Endoscopic resection of an intraventricular cavernoma: a case report.

Cerebral cavernous malformations occur in 0.5% of the population. They consist of thin-walled vessels and can be found as congenital or sporadic lesions. Most of them are asymptomatic, however, due to their anatomical features blood leakage into the surrounding tissue can cause severe neurological symptoms. Although risk of bleeding is low, symptomatic lesions should be treated, with microsurgical resection being the therapy of choice for surgically accessible cavernomas. Intraventricular cavernous malformations are a rare subtype, and due to their anatomical localization, they are eligible for endoscopic surgery. However, there are only a few reports on endoscopic resection of intraventricular cavernomas to be found in the literature. We report the case of a 48-year-old woman who suffers from multiple cerebral cavernous malformations. Since the first diagnosis, several of these cavernomas had been removed in open microsurgical interventions. Most recently, a new lesion arose intraventricularly, adjacent to the ependymal wall of the right lateral ventricle. In follow-up, cranial MR imaging microbleeding and an increasing size were detected. Eventually, the lesion was endoscopically removed. Presurgery the patient suffered from right-sided sensibility loss and gait disturbances as a consequence of prior surgeries. Postsurgery, no new neurological symptoms could be found. We here present MR images and intraoperative pictures as well as a short video of the resection itself. In our opinion, endoscopic resection of intraventricular cavernomas should be considered in selected cases.

Topical instillation of vancomycin lowers the rate of CSF shunt infections in children.

INTRODUCTION: Shunt surgery in pediatric patients still bears a significant risk of infection, in addition to mechanical complications of the shunt system. Antibiotic-impregnated systems and perioperative antibiotics have been extensively studied for their potential to reduce shunt infections. We examined the effectiveness of intrawound application of vancomycin powder during shunt surgery. PATIENTS AND METHODS: Patient records of 78 primary shunt implantations at a mean age of 40 months were reviewed. In total, 52 patients (mean age 50 months) had been treated according to standard surgical and perioperative procedures (Std), whereas 26 patients (mean age 20 months) additionally had received topical application of vancomycin powder before wound closure (Vmc). Overall infection rate was 3.8%, in Std patients 5.8%, and in Vmc patients 0%. The rates of CSF fistula and revision surgery were similar in both groups (5.8% vs 8% and 23.1% vs. 30%, respectively). CONCLUSION: To the best of our knowledge, this is the first report on topical vancomycin instillation, indicating its efficacy for the prevention of shunt infection in pediatric patients. Further studies with a higher number of patients are needed to verify this finding.

Late-onset hydrocephalus in a child with Joubert syndrome: a case report.

INTRODUCTION: The ciliopathy "Joubert syndrome" was first described in 1969 by Dr. Marie Joubert and most subtypes follow an autosomal recessive inheritance. The complex disorder shows typical clinical features, such as hyperventilation, abnormal eye movements, and retardation. A pathognomonic midbrain-hindbrain malformation, the molar tooth sign, can be found on magnetic resonance imaging of the brainstem. There are a little more than 200 reports of Joubert syndrome in the literature. CASE PRESENTATION: We report a case of a 9-year-old boy who developed a progressive hydrocephalus starting from the age of 4. He underwent VP shunt placement at 8 years, which relieved hydrocephalus-related clinical symptoms and put development of the macrocephalus to a halt. CONCLUSION: Neonatal hydrocephalus due to the altered anatomy of the posterior fossa has been reported earlier, but to our knowledge, this is the first case of a delayed onset of hydrocephalus in a patient with Joubert syndrome.

PTPIP51 levels in glioblastoma cells depend on inhibition of the EGF-receptor.

Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is upregulated in glioblastoma multiforme (GBM) and expression levels correlate with the grade of malignancy in gliomas. A similar correlation was reported for its interacting partner 14-3-3ß, which has been shown to facilitate the interaction of PTPIP51 with cRAF (Raf1). Since the interaction of these signalling partners stimulates growth factor signalling downstream of the epidermal growth factor receptor (EGFR), a major drug target in GBM, we here investigated the impact of EGFR inhibition by small molecule inhibitors or monoclonal antibody on PTPIP51. The effect of EGFR inhibition on PTPIP51 mRNA, protein expression and its interaction profile in GBM was analyzed using the U87 cell line as model system. The transferability of the results to in vivo conditions was evaluated in cultured tumour cells from GBM patients. Cells were treated either to the small molecule tyrosine kinase inhibitor of EGFR Gefitinib or the monoclonal antibody Cetuximab in a time and dose dependent manner. Gefitinib treatment decreased the proliferation rate and induced apoptosis in U87 and primary tumour cells. The PTPIP51 interaction profile changed in correlation to the applied Gefitinib. Despite unchanged mRNA levels PTPIP51 protein was reduced. In contrast, treatment with Cetuximab had no effects on PTPIP51 expression. In conclusion, our results demonstrate the impact of EGFR inhibition by Gefitinib on PTPIP51 protein expression, a downstream regulator of MAPK signalling. These data will serve as a basis to unravel the precise role of PTPIP51-mediated signalling in GBM and its potential implications for Gefitinib-mediated therapy in future studies.

Adult long-term outcome of patients after congenital hydrocephalus shunt therapy.

INTRODUCTION: Even though shunt surgery has been an established and widely accepted treatment for congenital hydrocephalus for five decades, long-term follow-up and functional outcome data is rare. PATIENTS AND METHODS: Sixty-nine patients were examined after congenital hydrocephalus had been treated between 1971 and 1987 at the Department of Pediatric Surgery (University of Leipzig) within the first 12 months of life. Median age of patients was 32 years (range 25-42 years). Patients agreed to undergo a contemporary hydrocephalus assessment. RESULTS: Seven patients (10.1%) became shunt-independent before adulthood. By the age of 20, 82% of the patients had needed at least one shunt revision, 100% by the age of 30. 21.7% of the primary valves (Spitz-Holter) remained intact without revision until today up to 35 years (mean functional intactness 23 years). Shunt infections occurred in 4.3% of primary implantations. 48% of the patients had a good functional outcome (mRS = 0-1). 40.9% of the patients attended regular school. In summary, 75% patients work on a daily basis. 44.6% live an independent life, 35.4% rely on parental supervision, and 20% depend on professional care institutions. CONCLUSION: Compared to the pre-shunt era, surgery within the first year of life is advantageous regarding visual function, educational progress, and social results. The outcome achieved throughout childhood remains stable during adult life as long as catastrophic events of shunt malfunction can be prevented. Epilepsy, motor deficits, acute shunt dysfunction, and problems of social integration as well as aging parental caregivers seem to be prominent factors of morbidity in adulthood.

Anatomic features of glioblastoma and their potential impact on survival.

BACKGROUND: Many reports on glioblastoma multiforme discuss the prognostic impact of anatomical features such as cysts, necrotic changes, extent of edema or subependymal spread of tumor cells. In the present study, we examined different growth patterns and their possible relations to patient survival. METHODS: To analyze whether anatomical characteristics are related to prognosis, we reviewed the prospectively collected pre- and postoperative MRIs of 83 patients in the 5-ALA study, provided by the 5-ALA Glioma Study Group. Following a standardized analytic work flow, the tumor volume and site, presence of necrosis or cysts, and perifocal edema were assessed preoperatively. In the same way, postoperative MRI and the MRI at first recurrence were analyzed. In addition, survival time of the patients was documented. RESULTS: Median survival time of all 83 patients was 15.1 months (range 1.5 to 70.1, mean 18). The site or volume of glioblastoma, as well as the presence of intratumoral necrosis or cysts, did not exert a significant effect on survival time; 96.4 % of recurrences occurred within the former resection margin. Tumors with initial contact with the subependymal zone had multifocal or ventricular recurrences significantly more often. In patients with residual tumor on early postoperative MRI, the follow-up images displayed enlargement of the remnants in 91.9 % of these cases. CONCLUSIONS: A merely anatomical analysis of the glioblastoma growth pattern cannot reliably provide prognostic information. The occurrence of most recurrences next to the resection margin and the high percentage of growing residual tumors underline the importance of complete resections.

