Preoperative word-finding difficulties in children with posterior fossa tumours: a European cross-sectional study.

PURPOSE: Posterior fossa tumour surgery in children entails a high risk for severe speech and language impairments, but few studies have investigated the effect of the tumour on language prior to surgery. The current crosslinguistic study addresses this gap. We investigated the prevalence of preoperative word-finding difficulties, examined associations with medical and demographic characteristics, and analysed lexical errors. METHODS: We included 148 children aged 5-17 years with a posterior fossa tumour. Word-finding ability was assessed by means of a picture-naming test, Wordrace, and difficulties in accuracy and speed were identified by cut-off values. A norm-based subanalysis evaluated performance in a Swedish subsample. We compared the demographic and medical characteristics of children with slow, inaccurate, or combined slow and inaccurate word finding to the characteristics of children without word-finding difficulties and conducted a lexical error analysis. RESULTS: Thirty-seven percent (n = 55) presented with slow word finding, 24% (n = 35) with inaccurate word finding, and 16% (n = 23) with both slow and inaccurate word finding. Children with posterior fossa tumours were twice as slow as children in the norming sample. Right-hemisphere and brainstem location posed a higher risk for preoperative word-finding difficulties, relative to left-hemisphere location, and difficulties were more prevalent in boys than in girls. The most frequent errors were lack of response and semantically related sideordinated words. CONCLUSION: Word-finding difficulties are frequent in children with posterior fossa tumours, especially in boys and in children with right-hemisphere and brainstem tumours. Errors resemble those observed in typical development and children with word-finding difficulties.

Postoperative speech impairment and cranial nerve deficits after secondary surgery of posterior fossa tumours in childhood: a prospective European multicentre study.

PURPOSE: Brain tumours constitute 25% of childhood neoplasms, and half of them are in the posterior fossa. Surgery is a fundamental component of therapy, because gross total resection is associated with a higher progression-free survival. Patients with residual tumour, progression of residual tumour or disease recurrence commonly require secondary surgery. We prospectively investigated the risk of postoperative speech impairment (POSI) and cranial nerve dysfunction (CND) following primary and secondary resection for posterior cranial fossa tumours. METHODS: In the Nordic-European study of the cerebellar mutism syndrome, we prospectively included children undergoing posterior fossa tumour resection or open biopsy in one of the 26 participating European centres. Neurological status was assessed preoperatively, and surgical details were noted post-operatively. Patients were followed up 2 weeks, 2 months and 1 year postoperatively. Here, we analyse the risk of postoperative speech impairment (POSI), defined as either mutism or reduced speech, and cranial nerve dysfunction (CND) following secondary, as compared to primary, surgery. RESULTS: We analysed 426 children undergoing primary and 78 undergoing secondary surgery between 2014 and 2020. The incidence of POSI was significantly lower after secondary (12%) compared with primary (28%, p = 0.0084) surgery. In a multivariate analysis adjusting for tumour histology, the odds ratio for developing POSI after secondary surgery was 0.23, compared with primary surgery (95% confidence interval: 0.08-0.65, p = 0.006). The frequency of postoperative CND did not differ significantly after primary vs. secondary surgery (p = 0.21). CONCLUSION: Children have a lower risk of POSI after secondary than after primary surgery for posterior fossa tumours but remain at significant risk of both POSI and CND. The present findings should be taken in account when weighing risks and benefits of secondary surgery for posterior fossa tumours.

Needs and preferences among patients with high-grade glioma and their caregivers - A longitudinal mixed methods study.

Previous reports on the patient perspective of daily life during a 1-year high-grade glioma (HGG) trajectory from the time of diagnosis are sparse. The aim of this longitudinal mixed methods study is to identify the specific needs and preferences for rehabilitation and supportive care and how it links with physical activity, psychological measures and health quality longitudinally over the first year after diagnosis among patients with HGG and their caregivers by integrating qualitative and quantitative findings. Using a longitudinal mixed methods design, patients with malignant glioma (n = 30) and their caregivers (n = 33) were interviewed and completed questionnaires (patients only) about physical activity level, anxiety/depression and quality of life five times during the 1-year period. Their needs and preferences included interventions designed to re-define hope after diagnosis, health promoting physical activities initiated early, psychological symptom management strategies, and life planning. Caregivers are committed to their caregiving role, but their engagement is nonetheless challenged over time by enormous caregiver burdens. The identified specific needs and preferences favour supportive care, education, information and rehabilitation. Guidelines attentive to these needs and implemented in clinical practice have the potential to improve patients' health-related quality of life and support caregivers by involving them more actively in care and management.

