Claudius Thomé

Effect of Intra-Arterial Papaverine on Regional Cerebral Blood Flow in Hemodynamically Relevant Cerebral Vasospasm

Background and Purpose — It remains controversial whether the intra-arterial administration of papaverine (IAP) is effective in reversing vasospasm-associated cerebral hypoperfusion after aneurysmal subarachnoid hemorrhage. The aim of the present study was to continuously assess regional cerebral blood flow (rCBF) during and after IAP with the use of quantitative, bedside thermal diffusion flowmetry. Methods — Eight patients with cerebral vasospasm after subarachnoid hemorrhage (mean flow velocity >120 cm/s; angiographic vessel constriction >33%; hemispheric cerebral blood flow [CBF] <32 mL/100 g per minute) were prospectively entered into the study. Before IAP, thermal diffusion microprobes were implanted into the white matter of each affected vascular territory (n=10) for rCBF monitoring. During and after IAP (300 mg papaverine/50 mL saline over 1 hour), mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, thermal diffusion rCBF (TD-rCBF), and cerebrovascular resistance (CVR) were recorded continuously. Results — IAP significantly increased TD-rCBF from 7.3±1.6 to 37.9±6.6 mL/100 g per minute (mean±SEM), indicating reversal of cerebral hypoperfusion. This TD-rCBF response was dependent on the degree of cerebral vasospasm and reduced perfusion within the vascular territory. Long-term analysis of TD-rCBF, however, demonstrated that this beneficial effect of IAP on cerebral hypoperfusion was only transient: within 3 hours after treatment, TD-rCBF and CVR returned to baseline values. Furthermore, a lack of correlation between transcranial Doppler sonography and thermal diffusion flowmetry suggested that transcranial Doppler sonography is not suited for CBF-based neuromonitoring after IAP. Conclusions — IAP is not effective in permanently reversing cerebral hypoperfusion in patients with cerebral vasospasm. The need to validate alternative therapeutic strategies that seek to improve cerebral perfusion in vasospasm warrants continued development of CBF-based neuromonitoring strategies.

Cortical Perfusion Measurement by Indocyanine-Green Videoangiography in Patients Undergoing Hemicraniectomy for Malignant Stroke

Background and Purpose— Assessment of cerebral perfusion during neurosurgical procedures would be beneficial to identify areas at risk and to guide placement of monitoring probes. Therefore, we have adapted near-infrared indocyanine-green (ICG) videoangiography to assess cortical perfusion intraoperatively. Methods— ICG videoangiography was performed intraoperatively in 6 patients after decompressive hemicraniectomy for middle cerebral artery stroke. Flow maps of cortical perfusion were generated with IC-CALC 1.1 software by calculating the ratio of difference in fluorescence intensity and rise time. Results— Excellent visualization of cerebral arteries, cortical perfusion and collateral circulation via leptomeningeal anastomoses could be demonstrated in all cases. Flow maps revealed high spatial resolution and showed heterogeneous maple-leaf-shaped hypoperfusion. 26.5±13.7% and 29.0±9.1% of the exposed cortical surface (141±18 cm2) demonstrated core and penumbral flow, respectively. Conclusions— ICG videoangiography appears to be a valuable tool to precisely detect relative cortical tissue perfusion. Thus, it may provide useful research data on the pathophysiology of human stroke, help surgeons to maintain adequate brain perfusion intraoperatively, and simplify adequate placement of tissue probes to monitor critically hypoperfused brain tissue.

