Ruth Thiex

Object: Fibrinolytic therapy with recombinant tissue plasminogen activator (rtPA) is considered a treatment option in patients with deep-seated intracerebral hemorrhage (ICH). Nevertheless, the results of animal experiments have shown that tPA exerts pleiotropic actions in the brain, including regulation of vasoactivity, amplification of calcium conductance by cleavage of the N-methyl-D-aspartate (NMDA) receptor subunit, and activation of metalloproteinases, which increase excitotoxicity, damage the blood–brain barrier, and worsen edema. The authors investigated whether the noncompetitive NMDA receptor antagonist MK801 can be used as an adjuvant therapy in combination with rtPA to attenuate the unfavorable delayed edema formation and inflammation observed following rtPA therapy in an experimental porcine model of ICH. Methods: Twenty pigs were used in this study; MK801 (0.3 mg/kg) was administered to each pig intravenously immediately after hematoma induction and on the 1st and 3rd day after hematoma induction. Ten of the 20 pigs were randomly assigned to fibrinolytic therapy with rtPA (MK801–tPA group), whereas in the remaining 10 control animals (MK801 group) the hematomas were allowed to follow their natural courses of resorption. The extent of edema formation was evaluated using magnetic resonance (MR) imaging volumetry on Days 0, 4, and 10 after hematoma induction and was compared with histopathological changes found at necropsy. The mean edema volumes in these two groups were also compared with that in the group of nine pigs examined in a preceding experimental series, in which the animals’ hematomas were only treated with rtPA (tPA group). In the 10 animals in the MK801–tPA group, the mean perihematoma edema volume on MR images had not significantly increased by Day 4 (p < 0.08) or Day 10 (p < 0.35) after hematoma induction. In the 10 animals in the MK801 group, the increase in mean perifocal edema size was significant after 4 days (p < 0.001) and nonsignificant after 10 days (p < 0.09). In the nine animals in the tPA group, the mean edema volume significantly increased by Days 4 (p < 0.002) and 10 (p < 0.03). Conclusions: As suggested by the reduction in delayed edema volume and the inflammatory response, MK801 modifies the neurotoxic properties of rtPA but not those of blood degradation products. Possibly, fibrinolytic therapy of ICH is more beneficial if combined with agents such as MK801.

The authors report on a 69-year-old man presenting with progressive leg weakness and gait ataxia over two years. A central intramedullary cord lesion ranging from T8-12 on MR imaging was misdiagnosed as a low-grade glioma and a biopsy was attempted followed by temporary clinical deterioration. Selective spinal angiography revealed a spinal dural arteriovenous (AV) fistula on the left L3 nerve root sheath despite the absence of pathological vessels on MR imaging. The fistula was successfully treated by microsurgical interruption of the arterialised intradural vein. The present case should remind us to include selective spinal angiography in our diagnostic work-up in patients predisposed for spinal dural AV fistula by male sex, advanced age and clinical presentation of slowly progressive sensorimotor symptoms with myelopathy on MR imaging, even in the absence of any pathological vascular structures. Die Autoren stellen einen 69-jährigen Patienten vor, der seit zwei Jahren unter einer progredienten Beinschwäche und Gangstörung litt. In der Magnetresonanztomographie (MRT) fand sich eine zentromedulläre Rückenmarksläsion mit einer Ausdehnung von T8-12. Letztere wurde als niedriggradiges Gliom fehlinterpretiert. Eine auswärts durchgeführte Biopsie des Prozesses zog eine klinische Verschlechterung nach sich. Die selektive spinale Angiographie vermochte den Nachweis einer spinalen duralen arteriovenösen Fistel mit Bezug zur linken Nervenwurzel L3 zu führen, wobei im MRT keine pathologischen Gefäße auffällig waren. Die Fistel wurde erfolgreich behandelt durch die mikrochirurgische Koagulation und Durchtrennung der arterialisierten, intraduralen Vene. Der vorliegende Fall sollte uns daran erinnern, bei Patienten mit männlichem Geschlecht, fortgeschrittenem Alter und dem klinischen Bild langsam progredienter sensomotorischer Symptome und einer Myelopathie im MRT auch bei Fehlen pathologischer Gefäße eine spinale Angiographie in die diagnostische Abklärung mit einfließen zu lassen.

