Biomedical subjects

D Van Roost

Publications and source records attributed to D Van Roost.

At least 19 recordsLinked to original sources

PubMed2004

Clonal evolution as pathogenetic mechanism in relapse of primary CNS lymphoma.

Comparative investigation of immunoglobulin (Ig) heavy chain gene rearrangements and DNA sequence analyses of a primary lymphoma of the CNS (PCNSL) and its recurrence revealed that both tumors used the same Ig gene segment. In addition to shared somatic mutations, the primary and the recurrent PCNSLs harbored somatic mutations unique to each tumor. Clonal evolution rather than subclone selection appears to underlie the development of tumor recurrence in this case.

Aged↗

PubMed2004

Characterization of hemorrhagic complications after surgery for temporal lobe epilepsy.

OBJECTIVES: To assess the significance of symptomatic hemorrhagic complications occurring after different temporal resections for temporal lobe epilepsy (TLE) and to compare this data to findings with postoperative hematomas after temporal surgery for mostly glial or metastatic tumors. PATIENTS AND METHODS: Patient charts were retrospectively reviewed for 442 patients who underwent surgery for refractory TLE between 1995 and 2000. Procedures were 247 transsylvian amygdalohippocampectomies (AH), 40 transcortical AH, 57 anterior temporal lobectomies (ATL), 23 lesionectomies plus AH, and 75 lesionectomies without AH. All patients with delayed awakening or new neurological deficits due to hemorrhages were included in the study. An identical procedure was performed to detect symptomatic hemorrhages after 208 procedures for temporal tumor resection during the same time period. RESULTS: Symptomatic postoperative hemorrhages were found in 17 patients (3.8 %) undergoing epilepsy surgery, while the incidence was 3.0 % in a group with space-occupying temporal tumors (six patients). Hemorrhages showed a characteristic distribution after epilepsy surgery: in eight patients they were located remote from the site of surgery in the upper cerebellar vermis and foliae. Five typical hemorrhages associated with dysphasia were found in the left frontal operculum, only three patients had hematomas in the resection cavity, and one was located epidurally. Two patients had more than one location of hemorrhage. Transsylvian AH and ATL had a similar risk for postoperative hemorrhage, whereas none was found after lateral lesionectomies or transcortical AH. Intraoperative manipulations were associated with opercular hemorrhages; the only predisposing factor for resection site hematomas was older age, whereas cerebellar hemorrhages were associated with cerebrospinal fluid (CSF) loss during AH and ATL. There was no mortality in the TLE group, and 0.75 % permanent mild deficits. Seizure outcome did not differ from the rest of the group (82.5 % satisfactory seizure control). In contrast, all intraaxial hematomas after tumor surgery (N = 4, incidence 1.9 %) were located in or adjacent to the resection cavity. Prognosis was much worse with parenchymal hemorrhages after tumor surgery: three of four patients died, one survived with a severe hemiparesis, only two patients with extraaxial hematomas (incidence 1 %) had a complete recovery. The 3 % incidence of symptomatic hemorrhages was only insignificantly lower compared to the TLE group, patients with tumor surgery were older than TLE patients (49 versus 33 years), and in five of six patients only incomplete tumor resection was achieved. CONCLUSION: Although associated with a low permanent morbidity, features of postoperative hemorrhages after TLE surgery are characteristically different to complications after surgery for other indications, which has to be kept in mind for patient counseling and obtaining informed consent.

Adolescent↗

PubMed2004

Collateral brain damage, a potential source of cognitive impairment after selective surgery for control of mesial temporal lobe epilepsy.

BACKGROUND: Highly selective epilepsy surgery in temporal lobe epilepsy is intended to achieve seizure freedom at a lower cognitive risk than standard en bloc resections, but bears the risk of collateral cortical damage resulting from the surgical approach. OBJECTIVE: To investigate cortical damage associated with selective amygdalo-hippocampectomy (SAH). METHODS: 34 epileptic patients were evaluated. They were randomly assigned to SAH using either a sylvian (9 left/10 right) or a transcortical surgical approach (5 left/10 right). Postoperative MRI signal intensity changes adjacent to the approach were correlated with performance changes in serial word and design list learning. RESULTS: Losses in verbal learning and recognition memory were positively related to signal intensity changes, independent of the side of the resection, the surgical approach, or the extent of the mesial resection. Losses in consolidation/retrieval (memory) were greater after left sided surgery. Losses in design learning were related to right sided surgery and signal intensity changes. Seizure outcome (85% seizure-free) did not differ depending on the side or type of surgery. CONCLUSIONS: Collateral damage to cortical tissues adjacent to the surgical approach contributes to postoperative verbal and figural memory outcome after SAH. Controlling for collateral damage may clarify the controversial memory outcomes after SAH reported by different surgical centres.

