Necessity of MRI-compatible deep brain stimulation systems - Hits and hints for decision making.

OBJECTIVES: Deep brain stimulation (DBS) is a safe and effective treatment option for patients with movement disorders as Parkinson's disease, essential tremor and dystonia[1]. For many of these patients the need for imaging may arise in the following years after implantation. The study's aim was to get an overview of the amount of patients with a DBS system who needed an MRI after successful implantation, and if they did, whether the imaging led to a surgical consequence. MATERIALS AND METHODS: In this retrospective descriptive work patients were included if they had their DBS implantation for at least 12 months at the time of analysis. Data were collected by retrospective analysis of the electronic patient files as well as a telephone interview. The reason of each imaging performed was assessed, if patients got MRI after the implantation, it was additionally recorded whether imaging led to a consequence (conservative treatment or surgery). An independent neurologist assessed if an MRI would have been better than a CT for the particular indication. RESULTS: From 54 included patients, 28 patients received imaging after implantation, either CT or MRI. 7 patients underwent MRIs, of whom 3 patients received cranial MRIs and 4 patients received lumbar spine MRIs. All cranial MRIs led to conservative therapy, in 2 lumbar MRIs the diagnosis led to surgery. Nearly 13 % of the imaging performed in our study population occurred because of fall events, 9 of the included patients developed or have had a tumor diagnosis. CONCLUSIONS: Safety of MRI for patients with implanted DBS-systems is and remains an important consideration. Since it can be assumed that patients at a younger age are more likely to get an MRI in the course of their disease, we suggest paying particular attention to the MRI's suitability of the DBS device by patients age. In the end it remains always an individual decision for the surgeon or the consulting physician, which system to use.

Tissue expansion for challenging DBS hardware erosions in patients with Parkinson's disease.

•Consider tissue expanders for challenging DBS cases in PD patients with hardware erosion.•Placement of tissue expander is essential in planning the reconstruction.•MRI-compatibility of the tissue expander is paramount for shortening the total duration of anesthesia.•Role of routine skin biopsies to identify PD patients at additional risk for developing scalp defects should be investigated.

Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided Continuous Infusion.

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20-30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

External validation and modification of the Oslo grading system for prediction of postoperative recurrence of chronic subdural hematoma.

Recently, Oslo grading system (OGS) for prediction of recurrence in chronic subdural hematoma (cSDH) was introduced. The aim of the study was to validate and if applicable to modify the grading system. Data of all patients admitted to the Goethe University Hospital between 2016 and 2018 with chronic subdural hematoma were prospectively entered into a database. Dataset of patients with uni- (n = 272) and bilateral cSDH (n = 177) were used for the validation of OGS via logistic regression analysis. Additional predictors were identified and integrated to build a modified OGS (mOGS). Internal validation of the modified OGS was performed using same dataset of patients. The OGS showed a significant good predictive value with correlating increase of recurrence rate depending on the level of score in unilateral cSDH (p = 0.002). Regarding bilateral cSDH, there was no significant predictive value found (p = 0.921). By performing uni- and multivariate analysis, additional predictors for recurrence in uni- and bilateral cSDH were identified and integrated into the score system. Accordingly, the mOGS for unilateral cSDH inherited 4 components: previous OGS with 3 components (OR1.6) and seizure (OR2.5) (0 point, 0% recurrence rate; 1-2 points, 17.4%; 3-4 points, 30.6%; ≥ 5 points, 80%). Regarding bilateral cSDH, the mOGS consisted of 4 components as well: hypodense/gradation subtypes (OR3.3), postoperative unilateral volume > 80 mL (OR7.4), postoperative unilateral air trapping > 80 mL (OR15.3), and seizure (OR5.5) (0 point, 3.6% recurrence rate; 1 point, 30.6%; 2 points, 53.5%; 3 points, 58.3%; ≥ 4 points, 100%). Furthermore, the mOGS was internally verified showing high significant predictive power for recurrent hematoma in uni- (p = 0.004) and bilateral cSDH (p < 0.001). External validation of OGS showed accurate risk stratification of recurrence in unilateral cSDH; however, the validation failed for bilateral cSDH. Thus, mOGS was developed to strengthen its clinical utility and applicability.

