Axel Goldammer

Permanent Middle Cerebral Artery Occlusion in Sheep: A Novel Large Animal Model of Focal Cerebral Ischemia

As effective stroke treatment by thrombolysis is bound to a narrow time window excluding most patients, numerous experimental treatment strategies have been developed to gain new options for stroke treatment. However, all approaches using neuroprotective agents that have been successfully evaluated in rodents have subsequently failed in clinical trials. Existing large animal models are of significant scientific value, but sometimes limited by ethical drawbacks and mostly do not allow for long-term observation. In this study, we are introducing a simple, but reliable stroke model using permanent middle cerebral artery occlusion in sheep. This model allows for control of ischemic lesion size and subsequent neurofunctional impact, and it is monitored by behavioral phenotyping, magnetic resonance imaging, and positron emission tomography. Neuropathologic and (immuno)-histologic investigations showed typical ischemic lesion patterns whereas commercially available antibodies against vascular, neuronal, astroglial, and microglial antigens were feasible for ovine brain specimens. Based on absent mortality in this study and uncomplicated species-appropriate housing, long-term studies can be realized with comparatively low expenditures. This model could be used as an alternative to existing large animal models, especially for longitudinal analyses of the safety and therapeutic impact of novel therapies in the field of translational stroke research.

Laser-induced thermotherapy of neoplastic lesions in the brain – underlying tissue alterations, MRI-monitoring and clinical applicability

SummaryLaser-induced thermotherapy (LITT) is a minimally invasive neurosurgical approach to the stereotactic treatment of brain tumors in poorly accessible regions. Its clinical applicability has been shown in several experimental and clinical studies under on-line monitoring by magnetic resonance imaging (MRI). This review characterizes LITT as an alternative neurosurgical approach with specific focus on the typical histological alterations and ultrastructural cellular changes following laser irradiation in the central nervous system. The spatial and temporal pattern of these changes is discussed in their relevance to the neurosurgical treatment of neoplastic lesions using LITT.

Präoperative Bildgebung – Grundlage der navigationsgestützten Neurochirurgie

ZusammenfassungDie bildgestützte Neurochirurgie erfährt mit der Entwicklung von Soft- und Hardware eine sprunghafte Akzeptanz. Zusätzliche Bilddaten dienen der Beurteilung von Charakter und Ausdehnung von pathologischen Prozessen und dem Umgebungsgewebe. In diesem Kontext sind fMRT, SPECT, PET und spezielle Modalitäten der CT- und MRT-Diagnostik zu nennen. Mittels sekundärer Bildbearbeitung können intrazerebrale Läsionen und benachbarte, funktionell eloquente Regionen im parenchymatösen Organ Gehirn prä- und intraoperativ detektiert werden. Die Integration verschiedener Bildinformationen garantiert eine präzise Planung und Realisierung von chirurgischen Manövern. Die Segmentation interessierender Strukturen, von Risikostrukturen und deren Implementation in Systeme der Neuronavigation helfen, eine zusätzliche intraoperative Traumatisierung zu vermeiden, und bieten eine größere Sicherheit und Präzision. Mit diesem Artikel werden der Wert und die Grenzen präoperativer Bilddiagnostik diskutiert.AbstractWith the progressive development of soft- and hardware, the acceptance of image-guided neurosurgery has increased dramatically. Additional image data are required to analyze the nature and the dimensions of pathological processes and the surrounding tissue. In this context, fMRI, SPECT, PET, as well as special modalities of CT and MR imaging, are routinely used. Secondary post-processing options are used to detect intracerebral lesions as well as adjacent functional eloquent regions in the parenchymatous organ pre- and intraoperatively. The integration of different image information guarantees the precise planning and realization of surgical maneuvers. The segmentation of interesting structures and risk structures, as well as their implementation in the neuronavigation systems, help to avoid additional intraoperative traumatization and offer a higher level of safety and precision. In this article the value and limitations of presurgical imaging will be discussed.