Choroid plexus aquaporin 1 and intracranial pressure are increased in obese rats: towards an idiopathic intracranial hypertension model?

BACKGROUND/OBJECTIVES: Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure (ICP) without identifiable cause. The majority of IIH patients are obese, which suggests a connection between ICP and obesity. The aim of the study was to compare ICP in lean and obese rats. We also aimed to clarify if any ICP difference could be attributed to changes in some well-known ICP modulators; retinol and arterial partial pressure of CO2 (pCO2). Another potential explanation could be differences in water transport across the choroid plexus (CP) epithelia, and thus we furthermore investigated expression profiles of aquaporin 1 (AQP1) and Na/K ATPase. METHODS: ICP was measured in obese and lean Zucker rats over a period of 28 days. Arterial pCO2 and serum retinol were measured in serum samples. The CPs were isolated, and target messenger RNA (mRNA) and protein were analyzed by quantitative PCR and western blot, respectively. RESULTS: Obese rats had elevated ICP compared to lean controls on all recording days except day 0 (P<0.001). Serum retinol (P=0.35) and arterial pCO2 (P=0.16) did not differ between the two groups. Both AQP1 mRNA and protein levels were increased in the CP of the obese rats compared to lean rats (P=0.0422 and P=0.0281). There was no difference in Na/K ATPase mRNA or protein levels (P=0.2688 and P=0.1304). CONCLUSION: Obese Zucker rats display intracranial hypertension and increased AQP1 expression in CP compared to lean controls. The mechanisms behind these changes are still unknown, but appear to be unrelated to altered pCO2 levels or retinol metabolism. This indicates that the increase in ICP might be related to increased AQP1 levels in CP. Although further studies are warranted, obese Zucker rats could potentially model some aspects of the IIH pathophysiology.

Postural influence on intracranial and cerebral perfusion pressure in ambulatory neurosurgical patients.

We evaluated postural effects on intracranial pressure (ICP) and cerebral perfusion pressure [CPP: mean arterial pressure (MAP) - ICP] in neurosurgical patients undergoing 24-h ICP monitoring as part of their diagnostic workup. We identified nine patients (5 women, age 44 ± 20 yr; means ± SD), who were "as normal as possible," i.e., without indication for neurosurgical intervention (e.g., focal lesions, global edema, abnormalities in ICP-profile, or cerebrospinal fluid dynamics). ICP (tip-transducer probe; Raumedic) in the brain parenchyma (n = 7) or in the lateral ventricles (n = 2) and cardiovascular variables (Nexfin) were determined from 20° head-down tilt to standing up. Compared with the supine position, ICP increased during 10° and 20° of head-down tilt (from 9.4 ± 3.8 to 14.3 ± 4.7 and 19 ± 4.7 mmHg; P < 0.001). Conversely, 10° and 20° head-up tilt reduced ICP to 4.8 ± 3.6 and 1.3 ± 3.6 mmHg and ICP reached -2.4 ± 4.2 mmHg in the standing position (P < 0.05). Concordant changes in MAP maintained CPP at 77 ± 7 mmHg regardless of body position (P = 0.95). During head-down tilt, the increase in ICP corresponded to a hydrostatic pressure gradient with reference just below the heart, likely reflecting the venous hydrostatic indifference point. When upright, the decrease in ICP was attenuated, corresponding to formation of a separate hydrostatic gradient with reference to the base of the skull, likely reflecting the site of venous collapse. ICP therefore seems to be governed by pressure in the draining veins and collapse of neck veins may protect the brain from being exposed to a large negative pressure when upright. Despite positional changes in ICP, MAP keeps CPP tightly regulated.

Controlled rehabilitative and supportive care intervention trials in patients with high-grade gliomas and their caregivers: a systematic review.