Comparing Programming Sessions of Vim-DBS.

Background: Essential Tremor (ET) is a progressive neurological disorder characterized by postural and kinetic tremor most commonly affecting the hands and arms. Medically intractable ET can be treated by deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM). We investigated whether the location of the effective contact (most tremor suppression with at least side effects) in VIM-DBS for ET changes over time, indicating a distinct mechanism of loss of efficacy that goes beyond progression of tremor severity, or a mere reduction of DBS efficacy. Methods: We performed programming sessions in 10 patients who underwent bilateral vim-DBS surgery between 2009 and 2017 at our department. In addition to the intraoperative (T1) and first clinical programming session (T2) a third programming session (T3) was performed to assess the effect- and side effect threshold (minimum voltage at which a tremor suppression or side effects occurred). Additionally, we compared the choice of the effective contact between T1 and T2 which might be affected by a surgical induced "brain shift." Discussion: Over a time span of about 4 years VIM-DBS in ET showed continuous efficacy in tremor suppression during stim-ON compared to stim-OFF. Compared to immediate postoperative programming sessions in ET-patients with DBS, long-term evaluation showed no relevant change in the choice of contact with respect to side effects and efficacy. In the majority of the cases the active contact at T2 did not correspond to the most effective intraoperative stimulation site T1, which might be explained by a brain-shift due to cerebral spinal fluid loss after neurosurgical procedure.

Age dependency and modification of the Subarachnoid Hemorrhage Early Brain Edema Score.

OBJECTIVE: The Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) system measures cerebral edema on CT and can be used to predict outcome after subarachnoid hemorrhage (SAH). The authors developed a modified SEBES (SEBES 6c) and assessed whether it could predict outcome after SAH better than the SEBES. Furthermore, they verified the age dependency of these scores. METHODS: In this retrospective study, all patients with aneurysmal SAH in the period from January 2011 to February 2017 at a single institution were analyzed. The SEBES, which is based on the absence of visible sulci at two defined CT levels (0-4 points), and the SEBES 6c were determined from the initial CT. The SEBES 6c system includes the two levels from the original SEBES and one level located 2 cm below the vertex (0-6 points). The authors investigated whether the various SEBESs are age dependent and if they can predict delayed infarction (DI) and outcome. RESULTS: Two hundred sixty-one patients met the study inclusion criteria. The SEBES was an independent predictor for DI (OR 1.6 per 1-point increase) and unfavorable outcome (OR 1.36 per 1-point increase), in accordance with findings in the first publication on SEBES. However, here the authors found that the SEBES was age dependent. In the age group younger than 60 years, the patients with high-grade SEBESs (3-4 points) had DIs and unfavorable outcomes significantly more often than the patients with low-grade scores (0-2 points). In the age groups 60-69 years and ≥ 70 years, no significant differences in DI and outcome were identified between high-grade and low-grade scores, although trends toward DI and unfavorable outcomes among the 60-69 age group were noted in patients with high-grade SEBESs.Receiver operating characteristic curve analysis showed that SEBES 6c had a higher prognostic value in predicting outcome than SEBES (p < 0.001). Furthermore, SEBES 6c predicted an unfavorable outcome (OR 1.31 per 1-point increase) and DI (OR 1.36 per 1-point increase) independent of vasospasms. SEBES 6c showed an age dependency similar to that of SEBES. CONCLUSIONS: SEBES 6c is more suitable for predicting outcome after SAH than SEBES. Furthermore, it predicts outcome and DI independently of vasospasm, so it can be used to differentiate between early brain injury- and vasospasm-dependent infarctions and outcome. However, SEBES and SEBES 6c are both age dependent and can be used for patients aged < 60 years and may have limited suitability for patients aged 60-69 years and no suitability for patients aged ≥ 70 years.

Thrombosis of the straight sinus and microbleedings due to deep seated arteriovenous fistula - Hemodynamic changes, cognitive impairment and improvement after microsurgery. A technical report.

