Intramedullary cavernous malformations: clinical features and surgical technique via hemilaminectomy.

OBJECTIVE: The purpose of this study was to define the clinical features and the surgical technique of unilateral hemilaminectomy for treating intramedullary cavernous malformations. MATERIALS AND METHODS: Retrospective chart was performed in 16 patients with histologically diagnosed intramedullary cavernous malformations. All patients were treated with unilateral hemilaminectomy and microsurgical resection of the malformations. The pre- and postoperative neurological state was evaluated using Frankel scale. RESULTS: There were nine females and seven males (mean age 38 years) harbouring symptomatic intramedullary cavernous malformations. The annual retrospective haemorrhage rate was 3.1% per patient/year. All cavernous malformations were completely resected. Twelve of 16 patients experienced the improvement of the neurological state and in four patients, clinical features remained unchanged during the follow-up period. Static and dynamic plain radiograph film showed none of them had spinal deformity or spinal instability. CONCLUSION: According to the defined bleeding risk, symptomatic and MRI-morphologically growing intramedullary cavernous malformations should be totally surgically removed, to avoid the recurrence and rebleeding of the residue. A least traumatic myelotomy, as well as a meticulous microsurgical technique and the intraoperative somatosensory evoked potentials monitoring, together with selection of a minimally invasive microsurgical approach (hemilaminectomy), leads to a favourable outcome and prevents additional morbidity.

Localization of precentral gyrus in image-guided surgery for motor cortex stimulation.

According to recent clinical data, motor cortex stimulation (MCS) is an alternative treatment for central pain syndromes. We present our minimal invasive technique of image guidance for the placement of motor cortex stimulating electrode and assess the clinical usefulness of both neuronavigation and vacuum headrest. Neuronavigation was used for identification of precentral gyrus and accurate planning of the single burr-hole. The exact location was reconfirmed by intraoperative phase reversal of somatosensory evoked potential (SSEP) and clinical response after electrical stimulation test. Implementation of navigation technique facilitated localization of the precentral gyrus with a high degree of accuracy. Determination of stimulating electrode placement was possible in every case. Postoperative clinical and neuroradiological evaluations were performed in each patient. All patients experienced postoperative relief from pain. Our preliminary series may confirm image guidance as a useful tool for surgery of MCS. Additionally, minimal and safe exposure can be performed using a single burr-hole and vacuum head rest.

Surgical management of dural arteriovenous fistulas with transosseous arterial feeders involving the jugular bulb.

Dural arteriovenous fistulas located in the vicinity of the jugular foramen are complex vascular malformations and belong to the most challenging skull base lesions to treat. The authors comprehensively analyze multiple features in a series of dural arteriovenous fistulas with transosseous arterial feeders involving the jugular bulb. Four patients who underwent surgery via the transcondylar approach to treat dural arteriovenous fistulas around the jugular foramen were retrospectively reviewed. Previously, endovascular treatment was attempted in all patients. The success of the surgical treatment was examined with postoperative angiography. Complete obliteration of the dural arteriovenous fistulas (DAVFs) was achieved in three patients, and significant flow reduction in one individual. All patients had a good postoperative outcome, and only one experienced mild hypoglossal nerve palsy. Despite extensive bone drilling, an occipitocervical fusion was necessary in only one patient with bilateral lesions. The use of an individually tailored transcondylar approach to treat dural arteriovenous fistulas at the region of the jugular foramen is most effective. This approach allows for complete obliteration of the connecting arterial feeders, and removal of bony structures containing pathological vessels.

Genetics of cerebral cavernous angioma.