BACKGROUND: Patients diagnosed with high-grade gliomas experience a varying and complex symptom burden, and face a high mortality rate. As a consequence, patients with high-grade gliomas and their caregivers have imminent and changing rehabilitative and supportive care needs. OBJECTIVES: To give a detailed overview of non-pharmacological rehabilitative and supportive care interventions for patients with high-grade gliomas and/or their caregivers, and provide an appraisal of the methodological quality of these studies. METHOD: PubMed, Cumulative Index of Nursing and Allied Health Literature and Embase were searched for literature published from 1995 to May 2013. Data from eight studies were reviewed for substantive methods and results. Methodological quality was described and assessed using the scoring system for appraising mixed methods research and concomitantly appraising qualitative, quantitative and mixed methods primary studies in mixed study reviews. RESULTS: The search yielded 914 unique publications, of which 9 were classified eligible for this review. There is preliminary evidence that cognitive group therapy improves memory skills in patients with high-grade gliomas, early physical training improves functional outcome and massage therapy reduces stress. Patients and caregivers found that telephone follow-up and a specialist nurse function was an effective and useful way to achieve information and support. Finally, psycho-education increased feelings of mastery among caregivers. CONCLUSIONS: As evidence is beginning to emerge, there is a need for well-designed longitudinal and randomised controlled trials of non-pharmacological interventions in high-grade glioma patients and their caregivers in order to develop clinical guidelines for supportive and rehabilitative approaches in this unique population.

The feasibility of a brain tumour website.

PURPOSE: Patients with a high-grade glioma (HGG) and their caregivers have imminent and changing informational and supportive care needs. The purpose of this study was to investigate the feasibility and safety of a Danish brain tumour website (BTW) in patients with HGG and their caregivers. We hypothesized that the BTW would be feasible, safe, helpful and convenient for individuals to obtain support and information. METHODS: This is an exploratory, prospective six-month feasibility study. Two separate samples were collected: 1) a nationwide sample consisting of BTW visitors over a six-month period and 2) a sample of patients with HGG (n = 9) and their caregivers (n = 8) interviewed three months after being introduced to the BTW. RESULTS: The BTW was accessed from 131 different Danish towns and cities, and from ten different countries. The website had 637 unique users. The interviews identified one overarching theme 'challenges and barriers'. Being newly diagnosed, patients described a chaotic and overwhelming life situation and had difficulties in identifying with their new and changed role. When using the BTW, some patients and caregivers experienced technological challenges, while the former also experienced cognitive difficulties. Caregivers greatly appreciated that the BTW was available and that easily accessible specialists could answer their questions. CONCLUSION: The BTW attracted nationwide interest and activity, but the burden of being newly diagnosed with HGG combined with a low level of internet skills and cognitive deficits were barriers to participation. TRIAL REGISTRATION NUMBER: ISRCTN22038059.

Health-related quality of life in patients with high-grade gliomas: a quantitative longitudinal study.

The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity levels, prevalence and severity of anxiety and depressive symptoms and health-related quality of life among patients with a highgrade glioma. This paper is based on a longitudinal mixed methods study. Patients (n = 30) completed questionnaires at 5 time points from time of diagnosis until the final follow-up after 1 year. Scores of Karnofsky Performance Status (KPS), physical activity, anxiety and depression and health-related quality of life (FACT-Br) are obtained. Patients' physical activity level and KPS decrease during the disease- and treatment trajectory. The majority of patients did not report any depressive symptoms, eight individuals (26.7 %) being depressed at various time points. Among a sub-group of participants who completed all study requirements for the entire study period the level of anxiety decreased significantly during the study. The FACT-Br sub-scale of emotional well-being increased significant, indicating a better HRQOL attend of followup. The diagnosis of a HGG leads to an ongoing functional decline measured as a decline of the KPS and a reduced physical activity during leisure time. Supportive care combined with rehabilitative and palliative approaches might well be valuable along the trajectory especially during the post-surgery period when anxiety is at its highest peak.

Syringomyelia: a practical, clinical concept for classification.

