[show abstract][hide abstract] ABSTRACT: OBJECTIVES: The aim of this study was to investigate the relationship between the pressure setting of the ventriculoperitoneal (VP) shunt valve and a magnetic resonance (MR)-based estimate of intracranial pressure (ICP) in children with shunt-treated hydrocephalus without clinical signs of shunt malfunction. MATERIALS AND METHODS: Institutional review board approval was obtained before the study, and all subjects and/or their legal guardians provided written informed consent. In this prospective study, 15 consecutive patients (median age, 8.25 years; range, 2.2-18.4 years; 6 girls and 9 boys) with shunt-treated hydrocephalus without signs of shunt malfunction were examined with retrospectively gated phase contrast sequences to quantify arterial inflow, venous outflow, and cerebrospinal fluid (CSF) flow to and from the cranial vault. The ratio of the maximal intracranial volume change and the pulse pressure gradient change was used to derive MR-ICP. Spearman ρ was used to test for the association of setting of the shunt valve opening pressure and MR-ICP. RESULTS: Shunt valve opening pressure settings and MR-ICP were positively correlated (Spearman ρ = 0.64, P < 0.01). Median MR-ICP was 8.67 mm Hg (interquartile range [IQR], 1.59 mm Hg) and median setting of the VP-shunt valve was 6.62 mm Hg (IQR, 1.47 mm Hg). The median MR-ICP was 1.9 mm Hg (IQR, 0.73 mm Hg) higher than the setting of the shunt valve. CONCLUSION: There is a positive correlation between MR-ICP and VP shunt valve opening pressure setting. The systematically higher assessment of MR-ICP is most likely a result of outflow resistance within the shunt tubing system and well within the known fluctuation rates of VP shunt systems.
[show abstract][hide abstract] ABSTRACT: CLINICAL ISSUE: Causes and imaging patterns of hydrocephalus differ depending on the age of the patient. Traditionally, hydrocephalus was classified into non-communicating and communicating hydrocephalus but more recent classifications also take the site of occlusion and the etiology into account. DIAGNOSTICS: For the diagnostic work-up computed tomography (CT), sonography and magnetic resonance imaging (MRI) are available and MRI is the method of choice for children and adolescents as it allows determination of the cause and location of a possible obstruction. In the first 12-18 months sonography allows evaluation of the lateral ventricles and the third ventricle and CT is usually only chosen in children in emergency situations and/or if no other modality is available. PERFORMANCE: We retrospectively evaluated a population of 785 children and adolescents (426 males aged 0-17 years) referred for MRI between April 2009 and March 2012 due to headaches, somnolence, concentration difficulties or developmental delay. Among these 80 (49 male) met the MRI criteria for hydrocephalus, 75 (46 male) had non-communicating hydrocephalus and 5 (3 male) communicating hydrocephalus. Of the patients 24 (15 male) had posthemorrhagic aqueductal stenosis, 16 (8 male) intracranial tumors, 9 (6 male) Chiari II malformations, 5 (4 male) other congenital malformations including malformations of the Dandy Walker spectrum, 9 (3 male) idiopathic aqueductal stenosis, 7 (5 male) arachnoidal cysts and 10 (8 male) other disorders, such as post-infections, macrocephaly cutis marmorata telangiectatica congenita (M-CMTC) syndrome, mesencephalic arteriovenous malformation (AVM), Langerhans cell histiocystosis. PRACTICAL RECOMMENDATIONS: It is important to take the age of the patient and the imaging pattern into account and to exclude tumors when reporting MR images of children with hydrocephalus.
Der Radiologe 09/2012; 52(9):813-20. · 0.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: CLINICAL/METHODICAL ISSUE: The intracranial pressure (ICP) is a crucially important parameter for diagnostic and therapeutic decision-making in patients with hydrocephalus. STANDARD RADIOLOGICAL METHODS: So far there is no standard method to non-invasively assess the ICP. Various approaches to obtain the ICP semi-invasively or non-invasively are discussed and the clinical application of a magnetic resonance imaging (MRI)-based method to estimate ICP (MR-ICP) is demonstrated in a group of pediatric patients with hydrocephalus. METHODICAL INNOVATIONS: Arterial inflow, venous drainage and craniospinal cerebrospinal fluid (CSF) flow were quantified using phase-contrast imaging to derive the MR-ICP. PERFORMANCE: A total of 15 patients with hydrocephalus (n=9 treated with shunt placement or ventriculostomy) underwent MRI on a 3 T scanner applying retrospectively-gated cine phase contrast sequences. Of the patients six had clinical symptoms indicating increased ICP (age 2.5-14.61 years, mean 7.4 years) and nine patients had no clinical signs of elevated ICP (age 2.1-15.9 years; mean 9.8 years; all treated with shunt or ventriculostomy). Median MR-ICP in symptomatic patients was 24.5 mmHg (25th percentile 20.4 mmHg; 75th percentile 44.6 mmHg). Median MR-ICP in patients without acute signs of increased ICP was 9.8 mmHg (25th percentile 8.6 mmHg; 75th percentile 11.4 mmHg). Group differences were significant (p < 0.001; Mann-Whitney U-test). ACHIEVEMENTS: The MR-ICP technique is a promising non-invasive tool for estimating ICP. PRACTICAL RECOMMENDATIONS: Further studies in larger patient cohorts are warranted to investigate its application in children with hydrocephalus.
