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Since the beginning of the 20th century, head transplantation (cephalosomatic anastomosis) has been studied in animal models including mice, rats and monkeys. A recently proposed protocol for head transplantation in humans has revived the... more
Since the beginning of the 20th century, head transplantation (cephalosomatic anastomosis) has been studied in animal models including mice, rats and monkeys. A recently proposed protocol for head transplantation in humans has revived the interest for the procedure. However, key elements in the procedure, such as functional spinal cord fusion, sufficient neuroprotection and post-operative pain control are still undocumented. Ethical issues remain concerning the scientific validity of the proposed project as well as general concerns regarding the entire concept of human head transplantation.
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Supplementary material S3. Association between changes in the overall burden of pain and clinical characteristics. (DOCX 31 kb)
Supplementary material S2 - Trigeminal neuralgia patient survey. (DOCX 27 kb)
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Background and Objectives. To investigate the effect of topical and subcutaneous administration of local anesthetics on the inflammatory response to thermal injury in human volunteers. Methods. Sixteen healthy volunteers received... more
Background and Objectives. To investigate the effect of topical and subcutaneous administration of local anesthetics on the inflammatory response to thermal injury in human volunteers. Methods. Sixteen healthy volunteers received identical burn injuries (49°C for 6 minutes) on the right and left calves with a 15 × 25 mm rectangular thermode. Eight subjects had topical 5% EMLA applied before and after burn injury, and another eight subjects were administered subcutaneous 0.5% bupivacaine infiltration before burn injury on the right or left leg. No treatment was applied to the contralateral leg in either group because this served as the control. The dermal response after burn injury in test areas with EMLA or bupivacaine and without treatment was compared 24 hours, 72 hours, 168 hours, and 14 days after burn injury. Results. No significant difference was found in the area of flare, development of blister and ulcerations, or the intensity of inflammation after burn injury between the c...
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The incidence of symptomatic brain metastases in Denmark is about 3500. In the present review, the aetiology, symptomatology, and diagnostic procedures are described. The main topic is a review of current treatments and the evidence for... more
The incidence of symptomatic brain metastases in Denmark is about 3500. In the present review, the aetiology, symptomatology, and diagnostic procedures are described. The main topic is a review of current treatments and the evidence for their efficacy. Treatment of brain metastases rarely cures the patient, the goal is rather to improve the quality of life and prolong survival. Without treatment, the median survival following diagnosis of brain metastases is about one month, with steroid treatment two months, with whole brain irradiation four to six months, and after surgery or stereotactic radiosurgery 10-12 months. A relatively simple treatment scheme based on the number of brain metastases and the overall condition of the patient is provided.
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Primary intracerebral haemorrhage (ICH) is a life threatening condition with a 60-70% risk for dependency or death at one year follow-up. Currently, acute neurointensive care and rehabilitation in a stroke unit is the only treatment that... more
Primary intracerebral haemorrhage (ICH) is a life threatening condition with a 60-70% risk for dependency or death at one year follow-up. Currently, acute neurointensive care and rehabilitation in a stroke unit is the only treatment that can improve survival and functional outcome. Evacuation of hematoma within 72 hours of symptom onset has not proved effective in general, but can be considered for selected patients. The question of whether the prevention of hematoma growth can improve outcome through medical haemostatic treatment needs to be proven in a randomised controlled trial.
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Research Interests: Reflex and Nociception
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Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin state and... more
Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin state and the accessibility of DNA lesions to DNA repair machineries are crucial for the maintenance of genomic stability. Understanding the functional impact of chromatin remodeling on DNA repair in GSCs may lay the foundation for advancing the efficacy of radio-sensitizing therapies. Here, we present the results of a high-content siRNA microscopy screen, revealing the transcriptional elongation factor SPT6 to be critical for the genomic stability and self-renewal of GSCs. Mechanistically, SPT6 transcriptionally up-regulates BRCA1 and thereby drives an error-free DNA repair in GSCs. SPT6 loss impairs the self-renewal, genomic stability and tumor initiating capacity of GSCs. Collectively, our results provide mechanistic insights into how SPT6 regulates DNA repa...
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Rampant genomic instability is a hallmark of glioblastoma (GBM). Despite recent advances in our understanding of this deadly disease, molecular mechanism contributing to treatment resistance are poorly understood. Histone chaperones... more
Rampant genomic instability is a hallmark of glioblastoma (GBM). Despite recent advances in our understanding of this deadly disease, molecular mechanism contributing to treatment resistance are poorly understood. Histone chaperones regulate chromatin structure and gene expression through interaction with histones and RNA polymerase II. Spt6 is a highly conserved transcription elongation factor and histone chaperone. We have identified a novel role of Spt6 in glioblastoma-derived cancer stem-like cells (GSCs) using high-throughput siRNA microscopy-based screening. Our data show that the loss of Spt6 in GSCs, but not their differentiated counterparts (non-GSCs), results in decreased proliferation rates, cell cycle arrest and increased double-strand DNA breaks due to hyper-activation of error-prone non-homologous end-joining DNA repair (NHEJ). Importantly, shRNA-mediated knockdown significantly impairs tumor initiation capacity of GSCs and extends survival of tumor-bearing mice. Our findings indicate an important role of Spt6 in glioblastoma maintenance and resistance to DNA damaging therapies.