BACKGROUND: The term syringomyelia describes many pathogenetically different disorders, and a variety of attempts to group these based on different criteria have been proposed in the literature. As a consequence a lack of consensus regarding classification and terminology exists. This inconsistency extends to the ICD-10 classification of diseases in regards to syringomyelia (G95.0) and hydromyelia (Q06.4). We propose a new unifying concept for classification that also incorporates diagnostics and treatment. METHODS: The PubMed online database was used to gain a general overview of the existing pathogenetic theories in relation to syringomyelia. Illustrative cases at our department were included and similar cases of the literature were found using the PubMed database. All material was reviewed with main focus on the classification and terminology used. RESULTS: Despite syringomyelia (G95.0) and hydromyelia (Q06.4) existing as independent ICD-10 entities, we have shown that the use of classifying terminology for fluid-filled cavities in the spinal cord is indiscriminate and inconsistent. Even though a general agreement on the believed pathogenetic mechanism exists, and the general treatment methods are used in accordance with this mechanism, the terminology fails to function as a simple and universal link between theory and treatment. CONCLUSIONS: We propose a new causal concept for an ICD classification with syringomyelia (G95.0) as the only describing terminology, thus abandoning the use of hydromyelia (Q06.4). Syringomyelia is divided into five subgroups according to the associated pathologies. The classification is based on applied diagnostics and serves as a clinical guidance for treatment.

A longitudinal, qualitative and quantitative exploration of daily life and need for rehabilitation among patients with high-grade gliomas and their caregivers.

INTRODUCTION: High-grade gliomas (HGGs) are the most malignant type of brain tumours. The 5-year survival is 10% and a significant part of the ongoing research aims to increase survival through surgical and oncological treatments. Accordingly, there is an increasing need for investigating the HGG trajectory in order to recommend specific guidelines for rehabilitative and supportive interventions. METHOD AND ANALYSIS: This study protocol (phase I) describes a longitudinal, qualitative, explorative and descriptive interview study of the life situation and need for rehabilitation among patients and their caregivers and a quantitative evaluation of health-related quality of life. Qualitative and quantitative data are collected in parallel, analysed separately and then merged. The finding of this study will, together with the existing literature, form the background for phase II, which is a feasibility study with a pre-experimental one-group design testing a rehabilitative and supportive intervention programme. The aim of this paper was to describe the design of an upcoming study. Interviews with 30 patients and 30 caregivers will provide information about how the life situation is experienced during the first year after being diagnosed with HGG. Quantitative measurements of quality of life, well-being and physical activity will provide additional information. More precisely, both qualitative and quantitative data will support the planning of the programme regarding the type of intervention(s), with or without supervision, the appropriate time along the trajectory, frequency, localisation, endpoint measurements and eligible patients and/or caregivers. ETHICS AND DISSEMINATION: According to the Research Ethics Committee, approval is not needed for phase I as it is a non-intervention part of the study. Ethical approval of phase II will be sought at the time where the content of the intervention programme has been developed. Dissemination will occur through presentation and findings will be published in peer-reviewed journals.

Pathophysiology of shunt dysfunction in shunt treated hydrocephalus.

BACKGROUND: We hypothesized that shunt dysfunction in the ventricular catheter and the shunt valve is caused by different cellular responses. We also hypothesized that the cellular responses depend on different pathophysiological mechanisms. METHODS: Removed shunt material was collected. Macroscopic tissue in the catheters was paraffin-embedded and HE-stained. Valves were incubated with trypsin-EDTA in order to detach macroscopically invisible biomaterial, which was then cytospinned and HE-stained. Associated aetiological and surgical data were collected by reviewing patient files, and ventricular catheter position was examined using preoperative radiology (CT scans). RESULTS: We examined eleven ventricular catheters and ten shunt valves. Catheters: 6/11 catheters contained intraluminal tissue consisting of vascularised glial tissue and inflammatory cells (macrophages/giant cells and a few eosinophils). Catheter adherence correlated with the presence of intraluminal tissue, and all tissue containing catheters had some degree of ventricle wall contact. All obstructed catheters contained intraluminal tissue, except one catheter that was dysfunctional because of lost ventricular contact. Valves: Regardless of intraoperative confirmation of valve obstruction, all ten valves contained an almost uniform cellular response of glial cells (most likely ependymal cells), macrophages/giant cells, and lymphomonocytic cells. Some degree of ventricle wall catheter contact was present in all examined valves with available radiology (9/10). CONCLUSIONS: The same cellular responses (i.e., glial cells and inflammatory cells) cause both catheter obstruction and valve obstruction. We propose two synergistic pathophysiological mechanisms. (1) Ventricle wall/parenchymal contact by the catheter causes mechanical irritation of the parenchyma including ependymal exfoliation. (2) The shunt material provokes an inflammatory reaction, either nonspecific or specific. In combination, these mechanisms cause obstructive tissue ingrowth (glial and inflammatory) in the catheter and clogging of the valve by exfoliated glial cells and reactive inflammatory cells.

