hippocampal-N300) and a large positive component, around 650 ms (hippocampal-P600), while the N300 was increased and the P600 was reduced in amplitude in response to unidentified objects. These findings demonstrate that the hippocampus proper contributes to the identification of visual objects discriminating from the very early between identified and unidentified meaningful visual objects.

Adult↗

PubMed2006

Chromosomal translocations fusing the BCL6 gene to different partner loci are recurrent in primary central nervous system lymphoma and may be associated with aberrant somatic hypermutation or defective class switch recombination.

Primary central nervous system lymphomas (PCNSLs) are diffuse large B cell lymphomas confined to the brain. Only minimal data exist on chromosomal aberrations underlying PCNSLs. We studied 41 PCNSLs by fluorescence in situ hybridization for breakpoints affecting the BCL6 locus in chromosomal band 3q27. Of 37 cases evaluable, 14 (38%) carried a breakpoint in the BCL6 locus. Two of these showed juxtaposition of BCL6 to the IGH locus. In 4 cases, the BCL6 breakpoints were cloned using long-distance inverse polymerase chain reaction. All breakpoints were located within the BCL6 major translocation cluster. The translocation partners were the IGH gene in 14q32.33, the IGL gene in 22q11.22, and the histone 1 H4I gene in 6p22.1. In the fourth case, a deletion in 3q leads to loss of an 837-kb fragment extending from the first intron of BCL6 to the third intron of the lipoma-preferred partner (LPP) gene. This deletion may bring the BCL6 gene under the control of regulatory elements of the LPP gene or the miRNA-28 gene located in intron 4 of LPP. DNA sequence analysis of the junctional sequences provided evidence that aberrant class switch recombination or somatic hypermutation may be involved in the generation of BCL6 translocations.

Base Sequence↗

PubMed2006

Habituation of auditory evoked potentials in intracranial and extracranial recordings.

Effects of stimulus repetition are investigated in short-term habituation experiments. In these experiments, trains of stimuli are applied with longer intervals of no stimulation between the trains. In scalp recordings, an amplitude and latency decrease of the auditory N100 is usually observed at the beginning of the train. This contrasts to a recent finding with intracranial recordings, exhibiting an effect on N100 amplitude, but not on its latency. In the current study, P50 and N100 were simultaneously recorded intra- and extracranially in epilepsy patients. The amplitudes of P50 and N100 decreased in both recordings, whereas the P50 latency was not significantly affected. A latency decrease was revealed for the extracranially recorded N100, but not for the intracranial N100. This dissociation between the intracranial and scalp recordings might be explained by a different sensitivity of the two measurements for N100 generators.

Adult↗

PubMed2006

Percutaneous fetoscopic patch coverage of spina bifida aperta in the human--early clinical experience and potential.

OBJECTIVE: The current operative approach for fetal repair of spina bifida aperta requires maternal laparotomy and hysterotomy. Following technical feasibility studies in sheep, we performed percutaneous fetoscopic patch coverage of this lesion in 3 human fetuses between 23 + 4 and 25 + 3 weeks of gestation. METHODS AND RESULTS: Whereas the patch detached in the first case 3 weeks after the procedure, it covered the exposed neural tissue in the 2 other fetuses beyond their delivery. Two of the three children survived, but 1 unexpectedly died from a ventilation problem in its 3rd week of life. In 1 of the 2 survivors, ventriculoperitoneal shunt insertion was delayed. CONCLUSIONS: Percutaneous fetoscopic patch coverage of spina bifida aperta is feasible in human fetuses and offers a substantial reduction of maternal trauma compared to open fetal repair. Further clinical experience is now required before the efficacy of the new approach to protect the exposed neural tissue from mechanical and chemical damage and to improve hindbrain herniation can be evaluated.

Aborted Fetus↗

PubMed2006

FLAIR-/T1-/T2-co-registration for image-guided diagnostic and resective epilepsy surgery.

