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The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1–10. CGRP levels were determined via competitive enzyme immunoassay and calculated as “area under the curve” (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t1: day 11–35) and at the 6-month follow-up (t2). AUC CGRP (total mean ± SD, 5.7 ± 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 ± 1.77) and pSAH group (5.68 ± 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t1 as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741, p = 0.018), anxiety (OR 7.748, p = 0.021), depression (OR 2.740, p = 0.005), the supplementary items (OR 2.392, p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177, p = 0.001). In contrast, at t2, CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior.

Objective Postoperative spinal epidural hematoma (pSEH) with symptomatic compression of nervous structures after spinal decompression surgery is a rare complication. Delayed evacuation may result in severe neurologic impairment. We present a large single-center analysis of the prevalence, potential risk factors, and functional recovery after pSEH. Methods A retrospective review of our institutional database of spinal decompression surgery over 15 years yielded 6,024 consecutive patients. A total of 42 patients who had undergone surgical revision due to postoperative neurologic deterioration or intractable radiating pain and radiographically confirmed pSEH were allocated to the pSEH group. A matched 3:1 control group was formed (126 patients with the same surgical procedure, same year, same sex, and similar age). Charts, surgical reports, and radiographic data were reviewed for demographics, duration of symptoms, history of medical treatment, medication, comorbidities, radiographic extension, surgical strategy, and pre- and postoperative neurologic performance. Median follow-up was 3 months. Risk factors for pSEH, complete recovery, and recovery of neurologic symptoms were analyzed with univariable and multivariable logistic regression models. Results The prevalence of pSEH in this population was 0.69% (n = 42) with these locations: 7 of 1,284 (0.54%) cervical, 1 of 774 (0.12%) thoracic, and 34 of 3,966 (0.85%) lumbar. Use of anticoagulants (p = 0.003), pathologic coagulation values in the preoperative blood test (p = 0.034), and cigarette smoking (p = 0.003) were identified as independent risk factors of pSEH. Surgery in more than one level showed a trend toward an increased risk of pSEH. Pain as the only symptom (p = 0.0001) was a significant predictor of complete recovery. Patients symptomatic with paraplegia (p = 0.026) had a significantly higher risk of a poor neurologic outcome without full recovery of neurologic symptoms. Conclusion The prevalence of pSEH was lower than previously reported incidences. Use of anticoagulants, pathologic coagulation values, and cigarette smoking were identified as independent risk factors of pSEH. Functional outcome was related to the duration between hematoma evacuation and the clinical presentation of symptomatic pSEH.

Neuropsychological dysfunction after treatment of spontaneous subarachnoid haemorrhage (sSAH) is common but underreported. The vasoconstrictor neuropeptide Y (NPY) is excessively released after sSAH and in psychiatric disorders. We prospectively analysed the treatment-specific differences in the secretion of endogenous cerebrospinal fluid (CSF) NPY during the acute stage after sSAH and its impact on cognitive processing.A total of 26 consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Ventricular CSF was drawn daily from day 1-10. CSF NPY levels were determined with competitive enzyme immunoassay. All patients underwent neuropsychological self-report assessment [36-Item Short Form Health Survey (SF-36) and ICD-10-Symptom-Rating questionnaire (ISR)] after the onset of sSAH (day 11-35; tAt tTo the best of our knowledge, this study is the first to correlate the levels of endogenous NPY in supratentorial CSF with cognitive outcome in good-grade sSAH patients. Excessive NPY release into CSF may have a short-term influence on the pathogenesis of neuropsychological deficits. The impact of cerebrovascular manipulation on NPY release has to be further elucidated.ANOVA: analysis of variance; aSAH: aneurysmal subarachnoid haemorrhage; AUC: area under the curve; CBF: cerebral blood flow; CSF: cerebrospinal fluid; CT (scan): computed tomography (scan); CV: cerebral vasospasm; DIND: delayed ischemic neurological deficit; DSA: digital subtraction angiography; EIA: enzyme immunoassay; EV: endovascular aneurysm occlusion; EVD: external ventricular drainage; FU: 6-month follow-up; GCS: Glasgow Coma Scale; Ghp: general health perceptions; GOS: Glasgow Outcome Scale; h: hour/s; HH: Hunt and Hess; ICU: intensive care unit; ISR: ICD-10-Symptom-Rating questionnaire; MCS: mental component summary; Mhi: general mental health; min: minute/s; min-max: minimum - maximum; ml: millilitre; mRS: modified Ranking Scale; MS: microsurgical clipping, microsurgical aneurysm occlusion; ng: nanograms; no. [n]: number; NPY: Neuropeptide Y; p: p value; Pain: bodily pain; PCS: physical component summary; Pfi: physical functioning; pSAH: perimesencephalic subarachnoid haemorrhage; PTSD: posttraumatic stress disorder; QoL: quality of life; Rawhtran: health transition item; Rolem: role limitations because of emotional problems; Rolph: role limitations due to physical health problems; SAH: subarachnoid haemorrhage; SD: standard deviation; SF-36: 36-Item Short Form Health Survey; Social: social functioning; sSAH: spontaneous subarachnoid haemorrhage; TCD: trans-cranial Doppler ultrasound; (test) t

Objectives We report on five patients with gadolinium-negative (non-enhancing magnetic resonance imaging–MRI) but 18F-fluoroethyl tyrosine positron-emission tomography (FET-PET) positive glioma (NEG) undergoing surgery under fluorescence-guidance with fluorescein sodium 10% (FL, Alkon, Germany) in combination with a dedicated light filter (YELLOW 560 nm, Carl Zeiss Meditec, Germany). Patients and method Since 2017, five patients (3 female, 2 male; mean age 45.4 years) underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. We reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area. Results In all patients we found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted. Discussion and conclusion Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery.

Space-occupying spinal metastases (SM), commonly diagnosed because of acute neurological deterioration, consequently lead to immediate decompression with tumor removal or debulking. In this study, we analyzed a series of patients with surgically treated spinal metastases and explicitly sought to determine individual predictors of functional outcome.94 patients (26 women, 68 men; mean age 64.0 years) with spinal metastases, who had been surgically treated at our department, were included retrospectively. We reviewed the pre- and postoperative charts, surgical reports, radiographic data for demographics, duration of symptoms, histopathology, stage of systemic disease, co-morbidities, radiographic extension, surgical strategy, neurological performance (Frankel Grade Classification), and the Karnofsky Performance Index (KPI).Emergency surgery within24 h after discharge had been conducted in 33% of patients. Prostate carcinoma (29.5%) and breast carcinoma (11.6%) were the most common histopathologies. Median KPI was 60% at admission that had significantly improved at discharge (KPI 70%; p = 0.01). The rate of complications without revision was 4.3%, the revision rate 4.2%. From admission to discharge, pain had been significantly reduced (p = 0.019) and motor deficits significantly improved (p = 0.003). KPI had been significantly improved during in-hospital treatment (median 60 vs 70, p = 0.010). In the multivariable analysis, predictors of poor outcome (KPI 70) were male sex, multiple metastases, and pre-existing bowel and bladder dysfunction. Median follow up was 2 months.In our series, surgery for spinal metastases (laminectomy, tumor removal, and mass reduction) significantly reduced pain as well as sensory and motor deficits. We identified male sex, multiple metastases, and pre-existing bowel and bladder dysfunction as predictors of negative outcome.

Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood–brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported. Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18). Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm3 (range, 1.3–87.8 cm3). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%. Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs. Clin Cancer Res; 24(1); 52–61. ©2017 AACR.