Cerebral cavernous malformations (CCM) are hamartomatous vascular anomalies characterized by densely packed, grossly enlarged immature capillaries without intervening neural tissue. Depending on their location and size (ranging from a few millimeters to several centimeters), the biologically dynamic lesions become symptomatic during the second to fourth decade of life. Clinical symptoms include recurrent headaches, seizures, intracranial hemorrhage, and stroke. There are sporadic and autosomal dominantly inherited forms of CCM. Causal mutations have been demonstrated in three genes, KRIT1, MGC4607, and PDCD10, but additional genes are likely to be discovered. These genes are therefore thought to play a role in angiogenesis. Their specific modes of actions, their contribution to and their likely penetrance in the genesis of CCM are the subject of current investigations. Genetic counseling is strongly advisable for patients with a positive family history and for seemingly sporadic cases with multiple lesions, and genetic testing should be considered on an individual basis. The identification of a mutation enables precise genetic testing of relatives. Given the 50 % a priori risk of autosomal dominant inheritance, the benefits of genetic testing are twofold: a positive test result in a presymptomatic carrier permits close neuroradiological surveillance and timely neurosurgical intervention; a negative test result relieves the proband of unwarranted anxiety and unnecessary medical supervision.

Image-guided ultrasonography for recurrent cystic gliomas.

BACKGROUND: Long-term survival of patients with recurrent gliomas depends on the extent of resection. Thus, the desirability of an intra-operative imaging modality that can augment the resection extension without affecting vital surrounding structures is more than obvious. It was the aim of the present study to evaluate a possible benefit of image-guided intra-operative ultrasonography for the surgery of recurrent gliomas. METHOD: The authors performed ultrasonography-assisted image-guided resection of recurrent gliomas in 16 patients. An ultrasound device (IGSonic) was integrated into the VectorVision2 navigation system (BrainLAB, Heimstetten, Germany). The IGSonic Probe 10V5 was connected to the VectorVision Navigation station via an IGSonic Device Box. Following patient registration, MRI based neuronavigation was used to determine the skin incision and the bone flap. Before opening the dura, the underlying structures were explored by ultrasound combined with the corresponding MR images. The navigated ultrasound displayed the sonographic image of the intracranial anatomy on the navigation screen in a composed overlay fashion. FINDINGS: The integration of intra-operative ultrasound into neuronavigation system offered quick and helpful intra-operative images in all 16 procedures. Due to the specific ultrasonic characteristics of the solid and the cystic parts, our technique created highly useful images in 10 patients with cystic recurrences. In these, user friendly images were obtained that were easy to understand even for neurosurgeons without major experience in intra-operative ultrasound. CONCLUSIONS: Neurosonography is a time- and cost-effective technology offering intra-operative imaging. The improved orientation and visualization of tumour remnants, adjacent ventricles, and the enhanced intra- and peri-tumoural vasculature is one of the main advantages of ultrasonography-assisted image-guided surgery, which is most obvious during surgery for cystic gliomas.

Comparative experimental study of argon plasma and bipolar coagulation techniques.

BACKGROUND: Argon plasma coagulation (APC) is based on the principle of ionised argon creating conductive plasma between an activating electrode and tissue surface and is used as an effective alternative coagulation technique in various surgical disciplines. This trial aims to compare thermal injury in rat brain caused by APC and conventional bipolar coagulation technique. METHODS: A controlled study design with constant power setting and application time was established. Twenty rats were randomised into the APC and bipolar groups. Each group of ten rats had 20 treated lesions. Early and late histopathological changes, as well as maximum extent of the lesion after 48 hours (h) and 12 days were studied in overall 20 lesions. FINDINGS: Although the maximum depth of the lesions was different in APC (2.2 mm) and bipolar (1.8 mm) groups after 48 h, this did not achieve statistical significance (p=0.151). The superficially coagulated area was significantly larger after APC compared with the bipolar technique at the 48 h time point (p=0.032). After twelve days there were no differences in penetration depth (p=0.310) or coagulated area (p=0.222). CONCLUSION: Tissue defects after APC application on rat brains were comparable to conventional bipolar technique in this trial. The results suggest that argon plasma coagulation (APC) is an effective coagulation technique.

Double electrodes simultaneous stimulation and implantation technique in deep brain stimulation.