OBJECTIVE: For technical reasons, T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences do not allow morphological orientation with high anatomic resolution, but they may show small epileptogenic lesions. Considering the peculiarities of diagnostic and resective epilepsy surgery the present study focused on the co-registration of various magnetic resonance sequences for guided epilepsy surgery. METHODS: Fifty patients (24 men; 26 women) aged 2 to 74 years (mean, 32 yr), in whom epileptogenic lesions were not readily identifiable on three-dimensional T1-weighted MRI scans underwent additional two-dimensional T2-weighted and FLAIR sequences before diagnostic and/or resective epilepsy surgery. FLAIR and/or T2-weighted images were co-registered to the T1-weighted data set and were displayed on the navigation station on site for guided invasive diagnostics and for resection according to an individualized resection plan. Postoperative MRI scanning was routinely performed for assessment of resection extent. RESULTS: Co-registered T1- and FLAIR-/T2-images allowed for image-guided intraoperative identification of all lesions (n = 50). Control MRI scans revealed that complete resection was performed as planned before the operation in 49 patients and incomplete resection was performed in one patient. Preliminary seizure outcome with a mean follow up of 14 months (range, 7-24 mo) was assigned according to the Engel classification: Class I, 78%; Class II, 12%; Class III, 4%; Class IV, 6%. CONCLUSION: Image guidance on the basis of image fusion/co-registration of T1- and FLAIR-/T2-images allows for intraoperative identification of otherwise poorly visible lesions on standard MRI sequences in good spatial resolution. Recall of this information during surgery from the navigation system's screen assists in achieving the goal of precise electrode placement, or complete resection of the lesion as well as of the perilesional epileptogenic tissue and improves the surgeon's intraoperative orientation.

Adolescent↗

PubMed2006

Skull base chordomas: management and results.

Growth patterns of skull base chordomas are related to important neurovascular structures. Local invasiveness results in "clinically malignant" behavior. A high rate of transient neurological deficits occurs following radical surgery. At our institution, the principle of radical removal is not followed at any price. This study compared the results of our management with recent series. Eleven patients, five females and six males aged 24-65 years (mean 41 years), underwent removal of skull base chordoma with size one <3 cm, five 3-5 cm, and five >5 cm. Mostly, standard operative approaches were chosen. All patients underwent postoperative radiotherapy. Resection was subtotal/partial in seven patients and total in four with no mortality. Neurological deterioration occurred due to transient cranial nerve deficits in six patients. Temporary surgical morbidity (including cranial nerve deficits) was observed in seven patients. Median Karnofsky performance status score improved compared to preoperative (80), early postoperative (70), and latest assessment (90) (median 36 months). Five patients underwent reoperation due to tumor recurrence after 4-48 months (mean 24 months). Most patients undergoing removal of skull base chordomas suffer from transient neurological deficits which are mainly nonsignificant as the patients return to preoperative functional status. The apparently high rate of incomplete tumor resection (64%) reflects the infiltrative behavior and relationship with neurovascular structures. The operative strategy should not be excessively aggressive at any price, but rather take into account the options of radiotherapy and observation of residual tumor.

Adult↗

PubMed2005

Rhinal-hippocampal connectivity determines memory formation during sleep.

Compared with waking state attention, volition and semantic processing play a minor role during sleep. Thus, investigating declarative memory formation during sleep may allow us to isolate mnemonic core processes. The most feasible approach to memory formation during sleep is the analysis of dream memories. Lesion and imaging studies have demonstrated that encoding of declarative memories, i.e. consciously accessible events and facts, depends on operations within the rhinal cortex and the hippocampus, two substructures of the medial temporal lobe. Successful memory formation is accompanied by a transient rhinal-hippocampal interaction. Consequently, the ability to memorize dreams may be related to mediotemporal connectivity. Therefore, we recorded EEG during sleep from rhinal and hippocampal depth electrodes implanted in 12 epilepsy patients (eight women, mean age 41.1 +/- 6.4 years). They were awakened during rapid eye movement sleep (REM) and asked to recall their dream. Via coherence analyses we show that rhinal-hippocampal connectivity values are approximately twice as large for patients with good dream recall versus those patients with poor recall. This suggests that rhinal-hippocampal connectivity is a key factor in determining declarative memory formation.

Adult↗

PubMed2005

Subdural recordings of the mismatch negativity (MMN) in patients with focal epilepsy.