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ObjectiveTo determine the diagnostic accuracy and clinical utility of electromagnetic source imaging (EMSI) in presurgical evaluation of patients with epilepsy.MethodsWe prospectively recorded magnetoencephalography (MEG) simultaneously... more
ObjectiveTo determine the diagnostic accuracy and clinical utility of electromagnetic source imaging (EMSI) in presurgical evaluation of patients with epilepsy.MethodsWe prospectively recorded magnetoencephalography (MEG) simultaneously with EEG and performed EMSI, comprising electric source imaging, magnetic source imaging, and analysis of combined MEG-EEG datasets, using 2 different software packages. As reference standard for irritative zone (IZ) and seizure onset zone (SOZ), we used intracranial recordings and for localization accuracy, outcome 1 year after operation.ResultsWe included 141 consecutive patients. EMSI showed localized epileptiform discharges in 94 patients (67%). Most of the epileptiform discharge clusters (72%) were identified by both modalities, 15% only by EEG, and 14% only by MEG. Agreement was substantial between inverse solutions and moderate between software packages. EMSI provided new information that changed the management plan in 34% of the patients, and...
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BackgroundBalancing survival versus risk of inducing functional deficits is a challenge when resecting gliomas in or near eloquent areas. Our objectives were to assess deficits prior to and at 6 and 12 months after awake craniotomies with... more
BackgroundBalancing survival versus risk of inducing functional deficits is a challenge when resecting gliomas in or near eloquent areas. Our objectives were to assess deficits prior to and at 6 and 12 months after awake craniotomies with cortical and subcortical mapping in patients with suspected grade 2 gliomas in eloquent areas. We analyzed whether pre- and intraoperative factors were linked to an increased risk of postoperative deficits.MethodRetrospective study of 92 consecutive patients operated between January 2010 and June 2014. All deficits reported by any healthcare professional and KPS-score preoperatively, immediately postoperatively (day 1–10), at 6 months and 12 months, were analyzed.ResultsA decrease in neurological and or cognitive function was common in the first days after surgery, with a significant improvement at 6 months after surgery and further improvement at 12 months. Immediately after surgery, 33% of the patients had severe deficits compared to 2% prior to surgery; this improved to 9% at 6 months and 3% at 12 months. However, at 12 months, 18% of the patients had new or worsened minor or moderate deficits and only 10% had no deficits compared to 39% prior to surgery. There were only minor changes in KPS. None of the recorded pre/intraoperative factors were found significantly to influence the risk of moderate/severe late postoperative deficits.ConclusionA significant amount of the patients in this study experienced new or worsened neurological and or cognitive deficits during follow-up. We found a higher frequency of deficits than normally reported. This is due to the inclusion of mild deficits, the use of patient-reported data, and our focus on cognitive deficits. Our study indicates that the impact of awake craniotomy with mapping on patient outcome is larger than expected. This in no way negates the use of the technique.
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Glioblastoma ranks among the most lethal cancers with current therapies offering only palliation. Paracrine vascular endothelial growth factor (VEGF) signaling has been targeted using anti-angiogenic agents, whereas autocrine VEGF/VEGF... more
Glioblastoma ranks among the most lethal cancers with current therapies offering only palliation. Paracrine vascular endothelial growth factor (VEGF) signaling has been targeted using anti-angiogenic agents, whereas autocrine VEGF/VEGF Receptor 2 (VEGFR2) signaling is poorly understood. Bevacizumab resistance of VEGFR2-expressing glioblastoma cells prompted interrogation of autocrine VEGF-C-VEGFR2 signaling in glioblastoma. Autocrine VEGF-C/VEGFR2 signaling was functionally investigated using RNA interference and exogenous ligands in patient-derived xenograft lines and primary glioblastoma cell cultures in vitro and in vivo. VEGF-C expression and interaction with VEGFR2 in a matched pre- and post-bevacizumab treatment cohort were analyzed by immunohistochemistry and proximity ligation assay. VEGF-C was expressed by patient-derived xenograft glioblastoma lines, primary cells and matched surgical specimens before and after bevacizumab treatment. VEGF-C activated autocrine VEGFR2 signa...
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Introduction There is a lack of high-quality prospective, systematic studies using independent assessors of outcome of microvascular decompression as treatment for trigeminal neuralgia. Methods Clinical characteristics and outcome data... more
Introduction There is a lack of high-quality prospective, systematic studies using independent assessors of outcome of microvascular decompression as treatment for trigeminal neuralgia. Methods Clinical characteristics and outcome data were recorded prospectively from consecutive classical trigeminal neuralgia patients, using standardized interviews. Degree of neurovascular contact was evaluated by a 3.0 Tesla MRI blinded to symptomatic side. Patients were assessed before and 12 months after surgery by a neurologist. Results Twenty-six men and 33 women completed 12 months follow-up. Forty-one patients (69%) had an excellent outcome (no pain, no medication). Ten (18%) patients had a good outcome. Eight (12%) patients had no improvement or had worsening of pain. MRI showed neurovascular contact with morphological changes in 34 patients (58%). Odds ratio between neurovascular contact with morphological changes and excellent outcome was 4.4 (Cl 1.16-16.26), p = 0.029. Odds ratio between...