Objective Cranioplasty reshapes the neurocranium and viscerocranium after craniectomy. Different materials have been used for cranioplasty. However, no consistent data are yet available comparing these different materials regarding indications, complications, and outcome. We report our experience with preformed titanium implants and freehand molded polymethylmethacrylate (PMMA) implants for cranioplasty. Methods This retrospective single-center analysis included 120 consecutive cranioplasty patients who had been operated between 2006 and 2013. A total of 60 patients (27 women, 33 men; mean age: 54 years) had received a preformed titanium implant and 60 patients (22 women, 38 men; mean age: 46 years) a freehand molded PMMA implant. We evaluated all demographic and procedure-related data, indications, and outcome. The longest follow-up was 5.5 years. Results The most frequent indications for cranioplasty were trauma (n = 48 [40%]), malignant infarction (n = 27 [23%]), tumor (n = 22 [18%]), spontaneous intracerebral or aneurysmal subarachnoid hemorrhage (n = 16 [13%]), revision surgery (n = 5 [4%]), and empyema (n = 2 [2%]). PMMA implants were more often associated with wound-healing disorders (p Conclusion Cranioplasty with preformed titanium implants seems to be superior to freehand molded PMMA implants regarding surgical morbidity, revision rate, and aesthetic results.

Background Surgical treatment of meningiomas next to venous sinuses is difficult because of their irregular growth patterns and infiltration into the venous sinuses, making gross total resection impossible in some patients. We evaluated the postoperative clinical and neurologic course of this tumor subgroup. Methods This study included 141 consecutive patients with meningioma located within 20 mm of a major venous sinus. Complete data sets were available for all patients. We reviewed patient charts and surgical reports for demographics, histology, and clinical and neurologic performance preoperatively and postoperatively and during follow-up. Radiographic images were screened for tumor extension, infiltration into the skull, sinus infiltration (Sindou grade), extent of resection (Simpson grade), and tumor recurrence. Results Immediate postoperative neurologic improvement was found in 53.7% ( n = 36) of patients with preoperative neurologic deficits ( n = 67). Follow-up was up to 13.5 years. Medical Research Council Neurological Performance Scale and Karnofsky performance scale postoperatively improved in 24.1% and 55.3% of patients, respectively. Local tumor recurrence was detected in 10.6% (n = 15) of patients. Higher World Health Organization grade ( P = 0.03), tumor size ( P = 0.001), and bone invasion ( P = 0.002) were predictors of local tumor recurrence. The median MIB-1 labeling index in patients with tumor recurrence was twice as high as in patients without recurrence. Conclusions Surgical removal of meningiomas adjacent to venous sinuses reduces neurologic impairment and enables local tumor control in most patients. Tumor size, bone infiltration, and higher World Health Organization grade are important predictors of tumor recurrence.

Objectives White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinson’s disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. Patients and methods 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia. All patients underwent comprehensive neuropsychological assessment and MRI before surgery. The extent of WML was assessed using an automated approach. WML volume was correlated to the onset of dementia and the decline of a cognitive composite score retrospectively. Results Patients with a rapid onset of dementia within one, respective three following DBS showed significant higher WML volumes compared to cognitive normal and MCI patients (55.8 cm3 ± 18.836 vs. 9.3 cm3 ± 12.2; p = 0.002). The same significant association was found in a multivariable model, including the covariables age, gender and PD disease duration (p = 0.01). WML volume was associated to the rate of decline in cognitive composite score within three years after DBS surgery (p = 0.006; R2 = 0.40) after correction for age. Conclusions Damaged white matter may lead to a reduced compensation of disconnections in cognitive circuits caused by the implantation of the DBS electrodes or by chronic stimulation. The role of WML as a prognostic factor for the cognitive outcome after DBS may be underestimated. The WML burden should be taken seriously in preoperative risk stratification.

Objectives Fluorescein Sodium (FL) enhances areas in the brain with a disrupted blood brain barrier (BBB). Solitary brain abscesses (BA) are characterized by the pathognomonic finding of BBB disruption. Consequently, FL may have the potential to improve the intra-operative visualization of BA. Here, we report a series of patients with BA that where treated surgically after application of FL in combination with a dedicated light filter integrated in the surgical microscope. Methods 7 patients (4 female, 3 male; mean age 53.8 years) with BA were included, all of them gave written informed consent. 5 mg/kg bodyweight of FL was administered via the central venous line at induction of anesthesia, approximately 30–45 min prior to surgery. We screened the surgical reports for any statement concerning the intensity of fluorescent staining. Results Fluorescent staining was bright in all patients. Surgical removal of all parts of the BA, aspiration of pus and dissection of the capsule, were performed in the fluorescence-mode under the filtered light. We encountered no adverse events. Conclusion The accumulation of FL resulted in brilliant visualization of the infected area under the YELLOW 560 nm filter. This small clinical study adds to the rapidly emerging clinical experiences of the use of fluorescein in neurosurgery, even for non-neoplastic lesions. However, prospective and randomized clinical trials are still necessary to establish the beneficial use of FL.

Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identification of tumor tissue. In 2012, we started evaluating fluorescein (FL) with the dedicated microscope filter in cerebral metastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients. Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25–85 years); 5 mg/kg bodyweight of FL was intravenously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events. Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL staining. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course. FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

Goal: Cerebral amyloid angiopathy (CAA) is the second-most common cause of nontraumatic intracerebral hemorrhages (ICH), surpassed only by uncontrolled hypertension. We characterized the percentage, risk factors, and comorbidities of patients suffering from CAA-related ICH in relation to long-term outcomes. Material and Methods: We performed retrospective analyses and clinical follow-ups of individuals suffering from ICH who were directly admitted to neurosurgery between 2002 and 2016. Findings: Seventy-four of 174 (42%) spontaneous nontraumatic lobar ICH cases leastwise satisfied the modified Boston criteria definition for at least “possible CAA.” Females suffered a higher risk of CAA-caused ICH (42 of 74, 56.8%, P= .035). Atrial fibrillation as a major comorbidity was observed in 19 patients (25.7%). Recovery (decrease of modified Rankin scale [mRS]) was highest during hospitalization in the acute clinic. One-year mortality was as follows: 14 of 25 patients (56%) with probable CAA without supporting pathology, 6 of 18, and 8 of 31 patients with supporting pathology and possible CAA, respectively. Only 10 of 74 (13.6%) had favorable long-term outcomes (mRS ≤2). Increasing numbers of lobar hemorrhages, low initial Glasgow Coma Scale, and subarachnoid hemorrhage were significantly associated with poor survivability, whereas statins, antithrombotic agents, an intraventricular hemorrhage, and midline shift played seemingly minor roles. Conclusions: Symptomatic ICH is a serious stage in CAA progression with high mortality. The high incidence of concurrent atrial fibrillation in these patients may support data on more widespread vascular pathology in CAA.

Background Few studies have addressed the effect of treatment of unruptured intracranial aneurysm (UIA) on cognitive function. Objective Neuropsychological assessment after UIA treatment is underreported, and prospective trials have repeatedly been demanded. In 2014, we conducted a prospective controlled study to evaluate the differences in cognitive processing caused by the treatment of anterior circulation UIAs. Patients and Methods Thirty patients were enrolled until September 2015. Ten patients received endovascular aneurysm occlusion (EV), 10 patients were treated microsurgically (MS), and 10 patients with surgically treated degenerative lumbar spine disease (LD) served as control. All patients underwent extended standardized neuropsychological assessment before (t 1 ) and 6 weeks after treatment (t 2 ). Tests included verbal, visual, and visuospatial memory, psychomotor functioning, executive functioning, and its subdomains verbal fluency and cognitive flexibility. We statistically evaluated intragroup and intergroup changes. Results Intragroup comparisons and group-rate analysis showed no significant impairment in overall neuropsychological performance, either postinterventionally or postoperatively. However, the postoperative performance in cognitive processing speed, cognitive flexibility, and executive functioning was significantly worse in the MS group than in the EV ( P = 0.038) and LD group ( P = 0.02). Compared with the EV group, patients with MS showed significant postoperative impairment in a subtest for auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. EV P = 0.011). The MS group trended toward posttreatment impairment in subtests for verbal fluency and semantic memory (Regensburg Word Fluency Test; MS vs. EV P = 0.083) and in auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. LD P = 0.06). Conclusions Our preliminary data showed no effect of anterior circulation UIA treatment on overall neuropsychological function but impaired short-term executive processing in surgically treated patients.

