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OBJECTIVE Diffusion-weighted MRI (DWI) and tractography allows noninvasive mapping of the structural connections of the brain, and may provide important information for neurosurgical planning. The hyperdirect pathway, connecting the subthalamic nucleus (STN) with the motor cortex, is assumed to play a key role in mediating the effects of deep brain stimulation (DBS), which is an effective but poorly understood treatment for Parkinson disease. This study aimed to apply recent methodological advances in DWI acquisition and analysis to the delineation of the hyperdirect pathway in patients with Parkinson disease selected for surgery. METHODS High spatial and angular resolution DWI data were acquired preoperatively from 5 patients with Parkinson disease undergoing DBS. The authors compared the delineated hyperdirect pathways and associated STN target maps generated by 2 different tractography methods: a tensor-based deterministic method, typically available in clinical settings, and an advanced probabilistic method based on constrained spherical deconvolution. In addition, 10 high-resolution data sets with the same scanning parameters were acquired from a healthy control participant to assess the robustness of the tractography results. RESULTS Both tractography approaches identified connections between the ipsilateral motor cortex and the STN. However, the 2 methods provided substantially different target regions in the STN, with the target center of gravity differing by > 1.4 mm on average. The probabilistic method (based on constrained spherical deconvolution) plausibly reconstructed a continuous set of connections from the motor cortex, terminating in the dorsolateral region of the STN. In contrast, the tensor-based method reconstructed a comparatively sparser and more variable subset of connections. Furthermore, across the control scans, the probabilistic method identified considerably more consistent targeting regions within the STN compared with the deterministic tensor-based method, which demonstrated a 1.9-2.4 times higher variation. CONCLUSIONS These data provide a strong impetus for the use of a robust probabilistic tractography framework based on constrained spherical deconvolution, or similar advanced DWI models, in clinical settings. The inherent limitations and demonstrated inaccuracy of the tensor-based method leave it questionable for use in high-precision stereotactic DBS surgery. The authors have also described a straightforward method for importing tractography-derived information into any clinical neuronavigation system, based on the generation of track-density images.

Giant prolactinomas are rare and usually associated with symptoms attributable to hypopituitarism and compression of juxtasellar structures such as the cranial nerves of the cavernous sinus and the optic chiasm. Occasionally, they masquerade as skull base tumors with atypical symptoms. We describe a patient who presented with a low-energy trauma in the neck region that led to the initial diagnosis of a large skull base tumor eroding the cervical vertebrae. After stabilizing surgery, the patient responded to dopamine agonist therapy with normalization of serum prolactin levels and pronounced reduction in tumor volume.

Objectives: We present a rare case of tension pneumocephalus (TP) after head trauma not involving mask ventilation but based on pathological respiration pattern, kussmaul breathing. TP is rare condition and exceptionally rare when positive airway pressure has not been applied. In this particular case, the vacuum and one-valve intracranial effects causing pneumocephalon were instead accentuated by a pathological pattern of respiration due to severe ketoacidosis - a condition not previously reported in the literature., Methods: This is a case report showing a rare cause of pneumocephalon caused by patients own respiration. We retrospectively reviewed the patients' journal to find the cause of his severe pneumocephalon. The patient has not been ventilated and the only cause of TP in this case seems to be his own rapid and pathological breathing caused by ketoacidosis., Conclusion: In the presented case, pathologic deep and rapid respiration exerted additional pressure on the dural fistula allowing ambient air at a pressure above ICP to drive itself into the intracranial space. The loss of CSF from skull base fractures created a void space and relative negative pressure, allowing air to bubble in and fill the void., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Deep brain stimulation has been performed at the Department of Neurosurgery, Aarhus University Hospital (AUH), for 16 years. The risk of infection related to implantable pulse generator (IPG) replacement constitutes a weakness in the long-term DBS treatment., Object: The aim of this study is to investigate the association between risk of infection and number of IPG replacements., Methods: All patients who underwent IPG replacement at the AUH from June 1996 until September 2012 were included in the study, and their medical records were systematically reviewed. The data was analyzed using Fisher's exact test on contingency tables., Results: 220 procedures of IPG replacement were completed on 105 patients who suffered from various movement disorders. Up to 5 IPG changes were registered in a single patient. Thirteen patients incurred infection requiring surgical intervention. Testing for risk of infection associated with number of IPG changes, this study found significantly different infection rates (p = 0.0052). In the groups with 3 and 4 IPG changes, infection rates reached over 20%., Conclusion: This study found significantly different rates of infection related to the number of IPG changes. Further investigation and resources should be directed towards improving the lifespan of IPGs., (© 2014 S. Karger AG, Basel.)