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OBJECTIVE The diagnostic accuracy of O-(2-[F]fluoroethyl)-l-tyrosine (FET) PET scanning in detecting the malignant transformation of low-grade gliomas (LGGs) is controversial. In this study, the authors retrospectively assessed the... more
OBJECTIVE The diagnostic accuracy of O-(2-[F]fluoroethyl)-l-tyrosine (FET) PET scanning in detecting the malignant transformation of low-grade gliomas (LGGs) is controversial. In this study, the authors retrospectively assessed the diagnostic potential of FET PET in patients with MRI-suspected malignant progression of LGGs that had previously been treated and the relationship between FET uptake and MRI and molecular biomarkers. METHODS Forty-two patients who had previously undergone surgical or multimodal treatment for a histologically verified LGG were referred for FET PET assessment because of clinical signs and/or MRI findings suggestive of tumor progression. Maximal and mean tumor-to-brain ratios (TBR and TBR, respectively) on FET PET as well as kinetic FET PET parameters (time to peak [TTP] and time-activity curve [TAC]) were determined. Final diagnoses were confirmed histologically. The diagnostic accuracy of FET parameters, separately and combined, for the detection of malign...
Research Interests: Neurosurgery, Magnetic Resonance Imaging, Nuclear medicine, Immunohistochemistry, Positron Emission Tomography, and 15 moreMedicine, Humans, Glioma, Female, Journal Article, Male, Clinical Sciences, Middle Aged, Adult, Retrospective Studies, Reproducibility of Results, Radiopharmaceuticals, Neurosciences, Predictive value of tests, and Neoplasm grading
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Medicine is rapidly changing, both in the level of collective medical knowledge and in how it is being delivered. The increased presence of administrators in hospitals helps to facilitate these changes and ease administrative workloads on... more
Medicine is rapidly changing, both in the level of collective medical knowledge and in how it is being delivered. The increased presence of administrators in hospitals helps to facilitate these changes and ease administrative workloads on physicians; however, tensions sometimes form between physicians and administrators. This situation is based on perceptions from both sides that physicians obstruct cost-saving measures and administrators put profits before patients. In reality, increasing patient populations and changes in health care are necessitating action by hospitals to prevent excessive spending as health care systems become larger and more difficult to manage. Recognizing the cause of changes in health care, which do not always originate with physicians and administrators, along with implementing changes in hospitals such as increased physician leadership, could help to ease tensions and promote a more collaborative atmosphere. Ethically, there is a need to preserve physician autonomy, which is a tenet of medical professionalism, and a need to rein in spending costs and ensure that patients receive the best possible care. Physicians and administrators both need to have a well-developed personal ethic to achieve these goals. Physicians need be allowed to retain relative autonomy over their practices as they support and participate in administrator-led efforts toward distributive justice.
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Patients with medically refractory epilepsy may benefit from resective epilepsy surgery. However even the best centers experience surgical failures. It is therefore important to find techniques that may aid in neurosurgical planning of... more
Patients with medically refractory epilepsy may benefit from resective epilepsy surgery. However even the best centers experience surgical failures. It is therefore important to find techniques that may aid in neurosurgical planning of epileptic focus resection. Recordings of electrical brain activity with EEG during seizures reveal abnormal cortical hypersynchronization. Between seizures the EEG often shows interictal depolarizing phenomena such as spikes reflecting an irritable focus of the brain. In the present study we investigated the effect of intravenous remifentanil on the spike activity in the temporal neocortex and hippocampus. We examined 65 patients with mesial temporal lobe epilepsy during surgery, prior to resection. We used a 20-lead grid on the cortex and a 4-lead strip in the lateral ventricle on the hippocampus. At least two 3-min periods of ECoG were recorded - before and after remifentanil injection. In a number of patients we examined the effect of repeated inje...
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The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating... more
The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven—they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Re...
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Introduction Persistent idiopathic facial pain (PIFP) is a poorly understood chronic orofacial pain disorder and a differential diagnosis to trigeminal neuralgia. To address the lack of systematic studies in PIFP we here report clinical... more
Introduction Persistent idiopathic facial pain (PIFP) is a poorly understood chronic orofacial pain disorder and a differential diagnosis to trigeminal neuralgia. To address the lack of systematic studies in PIFP we here report clinical characteristics and neuroimaging findings in PIFP. Methods Data collection was prospective and standardized in consecutive PIFP patients. All patients underwent 3.0 MRI. Results In a cohort of 53 PIFP patients, the average age of onset was 44.1 years. PIFP was found in more women 40 (75%) than men 13 (25%), p
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Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM),... more
Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator ofRRM2(catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which m...