Medical complications severely impair recovery of neurosurgical patients after craniotomy. The purpose of this study was to identify patients at risk of peri- and postoperative medical complications. Therefore, we present a large population of patients with different medical complications after elective craniotomy.We retrospectively screened all patients who had been consecutively treated at our department between June 2009 and June 2014. Patients with any postoperative thromboembolic complication or pulmonary or systemic infection were compared with a control group without any medical complication. Peri- and postoperative complications were statistically analyzed with regard to their association with age, sex, comorbidity, indication for craniotomy, duration of surgery, surgical position, type of anesthesia, and previous craniotomy by means of logistic regression models.Of 1800 patients screened, 133 patients (67 women and 66 men aged between 14 and 85 years) had developed medical complications (overall morbidity, 7.4%). We found statistically significant correlations between thromboembolic events and meningioma, previous craniotomy, duration of surgery, and hypertension (P = 0.002, P = 0.032, P0.001, and P0.001, respectively). Severe infection was associated with age, duration of surgery, and craniopharyngioma and pituitary adenoma (P = 0.012, P = 0.004, and P = 0.029, respectively). Prolonged stay in the intensive care unit was associated with increased duration of surgery and hypertension (P = 0.002 and P0.001).In this study, we identified predictors that help characterize patients at risk of medical complications after elective neurosurgical procedures. These correlations should be taken into account when advising patients on craniotomy.

Spinal synovial cysts (SSC) are a rare but important differential diagnosis for degenerative or space-occupying spinal lesions. There is controversy about the most beneficial treatment, which can be conservative or surgical. We provide a review of our surgical data for purposes of quality assessment and improvement. 5313 patients with surgically treated degenerative spinal diseases were analyzed retrospectively. The incidence of SSC was 1.14%. 61 patients (31 women, 30 men; mean age 65.3 years) with SSC were included in this study. The charts, surgical reports, and radiographic data were reviewed for demographics, duration of symptoms, size of SSC, anatomical site, surgical approach, Visual Analog Scale (VAS), and neurological performance including the Japanese Orthopedic Association Score (JOA score) and the Frankel score. Laminotomy was the most common surgical approach in 93.4% of the patients followed by hemilaminectomy in 6.6%. The predominant site of SSC was the lumbar spine in 86.9%. 95.1% had experienced local and radicular pain as the predominant symptom and 47.5% preoperative sensory and motor deficits. At discharge, the JOA score was significantly increased compared to admission (median value of 17). At follow-up, 94.4% had normal neurological function and 5.6% showed grade 1 neurological deficits. Leg pain had decreased in 94.4% and back pain in 70.6%. At long-term follow-up, all patients presented neurologically stable. The median value for pain classified with the VAS had decreased from 6 at admission to 1 at long-term follow-up. During long-term follow-up, 6 patients (9.8%) had developed spinal instability requiring stabilization, 5 patients had received facet joint infiltration due to symptomatic facet joint syndrome. The epidemiological and clinical patterns of symptomatic SSC are similar to those of other degenerative spinal diseases. Thus, SSC should always be considered as a rare but important differential diagnosis. Surgical outcome was excellent with immediate symptom relief and recovery, which further improved over time. Our data support the benefit of surgical treatment and may be useful in recommending neurosurgical therapy to patients with SSC.

Objective Subthalamic deep brain stimulation may alleviate bradykinesia in Parkinson patients. Research suggests that this stimulation effect may be mediated by brain networks like the corticocerebellar loop. This study investigated the connectivity between stimulation sites and cortical and subcortical structures to identify connections for effective stimulation. Methods We retrospectively investigated 21 patients with Parkinson disease with bilateral subthalamic deep brain stimulation. Stimulation effectiveness in reducing bradykinesia, tremor, and rigidity was evaluated for each electrode contact in brain hemispheres contralateral to the affected hemibody. Dysarthric side effects were also examined. Probabilistic tractography based on diffusion-weighted imaging was performed in individual patient-specific brains using electrode contacts as seeds. Connectivity profiles of contacts with effective and noneffective stimulation were compared. Results Connectivity profiles of effective and noneffective contacts differed. Moreover, the connectivity profile for bradykinesia differed from that for rigidity, tremor, or dysarthria. Regarding bradykinesia, effective contacts were significantly more often connected with the ipsilateral superior cerebellar peduncle and the ipsilateral dentate nucleus, which correspond to the ipsilateral portion of the cerebellothalamocortical pathway. Rigidity was mitigated by stimulation of ascending brainstem and intralaminar thalamic connections. Tremor alleviation was related to connections with the internal capsule (anterior limb) and the pallidum. Dysarthric side effects were associated with connections to the supplementary motor area and the decussating cerebellothalamocortical pathway. Interpretation Whereas bradykinesia seems to be mitigated by stimulation of the ascending, ipsilateral cerebellothalamocortical pathway, stimulation of the descending corticopontocerebellar pathway may be ineffective. Rigidity, tremor, and dysarthric side effects seem to be influenced by different neural networks. ANN NEUROL 2019;85:852-864.

Aim: Recently, D,L-methadone has been put forward as adjuvant treatment in glioblastoma (GBM). Methods: We analyzed the μ-opioid receptor expression in a set of GBM cell lines and investigated the efficacy of D,L-methadone alone and in combination with temozolomide (TMZ). Results & conclusion: Expression of the μ-opioid receptor was similar in the tested cell lines. High concentrations of D,L-methadone induced apoptosis in all cell lines and showed treatment interaction with TMZ. However, in lower dosages, reflecting clinically attainable concentrations, D,L-methadone alone showed no efficacy, and induced even higher proliferation in one specific cell line. Also, no interaction with TMZ was observed. These results suggest caution to the premature use of D,L-methadone in the treatment of GBM patients.

Background Perioperative seizure prophylaxis with antiepileptic drugs (AED) has been advocated in patients undergoing supratentorial craniotomy. The practice remains controversial. The reasoning presupposes that the possibility of an adverse drug reaction from the AED is lower than the probability of harm from a seizure. Even short periods of hypotension during the operation can lead to acute kidney and myocardial injury. We retrospectively evaluated cardiovascular effects and tolerability of levetiracetam (LEV) alone, LEV and lacosamid (LCM) as compared to phenytoin (PHT). Methods After IRB approval, the charts of individuals who underwent craniotomy from April 2007 to September 2011 were reviewed. Those receiving PHT were compared to those receiving LEV alone and LEV/LCM. The patient data included demographic, indication and procedure related data. The cumulative dose of norepinephrine (NET), atropine (ATR) and the change in systolic blood pressure during and after the administration of the AED were analyzed. Results Five hundred thirty-eight patients were screened of which 122 were included for analysis. 40 patients with primary or secondary supratentorial brain tumors received LEV (19 female, 21 male; mean age 56 years), 41 patients received LEV/ LCM (16 female, 25 male; mean age 56 years) and 41 patients received PHT (15 female, 26 male; mean age 50 years). The commonest indications for craniotomy were glioblastoma (N.=14 vs. N.=12 vs. N.=15), meningiomas (N.=9 vs. N.=7 vs. N.=10), low-grade gliomas (N.=6 vs. N.=13 vs. N.=6) and brain metastases (N.=5 vs. N.=4 vs. N.=5). 1 LEV/LCM patient (2%) and 4 PHT patients (4.5%) had a seizure despite prophylaxis. Possible side effects were observed in 2 patients associated with PHT. During anesthesia there was a significant drop in systolic blood pressure in the PHT group after administration of the AED perioperatively when compared to LEV (P=0.001) and LEV/LCM (P≤0.0001) respectively. The mean cumulative doses of NET and ATR over the course of the operation did not differ significantly. Conclusions LEV alone and in combination with LCM for patients without and with symptomatic epilepsy as seizure prophylaxis provides a safe and feasible alternative to PHT. PHT was associated with an unfavorable drop in blood pressure during anesthesia and more adverse reactions.

