SNP array genomic analysis of matched pairs of brain and liver metastases in primary colorectal cancer.

PURPOSE: Brain metastasis formation is a rare and late event in colorectal cancer (CRC) patients and associated with poor survival. In contrast to other metastatic sites, the knowledge on chromosomal aberrations in brain metastases is very limited. METHODS: Therefore, we carried out single nucleotide polymorphism (SNP) array analyses on matched primary CRC and brain metastases of four patients as well as on liver metastases of three patients. RESULTS: Brain metastases showed more chromosomal aberrations than primary tumors or liver metastases. Commonly occurring aberrations were gain of 8q11.1-q24.3 (primary CRC), gain of 13q12.13-q12.3 (liver metastases), and gain of 20q11.1-q13.33 (brain metastases). Furthermore, we found one copy-neutral loss of heterozygosity (cn-LOH) region on chromosome 3 in primary CRC, three cn-LOH regions in liver metastases and 23 cn-LOH regions in brain metastases, comprising 26 previously undescribed sites. CONCLUSION: The more frequent occurrence of cn-LOHs and subsequently affected genes in brain metastases shed light on the pathophysiology of brain metastasis formation. Further pairwise genetic analyses between primary tumors and their metastases will help to define the role of affected genes in cn-LOH regions.

Perioperative external ventricular drainage vs. no-EVD strategy in pediatric posterior fossa tumors-pilot study results.

INTRODUCTION: Pediatric brain tumors of the posterior fossa often present with occlusive hydrocephalus. Endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting (VPS) has been established for definite hydrocephalus treatment. The aim of the study was to analyze the impact and safety of perioperative temporary external ventricular CSF drainage (EVD) placement on postoperative hydrocephalus outcome compared to a no-EVD strategy. PATIENTS AND METHODS: In a prospective database, 36 posterior fossa tumor patients of 2-18 years were included with a follow-up of 1 year. Fifty-eight percent presented with preoperative hydrocephalus. Patients were assigned to non-hydrocephalus group: group I (n = 15) and to preoperative hydrocephalus, group IIa with EVD placement (n = 9), and group IIb without EVD (n = 12). RESULTS: Median age of patients was 8.1 years (range 3.17 to 16.58 years). One-third of 21 hydrocephalus patients required ETV or VPS (n = 7). Occurrence of de novo hydrocephalus in group I after surgery was not observed in our cohort. Age and histology were no confounding factor for EVD placement between group IIa and IIb (p = 0.34). The use of EVD did not result in better control of hydrocephalus compared to no-EVD patients considering pre- and postoperative MRI ventricular indices (p = 0.4). Perioperative placement of an EVD resulted in a threefold risk for subsequent VPS or ETV (group IIa 55.5% vs group IIb 16.6%): relative risk for EVD patients compared to no-EVD patients with hydrocephalus was 3.3 (CI = 1.06-13.43, p = 0.09). CONCLUSION: Perioperative EVD placement appears to harbor a threefold relative risk of requiring subsequent permanent CSF diversion in children above 2 years. EVD was not more effective to control ventricular enlargement compared to tumor removal alone. The no-EVD strategy was safe and did not result in postoperative complications. Thus, to evaluate potential adverse effects on hydrocephalus outcome by EVD placement, a prospective study is warranted to falsify the results.

Feasibility of ApoC1 serum levels as tumor biomarker in glioblastoma patients: a pilot study.

Apolipoprotein C1 (ApoC1) has been detected immunohistochemically in glioblastoma tissue, probably expressed by activated monocytes and microglia. The present study was conceived to determine whether the amount of intratumoral ApoC1 expression leads to measurable changes of serum levels after glioblastoma resection or during recurrence. 176 blood samples from 70 glioblastoma patients were collected perioperatively and during subsequent therapy. ApoC1 serum levels were determined using an enzyme linked immunosorbent assay (ELISA). High absorption values due to lipemic or hemolytic serum were removed from the final dataset using a stem and leaf plot. Samples were grouped according to the treatment stage to compare mean ApoC1 serum levels. The number of patients with falling or increasing perioperative values was assessed. 167 ApoC1 serum values from 68 glioblastoma patients were amenable to statistical evaluation. Mean ApoC1 serum level was 91.9 µg/ml (n = 167, sd = 36.0). In samples from patients undergoing first glioblastoma resection, the mean preoperative value was significantly higher (94.8 µg/ml, n = 37, sd = 29.5) than after surgery (77.4 µg/ml, n = 41, sd = 23.2, p = 0.009). Individually, falling ApoC1 levels were detected in 25 and rising levels in 9 patients (p = 0.0061). Single absolute serum levels of ApoC1 do not allow an estimation of glioblastoma activity or tumor response. Although pathophysiologically of interest, ApoC1 serum levels did not qualify as a potential biomarker in glioblastoma management. Our results do not seem to encourage larger, multicenter studies.