Differences in distribution and regulation of astrocytic aquaporin-4 in human and rat hydrocephalic brain.

AIMS: Aquaporin-4 (AQP4) is the most abundant cellular water channel in brain and could be a molecular basis for a cerebrospinal fluid absorption route additional to the arachnoid villi. In the search for 'alternative' cerebrospinal fluid absorption pathways it is important to compare experimental findings with human pathophysiology. This study compares expression of AQP4 in hydrocephalic human brain with human controls and hydrocephalic rat brain. METHODS: Cortical biopsies from patients with chronic hydrocephalus (n = 29) were sampled secondary to planned surgical intervention. AQP4 in human hydrocephalic cortex relative to controls was quantified by Western blotting (n = 28). A second biopsy (n = 13) was processed for immunohistochemistry [glial fibrillary acidic protein (GFAP), CD68, CD34 and AQP4] and double immunofluorescence (AQP4 + GFAP and AQP4 + CD34). Brain tissue from human controls and kaolin-induced hydrocephalic rats was processed in parallel. Immunohistochemistry and immunofluorescence were assessed qualitatively. RESULTS: Western blotting showed that AQP4 abundance was significantly increased (P < 0.05) in hydrocephalic human brain compared with controls. AQP4 immunoreactivity was present in both white and grey matter. In human brain (hydrocephalic and controls) AQP4 immunoreactivity was found on the entire astrocyte membrane, unlike hydrocephalic rat brain where pronounced endfeet polarization was present. Endothelial AQP4 immunoreactivity was not observed. CONCLUSIONS: This study shows a significant increase in astrocytic AQP4 in human hydrocephalic cortex compared with control. Cell type specific expression in astrocytes is conserved between rat and human, although differences of expression in specific membrane domains are seen. This study addresses direct translational aspects from rat to human, hereby emphasizing the relevance and use of models in hydrocephalus research.

Medication overuse as a cause of chronic headache in shunted hydrocephalus patients.

PURPOSE: To highlight the group of hydrocephalus patients known to have a long history of shunt revisions and refractory chronic headache. When a shunt in perfect working order has no effect on headache, other causes of headache should be investigated. In this paper, patients with medication overuse headache are identified and the positive effect of medication withdrawal are described. MATERIALS AND METHOD: Patients with hydrocephalus and shunt referred from the neurosurgical department to the Danish Headache Centre were identified. In all cases, over- and underdrainage was ruled out prior to referral. Six patients with medication overuse headache were documented and their charts were reviewed retrospectively with specific attention to: shunt revisions, inpatient and outpatient contacts, headache data and medication use before and after withdrawal of analgesic medication overuse. RESULTS: A marked reduction in shunt revisions and inpatient contacts in five out of six patients was found and a reduction in outpatient contacts in four out of six patients. Furthermore, an improvement in headache intensity was found in three out of six patients and a reduction in duration was found in two out of six patients. CONCLUSION: This study indicates that it is important to identify shunt patients with persistent chronic headache from causes other than shunt malfunction. By reducing their analgesic intake, it is possible to reduce headaches, the number of surgical interventions and hospital contacts. Hopefully this will raise awareness and lead to further research on the subject.

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit.

AIM: To evaluate the effect of fractionated stereotactic radiotherapy (FSRT) in acromegaly in a retrospective analysis. PATIENTS AND METHODS: Thirty-four patients (17 females, median 43 years (range 30-74)) with acromegaly were treated with FSRT (conformal dynamic arcing, dose 54 Gy, 27-30 fractions) between January 1998 and April 2007. Of the 34 patients, 32 had undergone transsphenoidal adenotomy, and 28 were on medical therapy before FSRT. Patients on medical therapy continued this during and after the irradiation. The treatment was gradually decreased/withdrawn after careful assessment. RESULTS: Magnetic resonance scanning of the pituitary gland 34 months (median, range 11-95) after irradiation showed stable or reduced volume of the remaining tumour tissue in 31 of 34 patients (91%). Seventeen patients (50%) were biochemically controlled (normalised nadir GH during oral glucose tolerance test and IGF1 <+2 S.D.) 30 months after FSRT (median, range 6-60), and ten of them had true biochemical remission (off medical therapy) 30 months after FSRT (median, range 12-69). Of 28 patients with one or more functioning pituitary axes before irradiation, 8 (29%) developed further deficit of one or two pituitary axes 48 months (median, range 6-102) after FSRT. Of 34 patients, 20 still required medical treatment for acromegaly at the end of this study, mainly those with a short follow-up period after irradiation. CONCLUSION: The FSRT seems promising in terms of treatment of acromegaly. Longer follow-up is, however, needed to assess the overall efficacy and safety of FSRT for acromegaly.

