The programmable shunt-system Codman Medos Hakim: A clinical observation study and review of literature.

OBJECTIVES: Hydrocephalus can be defined as clinically symptomatic dilatation of the internal ventricular system at the expense of brain and blood volume. Shunt insertion is the mainstay of therapy for communicating hydrocephalus. One of the most frequently used valves is the programmable Codman Medos Hakim valve which enables the pressure level to be adjusted from 30 to 200 mmH2O. The problem of functional over- or underdrainage and the associated complications should be significantly reduced if not excluded. Especially in the clinical application of the Codman Medos Hakim Shunt System in hydrocephalus of other etiology only a few studies can be found. This study aims to increase knowledge of both the safety of Codman Medos valves with SiphonGuard in the clinical application as well as the correct choice of the pressure level for different indications. PATIENTS AND METHODS: In this retrospective study, 101 patients were included who underwent surgery with the adjustable "Codman Medos Hakim" valve with "SiphonGuard" between January 2010 and July 2013. We analyzed the patient files and imaging (CCT, cMRT) data. The statistical examinations were performed using the WINStat program for Excel. RESULTS: Our results show that an initial pressure level of 120mmH2O proved to be suitable in all subgroups. After optimization of the initial pressure level 70.3% of the valves (71 valves) had a pressure level of 120mmH2O. Importantly, only in the SAH subgroup the clinical improvement was correlated with a reduction in the measured indices. But in all subgroups a clinical deterioration was associated with an increased ventricular size. CONCLUSION: Overall, the clinical data show that an initial pressure level of 120mmH2O seems to be appropriate for most patients treated in this series. Measured indices from the cranial imaging can provide valuable indications for the presence of a suboptimal valve setting for the individual patient.

Factors influencing the outcome (GOS) in reconstructive cranioplasty.

After performing a decompressive craniectomy, a cranioplastic surgery is usually warranted. The complications of this reconstructive procedure may differ from the initial operation. The authors of this study report on their experience to define patient-specific and procedural risk factors for possible complications following cranioplasty influencing the outcome (Glasgow Outcome Scale (GOS)), mobility, shunt dependency, and seizures. A retrospective analysis of 263 patients of all ages and both sexes who had undergone cranioplasty after craniectomy for traumatic brain injury (including chronic subdural hematoma), subarachnoidal hemorrhage (including intracerebral hemorrhage), ischemic stroke, and tumor surgery in one single center in 12 years from January 2000 to March 2012 has been carried out. A multiple logistic regression analysis was performed to identify potential risk factors (age, gender, used cranioplasty material, initial diagnosis, clipped or coil-embolized subarachnoidal hemorrhage (SAH) patients, time interval, complications especially hydrocephalus and seizures, mobility) upon the prognosis described as a dichotomized Glasgow Outcome Scale. Two hundred forty-eight patients met the study criteria. The overall complication rate after cranioplastic surgery was 18.5% (46 patients). Complications included: surgical site infection, epidural hematoma, hydrocephalus with or without former SAH, and new-onset seizures. Logistic regression analysis identified significant correlation between a low GOS (2 or 3) and postoperative seizures (OR 2.37, CI 1.35-4.18, p < 0.05), shunt-depending hydrocephalus (OR 5.83, CI 3.06-11.11, p < 0.05), and age between 51 and 70 years (OR 2.4, 95% CI 1.09-5.29, p = 0.029). However, gender, time interval between craniectomy and cranioplasty, initial diagnosis, and used cranioplasty material had no significant influence on post-cranioplasty complications as surgical site infections, hematoma, wound healing disturbance, seizures, or hydrocephalus. Evaluation of treatment modality in aneurysmal SAH clip vs. coil showed no significant relation to postoperative complications either. Complications after cranioplastic surgery are a common problem, as prognostic factors could identify a shunt-depending hydrocephalus and epilepsia to develop a major deficit after cranioplastic surgery (GOS 2 or 3). We detected a significant extra risk of people between the age of 51 and 70 years to end up in GOS level 2 or 3.

