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  • 151. Tisch, S
    et al.
    Zrinzo, L
    Limousin, P
    Bhatia, K P
    Quinn, N
    Ashkan, K
    Hariz, M
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Effect of electrode contact location on clinical efficacy of pallidal deep brain stimulation in primary generalised dystonia.2007In: Journal of neurology, neurosurgery, and psychiatry, ISSN 1468-330X, Vol. 78, no 12, p. 1314-1319Article in journal (Other academic)
  • 152. Tisch, Stephen
    et al.
    Limousin, Patricia
    Rothwell, John C
    Asselman, Peter
    Quinn, Niall
    Jahanshahi, Marjan
    Bhatia, Kailash P
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Changes in blink reflex excitability after globus pallidus internus stimulation for dystonia.2006In: Mov Disord, ISSN 0885-3185, Vol. 21, no 10, p. 1650-5Article in journal (Refereed)
  • 153. Tisch, Stephen
    et al.
    Rothwell, John C
    Bhatia, Kailash P
    Quinn, Niall
    Zrinzo, Ludvic
    Jahanshahi, Marjan
    Ashkan, Keyoumars
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Limousin, Patricia
    Pallidal stimulation modifies after-effects of paired associative stimulation on motor cortex excitability in primary generalised dystonia.2007In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 206, no 1, p. 80-85Article in journal (Other academic)
  • 154. Tisch, Stephen
    et al.
    Rothwell, John C
    Limousin, Patricia
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Corcos, Daniel M
    The physiological effects of pallidal deep brain stimulation in dystonia2007In: IEEE transactions on neural systems and rehabilitation engineering, ISSN 1534-4320, E-ISSN 1558-0210, Vol. 15, no 2, p. 166-172Article in journal (Other academic)
  • 155. Tisch, Stephen
    et al.
    Rothwell, John C
    Zrinzo, Ludvic
    Bhatia, Kailash P
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Limousin, Patricia
    Cortical evoked potentials from pallidal stimulation in patients with primary generalized dystonia.2008In: Movement disorders : official journal of the Movement Disorder Society, ISSN 1531-8257, Vol. 23, no 2, p. 265-73Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) of globus pallidus internus (GPi) has emerged as an effective treatment for primary generalized dystonia. However, the physiological mechanisms of improvement are not fully understood. Cortical activity in response to pallidal stimulation was recorded in 6 patients with primary generalized dystonia >6 months after bilateral GPi DBS. Scalp electroencephalogram was recorded using 60 surface electrodes during 10 Hz bipolar pallidal DBS at each electrode contact pair. Anatomical position of the electrode contacts in relation to the GPi, medial medullary lamina and globus pallidus externus (GPe) was determined from the postoperative stereotactic MRI. In all six patients an evoked potential (EP) was observed with average onset latency of 10.9 ms +/- 0.77, peak latency 26.6 ms +/- 1.6, distributed mainly over the ipsilateral hemisphere, maximal centrally. The mean amplitude of this potential was larger with stimulation in posteroventral GPi than in GPe (3.36 microV vs. 0.50 microV, P < 0.0001). The EP was absent in one patient-side, ipsilateral to a previous thalamotomy. Low frequency GPi stimulation produces an EP distributed centrally over the ipsilateral hemisphere. The latency and distribution of the EP are consistent with stimulation of pallidothalamic neurons projecting to the sensorimotor cortex. Because the EP is larger and more consistently present with stimulation of posteroventral GPi than GPe, it may provide a physiological tool to identify contacts within the optimal surgical target.

  • 156. Tripoliti, Elina
    et al.
    Zrinzo, Ludvic
    Martinez-Torres, Irene
    Tisch, Stephen
    Frost, Eleanor
    Borrell, Ellie
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Limousin, Patricia
    Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation.2008In: Movement disorders : official journal of the Movement Disorder Society, ISSN 1531-8257, Vol. 23, no 16, p. 2377-83Article in journal (Refereed)
    Abstract [en]

    Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN-DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off-stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1-minute monologue. Movement was assessed using the UPDRS-III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control.