Amygdala↗

PubMed2003

Dissecting out conscious and unconscious memory (sub)processes within the human medial temporal lobe.

The human medial temporal lobe (MTL) system mediates memories that can be consciously recollected. However, the specific natures of the individual contributions of its various subregions to conscious memory processes remain equivocal. Here we show a functional dissociation between the hippocampus proper and the parahippocampal region in conscious and unconscious memory as revealed by invasive recordings of limbic event-related brain potentials recorded during explicit and implicit word recognition: Only hippocampal and not parahippocampal neural activity exhibits a sensitivity to the implicit versus explicit nature of the recognition memory task. Moreover, only within the hippocampus proper do the neural responses to repeated words differ not only from those to new words but also from each other as a function of recognition success. By contrast parahippocampal (rhinal) responses are sensitive to repetition independent of conscious recognition. These findings thus demonstrate that it is the hippocampus proper among the MTL structures that is specifically engaged during conscious memory processes.

Brain Mapping↗

PubMed2003

The pathophysiology of motor symptoms in Parkinson's disease.

This review focuses on some of the known and hypothetical pathophysiological mechanisms underlying the motor symptoms in Parkinson's disease (PD). Current views on these mechanisms have largely been influenced by models of basal ganglia functioning and dysfunctioning. These models have allowed to explain some clinical findings and to predict a number of results of basal ganglia surgery in movement disorders. However, neurophysiological studies as well as neurochemical data have broadened our vision on basal ganglia functioning and dysfunctioning in PD. Moreover, these more fundamental insights in basal ganglia functioning allow new concepts on the development of treatment strategies, and on the prevention of motor fluctuations in PD.

Basal Ganglia↗

PubMed2001

Inferior temporal stream for word processing with integrated mnemonic function.

The participation of the inferior temporal cortex in visual word perception and recognition raises several questions: Is there a directed processing stream proceeding anteriorly by continuous cortical processing? How fast are words processed within such an inferior temporal stream? Does this stream support implicit or explicit memory? To answer these questions, we analyzed the spatio-temporal relationship of event-related potentials, recorded directly from the inferior temporal cortex in epilepsy patients performing a continuous visual word recognition paradigm. Event-related potentials elicited an inferior temporal positivity in a strip along the left collateral sulcus. This potential exhibited a linear (r = 0.74) peak latency progression from posterior to anterior inferior temporal regions (approximately 15 cm/sec), indicating a directed, intracortical processing stream. Peak amplitudes and latencies showed reliable old/new effects with smaller amplitudes and shorter latencies for old as opposed to new words. Although the amplitude-old/new-effect occurred for all repeated words (e.g., implicit memory), the latency-old/new-effect occurred for correctly recognized old words only (e.g., explicit recognition). These results seem to dissociate two distinct mnemonic processes. The graded decrease of mean ITP peak amplitudes and latencies, however, does not allow us to exclude a single trace model as assumed for explicit recognition memory based on familiarity (Mandler [1980]: Psychol Rev 87:252-271). Regardless whether there is a dissociation between implicit and explicit memory in inferior temporal cortex or not, our findings are in accordance with an integrated inferior temporal processing stream for words that performs continuously semantic and mnemonic operations supporting both implicit and explicit memory.

Adolescent↗

PubMed2001

Human herpes virus-8 is not associated with primary central nervous system lymphoma in HIV-negative patients.