Limited focus has been placed on neuropsychological patient profiles after spontaneous subarachnoid hemorrhage (sSAH). We conducted a prospective controlled study in good-grade sSAH patients to evaluate the time course of treatment-specific differences in cognitive processing after sSAH.Twenty-six consecutive sSAH patients were enrolled (drop out n=5). Nine patients received endovascular aneurysm occlusion (EV), 6 patients were treated microsurgically (MS), and 6 patients with perimesencephalic SAH (pSAH) underwent standardized intensive medical care. No patient experienced serious vasospasm-related ischemic or hemorrhagic complications. All patients were subjected to neuropsychological self-report assessment (36-Item Short Form Health Survey and ICD-10-Symptom-Rating questionnaire) subacutely (day 11 - 35) after the onset of bleeding (t1) and at the 6-month follow-up (FU; tsub2/sub).From t1 to tsub2/sub, MS and EV patients significantly improved in physical functioning (Pfi; p=.001 each) and the physical component summary (p=.010 vs. p=.015). Bodily pain (Pain; MS p=.034) and general health perceptions (EV p=.014) significantly improved, and nutrition disorder (EV p=.008) worsened. At FU, MS patients reported significantly better Pfi (vs. EV p=.046), less Pain (vs. EV p=.040), and more depression (vs. pSAH p=.035). Group-rate analyses of test differences showed a significant alleviation in nutrition disorder in MS (vs. EV p=.009).All sSAH groups reported a significant deterioration in health. Though both MS and EV patients, improved in several physical items over time, our data suggest a better short-term Pfi, less Pain and improved nutrition disorder in surgically treated patients. pSAH patients performed significantly better in various aspects of physical and psychological functioning than patients with aneurysmal SAH.

Severe cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone.Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6 months after the hemorrhage and compared to a historical control group.Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6 %) in the nimodipine group than in the control group (75.0 %). This result was reflected by a significantly higher proportion (76.0 %) of patients with good outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (p = 0.001).Continuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.

Surgical resection is a key element of the multidisciplinary treatment of cerebral metastases (CMs). Recent studies have highlighted the importance of complete resection of CMs for improving recurrence-free and overall survival rates. This study presents the first data on the use of fluorescein sodium (FL) under the dedicated surgical microscope filter YELLOW 560 nm (Zeiss Meditec, Germany) in patients with CM. Thirty patients with CMs of different primary cancers were included (15 females, 15 males; mean age 61.1 years); 200 mg of FL was intravenously injected directly before CM resection. A YELLOW 560 nm filter was used for microsurgical tumor resection and resection control. Surgical reports were evaluated regarding the degree of fluorescent staining, postoperative MRIs regarding the extent of resection [gadolinium (Gd)-enhanced T1-weighted sequence] and the postoperative courses regarding any adverse effects. Most patients (90.0 %, n = 27) showed bright fluorescent staining, which markedly enhanced tumor visibility. Three patients (10.0 %) (two with adenocarcinoma of the lung and one with melanoma of the skin) showed no or only insufficient FL staining. Another three patients (10.0 %) showed residual tumor tissue in the postoperative MRI examination. In two other patients, radiographic examination could not exclude the possibility of very small areas of residual tumor tissue. Thus, gross-total resection was achieved in 83.3 % (n = 25) of patients. No adverse effects were registered over the postoperative course. FL and the YELLOW 560 nm filter are safe and practical tools for the resection of CM, but further prospective research is needed to confirm that this advanced technique will improve the quality of CM resection.

Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) was reported to reduce symptoms in psychiatric disorders. The aim of our study was to find standardised parameters for diffusion tensor imaging (DTI) based fibre tracking to reliably visualise the MFB.Twenty-two cerebral hemispheres in 11 patients were investigated. Three different regions of interest (ROIs) were defined as seed regions for fibre tracking: the ipsilateral and contralateral superior cerebellar peduncle (SCP) and the nucleus raphe dorsalis (NRD). From each seed region the fibres were followed separately through the ventral tegmental area (VTA = second ROI) and their further courses and volumina were documented and compared. Minimal fibre length was set at 30 mm and the FA threshold at 0.12.The fibre tracts starting in seed regions in the ipsilateral SCP and the NRD follow a similar course along the lateral wall of the third ventricle (hypothalamus) and the anterior limb of the internal capsule (ALIC) to inferior fronto-medial brain areas. These fibres are in accordance with the course of the MFB as described in various anatomical atlases. Consistently, a branch leaves the main fibre tract laterally to take a course through the capsula externa to the temporo-parietal cortex. Fibre tracts starting from the contralateral SCP follow a more superior and lateral course, including the dentato-rubro-thalamic and the pyramidal tract.Deterministic fibre tracking with standardised ROIs provides constant and reproducible delineations of the medial forebrain bundle. Its visualisation might help to adjust targeting in DBS for psychiatric disorders.

Purpose: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, anti-inflammatory, neurotrophic and neurogenic properties. The effect of PEDF on traumatic brain injury (TBI) has not been explored. In this study, we aimed to show the in vivo effects of PEDF on lesion volume, cell death and cell proliferation after TBI. Methods: Rats were subjected to controlled cortical impact injury (CCII). PEDF mRNA brain levels were measured by RT-PCR. The lesion volume, cell proliferation, cell death and microglia activation were assessed in the brains of lesioned animals with intraventricular alzet infusion of PEDF or aCSF, and intraperitoneal injections of BrdU. Results: We detected a significant increase of PEDF mRNA levels after TBI. PEDF intraventricular infusion showed no significant effect on the contusion volume, whereas the number of dead cells, activated microglia, BrdU-positive cells around the lesion were significantly decreased. In contrast, PEDF application increased cell proliferation in the ipsilateral subventricular zone. No effect was found on cell proliferation in the dentate gyrus. Conclusion: The present work indicates that PEDF acts as a multifunctional agent after TBI influencing cell death, inflammation and cell proliferation.

Deep brain stimulation for Parkinson's disease has become an established treatment option in recent years. The method and its application in clinical practice has proved to be safe and effective. Nevertheless, procedure-related and hardware-related complications occur. We present a rare case of a patient with an allergic reaction to the impulse generator. The patient suffered from delayed wound-healing deficits with several wound revisions and generator repositionings. After diagnosis of an allergic reaction to components of the generator, a custom-made silicon-coated model was implanted. Hereafter, no wound healing-deficit occurred throughout long-term follow-up. Allergic reaction to hardware components may lead to wound-healing deficits. In such cases, custom-made silicon-coated models may be an effective treatment option.

Intraoperative test stimulation is established to optimize target localization in STN DBS, but requires a time-consuming awake surgery in off-medication state. The aim of this study was to compare the thresholds of stimulation-induced effects of test stimulation and the permanent electrode. Fifty-nine PD patients receiving bilateral STN DBS were clinically examined with stepwise increasing monopolar stimulation during surgery and DBS programming at matched stimulation depths. Thresholds of therapeutic and side effects were obtained from standardized examination protocols. Postoperative stimulation via the permanent electrode caused side effects at a significantly lower threshold than predicted during intraoperative test stimulation (P

Background Some patients under thalamic deep brain stimulation (DBS) for essential tremor (ET) experience habituation of tremor reduction. The nucleus ventralis intermedius (Vim) is the current main target side for ET in DBS. However, the dentatorubrothalamic tract (DRTT) is considered the relevant structure to stimulate. We investigated the distance between the active contact of the DBS electrode and the DRTT and compared this distance in patients with habituation of tremor reduction and good responders. Material and Methods In this retrospective study, we performed deterministic fiber tracking of the DRTT in 6 patients (12 hemispheres) with ET who underwent DBS in the Vim. We subsequently measured the distance between the active contact of the electrode and the ipsilateral DRTT in both hemispheres. The clinical tremor response of those 6 patients was analyzed accordingly. Results The distance between the active contact and the DRTT in patients with better and constant clinical tremor reduction was shorter (mean distance: 2.9 ± 2.2 mm standard deviation [SD]) than in patients who showed habituation of their response (mean distance: 6.1 ± 3.9 mm SD). After re-placement of a thalamic electrode inside the DRTT in one patient who experienced unsatisfying tremor reduction due to habituation of stimulation, the tremor alleviation was significant and persistent at a 13-month follow-up. Conclusion This retrospective analysis suggests that recurrence of ET tremor under chronic DBS might be associated with a larger distance between the DRTT and the active lead contact, in comparison with the smaller distances in patients with persistently good tremor control.