  • 157.
    Wahlström, Marie Rodling
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rydenhag, Bertil
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Naredi, Silvana
    Department of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Severe traumatic brain injury in pediatric patients: treatment and outcome using an intracranial pressure targeted therapy–the Lund concept2005In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 31, no 6, p. 832-839Article in journal (Refereed)
    Abstract [en]

    Objective: This study evaluated the outcome of treatment according to the Lund concept in children with severe traumatic brain injury and investigated whether the preset goals of the protocol were achieved.

    Design and setting: A two-center retrospective study in neurointensive care units at university hospitals.

    Patients: Forty-one children with severe traumatic brain injury from blunt trauma and arriving at hospital within 24 h after injury. Median age was 8.8 years (range 3 months–14.2 years), Glasgow Coma Scale 7 (3–8), and Injury Severity Score 25 (16–75). All children had pathological findings on initial computed tomography. All developed intracranial hypertension, and survivors required intensive care longer than 72 h.

    Interventions: Treatment according to the principles of the Lund concept.

    Measurements and results: Neurosurgery was required in 46% of the children. Survival rate was 93% and favorable outcome (Glasgow Outcome Score 4 or 5) was 80% at long-term follow-up (median 12 months postinjury, range 2.5–26). The preset physiological and biochemical goals were achieved in over 90% of observations.

    Conclusions: Treating pediatric patients with severe traumatic brain injury, according to the Lund concept, results in a favorable outcome when the protocol is followed.

  • 158.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery. Umeå University, Faculty of Science and Technology, Chemistry.
    Multivariate analyses of proteomic and metabolomic patterns in brain tumors2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Glioblastoma multiforme (GBM) is the most common primary brain tumor. Given the current standard of care, the prognosis for patients diagnosed with this disease is still poor. There consequently exists a need to improve current treatments, as well as to develop new ones. Many obstacles however need to be overcome to facilitate this effort and one of these involves the development of improved methods to monitor treatment effects. At present, the effects of treatment are typically assessed by radiological means several months after its initiation, which is unsatisfactory for a fast growing tumor like GBM. It is however likely that treatment effects can be detected on a molecular level long before radiological response, especially considering many of the targeted therapies that are currently being developed. Biomarkers for treatment efficacy may be of great importance in the future individualization of brain tumor treatment.

    The work presented herein was primarily focused on detecting early effects of GBM treatment. To this end, we designed experiments in the BT4C rat glioma model in which we studied effects of both conventional radiotherapy and an experimental angiogenesis inhibitor, vandetanib. Brain tissue samples were analyzed using a high throughput mass spectrometry (MS) based screening, known as Surface Enhanced Laser Desorption/Ionization - Time of Flight - Mass Spectrometry (SELDI-TOF-MS). The vast amounts of data generated were subsequently analyzed by established multivariate statistical methods, such as Principal Component Analysis (PCA), Partial Least Squares (PLS), and Orthogonal Partial Least Squares (OPLS), developed for analysis of large and complex datasets. In the radiotherapy study we detected a protein spectrum pattern clearly related to tumor progression. We notably observed how this progression pattern was hampered by radiotherapy. The vandetanib study also revealed significant alterations of protein expression following treatment of different durations, both in tumor tissue and in normal brain contralateral to the tumor.

    In an effort to further elucidate the pathophysiology of GBM, particularly in relation to treatment, we collected extracellular fluid (ECF) samples from 11 patients diagnosed with inoperable GBM. The samples were collected by means of stereotactic microdialysis, both from within the contrast enhancing tumor and the brain adjacent to tumor (BAT). Samples were collected longitudinally from each patient in a time span of up to two weeks, during which the patient received the first five fractions of radiotherapy. The ECF samples were then analyzed by Gas Chromatography Mass Spectrometry (GC-MS) to screen them with respect to concentrations of low molecular weight compounds (metabolites). Suitable multivariate analysis strategies enabled us to extract patterns of varying metabolite concentrations distinguishing between samples collected at different locations in the brain as well as between samples collected at different time points in relation to treatment.