Mismatch negativity (MMN) is elicited by discernible changes in an otherwise regular stream of auditory stimulation and reflects a pre-attentive detection mechanism. In the current study, auditory evoked potentials were recorded intracranially and electrode contacts sensitive for stimulus deviance were selected in order to further elucidate the contribution of different brain areas to MMN generation. Data were obtained from patients with frontal and temporal lobe epilepsy undergoing a presurgical evaluation by subdural and depth electrodes. In 13 of 29 patients under investigation an intracranial MMN could be observed, while in four other patients a response recovery of the N100 was revealed, mimicking an MMN. Most electrodes with an MMN signal were located in or close to the superior temporal lobe. In two patients an MMN was observed at electrode contacts over the lateral inferior frontal cortex and in one patient at a frontal interhemispheric electrode strip, giving evidence for a participation of the frontal gyrus in MMN generation. Current findings have, however, to be interpreted with caution owing to the placement and limited extension of the used electrode arrays.

Acoustic Stimulation↗

PubMed2005

Word imageability affects the hippocampus in recognition memory.

Concrete words, whose meanings are readily imagined, are better remembered than abstract words. However, the neural correlates of this effect are poorly understood. Here, we investigated the effect of imageability on brain activity in the medial temporal lobe (MTL) processes underlying recognition memory. We recorded event-related potentials (ERPs) via depth electrodes from within the MTL in 14 patients with drug-resistant epilepsy. Patients performed a continuous word recognition task with words of high and low imageability (controlled for word frequency). Behaviorally, recognition performance was better for high, compared to low, imageable words. Two ERP components associated with recognition memory, the AMTL-N400 and the hippocampal late negative component, showed an old/new effect, but only the hippocampal P600 showed a main effect of imageability. We suggest that the hippocampal effect of imageability in recognition memory may be associated with conceptual or pictorial information processing of concrete words.

Adult↗

PubMed2005

An adaptive level set method for interactive segmentation of intracranial tumors.

BACKGROUND: Meaningful segmentation of intracranial lesions can be of assistance for planning open navigated microneurosurgical procedures, as well as for radiotherapy. Meaningful segmentation, however, may be hampered by lack of computational power. The respective segmentation method should be based on state-of-the-art mathematical tools, and it should be suitable for real applications. METHODS: A three-dimensional computational method for interactive segmentation of intracranial tumors is presented. It is based on a front propagation method, in which the evolving front gradually approaches the boundary of a given segment. It generates and remembers the entire evolution of the interface. The segment boundary is chosen from a one parameter family. User interaction is realized by selecting "seed points" inside the object/lesion. External evolution velocity regulates the segmentation process, while approaching the boundary. Adaptively resolved grids ensure computational efficiency for larger segments. The resolution is steered by an image-based indicator, which allows coarse representation of the solution in low-frequency regions, but high resolution along suspected edges of the image. RESULTS: Model-based segmentation was performed on the imaging data of n = 12 patients and the results compared with manual segmentation of the same tumors. The method allowed for basic segmentation in all tumors <3 minutes. This increased 2-4 fold in four irregular tumors, where discrepancies existed in comparison with manually performed segmentation. DISCUSSION: The implicit formulations of this method establish methodical and topological flexibility in three dimensions. It is thus suitable for the segmentation of objects with non-sharp boundaries such as intracranial tumors.

Algorithms↗

PubMed2004

Phase-locking characteristics of limbic P3 responses in hippocampal sclerosis.

Amplitudes of the P3 recorded invasively from the medial temporal lobe (MTL-P3) have been reported to be reduced on the side of a mediotemporal epileptogenic focus. This reduction has been attributed to the massive cell loss within the hippocampus associated with hippocampal sclerosis. It has remained unclear how functional connectivity between the hippocampus and rhinal cortex, as well as within the hippocampus, is altered in hippocampal sclerosis. To investigate this issue, we analyzed to what extent stimulus-related phase-locking and power changes within the low-frequency range (2-30 Hz) and within the gamma band (32-48 Hz), as well as rhinal-hippocampal phase synchronization contribute to the averaged MTL-P3 potentials. Event-related responses were recorded via bilateral depth electrodes in epilepsy patients with unilateral hippocampal sclerosis, who performed a visual oddball experiment. On the contralateral (nonsclerotic) side, successful target detection was associated with an increase of power and phase locking of hippocampal activity in both the low-frequency range and in the gamma range. Besides, there were rhinal-hippocampal synchronization enhancements in the theta and gamma range. On the ipsilateral (sclerotic) side, the event-related power increase in the low-frequency range had almost disappeared, a finding likely to be explained by the loss of principle neurons. However, low-frequency phase-locking, rhinal-hippocampal synchronization, as well as event-related power changes in the gamma range persisted ipsilaterally, although there were differences in temporal and spectral characteristics. These findings support the hypothesis that functional connectivity between hippocampus and rhinal cortex, as well as intrahippocampal connectivity, are partially preserved in hippocampal sclerosis.