Kryotherapie am Hirn – ein neuer methodischer Ansatz

Cryodestruction of tissue is influenced by cooling and thawing rates, absolute tissue temperature, number of freeze-thaw cycles, and type of tissue. However, under clinical conditions a MRT visualization of the temperature distribution during cryo-procedures is not possible. Thus, the extent of necrotic areas within the cryo-influenced regions are not precisely predictable. This limitation is particularly relevant for the application of cryoablation in the brain. The present paper proposes the concept of a local, cryo-induced ischemic necrosis. The basic concept is that the MRT-observable and surgically well-manageable frozen region is ischemic. This cryo-induced ischemia causes a necrosis. The extent of the necrotic region is exclusively determined by the ischemia tolerance of the tissue. The effectiveness of this method is demonstrated on sheep brain in vivo. Compared to the freeze-thaw method, histological examinations show a sharper demarcation between regions of necrosis and healthy tissue. In conclusion, the method of MR-controlled local, cryo-induced ischemia enables an exact definition of the region of necrosis in the brain.

Epidermoid of the retromastoidal region with cutaneous wound infection, fistula and epidural abscess

Epidermoids constitute 0.5% to 1.8% of all intracranial tumor lesions and account for 2% to 6% of all cerebellopontine tumors. Epidermoids as ectodermal remnants within the central nervous system occur when ectodermal rests are included in the developing cranium. As a rule, the cyst contents are of flaky consistency and show a pearly white gross appearance. These benign, developmental, partly bony structures eroding lesions can reach enormous sizes and show a linear growth rate along normal cleavage planes and surround vital structures. The histologic examination of epidermoids confirms stratified squamous epithelium, keratin, cellular debris, and cholesterol. Epidermoids show a low attenuation on CT scans because of the presence of cholesterol and other fatty substances in their desquamated debris and erosion defects depending of adjacent bony structures, but they show no characteristic enhancement after infusion of contrast material. Conventional MRI data (T1and T2-weighted) are relatively nonspecific and do not allow preoperative differentiation of epidermoids from other lesions. Diffusion-weighted imaging can specifically reveal an epidermoid as a strongly hypertense leson, but isn’t routinely available in all cases of emergency. A disadvantage of MRI is the absence of a typical bone signal, making an exact detection of specific involvement of these structures difficult. Normally, patients’ symptoms vary depending on location. Typically, epidermoids of the cerebellopontine angle initially produce trigeminal neuralgia

Properative Bildgebung@@@Preoperative imaging as the basis for image-guided neurosurgery: Grundlage der navigationsgesttzten Neurochirurgie

ZusammenfassungDie bildgestützte Neurochirurgie erfährt mit der Entwicklung von Soft- und Hardware eine sprunghafte Akzeptanz. Zusätzliche Bilddaten dienen der Beurteilung von Charakter und Ausdehnung von pathologischen Prozessen und dem Umgebungsgewebe. In diesem Kontext sind fMRT, SPECT, PET und spezielle Modalitäten der CT- und MRT-Diagnostik zu nennen. Mittels sekundärer Bildbearbeitung können intrazerebrale Läsionen und benachbarte, funktionell eloquente Regionen im parenchymatösen Organ Gehirn prä- und intraoperativ detektiert werden. Die Integration verschiedener Bildinformationen garantiert eine präzise Planung und Realisierung von chirurgischen Manövern. Die Segmentation interessierender Strukturen, von Risikostrukturen und deren Implementation in Systeme der Neuronavigation helfen, eine zusätzliche intraoperative Traumatisierung zu vermeiden, und bieten eine größere Sicherheit und Präzision. Mit diesem Artikel werden der Wert und die Grenzen präoperativer Bilddiagnostik diskutiert.AbstractWith the progressive development of soft- and hardware, the acceptance of image-guided neurosurgery has increased dramatically. Additional image data are required to analyze the nature and the dimensions of pathological processes and the surrounding tissue. In this context, fMRI, SPECT, PET, as well as special modalities of CT and MR imaging, are routinely used. Secondary post-processing options are used to detect intracerebral lesions as well as adjacent functional eloquent regions in the parenchymatous organ pre- and intraoperatively. The integration of different image information guarantees the precise planning and realization of surgical maneuvers. The segmentation of interesting structures and risk structures, as well as their implementation in the neuronavigation systems, help to avoid additional intraoperative traumatization and offer a higher level of safety and precision. In this article the value and limitations of presurgical imaging will be discussed.