    In a separate study, we also applied SELDI-TOF-MS and multivariate statistical methods to unravel possible differences in protein spectra between invasive and non-invasive WHO grade I meningiomas. This type of tumor can usually be cured by surgical resection however sometimes it grows invasively into the bone, ultimately causing clinical problems. This study revealed the possibility to differentiate between invasive and non-invasive benign meningioma based on the expression pattern of a few proteins.

    Our approach, which includes sample analysis and data handling, is applicable to a wide range of screening studies. In this work we demonstrated that the combination of MS screening and multivariate analyses is a powerful tool in the search for patterns related to treatment effects and diagnostics in brain tumors.

  • 159.
    Wibom, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Mörén, Lina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Aarhus, Mads
    Knappskog, Per
    Lund-Johansen, Morten
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Proteomic profiles differ between bone invasive and noninvasive benign meningiomas of fibrous and meningothelial subtype2009In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 94, no 3, p. 321-331Article in journal (Refereed)
    Abstract [en]

    Meningiomas of WHO grade I can usually be cured by surgical resection. However, some tumors may, despite their benign appearance, display invasive growth behavior. These tumors constitute a difficult clinical problem to handle. By histology alone, bone invasive meningiomas may be indistinguishable from their noninvasive counterparts. In this study we have examined the protein spectra in a series of meningiomas in search of protein expression patterns that may distinguish between bone invasive and noninvasive meningiomas. Tumor tissue from 13 patients with fibrous (6 invasive and 7 noninvasive) and 29 with meningothelial (10 invasive and 19 noninvasive) grade I meningiomas were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI). Multivariate statistical methods were applied for data analyses. Comparing the protein spectra from invasive and noninvasive fibrous meningioma we found 22 peaks whose intensities were significantly different between the two groups (P < 0.001). Based on the expression pattern of these peaks we were able to perfectly separate the two entities (area under ROC curve = 1.0). In meningothelial meningioma the same comparison yielded six significantly differentially expressed peaks (P < 0.001), which to a large degree separated the invasive from noninvasive tissue (area under ROC curve = 0.873). By analyzing the protein spectra in benign meningiomas we could differentiate between invasive and noninvasive growth behavior in both fibrous and meningothelial meningiomas of grade I. A possibility for early identification of invasive grade I meningiomas may have a strong influence on the follow-up policy and the issue of early or late radiotherapy.

  • 160.
    Wibom, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Pettersson, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment2006In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 12, p. 1853-1863Article in journal (Refereed)
    Abstract [en]

    Radiotherapy is one of the mainstays of glioblastoma (GBM) treatment. This study aims to investigate and characterise differences in protein expression patterns in brain tumour tissue following radiotherapy, in order to gain a more detailed understanding of the biological effects. Rat BT4C glioma cells were implanted into the brain of two groups of 12 BDIX-rats. One group received radiotherapy (12 Gy single fraction). Protein expression in normal and tumour brain tissue, collected at four different time points after irradiation, were analysed using surface enhanced laser desorption/ionisation - time of flight - mass spectrometry (SELDI-TOF-MS). Mass spectrometric data were analysed by principal component analysis (PCA) and partial least squares (PLS). Using these multivariate projection methods we detected differences between tumours and normal tissue, radiation treatment-induced changes and temporal effects. 77 peaks whose intensity significantly changed after radiotherapy were discovered. The prompt changes in the protein expression following irradiation might help elucidate biological events induced by radiation. The combination of SELDI-TOF-MS with PCA and PLS seems to be well suited for studying these changes. In a further perspective these findings may prove to be useful in the development of new GBM treatment approaches.