Dural arteriovenous fistulas (dAVF) are rare vascular malformations accounting for only 10-15% that may lead to life threatening deficits due to hemodynamic changes in blood supply and pressure conditions. We present a 64-year old patient who was admitted with disorientation and aphasia. Following images confirmed an infratentorial dural fistula draining into the straight sinus. Additional findings were progressive thrombosis of the straight sinus, microbleedings and bithalamic edema due changes in hemodynamic conditions and venous congestion. Microsurgery was performed. After treatment improvement in clinical condition was observed and the venous congestion was regressive. Hemodynamic changes due to infratentorial dAVFs may lead to bleedings in deep regions and worsening of clinical condition fastly. Treatment requires carefully planning and visualization of angioarchitecture. Symptoms and hemodynamic changes are reversible after treatment, which are essential for treatment decisions.

Differences in bleeding patterns and outcome after intracerebral hemorrhage due to vascular malformations.

BACKGROUND: Atypical intracerebral hemorrhage is a common form of primary manifestation of vascular malformations. OBJECTIVE: The aim of the present study is to determine clues to the cause of bleeding according to hemorrhage pattern (lobar, basal ganglia, infratentorial). METHODS: We retrospectively evaluated 343 consecutive neurosurgical patients with intracerebral hemorrhage (ICH), who were admitted to our neurosurgical department between 2006 and 2016. The study cohort includes only neurosurgical patients. Patients who underwent treatment by neurologists are not represented in this study. We assessed location of hemorrhage, hematoma volumes to rule out differences and predicitve variables for final outcome. RESULTS: In 171 cases (49.9%) vascular malformations, such as arteriovenous malformations (AVMs), cavernomas, dural fistulas and aneurysms were the cause of bleeding. 172 (50.1%) patients suffered from an intracerebral hemorrhage due to amyloid angiopathy or long standing hypertension. In patients with infratentorial hemorrhage a malformation was more frequently detected as in patients with supratentorial hemorrhage (36% vs. 16%, OR 2.9 [1.8;4.9], p<0.001). Among the malformations AVMs were most common (81%). Hematoma expansion was smaller in vascular malformation than non-malformation caused bleeding (24.1 cm3 vs. 64.8 cm3, OR 0.5 [0.4;0.7], p < 0.001,). In 6 (2.1%) cases diagnosis remained unclear. Final outcome was more favorable in patients with vascular malformations (63% vs. 12%, OR 12.8 [4.5;36.2], p<0.001). CONCLUSION: Localization and bleeding patterns are predictive factors for origin of the hemorrhage. These predictive factors should quickly lead to appropriate vascular diagnostic measures. However, due to the inclusion criteria the validity of the study is limited and multicentre studies with further testing in general ICH patients are required.

Cerebral Vasospasm Due to Arteriovenous Malformation-Associated Hemorrhage: Impact of Bleeding Source and Pattern.

OBJECTIVE: Cerebral vasospasm (CVS) after a ruptured arteriovenous malformation (AVM) is rarely reported. This study is aimed at evaluating the predictive variables in AVM hemorrhage for CVS. METHODS: A total of 160 patients with ruptured AVMs were admitted to our neurosurgical department from 2002 to 2018. The frequency of cerebral vasospasm after AVM hemorrhage and the impact of AVM-associated aneurysms were evaluated. We compared different bleeding patterns, such as intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) or a combination of both (ICH + SAH) and evaluated predictive variables for outcome in last follow-up. RESULTS: A total of 62 (39%) patients had AAA, mostly located prenidal (75.8%). AVMs with ruptured aneurysms often resulted in ICH with SAH component (p < 0.001). Eighty-two patients (51%) presented a SAH component, and CVS occurred in 6 patients (7.3%), mostly due to a ruptured infratentorial AVM (p < 0.03). Infratentorial location and the amount of SAH component (p < 0.001) predicted the incidence of CVS significantly. Cerebral infarction was significantly associated with CVS (p < 0.02). CONCLUSION: SAH component and infratentorial location of ruptured AVMs may harbor a higher risk for CVS. Follow-up with angiographic imaging should be considered in patients with infratentorial AVM hemorrhage and delayed neurologic deterioration to rule out CVS.