Lumbar elastance and resistance to CSF outflow correlated to patency of the cranial subarachnoid space and clinical outcome of endoscopic third ventriculostomy in obstructive hydrocephalus.

OBJECT: The purpose of the present study was to elucidate the value of the lumbar and intraventricular infusion tests in the selection of patients with obstructive hydrocephalus (OH) for endoscopic third ventriculostomy (ETV), and whether the presence of a diminished cranial subarachnoid space was a source of error in the interpretation of the results. METHODS: In 32 consecutive adult patients (15 M, 17 F, mean age: 46 years) with possible treatment-requiring OH, the resistance to cerebrospinal fluid (CSF) outflow (Rout) and elastance was measured with a lumbar infusion test. Eleven of the patients underwent an additional intraventricular infusion test. An ETV was subsequently performed in 20 patients, of whom 11 presented with idiopathic aqueductal stenosis and 9 with other various causes of OH. RESULTS: The presence of a diminished cranial SAS correlated significantly with increased lumbar elastance, but not with lumbar Rout. However, distinctly increased Rout values (>24 mmHg/mL/min, n=4) were only measured in the presence of a diminished cranial SAS. No significant correlation was demonstrated between the clinical outcome of ETV and lumbar elastance or lumbar Rout, although seven out of the eight improving patients with aqueductal stenosis presented normal lumbar Rout values. In patients undergoing both a lumbar and an intraventricular infusion test and improving after ETV (n=6), lumbar elastance was significantly increased compared to the intraventricular elastance. CONCLUSION: A diminished cranial SAS correlates with increased lumbar elastance and may explain the highly increased lumbar Rout values, possibly by impeding the bulk flow from the infusion. The majority of patients improving after ETV and presenting a normal sized cranial SAS presented normal lumbar Rout values. Supplementing the lumbar infusion test with an intraventricular test may help in predicting the outcome of ETV.

Erythropoietin in patients with aneurysmal subarachnoid haemorrhage: a double blind randomised clinical trial.

BACKGROUND: Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH. METHODS: A larger scale clinical trial was planned but preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i.e. transcranial Doppler (TCD) flow velocity, symptomatic vasospasm, cerebral metabolism (microdialysis) and jugular venous oximetry, biochemical markers of brain damage (S-100beta and neuron specific enolase) and blood-brain barrier integrity. FINDINGS: The limited sample size precluded our primary hypotheses being verified and refuted. However, data from this study are important for any other study of SAH and as much raw data as possible are presented and can be included in future meta analyses. On admission the proportion of patients in a poor condition was higher in the EPO group compared with the placebo group but the difference was statistically insignificant. In the EPO-treated patients the CSF concentration of EPO increased 600-fold. Except for a higher extracelullar concentration of glycerol in the EPO group probably caused by the poorer clinical condition of these patients, there were no statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated. CONCLUSIONS: Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted.

Ultrasound-guided percutaneous placement of ventriculoatrial shunts.

INTRODUCTION: In accordance with the literature on ventriculoatrial (VA) shunts, a percutaneous approach to the internal jugular vein is preferable to surgical preparation of the vein before catheter placement. Inspired by the above and the problems still remaining in the percutaneous method and successful results from anaesthesiology with the use of ultrasound-guided placement of central venous catheters, we have implemented an ultrasound-guided percutaneous technique for placement of VA shunts including pre- and intraoperative ultrasound guidance. METHODS: Data on 26 VA shunt operations were collected and analysed with special reference to the applicability of the method to pediatric patients, surgical complications and differences between revisions and first-time VA shunts. CONCLUSIONS: All patients with VA shunt indications were operated successfully with this technique including children down to the age of 5 years. The ultrasound-guided percutaneous technique results in a safe, quick and easy procedure with preoperative knowledge of the diameter of the vein, no accidental carotid artery puncture or pneumothorax, a minimal blood loss, a short operative time, few infectious complications and a good cosmetic result. Results for all parameters were identical in first-time VA shunt operations and revisions.