Primary central nervous system lymphomas (PCNSL) are derived from germinal center B cells. Recent molecular studies indicate that the tumor cells or their precursors have experienced antigenic stimulation. Attractive candidates for such antigens are pathogens with the capacity to reside in the brain. The aim of the present study was to evaluate whether human herpes virus (HHV)-8 is involved in the pathogenesis of PCNSL. A series of 46 PCNSL, 31 from HIV-negative and 15 from HIV-positive patients, were analyzed using various molecular biological and immunological approaches. Nested PCR with two different protocols unequivocally demonstrated that PCNSL from HIV-negative patients did not harbor HHV-8 DNA. Among AIDS-associated PCNSL, HHV-8 DNA was found in only 1 tumor. In situ hybridization studies revealed that the lymphoma cells were HHV-8 negative in all cases. Single small mononuclear cells, most likely corresponding to bystander lymphocytes, were identified as the cellular source of HHV-8 in the HIV-positive patient with an HHV-8 PCR signal. These studies largely rule out a role for HHV-8 in the pathogenesis of PCNSL in both HIV-negative as well as HIV-positive patients.

Adult↗

PubMed2001

Changes of cerebral blood flow following dexamethasone treatment in brain tumour patients. A Xe/CT study.

BACKGROUND: It is not exactly known how dexamethasone improves the function of brain that is affected by tumour. Whether and in what sense dexamethasone influences cerebral blood flow has rarely been addressed and previous investigations have yielded inconsistent results. METHOD: Stable xenon-enhanced computed tomography (Xe/CT) was used to assess the regional cerebral blood flow (rCBF) in 67 patients with supratentorial primary and secondary brain tumours. rCBF studies were done at least once prior to resection or stereotactic biopsy of the tumours. In nine patients repeated studies before surgery and in 15 patients additional studies after resective surgery were obtained. Dexamethasone was administered according to the clinical needs before surgery and systematically after surgery. Of the preoperative studies 30 were obtained before and 47 during dexamethasone treatment. The rCBF data were analysed upon correlations with daily dose, cumulative dose, and duration of dexamethasone treatment. Moreover, individual courses before and after surgery were examined. FINDINGS: Mainly inverse correlations were found between the treatment parameters, particularly the daily dose of dexamethasone, and rCBF. Only in the subgroup of glioblastoma patients, a positive correlation was found of both duration and cumulative dose of dexamethasone with rCBF in oedema. Serial observations of individual patients confirmed the above findings, yet with possible exceptions. After tumour resection a clear improvement of rCBF was regularly observed. INTERPRETATION: The beneficial effect of dexamethasone is not attributed to an increase of cerebral blood flow, because rather decreases of rCBF are mostly observed.

Adult↗

PubMed2001

What factors are related to impairment of cerebrovascular reserve before and after arteriovenous malformation resection? A cerebral blood flow study using xenon-enhanced computed tomography.

OBJECTIVE: To examine the incidence and possible determinants of impaired vascular reserve in arteriovenous malformation (AVM)-affected brain, before and after surgery. METHODS: In a prospective study of 30 patients, the regional cerebrovascular reserve capacity (rCRC) and the vasodilated regional cerebral blood flow (rCBF) were assessed during an acetazolamide challenge, using xenon-enhanced computed tomography, before and after complete AVM resection. Single brain slices at the level of the basal ganglia were examined, and scanning through the AVMs was avoided. Five regions of interest in the AVM-bearing hemisphere were compared with their counterparts in the unaffected hemisphere. Vasodilated rCBF reductions of at least 20% in one or more regions of interest and rCRC values of less than 10 ml/100 g/min were considered to be significant. RESULTS: Ipsilateral vasodilated rCBF was significantly reduced in 17 patients before surgery and 15 patients after surgery. Ipsilateral rCRC was impaired in 14 patients before surgery and 12 patients after surgery. Large AVM size, venous congestion, and AVM-related vascular territories were correlated with impaired vascular reserve in AVM-nonadjacent brain tissue before surgery. Similar correlations were observed after surgery, except that not AVM size but a large number of AVM-supplying vascular territories was correlated. Moreover, the smallest AVMs and those supplied by a single vascular territory, as well as hemorrhage and nonhemorrhagic neurological deficits as presenting symptoms, were correlated with reduced ipsilateral vasodilated rCBF before surgery. Among patients with AVMs and nonhemorrhagic epilepsy, a trend of impaired cerebrovascular reserve was observed. In the only case of postresectional "breakthrough," the preoperative rCRC was not impaired but abnormally high. CONCLUSION: Among the determinants of impaired cerebrovascular reserve, AVM size is already a constituent of current grading scales and decision-making paradigms, whereas factors such as venous congestion have been less closely considered or less obvious but may deserve increased attention in the future. Nonhemorrhagic epilepsy in patients with AVMs may constitute the clinical equivalent of chronic cerebral ischemia in a murine model. Postresectional breakthrough may be partly attributable to individual predisposition to excessive vasoreactivity in the whole brain.