Der Radiologe 08/2012; 52(9):827-32. · 0.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: Isolated fourth ventricles as a consequence of shunted posthemorrhagic hydrocephalus can cause significant brainstem compression and subsequent clinical deficits in children. Several treatment options have been described. We report the clinical and radiological outcome after microsurgical fenestration of fourth ventricular outlet foramen via a suboccipital approach. METHODS: In nine patients (age, 9 to 87 months; median age, 21 months), microsurgical reopening of formerly occluded outlet foramen of the fourth ventricle was performed under electrophysiological monitoring. Pre- and postoperative clinical outcome as well as radiological results are reported. RESULTS: Mean follow-up for all children was 25 months. Three children older than 3 years were less significantly involved, the remaining six showed tremendous long tract signs and lower cranial nerve deficits. All children exhibited a remarkable improvement of their preexisting neurological deficits post-surgery. Despite successful fenestration, one child required additional internal drainage of fourth ventricle to the lateral ventricles due to malabsorption. Median diameters of the fourth ventricle changed markedly after surgery with anterior-posterior (a.p.) extension from 3.8 to 2.9 cm, lateral extension from 4.2 to 2.8 cm (p = 0.018), and craniocaudal extension from 5.8 to 4.7 cm, respectively. Also, the pontine a.p. diameter increased significantly from 0.8 to 1.5 cm (p = 0.022). CONCLUSION: The clinical and radiological outcomes after microsurgical fenestration in children with an isolated fourth ventricle are very promising. This treatment modality is a safe and effective shunt-free option when electrophysiological monitoring and thorough preoperative neuroradiological work-up are applied.
Child s Nervous System 08/2012; · 1.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: β1-class integrins play essential roles both in developmental biology as well as in cancer. Particularly, a Nestin-driven deletion of β1-integrin receptors results in severe abnormalities of brain development including a laminar disorganization of cerebellar granule neurons. However, since Nestin is expressed in all kinds of neural precursors, these data do not allow conclusions to be drawn about the role of β1-integrins in distinct neuronal and glial cell types. By generating conditional knockout mice using granule cell-specific Math1-promoter sequences, we show here that the expression of β1-integrins in granule neurons is dispensable for the development of the cerebellum. Also, deletion of β1-integrin from tumors that arise in a mouse model of granule cell precursor-derived medulloblastoma did not result in a significant survival benefit. Last, expression levels of β1-integrin in human medulloblastoma samples did not predict patient's outcome. However, a β1-integrin knockout using hGFAP-promoter sequences led to cerebellar hypoplasia, inappropriate positioning of Bergmann glia cells in the molecular layer, undirected outgrowth of radial glia fibers, and granule cell ectopia. We therefore conclude that β1-integrin expression in cerebellar granule neurons is not essential during normal development or medulloblastoma formation. In fact, it is the expression of β1-integrin in glia that is crucial for the proper development of the cerebellar cortex.
[show abstract][hide abstract] ABSTRACT: To compare the occurrence and localization of interictal epileptiform discharges (IEDs) and epileptic seizure patterns (ESPs) with the localization of MRI lesions.
We retrospectively analyzed the EEG and MRI data of a series of patients with focal epilepsies that had been studied from 1991 to 2009.
