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Marko Staender, Ulrich Maerz, Jörg Christian Tonn and Ulrich Steude

Object. The authors prospectively evaluated the therapeutic effect of computerized tomography (CT)—guided kryorhizotomy in the treatment of patients with lumbar facet joint syndrome (LFJS) and assessed prognostic factors that predict this effect.

Methods. Between February 2001 and March 2004, CT-guided kryorhizotomy of facet joints was performed in 76 patients with LFJS. A diagnosis was established after three positive CT-guided medial nerve branch blocks. Outcome was determined by evaluating the results of a standardized questionnaire, including visual analog scale (VAS) score, use of medication, ability to work, and physical conditions. Measurement was performed before treatment and repeated postoperatively at 3 days, 3 months, and every 6 months thereafter. On September 2004 all patients underwent clinical reevaluation.

The median follow-up period was 22.5 months (range 6–43 months); the median interval to pain reduction was 6 months (range 0.1–31 months) after the first kryorhizotomy. The mean VAS pain score was 6.7 preoperatively and 2.9, 3.2, and 3.4 at 3 days, 3 months, and 6 months postoperatively, respectively. In 40% of patients pain was reduced for 12 months or longer. In patients in whom there was no prior surgical treatment of the relevant spinal segment, the duration of pain relief was significantly longer than in patients who had previously undergone surgery (p < 0.03). Eighteen patients underwent a second, seven a third, and one a fourth kryorhizotomy. No patient reported any side effect. The use of CT guidance guarantees an exact needle-tip position control and documentation for repeated procedures.

Conclusions. Computerized tomography—guided kryorhizotomy is a minimally invasive and repeatable treatment that yields good long-term results in patients with LFJS.

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Claudius Thomé, Peter Vajkoczy, Peter Horn, Christian Bauhuf, Ulrich Hübner and Peter Schmiedek

Object. Temporary arterial occlusion (TAO) during aneurysm surgery carries the risk of ischemic sequelae. Because monitoring of regional cerebral blood flow (rCBF) may limit neurological damage, the authors evaluated a novel thermal diffusion (TD) microprobe for use in the continuous and quantitative assessment of rCBF during TAO.

Methods. Following subcortical implantation of the device at a depth of 20 mm in the middle cerebral artery or anterior cerebral artery territory, rCBF was continuously monitored by TD microprobe (TD-rCBF) throughout surgery in 20 patients harboring anterior circulation aneurysms; 46 occlusive episodes were recorded. Postoperative radiographic evidence of new infarction was used as the threshold for failure of occlusion tolerance.

The mean subcortical TD-rCBF decreased from 27.8 ± 8.4 ml/100 g/min at baseline to 13.7 ± 11.1 ml/100 g/min (p < 0.0001) during TAO. The TD microprobe showed an immediate exponential decline of TD-rCBF on clip placement. On average, 50% of the total decrease was reached after 12 seconds, thus rapidly indicating the severity of hypoperfusion. Following clip removal, TD-rCBF returned to baseline levels after an average interval of 32 seconds, and subsequently demonstrated a transient hyperperfusion to 41.4 ± 18.3 ml/100 g/min (p < 0.001). The occurrence of postoperative infarction (15%) and the extent of postischemic hyperperfusion correlated with the depth of occlusion-induced ischemia.

Conclusions. The new TD microprobe provides a sensitive, continuous, and real-time assessment of intraoperative rCBF during TAO. Occlusion-induced ischemia is reliably detected within the 1st minute after clip application. In the future, this may enable the surgeon to alter the surgical strategy early after TAO to prevent ischemic brain injury.

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Christian Geyer, Anett Ulrich, Gerd Gräfe, Barbara Stach and Holger Till

Object

During recent years, several biomarkers have been introduced for use in the diagnosis of traumatic brain injury (TBI). The primary objective of this investigation was to determine if S100B (or S100 calcium-binding protein B) and neuron-specific enolase (NSE) serum concentrations can effectively be used to discriminate between symptomatic and asymptomatic children with minor head trauma.

Methods

The authors conducted a prospective clinical study that involved patients age 6 months to 15 years who had sustained minor head trauma. Children with concomitant extracranial injuries were excluded. Blood samples were obtained within 6 hours of injury to measure S100B and NSE levels in serum. The authors defined 2 diagnostic groups: a mild TBI group (patients with Glasgow Coma Scale [GCS] scores of 13–15) in whom there were clinical signs of concussion (short loss of consciousness, amnesia, nausea, vomiting, somnolence, headache, dizziness, or impaired vision) and a head contusion group (patients with a GCS score of 15) in whom symptoms were absent. Both S100B and NSE concentrations were compared between the 2 groups. Secondary end points were defined as follows: correlation of S100B/NSE and a) the presence of scalp lacerations, b) GCS score, c) age, and d) correlation between S100B and NSE.

Results

One hundred forty-eight patients were enrolled (53 in the contusion group, 95 in the mild TBI group). After adjusting for differences in age and time of injury to blood sample withdrawal, there was no significant difference in S100B or NSE between patients in the 2 groups. Scalp lacerations and GCS score had no affect on posttraumatic S100B or NSE concentrations. The correlation between S100B and NSE was significant. Both markers showed a significant negative correlation with age.