Long-term basal forebrain cholinergic-rich graftsderived from trisomy 16 mice do not develop β-AMYLOID pathology and neurodegeneration butdemonstrate neuroinflammatory responses

Patients with Down syndrome (human trisomy 21) develop neuropathological andcholinergic functional defects characteristic of Alzheimers disease, which has been attributed tothe location of the Alzheimer β‐amyloid precursor protein on chromosome 21. Due tothe partial genetic homology between mouse chromosome 16 and human chromosome 21, murinetrisomy 16 was used as a model to study functional links between increased expression of theamyloid precursor protein, neurodegeneration and neuroinflammatory responses. Basal forebraincholinergic‐rich tissue derived from trisomy 16 mice at embryonic age of day 16 was transplantedinto the lateral ventricle of adult normal mice. At 1, 3, 6, 9 and 12 months after transplantation,the grafts were characterized by immunocytochemistry, molecular biological analysis, andstereological methods. Grafts survived up to one year and still demonstrated immunoreactivity forcholinergic, GABAergic and astroglial cells. Though a 1.5‐fold neuronal overexpression ofamyloid precursor protein was detected in brains from trisomy 16 embryos by Northern analysis, β‐amyloid deposits were found neither in control nor trisomic grafts. Detailedstereological analysis of trisomic grafts did not reveal any neurodegeneration or morphologicalchanges of cholinergic and GABAergic neurons during the course of graft maturation up to oneyear, as compared to grafts derived from euploid tissue. However, both euploid and trisomicgrafts demonstrated a strong infiltration with T‐ and B‐lymphocytes and a significant micro‐ andastroglial activation (hypertrophic astrocytes) within and around the grafts. These observationsfurther suggest that the trisomy 16‐induced neurodegeneration is seemingly due to a lack ofneuron supporting factors which are provided by either the metabolic interaction of trisomic graftwith surrounding healthy host tissue or by cells of the immune system infiltrating the graft.

Targeting the Subthalamic Nucleus for Deep Brain Stimulation in Parkinson Disease: The Impact of High Field Strength MRI

Functional neurosurgery is the only surgical alternative treatment for patients with Parkinson’s disease (PD) (Agid, 1999; Benzzouz & Hallett, 2000; Beric et al., 2001; DeLong & Wichmann, 2001; Dowsey-Limousin et al., 2001; Hariz & Fodstad, 2002; Kopper et al., 2003; Krause et al., 2001; Vesper et al., 2002). Dopamine deficiency in Parkinson’s disease leads to increased neuronal activity. Regulation of this overactivity using electrical stimulation of the basal ganglia (deep brain stimulation – DBS) has become an attractive neurosurgical option of alternative treatment strategy (Limousin et al., 1998; Kupsch & Earl, 1999). The subthalamic nucleus (STN) is the key structure for motor control through the basal ganglia and is mostly used as stimulation target since here, all cardinal symptoms of PD can be effectively ameliorated (Anderson et al., 2005; Benabid et al., 1998; Dujardin et al, 2001; Limousin et al., 1998; Martinez-Martin et al., 2002; Koller et al., 2001; Krack et al., 1998; Lopiano et al., 2001; Volkmann et al., 2001). Possible mechanisms of DBS include depolarization blockade, release of local inhibitory neurotransmitters, antidromic activation of inhibitory neurons, and jamming of abnormal neuronal firing patterns. The clinical experiences and practice confirm the beneficial effect of chronic bilateral STN-DBS.