The use of 5-aminolevulinic acid fluorescence guidance in resection of pediatric brain tumors.

INTRODUCTION: Whereas in the adult population 5-Aminolevulinic acid (5-ALA) fluorescence guidance has been widely accepted for improving the extent of tumor resection, the application in children remains an off-label use. Even though most pediatric study protocols require a complete resection for improving outcome parameters, only few pediatric patients have been operated with fluorescence guidance, and it remains questionable, whether and which pediatric tumors show useful fluorescence. We present casuistic reports of application of 5-ALA in children collected from three different neurosurgical departments. PATIENTS AND METHODS: In children with suspected malignant intracerebral tumor or recurrence, individual informed consent was obtained in each case from the parents. 5-ALA was administered according to the adult protocol, with 20 mg/kg, 2 h before induction of anesthesia. We retrospectively analyzed 18 patients (13 male, 5 female; age 3-18 years), using the intraoperative neurosurgical protocol, the postoperative MRI results, and the follow-up clinical examinations. RESULTS: The use of 5-ALA fluorescence guidance proved to be safe in our group of pediatric patients. Fluorescence guidance was most useful for recurrent glioblastoma resection. Medulloblastoma tissue displayed fluorescence only inconsistently, and most pilocytic astrocytoma remained without staining. Ganglioglioma showed partial staining in the central tumor areas, without allowing the use for circumferent resection. CONCLUSION: The off-label use of 5-ALA fluorescence guidance in pediatric patients appears to be most useful in recurrent high-grade gliomas. Fluorescence accumulation in other pediatric brain tumor entities is not predictable and should be evaluated in future clinical studies before being integrated into the current treatment protocols.

Acute two-compartment low pressure hydrocephalus--a case report.

A case of an 8-year-old-boy with shunt-dependent occlusive hydrocephalus after resection of a cerebellar medulloblastoma is presented, who experienced repeated episodes of severe neurologic deterioration with signs and symptoms of raised intracranial pressure after spinal tapping. However, intracranial pressure was recorded within low ranges, only up to the opening pressure of the implanted adjustable shunt valve. Multiple shunt revisions were performed, until the condition was recognized as acute normal pressure hydrocephalus. Either enforced recumbency and downadjustment of the valve system to 0 cm H(2)O alone or external ventricular drainage seems to be successful to resolve the critical condition, depending on severity of the symptoms. The case illustrates that acute pathologic enlargement of the ventricular system is not always associated with increased intracranial pressure, even when typical signs and symptoms are present. The very rare entity of acute normal pressure hydrocephalus by two separated compartments is postulated based on the pulsatile vector force theory of brain water circulation.

PTPIP51, a positive modulator of the MAPK/Erk pathway, is upregulated in glioblastoma and interacts with 14-3-3ß and PTP1B in situ.

Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumour. Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is an interaction partner of 14-3-3ß, which correlates with the grade of malignancy in gliomas. In this study PTPIP51 and its interacting partners 14-3-3ß, PTP1B, c-Src, Raf-1 as well as EGFR were investigated in human glioblastoma. Twenty glioblastoma samples were analyzed on transcriptional and translational level by immunohistochemistry, in situ hybridization and RT-PCR. To compare PTPIP51 expression in gliomas of different malignancies, quantitative RT-PCR for grade II astrocytoma and GBM samples was employed. Additionally, we analyzed the correlation between PTPIP51 and 14-3-3ß transcription, and checked for in situ interaction between PTPIP51 and 14-3-3ß and PTP1B, respectively. PTPIP51 and 14-3-3ß mRNA showed a tumour grade dependent upregulation in gliomas. Glioblastoma cells displayed a strong immunoreaction of PTPIP51, which co-localized with 14-3-3ß and PTP1B. The duolink proximity ligation assay corroborated a direct in situ interaction of PTPIP51 with both proteins, known to interact with PTPIP51 in vitro. The in vitro interacting partners Raf-1 and c-Src showed a partial co-localization. Besides, immune cells located in capillaries or infiltrating the tumour tissue and endothelial cells of pseudoglomerular vessels revealed a high PTPIP51 expression. The upregulation of PTPIP51 and its connection with the EGFR/MAPK pathway by 14-3-3ß via Raf-1 and by PTP1B via c-Src, argue for a functional role of PTPIP51 in the pathogenesis of human glioblastoma.

