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  • 1
    Language: English
    In: Clinical cancer research, 2008-01-01, Vol.14 (1), p.123-129
    Description: Purpose: The CD133 antigen has been identified as a putative stem cell marker in normal and malignant brain tissues. In gliomas, it is used to enrich a subpopulation of highly tumorigenic cancer cells. According to the cancer stem cell hypothesis, CD133-positive cells determine long-term tumor growth and, therefore, are suspected to influence clinical outcome. To date, a correlation between CD133 expression in primary tumor tissues and patients' prognosis has not been reported. Experimental Design: To address this question, we analyzed the expression of the CD133 stem cell antigen in a series of 95 gliomas of various grade and histology by immunohistochemistry on cryostat sections. Staining data were correlated with patient outcome. Results: By multivariate survival analysis, we found that both the proportion of CD133-positive cells and their topological organization in clusters were significant ( P 〈 0.001) prognostic factors for adverse progression-free survival and overall survival independent of tumor grade, extent of resection, or patient age. Furthermore, proportion of CD133-positive cells was an independent risk factor for tumor regrowth and time to malignant progression in WHO grade 2 and 3 tumors. Conclusions: These findings constitute the first conclusive evidence that CD133 stem cell antigen expression correlates with patient survival in gliomas, lending support to the current cancer stem cell hypothesis.
    Subject(s): AC133 Antigen ; Adult ; Antigens, CD - biosynthesis ; Antineoplastic agents ; Biological and medical sciences ; Brain Neoplasms - metabolism ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; CD133 ; Disease-Free Survival ; Female ; glioma ; Glioma - metabolism ; Glioma - mortality ; Glioma - pathology ; Glycoproteins - biosynthesis ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Medical sciences ; Middle Aged ; Neurology ; Peptides ; Pharmacology. Drug treatments ; Prognosis ; stem cells ; Stem Cells - metabolism ; Survival Analysis ; Tumors of the nervous system. Phacomatoses
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 2
    Language: English
    In: Neuromodulation (Malden, Mass.), 2021-08, Vol.24 (6), p.1115-1120
    Description: Introduction Subcutaneous trigeminal nerve field stimulation (sTNFS) is a neuromodulatory treatment for neuropathic trigeminal pain with the ability to reduce the intensity and frequency of pain attacks. However, hardware issues including lead migration, skin erosion, infection, so‐called pocket pain at the site of the implanted neurostimulator are reported. Implantable wireless neurostimulation technology promises not only an even less invasive sTNFS treatment and thinner and more flexible electrodes better suited for facial implants, but also provides further advantages such as lack of an implantable neurostimulator and 3T magnetic resonance imaging compatibility. Material and Methods All patients who had received trial stimulation with a partially implantable sTNFS system were analyzed for ICHD‐3 (3rd edition of the International Classification of Headache Disorders) diagnosis, success of trial stimulation, pre‐ and postoperative pain intensity, frequency of attacks, complications, and side‐effects of sTNFS. Results All patients (N = 3) responded to sTNFS (≥50% pain reduction) during the trial period. According to ICHD‐3, N = 2 of the patients were classified with trigeminal neuralgia (TN) with concomitant persistent facial pain and N = 1 patient with multiple sclerosis associated TN. The time of the test period was 44 ± 31.24 days (mean ± SD). The average daily duration of stimulation per patient amounted 2.5 ± 2.2 hours (range 1–5). The pain intensity (defined on a visual analog scale) was reduced by 80% ± 17% (mean ± SD). Reduction or cessation in pain medication was observed in all patients. No surgical complications occurred in the long‐term follow‐up period of 18.84 ± 6 (mean ± SD) months. Conclusion The partially implantable sTNFS device seems to be safe, effective, and reliable. Compared to conventional devices, the equipment is not limited to the length of trial stimulation. Furthermore, the daily stimulation duration was much shorter compared to previous reports.