The Extent of Neurologic Improvement and Social Life in Young Patients with Ruptured and Unruptured Brain AVM: A Long-Term Follow-Up.

BACKGROUND: Intracerebral hemorrhage, seizures, neurologic deficits, and cognitive impairments due to brain AVM in childhood are incriminating for brain and executive function with sequelae for further social life. Long-term follow-up data on brain AVM in young patients are rare, making it difficult to compare and evaluate treatment risks and outcomes. METHODS: We studied young patients with brain AVM who were referred to our institution between 2005 and 2012 and for whom follow-up data were available. We stratified the patients into those with ruptured AVM (rAVM) and unruptured AVM (uAVM) and compared treated and nontreated patients. Differences in outcome and social participation were assessed. RESULTS: A total of 29 young patients with brain AVM, median age 16 years, were included in our study with complete follow-up data of over 5 years (mean, 6 years). In 18 (62.1%) patients rAVM and in 11 (37.9%) patients uAVM were found. Twenty (69%) patients received treatment (rAVM 70% vs. uAVM 30%). Among treatment methods, microsurgery was most frequently used (rAVM 33.3% vs. uAVM 36.4%). In rAVM, 16 of 18 (88.9%) patients returned to work or school, and in uAVM, 11 (100%) patients did so. Concerning cognitive problems, no statistically significant difference was found in the 2 groups comparing treated and nontreated patients (P > 0.05). A favorable outcome was achieved in 13 (72.2%) patients with rAVM and in 11 (100%) patients with uAVM. CONCLUSION: Favorable outcome was achieved in the majority of patients. The rate of neurologic improvement and participation in social life was very high in the 2 groups.

A novel grading system for the prediction of the need for cerebrospinal fluid drainage following posterior fossa tumor surgery.

OBJECTIVE: Prophylactic placement of an external ventricular drain (EVD) is often performed prior to resection of a posterior fossa tumor (PFT); however, there is no general consensus regarding the indications. The purpose of this study was to establish a novel grading system for the prediction of required CSF drainage due to symptomatic elevated intracranial pressure (ICP) after resection of a PFT to identify patients who require an EVD. METHODS: The authors performed a retrospective analysis of data from a prospective database. All patients who had undergone resection of a PFT between 2012 and 2017 at the University Hospital, Goethe University Frankfurt, were identified and data from their cases were analyzed. PFTs were categorized as intraparenchymal (iPFT) or extraparenchymal (ePFT). Prior to resection, patients underwent EVD placement, prophylactic burr hole placement, or neither. The authors assessed the amount of CSF drainage (if applicable), rate of EVD placement at a later time point, and complication rate and screened for factors associated with CSF drainage. By applying those factors, they established a grading system to predict the necessity of CSF drainage for elevated ICP. RESULTS: A total of 197 patients met the inclusion criteria. Of these 197, 70.6% received an EVD, 15.7% underwent prophylactic burr hole placement, and 29.4% required temporary CSF drainage. In the prophylactic burr hole group, 1 of 32 patients (3.1%) required EVD placement at a later time. Independent predictors for postoperative need for CSF drainage due to symptomatic intracranial hypertension in patients with iPFTs were preoperative hydrocephalus (OR 2.9) and periventricular CSF capping (OR 2.9), whereas semi-sitting surgical position (OR 0.2) and total resection (OR 0.3) were protective factors. For patients with ePFTs, petroclival/midline tumor location (OR 12.2/OR 5.7), perilesional edema (OR 10.0), and preoperative hydrocephalus (OR 4.0) were independent predictors of need for CSF drainage. According to our grading system, CSF drainage after resection of iPFT or ePFT, respectively, was required in 16.7% and 5.1% of patients with a score of 0, in 21.1% and 12.5% of patients with a score of 1, in 47.1% and 26.3% of patients with a score of 2, and in 100% and 76.5% of patients with a score ≥ 3 (p < 0.0001). The rate of relevant EVD complications was 4.3%, and 10.1% of patients were shunt-dependent at 3-month follow-up. CONCLUSIONS: This novel grading system for the prediction of need for CSF drainage following resection of PFT might be of help in deciding in favor of or against prophylactic EVD placement.

