Wolf-Ingo Steudel

Biomechanical effect of different lumbar interspinous implants on flexibility and intradiscal pressure

Interspinous implants are used to treat lumbar spinal stenosis or facet joint arthritis. The aims of implanting interspinous devices are to unload the facet joints, restore foraminal height and provide stability especially in extension but still allow motion. The aim of this in vitro study was to compare four different interspinous implants––Colfex, Wallis, Diam and X-Stop––in terms of their three-dimensional flexibility and the intradiscal pressure. Twenty-four human lumbar spine specimens were divided into four equal groups and tested with pure moments in flexion/extension, lateral bending and axial rotation: (1) intact, (2) defect, (3) after implantation. Range of motion and the intradiscal pressure were determined.In each implant-group the defect caused an increase in range of motion by about 8% in lateral bending to 18% in axial rotation. Implantation had similar effects with all four implants. In extension, Coflex, Wallis, Diam, and X-Stop all overcompensated the instability caused by the defect and allowed about 50% of the range of motion of the intact state. In contrast, in flexion, lateral bending and axial rotation the values of the range of motion stayed about the values of the defect state. Similarly the intradiscal pressure after implantation was similar to that of the intact specimens in flexion, lateral bending and axial rotation but much smaller during extension. All tested interspinous implants had a similar effect on the flexibility: they strongly stabilized and reduced the intradiscal pressure in extension, but had almost no effect in flexion, lateral bending and axial rotation.

The Prodisc-c Prothesis: Clinical and Radiological Experience 1 Year After Surgery

Study Design. This is a prospective randomized and controlled study, approved by the local ethical committee of Saarland (Germany). Objective. The aim of the current study was to analyze segmental motion following artificial disc replacement using disc prosthesis over 1 year. A second aim was to compare both segmental motion as well as clinical result to the current gold standard (anterior cervical discectomy and fusion [ACDF]). Summary of Background Data. ACDF may be considered to be the gold standard for treatment of symptomatic degenerative disc disease within the cervical spine. However, fusion may result in progressive degeneration of the adjacent segments. Therefore, disc arthroplasty has been introduced. Among these, artifical disc replacement seems to be promising. However, segmental motion should be preserved. This, again, is very difficult to judge and has not yet been proven. Methods. A total of 49 patients with cervical disc herniation were enrolled and assigned to either study group (receiving a disc prosthesis) or control group (receiving ACDF, using a cage with bone graft and an anterior plate). Roentgen stereometric analysis (RSA) was used to quantify intervertebral motion immediately as well as 3, 6, 12, 24, and 52 weeks after surgery. Also, clinical results were judged using visual analog scale and neuro-examination at even RSA follow-up. Results. Cervical spine segmental motion decreased over time in the presence of disc prosthesis or fusion device. However, the loss segmental motion is significantly higher in the fusion group, when looked at 3, 6, 12, 24, and 52 weeks after surgery. We observed significant pain reduction in neck and arm after surgery, without significant difference between both groups. Conclusion. Cervical spine disc prosthesis remains cervical spine segmental motion within the first 1 year after surgery. The clinical results are the same when compared with the early results following ACDF.

Prognostic Significance of the Mitotic Index Using the Mitosis Marker Anti-Phosphohistone H3 in Meningiomas

Mitotic activity is one of the most reliable prognostic factors in meningiomas. The identification of mitotic figures (MFs) and the areas of highest mitotic activity in H&E-stained slides is a tedious and subjective task. Therefore, we compared the results from immunostaining for the mitosis-specific antibody anti-phosphohistone H3 (PHH3 mitotic index [MI]) with standard MF counts (H&E MI) and the Ki-67 labeling index (LI). The relationship between these proliferation indices and prognosis was investigated in a retrospective series of 265 meningiomas. The PHH3 staining method yielded greater sensitivity in the detection of MFs and facilitated MF counting. Mitotic thresholds of H&E MI of 4 or more per 10 high-power fields (HPF) and PHH3 MI of 6 or more per 10 HPF were found as the most appropriate prognostic cutoff values for the prediction of recurrence-free survival. All 3 proliferation indices were univariately associated with recurrences and deaths. In contrast with the Ki-67 LI, H&E MI and PHH3 MI also remained as independent predictors in the multivariate Cox hazards modeling (P = .0007 and P = .0004, respectively).

Autoantibodies against GLEA2 and PHF3 in glioblastoma: tumor-associated autoantibodies correlated with prolonged survival.