Extensive growth of an anaplastic meningioma.

We present the case of a 30-year-old male patient with an almost complete destruction of the calvarial bone through an anaplastic meningioma diagnosed in line with dizziness. Neuroimaging revealed an extensive growing, contrast enhancing lesion expanding at the supra- and infratentorial convexity, infiltrating and destroying large parts of the skull, and infiltrating the skin. Due to progressive ataxia and dysarthria with proven tumor growth in the posterior fossa in the continuing course, parts of the tumor were resected. A surgical procedure with the aim of complete tumor resection in a curative manner was not possible. Six months after the first operation, due to a new tumor progression, most extensive tumor resection was performed. Due to the aggressive and destructive growth with a high rate of recurrence and tendency of metastases, anaplastic meningiomas can be termed as malignant tumors. The extrinsic growth masks the tumor until they reach a size, which makes these tumors almost unresectable. In the best case scenarios, the five-year survival is about 50%. With the presented case, we would like to show the aggressive behavior of anaplastic meningiomas in a very illustrative way. Chemotherapy, radiotherapy, and surgery reach their limits in this tumor entity.

MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers.

The prognostic role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had received radiotherapy with concomitant and adjuvant TMZ as an initial treatment. Median overall survival (OS) did not significantly differ between 19 patients with MGMT promoter methylated tumors when compared to 28 patients with unmethylated tumors (18.9 vs 15.0 months; p = 0.1054). In the first-line BCNU + TMZ group, MGMT promoter methylation was associated with longer OS (21.0 vs 11.1 months, p = 0.0127), while no significant survival differences were detected in the other two subgroups. Progression-free survival did not significantly differ between patients with and without MGMT promoter methylated tumors in the entire patient cohort or any of the three subgroups. The first-line BCNU + TMZ group showed no significant difference in OS when compared to the first-line BCNU group (18.9 vs 14.7 months), but tended to have more therapy-related adverse effects (53% vs 24%, p = 0.105). In summary, MGMT promoter methylation showed a non-significant trend toward longer survival in our patient cohort. The combination of TMZ radiochemotherapy with local delivery of BCNU did not provide a significant survival benefit compared to local BCNU alone, but was associated with a higher rate of adverse effects. Owing to the small number of patients investigated, however, these findings would need to be corroborated in larger patient cohorts.

The combination of carmustine wafers and temozolomide for the treatment of malignant gliomas. A comprehensive review of the rationale and clinical experience.

Current treatment strategies in patients with newly-diagnosed glioblastoma include surgical resection with post-operative radiotherapy and concomitant/adjuvant temozolomide (the "Stupp protocol") or resection with implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the surgical cavity followed by radiotherapy. In clinical practice, patients with malignant glioma treated with BCNU wafer often also receive adjuvant temozolomide. However, current treatment guidelines are unclear on whether and how these treatment practices can be combined, and no prospective phase 3 study has assessed the safety and efficacy of combining BCNU wafers with temozolomide and radiation in high-grade malignant glioma. The rationale for multimodal therapy comprising surgical resection with adjunct local BCNU wafers followed by radiotherapy and temozolomide is based on complementary and synergistic mechanisms of action between BCNU and temozolomide in preclinical studies; a shared primary resistance pathway, methylguanine-DNA methyltransferase (MGMT); and the opportunity to overcome resistance through MGMT depletion to boost cytotoxic activity. A comprehensive review of the literature identified 19 retrospective and prospective studies investigating the use of this multimodal strategy. Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile.

Three dimensional rotational angiography in surgical planning of aneurysm clipping.