In patients with temporal lesions, the localization of IEDs was most congruent (58.6% with IEDs exclusively over the lesional lobe and 29.7% with a majority of temporal IEDs). This differed (p < 0.001) from frontal lesions (27.5% with exclusively frontal IEDs, 24.6% with a majority of frontal IEDs). In parieto-occipital lobe lesions, only 12.1% had IEDs exclusively over the lesional lobe compared to 48.5% with no parieto-occipital IEDs at all. Patients with central lesions often lacked any IEDs (54.5%, p < 0.001). The occurrence and localization of ESPs also differed between the regions. They were most congruent in temporal lesions (63.5% of patient had ESPs only over the lesional lobe, 23.4% had the majority of ESPs over the lesional lobe), which differed from frontal and parieto-occipital lesions (37.7% and 30.3% of patients with ESPs only over the lesional lobe). Patients with central lesions had ESPs very frequently only outside the lesional lobe (63.6%). Surgery outcome did not differ between the regions.
The occurrence and localization of interictal and ictal EEG findings differs vastly for lesions in different brain regions. These findings should be used to carefully weigh the results from EEG studies particularly in patients with extratemporal epilepsies considered for epilepsy surgery.
[show abstract][hide abstract] ABSTRACT: Medulloblastoma is the most common malignant brain tumor in childhood, and development of targeted therapies is highly desired. Although the molecular mechanisms of malignant transformation are not fully understood, it is known that medulloblastomas may arise from cerebellar granule neuron precursors. The homeodomain transcription factor Barhl1 is known to regulate migration and survival of granule cell precursors, but its functional role in medulloblastoma is unknown. We show here that the expression of BARHL1 is significantly upregulated during human cerebellar development and in human medulloblastoma samples as compared with the normal adult cerebellum. We also detected high levels of Barhl1 expression in medulloblastomas of Math1-cre:SmoM2 mice, a mouse model for Sonic hedgehog-associated medulloblastomas that we developed previously. To investigate Barhl1 function in vivo during tumor development, we generated Barhl1(-/-)Math1-cre:SmoM2 mice. Interestingly, tumors that developed in these mice displayed increased mitotic activity and decreased neuronal differentiation. Moreover, survival of these mice was significantly decreased. Similarly, low expression of BARHL1 in human medulloblastoma cases was associated with a less favorable prognosis for patients. These results suggest that the expression of Barhl1 decelerates tumor growth both in human and in murine medulloblastomas and should be further investigated with respect to potential implications for individualized therapeutic strategies.
[show abstract][hide abstract] ABSTRACT: A case of successful resuscitation of a patient with severe amitriptyline intoxication is reported. The measured amitriptyline serum levels far exceeded those assumed to be lethal according to the literature. Resuscitation was successful with the administration of intravenous fat emulsion and the patient recovered without any neurological sequelae.
Der Anaesthesist 03/2011; 60(6):541-5. · 0.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Zusammenfassung Es wird die erfolgreiche Behandlung einer Amitriptylinvergiftung mithilfe der repetitiven i.v.-Gabe einer Fettemulsion berichtet.
Die initial gemessenen Amitriptylinserumspiegel lagen weit in einem Bereich, der laut Literatur oftmals als tödlich beschrieben
wird. Die Patientin überlebte ohne neurologische Folgeschäden.
Der Anaesthesist 01/2011; 60(6):541-545. · 0.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Orbital and intracranial complications of acute sinusitis occur more frequently in the pediatric population compared to adults due to anatomic differences. Since the introduction of antibiotics the frequency of such complications has been dramatically reduced. Nevertheless, even in the era of modern antibiotics these complications continue to occur and it is therefore of utmost importance not only to know about these complications but also to include them in the differential diagnosis. Appropriate diagnosis mainly based on CT scanning or magnetic resonance tomography is the basis for a rapid and sufficient and if necessary interdisciplinary treatment. In this CME article the diagnostic and therapeutic interventions in four young patients suffering from orbital or intracranial complications due to acute sinusitis are described and discussed in the context of the current literature and a clinical algorithm is introduced.
[show abstract][hide abstract] ABSTRACT: Orbitale und intrakranielle Komplikationen akuter Sinusitiden treten aufgrund der unterschiedlichen anatomischen Situation
bei Kindern und Jugendlichen häufiger auf als bei Erwachsenen. Seit Einführung der Antibiotika sind derartige Komplikationen
selten geworden. Dennoch ist es von entscheidender Bedeutung, diese nicht nur zu kennen, sondern auch in die diagnostischen
und therapeutischen Erwägungen miteinzubeziehen. Die rasche Diagnostik und gezielte Therapie ist Voraussetzung, um bleibende
Schäden infolge dieser Komplikationen zu verhindern. Im vorliegenden Weiterbildungsbeitrag werden anhand von Fallbeispielen
die erforderlichen diagnostischen und therapeutischen Maßnahmen beschrieben, dann im Kontext mit der Literatur diskutiert,
und schließlich wird ein Handlungsalgorithmus vorgestellt.