We describe technical pitfalls of a porcine brain injury model for identifying primary and secondary pathological sequelae following brain retraction by brain spatula. In 16 anaesthetised male pigs, the right frontal brain was retracted in the interhemispheric fissure by a brain spatulum with varying pressures applied by the gravitational force of weights from 10 to 70 g for a duration of 30 min. The retracted brain tissue was monitored for changes in intracranial pressure and perfusion of the cortex using a Laser Doppler Perfusion Imager (MoorLDI). To evaluate the extent of oedema and cortical contusions, MRI was performed 30 min and 72 h after brain retraction. Following the MR scan, the retracted brain areas were histopathologically assessed using H&E and Fluoro-Jade B staining for neuronal damage. Sinus occlusion occurred in four animals, resulting in bilateral cortical contusions and extensive brain oedema. Retracting the brain with weights of 70 g (n=4) caused extensive oedema on FLAIR images that correlated clinically with a hemiparesis in three animals. Morphologically, an increased number of Fluoro-Jade B-positive neurons were found. A sequential decrease in weights prevented functional deficits in animals. A retraction pressure applied by 10-g weights (n=7) caused a mean rise in intracranial pressure to 4.0±3.1 mm Hg, and a decrement in mean cortical perfusion from 740.8±41.5 to 693.8±72.4 PU/cm² (P<0.24). A meticulous dissection of the interhemispheric fissure and a reduction of weights to 10 g were found to be mandatory to study the cortical impact caused by brain spatula reproducibly.

Toxic components released from the intracerebral blood clot, such as thrombin and hemoglobin, potentially trigger brain edema formation and therefore favor an early evacuation of the clot. Despite a significant reduction in hematoma size in our porcine model of hematoma induction by injecting autologous blood ICP-controlled into the right frontal white matter with subsequent fibrinolysis using recombinant tissue-plasminogen activator (rt-PA) and aspiration of the liquefied clot (n = 9), local rt-PA promoted delayed perihematomatous edema formation and invoked a substantial inflammatory reaction compared with controls (n = 11). We therefore modified our formerly developed porcine model of intracerebral hemorrhage in removing the hematoma by open craniotomy and suction of the clot in seven animals. The residual hematoma size and extent of perifocal edema were evaluated over 10 days on planimetry of the MRI data, and correlated to the histopathological changes of edema and inflammation found at autopsy. The edema volume on day 4 was significantly less in the surgical group compared with the lysis group (p < 0.03). On day 10, however, the difference in edema size was not statistically significant compared with the lysis group (p < 0.07) and the control group (p < 0.09). The inflammatory response was minor compared with the lysis and control group. In conclusion, despite a significant reduction in hematoma size by surgical removal of the clot, only the inflammatory response, but not the extent of delayed edema can be positively influenced.

Object. Because of the rarity of spinal subdural hematomas (SDHs), the literature offers scarce estimates of the outcome and predictive factors in patients suffering from these lesions. In addition, single-institution surgical series are still lacking. Therefore, the authors retrospectively evaluated the early and long-term functional outcomes measured in eight patients with spontaneous and nonspontaneous spinal SDHs in whom the clot had been evacuated. Methods. The patients' charts were evaluated for origin of the lesion, risk factors, and neurological deficits at symptom onset and at 28 days after extirpation of the spinal SDH. Long-term clinical outcome (Barthel Index [BI]) was evaluated by administering a telephone questionnaire to the patient or a relative. Only one patient with a spontaneous spinal SDH was identified. Four patients were undergoing anticoagulant therapy, and three patients had undergone a previous anesthetic/diagnostic spinal procedure. Twenty-eight days postoperatively, neurological deficits improved in six of eight patients; however, in two of the six patients, the improvement did not allow the patients to become independent again. In two patients, surgery did not affect the complete sensorimotor deficits. In the long-term survivors (median 45 months) a median BI of 55 was achieved. The latency between symptom onset and surgery did not correlate with functional outcome in this series. The preoperative neurological condition and location of the hematoma correlated positively with early and long-term functional outcome. Conclusions. To the best of their knowledge, the present study is the largest single-institutional study of patients with surgically treated spinal SDHs. Despite some postoperative improvement of sensorimotor deficits in most patients, the prognosis is poor because 50% of the patients remain dependent. Their outcome was determined by the preoperative sensorimotor function and spinal level of the spinal SDH.