Posttraumatic tremor is often one of the causes of disability in head injury patients. Usually, pharmacotherapy for this type of tremor is not effective. Since early 1970s, surgical ablation of the ventral thalamus has been used to treat various types of tremor. Nowadays, deep brain stimulation (DBS) confirms its efficacy in alleviating different forms of tremor, including posttraumatic tremor. Such therapy has been reported achieving around 80% success rate in the treatment of posttraumatic tremor. These successful results suggest that the application of DBS therapy can be considered as one of the alternative treatments for minimizing the tremor occurring from different pathologies.

[Familial cavernous malformations of the central nervous system. A clinical and genetic study of 15 German families]. / Familiäre Kavernome des Zentralnervensystems. Eine klinische und genetische Studie an 15 deutsche Familien.

In 1928, Hugo Friedrich Kufs reported on a family with cerebral, retinal, and cutaneous cavernous malformations. Since then, more than 300 families with inherited cavernous malformations have been reported. Genetic studies showed three loci, on chromosomes 7q21-q22 (with the gene CCM1), 7p15-p13 (CCM2), and 3q25.2-q27 (CCM3). The gene product of CCM1 is Krit 1 (Krev interaction trapped 1), a protein interacting with angiogenesis by various mechanisms. Recently, CCM2 has also been identified; its product is a protein which might have a function similar to that of Krit 1. However, the CCM3 gene has still not been found. In this study, we present clinical and genetic findings on 15 German families.

Argon plasma coagulation (APC) in brain tumor surgery: experimental study and clinical experiences.

OBJECTIVE: The present study aims to provide preliminary results of the thermal effects on rat brain tissue after argon plasma coagulation (APC). It also presents and discusses the clinical experiences in the treatment of brain tumor using APC. MATERIALS AND METHODS: A controlled study of APC in the rat brain was conducted. Twelve rats were randomly divided into 2 experimental groups. In the first group (n = 6), histopathological evaluation was performed 2 days following the coagulation. In the second group (n = 6), the evaluation was performed 12 days post operation. In a prospective study of APC-treated tumor tissue in 3 patients, the depth of plasma penetration and histological alteration were evaluated. RESULTS: In the animal experiment, extent of tissue defect became significantly smaller after 12 days (p = 0.010). The maximum depth of tissue alteration after APC application was limited to 2.15 mm (range: 1.5-2.15 mm) at day 2. The histological alteration of tissue after the thermal injury can be divided into 3 zones. In addition, the depth of tissue alteration in the APC-treated human brain tumor was measured in vertical and horizontal planes under light microscope. Similar to the animal experiment result, penetration of the plasma energy in human brain tumors was limited to a maximum of 2.13 mm (range: 1.6-2.13 mm). CONCLUSION: The limited depth of energy penetration may confirm APC as a safe and beneficial tool for coagulation of human brain tissue. However, further clinical studies are required to evaluate the suitability and indications of this method in brain tumor treatment.

Image-guided motor cortex stimulation in patients with central pain.

According to recent clinical data, motor cortex stimulation (MCS) is an alternative treatment for central pain syndromes. We present our minimally invasive technique of image guidance for the placement of the motor cortex-stimulating electrode and assess the clinical usefulness of both neuronavigation and vacuum headrest. Five patients suffering from central pain underwent MCS with the guidance of a frameless stereotactic system (BrainLab AG, Munich, Germany). The neuronavigation was used for identification of the precentral gyrus and accurate planning of the single burr hole. The exact location was reconfirmed by an intraoperative stimulation test. Postoperative clinical and neuroradiological evaluations were performed in each patient. The navigation system worked properly in all 5 neurosurgical cases. Determination of the placement of stimulating electrode was possible in every case. All patients obtained postoperative pain relief. No surgical complication occurred, and the postoperative course was uneventful in all patients. This preliminary experience may confirm image guidance as a useful tool for the surgery of MCS. Additionally, minimal and safe exposure can be achieved using a single burr hole and vacuum headrest.

