Alain Barth

Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V

Summary. We report on a 34‐year‐old woman whose plasma showed a marked prolongation of thrombin time (TT) (< 200 s) using bovine thrombin. The patient had previously been exposed twice to topical bovine thrombin contained in fibrin glue during cardiac surgery. TT was normal when human thrombin was used as reagent. The patients purified IgG reacted with bovine prothrombin and bovine thrombin in immunoblotting studies but showed virtually no cross‐reaction with human thrombin. In addition, following surgery, factor V clotting activity (FV:C) was reduced to 9% of normal. The inhibitor of bovine thrombin persisted over a period of more than a year, while the level of FV:C progressively returned to normal within this time period.

Isolated infarcts of the pons

Article abstract-We studied 36 patients with MRI-proven isolated acute pontine infarct. Corresponding to the constant territories of intrinsic pontine vessels, infarcts followed a predictable distribution, enabling us to delineate three main syndromes. Twenty-one patients had a ventral pontine infarct. Motor involvement varied from mild hemiparesis (ventrolateral pontine syndrome) to severe hemiparesis with bilateral ataxia and dysarthria (ventromedial pontine syndrome). In addition, three-fourths of the patients had clinical evidence for usually mild tegmental dysfunction. Eleven patients had a tegmental pontine infarct, presenting tegmental signs (eye movement disorders, cranial nerve palsies, sensory disturbances), and mostly mild motor deficits (tegmental pontine syndrome). Only four patients had alternating deficits, and these never corresponded to any of the so-called classic pontine syndromes. Infarcts in the medial and the extreme lateral tegmental territory were never observed in isolation, being always associated with cerebellar or larger (and multiple) infarctions in the posterior circulation. Four patients with a bilateral ventrotegmental pontine infarct presented with acute pseudobulbar palsy, bilateral motor deficits, and tegmental signs. The results of etiologic work-up emphasize the concept of basilar artery branch disease, which was the most common presumed cause of stroke (16/36, 44%). Basilar artery branch disease was particularly associated with large ventral infarcts, severe clinical symptomatology, progressive or fluctuating course, and local recurrence. Presumed small-artery disease (9/36, 25%) was usually associated with small ventral or tegmental infarcts and rapidly improving lacunar syndromes. Large-artery stenosis (8/36, 22%) and cardioembolism (1/36, 3%) were less common than in series of posterior circulation infarcts that include simultaneous pontine and extrapontine lesions. Recovery was good in two-thirds of the patients, the worse outcome being associated with large ventral infarcts. NEUROLOGY 1996;46: 165-175

Diffusion-weighted MRI for monitoring neurovascular interventions.

Abstract Carotid stenting is increasingly considered as treatment for carotid artery disease. A reliable noninvasive method is desirable for assessing the safety of the procedure. Diffusion-weighted MRI (DWI) is sensitive to early brain ischaemia which becoming widely available and might therefore serve this purpose. We prospectively studied 19 patients referred for investigation of carotid artery disease by echo-planar whole-brain DWI before and within 24 h of stenting. The images obtained at a high b value were examined by two independent blinded reviewers for new high-signal areas consistent with ischaemia. We found that 15 patients had no new changes after stenting. One patient showed enlargement of a posterior watershed lesion after the procedure, which correlated with an increase in neurological deficit. Three other patients had presumed small embolic infarcts on DWI; two were asymptomatic and one had weakness at the hand that corresponded to an embolic infarct with a lesion on DWI in the hand notch. There were no false- positive or -negative results on DWI, when compared to clinical findings. DWI is thus a new method that can demonstrate neurologically silent or asymptomatic infants. It can be used to help to assess the safety and efficacy of neurovascular intervention.

Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury

Summary¶Objective. The purpose of the study was to measure the effects of increased inspired oxygen on patients suffering severe head injury and consequent influences on the correlations between CPP and brain tissue oxygen (PtiO2) and the effects on brain microdialysate glucose and lactate. Methods. In a prospective, observational study 20 patients suffering severe head injury (GCS≤8) were studied between January 2000 and December 2001. Each patient received an intraparenchymal ICP device and an oxygen sensor and, in 17 patients brain microdialysis was performed at the cortical-subcortical junction. A 6 h 100% oxygen challenge (FIO2 1.0) (Period A) was performed as early as possible in the first 24 hours after injury and compared with a similar 6 hour period following the challenge (Period B). Statistics were performed using the linear correlation analysis, one sample t-test, as well as the Lorentzian peak correlation analysis. Results. FIO2 was positively correlated with PtiO2 (p<0.0001) over the whole study period. PtiO2 was significantly higher (p<0.001) during Period A compared to Period B. CPP was positively correlated with PtiO2 (p<0.001) during the whole study. PtiO2 peaked at a CPP value of 78 mmHg performing a Lorentzian peak correlation analysis of all patients over the whole study. During Period A the brain microdialysate lactate was significantly lower (p=0.015) compared with Period B. However the brain microdialysate glucose remained unchanged. Conclusion. PtiO2 is significantly positively correlated with FIO2, meaning that PtiO2 can be improved by the simple manipulation of increasing FIO2 and ABGAO2. PtiO2 is positively correlated with CPP, peaking at a CPP value of 78 mmHg. Brain microdialysate lactate can be lowered by increasing PtiO2 values, as observed during the oxygen challenge, whereas microdialysate glucose is unchanged during this procedure. Extension of the oxygen challenge time and measurement of the intermediate energy metabolite pyruvate may clarify the metabolic effects of the intervention. Prospective comparative studies, including analysis of outcome on a larger multicenter basis, are necessary to assess the long term clinical benefits of this procedure.

Silent Cerebral Ischemia Detected by Diffusion-Weighted MRI After Carotid Endarterectomy

BACKGROUND AND PURPOSE Small emboli arising from a friable plaque during carotid endarterectomy (CEA) constitute an important risk of perioperative ischemic complications. To evaluate the incidence and significance of silent cerebral ischemic lesions of embolic origin after CEA, we prospectively examined a series of surgical patients with high-grade carotid stenosis by using diffusion-weighted MRI (DWI). We also tried to correlate postoperative ischemic lesions with the occurrence of sonographic cerebral embolic signals, the presence of plaque ulcerations, and the use of intraoperative shunting. METHODS Of a consecutive series of 53 patients undergoing elective CEA for high-grade carotid stenosis, 48 patients with unchanged postoperative neurological status were prospectively studied with DWI of the brain the day before and the day after the operation. The magnetic resonance images were analyzed by 2 neuroradiologists blinded to the clinical result of the operation. Any new hyperintense signal was interpreted as a postoperative ischemic lesion. RESULTS Forty-six (95.8%) of 48 patients had unchanged postoperative brain DWI. In 2 patients (4.2%), a new single asymptomatic hyperintense signal was observed on the side of the operation. Both lesions were small and presumably of embolic origin. They were not related to sonographic embolic signals, plaque ulcerations, or intraoperative shunting. CONCLUSIONS These results suggest that the incidence of silent ischemic brain lesions of embolic origin after CEA is low and does not correlate with the occurrence of intraoperative sonographic microemboli. They confirm that CEA is a safe procedure that carries a low risk of postoperative cerebral events.

Cell replacement therapy for intracerebral hemorrhage

Intracerebral hemorrhage (ICH), for which no effective treatment strategy is currently available, constitutes one of the most devastating forms of stroke. As a result, developing therapeutic options for ICH is of great interest to the medical community. The 3 potential therapies that have the most promise are cell replacement therapy, enhancing endogenous repair mechanisms, and utilizing various neuroprotective drugs. Replacement of damaged cells and restoration of function can be accomplished by transplantation of cells derived from different sources, such as embryonic or somatic stem cells, umbilical cord blood, and genetically modified cell lines. Early experimental data showing the benefits of cell transplantation on functional recovery after ICH have been promising. Nevertheless, several studies have focused on another therapeutic avenue, investigating novel ways to activate and direct endogenous repair mechanisms in the central nervous system, through exposure to specific neuronal growth factors or by inactivating inhibitory molecules. Lastly, neuroprotective drugs may offer an additional tool for improving neuronal survival in the perihematomal area. However, a number of scientific issues must be addressed before these experimental techniques can be translated into clinical therapy. In this review, the authors outline the recent advances in the basic science of treatment strategies for ICH.

Noninvasive differentiation of meningiomas from other brain tumours using combined111indium-octreotide/99mtechnetium-DTPA brain scintigraphy