Two cases of Walker-Warburg syndrome complicated by hydrocephalus.

Walker-Warburg syndrome is a very rare autosomal recessive disorder with congenital muscular dystrophy, brain malformations on the basis of a neuronal migration defect and ocular abnormalities. We report our experience in treating two cases of Walker-Warburg syndrome complicated by hydrocephalus with shunting and endoscopic techniques.

Progressive biological behavior of a dysembryoplastic neuroepithelial tumor.

We present the case of a 13-month-old girl with a right occipital cortical alteration on MRI that proved to be a growing lesion. Tumor growth had been observed over a period of 15 months before total resection was performed, revealing a dysembryoplastic neuroepithelial tumor WHO grade I. This case shows that dysembryoplastic neuroepithelial tumors can present as growing neoplasias. It underlines the importance of obtaining histologic diagnosis and close follow-up examinations using MRI, even in so-called stable lesions that are only unveiling through epileptic seizures.

T-cell lymphoma mimicking schwannoma of a cervical nerve root.

T-cell lymphoblastic lymphoma is a rare form of non-Hodgkin lymphoma, which shows preponderance for young men. Most common symptoms are painless swelling of lymph nodes, accompanied by B symptoms and large mediastinal masses. Most often, an involvement of the nervous system is due to paraneoplastic symptoms or side effects of treatment. In a literature research, we could not find a case with affection of a cervical nerve root as the first symptom for T-cell lymphoblastic lymphoma. A 39-year-old man presented with right-sided C8 radiculopathy, including pareses and paresthesia. Since the magnetic resonance image disclosed a right-sided mass lesion in the region of the neuroforamen C8, compressing the corresponding nerve root, a schwannoma was suspected. The tumor was removed using a dorsal approach. Neuropathological examination revealed the diagnosis of T-cell lymphoblastic lymphoma. The patient underwent diagnostic staging and received further treatment. He experienced a very grim course and succumbed to his disease 12 months after surgery. T-cell lymphoblastic lymphoma is a rare disease, and tropism of lymphoma cells to neural structures is seldom encountered. However, the presence of radiculopathy, together with signs, referring to B symptoms, should prompt the physician to consider this coincidence in the differential diagnosis of schwannoma.

Metastatic tumours mimicking vestibular schwannoma.

In this review of the literature we discuss the rare occurrence of metastatic tumours mimicking bilateral vestibular schwannoma and present an own case with pancreatic signet-ring cell carcinoma as primary tumour.

Measurement of intradiscal pressure after lumbar discectomy.

OBJECT: Early physiotherapeutic exercises after lumbar discectomy have been shown to be helpful for pain control and in reducing the delay until the return to work. Many strategies exclude sitting body positions during the first weeks, because raised intradiscal pressure and an increased motion range in the lower lumbar disc levels have been found in unoperated individuals when seated. To evaluate whether these results can be extrapolated to the situation of an operated patient, we examined the feasibility of an intracranial pressure sensor for measuring intradiscal pressure after lumbar discectomy. PATIENT AND METHOD: An otherwise healthy patient underwent lumbar discectomy for a right-sided lumbar disc herniation at the level L4/5. Before surgery he had agreed voluntarily to the implantation of a pressure sensor and the manufacturer had provided data on the safe use of the sensor in the disc space. Intraoperatively the sensor was positioned in the disc space from the right side. Measurements were performed by means of individual readings by three different examiners at different time points. Before removal of the sensor its correct position was demonstrated by X-ray and computed tomography. RESULTS: The patient tolerated surgery very well, recovery and wound healing were un-eventful, and symptoms improved. The pressure monitoring system showed reproducible results without any signs of technical problems. The intradiscal pressure values were about ten times lower than the values known from unoperated individuals (lying: up to 130 mmHg, sitting: up to 50 mmHg, standing: up to 450 mmHg. 100 mmHg=0.013332 MPa). CONCLUSION: We present an easy to perform and technically safe technique for the measurement of intradiscal pressure after lumbar discectomy using an intracranial sensor. To assess the impact of intradiscal pressure on recovery after lumbar microdiscectomy a study with a larger cohort of patients and with long-term follow-up will be needed.

