Ullrich Meier

Idiopathic normal-pressure hydrocephalus (iNPH) is a distinct form of dementia, characterized by gait ataxia, cognitive impairment and urinary incontinence. In contrast to all other causes of dementia (e.g., Alzheimer-type and others), ventriculoperitoneal (VP) shunt surgery may offer a curative treatment option to patients. While being a rather low-risk type of surgery, it may cause significant over- or underdrainage complications (e.g., headaches, dizziness, vomiting, intracerebral bleeding, etc.) during posture change. Anti-siphon devices (ASDs) are a group of technically different additional valves used in shunt surgery. They are designed to maintain intraventricular pressure within a normal physiological range regardless of patient position. Fixed ASDs proved to substantially lower the rate of overdrainage complications. No significant differences, however, were noted regarding underdrainage complications. Technical successors of fixed ASDs are programmable ASDs. The aim of this study is to evaluate whether programmable ASDs compared to fixed ASDs are able to avoid both over- and underdrainage complications. In this investigator-initiated, multicenter randomized trial, 306 patients are planned to be recruited. Male and female patients aged ≥18 years with iNPH who are eligible for VP shunt surgery and meet all other entry criteria can participate. Patients will be randomized in a balanced 1: 1 fashion to a VP shunt with a programmable valve either supplemented with a fixed ASD, or a programmable ASD. Patients will be followed-up 3, 6 and, on an optional basis, 12 months after surgery. The primary outcome measure is the cumulative incidence of over- or underdrainage 6 months post surgery, as defined by clinical and imaging parameters. SYGRAVA is the first randomized trial to determine whether programmable ASDs reduce complications of drainage compared to fixed ASDs in patients with iNPH. The results of this study may contribute to health-technology assessment of different valve systems used for VP-shunt surgery, and determination of the future standard of care. International Standard Randomised Controlled Trial Number: ISRCTN13838310 . Registered on 10 November 2016.

Background: Posterior lumbar decompression and interspinous fixation is a surgical technique used in the treatment of the spinal stenosis, degenerative spondylolisthesis, and facet joint arthosis complex. Interspinous fixation implants are less invasive than posterior lumbar internal fixator and therefore, are well suited for use as an implant in cases of low-grade spondylolisthesis. The aim of this study was to examine the clinical and radiographic outcome of patients treated with lumbar decompression and interspinous fixation. Methods: Forty-two patients treated by lumbar decompression and interspinous fixation using the “Le U” and cared for in a specialized urban hospital for degenerative spinal stenosis, together with low-grade spondylolisthesis and facet joint arthrosis, were reviewed. The follow-up rate was 88% (42 of 48 patients) at 1 year. The patients were assessed clinically and radiographically. Results: At 6 months of follow-up, there were 20/42 patients (48%) with an excellent clinical outcome in terms of back pain and the sciatia. Twelve months after surgery, 15/42 patients (36%) showed an excellent outcome in relation to back pain and 21/42 patients (50%) showed an excellent outcome in relation to sciatia. The interspinous implant was dislocated in one of the 42 patients. No differences were found between female and male patients, but there were differences between patients with a normal weight and overweight patients. Conclusions: The study demonstrated that lumbar decompression and interspinous fixation with the “Le U” in patients with degenerative spinal stenosis, low-grade spondylolisthesis, and facet joint arthosis results in excellent and good clinical outcomes. Although all patients showed a significant improvement in relation to back pain and sciatia, overweight and obese patients showed a tendency to benefit more than those with a normal weight.

Although inflammatory processes play an essential role in painful intervertebral disc (IVD) degeneration, the underlying regulatory mechanisms are not well understood. This study was designed to investigate the expression, regulation and importance of specific toll-like receptors (TLRs)—which have been shown to play an essential role e.g. in osteoarthritis—during degenerative disc disease. The expression of TLRs in human IVDs was measured in isolated cells as well as in normal or degenerated IVD tissue. The role of IL-1β or TNF-α in regulating TLRs (expression/activation) as well as in regulating activity of down-stream pathways (NF-κB) and expression of inflammation-related genes (IL-6, IL-8, HSP60, HSP70, HMGB1) was analyzed. Expression of TLR1/2/3/4/5/6/9/10 was detected in isolated human IVD cells, with TLR1/2/4/6 being dependent on the degree of IVD degeneration. Stimulation with IL-1β or TNF-α moderately increased TLR1/TLR4 mRNA expression (TNF-α only), and strongly increased TLR2 mRNA expression (IL-1β/TNF-α), with the latter being confirmed on the protein level. Stimulation with IL-1β, TNF-α or Pam3CSK4 (a TLR2-ligand) stimulated IL-6 and IL-8, which was inhibited by a TLR2 neutralizing antibody for Pam3CSK4; IL-1β and TNF-α caused NF-κB activation. HSP60, HSP70 and HMGB1 did not increase IL-6 or IL-8 and were not regulated by IL-1β/TNF-α. We provide evidence that several TLRs are expressed in human IVD cells, with TLR2 possibly playing the most crucial role. As TLRs mediate catabolic and inflammatory processes, increased levels of TLRs may lead to aggravated disc degeneration, chronic inflammation and pain development. Especially with the identification of more endogenous TLR ligands, targeting these receptors may hold therapeutic promise.