Adult↗

PubMed2004

VH gene analysis of primary CNS lymphomas.

Primary CNS lymphomas (PCNSL) are highly malignant non-Hodgkin's lymphomas of B cell origin associated with a poor prognosis. These neoplasms show variable sensitivity to radio- and chemotherapy. A molecular basis for these differences in treatment responses has not yet been established for primary CNS lymphomas in a comprehensive series of patients. Here, we performed PCR analyses of the immunoglobulin (Ig) gene rearrangements of 18 PCNSL, including nine patients who responded well to therapy and nine patients who showed resistance to treatment. Variable gene segment distribution, mutation frequency of variable region genes, and clinical course were analyzed. Our data suggest a tendency towards a higher mean mutation frequency (17.2%) in patients responding to treatment and a lower mutation frequency (11.8%) in patients exhibiting a poor response to therapy, respectively. Furthermore, a restricted usage of the VH4 gene family was observed in the majority of nonresponding patients. To further validate the prognostic impact of these molecular parameters, studies in a larger cohort of patients will be required.

Adult↗

PubMed2004

Short-term habituation of the intracranially recorded auditory evoked potentials P50 and N100.

At an interstimulus interval (ISI) of 500-ms stimulus repetition leads to a strong decrease in cortical response. The functional foundation of this response suppression (or sensory gating) is yet not fully understood. Experiments on short-term habituation using the same stimulus material as sensory gating experiments and same ISI might help to elucidate the mechanisms behind the P50 suppression. Event-related potentials were recorded intracranially in epileptic patients undergoing presurgical evaluation with subdural and depth electrodes. Stimulus material consisted of trains of six clicks, with the last stimulus deviating in pitch and duration. P50 and N100 were calculated for each stimulus in the train separately and compared by analysis of variance (ANOVA). A highly significant amplitude reduction was found from the 1st to 2nd stimulus for both P50 and N100. From the 2nd to 5th stimulus no further amplitude decrease was observable. The deviating 6th stimulus led to a response recovery of both components, but the P50 elicited by the 6th stimulus was still smaller than the P50 of the 1st stimulus. Current results indicate that the P50 suppression as investigated in sensory gating experiments seems to be completed after the 2nd stimulus.

Acoustic Stimulation↗

PubMed2004

Vascular endothelial growth factor and transforming growth factor-beta1 are highly expressed in the cerebrospinal fluid of premature infants with posthemorrhagic hydrocephalus.

The expression of specific growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) is of importance during brain development and in the pathogenesis of neurodegenerative disorders. VEGF and TGF-beta1 was studied in the cerebrospinal fluid (CSF) of neonates with posthemorrhagic hydrocephalus (PHHC) and nonhemorrhagic hydrocephalus. For determining the interference of inflammatory cytokine interaction with the expression of VEGF and TGF-beta1, IL-6 and IL-10 CSF concentrations were measured. Eighteen neonates who had PHHC and underwent serial reservoir puncture and nine neonates who had congenital nonhemorrhagic hydrocephalus (CHC) and underwent first shunt surgery were included in the study. CSF samples of 11 neonates with lumbar puncture for the exclusion of meningitis served as control subjects. VEGF, TGF-beta1, IL-6, and IL-10 concentrations in the CSF were measured by ELISA technique. VEGF concentrations in the CSF of patients with PHHC were significantly higher (median: 377 pg/mL; range: 101-1301 pg/mL) when compared with patients with CHC (median: 66 pg/mL; range: 3-1991; p < 0.001) and control subjects (median: 2 pg/mL; range: 0-12 pg/mL; p < 0.0001). TGF-beta1 CSF concentrations did not differ from control infants in all groups. Median IL-6 and IL-10 concentrations in the CSF were found to be low in all patient groups. Increased release of VEGF in the CSF of neonates with PHHC and nonhemorrhagic hydrocephalus may serve as an indicator of brain injury from progressive ventricular dilation. TGF-beta1 CSF concentrations are not elevated in the phase of acute fibroproliferative reactions in patients with PHHC.

Biomarkers↗

PubMed2004

Neural bases of cognitive ERPs: more than phase reset.