Glioblastoma simultaneously present with meningioma--report of three cases.

BACKGROUND: Most primary intracranial tumors occur as solitary lesions; multiple locations of one tumor, the occurrence of two different tumors or even collision tumors have been described only in a few patients. From a statistical point of view, in less than 100 glioblastoma cases will a meningioma be simultaneously present in the brain. We report three cases with this coincidence and display the results of CGH and chromosome analysis in two patients, in whom the tumors arose in very close spatial correlation to each other. PATIENTS: We describe three case histories with simultaneous occurrence of meningioma and glioblastoma as shown by MRI on admission. After neurosurgical removal of mass lesions, specimens from two patients were cultivated in cell culture and the cells were examined for chromosomal aberrations by conventional karyotyping as well as comparative genomic hybridization (CGH). RESULTS: Examinations disclosed characteristic genetic aberrations for one meningioma and two glioblastomas. In one patient it was possible to compare the data for the meningioma and the glioblastoma; in this case we did not find a common genetic aberration in tumor cells with a different histology. CONCLUSION: Genetic testing of tumor cells should be performed routinely when different histological types of brain tumors are present in a close spatial relationship. We favor the hypothesis of statistical coincidence for the simultaneous occurrence of the two tumors rather than a common pathway giving rise to two tumor entities.

Liponeurocytoma of the left lateral ventricle--case report and review of the literature.

The reported liponeurocytoma of the left lateral ventricle in a 35-year-old man represents the fifth recorded case of a supratentorial intraventricular liponeurocytoma. In this location, liponeurocytomas are very exceptional, whereas it is the typical site for classic central neurocytomas. Conversely, neurocytomas of the cerebellum are predominantly liponeurocytomas with until now more than 25 reported cases. Thus, cerebellar liponeurocytoma is the most frequent neuroepithelial CNS tumor with adipose-like cells followed by ependymomas with a lipid component and supratentorial intraventricular liponeurocytoma. Adipose-like cells in neurocytomas may originate by lipidization of tumor cells, metaplastic transformation of neuroectodermal cells into fat cells or by true adipocytic differentiation. The present case showed also focal glial differentiation with GFAP-positivity of some tumor cells as often seen in cerebellar liponeurocytomas but much rarer in central neurocytomas. Pathogenetic and nosologic implications of supratentorial intraventricular liponeurocytomas are discussed. Future WHO tumor classification should consider that liponeurocytomas are not restricted to the cerebellum. Reports on cerebellar liponeurocytomas with a less favorable clinical course suggest a WHO grade II for liponeurocytomas.

Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study.

The owl monkey (Aotus trivirgatus) has served as the standard non-human primate model of herpes simplex virus-1 (HSV-1) infection because it is highly susceptible to HSV-1 encephalitis. Owl monkeys, however, are expensive, difficult to obtain, and difficult to maintain in captivity, thus greatly hampering the efficiency of preclinical gene therapy trials for brain tumors using HSV-1-based vectors. We have therefore compared the susceptibility of the common marmoset (Callithrix jacchus) with the owl monkey in a model of intracerebral inoculation of wildtype HSV-1 F-strain at increasing titers. The common marmosets consistently succumbed earlier to viral encephalitis than the owl monkeys. The histological evaluation of the common marmoset revealed extensive HSV-1 infection with a concomitant yet less marked inflammatory response compared to the owl monkeys. PCR for HSV-1 demonstrated a similar extra-CNS shedding route in both experimental models. Our findings show that the common marmoset is at least as susceptible to intracerebral HSV-infection as the owl monkey and that it can therefore serve as a valid and reliable experimental model for the important preclinical safety tests of HSV-based therapeutic viral vector constructs in the brain.