Acetazolamide↗

PubMed2001

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study.

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL). From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C. Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse). In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70 years.

Adult↗

PubMed1999

Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors.

Studies in rodents and nonhuman primates have linked the activity of N-methyl-D-aspartate (NMDA) receptors within the hippocampus to animals' performance on memory-related tasks. However, whether these receptors are similarly essential for human memory is still an open question. Here we present evidence suggesting that hippocampal NMDA receptors, most likely within the CA1 region, do participate in human verbal memory processes. Words elicit a negative event-related potential (ERP) peaking around 400 ms within the anterior mesial temporal lobe (AMTL-N400). Ketamine, an NMDA-receptor antagonist, reduces the amplitude of the AMTL-N400 (in contrast to other hippocampal potentials) on initial presentation, eliminates the typical AMTL-N400 amplitude reduction with repetition, and leads to significant memory impairment. Of the various hippocampal subfields, only the density of CA1 neurons correlates with the word-related ERPs that are reduced by ketamine. Altogether, our behavioral, anatomical, and electrophysiological results indicate that hippocampal NMDA receptors are involved in human memory.

Adult↗

PubMed1999

Real-time tracking of memory formation in the human rhinal cortex and hippocampus.

A fundamental question about human memory is which brain structures are involved, and when, in transforming experiences into memories. This experiment sought to identify neural correlates of memory formation with the use of intracerebral electrodes implanted in the brains of patients with temporal lobe epilepsy. Event-related potentials (ERPs) were recorded directly from the medial temporal lobe (MTL) as the patients studied single words. ERPs elicited by words subsequently recalled in a memory test were contrasted with ERPs elicited by unrecalled words. Memory formation was associated with distinct but interrelated ERP differences within the rhinal cortex and the hippocampus, which arose after about 300 and 500 milliseconds, respectively. These findings suggest that declarative memory formation is dissociable into subprocesses and sequentially organized within the MTL.

Adult↗

PubMed1999

Amobarbital effects on the posterior hippocampus during the intracarotid amobarbital test.

OBJECTIVE: To relate functional effects on the hippocampus during the intracarotid amobarbital test (IAT) to its direct perfusion with amobarbital. METHODS: In 17 patients with intractable temporal lobe epilepsy, 28 hemispheres were perfused with 2.3 mL of 10% solution of 200 mg amobarbital and 37 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO). For evaluation of amobarbital effects, data were combined from stereo-EEG (S-EEG) recordings from intrahippocampal depth electrodes and high-resolution SPECT after intracarotid injection of HMPAO. RESULTS: Perfusion of the entire hippocampus was observed only in hemispheres with a fetal origin of the posterior cerebral artery (PCA). In 10 hemispheres, S-EEG recordings could not unequivocally be assigned to either the anterior or the posterior part of the hippocampus. In the remaining 18 hemispheres, only the two with a fetal type of PCA showed perfusion of the entire hippocampus. In both, hippocampal electrical activity changed under the influence of amobarbital but did not differ in anterior and posterior contacts. In 15 of 16 hemispheres in which SPECT demonstrated perfusion of the anterior hippocampus only, amobarbital injection resulted in significant S-EEG activity change in both the anterior and the posterior parts of the hippocampus. CONCLUSION: S-EEG effects on the posterior hippocampus during the IAT can occur without direct perfusion of those brain areas.

Adolescent↗

PubMed1999

Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4-34 gene segment.