Objectives: To assess the effect of peripheral nerve stimulation on neuropathic testicular pain., Material and Methods: A 30-year-old man with a four-year history of chronic testicular pain following scrotal hydrocele surgery had two percutaneous leads implanted in his groin and low-frequency stimulation of the cutaneous branch of the ilioinguinal and genital branch of the genitofemoral nerves., Result: At seven-month follow-up, the pain intensity had declined from 9/10 to 2/10 on the numeric rating scale., Conclusion: We report the successful implantation of an ilioinguinal and genitofemoral nerve stimulator for sustained suppression of intractable neuropathic testicular pain., (© 2011 International Neuromodulation Society.)

In this article, we report on a rare case of spinal seeding from a cerebral anaplastic oligodendroglioma presenting with signs of medullar compression. We discuss the prevalence, mechanisms and imaging findings of spinal seeding in various gliomas. A suitable clinical treatment and follow up for these patients is suggested.

The Göttingen minipig has been established as a translational research animal for neurological and neurosurgical disorders. This animal has a large gyrencephalic brain suited for examination at sufficient resolution with conventional clinical scanning modalities. The large brain, further, allows use of standard neurosurgical techniques and can accommodate clinical neuromodulatory devises such as deep brain stimulation (DBS) electrodes and encapsulated cell biodelivery devices making the animal ideal for basic scientific studies on neuromodulation mechanisms and preclinical tests of new neuromodulation technology for human use. The use of the Göttingen minipig is economical and does not have the concerns of the public associated with the experimental use of primates, cats, and dogs, thus providing a cost-effective research model for translation of rodent data before clinical trials are initiated., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The intercommissural line joining the anterior and posterior commissures defines stereotactic coordinate systems used in functional neurosurgical procedures. Such coordinate systems are generally accepted in humans and nonhuman primate experimental settings and provide high stereotactic precision and reproducibility. The ethical concern surrounding the use of nonhuman primates has motivated and helped popularize the use of the Göttingen minipig as an alternative experimental model for experimental functional neurosurgery. We investigated the position and variability of the intercommissural line in the minipig brain using in vivo MRI. From these data, standard coordinates for the minipig basal ganglia were estimated. We found the variability of the intercommissural line to be small in the Göttingen minipig and the variability of the basal ganglia structures to the mid-commissural point to be minor.

Advanced and exclusive software solutions are offered to reduce susceptibility artefacts on MRI echo-planar sequences. We present a straightforward surgical technique to reduce the cortical distortion and signal loss that normally occur using diffusion tensor imaging (DTI) of the Göttingen minipig brain. Pronounced pneumatisation of the minipig cranium causes considerable susceptibility artefacts at the air/tissue interface around the frontal sinuses. Five Göttingen minipigs had burr holes drilled through the outer lamina of the skull bilaterally at the level of bregma. The underlying frontal sinuses were filled with a suspension of an MRI-compatible alginate. DTI was obtained before and after placing the medium in the sinus, quantifying the change using mutual information and Wilcoxon's rank-sum test. Fibertracking algorithms were applied to visualize the effect of treatment. We showed that the susceptibility artefacts were reduced at the air, bone and brain interfaces and that major cortical fiberbundles could be reliably visualized. This study demonstrated that DTI fibertracking of cortical bundles in experimental animals with extensive skull pneumatisation is feasible even when advanced software is unavailable.