Using serological identification of recombinantly expressed tumor antigens (SEREX), we identified several autoantibodies against glioma‐expressed antigens including GLEA1, GLEA2 and PHD‐finger protein3 (PHF3). Analysing sera of 62 glioblastoma patients, we found an antibody response against GLEA1 in 15 sera (24.2%), against GLEA2 in 30 sera (48.4%) and against PHF3 in 35 sera (56.5%). Relating patient survival to the occurrence of autoantibodies against either GLEA1, GLEA2 or PHF3, we found a significant prolonged survival for glioblastoma patients positive for autoantibodies against GLEA2 (p = 0.0115) and PHF3 (p = 0.0031), respectively. The median survival of patients with GLEA2 antibodies was increased to 17.4 months and for patients with PHF3 antibodies to 14.7 months, as compared to 7.2 months for patients without GLEA2 or PHF3 antibodies. There was no significant correlation between patient survival and GLEA1‐autoantibodies (p = 0.1611). Herein we present autoantibodies that are: (i) most frequent in glioblastoma patients; (ii) specific for glioblastoma‐associated antigens; and (iii) significantly correlated with prolonged survival in patients with glioblastoma.

Epidemiology and prevention of fatal head injuries in Germany – trends and the impact of the reunification

SummaryA review of the data published on the epidemiology of traumatic brain injuries (TBI) reveals that the data of almost all studies are drawn from local or regional series. Nationwide data are rarely available, or are extrapolated from regional data. In Germany, there has been a nationwide mortality register with ICD-9-coded diagnoses since 1968. In addition, it has been compulsory since 1994 that all hospitals in Germany provide ICD-9 data on all admissions and discharges.Based on data provided by the Federal Bureau of Statistics (Statistisches Bundesamt) in Wiesbaden, all head injuries between 1972 and 1998 were analyzed according to ICD-9 and after 1998 according to the updated ICD-10. The data of hospitalized cases and fatal cases were correlated with population data to calculate incidences and mortality rates. Age-group specific data were also available and analyzed.Head injuries in Germany accounted in 1998 for 19.59% of all injuries. The incidence is 337/100,000. The incidence rate of serious head injury is 33.5/100,000. Mortality decreased continuously from 27.2/100,000 in 1972 to 9.0/100,000 in 2000. The mortality is highest in the group older than 75 years. 68.4% of persons with head injury die before admission to a hospital.After the reunification in 1989/1990, the number of fatal head injuries showed a temporary increase. The number of patients treated in-hospital remained essentially unchanged (276/564 patients in 1998). The majority of hospitalized patients suffered minor head injury.Conclusion: Analysis of the admission/discharge data of all German hospitals reveals surprising inside views of age group-related incidence and mortality rates of head injuries in this country. Future research should be focused on patients with minor head injuries who account for nearly 200,000 cases of in-hospital treatment.

Loss of Alkaline Phosphatase Activity in Meningiomas: A Rapid Histochemical Technique Indicating Progression-associated Deletion of a Putative Tumor Suppressor Gene on the Distal Part of the Short Arm of Chromosome 1

Apart from defined histomorphologic features, increased Ki-67 indices and various numeric and structural chromosome aberrations, meningiomas of the intermediate (WHO grade II, atypical meningioma) and anaplastic type (WHO grade III) are cytogenetically distinguished from common-type meningiomas (WHO grade I) by frequent loss of the distal part of the short arm of one chromosome 1 (1p-), which formerly proved to be an independent predictor of shorter recurrence-free intervals. Histochemically, loss of alkaline phosphatase activity (ALPL, liver/bone/kidney type, EC 3.1.3.1) was another frequent, specific finding in meningiomas with signs of dedifferentiation. In a prospective study including 66 meningiomas, all common-type meningiomas except one case (18/19) were reactive for ALPL, whereas 75% (30/39) of intermediate type and all anaplastic meningiomas (8/8) showed loss of enzyme activity in large areas of the tumor. Exclusively, the ALPL negative phenotype was associated with 1p loss (15/19). Our data suggest that ALPL, which is coded as a single copy gene on chromosome 1p36.1-p34, is a useful marker enzyme for the loss of a putative regulatory (tumor suppressor) gene on chromosome 1p, or that ALPL itself represents a new tumor suppressor gene homozygously inactivated in meningiomas.

Ultrasound-based navigation during intracranial burr hole procedures: experience in a series of 100 cases.