Primary central nervous system lymphomas (PCNSLs) have recently received considerable clinical attention due to their increasing incidence. To clarify the histogenetic origin of these intriguing neoplasms, PCNSLs from 10 HIV-negative patients were analyzed for immunoglobulin (Ig) gene rearrangements. All tumors exhibited clonal IgH gene rearrangements. Of the 10 cases, 5 used the V4-34 gene segment, and all of these lymphomas shared an amino acid exchange from glycine to aspartate due to a mutation in the first codon of the complementarity-determining region 1. No preferential usage of D(H), J(H), V(kappa), J(kappa), V(lambda), or J(lambda) gene segments was observed. All potentially functional rearrangements exhibited somatic mutations. The pattern of somatic mutations indicated selection of the tumor cells (or their precursors) for expression of a functional antibody. Mean mutation frequencies of 13. 2% and 8.3% were detected for the heavy and light chains, respectively, thereby exceeding other lymphoma entities. Cloning experiments of three tumors showed ongoing mutation in at least one case. These data suggest that PCNSLs are derived from highly mutated germinal-center B cells. The frequent usage of the V4-34 gene and the presence of a shared replacement mutation may indicate that the tumor precursors recognized a shared (super) antigen.

B-Lymphocytes↗

PubMed1999

Limbic P300s in temporal lobe epilepsy with and without Ammon's horn sclerosis.

Limbic P300 potentials can be recorded within the mesial temporal lobes of patients with temporal lobe epilepsy (TLE). To delineate possible mechanisms of their generation and pathological alteration, we analysed limbic P300s in 55 TLE patients with and 29 without Ammon's horn sclerosis (AHS) and correlated their amplitudes with neuronal cell counts in 30 histopathological specimens. Limbic P300 amplitudes were reduced on the side of the epileptogenic focus only in patients with AHS. Moreover, in AHS patients, limbic P300 latencies were prolonged bilaterally; and in patients with left-sided AHS, amplitudes were reduced bilaterally. Both findings suggest bilateral functional deficits in TLE with unilateral AHS. Limbic P300 areas correlated significantly with neuronal densities of dentate gyrus granule cells but not hippocampal pyramidal cells in the CA1-4 (cornu ammonis) subfields. This finding points to a potential mechanism for the bilateral effects of unilateral AHS as both dentate gyri exhibit strong reciprocal contralateral connectivity.

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

Recombinant human thyrotropin in thyroid cancer and hypopituitarism due to sella metastasis.

We present a patient with thyroid cancer and hypopituitarism who required recombinant human thyrotropin (rhTSH) for 131I scanning with respect to subsequent therapy. The thyroid cancer had been unknown until central neurological symptoms developed, leading to the diagnosis of a huge metastasis to the sella that was the only manifestation of metastatic spread. The failure to generate endogenous thyrotropin (TSH) was overcome by the use of rhTSH for performing a 131I test. Unfortunately, the 131I uptake was not sufficient for therapy. This subject is the first reported case who required the application of rhTSH due to a single thyroid cancer metastasis in the sella region with secondary failure to generate endogenous TSH.

Aged↗

PubMed1999

Prediction of postoperative seizure control by hippocampal event-related potentials.

PURPOSE: In spite of unequivocal results of the presurgical evaluation, between 10 and 30% of patients with medial temporal lobe epilepsy (MTLE) do not become seizure free by temporal lobe surgery. Because event-related potentials (ERPs) recorded within the hippocampal formation have been shown to be sensitive to the epileptogenic process, we examined whether ERPs can help to improve the prediction of postoperative seizure control. METHODS: We recorded ERPs to words from bilateral intrahippocaampal electrodes by using a visual word-recognition paradigm in 70 patients with unilateral hippocampal pathology and related these measurements to seizure outcome after temporal lobe surgery. RESULTS: Words elicited N400 potentials, which were reduced in amplitude on repetition on the side contralateral to hippocampal sclerosis. This contralateral repetition effect, however, was significantly diminished in the group of patients who experienced seizure recurrence after the operation. Contralateral repetition effects thus permitted correct prediction of postoperative seizure control in 94% of all patients. CONCLUSIONS: Recording ERPs to words within the medial temporal lobes can improve the prediction of postoperative seizure control. Reduced repetition effects contralateral to the side of hippocampal sclerosis may indicate bilateral epileptogenicity.

Adolescent↗