Kay Mursch

Localized proton NMR spectroscopy of brain tumors using short-echo time STEAM sequences.

Recent progress in localized proton NMR spectroscopy has been utilized to improve the spatial resolution and the metabolic specificity in a study of 19 patients with intracranial tumors. Selected examples demonstrate that short echo time stimulated echo acquisition mode sequences are able (a) to account for macroscopic tissue heterogeneity by reducing the volume of interest to 2-8 ml and (b) to facilitate a reasonable characterization of tumor metabolism by increasing the number of accessible metabolites. Proton NMR spectra were acquired within measuring times of 6.5 min on a 2.0 T whole-body system using the imaging headcoil.

Cisternal S100 protein and neuron-specific enolase are elevated and site-specific markers in intractable temporal lobe epilepsy.

In the brain, S100 protein and neuron-specific enolase (NSE) are mainly found in glial cells and neurons, respectively. We investigated concentrations of S100 protein and NSE in cisternal cerebrospinal fluid obtained during implantation of foramen ovale electrodes in eight patients with temporal lobe epilepsy (TLE). In addition, the meningeal markers cystatin-C and beta-trace as well as total protein were measured. Patients with trigeminal neuralgia (TN) undergoing glycerol rhizotomy served as controls. S100 protein and NSE levels ipsilateral to the site of seizure onset were significantly higher than in TN. Contralateral TLE values were also markedly but not significantly elevated. The meningeal markers cystatin-C and beta-trace protein as well as total protein did not differ in TLE and TN. We conclude that interictal temporal lobe dysfunction corresponds with neuronal and glial marker elevations in the extracellular space and that site-specific elevations may predict the site of seizure origin biochemically.

Successful treatment of multiple Pseudallescheria boydii brain abscesses and ventriculitis/ependymitis in a 2-year-old child after a near-drowning episode

RationaleWe report on a cerebral infection by Pseudallescheria boydii in a 21-month-old boy after a near-drowning episode. MRI revealed multiple (>60) intracerebral abscesses.MethodsThe surgical therapy included CSF drainage and microsurgical resection of one abscess for microbiological diagnosis. Antimycotic therapy included terbinafine and intraventricular caspofungin in addition to voriconazole.ResultsSystemic side effects of chemotherapy were not observed. After placement of a ventriculoperitoneal shunt, the boy was transferred to a rehabilitation clinic and improved neurologically. After 20 months, MRI documented a continuing remission of the disease.ConclusionOur case proves that an aggressive treatment should be undertaken and can be successful in CNS pseudallescheriasis.

Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib. Laboratory investigation.

OBJECT The authors have previously reported that erlotinib, an EGFR tyrosine kinase inhibitor, exerts widely variable antiproliferative effects on 9 human glioblastoma multiforme (GBM) cell lines in vitro and in vivo. These effects were independent of EGFR baseline expression levels, raising the possibility that more complex genetic properties form the molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the present study was to determine candidate genes for mediating the cellular response of human GBMs to erlotinib. METHODS Complementary RNA obtained in cell lines selected to represent the sensitive, somewhat responsive, and resistant phenotypes were hybridized to CodeLink Human Whole Genome Bioarrays. RESULTS Expression analysis of 814 prospectively selected genes involved in major proliferation and apoptosis signaling pathways identified 19 genes whose expression significantly correlated with phenotype. Functional annotation analysis revealed that 2 genes (DUSP4 and STAT1) were significantly associated with sensitivity to erlotinib, and 10 genes (CACNG4, FGFR4, HSPA1B, HSPB1, NFATC1, NTRK1, RAC1, SMO, TCF7L1, and TGFB3) were associated with resistance to erlotinib. Moreover, 5 genes (BDNF, CARD6, FOSL1, HSPA9B, and MYC) involved in antiapoptotic pathways were unexpectedly found to be associated with sensitivity. Gene expressions were confirmed by quantitative polymerase chain reaction. CONCLUSIONS Based on an analysis of gene expressions in cell lines with sensitive, somewhat responsive, and resistant phenotypes, the authors propose candidate genes for GBM response to erlotinib. The 10 gene candidates for conferring GBM resistance to erlotinib may represent therapeutic targets for enhancing the efficacy of erlotinib against GBMs. Five additional genes warrant further investigation into their role as putative cotargets of erlotinib.

Visually Evoked Potentials in 52 Children Requiring Operative Repair of Craniosynostosis

We evaluated the prevalence of pathological visually evoked potentials (VEP) before the apppearance of papilledema or other signs of elevated intracranial pressure in children suffering from craniosynostosis. In 52 children (19 girls, 33 boys, median age 7.6 months, mean age 7.6 months, range from 3 to 34 months) preoperative VEP were analyzed. In 13 patients, pathological VEP were observed. In all children, both eyes were involved. Only 1 child suffered from papillar anomalies. Latency was pathological in 12 children, whereas the amplitude was suppressed in only 2 children. In all children with preoperative pathological VEP, postoperative controls (n = 4) were improved or normal. Thus, VEP may be the first test for neuronal damage in craniosynostosis.