In the human brain, the potent vasoconstrictive neuropeptide Y (NPY) is abundantly expressed. Neuropeptide Y, which is stored in perivascular nerve fibers of the cerebral arteries, regulates the cerebral vascular diameter as well as cerebral blood flow. However, the role of NPY in the pathogenesis of cerebral vasospasm (CV) related to subarachnoid hemorrhage (SAH) is unclear. We prospectively analyzed and compared the release of endogenous NPY in the cerebrospinal fluid (CSF) of 66 patients with SAH to NPY release in a control group. Additionally, we correlated the levels of NPY with CV and consecutive ischemic stroke.Sixty-six consecutive patients (40 women, 26 men; mean age 53·1 years) with aneurysmal SAH were included. In the SAH group, CSF was drawn daily from day 1 to day 10 after the onset of SAH. The CSF of 29 patients undergoing spinal anesthesia for orthopedic surgery served as control samples. The NPY levels were determined in duplicate CSF samples by means of a competitive enzyme immunoassay (EIA). The levels of NPY in CSF were correlated with the development of CV over the 10-day period after the onset of SAH and to the occurrence of consecutive ischemic stroke. To evaluate CSF NPY levels as a predictive biomarker for vasospasm, we calculated the sensitivity and specificity as well as the positive and negative predictive values.The NPY levels were significantly higher in the SAH group than in the control group (p0·001). The treatment modality (clip versus coil) did not influence the level of NPY in CSF (p0·05). Patients with CV showed significantly higher NPY levels than patients without CV during the entire observation period. The NPY levels of the non-CV group dissipated over time, whereas the CV group showed continuously increasing values. The NPY levels from day 4 to 10 were significantly higher in patients with CV-related stroke than in non-stroke patients. Using 0·3 ng/ml as a cut-off value, NPY levels on day 3 predicted the occurrence of CV with a sensitivity and specificity of 82% and 72%, respectively. High NPY levels, starting on day 4, significantly correlated with poor Glasgow Outcome Score grading at the follow-up (p0·05).Our data indicate that NPY is involved in the pathogenesis of SAH-related CV and ischemia. Neuropeptide Y represents an early and reliable biomarker for the prediction of CV and consecutive stroke due to aneurysmal SAH.

Background: Neuropeptide Y (NPY) is one of the most potent endogenous vasoconstrictors, and its contribution to the multifactorial cascade of cerebral vasospasm due to nontraumatic subarachnoid hemorrhage (SAH) is not yet fully understood. This experimental study compared the hemorrhage-specific course of NPY secretion into cerebrospinal fluid (CSF) and into plasma between 2 groups: patients with SAH and patients with basal ganglia hemorrhage (BGH) or cerebellar hemorrhage (CH) over the first 10 days after hemorrhage. Materials and Methods: Seventy-nine patients were prospectively included: SAH patients (n = 66) (historic population) and intracerebral hemorrhage patients (n = 13). All patients received an external ventricular drain within 24 hours of the onset of bleeding. CSF and plasma were drawn daily from day 1 to day 10. The levels of NPY were determined by means of competitive enzyme immunoassay. The CSF samples of 29 patients (historic population) who had undergone spinal anesthesia due to orthopedic surgery served as the control group. Results: NPY levels in CSF were significantly higher in the 2 hemorrhage groups than in the control group. However, the 2 hemorrhage groups showed significant differences in NPY levels in CSF (SAH mean, 0.842 ng/mL vs. BGH/CH mean, 0.250 ng/mL; P < 0.001) as well as in the course of NPY secretion into CSF over the 10-day period. NPY levels in plasma did not differ significantly among SAH, BGH/CH, and controls. Conclusions: Our findings support the hypothesis that excessive release of NPY into CSF but not into plasma is specific to aneurysmal SAH in the acute period of 10 days after hemorrhage. In BGH/CH, CSF levels of NPY were also increased, but the range was much lower.

Although chronic subdural hematoma (CSH) can be treated by surgery, little is known about age-dependent symptoms and age-adjusted rates of restoring functional integrity. To evaluate the clinical symptoms and the course of CSH in patients of different age groups (AGs), we reviewed patients with CSH treated at our department over the past 22 years.This retrospective analysis included 697 patients with CSH (461 men, 236 women; mean age 70.1 years). Subgroup analysis was done according to AG 1)65 years, 2) 66-75 years, 3) 76-85 years, 4) 86-95 years, and 5)95 years.Most patients had been treated with burr-hole trephination and implantation of a subdural drain (96.5%; n = 673). No significant difference concerning surgical morbidity and mortality was found between the AGs, but patients75 years more frequently required reoperation (P = 0.001). Preoperatively, the most common symptoms were headache in AGs 1 and 2 (56.3% and 48.5%) and mnestic deficits in AGs 3-5 (54.9%, 51.9%, and 50.0%). After surgery, the clinical symptoms of CSH had significantly abated in all age groups. The most common clinical residuals were motor deficits in AG 1 (10.4%), mnestic deficits in AG 2 (10.7%), AG 4 (24.1%), and AG 5 (50.0%), and organic brain syndrome in AG 3 (15.0%).CSH predominantly caused unspecific symptoms such as headache and cognitive decline. CSH surgery immediately relieved symptoms in patients of all AGs. However, improvement rates significantly depended on patient age. This should be taken into consideration when advising on surgical treatment of CSH.

Carbonic anhydrase (CA) IX is over-expressed in glioblastoma; however, its functions in this context are unknown. Metabolically, glioblastomas are highly glycolytic, leading to a significant lactic acid load. Paradoxically, the intracellular pH is alkaline. We hypothesized that CAIX contributes to the extrusion of hydrogen ions into the extracellular space, thereby moderating intra- and extracellular pH and creating an environment conductive to enhanced invasion. We investigated the role of CAIX as a prognostic marker in patients with glioblastoma and its biological function in vitro. CAIX expression was analyzed in 59 patients with glioblastoma by immunohistochemistry. The expression levels were correlated to overall survival. In vitro, U251 and Ln 18 glioblastoma cells were incubated under hypoxia to induce CAIX expression, and RNA interference (RNAi) was used to examine the function of CAIX on cell attachment, invasion, intracellular energy transfer, and susceptibility to adjuvant treatment. High CAIX expression was identified as an independent factor for poor survival in patients with glioblastoma. In vitro, cell attachment and invasion were strongly reduced after knockdown of CAIX. Finally, the effects of radiation and chemotherapy were strongly augmented after CAIX interference and were accompanied by a higher rate of apoptotic cell death. CAIX is an independent prognostic factor for poor outcome in patients with glioblastoma. Cell attachment, invasion, and survival during adjuvant treatment are significantly influenced by high CAIX expression. These results indicate that inhibition of CAIX is a potential metabolic target for the treatment of patients with glioblastoma.