BACKGROUND To establish a rational basis for intraoperative ultrasound guidance in neurosurgical procedures via a single burr hole approach based on the experience of one hundred cases. METHODS The single burr hole approach is carried out using a bayonet-shaped ultrasound transducer with a tip dimension of 8 x 8 mm. The ultrasound probe with a mounted puncture adapter fits a standard burr hole and allows real-time imaging of the ongoing surgical steps. RESULTS One hundred cases with five indications have been operated on so far: tapping of the ventricular system (46 patients), tapping of intracranial cysts (23 patients), biopsy of intracranial tumors (15 patients), evacuation of intracranial abscesses (9 patients), and evacuation of intracerebral hematomas (7 patients). Depending on their size, the ventricles could be clearly visualized in 34 of 46 patients. In the remaining patients the free margin of the falx served as orientation. Two ventricles could neither be visualized nor entered. Visualization and puncture of intracranial cysts were easy to achieve throughout, as was the case with abscesses. Tumor biopsy was unsuccessful in two patients harboring lymphomas at distances of more than 50 mm from probe to target. Intracerebral hematomas were easily visualized but, due to the presence of clots, aspiration was impossible in two patients. One patient with a giant glioblastoma died the day after the uneventful biopsy due to increased cerebral edema. No other complications occurred. CONCLUSIONS The presented method of ultrasound-based neuronavigation is an easy-to-use, fast, and safe technique of real-time imaging for free-hand single burr hole procedures.

Changes in regional energy metabolism after closed head injury in the rat

We examined in the present investigation regional ATP, glucose, and lactate content in the cortical and subcortical structures, in a rat model of closed head injury (CHI). In serial tissue sections bioluminescence imaging of ATP, glucose, and lactate was performed at 4 h, 12 h and 24 h (n=4/5 per time point with) after the induction of CHI or sham surgery. Bioluminescence images were analyzed by computer-assisted densitometry, at the lesion site, in remote cortical areas, and in the subcortical structures (thalamus and caudate nucleus). ATP content was significantly decreased at the lesion site after 4 h and in the remote cortex at 12 h post-injury. At 12 h, the ATP content reached baseline levels on the ipsilateral side and at 24 h also at remote lateral parietal sites. In the contralateral cortex, ATP increased transiently above the baseline at 12 h. No significant changes in ATP were found in the thalamus and caudate nucleus. Cortical glucose and lactate contents could not be discerned over time.Following CHI there is an acute and progressive, yet transient, ischemic cortical profile, which is not reflected in subcortical areas.

Correspondence of tumor localization with tumor recurrence and cytogenetic progression in meningiomas.

OBJECTIVEMeningiomas are mostly benign tumors that originate from the coverings of the brain and spinal cord. Cytogenetically, they reveal a normal karyotype or, typically, monosomy of chromosome 22. Progression of meningiomas is associated with a non-random pattern of secondary losses of other autosomes. Deletion of the short arm of one chromosome 1 is a decisive step to anaplastic growth in meningiomas. METHODSStatistical analyses were performed for the karyotypes of 661 meningiomas with respect to localization, progression, and recurrence of the tumor. A mathematical mixture model estimates typical pathogenetic routes in terms of the accumulation of somatic chromosome changes in tumor cells. The model generates a genetic progression score (GPS) that estimates the prognosis as related to the cytogenetic properties of a given tumor. RESULTSIn 53 patients, one or several recurrences were documented over the period of observation. This corresponds to a total rate of recurrence of 8.0% after macroscopically complete tumor extirpation. Higher GPS values were shown to be strongly correlated with tumor recurrence (P = 2.9 × 10−7). High-risk tumors, both in terms of histology and cytogenetics, are localized much more frequently at the brain surface than at the cranial base (P = 1.2 × 10−5 for World Health Organization grade and P = 3.3 × 10−12 for GPS categorization). CONCLUSIONThe tendency of cranial base meningiomas to recur seems to depend on surgical rather than biological reasons. As a quantitative measure, the GPS allows for a more precise assessment of the prognosis of meningiomas than the established categorical cytogenetic markers.

The ependyma in chronic hydrocephalus

H-Tx rats produce congenitally hydrocephalic offspring with varying severity of the condition. We used moderately hydrocephalic rats without evident clinical signs of hydrocephalus and normal controls from the same stock when they were at least 1.5 years old. Macroscopic anatomy was studied by MRI and in fixed brain slices and the ultrastructure of the ependyma, with REM. Apart from markedly stretched areas, where the ependyma was totally destroyed and subependymal structures directly exposed to the CSF, the density of ependymal microvilli and of tufts of cilia was reduced in proportion to the ventricular distension of a given area. A supraependymal “network”– never seen before in acute hydrocephalus – was found, whose purpose is probably to prevent further ventricular enlargement. We conclude that even in arrested hydrocephalus the ependymal sequelae of hydrocephalus are similar to those of the acute stage, illustrating the extremely limited potenctial for recovery, but the organism seems nevertheless to react with an internal stabilization of the ventricular system.