    Subject(s): Analgesics ; Care and treatment ; Health aspects ; Implants, Artificial ; Multiple sclerosis ; Neuropathic trigeminal pain ; Pain ; peripheral nerve stimulation ; Prosthesis ; refractory pain ; Skin ; subcutaneous nerve stimulation ; wireless stimulation
    ISSN: 1094-7159
    E-ISSN: 1525-1403
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: The Journal of clinical investigation, 2008-05, Vol.118 (5), p.1739-1749
    Description: The molecular pathogenesis of pediatric astrocytomas is still poorly understood. To further understand the genetic abnormalities associated with these tumors, we performed a genome-wide analysis of DNA copy number aberrations in pediatric low-grade astrocytomas by using array-based comparative genomic hybridization. Duplication of the BRAF protooncogene was the most frequent genomic aberration, and tumors with BRAF duplication showed significantly increased mRNA levels of BRAF and a downstream target, CCND1, as compared with tumors without duplication. Furthermore, denaturing HPLC showed that activating BRAF mutations were detected in some of the tumors without BRAF duplication. Similarly, a marked proportion of low-grade astrocytomas from adult patients also had BRAF duplication. Both the stable silencing of BRAF through shRNA lentiviral transduction and pharmacological inhibition of MEK1/2, the immediate downstream phosphorylation target of BRAF, blocked the proliferation and arrested the growth of cultured tumor cells derived from low-grade gliomas. Our findings implicate aberrant activation of the MAPK pathway due to gene duplication or mutation of BRAF as a molecular mechanism of pathogenesis in low-grade astrocytomas and suggest inhibition of the MAPK pathway as a potential treatment.
    Subject(s): Astrocytoma ; Astrocytoma - enzymology ; Astrocytoma - genetics ; Astrocytoma - pathology ; Brain Neoplasms - enzymology ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Cancer ; Care and treatment ; Cell Cycle - physiology ; Child ; Chromosome Aberrations ; Cyclin D ; Cyclins - genetics ; Cyclins - metabolism ; Diagnosis ; Enzyme Activation ; Enzyme Inhibitors - metabolism ; Female ; Gene Duplication ; Gene mutations ; Genetic aspects ; Health aspects ; Humans ; Identification and classification ; Male ; MAP Kinase Signaling System - physiology ; Methods ; Microarray Analysis ; Mitogen-Activated Protein Kinases - genetics ; Mitogen-Activated Protein Kinases - metabolism ; Mutation ; Nucleic Acid Hybridization - methods ; Prognosis ; Proto-Oncogene Proteins B-raf - genetics ; Proto-Oncogene Proteins B-raf - metabolism ; Research ; Risk factors
    ISSN: 0021-9738
    E-ISSN: 1558-8238
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: PubMed Central
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  • 4
    Language: English
    In: Acta neurochirurgica, 2018-12, Vol.160 (12), p.2509-2519
    Description: Spinal cord stimulation (SCS) is an established treatment option for patients with refractory chronic pain conditions. While effects of SCS on dorsal horn neuronal circuitries are intensively studied, current knowledge on the impact of SCS on descending pain pathways is scarce and relies on preclinical data. We aimed to address this topic and hypothesized a significant effect of SCS on descending pain modulation. In light of current efforts to determine the sensitivity of “static” versus “dynamic” somatosensory parameters to characterize pathophysiological pain conditions, all SCS patients were carefully investigated using both classes of somatosensory outcome parameters.Descending pain pathways were investigated by using a “Cold Pressor Test.” This test enables to evaluate the efficacy of conditioned pain modulation (CPM) at the individual level. CPM efficacy was assessed in eight neuropathic pain patients (age 55.5 ± 10.6) during the two conditions stimulator “ON” and “OFF.” The impact of SCS on “static” and “dynamic” somatosensory parameters was explored by using a quantitative sensory testing (QST) battery.CPM efficacy on pressure pain sensitivity was nearly absent during “OFF” (− 1.2 ± 5.6% facilitation), but increased significantly to 16.3 ± 3.4% inhibition during “ON” (p = 0.03). While most “static” nociceptive QST parameters, represented by mechanical/thermal pain thresholds, exhibited only small effects of SCS (p 〉 0.05), the wind-up ratio was strongly reduced to within the normal range during “ON” (p = 0.04; Cohen’s d = 1.0). Dynamic mechanical allodynia was abolished in six of seven patients.Our study provides first human evidence for an impact of SCS on descending pain pathways in the dorsolateral funiculus and emphasizes the significance of “dynamic” pain measures like “CPM”-efficacy and “temporal summation” to evaluate SCS treatment effects. Future prospective studies may use these measures of nociceptive processing to predict SCS therapy response.