BACKGROUND: Little is known about variables associated with overdrainage complications and neurofunctional and health-related quality of life outcomes in idiopathic normal-pressure hydrocephalus (iNPH) patients after shunt surgery. OBJECTIVE: To identify candidate demographic and disease-specific predictors of overdrainage and patient-related outcomes, allowing for more personalized care of patients with iNPH. METHODS: This was a secondary analysis of the dataset of the SVASONA study, a multicenter randomized trial comparing gravitational and conventional gravitational valves for treating iNPH. We evaluated the association between baseline items and the incidence of overdrainage, using different endpoint definitions. RESULTS: We identified only a few variables associated with a possible increased risk of overdrainage. Apart from using conventional rather than gravitational valves, longer duration of surgery and female sex were associated with a higher risk of clinical signs and symptoms suggestive of overdrainage (hazard ratio: 1.02, 95% confidence interval: 1.01-1.04 and 1.84, 95% confidence interval: 0.81-4.16). The occurrence of clinical symptoms of overdrainage, and the need for exchanging a programmable by a gravitational valve may adversely affect disease-specific outcomes like the Kiefer score. CONCLUSION: Few, if any, baseline and treatment characteristics may be helpful in estimating the individual risk of complications and clinical outcomes after shunt surgery for iNPH. Patients should be informed that longer surgery for any reason may increase the risk of later overdrainage. Also, women should be counseled about a sex-associated increased risk of the development of clinical symptoms of overdrainage, although the latter cannot be distinguished from a generally higher prevalence of headaches in the female population.

There are about 33,000 deaths caused by gunshot wounds in the USA each year. Probably half of these deaths result from head wounds. Among US Army soldiers, 17% of all ballistic injuries are head wounds. This means that, even in those protected by ballistic helmets, gunshot injuries to the head represent a danger. The aim of this study was to examine the effects of shelling of computer-aided designed (CAD) cranioplasty implants made of two different materials. An experimental model was developed in an indoor gun range. CAD cranioplasties with a material thickness of 2-6 mm, made of titanium or PEEK-OPTIMA(®) were fixed in a watermelon and shot at with a .222 Remington rifle at a distance of 30 m distance, a .30-06 Springfield rifle at a distance of 30 m, a Luger 9 mm pistol at a distance of 8 m, or a .375 Magnum revolver at a distance of 8 m. The CAD cranioplasties were subsequently inspected for ballistic effects by a neurosurgeon. Titanium CAD cranioplasty implants resisted shots from the 9 mm Luger pistol and were penetrated by both the .222 Remington and the .30-06 Springfield rifle. Shooting with the .357 Magnum revolver resulted in the titanium implant bursting. PEEK-OPTIMA(®) implants did not resist bullets shot from any weapon. The implants burst on shooting with the 9 mm Luger pistol, the .222 Remington, the .30-06 Springfield rifle, and the .357 Magnum revolver. Titanium CAD cranioplasty implants may offer protection from ballistic injuries caused by small caliber weapons fired at short distances. This could provide a life-saving advantage in civilian as well as military combat situations.

Modern ventriculoperitoneal shunts (VPS) are programmable, which enables clinicians to adjust valve-pressure according to their patients' individual needs. The aim of this retrospective analysis is to evaluate indications for valve-pressure adjustments in idiopathic normal pressure hydrocephalus (iNPH). Patients operated between 2004 and 2011 diagnosed with iNPH were included. Kiefer-Scale was used to classify each patient. Follow-up exams were conducted 3, 6, and 12 months after shunt implantation and yearly thereafter. Initial valve-pressure was 100 or 70 mmH2O. Planned reductions of the valve-pressure to 70 and 50 mmH2O, respectively, were carried out and reactive adjustment of the valve-pressure to avoid over- and under-drainage were indicated. A total of 52 patients were provided with a Medos-Hakim valve(Codman®) with a Miethke shunt-assistant(Aesculap®) and 111 patients with a Miethke-proGAV(Aesculap®). 180 reductions of the valve-pressure took place (65% reactive, 35% planned). Most patients (89%) needed one or two adjustments of their valve-pressures for optimal results. In 41%, an improvement of the symptoms was observed. Gait disorder was improved most often after valve-pressure adjustments (32%). 18 times an elevation of valve-pressure was necessary because of headaches, vertigo, or the development of subdural hygroma. Optimal valve-pressure for most patients was around 50 mmH2O (36%). The goal of shunt therapy in iNPH should usually be valve-pressure settings between 30 and 70 mmH2O. Reactive adjustments of the valve-pressure are useful for therapy of over- and underdrainage symptoms. Planned reductions of the valve opening pressure are effective even if postoperative results are already satisfactory.