  • 161.
    Wibom, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Vandetanib alters the protein pattern in malignant glioma and normal brain in the BT4C rat glioma model2010In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 37, no 4, p. 879-890Article in journal (Refereed)
    Abstract [en]

    The treatment of glioblastoma is unsatisfactory. Improved understanding of the biological effects of treatment, together with development of new tools to predict outcome of the initiated treatment are therefore of great need. Vandetanib (ZD6474) is mainly a vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) receptor tyrosine kinase inhibitor. This study investigated the pattern of protein expression in brain tumor and normal brain tissue, following treatment with vandetanib in a rat glioma model. BT4C-cells were stereotactically implanted into the brain of BD IX rats. The rats were divided into three different experiments. The treatment schedule for experiments one and two consisted of daily, oral doses of vandetanib from day 6 until day 12 or 20 after implantation, respectively. In the third experiment, each animal received a single dose of vandetanib on day 19 after implantation and was then sacrificed 2, 8 or 24 h thereafter. The protein expression profiles were analyzed by SELDI-TOF-MS and evaluated with multivariate statistical methods. Following treatment with vandetanib, we found significantly altered protein expression pattern in malignant glioma and normal brain. Analyzing protein spectra is an interesting option to assess biological effects induced in brain tissue by signal transduction inhibitors such as vandetanib.

  • 162.
    Wiklund, U
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Niklasson, U
    Bjerle, P
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Elfversson, J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Endoscopic transthoracic sympathicotomy affects the autonomic modulation of heart rate in patients with palmar hyperhidrosis2000In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 142, no 6, p. 691-696Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Palmar hyperhidrosis has been associated with an increased activity of the sympathetic nervous system. The objective of this study was to assess the immediate and long-term effects of endoscopic transthoracic sympathicotomy on the autonomic modulation of the heart rate in patients with palmar hyperhidrosis.

    METHODS: Power spectrum analysis of heart rate variability in the lying position and after passive tilt to the upright position was performed in thirteen patients the day before and after sympathicotomy. A follow-up recording was performed in ten patients approximately six months later. Recordings from 26 healthy subjects were used as a reference group.

    FINDINGS: The patients had a tendency to higher power of the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF; above 0.15 Hz) components than controls in the upright position. After sympathicotomy LF power was reduced, but HF power was unchanged. At follow-up LF power remained at a lower level, but now HF power was reduced.

    INTERPRETATION: Patients with palmar hyperhidrosis have a sympathetic overactivity but also a compensatory high parasympathetic activity. Sympathicotomy results in an initial sympathovagal imbalance with a parasympathetic predominance, which is restored on a long-term basis.

  • 163. Wårdell, Karin
    et al.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Richter, Johan
    Antonsson, Johan
    Eriksson, Ola
    Zsigmond, Peter
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Intracerebral microvascular measurements during deep brain stimulation implantation using laser Doppler perfusion monitoring2007In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 85, no 6, p. 279-286Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate if laser Doppler perfusion monitoring (LDPM) can be used in order to differentiate between gray and white matter and to what extent microvascular perfusion can be recorded in the deep brain structures during stereotactic neurosurgery. An optical probe constructed to fit in the Leksell Stereotactic System was used for measurements along the trajectory and in the targets (globus pallidus internus, subthalamic nucleus, zona incerta, thalamus) during the implantation of deep brain stimulation leads (n = 22). The total backscattered light intensity (TLI) reflecting the grayness of the tissue, and the microvascular perfusion were captured at 128 sites. Heartbeat-synchronized pulsations were found at all perfusion recordings. In 6 sites the perfusion was more than 6 times higher than the closest neighbor indicating a possible small vessel structure. TLI was significantly higher (p < 0.005) and the perfusion significantly lower (p < 0.005) in positions identified as white matter in the respective MRI batch. The measurements imply that LDPM has the potential to be used as an intracerebral guidance tool.