Orbital and intracranial complications of acute sinusitis occur more frequently in the pediatric population compared to adults
due to anatomic differences. Since the introduction of antibiotics the frequency of such complications has been dramatically
reduced. Nevertheless, even in the era of modern antibiotics these complications continue to occur and it is therefore of
utmost importance not only to know about these complications but also to include them in the differential diagnosis. Appropriate
diagnosis mainly based on CT scanning or magnetic resonance tomography is the basis for a rapid and sufficient and if necessary
interdisciplinary treatment. In this CME article the diagnostic and therapeutic interventions in four young patients suffering
from orbital or intracranial complications due to acute sinusitis are described and discussed in the context of the current
literature and a clinical algorithm is introduced.
[show abstract][hide abstract] ABSTRACT: A 47-year-old man with a history of heart transplant was admitted after severe traumatic brain injury and seizures. During mechanical ventilation, the patient developed bronchospasm that severely compromised respiratory function that led to cardiac arrest. After resuscitation, application of isoflurane through the Anaesthetic Conserving Device (AnaConDa) in the ICU successfully treated bronchospasm, provided adequate sedation, and enabled appropriate ventilation and diagnostic bronchoscopy. A subsequent bronchoalveolar lavage revealed a high amount of Herpes simplex DNA. Herpes simplex pneumonia was diagnosed and treated with acyclovir. Isoflurane treatment was applied for twelve days total without side effects on renal and cerebral function. The patient recovered quickly after the termination of sedation. At discharge, he was fully awake without focal neurological deficiency and his long-term outcome was excellent. This case demonstrates that isoflurane is a treatment option in life-threatening cases of bronchospasm and a safe option for long-term sedation.
[show abstract][hide abstract] ABSTRACT: According to the new WHO classification, embryonal tumors comprise medulloblastomas, primitive neuroectodermal tumors (PNET),
medulloepitheliomas, ependymoblastomas, and neuroblastomas. We include here also craniopharyngiomas.
A detailed description of medulloblastomas, PNETs, craniopharyngiomas, and ependymomas is given in the pediatric chapter.
We will focus in the following on specific features that characterize adult tumors of these entities. Neuroblastomas are rarely
found in neuro-oncological patients except when they metastasize in the central nervous system (CNS).
[show abstract][hide abstract] ABSTRACT: Various causes for the development of syringomelia are discussed. The influence of hydrocephalus upon syringomyelia is rarely reported and its role remains unclear.
We report a young female patient with shunt dysfunction and consequent syrinx development after child delivery.
The patient showed rapid clinical deterioration after delivery. Treatment was shunt revision and reconstitution of CSF flow in the posterior fossa. After surgery, the patient showed regressive syringomyelia going along with a quick and pronounced clinical improvement.
Development of syringomyelia can be caused by CSF flow disorders and hydrocephalus and may be aggravated by increased intra-abdominal pressure.
Child s Nervous System 12/2008; 25(2):263-6. · 1.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report, for the first time, how intraspinal carcinoma metastasis can cause reversible dementia accompanied by distinct cerebrospinal fluid (CSF) alterations. A 73-year-old male patient who suffered from rapidly progressive dementia and gait disturbance showed marked abnormalities of CSF tau protein, amyloid beta(1-42), and prostate-specific antigen. A lumbosacral, intraspinal metastasis from a prostate carcinoma was found, and after microsurgical removal, CSF alterations normalized and the clinical symptoms regressed. This case illustrates how malignant tumors can disturb brain function via indirect mechanisms.
European Journal of Neurology 01/2008; 14(12):1400-2. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: The optimal therapeutic management of children with World Health Organization grade I and II gliomas not accessible to complete resection is poorly defined. Radical surgical resection is the first-line treatment for large hemispheric tumors, whereas interstitial iodine-125 radiosurgery (IRS) might be an attractive treatment concept for selected patients with small (tumor diameter in the range of 4 cm) and circumscribed tumors in any location of the brain. Precise high-dose application, maximal sparing of surrounding normal tissue, and the absence of long-term complications have been reported to be the hallmark of IRS. Therefore, the therapeutic impact and the risk of IRS alone or in combination with microsurgery (in case of larger tumor volumes) were prospectively examined.