BACKGROUND: Three-dimensional (3D) angiography is increasingly used in the diagnostics of brain aneurysms. Aim of the present study was to evaluate the accuracy of 3D angiograms with respect to its value for preoperative planning of aneurysm clipping. PATIENTS AND METHODS: The 3D angiograms of 42 patients with subarachnoid bleeding caused by aneurysm rupture of the anterior circle of Willis and the intradural carotid have been compared to intraoperative photographs of the aneurysms. RESULTS: Neighbouring vessels, aneurysm anatomy, arteries originating from the aneurysm wall were accurately shown decreasing the surgical risk of aneurysm clipping. CONCLUSIONS: The 3D images enabled a perfect preoperative planning through the operation by illuminating the aneurysm anatomy, neck localisation and shape and relation of the aneurysm to neighbouring vessels. Operative approach, use of an accurate clip and avoidance of clipping arteries close to the aneurysm have become predictable and safer by the use of 3D angiography.

Resistant vasospasm in subarachnoid hemorrhage treated with continuous intraarterial nimodipine infusion.

Cerebral vasospasm complicating aneurysmal subarachnoid hemorrhage is a well-known medical entity. The delayed ischemic neurological deficits (DIND) as a result of vasospasm remain the main cause of morbidity among patients who manage to survive this severe disease pattern. When the traditional treatment options, either medical or interventional, fail to reverse vasospasm, continuous intraarterial infusion of nimodipine through catheters directly into the spastic arteries presents a promising treatment modality. Of 73 patients with aneurysmal subarachnoid hemorrhage between 2008 and 2009, a total of 27 had Hunt and Hess grades of 4 and 5. Fifteen percent of them showed refractory vasospasms and were treated with continuous nimodipine infusion via catheters in both internal carotid arteries. We present the method's indications and possible complications.

Deep brain stimulation of the posterior hypothalamic area in intractable short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT).

BACKGROUND: SUNCT (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing) is a rare syndrome characterized by the sudden onset of excruciating unilateral periorbital pain that is accompanied by conjunctival injection and lacrimation or further autonomic signs. Similar to patients with chronic cluster headache, Leone and Lyons showed a beneficial effect of deep brain stimulation of the posterior hypothalamic region in two patients with a chronic SUNCT. CASE: Here, we present the case of a man with a chronic SUNCT responding to deep brain stimulation of the posterior hypothalamic area. CONCLUSION: This case supports the idea of a central origin of SUNCT and shows that deep brain stimulation of the hypothalamic region can be effective in the treatment of the chronic form of this rare disorder.

Transorbital impalement injury with massive intracranial lesion not detected by cranial CT scan.

An extraordinary case of transorbital penetration injury is presented. A 24-year-old male patient was involved in a fight and was pushed against a shelf. He immediately lost consciousness and was brought to hospital. A cranial computed tomogaphy (CT) scan showed a hemorrhage and brain edema over the left hemisphere with orbital roof fracture. A decompressive craniectomy was performed. Intraoperatively, an orbital roof fracture with penetration of the frontobasal dura could be seen which could not be explained by the trauma mechanism. The postoperative magnetic resonance imaging (MRI) with susceptibility-weighted image (SWI) showed two injury tracks from the orbit through the brain which appeared to be penetration injuries. The forensics department was consulted and penetration by a falling candleholder was found to be the cause of the injuries. In this case, the cranial CT alone did not show any indication of a penetration injury. Only MRI revealed the penetration track, which stresses the diagnostic value of this modality and especially the SWI in cases where the trauma mechanism does not correspond to the injury shown in the CT scan.

Distress in patients with newly diagnosed brain tumours.

OBJECTIVE: Patients with intracranial tumours often suffer from clinically relevant psychological distress. However, levels of distress and contributing factors have not been systematically evaluated for the early course of the disease. Using the National Comprehensive Cancer Network's Distress Thermometer (DT), we evaluated the extent and sources of distress within a population of patients with intracranial neoplasms. METHODS: One hundred and fifty-nine patients were included who underwent craniotomy for newly diagnosed intracranial tumours at our department. All patients completed the DT questionnaire, a single-item 11-point visual analogue scale measuring psychological distress. The appendant problem list (PL) consists of 40 items representing problems commonly experienced by cancer patients. Patients were asked to mark any experienced sources of distress. RESULTS: Percentage of patients suffering from relevant distress was 48.4% (cut-off ≥6). DT-scores were significantly associated with depression and anxiety as well as reported number of concerns. On average, patients reported 6.9 sources of cancer-related distress. Objective medical data (e.g. tumour stage) as well as sociodemographic data (e.g. gender, IQ) were not associated with psychological distress at this early phase. CONCLUSIONS: Prevalence of elevated distress is high shortly after primary neurosurgical treatment in patients with intracranial tumours and cannot be predicted by objective data. As a consequence, sources of distress can and should be routinely assessed and targeted in these individuals in this particular period. Further studies are needed to help to identify patients who are at risk of suffering from long-term emotional distress in order to enable targeted psychosocial intervention.