  • 164. Wårdell, Karin
    et al.
    Johansson, Johannes
    Richter, Johan
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Optical measurements for guidance during deep brain stimulation surgery2009In: World Congress on Medical Physics and Biomedical Engineering September 7 - 12, 2009 Munich, Germany: Vol. 25/9 Neuroengineering, Neural Systems, Rehabilitation and Prosthetics / [ed] Dössel, Olaf; Schlegel, Wolfgang C., Springer , 2009, p. 516-517Conference paper (Other academic)
  • 165. Yi, W
    et al.
    Haapasalo, H
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Järvelä, S
    Raheem, O
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age2009In: Clinical Neuropathology, ISSN 0722-5091, Vol. 28, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Three human leucine-rich repeats and immunoglobulin-like domains (LRIG1-3) genes and proteins have recently been characterized. LRIG1 has been shown to be a suppressor of tumor growth by counteracting the signaling of epidermal growth factor receptor (EGFR) family members, including EGFR (ERBB1). Expression of LRIG proteins seems to be of importance in the pathogenesis of astrocytic tumors. In this study, the expression of LRIG1-3 was evaluated in 51 human ependymomas by immunohistochemistry. LRIG proteins were detected in all ependymomas analyzed, however, with a pronounced heterogeneity in expression and subcellular localization. Higher cytoplasmic immunoreactivity of LRIG1 correlated with older patient age and higher LRIG1 nuclear immunoreactivity with lower WHO Grade. LRIG1 displayed a stronger immunoreactivity in the cytoplasm and nuclei in spinal ependymomas than in the posterior fossa or supratentorial ependymomas, while perinuclear LRIG3 was more highly expressed in supratentorial than in infratentorial ependymomas. The indications that expression and subcellular localization of LRIG proteins could be pathogenetically associated with specific clinicopathological features of ependymoma tumors might be of importance in the carcinogeneses and tumor progression of human ependymomas.

  • 166. Yi, Wei
    et al.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Öhman, Kjell
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Percutaneous biopsy of cavernous sinus tumour via the foramen ovale2009In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, no 4, p. 401-407Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tumours involving the cavernous sinus may be challenging to neurosurgeons and neuro-oncologists to treat. Operation may be hazardous for lesions in this area, radical resection is seldom obtained, and other treatments are often needed. Different types of tumour occur at this location. Radiological examination may not be diagnostic so that a histopathological diagnosis is often needed before treatment can be recommended for the individual patient. If surgical resection is less feasible a biopsy will be necessary. CONCLUSION: We describe a technique for image-guided percutaneous biopsy through the oval foramen ovale and its use in two patients with a cavernous sinus tumour. We also describe and highlight the importance of pre- and intraoperative CT imaging in obtaining a safe and conclusive biopsy.

  • 167. Yi, Wei
    et al.
    Liu, Renzhong
    Chen, Jian
    Tao, Shengzhong
    Humphrey, Okechi
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Trauma infant neurologic score predicts the outcome of traumatic brain injury in infants2010In: Pediatric Neurosurgery, ISSN 1016-2291, E-ISSN 1423-0305, Vol. 46, no 4, p. 259-266Article in journal (Refereed)
    Abstract [en]

    To investigate the clinical features of infancy traumatic brain injury (TBI) and the prognostic value of the Trauma Infant Neurologic Score (TINS), infants < 2 years of age with TBI who were admitted from 2000 to 2007 were retrospectively studied. Fifty-six patients with a mean age of 13.3 ± 6.5 months (range = 2-24) were identified. The clinical diagnoses, in terms of the severest injury, included scalp hematomas (n = 2), skull bone fractures (n = 3), epidural hematomas (n = 21), subdural hematomas (n = 14), cerebral contusion and laceration (n = 4), intracerebral hematomas (n = 7), traumatic subarachnoid hemorrhage (n = 2), diffuse axonal injury (n = 2) and diffuse brain swelling (n = 1). The most common clinical presentations were vomiting (66.1%), paleness (55.4%), irritability (37.3%), pupillary abnormalities (35.7%) and altered consciousness (32.1%). The mechanism of injury included falls (n = 41), vehicle accident (n = 9), abuse (n = 4) and unknown (n = 2). The TINS score ranged from 1 to 10 with a mean of 3.6 (SD = 2.4) in the whole patient cohort. The Children's Coma Scores (CCS) on admission were 13-15 (n = 31), 9-12 (n = 7) and 3-8 (n = 18). Thirty-nine of the infants were operated on and the other 17 infants were treated nonsurgically. Forty-eight patients (86%) were followed up for a period of 1-8 years (mean = 4.4) after discharge. In the followed-up patient cohort, the mean TINS score at admission was 3.8 ± 2.5. The total clinical outcome, according to the Glasgow Outcome Scale (GOS), was: 37 (77.1%) good recovery, 4 (8.3%) moderately disabled, 1 (2.1%) vegetative and 6 (12.5%) dead. For those who were operated on the outcome was: 25 (78.1%) good recovery, 4 (12.5%) moderately disabled and 3 (9.4%) dead, and for those who were not operated on: 12 (75.0%) good recovery, 1 (6.3%) vegetative and 3 (25.0%) dead. At two years of follow-up, the GOS included 34 (73.9%) good recovery, 3 (6.5%) moderately disabled, 2 (4.3%) severely disabled, 1 (2.2%) vegetative and 6 (13.0%) dead. Statistical tests revealed that the TINS scores were highly associated with the GOS. Higher TINS scores resulted in worse clinical outcome. The CCS scores were also to some degree associated with the GOS score. However, the CCS score on admission was not as discriminating as TINS, predicting only the best and worst outcome in our series. Our study showed that the clinical features of TBI in infants were different from those seen in adults regarding both the distribution of the pathology type and the clinical presenting symptoms. We found that the TINS scoring system is useful for predicting prognosis and outcome in infancy TBI and suggest that it could be routinely used in the infantile population.