Seven boys and four girls were included (mean age, 6.8 years; range, 11 months to 16 years). IRS (after stereotactic biopsy) was considered to be indicated for circumscribed tumors with a diameter in the range of 4 cm (four cases). For larger tumors, a combined microsurgical/radiosurgical approach was preferred (seven patients). Temporary iodine-125 seeds were used exclusively (tumor dose calculated to the boundary, 54 Gy; dose rate, 10 cGy/h). Tumor location was hypothalamic/suprasellar in four, lobar in three, deep (thalamus and pineal gland) in two, and within the brain stem in two children. Treatment effects of IRS were estimated according to the MacDonald criteria.
A complete response after IRS was seen in four patients, and a partial response was seen in seven patients (median follow-up, 31.5 months). There was no perioperative morbidity after microsurgery and/or IRS, and no radiogenic complications occurred during the follow-up period. Five patients experienced an improvement in their deficits, and no deterioration in neurological/endocrine function was seen in any of the patients at the time of last follow-up evaluation.
IRS alone or in combination with microsurgery (in the case of larger tumors) is a safe, effective, and minimally invasive treatment strategy for eloquently located pediatric low-grade gliomas and deserves further prospective evaluation.
Child s Nervous System 02/2007; 23(1):39-46. · 1.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dysembryoplastic neuroectodermal or neuroepithelial tumor (DNET) was initially described by Daumas-Duport et al.  in 1988
as a mixed tumor with glial and neuronal elements, and has been included in the World Health Organization classification of
brain tumors as a separate entity . It is considered as hamartomatous, low-grade lesion (WHO grade I) due to the dysplastic
appearance of the lesion and the surrounding cortex. It constitutes about 1.5% of all pediat-ric intracranial tumors. They
mainly occur in the temporal lobe followed by the frontal and occipital lobe or the cerebellum and brain stem . Macroscopically,
DNETs are most of the time confined to the cerebral cortex, but may extend into the adjacent white matter. DNETs typically
manifest during childhood or early adulthood with often medically refractory epileptic seizures. The seizure focus is frequently
in the temporal location, and the lesion most often found in the temporal lobe, followed by the frontal lobes, and is only
rarely located in other lobes. Associated cranial bone deformities with thinning of the overlying calvarium may be present.
Histologically, DNETs are characterized by the presence of a specific element and by a nodular component. The specific elements
consist of oligoden-droglia-like cells that are distributed within a mucinous matrix, in which normal and dysplastic ganglion-like
neurons appear to be floating (“floating neurons”). Although increased cellularity and some pleomorphism may be present, these
lesions are devoid of anaplastic features. Based on the results of immunohistochemical studies, DNETs are considered to originate
from progenitor cells with potential for glial and neuronal differentiation. The surgical outcome is excellent. Even after
subtotal resection recurrences are rare.
[show abstract][hide abstract] ABSTRACT: To examine the role of p57KIP2 in human malignant glioma cells, we studied its expression in a panel of human malignant glioma specimens by western blot and immunohistochemical analysis. To determine the effects of p57KIP2 expression on the phenotype of glioma cells, we analyzed two inducible stably transfected p57KIP2 expressing glioma cell lines. Expression of p57KIP2 was induced in U373 and U87 malignant glioma cells with doxycycline using the tetracycline repressor system. A phagokinetic track assay on gold particles was used to investigate differences in cell migration between p57KIP2 expressing and non-expressing control cells. The effects of the extracellular matrix (ECM) on U373 motility was determined in p57+ and p57-cells on surfaces coated with 5 microg/cm2 of fibronectin, laminin, type I and type IV collagens. The invasion of p57+ and p57- glioma cells across BD Biocoat Matrigel invasion chambers was then determined. p57KIP2 was weakly expressed in 4/6 glioblastoma (GBM) specimens by western blot. By immunohistochemistry, p57KIP2 immunoreactivity was positive in 8/40 GBMs, and was primarily nuclear in location. The motility of U373 glioma cells was significantly reduced after p57KIP2 induction. The presence of ECM proteins did not further alter the motility of p57+ and p57- glioma cells. The results of the invasion chamber assay showed that p57+ cells exhibited a 35% reduction in their invasive capacity as compared to p57- cells. These data suggest that p57KIP2 is expressed in at least some malignant gliomas. Inducible expression of 57KIP2 in cell lines deficient in this cyclin-dependent kinase inhibitor reduces their otility and invasiveness.
Journal of Neuro-Oncology 08/2004; 68(3):217-23. · 3.12 Impact Factor