The Mean ApoC1 Serum Level in Postoperative Samples from Neurosurgical Patients Is Lower than in Preoperative Samples and during Chemotherapy.

Serum levels of apolipoprotein ApoC1 have been described in a number of systemic tumor entities as potential biomarkers, but little is known about ApoC1 in neurosurgical patients. A total of 230 serum samples from 96 patients were analyzed using an ELISA technique. Patient diagnoses comprised 70 glioblastomas WHO IV°, 10 anaplastic astrocytomas III°, one anaplastic oligodendroglioma III°, one oligodendroglioma II°, one diffuse astrocytoma II°, one pilocytic astrocytoma I°, and a single case of a spindle cell tumor without WHO grading, as well as 11 spinal interventions. The mean ApoC1 level of the 230 samples was 132.03 µg/mL (median 86.83, SD 292.91). In the 176 glioblastoma samples, the mean ApoC1 level was 130.0 µg/mL (median 86.23, SD 314.9), which was neither different from the whole group nor from patients with spinal interventions (215.1 µg/mL, median 63.6, SD 404.9). In the postoperative samples, the mean ApoC1 level was significantly lower (85.81 µg/mL) than in the preoperative samples (129.64 µg/mL) and in samples obtained during adjuvant chemotherapy (168.44 µg/mL). While absolute ApoC1 serum levels in a patient do not allow for the distinction between neurosurgical histological entities, future analyses will examine whether the time course of ApoC1 in an individual patient can be related to certain treatment stages.

Usefulness and Limits of Tractography for Surgery in the Precentral Gyrus-A Case Report.

The resection of tumors within the primary motor cortex is a constant challenge. Although tractography may help in preoperative planning, it has limited application. While it can give valuable information on subcortical fibers, it is less accurate in the cortical layer of the brain. A 38-year-old patient presented with paresis of the right hand and focal epileptic seizures due to a tumor in the left precentral gyrus. Transcranial magnetic stimulation was not applicable due to seizures, so microsurgical resection was performed with preoperative tractography and intraoperative direct electrical stimulation. A histopathological assessment revealed a diagnosis of glioblastoma. Postoperative magnetic resonance imaging (MRI) showed complete resection. The paresis dissolved completely during follow-up. Surgery within the precentral gyrus is of high risk and requires multimodal functional planning. If interpreted with vigilance and consciousness of the underlying physical premises, tractography can provide helpful information within its limitations, which is especially subcortically. However, it may also help in the identification of functional cortex columns of the brain in the presence of a tumor.

The Relation of Surgical Procedures and Diagnosis Groups to Unplanned Readmission in Spinal Neurosurgery: A Retrospective Single Center Study.

BACKGROUND: Unplanned readmission has gained increasing interest as a quality marker for inpatient care, as it is associated with patient mortality and higher economic costs. Spinal neurosurgery is characterized by a lack of epidemiologic readmission data. The aim of this study was to identify causes and predictors for unplanned readmissions related to index diagnoses and surgical procedures. METHODS: In this study, from 2015 to 2017, spinal neurosurgical procedures were recorded for surgical and non-surgical treated patients. The main reasons for an unplanned readmission within 30 days following discharge were identified. Multivariate logarithmic regression revealed predictors of unplanned readmission. RESULTS: A total of 1172 patient records were examined, of which 4.27% disclosed unplanned readmissions. Among the surgical patients, the readmission rate was 4.06%, mainly attributable to surgical site infections, while it was 5.06% for the non-surgical patients, attributable to uncontrolled pain. A night-time surgery presented as the independent predictive factor. CONCLUSION: In the heterogeneous group of spinal neurosurgical patients, stratification into diagnostic groups is necessary for statistical analysis. Degenerative lumbar spinal stenosis and spinal abscesses are mainly affected by unplanned readmission. The surgical procedure dorsal root ganglion stimulation is an independent predictor of unplanned re-hospitalizations, as is the timing of surgery.