The aim of our study was to evaluate discrepancies between the electrophysiologically and MRI-defined subthalamic nucleus (STN) in order to contribute to the ongoing debate of whether or not microelectrode recording (MER) provides additional information to image-guided targeting in deep brain stimulation.Forty-four STNs in 22 patients with Parkinson's disease were investigated. The three-dimensional MRI-defined STN was derived from segmentations of axial and coronal T2-weighted images. The electrophysiological STNs were generated from intraoperative MERs in 1,487 locations. The stereotactical coordinates of positive and negative STN recordings were re-imported to the planning software, where a three-dimensional reconstruction of the electrophysiological STN was performed and fused to the MRI data set. The estimated borders of the MRI- and MER-STN were compared. For statistical analysis Student's t, Mann-Whitney rank sum and Fisher's exact tests were used.MER-STN volumes, which were found outside the MRI-STN, ranged from 0 mm(3) to 87 mm(3) (mean: 45 mm(3)). A mean of 44% of the MER-STN volumes exceeded the MRI-STN (maximum: 85.1%; minimum: 15.1 %); 53.4% (n = 793) of the microelectrode recordings were concordant and 46.6% (n = 694) discordant with the MRI-defined anatomical STN. Regarding the dorsal borders, we found discrepancies between the MER- and MRI-STN of 0.27 mm (= mean; SD: 0.51 mm) on the first operated side and 1.51 mm (SD: 1.5 mm) on the second (p = 0.010, t-test).MER provides additional information to high-resolution anatomical MR images and may help to detect the amount and direction of brain shift.

Objective Dizziness, a common postoperative symptom in patients with vestibular schwannomas (VSs) has a negative effect on the course of recovery, particularly in patients with severe symptoms. Reports on incidence and possible risk factors contributing to these symptoms are inconsistent and sometimes even contradictory. In order to establish a profile of patients at risk of severe symptoms in the immediate postoperative phase we retrospectively analyzed data of patients with unilateral VSs focusing on the incidence of severe dizziness and nausea during the immediate postoperative period and up to 1 year after surgery. Methods In a retrospective study data of 104 consecutive patients with VSs were analyzed. All patients underwent microsurgical tumor resection via a lateral-suboccipital approach. Factors that were assumed to affect the development of severe dizziness, such as age, gender, tumor size, tumor side, and cranial nerve function, were analyzed by means of univariate and multivariate logistic regression analyses. A three step grading system was used to describe symptoms of patients included in this study: 0 = no symptoms of dizziness, 1 = slight dizziness including light-headedness or feeling of disequilibrium and 2 = severe dizziness with nausea including imbalance or insecurity when walking, requiring antiemetic treatment. Results Data of 92 patients, 41 men and 51 women, were available for analyses. Mean age of treated patients was 53 years (range 17–81). There was no predilection of side (52.2% right/47.8% left). Before surgery 39 patients (42.4%) were symptom free (grade 0), 13 patients (14.1%) had slight symptoms (grade 1) and 40 patients (43.5%) suffered from severe symptoms (grade 2). Immediately after surgery two patients (2.2%) where symptom free (grade 0), 19 patients (20.7%) had slight symptoms (grade 1) and 71 patients (77.2%) suffered from severe symptoms (grade 2). All patients with grade 2 symptoms required antiemetic treatment ranging between 1 and 10 days (mean 4 days). Logistic regression analyses showed young age, large tumor size (T3/T4), female gender, and severe preoperative symptoms to be main factors increasing the odds for patients to develop severe symptoms postoperatively. Conclusion Patients at risk to develop severe symptoms should receive antiemetic treatment even before surgery. If in doubt about the actual risk for a specific patient with a large tumor (T3 or T4) available data suggests that patients will benefit if antiemetic treatment is started early, even before surgery.

The best treatment for solitary brain metastases from lung cancer is surgical resection followed by adjuvant treatment. However, about 50% of these patients develop recurrent brain metastases. There is no established treatment standard for this patient group. We therefore analyzed the survival, neurological function, and overall performance status of patients with recurrent solitary brain metastases from lung cancer after second microsurgical resection. Treatment outcome was analyzed in 25 patients (19 men, 6 women) with a mean age of 55.8 years (range, 38–78 years) who received a resection of recurrent solitary brain metastases. Eighty-four percent of all patients had non-small-cell lung cancer and 16% small cell lung cancer (SCLC). Eighty percent of the lesions were located supratentorially, 20% infratentorially. The median overall survival after initial diagnosis was 26.9 months, 13.6 months after the first and 8.3 months after the second brain surgery, respectively. The median Karnofsky index improved significantly from 80 to 100 after the second brain surgery; 66.6% of all patients presenting with neurological impairment improved, and 50% regained normal function. No surgery-related morbidity or mortality was noted. Multivariate analysis indicated that the interval until first brain metastasis and between first and recurrent metastases was significantly predictive of survival. The majority of patients in our study group showed significant functional benefit from surgical resection of recurrent brain metastases. This contributes to a better quality of life in this patient group showing a short overall survival time.

Background An elevated body mass index (BMI) is suggested to be a risk factor for a poor outcome after intracranial aneurysm rupture and is considered to be associated with cerebral infarction in patients with aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to analyze the association between permorbid BMI and neurological outcome. Methods In this retrospective study, the patients' BMI at the time of their admission to hospital was correlated to their neurological outcome as measured by the Glasgow outcome score after two weeks and two months of treatment. Results In contrast to other studies, there were no significant correlations between premorbid BMI and neurological outcome, shunt requirement, tracheotomy requirement and duration of stay on the intensive care unit (ICU). Conclusions Overweight patients have no higher risk of a poor neurological outcome after aneurysmal SAH if premorbid risk factors such as hypertension and hyperglycemia are carefully modified throughout the period of critical care.

Background Despite a broad clinical use, the mechanism of action of SCS is poorly understood. Current information suggests that the effects of SCS are mediated by a complex set of interactions at several levels of the nervous system including spinal and supraspinal mechanisms. Aims The study was undertaken to investigate the influence of SCS on distinct parameters of cortical excitability using single- and paired-pulse transcranial magnetic stimulation (TMS). Methods Five patients with chronic neuropathic pain were examined with the SCS stimulator on and off by means of TMS. Pain was assessed using a visual-analogue scale. Electrophysiological and pain parameters of patients during this procedure were compared by means of a linear mixed effect model. Results SCS induced a significant modulation of cortical excitability, especially by influencing the parameter “intracortical facilitation” ( t = −2.657; df = 8; p = 0.029). A significant relationship between this parameter and “perceived pain” could be obtained ( t = −4.798; df = 8; p = 0.002). Conclusions These results suggest that SCS is able to influence neurobiological processes at the supraspinal level and that clinical effects of SCS may be at least in part of cortical origin.

Objectives Growth and progress of primary central nervous lymphoma (PCNSL) severely disrupt the blood brain barrier (BBB). Such disruptions can be intraoperatively visualized by injecting fluorescein sodium (FL) and applying a YELLOW 560 nm surgical microscope filter. Here, we report a small cohort of patients with PCNSL that mimicked high grade gliomas (HGG) or cerebral metastases (CM), who had been operated on with the use of FL. Patients and methods Retrospectively, seven patients with PCNSL were identified, who had been operated on by means of microsurgery after intravenous FL injection. The surgical reports were screened for statements on the grade of fluorescent staining in the tumor area. One representative case was chosen to show the staining under white light as well as under filtered light at different distances to the tumor area. Results All patients had shown bright and homogenous fluorescent staining of the tumor (n = 7. 100%). No adverse effects had been observed. Conclusion Similar to patients with HGG or CM, patients with PCNSL may benefit from use of FL and the dedicated YELLOW 560 nm filter in open surgery.