    Subject(s): Cold pressor test ; Descending pain modulation ; Interventional Radiology ; Medicine & Public Health ; Minimally Invasive Surgery ; Neurology ; Neuropathic pain ; Neuroradiology ; Neurosurgery ; Quantitative sensory testing ; Spinal cord stimulation ; Surgical Orthopedics
    ISSN: 0001-6268
    E-ISSN: 0942-0940
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: Neuromodulation (Malden, Mass.), 2021-04, Vol.24 (3), p.591-595
    Description: Objectives A new wireless spinal cord stimulation (SCS) technology, which was introduced in recent years, promises minimal invasive SCS as well as additional advantages such as a wide range of stimulation paradigms and 3‐T magnetic resonance imaging (MRI) conditionality. Materials and Methods We prospectively evaluated 12 patients suffering from therapy‐resistant neuropathic pain, who were implanted with a wireless SCS system from 2017 to 2019. Potential issues pertaining to handling and usability of the SCS device were evaluated from a patients' as well as from a surgeon's perspective. Results Mean follow‐up was 228.0 days (95% CI, 20.0–518.0 days). We did not record any handling issues nor did we record any relevant local discomfort associated with the implanted SCS device. N = 3/12 patients reported discomfort from wearing the SCS antenna and one patient complained about a short battery life of the controller device. There were no reported incidents during 3‐T MRI studies. After an average test period of 51.7 days (95% CI, 11.0–104.0 days), N = 9/12 patients (75%) had reached pain relief of 50% or more with an average pain relief (responders and partial responders) of 67.4% (95% CI, 50.0%–85.0%). On average, patients tested 2.2 different stimulation paradigms, with frequencies ranging from 60 Hz to 10 kHz, but there was no preferred stimulation paradigm. Conclusions Minimal invasive implantation of wireless SCS systems was feasible and safe. The device offered a broader range of stimulation paradigms compared to conventional SCS devices, an allowed for a prolonged testing phase and continuous adjustment of SCS programs.
    Subject(s): Antennas (Electronics) ; Batteries ; Care and treatment ; neuropathic pain ; Pain ; Patient satisfaction ; spinal cord stimulation ; wireless stimulation
    ISSN: 1094-7159
    E-ISSN: 1525-1403
    Source: Alma/SFX Local Collection
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  • 6
    Language: English
    In: Acta neurochirurgica, 2009-11, Vol.151 (11), p.1359-1365
    Description: The appropriate management of low-grade gliomas is still a matter of debate. So far, there are no randomized studies that analyze the impact of surgical resection on patient outcome. The value of the data obtained from the few retrospective reports available is often limited. In the present study, we performed an analysis on data of 130 adult low-grade glioma patients. Extent of the resection was evaluated in correlation to the overall survival (OS) and progression-free survival (PFS) using Cox regression multivariate analysis. Extended surgery was shown to prolong OS and PFS significantly. Re-surgery in the case of a tumor relapse has a significant impact on OS and PFS, too. In summary, we could retrospectively evaluate a large case series of well-defined low-grade gliomas patients with a long follow-up period showing that extended surgery would be the most effective therapy for low-grade glioma patients even in recurrent diseases.
    Subject(s): Adolescent ; Adult ; Age Factors ; Aged ; Analysis ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Brain Neoplasms - surgery ; Brain tumors ; Cancer ; Care and treatment ; Combined Modality Therapy - methods ; Combined Modality Therapy - statistics & numerical data ; Drug Therapy - methods ; Drug Therapy - statistics & numerical data ; Female ; Glioma - mortality ; Glioma - pathology ; Glioma - surgery ; Gliomas ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Monitoring, Intraoperative ; Neoplasm Invasiveness - physiopathology ; Neoplasm Invasiveness - prevention & control ; Neoplasm Recurrence, Local - epidemiology ; Neoplasm Recurrence, Local - prevention & control ; Neoplasm Recurrence, Local - surgery ; Neuronavigation ; Neurosurgical Procedures - methods ; Neurosurgical Procedures - statistics & numerical data ; Oncology, Experimental ; Patient outcomes ; Preoperative Care ; Prognosis ; Radiotherapy - methods ; Radiotherapy - statistics & numerical data ; Research ; Retrospective Studies ; Stereotaxic Techniques ; Survival Rate ; Treatment Outcome ; Universities and colleges ; Young Adult
