Johanna Quick-Weller

Intratumoral Concentrations and Effects of Orally Administered Micellar Curcuminoids in Glioblastoma Patients

ABSTRACT Background: The oral bioavailability of curcuminoids is low, but can be enhanced by incorporation into micelles. The major curcuminoid curcumin has antitumor effects on glioblastoma cells in vitro and in vivo. We therefore aimed to determine intratumoral concentrations and the clinical tolerance of highly bioavailable micellar curcuminoids in glioblastoma patients. Methods: Thirteen glioblastoma patients ingested 70 mg micellar curcuminoids [57.4 mg curcumin, 11.2 mg demethoxycurcumin (DMC), and 1.4 mg bis-demethoxycurcumin (BDMC)] three times per day for 4 days (total amount of 689 mg curcumin, 134 mg DMC, and 17 mg BDMC) prior to planned resection of their respective brain tumors. Tumor and blood samples were taken during the surgery and analyzed for total curcuminoid concentrations. 31P magnetic resonance spectroscopic imaging was performed before and after curcuminoid consumption. Results: Ten patients completed the study. The mean intratumoral concentration of curcumin was 56 pg/mg of tissue (range 9–151), and the mean serum concentration was 253 ng/ml (range 129–364). Inorganic phosphate was significantly increased within the tumor (P = 0.034). The mean ratio of phosphocreatine to inorganic phosphate decreased, and the mean intratumoral pH increased (P = 0.08) after curcuminoid intervention. Conclusion: Oral treatment with micellar curcuminoids led to quantifiable concentrations of total curcuminoids in glioblastomas and may alter intratumoral energy metabolism.

Combination of 5-ALA and iMRI in re-resection of recurrent glioblastoma

Abstract Background Tumour resection plays a role in the initial treatment but also in the setting of recurrent glioblastoma (rGBM). To achieve maximum resection, 5-aminolevulinic acid (5-ALA) and intraoperative MRI (iMRI) are used as surgical tools. Aiming at complete tumour re-resection, we started combining iMRI with 5-ALA to find out if this leads to better surgical results. Methods We performed tumour resections in seven patients with rGBM, combining 5-ALA (20 mg/kg bodyweight) with iMRI (0.15 T). Radiologically complete resections were intended in all seven patients. We assessed intraoperative fluorescence findings and compared these with intraoperative imaging. All patients had early postoperative MRI (3 T) to verify final iMRI scans and received adjuvant treatment according to interdisciplinary tumour board decision. Results Median patient age was 63 years. Median KPS score was 90, and median tumour volume was 8.2 cm3. In six of seven patients (85%), 5-ALA induced fluorescence of tumour-tissue was detected intraoperatively. All tumours were good to visualise with iMRI and contrast media. One patient received additional resection of residual contrast enhancing tissue on intraoperative imaging, which did not show fluorescence. Radiologically complete resections according to early postoperative MRI were achieved in all patients. Median survival since second surgery was 7.6 months and overall survival since diagnosis was 27.8 months. Conclusions 5-ALA and iMRI are important surgical tools to maximise tumour resection also in rGBM. However, not all rGBMs exhibit fluorescence after 5-ALA administration. We propose the combined use of 5-ALA and iMRI in the surgery of rGBM.

Impact of Stereotactic Biopsy in HIV Patients

OBJECTIVE During their disease a significant number of human immunodeficiency virus (HIV)-infected patients develop neurologic symptoms due to intracerebral pathologies. Entities commonly found are toxoplasmosis, lymphomas, or progressive multifocal leukoencephalopathy. In some patients, diagnosis is not feasible with imaging alone, requiring biopsy. The objective of this study was to evaluate the impact of stereotactic biopsy in HIV patients on adjustment of therapy. METHODS Between January 2004 and May 2015 at our clinic, 26 HIV-infected patients underwent stereotactic biopsy. Thin-layer magnetic resonance images were obtained and fused with computed tomography scans, taken with the stereotactic frame (Leksell) mounted. Biopsy material was evaluated pathologically and microbiologically. RESULTS Histologic analysis revealed B-cell lymphoma in 6 patients (23.1%) and progressive multifocal leukoencephalopathy in 2 patients (7.7%). Abscess and toxoplasmosis were found in 3 patients each (11.5% and 11.5%), and encephalitis occurred in 4 patients (15.4%). In 2 patients each (7.7%), vasculitis, metastasis, and glioblastoma were diagnosed. Further findings comprised non-Hodgkin lymphoma and Burkitt lymphoma in 1 patient each. After biopsy, treatment was significantly changed in 18 (69.2%) patients (P < 0.01). Antibiotic therapy was adjusted in 6 patients (23.1%), and chemotherapy in 3 patients (16.7%). Other changes included antibiotic/antiviral therapy to chemotherapy in 3 patients (16.7%), chemotherapy to radiation, cortisone to chemotherapy, and aciclovir to cortisone in 1 patient each. One patient with glioblastoma underwent resection, and another patient received radiation. One patient underwent palliative care. CONCLUSION Stereotactic biopsy in HIV-infected patients results in significant changes of therapy in more than two thirds of the patients.