Surgical treatment for brain metastases: Prognostic factors and survival in 309 patients with regard to patient age.

Brain metastases are the most common intracranial tumors. Overall, the only accepted prognostic factors are patient age and performance status. However, several other factors are considered before surgery. We performed a retrospective analysis of 309 patients who underwent surgical resection of newly diagnosed brain metastases between 1994 and 2004. Univariate survival analysis revealed age, performance status, extracranial metastases, complete resection, radiotherapy and re-craniotomy as prognostic indicators. Multivariate analysis determined that patient age, performance status, extracranial metastases, radiotherapy and re-craniotomy are independent factors of prolonged survival. We statistically estimated the age threshold separating patients with favorable outcomes from those with unfavorable prognoses. Using the Kaplan-Meier analysis this threshold can be set at 65 years. Multivariate analysis of patients >65 years revealed the presence of co-morbidities, the number of brain metastases, post-operative performance status and radiotherapy as independent prognostic factors.

[Brachytherapy in combination with function-preserving surgery of cancer of the paranasal sinus]. / Kombination von Brachytherapie und Chirurgie bei Tumoren mit Orbita-/Schädelbasisinfiltration.

BACKGROUND: Prognosis of patients with advanced/recurrent cancer of paranasal sinuses and orbit with infiltration of the skull base is very bad. Radical surgery does not improve prognosis. A disadvantage of the radical surgery is the functional loss and the residual cosmetic defect. We present the results of a function-preserving surgery in combination with interstitial, image adapted brachytherapy (IABT) for the treatment of these cancers. METHODS AND PATIENTS: Ten patients with paranasal sinus cancer and 16 patients with sarcomas (n=26) were retrospectively analysed. After a maximum tumor resection (mostly R1-R2 resections), 2-12 flexible afterloading plastic tubes were implanted. The postoperative IABT total dose was 10-25 Gy in 2.5 Gy fractions twice daily fractions for 5 days. RESULTS: In all cases the eye was obtained without functional damage. The IABT was well tolerated. The visual and cosmetic results were satisfactory. Postoperative complications occurred in 7 out of 26 cases without a serious long-term adverse event. Significant radiation-induced complications were found in patients with orbital or skull base involvement. The three years overall survival was 60% for rhabdomyosarcoma, and 33% for the paranasal sinus cancers. CONCLUSIONS: These results show that a combined treatment of function-preserving surgery and a IABT is a feasible, successful and well-tolerated option for curative, salvage and palliative therapy for selected patients with advanced or recurrent carcinoma of the paranasal sinuses and orbit.

A new tool for the navigated placement of intracerebral chemotherapy catheters.

OBJECTIVE: The aim of this report is to illustrate a method for the precise placement of chemotherapeutic delivery catheters with the aid of computer-assisted navigation systems. MATERIALS AND METHODS: We have developed a cannula which can be referenced to our navigation system (BrainLab (®)) to advance and position catheters. The cannula has a length of 10 cm. In the case of a ventricular puncture, CSF will drain through holes at the tip and a side port of the cannula to caution the surgeon. The cannula is fixed to the BrainLab (®) adapter ML and navigated with a BrainLab (®) vector vision (®) system. Using the puncture software, the placement is planned and executed. After placing the cannula as planned, the mandrin is removed and the primed catheter moved forward. When resistance is felt the cannula is withdrawn over the catheter. Further catheters can be placed similarly. RESULTS: Initial phantom tests showed a good target accuracy. Clinically we have used the cannula in 7 cases with good accuracy. CONCLUSION: This newly designed tool is easy to handle and well integrated into the navigation system. It provides the means to place catheters precisely to the planned position. Potentially it can be combined with every navigation system using adaptable reference systems.