Intramedullary tumors account for 2-4% of all CNS neoplasms. Surgical resection is challenging because of aggravated neurological impairment in up to 64% of patients. We analyzed a consecutive series of patients with intramedullary tumors and focused on the extent of resection, functional outcome, and tumor recurrence.53 patients (23 women and 30 men; mean age 46.3 years) were included who had undergone microsurgical resection for intramedullary spinal tumors. We reviewed the patient records for tumor size, edema, intratumoral hemorrhage, consistency, midline detection, resection method, extent of resection, histopathology, and recurrence. Outcome was measured by the Karnofsky Score (KPI), the McCormick score (MCS), and the Medical Research Council Neurological Performance Score (MRC-NPS).The most frequent diagnosis was ependymoma (37.7%), lymphoma (13.2%) and astrocytoma (11.3%). The majority of tumors were located in the thoracic spine (62.2%). Gross total resection was achieved in 73.6% and most successful in patients with ependymal histology (p0.01). Tumor recurrence - observed in 11.3% - was significantly associated with age65 years, astrocytic histology, higher tumor grades, and higher Ki-67 labeling. At follow-up, MCS and MRC-NPS showed significantly better results than prior to resection (p0.001), and pain and sensory deficits had improved in 67.9% and 64.2% of patients, respectively. Microsurgical resection improved the neurological status significantly. Pain and sensory deficits showed higher improvement rates than paresis and vegetative dysfunction.Our data help identify patients at risk of tumor recurrence and classify the course of postoperative neurological performance.

Although multimodal monitoring sets the standard in daily practice of neurocritical care, problem-oriented analysis tools to interpret the huge amount of data are lacking. Recently a mathematical model was presented that simulates the cerebral perfusion and oxygen supply in case of a severe head trauma, predicting the appearance of distinct correlations between arterial blood pressure and intracranial pressure. In this study we present a set of mathematical tools that reliably detect the predicted correlations in data recorded at a neurocritical care unit. The time resolved correlations will be identified by a windowing technique combined with Fourier-based coherence calculations. The phasing of the data is detected by means of Hilbert phase difference within the above mentioned windows. A statistical testing method is introduced that allows tuning the parameters of the windowing method in such a way that a predefined accuracy is reached. With this method the data of fifteen patients were examined in which we found the predicted correlation in each patient. Additionally it could be shown that the occurrence of a distinct correlation parameter, called scp, represents a predictive value of high quality for the patients outcome.

In many centers the standard anesthesiological care for deep brain stimulation (DBS) surgery in Parkinson's disease patients is an asleep-awake-asleep procedure. However, sedative drugs and anesthetics can compromise ventilation and hemodynamic stability during the operation and some patients develop a delirious mental state after the initial asleep phase. Further, these drugs interfere with the patient's alertness and cooperativeness, the quality of microelectrode recordings, and the recognition of undesired stimulation effects. In this study, we correlated the incidence of intraoperative delirium with the amount of anesthetics used intraoperatively.The anesthesiologic approach is based on continuous presence and care, avoidance of negative suggestions, use of positive suggestions, and utilization of the patient's own resources. Clinical data from the operations were analyzed retrospectively, the occurrence of intraoperative delirium was extracted from patients' charts. The last 16 patients undergoing the standard conscious sedation procedure (group I) were compared to the first 22 (group II) psychologically-guided patients.The median amount of propofol decreased from 146 mg (group I) to 0mg (group II), remifentanyl from 0.70 mg to 0.00 mg, respectively (P0.001 for propofol and remifentanyl). Using the new procedure, 12 of 22 patients (55%) in group II required no anesthetics. Intraoperative delirium was significantly less frequent in group II (P=0.03).The occurrence of intraoperative delirium correlates with the amount of intraoperative sedative and anesthetic drugs. Sedation and powerful analgesia are not prerequisites for patients' comfort during awake-DBS-surgery.

The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p

Approximately 5% of patients with malignant glioma achieve complete response (CR) after first-line combined modality treatment. Although these patients will invariably suffer from tumor recurrence, they usually do not receive any further treatment to maintain remission. According to in vitro and in vivo clinical studies, 13-cis retinoic acid (cRA) may be a promising agent for maintenance therapy in these patients.We initiated a clinical study to evaluate the feasibility and toxicity of high-dose cRA as maintenance therapy in patients with high-grade glioma in complete remission after first-line multimodal treatment.A prospective single-arm phase-II study in patients with CR after combined first-line therapy (neurosurgery, radio- and chemotherapy) was performed. Patients were treated with cRA at 60 mg/m2 BS from day 1 to 21 in four-weekly cycles with a dose escalation of up to 100 mg/m2 BS until tumor recurrence. Clinical controls were performed every 4 weeks, magnetic resonance imaging every 8 weeks.Twenty-three patients (10, grade IV; 13, grade III) were evaluable using an intention-to-treat analysis. Treatment was well tolerated for up to 149 weeks with moderate dermatological symptoms in all patients. No grade 4 toxicities were observed. Median time to progression was 41 weeks, median overall survival 74 weeks after inclusion in the protocol.There is an urgent need for strategies maintaining remission in patients with malignant glioma. Maintenance therapy with high-dose cRA is feasible and well tolerated over long periods of time. A controlled clinical trial to test the efficacy of cRA as a maintenance treatment in malignant glioma is warranted.

BACKGROUND Doxorubicin exhibits high efficacy in malignant glioma cell cultures. Nonetheless, as a standard formulation, doxorubicin has not been used clinically, due to poor penetration of the blood-brain barrier. Furthermore, doxorubicin is known to induce tumor resistance genes. To address both of these issues, the authors investigated the use of pegylated liposomal doxorubicin (Caelyx™; Essex Pharma, Munich, Germany) alone (Trial 1) and in combination with tamoxifen (Trial 2) in two sequentially performed nonrandomized prospective Phase II trials involving patients with recurrent high-grade glioma. METHODS Twenty patients were included in each trial. Progression-free survival at 6 months (PFS-6) and toxicity were the primary endpoints. Expression of the tumor resistance proteins multidrug resistance protein 1 (MDR-1) and multiple resistance protein (MRP) was evaluated by immunohistochemical methods and by sestamibi–single-photon emission computed tomography (SPECT). RESULTS The overall response rate (including cases of disease stabilization) was 40% in both Trial 1 and Trial 2. PFS-6 was 15%, and the median time to disease progression was 17 weeks. It is noteworthy that 40% of patients with Grade III tumors had long-term responses, which lasted for up to 3 years. There was no significant difference between Trial 1 and Trial 2 in terms of efficacy. Both regimens were well tolerated, with the main side effect being palmoplantar erythrodysesthesia. The authors found no correlation between clinical response and expression of tumor resistance genes or between clinical response and SPECT data. CONCLUSIONS Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND Survival after first-line therapy is poor for patients with glioblastoma. The role of second-line treatment for recurrent disease is controversial. The authors studied the outcome in a subset of patients with glioblastoma who were selected for an aggressive reintervention strategy at the time of progression. Their objectives were to improve patients' overall survival with sustained quality of life and to make comparisons with overall survival in unselected patients. METHODS Overall, 168 patients were eligible for retrospective analysis. Ninety patients received specific therapy for disease recurrence (reintervention group) by specific criteria. RESULTS In the reintervention group, promising median overall survival (mOS) results after diagnosis (61.5 weeks) and progression (33 weeks) were obtained. The progression-free survival (PFS) rate at 12 months and the overall survival rate were superior in the reintervention group (71% at 12 months and 32% at 24 months) compared with the total cohort (45% and 20%, respectively) and the standard group (15% and 5%, respectively). A matched-pair analysis (n = 46 in each group), with an mOS period of 65.5 versus 28.5 weeks, confirmed these data. Quality of life was stable or slightly improved during reinterventions in a subset of patients treated within clinical studies. CONCLUSIONS The majority of patients in the current series were treated with a reintervention strategy, which had an impact on PFS and mOS. A second resection, focal radiotherapy (in selected cases), and additional chemotherapeutic regimens should be considered for patients with recurrent glioblastoma. Cancer 2003;98:2678–86. © 2003 American Cancer Society.