  • 168.
    Zrinzo, Ludvic
    et al.
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, United Kingdom.
    Foltynie, Thomas
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, United Kingdom.
    Limousin, Patricia
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, United Kingdom.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Image-guided and image-verified deep brain stimulation2013In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 28, no 2, p. 254-254Article in journal (Refereed)
  • 169. Zrinzo, Ludvic
    et al.
    van Hulzen, Arjen L J
    Gorgulho, Alessandra A
    Limousin, Patricia
    Staal, Michiel J
    De Salles, Antonio A F
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Avoiding the ventricle: a simple step to improve accuracy of anatomical targeting during deep brain stimulation2009In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 110, no 6, p. 1283-1290Article in journal (Refereed)
    Abstract [en]

    OBJECT: The authors examined the accuracy of anatomical targeting during electrode implantation for deep brain stimulation in functional neurosurgical procedures. Special attention was focused on the impact that ventricular involvement of the electrode trajectory had on targeting accuracy. METHODS: The targeting error during electrode placement was assessed in 162 electrodes implanted in 109 patients at 2 centers. The targeting error was calculated as the shortest distance from the intended stereotactic coordinates to the final electrode trajectory as defined on postoperative stereotactic imaging. The trajectory of these electrodes in relation to the lateral ventricles was also analyzed on postoperative images. RESULTS: The trajectory of 68 electrodes involved the ventricle. The targeting error for all electrodes was calculated: the mean +/- SD and the 95% CI of the mean was 1.5 +/- 1.0 and 0.1 mm, respectively. The same calculations for targeting error for electrode trajectories that did not involve the ventricle were 1.2 +/- 0.7 and 0.1 mm. A significantly larger targeting error was seen in trajectories that involved the ventricle (1.9 +/- 1.1 and 0.3 mm; p < 0.001). Thirty electrodes (19%) required multiple passes before final electrode implantation on the basis of physiological and/or clinical observations. There was a significant association between an increased requirement for multiple brain passes and ventricular involvement in the trajectory (p < 0.01). CONCLUSIONS: Planning an electrode trajectory that avoids the ventricles is a simple precaution that significantly improves the accuracy of anatomical targeting during electrode placement for deep brain stimulation. Avoidance of the ventricles appears to reduce the need for multiple passes through the brain to reach the desired target as defined by clinical and physiological observations.

  • 170.
    Zrinzo, Ludvic
    et al.
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Yoshida, Fumiaki
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thornton, John
    UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Foltynie, Thomas
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Yousry, Tarek A.
    UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK .
    Limousin, Patricia
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Clinical safety of brain magnetic resonance imaging with implanted deep brain stimulation hardware: large case series and review of the literature2011In: World Neurosurgery, ISSN 1878-8750, Vol. 76, no 1-2, p. 164-172Article in journal (Refereed)
    Abstract [en]

    Background: Over 75,000 patients have undergone deep brain stimulation (DBS) procedures worldwide. Magnetic resonance imaging (MRI) is an important clinical and research tool in analyzing electrode location, documenting postoperative complications, and investigating novel symptoms in DBS patients. Functional MRI may shed light on the mechanism of action of DBS. MRI safety in DBS patients is therefore an important consideration.