    ISSN: 0001-6268
    E-ISSN: 0942-0940
    Source: Alma/SFX Local Collection
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  • 7
    Language: English
    In: Acta neurochirurgica, 2016-09, Vol.158 (9), p.1767-1774
    Description: Neurosurgical pain management of drug-resistant trigeminal neuralgia (TN) is highly challenging. Microvascular decompression is a first-line neurosurgical approach for classical TN with neurovascular conflict, but can show clinical relapse despite proper decompression. Second-line destructive techniques like radiofrequency thermocoagulation have become reluctantly used due to their potential for irreversible side effects. Subcutaneous peripheral nerve field stimulation (sPNFS) is a minimally invasive neuromodulatory technique which has been shown to be effective for chronic localised pain conditions. Reports on sPNFS for the treatment of trigeminal pain (sTNFS) are still sparse and primarily focused on pain intensity as outcome measure. Detailed data on the impact of sTNFS on attack frequency are currently not available.Patients were classified according to the International Headache Society classification (ICHD-3-beta). Three patients had classical TN without (n = 3) and another three TN with concomitant persistent facial pain (n = 3). Two patients suffered from post-herpetic trigeminal neuropathy (n = 2). All eight patients underwent a trial stimulation of at least 7 days with subcutaneous leads in the affected trigeminal area connected to an external neurostimulator. Of those, six patients received permanent implantation of a neurostimulator. During the follow-up (6–29 months, mean 15.2), VAS-scores, attack frequencies, oral drug intake, complications and side effects were documented.Seven out of eight patients responded to sTNFS (i.e. ≥50 % pain reduction) during the test trial. The pain intensity (according to VAS) was reduced by 83 ± 16 % (mean ± SD) and the number of attacks decreased by 73 ± 26 % (mean ± SD). Five out of six patients were able to reduce or stop pain medication. One patient developed device infection. Two patients developed stimulation-related side effects which could be resolved by reprogramming.Treatment by sTNFS is a beneficial option for patients with refractory trigeminal pain. Prospective randomised trials are required to systematically evaluate efficacy rates and safety of this low-invasive neurosurgical technique.
    Subject(s): Adult ; Aged ; Aged, 80 and over ; Chronic neuropathic pain ; Cohort Studies ; Electric Stimulation Therapy - methods ; Female ; Humans ; Interventional Radiology ; Male ; Medicine & Public Health ; Middle Aged ; Minimally Invasive Surgery ; Neurology ; Neuromodulation ; Neuroradiology ; Neurosurgery ; Peripheral nerve field stimulation ; Post-herpetic trigeminal neuropathy ; Surgical Orthopedics ; Trigeminal Nerve ; Trigeminal neuralgia ; Trigeminal Neuralgia - therapy
    ISSN: 0001-6268
    E-ISSN: 0942-0940
    Source: Alma/SFX Local Collection
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  • 8
    Language: English
    In: Neuromodulation (Malden, Mass.), 2019-12, Vol.22 (8), p.978-985
    Description: Introduction Sphenopalatine ganglion stimulation (SPG‐S) is an invasive form of neuromodulation by which a neurostimulator is implanted into the pterygopalatine fossa to treat refractory chronic cluster headache. The implant is MRI conditional, up to 3 T, however there is no clinical data on the shape, size, and location of the artifact produced by the implant. Materials and Methods Records of patients with SPG‐S were analyzed for postoperative cranial MRI scans. MRI and intraoperative CT scans for visualization of the implant were fused and volumetry was performed for both the implant and the MRI artifact in different MRI sequences. Results In total, n = 3 patients with postoperative MRI scans were identified. The mean CT artifact volume was 0.73 cm3 (±0.15 cm3). MRI artifact volume differed between sequences (range: 25.2–220.7 cm3). The intracranial space was largely unaffected besides the pole of the ipsilateral temporal lobe and the basal frontal gyrus. MRI artifacts affected the extracranial space (orbit, maxillary and ethmoid sinuses, and parts of the parotid gland). No adverse events occurred during or after MRI scans. Conclusions Cranial MRI scans with SPG‐S implants were safely performed in three patients following the manufacturer's MRI conditions. MRI artifacts were mostly located in the extracranial space. Brain MRI imaging is largely unaffected. Conflict of Interest The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article.