Background: The Göttingen minipig is increasingly used as an animal model in experimental neuroscience as a much needed alternative to non-human primates. Accurate spatial targeting in this species in vivo is challenging, and most clinically available magnetic resonance imaging (MRI) protocols do not provide sufficient spatial resolution for this purpose. Thus, the aim of this study was to develop an in vivo pre-operative MRI protocol allowing direct visualization of individual nuclei of major interest in the minipig brain., Materials and Methods: Three Göttingen minipigs underwent MRI using an inversion-recovery fast spin-echo sequence that was optimized with regards to the following parameters: inversion time, relaxation time, echo time and spatial and temporal resolution, giving a scan duration acceptable for the tight schedule usually employed in a neurosurgical procedure. The most optimal pulse sequence was applied in 8 Göttingen minipigs and the anatomical structures were identified., Results and Conclusion: High-resolution images with excellent contrast were acquired, presenting negligible geometric distortions. Minor flow artifacts from the large neck vessels generated the most prominent artifact. Determination of coordinates necessary in experimental neurosurgery in the Göttingen minipig was considerably improved with this MRI protocol.

Background: Electron spin resonance (EPR) is used to determine the absorbed dose of alanine dosimeters exposed to clinical photon beams in a solid-water phantom. Alanine is potentially suitable for medical reference dosimetry, because of its near water equivalence over a wide energy spectrum, low signal fading, non-destructive measurement and small dosimeter size., Material and Methods: A Bruker EMX-micro EPR spectrometer with a rectangular cavity and a measurement time of two minutes per dosimeter was used for reading of irradiated alanine dosimeters. Under these conditions a new algorithm based on scaling of known spectra was developed to extract the alanine signal., Results: The dose accuracy, including calibration uncertainty, is less than 2% (k=1) above 4 Gy (n=4). The measurement uncertainty is fairly constant in absolute terms (approximately 30 mGy) and the relative uncertainty therefore rises for dose measurements below 4 Gy. Typical reproducibility is <1% (k=1) above 10 Gy and <2% between 4 and 10 Gy. Below 4 Gy the uncertainty is higher. A depth dose curve measurement was performed in a solid-water phantom irradiated to a dose of 20 Gy at the maximum dose point (d(max)) in 6 and 18 MV photon beams. The typical difference between the dose measured with alanine in solid water and the dose measured with an ion chamber in a water tank was about 1%. A difference of 2% between 6 and 18 MV was found, possibly due to non-water equivalence of the applied phantom., Discussion: Compared to previously published methods the proposed algorithm can be applied without normalisation of phase shifts caused by changes in the g-value of the cavity. The study shows that alanine dosimetry is a suitable candidate for medical reference dosimetry especially for quality control applications.

Large animal neuroscience enables the use of conventional clinical brain imagers and the direct use and testing of surgical procedures and equipment from the human clinic. The greater complexity of the large animal brain additionally enables a more direct translation to human brain function in health and disease. Economical, ethical, scientific and practical issues may on the other hand hamper large animal neuroscience. Large animal neuroscience should therefore either be performed in order to examine large animal species dependent problems or to complement promising small animal basic studies by constituting an intermediate research system, bridging small animal CNS research to the human CNS. We have, accordingly, during the last ten years used the Gottingen minipig to examine neuromodulatory treatment modalities such as stem cell transplantation and deep brain stimulation directed towards Parkinson disease. This has been accomplished by the development of a MPTP-based large animal model of Parkinson disease in the Gottingen minipig and the development of stereotaxic and surgical approaches needed to manipulate the Gottingen minipig CNS. The instituted changes in the CNS can be evaluated in the live animal by brain imaging (PET and MR), cystometry, gait analysis, neurological evaluation and by post mortem examination based on histology and stereological analysis.