    Methods: We report our experience with MRI in patients with implanted DBS hardware and examine the literature for clinical reports on MRI safety with implanted DBS hardware.

    Results: A total of 262 MRI examinations were performed in 223 patients with intracranial DBS hardware, including 45 in patients with an implanted pulse generator. Only 1 temporary adverse event occurred related to patient agitation and movement during immediate postoperative MR imaging. Agitation resolved after a few hours, and an MRI obtained before implanted pulse generator implantation revealed edema around both electrodes. Over 4000 MRI examinations in patients with implanted DBS hardware have been reported in the literature. Only 4 led to adverse events, including 2 hardware failures, 1 temporary and 1 permanent neurological deficit. Adverse neurological events occurred in a unique set of circumstances where appropriate safety protocols were not followed. MRI guidelines provided by DBS hardware manufacturers are inconsistent and vary among devices.

    Conclusions: The importance of MRI in modern medicine places pressure on industry to develop fully MRI-compatible DBS devices. Until then, the literature suggests that, when observing certain precautions, cranial MR images can be obtained with an extremely low risk in patients with implanted DBS hardware.

  • 171. Zrinzo, Ludvic
    et al.
    Zrinzo, Laurence V
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    The pedunculopontine and peripeduncular nuclei: a tale of two structures.2007In: Brain : a journal of neurology, ISSN 1460-2156, Vol. 130, no Pt 6, p. e73; author reply e74-Article in journal (Refereed)
  • 172. Zrinzo, Ludvic
    et al.
    Zrinzo, Laurence V
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    The peripeduncular nucleus: a novel target for deep brain stimulation?2007In: NeuroReport, ISSN 0959-4965, E-ISSN 1473-558X, Vol. 18, no 12, p. 1301-2Article in journal (Refereed)
    Abstract [en]

    The pedunculopontine nucleus, a promising new target for deep brain stimulation in Parkinson's disease, straddles the pontomesencephalic junction--unfamiliar territory to most functional neurosurgeons. This contribution reviews the anatomy of the pedunculopontine and peripeduncular nuclei. Given the reported findings of Mazzone et al. in NeuroReport, the authors postulate that the peripeduncular nucleus might be of previously unexpected clinical relevance.

  • 173. Zrinzo, Ludvic
    et al.
    Zrinzo, Laurence V
    Tisch, Stephen
    Limousin, Patricia Dowsey
    Yousry, Tarek A
    Afshar, Farhad
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Stereotactic localization of the human pedunculopontine nucleus: atlas-based coordinates and validation of a magnetic resonance imaging protocol for direct localization.2008In: Brain : a journal of neurology, ISSN 1460-2156, Vol. 131, no Pt 6, p. 1588-98Article in journal (Refereed)
    Abstract [en]

    The pedunculopontine nucleus (PPN) is a promising new target for deep brain stimulation (DBS) in parkinsonian patients with gait disturbance and postural instability refractory to other treatment modalities. This region of the brain is unfamiliar territory to most functional neurosurgeons. This paper reviews the anatomy of the human PPN and describes novel, clinically relevant methods for the atlas-based and MRI-based localization of the nucleus. These two methods of PPN localization are evaluated and compared on stereotactic MRI data acquired from a diverse group of 12 patients undergoing implantation of deep brain electrodes at sites other than the PPN. Atlas-based coordinates of the rostral and caudal PPN poles in relation to fourth ventricular landmarks were established by amalgamating information sourced from two published human brain atlases. These landmarks were identified on acquired T1 images and atlas-derived coordinates used to plot the predicted PPN location on all 24 sides. Images acquired using a specifically modified, proton-density MRI protocol were available for each patient and were spatially fused to the T1 images. This widely available and rapid protocol provided excellent definition between gray and white matter within the region of interest. Together with an understanding of the regional anatomy, direct localization of the PPN was possible on all 24 sides. The coordinates for each directly localized nucleus were measured in relation to third and fourth ventricular landmarks. The mean (SD) of the directly localized PPN midpoints was 6.4 mm (0.5) lateral, 3.5 mm (1.0) posterior and 11.4 mm (1.2) caudal to the posterior commissure in the anterior commissure-posterior commissure plane. For the directly localized nucleus, there was similar concordance for the rostral pole of the PPN in relation to third and fourth ventricular landmarks (P>0.05). For the caudal PPN pole, fourth ventricular landmarks provided greater concordance with reference to the anteroposterior coordinate (P<0.001). There was a significant difference between localization of the PPN poles as predicted by atlas-based coordinates and direct MRI localization. This difference affected mainly the rostrocaudal coordinates; the mean lateral and anteroposterior coordinates of the directly localized PPN poles were within 0.5 mm of the atlas-based predicted values. Our findings provide simple, rapid and precise methods that are of clinical relevance to the atlas-based and direct stereotactic localization of the human PPN. Direct MRI localization may allow greater individual accuracy than that afforded by atlas-based coordinates when localizing the human PPN and may be relevant to groups evaluating the clinical role of PPN DBS.