Clinical application of neuro-navigation in a series of single burr-hole procedures.

With recent developments in computer technology and the improvement of neuroimaging, modern optical neuro-navigation systems are increasingly being used in neurosurgery. In this study, we present our experience with 51 operations using a frameless optical navigation system in a variety of single burr-hole procedures. The procedures include neuroendoscopic surgery, frameless stereotactic biopsy, cyst aspiration and catheter placement. Both the VectorVision and the VectorVision(2) neuro-navigation systems (BrainLab AG, Munich, Germany) were used. The reliability and accuracy of the neuro-navigation system, postoperative complications and the clinical usefulness of image-guidance were analyzed. The navigation system worked properly in all 51 neurosurgical cases. Exact planning of the approach and determination of the ideal trajectory were possible in all cases. The mean registration error of the system, given as a computer-calculated value, was 2.1 mm (0.4-3.1 mm). Postoperative clinical evaluations and imaging were performed on every patient in order to confirm the success of the surgical procedure. All patients recovered well and without any postoperative complications. We conclude that image guidance in single burr-hole procedures provides a high degree of accuracy in lesion targeting, permits good anatomical orientation and minimizes brain trauma. The navigation system has proven to be a helpful tool since it increases the safety of single burr-hole procedures.

CCM1 mutation screen of sporadic cases with cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) are CNS vascular anomalies associated with seizures, headaches, and hemorrhagic strokes. The CCM1 gene was screened in 35 sporadic cases with either single or multiple CCM. It was found that 29% of the individuals with multiple CCM have a CCM1 mutation, whereas cases with only one malformation have none. Sporadic cases with multiple malformations warrant the same approach as individuals who have a familial history of CCM.

The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas.

BACKGROUND: Gliomas are the most common primary tumours of the central nervous system and exhibit rapid growth that is associated with neovascularisation. Adrenomedullin is an important tumour survival factor in human carcinogenesis. It has growth promoting effects on gliomas, and blockade of its actions has been experimentally shown to reduce the growth of glioma tissues and cell lines. There is some evidence that the calcitonin receptor-like receptor (CRLR) mediates the tumorigenic actions of adrenomedullin. AIM: To determine whether CRLR is expressed in human gliomas and the probable cellular targets of adrenomedullin. METHODS: Biopsies from 95 human gliomas of varying grade were processed for immunohistochemical analysis using a previously developed and characterised antibody to CRLR. RESULTS: All tumour specimens were positive for CRLR. As previously found in normal peripheral tissues, CRLR immunostaining was particularly intense in the endothelial cells. This was evident in all the various vascular conformations that were observed, and which are typical of gliomas. In addition, clear immunostaining of tumour cells with astrocyte morphology was observed. These were preferentially localised around vessels. CONCLUSIONS: This study has shown for the first time that the CRLR protein is present in human glioma tissue. The expression of the receptor in endothelial cells and in astrocytic tumour cells is consistent with the evidence that its endogenous ligand, adrenomedullin, may influence glioma growth by means of both direct mitogenic and indirect angiogenic effects. CRLR may be a valuable target for effective therapeutic intervention in these malignant tumours.

[Aneurysmal subarachnoid hemorrhage: role of computerized tomography for correct prediction of the ruptured aneurysm site]. / Erlaubt die Computertomographie nach aneurysmatischer Subarachnoidalblutung die korrekte Vorhersage der Aneurysmalokalisation?

