Objectives To investigate whether gravitational valves reduce the risk of overdrainage complications compared with programmable valves in ventriculoperitoneal (VP) shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). Background Patients with iNPH may benefit from VP shunting but are prone to overdrainage complications during posture changes. Gravitational valves with tantalum balls are considered to reduce the risk of overdrainage but their clinical effectiveness is unclear. Methods We conducted a pragmatic, randomised, multicentre trial comparing gravitational with non-gravitational programmable valves in patients with iNPH eligible for VP shunting. The primary endpoint was any clinical or radiological sign (headache, nausea, vomiting, subdural effusion or slit ventricle) of overdrainage 6 months after randomisation. We also assessed disease specific instruments (Black and Kiefer Scale) and Physical and Mental Component Scores of the Short Form 12 (SF-12) generic health questionnaire. Results We enrolled 145 patients (mean (SD) age 71.9 (6.9) years), 137 of whom were available for endpoint analysis. After 6 months, 29 patients in the standard and five patients in the gravitational shunt group developed overdrainage (risk difference −36%, 95% CI −49% to −23%; p<0.001). This difference exceeded predetermined stopping rules and resulted in premature discontinuation of patient recruitment. Disease specific outcome scales did not differ between the groups although there was a significant advantage of the gravitational device in the SF-12 Mental Component Scores at the 6 and 12 month visits. Conclusions Implanting a gravitational rather than another type of valve will avoid one additional overdrainage complication in about every third patient undergoing VP shunting for iNPH.

BACKGROUND: Ventriculoperitoneal shunt (VP-shunt) is the standard of treatment for idiopathic normal pressure hydrocephalus (iNPH). However, a thorough investigation of VP-shunt complications in this population is lacking. OBJECTIVE: To present the analysis and the rates of complications progressively occurring during the first year after shunt surgery in the patients with iNPH included in the European multicenter (EU-iNPH) study. METHODS: Patients (n = 142) were prospectively included in the EU-iNPH study by 13 institutions. All patients received a programmable VP-shunt. One hundred fifteen patients completed the 12-mo follow-up. Reexaminations were performed 1, 3, and 12 mo after surgery. Data regarding symptomatic over- or underdrainage, infections, malposition, subdural collections, and shunt surgery were collected and analyzed. RESULTS: Thirty patients (26%) experienced symptoms due to shunt underdrainage. Symptomatic overdrainage was reported in 10 (9%). Shunt adjustments were made in 43 (37%). Shunt malposition was recognized as the primary cause of shunt malfunction in 8 (7%), while only 1 infection (0.9%) occurred. Subdural hematoma was diagnosed in 7 (6%) and was treated by increasing the opening pressure of the valve in 5 patients. Hygroma was diagnosed in 10 (9%), requiring surgery in 1 patient. Overall, 17 patients (15%) underwent 19 shunt surgeries. CONCLUSION: The advances in valve technology, a careful opening pressure setting, and rigorous follow-up allow a significant reduction of complications, which can be usually managed nonsurgically within the first 3 to 6 mo.

Object: Shunt therapy in idiopathic normal pressure hydrocephalus (iNPH) can improve symptoms in 84% of patients 1 year postoperatively. Therefore, implantation of a ventriculoperitoneal shunt (VPS) prevents or at least prolongs the time during which patients are not dependent on care from others because of gait disorder or dementia. In this study, the medium-term results of modern shunt therapy were evaluated. Methods: The authors retrospectively studied outcome in iNPH patients in whom VPSs were implanted. At yearly follow-up examinations over at least 6 years, clinical symptoms were recorded according to the NPH recovery rate (NPH-RR): (preoperative Kiefer Scale [KS] score − postoperative KS score)/(preoperative KS score × 10). Time and cause of death over this period were also analyzed. Results: Among the 147 patients treated for iNPH in the period between 1997 and 2006, 69 had died at the time of the authors' survey. Sixty-one patients reached the 6-year examination. The median age was 64 years (range 33–83 years) at the time of VPS implantation and 73 years (range 41–91 years) at the time of this study. Six years after shunt implantation, the median KS score was significantly lower than the preoperative score (4.3 vs 8.1 points). Fifty-nine percent of 61 patients had an excellent outcome, 15% had satisfactory benefit, and 26% had unsatisfactory results 6 years postoperatively. Three of the 147 patients who underwent implantation of a VPS died of cerebral diseases 4–10 years postoperatively. Conclusions: Implantation of a VPS is a safe procedure and can improve symptoms in 74% of patients with iNPH in the longer term.

To evaluate the reliability of the gravitation-assisted adjustable proGAV shunt system with a prospective multicenter study conducted in 10 German hospitals. Enrollment for this observational study began in April 2005 and concluded in February 2006. The protocol required re-examinations 3 and 6 months postoperatively and fixed the endpoint of follow-up at 12 months after implantation. Patients with different types of adult, juvenile, and pediatric hydrocephalus were included and 165 patients were enrolled; 9 died and 12 had incomplete follow-up. Of the assessable 144 patients, 130 completed the protocol after 12 months, whereas 14 failed because of the need to explant the device, mainly because of infection. In 12 patients, components of the shunt, not the valve, were revised. In 65 of the 144 patients, there were 102 readjustments of the valve in 67 incidences because of underdrainage and in 35 because of overdrainage. In 1 case, readjustment was not possible. Determination of pressure level with the verification instrument was safe and corresponded to the required x-ray controls after adjustments. No unintended readjustments were noted. The proGAV is a safe and reliable device.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a common autoimmune encephalitis presenting with psychosis, dyskinesias, autonomic dysfunction and seizures. The underlying autoantibodies against the NR1 subunit are directly pathogenic by disrupting synaptic NMDAR currents. However, antibody titers correlate only partially with the clinical outcome, suggesting the relevance of other factors such as antibody affinity. We thus determined the binding curves of human monoclonal autoantibodies and patients’ cerebrospinal fluid (CSF) against NR1-expressing HEK293 cells using flow cytometry. Antibody affinity was highly variable with binding constants (half-maximal concentration, c₅₀) ranging from 1 to 74 µg/ml for monoclonal antibodies. Comparing values of individual monoclonal antibodies with human CSF samples suggested that the CSF signal is predominantly represented by higher-affinity antibodies, potentially in a concentration range of NR1 antibodies between 0.1 and 5 µg/ml, roughly reflecting 1–10% of total CSF IgG in NMDAR encephalitis. Binding curves further depended on the CSF composition which must be considered when interpreting established clinical routine assays. Normalization of measurements using reference samples allowed high reproducibility. Accurate and reproducible measurement of NR1 antibody binding suggested that biophysical properties of the antibody might contribute to disease severity. Normalization of the data can be an elegant way to allow comparable inter-laboratory quantification of CSF NR1 antibody titers in autoimmune encephalitis patients, a prerequisite for use as surrogate markers in clinical trials. Based on our calculations, low-affinity antibodies can easily remain undetected in routine cell-based assays, indicating that their relation to clinical symptoms should be analyzed in future studies.