Conclusions

The authors demonstrated that S100B and NSE do not discriminate between symptomatic and asymptomatic children with minor head injury. There seem to be limitations in marker sensitivity when investigating pediatric patients with mild TBI.

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Florian Stockhammer, Ulrich-Wilhelm Thomale, Michail Plotkin, Christian Hartmann and Andreas von Deimling

Object

Oligodendroglial tumors harboring combined 1p and 19q loss (1p/19q LOH) are characterized by a favorable prognosis and response to chemotherapy and radiotherapy, but detection of 1p/19q LOH relies on postoperative procedures. The authors investigated the potential of fluorine-18–labeled fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) to predict 1p/19q LOH preoperatively in tumors whose appearance on initial magnetic resonance images was consistent with that of low-grade glioma.

Methods

The study population comprised 25 patients who had undergone preoperative FDG-PET followed by tumor resection. Neuronavigation ensured a precise match of FDG uptake wi th the site of biopsy. All tumor specimens were graded according to the World Health Organization (WHO) classification system. Microsatellite analysis was used to identify 1p/19q LOH.

In this series, 16 of 25 gliomas corresponded to WHO Grade II. In eight of these 16, 1p/19q LOH was detected. Raised glucose utilization within the tumor was seen in the six of eight WHO Grade II gliomas with 1p/19q LOH and in none of the WHO Grade II gliomas without this genetic alteration (p = 0.003).

Conclusions

These findings demonstrate the potential of FDG-PET to predict 1p/19q LOH in WHO Grade II gliomas.

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Jan-Helge Klingler, Marie Therese Krüger, Evangelos Kogias, Stefanie M. Brendecke, Ulrich Hubbe and Christian Scheiwe

Malignant meningiomas are a rare but aggressive subset of intracranial meningiomas leading to a very limited life expectancy. The occurrence of spinal metastases in these tumors is an even rarer event. The described patient had an intracranial malignant meningioma and developed a symptomatic osteolytic contrast-enhancing lesion in the left C-1 lateral mass suspicious for metastasis. The authors performed a minimally invasive posterior resection of the lesion with vertebroplasty of C-1. Histopathology verified metastasis of the malignant meningioma. The surgical procedure resulted in prompt and permanent pain reduction until the patient died 18 months later. Given the very limited life expectancy in this case, the authors did not consider occipitocervical fusion because of their desire to preserve the range of motion of the head. Therefore, they suggest minimally invasive tumor resection and vertebroplasty in selected palliative tumor patients.

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Michael Fiechter, Jens Fichtner, Sergej Feiler, Radu Olariu, Jürgen Beck, Andreas Raabe and Christian T. Ulrich

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Yuan Zhu, Christian Peters, Monika Hallier-Neelsen, Dorothea Miller, Axel Pagenstecher, Helmut Bertalanffy and Ulrich Sure

Object

Cerebral cavernous malformations (CCMs) are the most common vascular malformation of the central nervous system and involve dysregulated angiogenesis. However, the underlying mechanism of this disease is poorly understood. Phosphatase and tensin homolog (PTEN) plays a crucial role in regulating angiogenesis. The authors attempted to determine whether PTEN is involved in the pathological angiogenesis of CCM.

Methods

The authors used Western blot analysis and immunohistochemical methods to detect the expression of PTEN, PCNA, and P-Akt in the surgical specimens of CCMs and controls. The function of PTEN in cell proliferation was studied after PTEN silencing in endothelial cultures by using the short interfering RNA technique.

Results

Western blot analysis showed significant reduction of PTEN protein expression in CCMs compared with control brain tissue (p < 0.01). Immunohistochemical analysis confirmed PTEN insufficiency in 33% of vascular endothelia of CCMs, which was significantly higher than that of controls (2%, p < 0.01). Furthermore, PTEN insufficiency occurred more frequently in multiple CCMs (44%) and in small lesions (39%) than in single CCMs (28%, p < 0.05) and large lesions (30%, p < 0.05), respectively, suggesting a potential role of PTEN in the progression of the lesions. Of note, a negative correlation was observed between the expression of PTEN and PCNA in CCM endothelial cells. However, Akt was not constitutively activated in CCMs. Using cultured endothelial cells, the authors demonstrated that PTEN silencing by short interfering RNA increased Akt activation, PCNA expression, and cell proliferation (p < 0.001). Surprisingly, the PTEN silencing–mediated increase in endothelial proliferation was not reversed by the PI3K inhibitor wortmannin.

Conclusions

In this study, the authors report for the first time a significant PTEN insufficiency in CCM vessels associated with endothelial proliferation. The in vitro study provides direct evidence for a pivotal role of PTEN in regulating endothelial proliferation, most likely through a PI3K-independent pathway. The authors suggest that PTEN insufficiency is potentially involved in CCM by stimulating angiogenesis.