Idiopathic normal-pressure hydrocephalus: clinical comorbidity correlated with cerebral biopsy findings and outcome of cerebrospinal fluid shunting.

OBJECTIVES: To elucidate the importance of clinically diagnosed cerebral comorbidity in idiopathic normal-pressure hydrocephalus (INPH) and its effect on improvement after shunt surgery as well as concordance with parenchymal pathological changes described in frontal cerebral biopsy specimens. METHODS: In 28 consecutive patients diagnosed with INPH and shunted according to clinical, radiological and cerebrospinal fluid dynamic criteria, concomitant disorders were carefully registered, with special emphasis on cerebrovascular disease (CVD) and possible Alzheimer's disease. During shunt surgery, a frontal cerebral biopsy specimen was obtained and subsequently analysed for pathological changes. RESULTS: One or several concurrent disorders were present in 89% of the patients, most often CVD (n = 17) and possible Alzheimer's disease (n = 12), of which eight patients presented both, diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The shunt success rate was 33%. A clear tendency towards increasing prevalence of CVD or Alzheimer's disease was found in the subgroups with no improvement or clinical deterioration compared with the patients improving after shunt surgery. The presence of CVD tended towards an unfavourable shunt outcome. The pathological parenchymal changes reflected the clinical diagnoses of comorbidity, and were described in about half of the biopsy specimens, with Alzheimer's disease (n = 7) and vascular changes (n = 7) being the most common findings. However, no significant correlation was found with the clinical diagnoses of Alzheimer's disease and CVD. The presence of cerebral comorbidity, whether diagnosed clinically or by brain biopsy, did not preclude clinical improvement after shunt operation. CONCLUSIONS: A high prevalence of CVD and Alzheimer's disease was found in patients shunted for INPH, which was reflected, although less commonly, by similar neuropathological biopsy findings. No significant correlation was found between the presence of comorbidity and shunt outcome. The findings support the perception of INPH as a multiaetiological clinical entity, possibly overlapping pathophysiologically with CVD and Alzheimer's disease.

New evidence for the origin of intracranial germ cell tumours from primordial germ cells: expression of pluripotency and cell differentiation markers.

Primary intracranial germ cell tumours are rare neoplasms that occur in children and adolescents. This study examined both the biology and the origin of these tumours, as it has been hypothesized that they originate from a totipotent primordial germ cell. We applied recent knowledge from gonadal germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected with their gonadal equivalents, including a close similarity with primordial germ cells. A notable difference was the sex-specific expression of TSPY, a gene previously implicated in the origin of gonadoblastoma. TSPY was only detected in germ cell tumours in the central nervous system (CNS) from males, suggesting that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which is a hallmark of primordial germ cells.

Intraventricular or lumbar infusion test in adult communicating hydrocephalus? Practical consequences and clinical outcome of shunt operation.

BACKGROUND: To investigate the therapeutic consequences of restricting the CSF dynamic evaluation to a lumbar infusion test (LIT), as opposed to our formerly applied intraventricular assessment (VIT), in patients with communicating hydrocephalus (CH). METHOD: All patients over 18 years of age referred with clinical and radiological indication of treatment-requiring secondary CH (n = 50) or idiopathic normal-pressure hydrocephalus (INPH, n = 33) were subjected to a LIT. Subsequently, a combination of the results of the LIT (mainly the resistance to CSF outflow) and the clinical presentation determined whether to proceed with (a) VIT before a decision about shunt surgery, (b) shunt surgery or (c) no further diagnostic investigation or surgery. FINDINGS: In 88 percent of the patients with secondary CH and 80 percent of the patients with INPH the decision on shunt surgery was made after performing exclusively a LIT. The shunting success rate was 90 percent in patients with secondary CH and 82 percent in patients with INPH, which however in the latter group decreased to 76 percent, when including the patients undergoing an additional VIT. The achieved shunt success rates are equal or better, compared to the results from previous studies using intraventricular assessment. CONCLUSIONS: LIT and VIT are equally reliable for selecting shunt responsive patients with CH, using clinical improvement rate as the main criterion for comparison. The practical and economic consequences are substantial: the LIT can be performed in an outpatient setting, whereas VIT necessitates hospitalisation for 1-2 days including occupation of the neurosurgical theatre and postoperative neuro-intensive monitoring.