Benefit of Stereotactic Procedures in a Series of 43 Children

Objectives: Stereotactic biopsies are procedures that enable neurosurgeons to obtain tissue samples of brain tumors located in eloquent areas with a low risk of perioperative complications. In this study, we examined stereotactic procedures (STX) in children. We focused on effectiveness, safety, and histopathological results to evaluate the benefits of the procedure. Methods: We performed a retrospective analysis of our prospective database and included 43 children aged less than 18 years who underwent STX between 1998 and May 2015. All MRIs were evaluated by a single, experienced neuroradiologist. For all biopsies, Leksell stereotactic frame was used and fixed to the children’s head with four pins. Entry and targetpoints were calculated by BrainLab navigation system. We assessed age, tumor localization, number of samples, histological diagnosis, and postoperative treatment. Results: Median age of the patients was 11 years (range 1-18 years), and median number of tissue samples taken was 12 (range 1 with mere puncture of a cyst to 36). Histopathological examination revealed a final diagnosis in all patients. 3 patients underwent puncture of a cyst. 27 patients had a postoperative imaging. Only in 3 patients, CT scan revealed blood in the area where the biopsy had been taken. All bleedings were small and without clinical sequelae. Conclusion: Stereotactic procedures are accurate and save surgeries to obtain tumor tissue from eloquent areas to base further therapy on. This not only applies to adults but also to children of all ages.

Management of Patients with Primary Intramedullary Spinal Cord Glioblastoma.

BACKGROUND Primary intramedullary spinal cord glioblastomas are very rare tumors of the spinal cord. They imply a very poor prognosis because complete surgical resection is not possible as the result of the infiltrative growth of these tumors. The aim of this study is to present our data achieved with an aggressive multimodality treatment. METHODS We retrospectively reviewed our clinical database. All patients with histologically proven intramedullary spinal cord glioblastoma treated in our department were included in this study. RESULTS Four patients with intramedullary spinal cord glioblastoma were identified between 2006 and 2015, all of whom were female. Mean age at the time of surgery was 33.5 years (range 14-50 years). Tumors were located in the cervical region in 2 patients and in the thoracic region in 2 patients. All 4 patients underwent microsurgical biopsy of the tumor. After surgery, all patients received radiation and temozolomide treatment. One patient underwent additional therapy with Bevacizumab, another patient received Rapamycin and Sunitinib, and the third patient received Chlorethyl-cyclohexyl-nitroso-urea and Etoposide as additional therapy after tumor regrowth. Tumor progression occurred in a mean time of 18.2 months (6-32 months). In this series, all patients died as the result of progression of the malignancy; median survival after diagnosis was 32.5 months. CONCLUSIONS The surgical outcome of intramedullary spinal cord glioblastoma still remains poor. Severe disability and amelioration of the neurologic status lead to reduced quality of life; however, an aggressive multimodal and interdisciplinary treatment for the disease may be associated with longer survival.

Noninvasive epicutaneous transfontanelle intracranial pressure monitoring in children under the age of 1 year: a novel technique

Monitoring of intracranial pressure (ICP) may be indicated in children with traumatic brain injury, premature intraventricular hemorrhage, or hydrocephalus. The standard technique is either a direct measurement with invasive intracranial insertion of ICP probes or indirect noninvasive assessment using transfontanelle ultrasonography to measure blood flow. The authors have developed a new technique that allows noninvasive epicutaneous transfontanelle ICP measurement with standard ICP probes. They compared the ICP measurements obtained using the same type of standard probe used in 2 different ways in 5 infants (age < 1 year) undergoing surgery for craniosynostosis. The first ICP probe was implanted epidurally (providing control measurements) and the second probe was fixed epicutaneously on the skin over the reopened frontal fontanelle. ICP values were measured hourly for the first 24 hours after surgery and the values obtained with the 2 methods were compared using Bland-Altman 2-methods analysis. A total of 110 pairs of measurements were assessed. There was no significant difference between the ICPs measured using the epicutaneous transfontanelle method (mean 13.10 mm Hg, SEM 6.68 mm Hg) and the epidural measurements (mean 12.46 mm Hg, SEM 6.45 mm Hg; p = 0.4643). The results of this analysis indicate that epicutaneous transfontanelle measurement of ICP is a reliable method that allows noninvasive ICP monitoring in children under the age of 1 year. Such noninvasive ICP monitoring could be implemented in the therapy of children with traumatic brain injury or intraventricular hemorrhage or for screening children with elevated ICP without invasive intracranial implantation of ICP probes.