Comparison of two minimally invasive procedures for the treatment of intracerebral hemorrhage and subsequent lysis with regard to technical implications and clinical outcome of the patients. Retrospective analysis of 126 patients with spontaneous supratentorial intracerebral hemorrhage treated by frame-based (n=53) or frameless (n=75) hematoma aspiration and subsequent fibrinolysis with recombinant tissue plasminogen activator (rt-PA). Data were analysed for the whole group as well as for the two subsets of patients with regard to hematoma reduction, procedure-related complications, and the early and long term clinical outcome of the patients. Functional outcome was rated using the Glasgow Outcome Scale (GOS) and Barthel-Index (median follow-up 178 weeks). The prognostic impact of patient related covariates on the GOS was analysed using logistic regression analysis. 49 out of 126 patients (38.9 %) died, 25 of them in the early postoperative period. Only 22/126 (17.5 %) had a favorable long term outcome (GOS >3). Age > 65 years was significantly (p<0.03, OR 3.6) associated with a higher risk for an unfavorable long term outcome (GOS ≤ 3). Treatment had no impact on outcome. Both techniques were highly effective in reducing the intracerebral blood volume by 75.8±21.4% of the initial hematoma volume in frame-based and 64.8±25.4 % in frameless stereotaxy within 2 days of rt-PA-therapy. Malpositioning of the catheter occurred more often in the frameless group (21.3% vs. 9.4 % in the frame-based procedure) without gaining statistical significance. Frame-based and frameless stereotactic hematoma aspirations with subsequent fibrinolysis are effective in volume reduction of intracerebral hemorrhage with comparable clinical outcome. The frameless procedure is associated with a higher risk for malpositioning of the catheter. Despite effective hematoma reduction with both techniques, the percentage of patients with a good clinical outcome remained limited especially in the elder subpopulation.

Aneurysm configuration and neck morphology are important factors in the decision for cerebral aneurysm therapy, i.e., clipping versus coiling. The aim of our study was to create various aneurysm configurations in a predictable and reproducible way in an animal model. In our recently proposed endovascular approach to produce bifurcation aneurysms in the rabbit, the right common carotid artery (CCA) is surgically exposed and distally ligated, and a sheath is advanced retrogradely into the CCA, the base of which is proximally occluded using a Fogarty balloon. Subsequently, elastase is injected via a microcatheter that is placed directly distal to the balloon and allowed to incubate for 20 min. After removal of the sheath, saccular aneurysms begin to form within 2 weeks. For greater variability in aneurysm size and neck morphology, we modified two parameters of this formerly established elastase-induced aneurysm model—the distance between the balloon and sheath and the level of balloon position—before the elastase was endoluminally incubated in 15 rabbits. Three weeks after aneurysm induction, the size and configuration of the aneurysms were controlled using DSA. Our results confirm that balloon occlusion in the brachiocephalic trunk results in broad-based aneurysms, whereas balloon occlusion in the CCA gives rise to circumscribed aneurysm necks. By increasing the distance between the balloon and sheath, the rabbits developed significantly larger aneurysms. The balloon-sheath distance and the level of balloon occlusion proved to be parameters whose modifications result in predictable and reproducible aneurysm variants that can be used for the testing of endovascular devices.