OBJECTIVE: To investigate if the intracisternal distribution of subarachnoid hemorrhage (SAH) following aneurysm rupture allows the correct prediction of the symptomatic aneurysm site. [nl] METHODS: Ninety-nine consecutive patients with acute SAH and angiographically proven aneurysm were included into the study. The parent vessel of the diagnosed aneurysms were the anterior communicating artery (ACoA) in 38 patients, the middle cerebral artery (MCA) in 26 patients, the internal carotid artery (ICA) in 25 patients, the pericallosal artery (A2) in 5 patients, the basilar artery (BA) in 4 patients and the vertebral artery (VA) in 1 patient. In 21 patients, an additional asymptomatic aneurysm was diagnosed. The initial computerized tomography (CT) scans of the 99 patients were given to 2 experienced vascular neurosurgeons, who were blinded for the angiography findings. The 2 investigators had to predict the site of the ruptured aneurysm. [nl] RESULTS: Investigator 1 correctly predicted the aneurysm site in 56 (57 %), investigator 2 in 59 of the 99 patients (60 %). Investigator 1 correctly identified 81 % of the MCA aneurysms, and investigator 2 74 % of the ACoA aneurysms. However, in only 46 of the 99 patients (47 %), the aneurysm site was correctly predicted by both investigators together. [nl] CONCLUSION: The results indicate, that the distribution of the subarachnoid blood as shown on the first CT scan after aneurysm rupture barely allows to predict the symptomatic aneurysm site. Thus, neurosurgical decision making (identification of the ruptured aneurysm in patients with multiple aneurysms; surgical exploration in patients with non-perimesencephal SAH, but negative angiography) should not rely on the first CT scan after SAH.

The Doppler-guided transfalcine venous approach in selected cases of vein of Galen malformations.

OBJECTIVE: This investigation was performed to evaluate the specific procedural issues and indications of a surgically assisted Doppler-guided endovascular transfalcine venous approach for the treatment of vein of Galen aneurysmal malformations (VGAM) in critically ill neonates. PATIENTS AND METHODS: Two neonates out of a clinical series of 15 children (8 males and 7 females) with vein of Galen malformations were treated by our neurovascular team, using a combined surgically assisted endovascular transfalcine approach. In the biplanar angiography room a radiographically guided craniotomy (1.5 cm) was placed over the cranial projection of the falciforme sinus. After craniotomy the orthograd flow of the falciforme sinus was identified by Doppler ultrasonography. The sinus was punctured by an i. v. cannula with injection port and was sutured to the skin. A microcatheter was maneuvered over a guide into the malformation under fluoroscopic control. For embolization Guglielmi electrolytically detachable platinum coils were placed into the malformation as an embolic agent. Neurological examination records, available MR images, computed tomographic scans, pre- and postembolization angiograms and follow-up data were analyzed. RESULTS: In both individuals the malformation was classified as VGAM. The follow-up was 6 and 7 months, respectively. No technique associated morbidity or mortality occurred in the present series. At discharge both selected neonates were in stable condition and the flow in the VGAMs could be significantly reduced by a combination of approaches including the venous transfalcine approach. Meanwhile, 6 months after birth one neonate died due to a deterioration of the pulmonary hypertension. CONCLUSIONS: Endovascular treatment is presently the most efficient strategy to allow neonates and infants survive the early manifestation of vein of Galen malformations and probably render a normal neurological development. Consequently, a combination of approaches in selected cases including the Doppler guided venous transfalcine route should be regarded as a preferential treatment modality, especially in patients with arterial vasospasms and venous stenosis.

Helium (argon) plasma coagulation in neurosurgery. morphology of tissue damage and reparation.

Plasma coagulation, used in some neurosurgical operative settings, is currently under experimental investigation for the precise assessment of the kind and extent of tissue damage. We established a standardised trial to investigate the effects of helium (argon) plasma coagulation - H(A)PC - on rat brain tissue. The tissue reactions were observed with common methods of morphology including immunohistology and electron microscopy. A time dependent profile of the tissue reactions was performed from day 1 after operation up to 6 weeks. The tissue reaction consisted of clearly demarcated concentric zones. The depth of the lesion was about 1 mm maximally, at the beginning. Reparative forces acted at variance both in the different layers and at the edges versus the center of the damage. A manifold but reproducible picture emerges in the various compartments allowing the study of different aspects of organisation and/or elimination of tissue components. This study has demonstrated that a defined circumscribed and reproducible small lesion can be performed with H(A)PC. As in other areas of surgery, this technique has proven to be minimally traumatic. Clinical application of this technique in neurosurgery is therefore promising. In addition, H(A)PC lesions are obviously best suited for morphological studies of early and late reparative reactions in cells and tissues.