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Diana Rudolph, Ina Sterker, Gerd Graefe, Holger Till, Anett Ulrich and Christian Geyer

Object

Many ophthalmological abnormalities are described in conjunction with hydrocephalus. The results of visual field diagnosis remain a matter of further discussion. The aim of this study was to investigate visual field deficits in children with shunt-treated hydrocephalus.

Methods

All children over 6 years of age treated for hydrocephalus at the authors' institute between December 2007 and December 2008 were included in the study. The children underwent an ophthalmological investigation for strabismus and binocular function, ophthalmoscopy, visual acuity, and refraction.

The special focus was the visual field diagnosis, which the authors established in all children with cognitive conditions. The investigation was made by using the Goldmann visual field examination (kinetic perimetry). Children with and without visual field defects were compared concerning age at the time of ophthalmological examination, genesis of hydrocephalus, and frontooccipital horn ratio measured on current CT or MR images.

Results

Complete investigations were undertaken in 56 children (24 girls and 32 boys, mean age 15.1 years). The following orthoptic pathological entities were diagnosed: 29 children have a strabismus in 29 cases, 17 of these have an exotropia, 12 an esotropia, 4 children a hypotropia, 2 a hypertropia and 3 children a heterophoria. A nystagmus was found in 10 children. The ocular fundus investigation showed 13 children with an optic nerve atrophy.

A visual field diagnosis was possible in 44 of the 56 patients and was incomplete in 12 patients with cognitive deficits or inadequate compliance. In 24 of 42 children there was a concentric visual field constriction between 10° and 50° out of the center. Children with visual field deficits were older than those with a normal visual field (p = 0.051). Nine of 10 children with postmenigitic hydrocephalus had a visual field defect (p = 0.025). In children with visual field defects the frontooccipital horn ratio was significantly higher (p = 0.013).

Conclusions

The results suggest that children with shunt-treated hydrocephalus have a higher risk of having ophthalmological abnormalities. Visual field deficits are often a problem in these patients. A diagnostic visual field examination can complete the ophthalmological monitoring in patients with hydrocephalus, especially in patients with large ventricles. Children with postmeningitic hydrocephalus should be ophthalmologically monitored more frequently and intensively.

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Patrick Cramer, Ulrich-Wilhelm Thomale, Ali Fuat Okuducu, Arne J. Lemke, Florian Stockhammer and Christian Woiciechowsky

✓ The authors report the case of a 23-year-old man who presented with a C1–3 spinal mass. Following intraspinal decompression the tumor was histologically classified as an atypical meningioma (World Health Organization grade II). Two further surgical interventions resulted in almost total removal of the meningioma. In addition, radiotherapy was performed. During the 1.5-year follow-up period the diagnostic examinations identified a local tumor recurrence, an intraspinal C-6 metastasis, and a segmental instability with anterior C2–3 slippage and C3–4 kyphosis. The tumor was resected and occipitocervical stabilization was performed. Histological examination showed no change in malignancy. Despite additional hydroxyurea-based chemotherapy, the patient presented 4 months later with a hemiparesis and a massive recurrence of the tumor mass involving the posterior fossa and the upper thoracic spine. Because there were no further therapeutical options, the patient died. The authors discuss more aggressive therapeutic options in addition to surgery in patients with metastatic atypical meningiomas. The results in the reported case indicate that meningiomas associated with cerebrospinal fluid metastasis may represent a higher grade of malignancy.

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Piotr Jachimczak, Ulrich Bogdahn, Jörg Schneider, Christian Behl, Jürgen Meixensberger, Rainer Apfel, Rüdiger Dörries, Karl-Hermann Schlingensiepen and Wolfgang Brysch

✓ This in vitro study was aimed at restitution of transforming growth factor (TGF)-β2-mediated suppression of T-lymphocyte activation within malignant gliomas. In early-passage tumor cell cultures of two glioblastomas (HTZ-153 and HTZ-209) and one malignant astrocytoma classified as World Health Organization Grade III (HTZ-243), autologous peripheral blood mononuclear cells were activated by interleukin-lα and interleukin-2 in vitro (lymphokine-actived killer cells) and tested for cytotoxic and proliferative activity. In expression studies (Western blot and Northern hybridization) of all three tumors, TGF-β could be detected at the protein and messenger ribonucleic acid (mRNA) levels. A polyclonal anti-TGF-β neutralizing antibody did not enhance lymphocyte proliferation upon stimulation with tumor targets (3H-thymidine incorporation) and slightly stimulated lymphocyte cytotoxicity against autologous target cells. Preincubation of target cells for 12 hours with TGF-β2-specific phosphorothioate-anti-sense oligodeoxynucleotides (S-ODN's) did, however, enhance lymphocyte proliferation up to 2.5-fold and autologous tumor cytotoxicity up to 60%, compared to controls not treated with S-ODN's. Incubation of tumor cells with TGF-β2-specific S-ODN's resulted in decreased TGF-β-specific immunoreactivity in cultured glioma cells, in reduced TGF-β2 protein concentration (Western blot), and in a change in the expression pattern of TGF-β2 mRNA's. These observations may have implications for in vivo and in vitro activation of a cellular immune response against autologous malignant glioma cells.