    Subject(s): Clinical Neurology ; Cluster headache ; Life Sciences & Biomedicine ; Medicine, Research & Experimental ; MRI ; neuromodulationsphenopalatine ganglion ; Neurosciences & Neurology ; Research & Experimental Medicine ; Science & Technology
    ISSN: 1094-7159
    E-ISSN: 1525-1403
    Source: Academic Search Ultimate
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: Alma/SFX Local Collection
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  • 9
    Language: English
    In: Trials, 2021-01-25, Vol.22 (1), p.87-87
    Description: Spinal cord stimulation (SCS) is an effective method to treat neuropathic pain; however, it is challenging to compare different stimulation modalities in an individual patient, and thus, it is largely unknown which of the many available SCS modalities is most effective. Specifically, electrodes leading out through the skin would have to be consecutively connected to different, incompatible SCS devices and be tested over a time period of several weeks or even months. The risk of wound infections for such a study would be unacceptably high and blinding of the trial difficult. The PARS-trial seizes the capacity of a new type of wireless SCS device, which enables a blinded and systematic intra-patient comparison of different SCS modalities over extended time periods and without increasing wound infection rates. The PARS-trial is designed as a double-blinded, randomized, and placebo-controlled multi-center crossover study. It will compare the clinical effectiveness of the three most relevant SCS paradigms in individual patients. The trial will recruit 60 patients suffering from intractable neuropathic pain of the lower extremities, who have been considered for SCS therapy and were already implanted with a wireless SCS device prior to study participation. Over a time period of 35 days, patients will be treated consecutively with three different SCS paradigms ("burst," "1 kHz," and "1.499 kHz") and placebo stimulation. Each SCS paradigm will be applied for 5 days with a washout period of 70 h between stimulation cycles. The primary endpoint of the study is the level of pain self-assessment on the visual analogue scale after 5 days of SCS. Secondary, exploratory endpoints include self-assessment of pain quality (as determined by painDETECT questionnaire), quality of life (as determined by Quality of Life EQ-5D-5L questionnaire), anxiety perception (as determined by the Hospital Anxiety and Depression Scale), and physical restriction (as determined by the Oswestry Disability Index). Combining paresthesia-free SCS modalities with wireless SCS offers a unique opportunity for a blinded and systematic comparison of different SCS modalities in individual patients. This trial will advance our understanding of the clinical effectiveness of the most relevant SCS paradigms. German Clinical Trials Register, DRKS00018929 . Registered on 14 January 2020.
    Subject(s): Adult ; Analysis ; Care and treatment ; Chronic Pain - diagnosis ; Chronic Pain - therapy ; Clinical trials ; Cross-Over Studies ; Diagnostic Self Evaluation ; Double-Blind Method ; Female ; Health aspects ; Humans ; Implantable Neurostimulators - adverse effects ; Infection ; Male ; Medical research ; Medicine, Experimental ; Multicenter Studies as Topic ; Neuralgia - diagnosis ; Neuralgia - therapy ; Neuropathic pain ; Pain ; Pain Measurement ; Physiological aspects ; Quality of Life ; Randomized controlled trial ; Randomized Controlled Trials as Topic ; Spinal cord ; Spinal cord stimulation ; Spinal Cord Stimulation - adverse effects ; Spinal Cord Stimulation - instrumentation ; Spinal Cord Stimulation - methods ; Study Protocol ; Treatment Outcome ; Wireless stimulation ; Wireless Technology - instrumentation
    ISSN: 1745-6215
    E-ISSN: 1745-6215
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 10
    Language: English
    In: BMC medicine, 2010-11-18, Vol.8 (1), p.74-74
    Description: An accident or a catastrophic disease may occasionally lead to brain death (BD) during pregnancy. Management of brain-dead pregnant patients needs to follow special strategies to support the mother in a way that she can deliver a viable and healthy child and, whenever possible, also be an organ donor. This review discusses the management of brain-dead mothers and gives an overview of recommendations concerning the organ supporting therapy. To obtain information on brain-dead pregnant women, we performed a systematic review of Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The collected data included the age of the mother, the cause of brain death, maternal medical complications, gestational age at BD, duration of extended life support, gestational age at delivery, indication of delivery, neonatal outcome, organ donation of the mothers and patient and graft outcome. In our search of the literature, we found 30 cases reported between 1982 and 2010. A nontraumatic brain injury was the cause of BD in 26 of 30 mothers. The maternal mean age at the time of BD was 26.5 years. The mean gestational age at the time of BD and the mean gestational age at delivery were 22 and 29.5 weeks, respectively. Twelve viable infants were born and survived the neonatal period. The management of a brain-dead pregnant woman requires a multidisciplinary team which should follow available standards, guidelines and recommendations both for a nontraumatic therapy of the fetus and for an organ-preserving treatment of the potential donor.
    Subject(s): Brain ; Brain Death ; Brain Injuries - complications ; Brain Injuries - mortality ; Care and treatment ; Coma ; Delivery, Obstetric - methods ; Donation of organs, tissues, etc ; Female ; Health aspects ; Humans ; Injuries ; Life ; Nervous system ; Pregnancy ; Pregnancy Complications ; Pregnant women ; Surgery ; Tissue and Organ Procurement ; Usage
    ISSN: 1741-7015
    E-ISSN: 1741-7015
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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