[Recommendations for the management of unruptured intracranial aneurysms]. / Empfehlungen zum Management nichtrupturierter intrakranieller Aneurysmen.

Optimal management of patients with unruptured intracranial aneurysms (UIAs) remains controversial. Recent studies have found conflicting data regarding the natural history and the treatment outcome of UIAs. Based on the recommendations published by the American Heart Association, the Section of Vascular Neurosurgery of the German Society of Neurosurgery has formed a task force to summarize the available data and to develop a practical framework for the management of UIAs. For UIAs, only evidence from nonrandomized historical cohort comparisons and case series without control subjects are available, supporting only grade C recommendations (options), but no standards (grade A) and no guidelines (grade B). The present recommendations have been developed as a neurosurgical, neuroradiological and neurological consensus. They are based on the existing data of both treatment risks and the risks of the natural history of UIAs.

Phase I clinical trial on adjuvant active immunotherapy of human gliomas with GD2-conjugate.

The objective of this study was to determine the feasibility, toxicity, and potential therapeutic benefits of an adjuvant active immunotherapy using a tumour specific ganglioside (GD2) conjugate for the adjuvant treatment of recurrent or progressive gliomas. Seven patients with proven GD2 expression in surgical specimens underwent a vaccination course with GD2-KLH/MPL-A conjugate. The follow-up was performed according to WHO guidelines regarding common toxicity criteria. Antibody titres against the ganglioside and the adjuvants were analysed. All patients developed a local type 4 reaction. Anti-GD2-antibody titres could not be detected, despite high titres against the immunoadjuvants. No tumour regression was observed. The disease remained stable for a median of 21.5 weeks (6-34 weeks). The median survival time after the first immunization was 47 weeks. The medial total survival time was 76 weeks. Adverse effects have not been observed. Active GD2-KLH/MPL-A immunization was technically feasible, but did not elicit anti-GD2 antibody generation.

[Analysis of factors affecting the prognosis of vertebral metastases]. / Faktorenanalyse zur Prognose vertebraler Metastasen.

The goal of this study was to evaluate factors for the prognosis of patients with metastatic spinal tumors. 139 patients with vertebral metastases were studied. The modified Tokuhashi Score (a preoperative score composed of six parameters) and single factors were analysed with statistical methods. The modified Tokuhashi Score showed a significant correlation (p = 0,0019) with survival time of patients. Additionally, only the Karnofsky Index as single parameter showed statistically significant correlation(p = 0.0016). Regarding the logistic regression, primary tumor, age, sex and Karnofsky Index were identified as prognostic factors for survival time. This trial could demonstrate that the Tokuhashi Score is a successful predicting tool for the assessment of prognosis of patients with vertebral metastases.

Combined intrathecal baclofen and morphine infusion for the treatment of spasticity related pain and central deafferentiation pain.

OBJECTIVES: Complex pain syndromes due to spasticity and central deafferentation often fail to respond to medical therapy and create challenging problems in the pain management. So far, only spasticity associated musculosceletal pain has been reported to respond to intrathecal baclofen application [1, 2]. METHODS: We report the treatment of severe neuropathic pain in a patient with ED and the combined intrathecal application of baclofen and morphine in 5 patients with severe spasticity related pain. RESULTS: Continuous intrathecal baclofen infusion resulted in a pain free period of 20 months in the patient with ED. Patients with spasticity treated with intrathecal application of baclofen and morphine were pain free for a mean period of 2 years. CONCLUSION: Intrathecal baclofen and morphine application proved to be effective in spasticity related and central deafferentation pain and should therefore be considered in the management of these patients.