Abstract BACKGROUND Prospective data suggested a superiority of intraoperative MRI (iMRI) over 5-aminolevulinic acid (5-ALA) for achieving complete resections of contrast enhancement in glioblastoma surgery. We investigated this hypothesis in a prospective clinical trial and correlated residual disease volumes with clinical outcome in newly diagnosed glioblastoma. MATERIAL AND METHODS This is a prospective controlled multicenter parallel-group trial with two center-specific treatment arms (5-ALA and iMRI) and blinded evaluation. The primary endpoint was complete resection of contrast enhancement on early postoperative MRI. We assessed resectability and extent of resection by an independent blinded centralized review of pre- and post-operative MRI with 1mm slices. Secondary endpoints included progression-free (PFS) and overall survival (OS), patient-reported quality of life and clinical parameters. RESULTS We recruited 314 patients with newly diagnosed glioblastomas at eleven German centers. 127 patients in the 5-ALA and 150 in the iMRI arm were analyzed in the as treated analysis. Complete resections, defined as a residual tumor ≤0.175 cm³, were achieved in 90 patients (78%) in the 5-ALA and 115 (81%) in the iMRI arm (p=0.79). Incision-suture times (p<0.001) were significantly longer in the iMRI arm (316 vs. 215 [5-ALA] minutes). Median PFS and OS were comparable in both arms. The lack of any residual contrast enhancing tumor (0cm³) was a significant favorable prognostic factor for PFS (p<0.001) and OS (p=0.048), especially in MGMT unmethylated tumors (p=0.006). CONCLUSION We could not confirm superiority of iMRI over 5-ALA for achieving complete resections. Neurosurgical interventions in newly diagnosed glioblastoma shall aim for safe complete resections with 0 cm³ contrast-enhancing residual disease, as any other residual tumor volume is a negative predictor for PFS and OS.
Abstract Objective Intraneural perineurioma is a rare tumor entity. It is a benign, very slow growing peripheral nerve sheath tumor that typically occurs in children and young adults. Motor deficits and muscle atrophy are classic presenting symptoms, while sensory deficits are rare at the onset of the disease. Recommended treatment strategies are lacking. We have evaluated the clinical follow-up and our experience with treatment of this rare entity. Methods A total of 30 patients with intraneural perineuriomas were assessed retrospectively. Demographic data, clinical symptoms, diagnostic examinations, therapy strategies, and clinical outcome were analyzed. Descriptive statistical methods were used for evaluation. Results The mean age was 22 years. Eleven women and 19 men were affected. The lesion occurred in the area of the upper extremity in 16 patients and in the area of the lower extremity in 14 patients. The most frequently affected nerve was the sciatic nerve, followed by the radial nerve. All patients showed a motor deficit to some extent. Seventy percent (n = 21) revealed atrophy, 43.3% (n = 13) had sensitive deficits, and 17% (n = 5) suffered of pain. Fascicle biopsies were performed in 26 patients (87%). In four patients (13%), the tumor was completely resected and then reconstructed via nerve grafts. Seventy percent of the patients (n = 21) received a magnetic resonance imaging (MRI) within 5 years postoperatively, in which no progress was shown. Conclusions To diagnose perineurioma, it is essential to take a biopsy of an enlarged, nonfunctional fascicle. Furthermore, a long-distance epineuriotomy to decompress the hypertrophic fascicle is reasonable. To preserve the nerves' residual function, a complete resection is not recommended. Results after grafting are poor. One reason for this might be residual tumor cells along the nerve that cannot be visualized. Malignant transformation is not yet reported and tumor growth is stable for years.
Mammals differ in their regeneration potential after traumatic injury, which might be caused by species-specific regeneration programs. Here, we compared murine and human Schwann cell (SC) response to injury and developed an ex vivo injury model employing surgery-derived human sural nerves. Transcriptomic and lipid metabolism analysis of murine SCs following injury of sural nerves revealed down-regulation of lipogenic genes and regulator of lipid metabolism, including Pparg (peroxisome proliferator-activated receptor gamma) and S1P (sphingosine-1-phosphate). Human SCs failed to induce similar adaptations following ex vivo nerve injury. Pharmacological PPARg and S1P stimulation in mice resulted in up-regulation of lipid gene expression, suggesting a role in SCs switching towards a myelinating state. Altogether, our results suggest that murine SC switching towards a repair state is accompanied by transcriptome and lipidome adaptations, which are reduced in humans.
Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are major factors that limit good outcome in patients with spontaneous subarachnoid hemorrhage (SAH). Continuous therapy with intra-arterial calcium channel blockers has been introduced as a new step in the invasive treatment cascade of CV and DCI. Sedation is routinely necessary for this procedure. We report about the feasibility to apply this therapy in awake compliant patients without intubation and sedation. Out of 67 patients with invasive endovascular treatment of cerebral vasospasm due to spontaneous SAH, 5 patients underwent continuous superselective intracarotid nimodipine therapy without intubation and sedation. Complications, neurological improvement, and outcome at discharge were summarized. Very good outcome was achieved in all 5 patients. The Barthel scale was 100 and the modified Rankin scale 0–1 in all cases at discharge. We found no severe complications and excellent neurological monitoring was possible in all cases due to patients’ alert status. Symptoms of DCI resolved within 24 h in all 5 cases. We could demonstrate the feasibility and safety of selective intracarotid arterial nimodipine treatment in awake, compliant patients with spontaneous SAH and symptomatic CV and DCI. Using this method, an excellent monitoring of neurological function as well as early detection of other complications is possible. It might be an important step in the risk reduction of invasive CV therapy to improve the outcome with CV and DCI after SAH in selected patients.
Objective The aim of the study was to compare two techniques for external ventricular drainage (EVD) placement with respect to their complication rates. Methods A retrospective descriptive study was performed to analyze all patients who had undergone EVD implantation for acute hydrocephalus between January 2010 and December 2013 with a focus on surgical technique and rate of complications. The burr hole technique (BHT) was used in one group and the twist-drill technique (TDT) in the other. Particular attention was paid to malposition, hemorrhage, and catheter-associated infection. Results A total of 350 consecutive patients underwent EVD implantation for acute hydrocephalus: BHT was performed in 201 and TDT in 147 of the patients, whereas in two patients the technique used was unknown. The overall infection rate was 6.3% ( n =22). Fourteen patients (4%) in the BHT group developed an infection compared with eight patients (9.5%) in the TDT group ( p =0.154). In 16 (4.5%) of all cases, postoperative computed tomography revealed catheter-induced hemorrhage. In one case (0.3%), surgery was necessary due to acute subdural hematoma. The difference between both techniques was not statistically significant ( p =0.343). In 44 (12.6%) of all cases, the position of the EVD tip was contralateral; in 36 (10.3%) of all cases, the EVD tip was in the brain parenchyma. The rate of malposition was 11.6% ( n =17) in the TDT group and 9.5% ( n =19) in the BHT group ( p =0.078). Conclusion Neither technique showed significantly different numbers in terms of infection, malposition, and hemorrhagic complications. EVD implantation using the TDT is an adequate method compared with BHT. The advantages of TDT are clear: the duration of surgery is shorter, the size of the wound is smaller, and the surgeon is not confined to the operating room.
OBJECTIVE: Quality of life is an important factor in the decision making for the treatment of unruptured intracranial aneurysms (UIA). The data dealing with QoL in patients after the treatment are spare. We have evaluated QoL of patients after endovascular or surgical treatment of incidental intracranial aneurysm. METHODS: We performed a prospective analysis of retrospectively collected data. All patients received 36-Item Short Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), German questionnaire for self-perceived deficits in attention (FEDA) and not standardized questionnaire analyzing personal job-related situation, family circumstances and chronic illnesses. RESULTS: 177 patients were treated during the evaluated period. 79 (44.6%) patients responded. In this cohort, 62.03% of patients underwent coiling. Complications were noted in 13.9% of patients. Stroke was the most common complication (7.6%). All SF-36 related data except for pain showed significant lower mean, if compared to the standard German population (p < 0.01). For both genders, anxiety (males, P = 0.003 and females, P = 0.002) but not depression was more common than in the standard population. According to the FEDA test, treated patients showed significant difference only for fatigue in comparison to healthy population (P < 0.001). 54.4% of patients suffered from chronic illnesses, and among them only 1 patient (1.3%) had aneurysm associated chronic disease. No significant differences were found between treatment modalities. CONCLUSIONS: The risk for depression and pain is not significantly increased after elective treatment of UIA. According to our results, decreased QoL is common in this cohort of patients but often related to factors not associated with aneurysm treatment.
Traumatische Nerven- und Plexusläsionen sind aufgrund ihrer oft verheerenden Funktionsausfälle gefürchtete Verletzungskomplikationen. Die Prognose hängt dabei maßgeblich von einer korrekten frühzeitigen Diagnose und dem richtig gewählten Behandlungsregime ab, wobei zwischen offenen und geschlossenen Verletzungen unterschieden werden muss.