Comparison of the unruptured intracranial aneurysm treatment score recommendations with clinical treatment results - A series of 322 aneurysms.

Intracranial aneurysms occur with a prevalence of 3-5 %. Subarachnoid hemorrhage (SAH) due to aneurysm rupture is a rare but possibly fatal complication, so that occlusion of unruptured intracranial aneurysms (UIA) must be considered. The Unruptured Intracranial Aneurysm Treatment Score (UIATS) offers support for clinical decision making and has been shown to correlate with real life decisions in clinical practice. However, there is no data concerning the correlation of patient outcome and UIATS. Patients presenting to our outpatient clinic between January 1st, 2014 and December 31st, 2017 were retrospectively analyzed. We recorded the Extended Glasgow Outcome Scale (GOS-E) for longest possible follow-up, the choice of treatment, complications and UIATS recommendation. We included 221 patients with 322 UIA. 124 (38.5 %) UIA were observed and 198 (61.5 %) were occluded, of which 62 (31.3 %) underwent open surgery and 136 (68.7 %) were treated endovascularly. Spearman's rank correlation between our treatment choice and conclusive UIATS recommendation was 0.362 (p < 0.001). If UIATS was inconclusive, there were significantly more treatment-associated deteriorations (10/66 versus 7/132, p = 0.020). Otherwise, UIATS was not significantly associated with outcome. Therefore, treatment choice for UIA remains an individual decision. However, inconclusive UIATS must trigger vigilance and may be a negative prognostic marker for complications.

Causes and Predictors of Unplanned Readmission in Cranial Neurosurgery.

OBJECTIVE: A better understanding of the risks and reasons for unplanned readmission is an essential component in reducing costs in the health care system and in optimizing patient safety and satisfaction. The reasons for unplanned readmission vary between different disciplines and procedures. The aim of this study was to identify reasons for readmission in view of different diagnoses in cranial neurosurgery. METHODS: In this single-center retrospective study, adult patients after neurosurgical treatment were analyzed and grouped according to the indication based on International Classification of Diseases and Related Health Problems, Tenth Revision, German Modification diagnosis codes. The main outcome measure was unplanned readmission within 30 days of discharge. Further logistic regression models were performed to identify factors associated with unplanned rehospitalization. RESULTS: Of the 2474 patients analyzed, 183 underwent unplanned rehospitalization. Readmission rates differed between the diagnosis groups, with 9.19% in neoplasm, 8.26% in hydrocephalus, 5.76% in vascular, 6.13% after trauma, and 8.05% in the functional group. Several causes were considered to be preventable, such as wound healing disorders, seizures, or social reasons. Younger age, length of first stay, surgical treatment, and side diagnoses were predictors for unplanned readmission. Diagnoses with an increased risk of readmission were glioblastoma, traumatic subdural hematoma, or chronic subdural hematoma. CONCLUSIONS: Reasons and predictors for an unplanned readmission differ considerably among the index diagnosis groups. In addition to well-known reasons for readmission, we identified social indication, meaning a lack of home care, which is particularly prevalent in oncologic and elderly patients. A transitional care program could benefit these vulnerable patients.

A late systemic and brain metastasis from subcutaneous leiomyosarcoma of the right forearm: a case report and review of the literature.

BACKGROUND: Leiomyosarcomas are rare malignant tumors which originate from smooth muscle cells and very seldom give rise to intracerebral metastases. Nearly all cases of intracranial metastases stem from leiomyosarcomas of the uterus. We present a 61-year-old Caucasian man who developed multiple intracranial and extracranial metastases from leiomyosarcoma of the right forearm, diagnosed and treated 9 years before the current presentation. CASE PRESENTATION: The Caucasian patient presented to the emergency department due to a progressive hemiparesis on the left side. Magnetic resonance imaging scans of the neurocranium showed multiple intracerebral masses with perifocal edema. One of these was located in the right parietal lobe, corresponding to the hemiparesis. The patient underwent microsurgical complete resection of the parietal mass and was subsequently subjected to further radiotherapy. Histopathological studies revealed metastasis of the former leiomyosarcoma. CONCLUSIONS: Leiomyosarcomas represent a rare entity of mesenchymal tumors. Intracerebral metastasis of these tumors is even less frequent. This case shows the importance of long-term follow-up in patients with leiomyosarcoma.