Up to now, two conflicting theories have tried to explain the genesis of averaged event-related potentials (ERPs): Whereas one hypothesis claims that ERPs originate from an event-related activation of neural assemblies distinct from background dynamics, the other hypothesis states that ERPs are produced by phase resetting of ongoing oscillatory activity. So far, this question has only been addressed for early ERP components. Late ERP components, however, are generally thought to represent superimposed activities of several anatomically distinct brain areas. Thus, the question of which mechanism underlies the genesis of late ERP components cannot be easily answered based on scalp recordings. In contrast, two well-investigated late ERP components recorded invasively from within the human medial temporal lobe (MTL) in epilepsy patients, the so-called MTL-P300 and the anterior MTL-N400 (AMTL-N400), are based on single source activity. Hence, we investigated whether the MTL-P300 and the AMTL-N400 are based on an event-related activity increase, a phase reset of ongoing oscillatory activity or both. ERPs were recorded from the hippocampus and rhinal cortex in subjects performing a visual oddball paradigm and a visual word recognition paradigm. With wavelet techniques, stimulus-related phase-locking and power changes were analyzed in a frequency range covering 2 to 48 Hz. We found that the MTL-P300 is accompanied by both phase reset and power increase and that both effects overlap partly in time. In contrast, the AMTL-N400 is initially associated with phase locking without power increase and only later during the course of the AMTL-N400 we observed an additional power increase. In conclusion, both aspects, event-related activation of neural assemblies and phase resetting of ongoing activity seem to be involved in the generation of late ERP components as recorded in cognitive tasks. Therefore, separate analysis of event-related power and phase-locking changes might reveal specific insights into the mechanisms underlying different cognitive functions.

Adult↗

PubMed2004

Rate of vasospasm following the transsylvian versus transcortical approach for selective amygdalohippocampectomy.

Affection of the cerebral circulation following the extraaxial transsylvian approach has been reported. This study aims at the comparison of the risk for the development of vasospasm in the transparenchymal transcortical versus the transsylvian approach for selective amygdalohippocampectomy in patients with Ammon's horn sclerosis. n = 80 consecutive patients (13-58 years) were randomized and allotted to either the transsylvian (TS) or transcortical (TC) group. Bilateral middle cerebral arteries (MCA) and internal carotid arteries (ICA) were examined with transcranial Doppler pre-operatively, and from post-operative day 1 to 7. Blood flow velocities (BFV) were compared via ANOVA. Post-operatively, ipsilateral (= side of operative approach) mean BFV increased significantly in both groups with a mean ipsilateral increase of 79.2% in the TS group, and 48.8% in the TC group. This intergroup difference was also statistically significant. In addition, contralateral BFV increased significantly to a maximum mean of 26.3% in the TS group with no significant increase in the TC group. The results in the TS group are interpreted as vasospasm and not hyperemia - due to dissection of the sylvian vessels and the breakdown of blood within the basal cisterns. Factors such as the extent of visual field cuts and results from neuropsychological testing must be taken into account before drawing a conclusion leading to a fundamental change in surgical strategy.

Adolescent↗

PubMed2003

Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy.

PURPOSE: To evaluate response rate, response duration, overall survival (OS), and toxicity in primary CNS lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy. PATIENTS AND METHODS: From September 1995 to July 2001, 65 consecutive patients with PCNSL (median age, 62 years) were enrolled onto a pilot and phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX; cycles 1, 2, 4, and 5) and cytarabine (ARA-C; cycles 3 and 6)-based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ARA-C. RESULTS: Sixty-one of 65 patients were assessable for response. Of these, 37 patients (61%) achieved complete response, six (10%) achieved partial response, and 12 (19%) progressed under therapy. Six (9%) of 65 patients died because of treatment-related complications. Follow-up is 0 to 87 months (median, 26 months). The Kaplan-Meier estimates for median time to treatment failure (TTF) and median OS were 21 months and 50 months, respectively. For patients older than 60 years, median survival was 34 months, and the median TTF was 15 months. In patients younger than 61 years, median survival and median TTF have not been reached yet; the 5-year survival fraction is 75%. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 12 patients (19%), and permanent cognitive dysfunction possibly as a result of treatment occurred in only two patients (3%). CONCLUSION: Primary chemotherapy based on high-dose MTX and ARA-C is highly efficient in PCNSL. Response rate and response duration in this series are comparable to the response rates and durations reported after combined radiotherapy and chemotherapy. Neurotoxicity was infrequent.

Adult↗