BACKGROUND: The presence of residual tumor is crucial in decision-making for low-grade gliomas (LGGs), because patients older than 40 years of age with residual tumor are considered for adjuvant treatment. There are hints that early postoperative fluid-attenuated inversion recovery (FLAIR) and T2 (within 48 hours) may overestimate residual tumor volume in LGG. Intraoperative magnetic resonance imaging (MRI) without subsequent resection or ultra-early postoperative MRI may assess the amount of residual tumor more adequately. To evaluate the utility of postoperative imaging in LGG, we volumetrically analyzed intraoperative, early, and late (3-4 months after surgery) postoperative MRIs of LGGs.PATIENTS AND METHODS: A total of 33 patients with LGG were assessed retrospectively. Residual tumor was defined as signal-enhanced tissue in T2 and FLAIR. Volumetric assessment was performed with intraoperative, early, and late postoperative T2/FLAIR via Brainlab-iPlan 3.0. Wilcoxon and chi(2) tests were used for statistical analysis.RESULTS: A significant difference of FLAIR/T2 abnormalities was found in intraoperative and early postoperative MRIs (FLAIR mean volume = 5.433 cm(3), T2 mean volume = 3.374 cm(3) vs. FLAIR mean volume = 14.090 cm(3), P = 0.002, T2 mean volume = 7.597 cm(3), P = 0.006). There was no significant difference between intraoperative and late postoperative FLAIR/T2 abnormalities (late cm(3), P = 0.520, P = 0.398), whereas a significant difference was detected between early and late postoperative images (FLAIR, P < 0.0001; T2, P < 0.00001).CONCLUSION: Intraoperative MRI without further resection or ultra-early postoperative MRI seems to reflect the actual volume of residual tumor in LGG more precisely compared with early postoperative MRI and therefore seems to be more useful regarding decisions for adjuvant therapy.
BACKGROUND: We compare the outcome after decompressive craniectomy for various neurologic diseases with the final common pathway of coma, compression of the basal cisterns, a midline shift, or refractory intracranial hypertension.METHODS: Between January 2005 and June 2009, 134 patients underwent decompressive craniectomy for traumatic brain injury (n = 74), intracerebral hemorrhage (n = 21), spontaneous subarachnoid hemorrhage (n = 11), malignant cerebral infarction (n = 27), or encephalitis (n= 1). The outcome was classified at discharge and up to 12 months after treatment in accordance with the Glasgow Outcome Scale (GOS), as well as the Glasgow Coma Scale, Marshall classification, or National Institutes of Health Stroke Scale. Significance was established as P <= 0.05.RESULTS: Median and mean scores on the Glasgow Coma Scale at time of neurosurgical assessment in all patients were <= 7. Midline shift was reduced in each subset as a result of surgery (mean, 0.26-0.46 cm; P <= 0.049). Overall outcome based on the median GOS score at discharge ranged from death to severe disability. After 12 months, the median range narrowed to a range of death to persistent vegetative state. At various time points, mean GOS score was not found to differ significantly between the subsets. Unfavorable outcome after 3 months was found in a smaller group of patients after traumatic brain injury than was found in patients with other diseases (P = 0.016).CONCLUSIONS: The outcome after decompressive craniectomy does not differ significantly in different diseases once the final pathophysiologic pathway of refractory intracranial hypertension, coma, compression of the basal cisterns, or midline shift has been reached.
Objective. The exact cause of cognitive deficits following intracranial haemorrhage is unclear. This prospective study examines the abilities after spontaneous subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH) and chronic subdural haematoma (SDH) to elucidate the cognitive outcome. Patients and methods. Ninety-nine patients with SAH (N = 60), ICH (N = 25), and SDH (N = 14) were followed up for an average of 6 and 12 months post-haemorrhage. Cognitive tests were used to examine attention, memory, concentration, and executive function. Following were used for analysis: 1. the percentage of patients falling below the 25th percentile per test, 2. the general development from the first to second test point and 3. the incidence of significant changes between the test points. Significance was established as p <= 0.05. Results. All three types of haemorrhage resulted in deficits as concerns abstract language (53%-75%). The processing speed was below the normal levels in more than 70% of the patients tested. The cognitive performance of SAH patients was similar to that of patients with SDH and ICH patients after 6 months. The number of patients with outcomes falling below the 25th percentile (to some extent more than 75% in patients post-SAH) is high in all patient groups and mostly decreases over the course. Nevertheless, patients with SAH reveal improvements in many more areas than with ICH and SDH (p <= 0.006). Conclusions. The cognitive impairments following SAH, ICH and SDH deficits appear to develop in a similar way regardless of the type of haemorrhage. Cognitive improvement is most pronounced in patients with SAH.