Characterization of an Anterior Circulation Rat Subarachnoid Hemorrhage Model

BACKGROUND AND PURPOSEnOur aim was to demonstrate the feasibility of an angiographically controlled rat model for the study of macrocirculatory and microcirculatory changes of the anterior intracranial circulation after subarachnoid hemorrhage.nnnMETHODSnSubarachnoid hemorrhage was induced by transorbital injection of 0.3 mL of nonheparinized autologous arterial blood into the chiasmatic cistern. Changes in regional cerebral blood flow were continuously recorded with the use of laser-Doppler flowmetry over the parietal cortex. Angiographic verification of middle cerebral artery diameter was performed by carotid catheterization at baseline and 2 days after injection of blood or artificial cerebrospinal fluid. We monitored intracranial and systemic blood pressure during and after injections.nnnRESULTSnInjection of artificial cerebrospinal fluid in the control group did not change the diameter of the middle cerebral artery. Injection of blood caused a significant arterial narrowing of 17.5%, from 0.37 +/- 0.04 mm to 0.31 +/- 0.04 mm after 2 days (P = .0001). In the control group regional cerebral blood flow decreased to 75.9 +/- 16.8% of preinjection control but quickly recovered to 99.7 +/- 19.4%. Intracranial pressure increased for 5 minutes after the injection to a maximum of 27.3 +/- 8.9 mm Hg, accompanied by a 10% decrease in mean arterial pressure. A fall in cerebral blood flow to 53.1 +/- 26.3% in blood-injected animals that recovered to only 80.7 +/- 16.9% of baseline values during the observation period of 30 minutes was noted. A peak intracranial pressure of 45.7 +/- 11.5 mm Hg occurred 2 minutes after injection with a decrease in mean arterial pressure of 13%, resulting in a markedly lower cerebral perfusion pressure than in the control group.nnnCONCLUSIONSnAn angiographically controlled model of subarachnoid hemorrhage primarily involving the anterior circulation is feasible in the rat. The resulting narrowing of the middle cerebral artery reflects moderate vasospasm and will allow further microcirculatory studies with cranial windows.

Ubiquitin immunoreactivity in cerebrospinal fluid after traumatic brain injury : Clinical and experimental findings

Objective:Recent data indicate that ubiquitin is increased in serum after trauma and might regulate immune functions. Its cellular source is unknown. Because there have been no previous studies after traumatic brain injury (TBI), we determined whether ubiquitin immunoreactivity is increased in cerebrospinal fluid (CSF) after TBI. Design and Setting:Prospective observational study of patients, with a subsequent interventional study of animals. Subjects:The subjects were 14 patients with TBI, five patients with nontraumatic subarachnoid hemorrhage, ten nonneurologic controls, and seven cross-bred swine. Interventions:Standardized TBI. Measurements and Main Results:Ubiquitin immunoreactivity was analyzed by enzyme-linked immunosorbent assay and immunoblotting. Hemolysis was assessed spectrophotometrically. CSF ubiquitin levels (mean ± sd) were 19 ± 3 ng/mL in nonneurologic control patients, 81 ± 48 ng/mL at 7 ± 2 hrs after TBI (p = .002), and at the end of operation in patients with nontraumatic subarachnoid hemorrhage they were 104 ± 68 ng/mL (p = .001). CSF and serum ubiquitin were measured for 7 days in six patients with TBI. In survivors (n = 3), CSF ubiquitin levels progressively recovered, whereas in nonsurvivors (n = 3), the levels increased until death. There was no difference in serum ubiquitin levels between survivors/nonsurvivors and there was no correlation between serum and CSF ubiquitin levels. In swine, CSF ubiquitin levels peaked at 8- to 30-fold higher than baseline at 60 min post-TBI and then declined with a half-life of 1.3 hrs. In CSF with hemolysis, peak ubiquitin levels were five-fold higher than without hemolysis (p < .05). Ubiquitin and hemoglobin correlations in CSF and after in vitro lysis of erythrocytes suggested that erythrolysis could account for no more than 23 ± 16% of the CSF ubiquitin. Conclusions:CSF ubiquitin levels are increased more than four-fold in patients after TBI and nontraumatic subarachnoid hemorrhage. Peak CSF ubiquitin measurements in patients with TBI probably underestimated the actual peak, on the basis of data from the animal model. The progressive rise in CSF ubiquitin in patients with TBI who died suggests that lack of clearance could reflect lethal progression to irreversible brain damage. Erythrolysis is one potential source of CSF ubiquitin.

Biomechanical testing of a polymer-based biomaterial for the restoration of spinal stability after nucleotomy.