Epidemiologic and anatomic aspects comparing incidental and ruptured intracranial aneurysms: A single centre experience.

The feasibility of multicentric international data such as integrated in the PHASES score for patient counseling in unruptured intracranial aneurysms has recently been challenged. To determine, whether this data is applicable to local populations in a restricted catchment area, we performed a retrospective mono-centric analysis comparing patients with ruptured aneurysms to patients with incidental aneurysms. 200 patients with unruptured aneurysms and 197 patients after aneurysmal subarachnoid hemorrhage were analyzed for risk factors differing between the groups and to the general German population. Subgroup analysis was performed for 25 patients harboring multiple aneurysms, in 19 patients with intracavernous aneurysms and in 77 women of childbearing potential. While the preponderance of female patients was confirmed, significantly more men figured in the patient group with subarachnoid hemorrhage (36.4%) than among unruptured aneurysms (25%). Patients with bleeding events were significantly younger (51.6 years) than patients with incidental aneurysms (57.8 years). The rupture risk prediction of the PHASES score concerning aneurysm size below 7 mm and patient age over 70 years could not be confirmed, instead score points correlated to the clinical outcome after rupture. In our population, pregnant women were not overrepresented. Intracavernous carotid aneurysms contributed to the low risk profile of giant aneurysms. Thus, recommendations from pooled international data have to be adapted cautiously to local circumstances. We retained seven items with predictive value for outpatient counseling: age, smoking, hypertonus and concurrent vascular aberrations as patient characteristics and irregular shape, (increasing) largest diameter and the harboring vessel for the aneurysm.

Persistent hyperprolactinemia, transient hypopituitarism, and transient contralateral third nerve palsy after endovascular treatment of an internal carotid artery aneurysm: Case report and review of the literature.

Intracranial aneurysms have an estimated prevalence of about 3%. A rare subgroup are aneurysms of the internal carotid artery that develop medially into the sellar region. Due to the risk of rupture with subsequent subarachnoid hemorrhage and of compression of surrounding structures, mechanical occlusion is advised. Hypopituitarism is not a rare disease and most often related to pituitary adenoma. Only 0.17% of cases with hypopituitarism are caused by unruptured intracranial aneurysms. Today, the predominant treatment of these aneurysms is endovascular coiling or application of flow diverting stents. We present the case of a 60-year-old female patient, who was treated with endovascular coiling for a right-sided, intracavernous, incidental internal carotid artery aneurysm. On postinterventional day 6, she was readmitted with contralateral third nerve palsy, mild hyponatremia und thyreotropic insufficiency. The symptoms recovered after anti-edematous treatment with corticosteroids; only an asymptomatic hyperprolactinemia persisted. To the best of our knowledge, this is the first case report of transient contralateral cranial nerve palsy combined with transient hypopituitarism after endovascular treatment of an internal carotid aneurysm. As treatment we propose corticosteroids, if necessary in combination with nonsteroidal anti-inflammatory drugs, in order to inhibit inflammatory reactions of the aneurysm wall compromising the nearby, partially compressed neural structures.

Early unplanned readmission of neurosurgical patients after treatment of intracranial lesions: a comparison between surgical and non-surgical intervention group.

BACKGROUND: Recent health care policy making has highlighted the necessity for understanding factors that influence readmission. To elucidate the rate, reason, and predictors of readmissions in neurosurgical patients, we analyzed unscheduled readmissions to our neurosurgical department after treatment for cranial or cerebral lesions. METHODS: From 2015 to 2017, all adult patients who had been discharged from our Department of Neurosurgery and were readmitted within 30 days were included into the study cohort. The patients were divided into a surgical and a non-surgical group. The main outcome measure was unplanned inpatient admission within 30 days of discharge. RESULTS: During the observation period, 183 (7.4%) of 2486 patients had to be readmitted unexpectedly within 30 days after discharge. The main readmission causes were surgical site infection (34.4 %) and seizure (16.4%) in the surgical group, compared to natural progression of the original diagnosis (38.2%) in the non-surgical group. Most important predictors for an unplanned readmission were younger age, presence of malignoma (OR: 2.44), and presence of cardiovascular side diagnoses in the surgical group. In the non-surgical group, predictors were length of stay (OR: 1.07) and the need for intensive care (OR: 5.79). CONCLUSIONS: We demonstrated that reasons for readmission vary between operated and non-operated patients and are preventable in large numbers. In addition, we identified treatment-related partly modifiable factors as predictors of unplanned readmission in the non-surgical group, while unmodifiable patient-related factors predominated in the surgical group. Further patient-related risk adjustment models are needed to establish an individualized preventive strategy in order to reduce unplanned readmissions.