  • 174.
    Ågren-Wilsson, A
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lekman, A
    Sjöberg, W
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Rosengren, L
    Blennow, K
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus2007In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 116, no 5, p. 333-339Article in journal (Refereed)
    Abstract [en]

    BACKGROUND To evaluate cerebrospinal fluid (CSF) markers for neuronal degeneration and demyelination in idiopathic normal pressure hydrocephalus (INPH), subcortical arteriosclerotic encephalopathy (SAE), and neurologically healthy subjects.

    METHODS Lumbar CSF concentrations of sulfatide, neurofilament protein light (NFL), total-tau (T-tau), hyperphosphorylated tau (P-tau), and beta-amyloid(1-42) (Abeta42) were analyzed in 62 INPH patients, 26 SAE patients, and 23 neurologically healthy controls. In INPH patients, samples before and after shunt surgery were analysed.

    RESULTS The CSF concentration of NFL was elevated in INPH and SAE compared with the controls, and levels of T-tau, P-tau, and Abeta42 were lower in INPH compared with SAE and controls. No difference was seen for sulfatide. All markers except Abeta42 were significantly elevated after shunt surgery.

    CONCLUSIONS The most striking finding was the power of the combined pattern of NFL, P-tau, and Abeta42 in distinguishing between the clinical diagnoses of INPH, SAE, and neurologically healthy elderly.

  • 175.
    Ågren-Wilsson, Aina
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, L-O D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Brain energy metabolism and intracranial pressure in idiopathic adult hydrocephalus syndrome2005In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, no 8, p. 1088-1093Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance. OBJECTIVE: To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter. METHODS: A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate. RESULTS: When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p < 0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage. CONCLUSIONS: Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.

  • 176. Åström, Mattias
    et al.
    Tripoliti, Elina
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Zrinzo, Ludvic U
    Martinez-Torres, Irene
    Limousin, Patricia
    Wårdell, Karin
    Patient-specific model-based investigation of speech intelligibility and movement during deep brain stimulation2010In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 88, no 4, p. 224-233Article in journal (Refereed)
    Abstract [en]

    Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus.

  • 177. Åström, Mattias
    et al.
    Tripoliti, Elina
    Martinez-Torres, Irene
    Zrinzo, Ludvic U
    Limousin, Patricia
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Wårdell, Karin
    Patient-specific models and simulations of deep brain stimulation for postoperative follow-up2009In: World Congress on Medical Physics and Biomedical Engineering September 7 - 12, 2009 Munich, Germany: Vol. 25/9 Neuroengineering, Neural Systems, Rehabilitation and Prosthetics / [ed] Dössel, Olaf; Schlegel, Wolfgang C., Springer , 2009, p. 331-334Conference paper (Other academic)
  • 178. Åström, Mattias
    et al.
    Zrinzo, Ludvic U
    Tisch, Stephen
    Tripoliti, Elina
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Wårdell, Karin
    Method for patient-specific finite element modeling and simulation of deep brain stimulation.2009In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 47, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS.

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