Twenty percent of the patients immunosuppressed with cyclosporine A (CsA) develop neurological side effects such as tremor, paresthesias, headache, seizures, visual disorders, paresis, and coma-CsA encephalopathy. The encephalopathy resolves on CsA discharge; autopsies of recovered patients are normal. Characteristic lesions are seen on magnetic resonance imaging (MRI) during the period of encephalopathy. MRI of asymptomatic patients receiving CsA as well as most recovered patients are normal. Several theories of pathogenesis have been proposed, but none has been firmly established. The current placebo-controlled study, blinded to the investigator, was accordingly initiated to elucidate histopathological changes in the brain. Twelve adult Göttingen minipigs were randomized into two groups treated with either low-dose CsA (10 mg/kg/d) or no treatment for 6 months. Behavior, blood pressure, and blood parameters were measured throughout the study. All animals had a cerebral MRI before sacrifice. Three control pigs and one CsA-treated pig died during observation and were excluded from the study. None of the remaining eight pigs displayed behavioral signs or MRI-visible lesions characteristic of CsA encephalopathy. The brains appeared all normal on the gross pathological examination, but microscopy revealed perivascular, meningeal, and neuronal tissue infiltration with granulocytes and mononuclear cells in one CsA-treated pig, while the remaining pigs were without histopathological lesions. Pathological changes were noticed in one out of five CsA-treated animals, corresponding to the percentage of patients treated with CsA who develop CsA encephalopathy. To pursue this finding, two studies, one using CsA 20 mg/kg/d for 6 months and one using CsA 10 mg/kg/d for 12 months, have been initiated.

Purpose: Pulsed dose rate (PDR) brachytherapy is a new treatment option permitting dose distribution optimization in interstitial implants. It possesses the advantage of equipment simplification and radiation protection to the staff, compared to the manually afterloading technique. This study presents the first clinical results from The Finsen Center with PDR-brachytherapy in patients with locally advanced or recurrent gynecologic cancer., Methods and Materials: Between June 1993 and August 1996, 34 patients with gynecologic malignancies (22 pelvic recurrences, 12 primary locally advanced) have been treated with external irradiation, four-field box technique, to 46 Gy/23 fractions, 5 F/week and 192Ir-interstitial PDR-brachytherapy in pulses of 0.6 Gy, one pulse per hour to a total of 30 Gy. The Martinez Universal Perineal Interstitial Template applicator was used for all implantations., Results: The overall complete response rate was 74%. At median 14 months follow-up (range 3-40) 15 patients were alive with no evidence of disease. Seven of 14 patients with a second recurrence or progressive disease were still alive. The overall 1- and 2-year survival was 71% and 63%, respectively. There was no difference in survival probability when stratifying the patients by primary diagnosis (recurrent vs. primary advanced), relapse locations (central vs. central + pelvic wall mass) or treatment volume. Seventeen chronic grade III complications were observed in 10 patients. Large treatment volumes significantly correlated to severe gastrointestinal complications. Fifteen of 17 chronic grade III complications were observed in patients treated for recurrent disease., Conclusion: PDR-brachytherapy in combination with external irradiation is an effective treatment option for patients with locally advanced or recurrent gynecologic cancer, although substantial toxicity is observed in patients with large treatment volumes and recurrent disease.

Background and Purpose: With radiotherapy of anal carcinomas, sphincter preservation can be obtained at survival rates similar to those obtained with radical surgery. By combining external beam irradiation with interstitial irradiation, superiority over standard external irradiation has been obtained. With the introduction of pulsed dose rate equipment, where a single high activity source moves through catheters, a more individualized dose distribution and a further elimination of radiation exposure to the staff can be achieved., Materials and Methods: Between June 1993 and November 1994, 17 patients with anal carcinoma (T1:4, T2:4, T3:6, T4:3) have been treated at the Finsen Center. The treatment consisted of three-field external irradiation 46 Gy/23 fractions with five fractions a week to the anal canal and regional pelvic lymph nodes. Seven to 33 days after completion of external irradiation, the tumorspace was given 25.2 Gy PDR brachytherapy with 42 pulses of 0.6 Gy, one pulse every hour., Results: One isolated local recurrence has been noted 13 weeks after implantation. One additional local recurrence was seen in a patient with concomitant hepatic and inguinal recurrence. In three patients inguinal recurrence had occurred, two of these patients were irradiated without any further evidence of disease, and one patient with a primary advanced tumour, had local failure. So far necrosis has been observed in 13 patients within 1-49 weeks (median 16 weeks) after implantation. Eight of these patients required colostomy. No relation was observed between the number of implanted needles and the occurrence of necrosis., Conclusions: The results indicate that the treatment is highly effective, but with substantial toxicity.