Posterior fossa AVMs: Increased risk of bleeding and worse outcome compared to supratentorial AVMs.

Infratentorial AVMs are often considered as potentially hazardous as they are thought to present more often with hemorrhage, may harbor AVM-associated aneurysms more frequently and to be associated with poor outcome. The aim of our study is to compare features of supratentorial and infratentorial AVMs. We retrospectively analyzed 316 consecutive patients with cerebral AVM presenting to our neurovascular center between 2005 and 2015. Location and angioarchitecture of the AVM including AVM-associated aneurysms, bleeding events, and outcome during follow up were analyzed. Outcome was assessed using the modified Rankin Scale (mRS) and stratified into favorable (mRS 0-2) and unfavorable (mRS 3-6). 41.6% of the patients with a supratentorial AVM (stAVM) and 69.2% of the patients with an infratentorial AVM (itAVM) were presented with a hemorrhage initially (p < .001). Patients with itAVMs were older at presentation (mean 48.1 vs. 37.9 years, p < .001). ItAVMs furthermore were smaller (95.1% <3 cm nidus-diameter, p < .001) and had lower Spetzler-Martin-Grades (p = .04). Associated aneurysms were more frequent in itAVMs (38.5% vs. 20.7%, p < .004) and were associated with an increased risk of hemorrhage at presentation (30.9% vs. 18.7%, p = .013). Outcome was poor in 10.8% of the patients with stAVM and in 28.3% of patients with itAVM (p < .001). The risk of a new hemorrhage-associated deficit was significantly higher in itAVMs (p < .001). Most posterior fossa AVMs are associated with an increased hemorrhage rate. Thus they are a predictor for poor outcome and should be treated even if unruptured to maintain good neurological function.

The metalloprotease-disintegrin ADAM8 contributes to temozolomide chemoresistance and enhanced invasiveness of human glioblastoma cells.

BACKGROUND: Despite multimodal treatment, glioblastoma (GBM) therapy with temozolomide (TMZ) remains inefficient due to chemoresistance. Matrix metalloproteinase (MMP) and a disintegrin and metalloprotease (ADAM), increased in GBM, could contribute to chemoresistance and TMZ-induced recurrence of glioblastoma. METHODS: TMZ inducibility of metalloproteases was determined in GBM cell lines, primary GBM cells, and tissues from GBM and recurrent GBM. TMZ sensitivity and invasiveness of GBM cells were assessed in the presence of the metalloprotease inhibitors batimastat (BB-94) and marimastat (BB-2516). Metalloprotease-dependent effects of TMZ on mitochondria and pAkt/phosphatidylinositol-3 kinase (PI3K) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) pathways were analyzed by fluorescence activated cell sorting, morphometry, and immunoblotting. Invasiveness of GBM cells was determined by Matrigel invasion assays. Potential metalloprotease substrates were identified by proteomics and tested for invasion using blocking antibodies. RESULTS: TMZ induces expression of MMP-1, -9, -14, and ADAM8 in GBM cells and in recurrent GBM tissues. BB-94, but not BB-2516 (ADAM8-sparing) increased TMZ sensitivity of TMZ-resistant and -nonresistant GBM cells with different O(6)-methylguanine-DNA methyltransferase states, suggesting that ADAM8 mediates chemoresistance, which was confirmed by ADAM8 knockdown, ADAM8 overexpression, or pharmacological inhibition of ADAM8. Levels of pAkt and pERK1/2 were increased in GBM cells and correlated with ADAM8 expression, cell survival, and invasiveness. Soluble hepatocyte growth factor (HGF) R/c-met and CD44 were identified as metalloprotease substrates in TMZ-treated GBM cells. Blocking of HGF R/c-met prevented TMZ-induced invasiveness. CONCLUSIONS: ADAM8 causes TMZ resistance in GBM cells by enhancing pAkt/PI3K, pERK1/2, and cleavage of CD44 and HGF R/c-met. Specific ADAM8 inhibition can optimize TMZ chemotherapy of GBM in order to prevent formation of recurrent GBM in patients.