The aim of this study was to assess the influence of inflammatory reactions in herniated lumbar disc specimens on pain resolution after lumbar disc surgery. Disc specimens of 200 patients who underwent surgery for lumbar disc herniation were studied immunohistologically. Preoperatively each patient received a verbal rating scale (VRS) for classification of the pain level and general clinical data were recorded prospectively. Varying amounts of macrophages could be demonstrated. Eighty-nine percent of patients could be followed up for a mean period of 7 months. A statistically significant correlation between the histologically observed macrophage infiltration and postoperative pain grading according to the VRS was found. Patients with evidence of inflammatory reactions rated their postoperative complaints lower than patients with no evidence of inflammatory reactions on the VRS (P=0.04). In our study, a statistically significant correlation between inflammatory changes in the herniated lumbar disc specimen and outcome after lumbar disc surgery could be demonstrated.

Monitoring of local oxygen pressure in brain white matter (tipo2) and of local hemoglobin oxygen saturation (rSo2) with near-infrared spectroscopy (NIRS) are increasingly employed techniques in neurosurgical intensive care units. Using frequency-based mathematical methods, the authors sought to ascertain whether both techniques contained similar information. Twelve patients treated in the intensive care unit were included (subarachnoid hemorrhage, n = 3; traumatic brain injury, n = 9). A tipo2 probe and an NIRS sensor were positioned over the frontal lobe with the most pathologic changes on initial computed tomography scan. The authors calculated coherence of tipo2 and rSo2, its overall density distribution, its distribution per data set, and its time evolution. The authors identified a band of significantly correlated frequencies (from 0 to 1.3 × 103 Hz) in more than 90% of the data sets for coherence and overall density distribution. Time evolution showed slow but marked changes of significant coherence. By means of spectral analysis the authors show that tipo2 and rSo2 signals contain similar information, albeit using completely different registration methodologies.

S-100B protein is a new possible indicator of brain damage after severe head injury. In outcome assessment there is an increasing focus on measures of health outcome incorporating the person's own perspective. Therefore, the aim of the study was to investigate the correlation of early S-100B serum level to the quality of life.fifty-one patients with severe head injury were included in a prospective study. Blood samples were taken on admission (mean 2.5 hours). The outcome was assessed at follow-up using the Glasgow Outcome Scale and a questionnaire according to Blau to assess the quality of life.high serum concentrations of S-100B on admission correlate to unfavourable outcome according to the GOS (4.9 micro g/l vs 1.6 micro g/l, mean, p0.0008). In addition, the S-100B serum concentrations on admission correlate to quality of life in the survivor group. Patients with S-100B serum levelsor = 0.5 micro g/l scored 71.4 points (mean) on the QoL index compared to patients with elevated S-100B concentrations, who scored 55.4 points (mean, p0.05).S-100B seems to be able to assess the extent of primary brain damage after trauma.

ObjectiveRecent studies have investigated the role of spinal image guidance for pedicle screw placement. Many authors have observed an elevated placement accuracy and overall improvement of outcome measures. This study assessed a bi-institutional experience following introduction of the Renaissance miniature robot for spinal image guidance in Europe.MethodsThe medical records and radiographs of all patients who underwent robot-guided implantation of spinal instrumentation using the novel system (between October 2011 and March 2015 in Mainz and February 2014 and February 2016 in Regensburg) were reviewed to determine the efficacy and safety of the newly introduced robotic system. Screw position accuracy, complications, exposure durations to intraoperative radiation, and reoperation rate were assessed.ResultsOf the 413 surgeries that used robotic guidance, 406 were via a minimally invasive approach. In 7 cases the surgeon switched to conventional screw placement, using a midline approach, due to referencing problems. A total of 2067 screws were implanted using robotic guidance, and 1857 screws were evaluated by postoperative CT. Of the 1857 screws, 1799 (96.9%) were classified as having an acceptable or good position, whereas 38 screws (2%) showed deviations of 3–6 mm and 20 screws (1.1%) had deviations > 6 mm. Nine misplaced screws, implanted in 7 patients, required revision surgery, yielding a screw revision rate of 0.48% of the screws and 7 of 406 (1.7%) of the patients. The mean ± SD per-patient intraoperative fluoroscopy exposure was 114.4 (± 72.5) seconds for 5.1 screws on average and any further procedure required. Perioperative and direct postoperative complications included hemorrhage (2 patients, 0.49%) and wound infections necessitating surgical revision (20 patients, 4.9%).ConclusionsThe hexapod miniature robotic device proved to be a safe and robust instrument in all situations, including those in which patients were treated on an emergency basis. Placement accuracy was high; peri- and early postoperative complication rates were found to be lower than rates published in other series of percutaneous screw placement techniques. Intraoperative radiation exposure was found to be comparable to published values for other minimally invasive and conventional approaches.

Background During awake craniotomies, patients may either be awake for the entire duration of the surgical intervention (awake-awake-awake craniotomy, AAA) or initially sedated (asleep-awake-asleep craniotomy, SAS). Objective To examine whether prior sedation in SAS may restrict brain mapping, we conducted neuropsychological tests in patients by means of a standardized anesthetic regimen comparable to an SAS. Methods We prospectively examined patients undergoing surgery either under total intravenous anesthesia (TIVA) or under regional anesthesia with slight sedation (RAS). The tests included the DO40 picture-naming test, the digit span, the Regensburg Word Fluency Test, and the finger-tapping test. Each test was conducted 3 times for every patient in the TIVA and RAS groups, once before surgery and twice within about 35 minutes after the end of sedation. Patients undergoing AAA were examined preoperatively and intraoperatively. Results In the AAA group, no significant difference was found between preoperative and intraoperative test results. In the TIVA and RAS groups, postoperative tests showed worse results than preoperative tests. In most tests, patients improved from the first to the second postoperative test. Conclusion Cognitive and motor performance were significantly influenced by prior sedation in the TIVA and RAS groups, but not in the AAA group. Therefore, prior sedation may be assumed to cause a change in the baselines, which may compromise brain mapping and thus endanger a patient's neurological outcome in the case of an SAS.

Different authors recommend different time spans for conservative treatment before considering surgery in patients suffering from lumbar disc herniation. We analyzed the time of onset of symptoms such as pain, sensory deficit, and motor deficit in a surgically treated group in comparison to outcome after surgery in order to define a time threshold when surgical results deteriorate and operation should therefore be considered. General data, symptoms, signs, and neurological findings of 219 patients were preoperatively recorded. The outcome was evaluated according to the Prolo scale after a mean of 9.9 months. In the statistical workup, we calculated the duration of symptoms, sensory deficits, and motor deficit as continuous variables. Additionally, the population was divided into three groups of duration of symptoms, sensory deficit, or motor deficit foror = 30 days, 30-60 days, and60 days. Statistically significant predictors for unfavourable outcome were, for example, a longer duration of preoperative pain and motor and sensory deficit. Patients suffering for more than 60 days from disc herniation were found to have statistically worse outcome than patients suffering for 60 days or less. Findings were similar for the different time groups concerning the duration of sensory deficit but not for duration of motor deficit. The overall outcome seems to be better when patients are operated on for lumbar disc herniations within 2 months after onset of symptoms and sensory deficits. Due to these findings, we recommend conservative treatment up to 2 months and, if conservative management does not succeed, consideration of surgery.

We recently demonstrated the effectiveness of dorsal foraminotomy in lateral herniated cervical disc after 1 year follow-up in a prospective study. 1 The goal of this paper is to confirm these results concerning long term outcome. We carried out a prospective, consecutive study on 54 patients, operated on for lateral herniated cervical disc. We analysed demographic data, the case history, the neurological examination on admission and imaging data. Ninety per cent were followed up for 3.5 years postoperatively. According to their ratings on a pain scale the group were divided into favourable and unfavourable outcomes. These groups were analysed in relation to the patient’s initial condition. At follow up, 90% of patients showed complete recovery or improvement. A long standing preoperative neurological deficit seems to be an important prognostic factor for unfavourable long term outcome after cervical foraminotomy.