Endothelin-converting Enzyme Activity in Human Cerebral Circulation

OBJECTIVE An increased level of endothelin (ET)-1 seems to be involved in the development of augmented cerebrovascular resistance in different pathological conditions, most notably vasospasm after subarachnoid hemorrhage. Therefore, interfering with the ET synthesis or ET receptor blockade may be a promising approach in the treatment of cerebral vasospasm after subarachnoid hemorrhage. Although the receptors mediating the effects of ET-1 human cerebrovasculature are well characterized, data concerning the functionally relevant ET-converting enzyme (ECE) activity are scarce. METHODS ECE activity was determined in organ bath studies by the use of intraoperatively harvested human pial arteries. The level of ECE activity was analyzed by comparing the shift in the concentration effect curves obtained for ET-1 and its precursor, big ET-1. In addition, the presence of ECE-1&agr; immunoreactivity was studied in human cerebral tissue. RESULTS ECE-1&agr; immunoreactivity was found, although not consistently, in human cerebral arteries and was restricted to the endothelium. In isolated pial arterial segments, ET-1 and big ET-1 induced concentration-related contractions with mean pD2 values of 9.25 ± 0.34 and 7.13 ± 0.17, respectively, yielding a 123-fold shift of big ET-1 versus mature ET-1. Preincubation with phosphoramidon (10−4 mol/L) resulted in a small yet significant inhibition of the contraction induced by big ET-1. CONCLUSION The results of our study indicate the presence of functional ECE activity and ECE-1&agr; immunoreactivity in human cerebral arteries. Furthermore, the data suggest the presence of ECE-like activity that differs from that of ECE-1&agr;.

Intra-axial endophytic tumors in the pons and/or medulla oblongata. II. Intraoperative findings, postoperative results, and 2-year follow up in 25 children.

Abstract Between July 1987 and June 1994 we operated upon 30 consecutive children suffering from endophytic intra-axial tumors located in the pons and/or medulla oblongata. The 25 children operated on between July 1987 and October 1993 whose postoperative course could be assessed for a minimum of 2 years after operation were included in this study. Operability of a brain stem tumor was shown to be independent of its size. A gross tumor resection between 80% and 100% could be performed in half these cases, and subtotal or partial resection in the other half. The radicality of resection was not influenced by tumor histopathology, but was dependent on intraoperative findings relating to its consistency, infiltration, and visibility. On follow up, 15 of the 25 children were found to have died within the period of 2 years. Two children died in the immediate postoperative period (at 2 days and 2 weeks after surgery), of acute brain stem swelling and an unsuspected bleeding disorder, respectively. The other 13 of these 15 children died of tumor progression between 1 and 19 months after operation, with a median survival time of 9 months. In the group of the surviving 10 children the histopathology was grade I astrocystoma in 6 cases, angioma in 2 cases, and grade II oligodendroglioma and grade II ependymoma in 1 case each. Postoperatively, most of the children showed some increase in their preoperative deficits, but recovered after 2–3 months. After 2 years, 10 of the 25 children who were followed up are alive and 9 of them attend regular school or kindergarten.

Intra-axial endophytic primitive neuroectodermal tumors in the pons: clinical, radiological, and immunohistochemical aspects in four children.

We present the clinical findings, radiological aspects, operative results, and histopathological features of four typical primitive neuroectodermal tumors (PNET) located in the pontine region in children. All the tumors had an endophytic intra-axial growth pattern. All the children had a short history of severe neurological deficits with involvement of the cranial nerves and pyramidal tract. MRI did not reveal any common feature of malignancy. Compared to our successful experience in operations of intra-axial endophytic brainstem tumors in a total of 32 children, the outcome was poor: all 4 children died within 13 months. We conclude that PNET occurring in the pons is not as rare as was believed, and, compared to PNET in other areas the prognosis is worse.

Intrinsic brainstem tumours in adults: results of microneurosurgical treatment of 16 consecutive patients

Intrinsic brainstem tumours in adults have a poor prognosis and surgical resection is rarely performed. Encouraged by successful operations on children performed in our department, we began a more aggressive strategy of open operations. Between 1986 and 1997, we operated upon 16 consecutive patients over 16 years of age (five female, 11 male, mean age 36.9 years) who were suffering from intrinsic tumours located in the pons and/or medulla oblongata. The extent of first open resection was 80 – 100% in two of the cases and more than 50% in nine cases. The mean survival time after the first occurrence of symptoms was 88.1 (median 34.5) months, and 39.9 (median 11) months after the first open operation. The rate of 5-year survival from the first occurrence of symptoms was 37.5% (25% after the first open surgical procedure). Thirteen out of 16 patients died within the follow-up period of at least 6.3 years, two of them within the immediate postoperative period. Eleven patients experienced a postoperative deterioration of symptoms from which only four recovered. Eight patients had from WHO grade II astrocytoma and a similar course as patients with higher-grade gliomas (n = 4). Our results indicate that open microneurosurgery for intrinsic brainstem tumours is of questionable benefit for the patient. Although surgery offers the advantages of reliable confirmation of histopathology and may be associated with prolonged survival, neurological deterioration was common and, unlike in paediatric patients, often irreversible.

Venous intracranial haemodynamics in children undergoing operative treatment for the repair of craniosynostosis A prospective study using transcranial colour-coded duplex sonography

Abstract To evaluate intracranial venous haemodynamics in craniosynostosis noninvasively, we measured the blood flow velocities and pulsatility indices in the superior sagittal sinus (SSS) and the middle and the anterior cerebral artery during the perioperative course in 21 children undergoing repair of craniosynostosis involving the midline sutures, using transcranial colour-coded duplex sonography (TCCS). An age-matched group of 12 healthy children was examined in like manner for comparison. In the healthy group, the mean pulsatility index (PI) in the SSS was 0.22 and the mean resistance index (RI) 0.20. The mean preoperative PI and RI in the synostosis group were significantly higher [0.41 and 0.34, respectively (P<0.01)], but fell to 0.19 and 0.17 (P<0.01) in the postoperative course. Our results indicate that in craniosynostosis there is an altered venous haemodynamics in the SSS, which can be observed noninvasively by TCCS.