Outcome evaluation in glioblastoma patients using different ranking scores: KPS, GOS, mRS and MRC.

Patient performance is an overall accepted independent prognostic factor in glioblastoma patients. Its estimation is essential for treatment planning, follow-up and clinical trials. Patient performance is mostly determined by usage of the Karnofsky Performance Score (KPS) for cancer patients. However, several other ranking scores have been developed specifically for patients with neurological diseases: Glasgow Outcome Score (GOS) for trauma patients, modified Ranking Score for stroke patients and Medical Research Council brain prognostic index (MRC) for brain tumour patients. The aims of this study were: (1) to compare these four performance scores in their ability to determine patient survival; and (2) to compare the prognostic value of performance with that of other prognostic factors. Univariate and multivariate survival analysis was used. Survival analysis revealed a high correlation to survival for all four scores. The maximum derivation of the curves was shown for the MRC and GOS. Performance had more clinical impact in determining patient survival than age and tumour resection. Differential treatment planning may need the formation of more than two patient groups. This was possible with the MRC, as well as the GOS and KPS. Forming more than three patient groups was not effective with any score.

Increase in tumor size following intratumoral injection of immunostimulatory CpG-containing oligonucleotides in a rat glioma model.

The immunosuppressive environment of malignant gliomas is likely to suppress the anti-tumor activity of infiltrating microglial cells and lymphocytes. Macrophages and microglial cells may be activated by oligonucleotides containing unmethylated CpG-motifs, although their value in cancer immunotherapy has remained controversial. Following injection of CpG-containing oligonucleotides (ODN) into normal rat brain, we observed a local inflammatory response with CD8+ T cell infiltration, upregulation of MHC 2, and ED1 expression proving the immunogenic capacity of the CpG-ODN used. This was not observed with a control ODN mutated in the immunostimulatory sequence (m-CpG). To study their effect in a syngeneic tumor model, we implanted rat 9L gliosarcoma cells into the striatum of Fisher 344 rats. After 3 days, immunostimulatory CpG-ODN, control m-CpG-ODN, or saline was injected stereotactically into the tumors (day 3 group). In another group of animals (day 0 group), CpG-ODN were mixed with 9L cells prior to implantation without further treatment on day 3. After 3 weeks, the animals were killed and the brains and spleens were removed. Rather unexpectedly, the tumors in several of the animals treated with CpG-ODN (both day 0 and day 3 group) were larger than in saline or m-CpG-ODN treated control animals. The tumor size in CpG-ODN-treated animals was more variable than in both control groups. This was associated with inflammatory responses and necrosis which was observed in most tumors following CpG treatment. This, however, did not prevent excessive growth of solid tumor masses in the CpG-treated animals similar to the control-treated animals. Dense infiltration with microglial cells resembling ramified microglia was observed within the solid tumor masses of control- and CpG-treated animals. In necrotic areas (phagocytic), activation of microglial cells was suggested by ED1 expression and a more macrophage-like morphology. Dense lymphocytic infiltrates consisting predominantly of CD8+ T cells and fewer NK cells were detected in all tumors including the control-treated animals. Expression of perforin serving as a marker for T cell or NK cell activation was detected only on isolated cells in all treatment groups. Tumors of all treatment groups revealed CD25 expression indicating T cells presumed to maintain peripheral tolerance to self-antigens. Cytotoxic T cell assays with in vitro restimulated lymphocytes ((51)chromium release assay) as well as interferon-gamma production by fresh splenocytes (Elispot assay) revealed specific responses to 9L cells but not another syngeneic cell line (MADB 106 adenocarcinoma). Surprisingly, the lysis rates with lymphocytes from CpG-ODN-treated animals were lower compared to control-treated animals. The tumor size of individual animals did not correlate with the response in both immune assays. Taken together, our data support the immunostimulatory capacity of CpG-ODN in normal brain. However, intratumoral application proved ineffective in a rat glioma model. CpG-ODN treatment may not yield beneficial effects in glioma patients.