Stereotactic Biopsy of Pineal Lesions

BACKGROUND Stereotactic biopsies are carried out to obtain tumor tissue of unknown entity from cerebral lesions. Thus, tumor tissue can be examined, resulting in correct diagnosis and treatment. These procedures go in hand with high accuracy, high diagnostic yield, and low complication rates. OBJECTIVES The aim of this study is to evaluate the results and complications of stereotactic biopsies carried out for lesions of the pineal region. METHODS We performed a retrospective analysis of our prospective database and included 14 patients who underwent stereotactic biopsy of a pineal lesion between 2006 and February 2016. The Leksell stereotactic frame was used in all patients, and entry and target points were calculated using the BrainLab stereotactic system. We evaluated histopathologic results and postoperative complications such as hydrocephalus and hemorrhage. RESULTS Histopathologic diagnosis was established in all patients. On postoperative computed tomography, 7 patients (50%) showed a circumscribed blood collection at the site of biopsy. Six patients (42.8%) required a cerebrospinal fluid drain preoperatively. Two patients needed external ventricular drain postoperatively (14.2%). One of these patients showed a small hemorrhage area that caused the hydrocephalus. The other patient showed only postoperative swelling. Preoperatively, 2 patients (14.2%) already had a ventriculoperitoneal (VP) shunt, whereas postoperatively, another 4 patients (28.5%) needed a VP shunt. Thus, of the 14 patients, 6 (42.8%) required a VP shunt. CONCLUSIONS Because of their localization, pineal lesions may result in emergence of a hydrocephalus. Stereotactic biopsies in this area may increase this effect and, thus, even VP shunts are necessary in some patients.

Oblique Positioning of the Stereotactic Frame for Biopsies of Cerebellar and Brainstem Lesions.

BACKGROUND Frame-based stereotactic biopsy has proven to be a safe procedure with a high diagnostic yield for patients. Different supratentorial localizations can easily be accessed by standardized stereotactic approaches. Cerebellar and brainstem lesions, however, are not easy to reach because the positioning of the frame pins often makes it impossible to address the entry point properly. METHODS By oblique positioning of the frame, cerebellar and brainstem lesions also can easily be accessed to take tissue samples. CONCLUSION Modification of the standardized positioning of the frame allows for safe and straightforward stereotactic access even to cerebellar and brainstem lesions.

Outcome, Prognostic Factors, and Follow-Up Results After Subarachnoid Hemorrhage from Pericallosal Artery Aneurysms

OBJECTIVE Pericallosal artery aneurysms (PAAs) are usually rare (2%-5%), and treatment is challenging for both surgical and endovascular modalities. We performed this analysis to determine the outcome and prognostic factors after subarachnoidal hemorrhage (SAH) caused by ruptured PAAs. METHODS A total of 32 patients with ruptured PAA were admitted to our hospital between 1999 and 2014, added to our prospective database, and analyzed retrospectively. Outcome was measured based on the modified Rankin Scale (mRS) at 6 months after ictus (favorable mRS score, 0-2 vs. unfavorable mRS score, 3-6). RESULTS Only 16 (50%) patients had a good clinical status at admission (World Federation of Neurological Surgeons Grading System [WFNS] grades I-III), whereas 12 patients (37.5%) were comatose (WFNS grade V). In 18 patients (56%), intracerebral hemorrhage was confirmed, in 18 patients (56%) cerebrospinal fluid drainage was required immediately after admission, and in 5 cases (16%) decompressive craniectomy was performed. There were 17 patients (53.1%) who achieved a favorable outcome (mRS score 0-2) at follow-up. Unfavorable outcome was associated with smoking, cerebral infarction, and worse admission status after multiple logistic regression analysis. CONCLUSIONS Poor admission status, cerebral infarction, and smoking seem to be crucial factors for unfavorable outcome after SAH from PAA.

Postoperative rehabilitation after deep brain stimulation surgery for movement disorders

Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy for a set of neurological and psychiatric conditions and especially movement disorders such as Parkinsons disease, essential tremor and dystonia. Recent developments have improved the DBS technology. However, no unequivocal algorithms for an optimized postoperative care exist so far. The aim of this review is to provide a synopsis of the current clinical practice and to propose guidelines for postoperative and rehabilitative care of patients who undergo DBS. A standardized work-up in the DBS centers adapted to each patients clinical state and needs is important, including a meticulous evaluation of clinical improvement and residual symptoms with a definition of goals for neurorehabilitation. Efficient and complete information transfer to subsequent caregivers is essential. A coordinated therapy within a multidisciplinary team (trained in movement disorders and DBS) is needed to achieve the long-range maximal efficiency. An optimized postoperative framework might ultimately lead to more effective results of DBS.