BackgroundSurgery for disc herniations can be complicated by two major problems: painful degeneration of the spinal segment and re-herniation. Therefore, we examined an absorbable poly-glycolic acid (PGA) biomaterial, which was lyophilized with hyaluronic acid (HA), for its utility to (a) re-establish spinal stability and to (b) seal annulus fibrosus defects. The biomechanical properties range of motion (ROM), neutral zone (NZ) and a potential annulus sealing capacity were investigated.MethodsSeven bovine, lumbar spinal units were tested in vitro for ROM and NZ in three consecutive stages: (a) intact, (b) following nucleotomy and (c) after insertion of a PGA/HA nucleus-implant. For biomechanical testing, spinal units were mounted on a loading-simulator for spines. In three cycles, axial loading was applied in an excentric mode with 0.5 Nm steps until an applied moment of ± 7.5 Nm was achieved in flexion/extension. ROM and NZ were assessed. These tests were performed without and with annulus sealing by sewing a PGA/HA annulus-implant into the annulus defect.ResultsSpinal stability was significantly impaired after nucleotomy (p < 0.001). Intradiscal implantation of a PGA-HA nucleus-implant, however, restored spinal stability (p < 0.003). There was no statistical difference between the stability provided by the nucleus-implant and the intact stage regarding flexion/extension movements (p = 0.209). During the testing sequences, herniation of biomaterial through the annulus defect into the spinal canal regularly occurred, resulting in compression of neural elements. Sewing a PGA/HA annulus-implant into the annulus defect, however, effectively prevented herniation.ConclusionPGA/HA biomaterial seems to be well suited for cell-free and cell-based regenerative treatment strategies in spinal surgery. Its abilities to restore spinal stability and potentially close annulus defects open up new vistas for regenerative approaches to treat intervertebral disc degeneration and for preventing implant herniation.

Hypothermia Reduces Acute Vasospasm Following SAH in Rats

Subarachnoid hemorrhage (SAH) due to rupture of an aneurysm results in acute brain injury manifesting itself clinically as an acute neurologic deficit. Depending on the severity of the bleeding, the patients are classified according to clinical grading scales. This classification allows estimation of individual prognosis, as the extent of acute injury constitutes the crucial parameter for outcome following SAH. This statement has only recently been confirmed by Proust et al. [8], who reported a favorable outcome after Hunt and Hess grades IV and V in only 10% of cases.

Watertight Dural Closure: Is It Necessary? A Prospective Randomized Trial in Patients with Supratentorial Craniotomies

OBJECTIVE The aim of the current study was to prospectively analyze complication rates and costs associated with dural closure in patients undergoing supratentorial craniotomies, randomized for watertight and adaptive dural closures. METHODS One hundred fifty consecutive patients with supratentorial lesions who were between 18 and 70 years of age were prospectively included. A watertight dural closure was the primary goal (Group A). Whenever this goal could not be achieved, patients were intraoperatively randomized for secondary watertight (Group B) or adaptive dural closure (Group C). Within a follow-up period of 4 weeks, study end points were the occurrence of complications such as subcutaneous fluid collections, impaired wound healing with and without cerebrospinal fluid leakage, and infection. Moreover, we analyzed costs for dural closure for each group separately. RESULTS Of 150 eligible patients, 13 were excluded according to predefined criteria (Group A, n = 3; Group B, n = 7; Group C, n = 3). From those patients, a primary watertight dural closure could be obtained in 44 (29.4%) patients. A secondary watertight dural closure was performed in 53 (35.3%) patients, and an adaptive dural closure was performed in 53 (35.3%) patients. Complications that were related to dural closure or wound closure were found in 7 patients in Group A, 6 patients in Group B, and 12 patients in Group C (all not significant). The mean total costs, based on time and additional material required in Group A (US

Feasibility of intraventricular nicardipine prolonged release implants in patients following aneurysmal subarachnoid haemorrhage.

436 ± 119) or Group B (US

Comparison of different intravascular thread occlusion models for experimental stroke in rats

681 ± 286) were significantly greater compared with adaptive dural closure in Group C (US

Hypoperfusion in the Acute Phase of Subarachnoid Hemorrhage

213 ± 142, P < 0.05). CONCLUSION In supratentorial craniotomies, an adaptive dural closure may represent a safe and cost-effective alternative to watertight dural closure.