Familial glioblastoma clustering in adult patients: a case report of two non-twin siblings and review of the literature.

Purpose: Familial glioblastoma multiforme (gbm) has been described in children with hereditary tumor syndromes. The occurrence of gbm in adult members of the same family and in the absence of tumor syndromes is extremely rare. We describe the cases of a brother and a sister with multifocal gbm diagnosed at the age of 63 years. We discuss three further paired gbm in adult patients from the literature. Patients and results: The sister was diagnosed with multifocal primary gbm in 2014 at the age of 63 years and 6 months. In 2018, her younger brother had to be operated on for a multifocal primary gbm at the age of 63 years and 9 months. Extended neuropathological examination revealed most markers to be similar, except for the percentage of O6-methylguanine-DNA methyltransferase promotor methylation, the presence of intratumoral immune cells and the immunohistochemical expression of C12ORF75. Comparison with further published cases of familial adult GBM reveals that most of these patients are male, about 65 years old and the tumor is localized predominantly in the left temporal lobe. Conclusion: Paired adult familial gbm occurs mainly in the elderly male patient with an integrative diagnosis of primary gbm. Whereas a statistical coincidence seems to be most likely in these rare cases, supplementary and improved genetic studies may identify pathogenetic causes of gbm.

Flow diversion beyond the circle of Willis: endovascular aneurysm treatment in peripheral cerebral arteries employing a novel low-profile flow diverting stent.

BACKGROUND: Flow diversion (FD) has emerged as superior minimally invasive therapy for cerebral aneurysms. However, aneurysms of small peripheral vessel segments have not yet been adequately treatable. More specifically, currently established devices necessitate large microcatheters which impede atraumatic maneuvering. The Silk Vista Baby (SVB), a novel flow diverter, offers the as yet unique feature of deliverability via a 0.017 inch microcatheter. This study reports our first experience with the SVB in challenging intracranial vessels employing a vessel-specific tailored microcatheter strategy. MATERIALS AND METHODS: 25 patients (27 aneurysms) were prospectively included. A total of 30 SVBs were employed, predominantly targeting demanding aneurysms of the anterior communicating artery complex. The efficacy of the FD was assessed using two-dimensional vector-based perfusion and conventional digital subtraction angiography (DSA) after implantation and at the first follow-up at 3 months. The first follow-up was available in 22 patients. RESULTS: All devices were implanted without technical or clinical complications. Eleven treatments were performed using the recommended Headway 17. In 14 interventions the even more maneuverable Excelsior SL10 was used, which was previously tried and tested for safety 'in vitro' as an alternative delivery system. Aneurysmal influx was strongly reduced after implantation. All parent vessels remained patent. 17/27 aneurysms were completely occluded at first follow-up (∼2.7 months), 6/27 aneurysms showed decreased influx or delayed washout and one remained unchanged. In three cases follow-up DSAs are remaining. CONCLUSIONS: SVB provides enhanced controllability in vulnerable segments beyond the circle of Willis. Smaller variants (2.25 mm and 2.75 mm) can safely be implanted via the superiorly navigable Excelsior SL10. Hence, the SVB represents the next evolutionary step in minimally invasive treatment of cerebral aneurysms.

Assessment of ApoC1, LuzP6, C12orf75 and OCC-1 in cystic glioblastoma using MALDI-TOF mass spectrometry, immunohistochemistry and qRT-PCR.

Mass spectrometric analysis of glioblastoma cyst fluids has disclosed a protein peak with m/z 6424-6433. Among the proteins, potentially generating this peak are ApoC1 and LuzP6. To further elucidate protein expression of glioblastoma cells, we analyzed MALDI-TOF results of cyst fluid, performed immunohistochemistry and mRNA analysis. MALDI-TOF protein extraction from 24 glioblastoma cyst fluids was performed with a weak cation exchange. 50 glioblastoma samples were stained with two custom-made antibodies against LuzP6 and commercial antibodies against ApoC1, C12orf75 and OCC-1 and analyzed. For mRNA detection, 16 tissue samples were stored in RNAlater, extracted using the miRNeasy kit and reversely transcribed. For 12 patients, synopsis of results from all three examinations was possible. MALDI-TOF confirmed the peak at 6433 Da in 75% of samples. Immunohistochemically, LuzP6 was detected in 92% (LuzP61-29) and 96% (LuzP630-58) of samples and ApoC1 in 66%. Mean mRNA levels were highest for ApoC1, followed by LuzP6. No correlation between mRNA expression, immunohistochemical staining and intensity of the MALDI-TOF peaks was found. An unequivocal identification of one protein as the source for the 6433 peak is not possible, but our results point to ApoC1 and LuzP6 as the underlying proteins.