A subarachnoid haemorrhage primarily presenting as Terson's syndrome.

We present a case of a subarachnoid haemorrhage due to a ruptured basilar artery aneurysm in a 61-year-old woman. She presented with visual deterioration as the only clinical sign, no previous episodes of headache were reported. Fundoscopy showed a bilateral vitreous haemorrhage. A consecutively performed cranial computer tomography demonstrated subarachnoid bleeding. Further diagnostics revealed a basilar artery aneurysm that was successfully treated with coil embolisation. As a scarring of the vitreous bodies developed, they had to be removed. The patient's eyesight improved gradually and no further complications occurred.

Deep brain stimulation of the internal globus pallidus in dystonia: target localisation under general anaesthesia.

UNLABELLED: Deep brain stimulation (DBS) of the internal globus pallidus (Gpi) is an effective therapy for various types of dystonia. The authors describe their technical approach for securing appropriate placement of the stimulating electrodes within the Gpi under general anaesthesia, including MRI based individualised anatomical targeting combined with electrophysiological mapping of the Gpi using micro-recording (MER) as well as macrostimulation and report the subsequent clinical outcome and complications using this method. METHOD: We studied 42 patients (male-female ratio 25:17; mean age 43.6 years, range 9 to 74 years) consecutively operated at the Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel, between 2001 - 2006. One patient underwent unilateral implantation after a right-sided pallidotomy 30 years before and strictly unilateral symptoms; all other implantations were bilateral. Two patients had repeat surgery after temporary removal of uni- or bilateral implants secondary to infection. Overall, 86 DBS electrodes were implanted. In 97% of the implantations, at least three microelectrodes were inserted simultaneously for MER and test stimulation. Initial anatomical targeting was based on stereotactic atlas coordinates and individual adaptation by direct visualisation of the Gpi on the stereotactic T2 or inversion-recovery MR images. The permanent electrode was placed according to the results of MER and test stimulations for adverse effects. FINDINGS: The average improvement from baseline in clinical ratings using either the Burke-Fahn-Marsden-Dystonia (BFMDRS) or Toronto-Western-Spasmodic-Torticollis (TWSTR) rating scale at the last post-operative follow-up (mean 16.4 ; range 3-48 months) was 64.72% (range 20.39 to 98.52%). The post-operative MRI showed asymptomatic infarctions of the corpus caudatus in three patients and asymptomatic small haemorrhages in the lateral basal ganglia in two patients. One patient died due to a recurrent haemorrhage which occurred three months after the operation. The electrodes were implanted as follows: central trajectory in 64%, medial trajectory in 20%, anterior in 9% and lateral dorsal trajectories in 3.5% each. The reduction in BFMDRS or TWSTR motor score did not differ between the group implanted in the anatomically defined (central) trajectory bilateral (-64.15%, SD 23.8) and the physiologically adopted target (uni- or bilateral) (-63.39%, SD 23.1) indicating that in both groups equally effective positions were chosen within Gpi for chronic stimulation (t-test, p > 0.4). CONCLUSIONS: The described technique using stereotactic MRI for planning of the trajectory and direct visualisation of the target, intra-operative MER for delineating the boundaries of the target and macrostimulation for probing the distance to the internal capsule by identifying the threshold for stimulation induced tetanic contractions is effective in DBS electrode implantation in patients with dystonia operated under general anaesthesia. The central trajectory was chosen in only 64%, despite individual adaptation of the target due to direct visualisation of the Gpi in inversion recovery MRI in 43% of the patients, demonstrating the necessity of combining anatomical with neurophysiological information.