SummaryWe have studied prospectively 47 patients with CNS tumours including 16 meningiomas and 33 other tumours using combined111In-octreotide and99mTc-DTPA brain scintigraphy.111In-octreotide scintigraphy was used to image somatostatin receptors (SSR) and99mTc-DTPA scintigraphy was used to assess the integrity of the blood-brain barrier (BBB). A total of 32 tumours (65%) were detected. All SSR positive tumours also had positive99mTc-DTPA scans and all SSR negative tumours were negative on99mTc-DTPA scans. Among the tumours located outside the BBB, all meningiomas and two out of six schwannomas were positive on combined SSR/99mTc-DTPA scintigraphy. Among the tumours located inside the BBB, seven out of nine gliomas grade I–III were negatitve, whereas all glioblastomas were positive. Other positive tumours included one malignant non-Hodgkin lymphoma and two cerebral metastases. SSR scintigraphy alone was non-specific in the diagnosis of meningiomas, as 16 non-meningiomatous tumours also had positive SSR scans probably due to a breakdown of the BBB (excluding the malignant lymphoma). Measuring the tumour-to-background ratio on SSR scans improved specificity, but sensitivity was decreased below 70% because some meningiomas were only slightly positive. Only the ratio of SSR scintigraphy to conventional99mTc-DTPA brain scintigraphy (SSR-to-BS index) allowed a reliable differentiation of meningiomas from other CNS tumours, most notably from schwannomas (sensitivity: 94%; specificity: 100%). Our results support the usefulness of combined SSR and conventional brain scintigraphy in the noninvasive pre-operative diagnosis of meningiomas.

Contribution of the apparent diffusion coefficient in perilesional edema for the assessment of brain tumors

OBJECTIVES Diffusion-weighted MRI is sensitive to molecular motion and has been applied to the diagnosis of stroke. Our intention was to investigate its usefulness in patients with brain tumor and, in particular, in the perilesional edema. METHODS We performed MRI of the brain, including diffusion-weighted imaging and mapping of the apparent diffusion coefficient (ADC), in 16 patients with brain tumors (glioblastomas, low-grade gliomas and metastases). ADC values were determined by the use of regions of interest positioned in areas of high signal intensities as seen on T2-weighted images and ADC maps. Measurements were taken in the tumor itself, in the area of perilesional edema and in the healthy contralateral brain. RESULTS ADC mapping showed higher values of peritumoral edema in patients with glioblastoma (1.75 x 10(-3)mm(2)/s) and metastatic lesions (1.61 x 10(-3)mm(2)/s) compared with those who had low-grade glioma (1.40 x10(-3)mm(2)/s). The higher ADC values in the peritumoral zone were associated with lower ADC values in the tumor itself. CONCLUSIONS The higher ADC values in the more malignant tumors probably reflect vasogenic edema, thereby allowing their differentiation from other lesions.

Contrast-Enhanced 3-D MRA in Decision Making for Carotid Endarterectomy: A 6-Year Experience

Background: Systematic need for angiography in diagnosis of carotid artery stenosis and indication of surgical therapy is still debated. Noninvasive imaging techniques such as MR angiography (MRA) or CT angiography (CTA) offer an alternative to digital subtraction angiography (DSA) and are increasingly used in clinical practice. In this study, we present the radiological characteristics and clinical results of a series of patients operated on the basis of combined ultrasonography (US)/MRA. Methods: This observational study included all the patients consecutively operated for a carotid stenosis in our Department from October 1998 to December 2004. The applied MRA protocol had previously been established in a large correlation study with DSA. DSA was used only in case of discordance between US and MRA. The preoperative radiological information furnished by MRA was compared with intraoperative findings. The outcome of the operation was assessed according to ECST criteria. Results: Among 327 patients, preoperative MRA was performed in 278 (85%), DSA in 44 (13.5%) and CT angiography in 5 (1.5%). Most of DSA studies were performed as emergency for preparation of endovascular therapy or for reasons other than carotid stenosis. Eleven additional DSA (3.3%) complemented US/MRA, mostly because diverging diagnosis of subocclusion of ICA. No direct morbidity or intraoperative difficulty was related to preoperative MRA. Combined mortality/major morbidity rate was 0.9% (3 patients) and minor morbidity rate 5.5% (18 patients). Conclusions: This observational study describes a well-established practice of carotid surgery and supports the exclusive use of non invasive diagnostic imaging for indicating and deciding the operation.

bFGF enhances the protective effects of MK-801 against ischemic neuronal injury in vitro.

The neuroprotective activity of basic fibroblast growth factor (bFGF) in combination with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 was evaluated in organotypic hippocampal slice cultures. Oxygen/glucose deprivation produced neuronal damage which was assessed using propidium iodide fluorescence. Treatment with increasing doses of bFGF demonstrated significant neuroprotection that was optimal at 10 ng ml-t. This effect was diminished at higher concentrations. MK-801, at the optimal concentration of 30 microM, demonstrated greater neuroprotective efficacy than bFGF. However, bFGF significantly enhanced the protection conferred by MK-801 alone. These results suggest that neurotrophic factors such as bFGF may augment the neuroprotective effects of NMDA antagonists against ischemic neuronal injury.