Segment Occlusion vs. Reconstruction-A Single Center Experience With Endovascular Strategies for Ruptured Vertebrobasilar Dissecting Aneurysms.

Objective: Ruptured dissecting aneurysms of the intracranial vertebral arteries exhibit an extraordinarily high risk for morbidity and mortality and are prone to re-rupture. Therefore, early treatment is mandatory to induce stagnation of the critical dynamic mural process. Appropriate endovascular approaches are segment sacrifice and reconstruction, however, both carry specific risks and benefits. To date most studies discuss only one of these approaches and focus on one specific device or technique. Therefore, our study aimed to present our experiences with both techniques, providing a considered approach on when to perform endovascular reconstruction or sacrifice. Materials and Methods: We retrospectively reviewed patients with subarachnoid hemorrhage in our database, suffering from dissecting aneurysms of the intradural vertebral arteries and treated endovascularly in the acute setting. A total of 16 cases were included. Clinical history, radiologic findings and outcomes were analyzed. Results: In 7 patients a reconstructive approach was chosen with 4 of them receiving stent-assisted coiling as primary strategy. One of the 7 patients suffered early re-bleeding due to progression of the dissection and therefore treatment was augmented with implantation of 2 flow diverters. The remaining 2 patients were primarily treated with flow diverters in telescoping technique. In 9 patients a deconstructive approach was followed: 6 patients were treated with proximal coil-occlusion of the V4 segment, 3 patients received distal coiling of the V4 segment. Two patients died (GOS 1) in the subacute stage due to sequelae of recurrent episodes of raised intracranial pressure and parenchymal hemorrhage. Two patients kept severe disability (GOS 3), six patients had moderate disability (GOS 4) and seven patients showed full recovery (GOS 5). None of the patients suffered from a procedural or postprocedural ischemic stroke. Conclusions: In patients with good collateral vascularization, proximal, or distal partial segment sacrifice via with endovascular coil occlusion seems to yield the best risk-benefit ratio for treatment of ruptured dissecting V4 aneurysms, especially since no continued anticoagulation is required and possibly essential surgery remains feasible in this scenario. If possible, PICA occlusion should be avoided-although even proximal PICA occlusion can become necessary, when weighing against the risk of an otherwise untreated ruptured V4 dissecting aneurysm. Contrarily, if the dominant V4 segment is affected, the hemodynamic asymmetry prohibits occlusion and necessitates reconstruction of the respective segment. For this, implants with high metal coverage treating the entire affected segment appear to be the most promising approach.

Increased L1CAM (CD171) levels are associated with glioblastoma and metastatic brain tumors.

L1 cell adhesion molecule (L1CAM) is a member of the immunoglobulin-like cell-adhesion molecule family that was shown to be associated with a worse prognosis in several human cancers. L1 ectodomain shedding via vesicles or exosomes has been detected in extracellular fluids after cleavage from the cell surface by metalloproteases. We evaluated the presence of L1CAM in cyst fluid and tissue from glioblastomas or brain metastases.The amount of L1CAM in cyst fluid of 9 glioblastomas and 11 brain metastases was assessed using enzyme-linked immunosorbent assay (ELISA). Corresponding tumor tissue slices were stained immunohistochemically for L1CAM. Cerebrospinal fluid of 20 non-tumor patients served as controls.Mean levels of L1CAM in tumor cyst fluid were significantly higher in glioblastoma (6118 ±â€Š4095 ng/mL) and metastasis patients (8001 ±â€Š6535 ng/mL) than in CSF of control patients (714 ±â€Š22 ng/mL). The immunohistochemical expression of L1CAM in corresponding tissue was significantly higher in metastases than in glioblastomas.The present study demonstrates high levels of L1CAM in cyst fluid of glioblastoma and metastatic brain tumors. Soluble L1CAM may represent a motility promoting molecule in cancer progression, a co-factor for development of tumor cysts and a target for new treatment strategies.

The Cerebral Surfactant System and Its Alteration in Hydrocephalic Conditions.

INTRODUCTION: Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to host's innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects. PATIENTS AND METHODS: CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0-84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated. RESULTS: SP A-D are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations. CONCLUSION: The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SP's requires further thorough investigations.

Hydrocephalus in aqueductal stenosis--a retrospective outcome analysis and proposal of subtype classification.

UNLABELLED: Treatment of aqueductal stenosis (AQS) has undergone several paradigm shifts during the past decades. Currently, endoscopic ventriculostomy (ETV) is recommended as treatment of choice. Several authors have addressed the issue of variable ETV success rates depending on age and pathogenetic factors. However, success rates have usually been defined as "ETV non-failure." The aim of the study was a retrospective analysis of radiological and neurological treatment response after ETV or VP-shunting (VPS) in age-dependent subtypes of AQS. PATIENTS AND METHODS: Eighty patients (median age 12.0 years, range 0-79 years) have been treated for MRI-proven aqueductal stenosis. Neurological treatment success was defined by neurological improvement and, in childhood, head circumference. Radiological response was measured as Evan's index in follow-up MRI. Initial signs and symptoms, type of surgery, and complications were analyzed. RESULTS: Four types of AQS have been defined with distinct age ranges and symptomatology: congenital type I (n = 24), chronic progressive (tectal tumor-like) type II (n = 23), acute type III (n = 10), and adult chronic (normal-pressure hydrocephalus-like) type IV (n = 23). Retrospective analysis of neurological and radiological outcome suggested that congenital type I (<1 years of age) may be more successfully treated with VPS than with ETV (81 vs. 50 %). Treatment of chronic juvenile type II (age 2-15) by ETV 19 % compared to 57 % after VP-shunt, but similar neurological improvement (>80 %). There has been no influence of persistent ventriculomegaly in type II after ETV in contrast to VPS therapy for neurological outcome. Adult acute type III (age > 15 years) responded excellent to ETV. Chronic type IV (iNPH-like) patients (age > 21) responded neurologically in 70 % after ETV and VPS, but radiological response was low (5 %). CONCLUSION: AQS can be divided into four distinct age groups and types in regards of clinical course and symptomatology. Depending on the AQS type, ETV cannot be unequivocally recommended. Congenital type I AQS may have a better neurological outcome with VP-shunt whereas acute type III offers excellent ETV results. Chronic progressive type II still requires prospective investigation of long-term ETV outcome, especially when ventriculomegaly persists. Late chronic type IV seems to result in similar outcome after VP-shunt and ETV.

Idiopathic normal pressure hydrocephalus: diagnostic and predictive value of clinical testing, lumbar drainage, and CSF dynamics.

OBJECTIVE The aim of the study was to analyze the diagnostic and predictive values of clinical tests, CSF dynamics, and intracranial pulsatility tests, compared with external lumbar drainage (ELD), for shunt response in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS Sixty-eight consecutive patients with suspected iNPH were prospectively evaluated. Preoperative assessment included clinical tests, overnight intracranial pressure (ICP) monitoring, lumbar infusion test (LIFT), and ELD for 24-72 hours. Simple and multiple linear regression analyses were conducted to identify predictive parameters concerning the outcome after shunt therapy. RESULTS Positive response to ELD correctly predicted improvement after CSF diversion in 87.9% of the patients. A Mini-Mental State Examination (MMSE) value below 21 was associated with nonresponse after shunt insertion (specificity 93%, sensitivity 67%). Resistance to outflow of CSF (ROut) > 12 mm Hg/ml/min was false negative in 21% of patients. Intracranial pulsatility parameters yielded different results in various parameters (correlation coefficient between pulse amplitude and ICP, slow wave amplitude, and mean ICP) but did not correlate to outcome. In multiple linear regression analysis, a calculation of presurgical MMSE versus the value after ELD, ROut, and ICP amplitude quotient during LIFT was significantly associated with outcome (p = 0.04). CONCLUSIONS Despite a multitude of invasive tests, presurgical clinical testing and response to ELD yielded the best prediction for improvement of symptoms following surgery. The complication rate of invasive testing was 5.4%. Multiple and simple linear regression analyses indicated that outcome can only be predicted by a combination of parameters, in accordance with a multifactorial pathogenesis of iNPH.