Albrecht Aulich

Reliability and Validity of Noninvasive Imaging of Internal Carotid Artery Pseudo-Occlusion

BACKGROUND AND PURPOSE Our study evaluated noninvasive tests for the diagnosis of atheromatous internal carotid artery (ICA) pseudo-occlusion. METHODS Twenty patients (17 men, 3 women; mean age +/-SD, 64.3+/-11.6 years) with angiographically proven atheromatous ICA pseudo-occlusion (20 vessels) were prospectively examined with MR angiography (MRA; 2D and 3D time-of-flight techniques), color Doppler-assisted duplex imaging (CDDI) and power-flow imaging (PFI) with and without an intravenous ultrasonic contrast agent. As a control group, 13 patients (13 men; mean+/-SD age, 63.0+/-9.0 years) with angiographically proven ICA occlusion (13 vessels) were studied with the same techniques. For the determination of interobserver agreement (kappa statistics), the findings of each diagnostic technique were read by 2 blinded and independent observers who were not involved in patient recruitment and initial data acquisition. Specificity and sensitivity were calculated for all noninvasive techniques (observer consensus) in comparison to the standard of reference (intra-arterial angiography). RESULTS Interobserver reliabilities were kappa=0.86 for intra-arterial angiography, kappa=0.90 for unenhanced CDDI, kappa=0. 93 for enhanced CDDI, kappa=0.93 for unenhanced PFI, kappa=1.0 for enhanced PFI, kappa=0.93 for 2D MRA, and kappa=0.77 for 3D MRA, respectively (P<0.0001). Specificities and sensitivities were 0.92 and 0.70 for unenhanced CDDI, 0.92 and 0.83 for enhanced CDDI, 0.92 and 0.95 for unenhanced PFI, 1.0 and 0.94 for enhanced PFI, 1.0 and 0.65 for 2D MRA, and 0.89 and 0.47 for 3D MRA, respectively. CONCLUSIONS Advanced ultrasonographic techniques, especially PFI (with only 1 false-positive diagnosis of occlusion in the present series), can provide reliable and valid data to differentiate between ICA pseudo-occlusion and complete occlusion. In contrast, time-of-flight MRA at its present state is not capable of predicting minimal residual flow within a nearly occluded ICA.

Striatal glucose consumption in chorea-free subjects at risk of Huntington's disease.

Controversial data have been reported with regard to the diagnostic value of the positron emission tomographic (PET) measurement of striatal glucose consumption (rCMRGlc) in chorea-free subjects at risk of Huntingtons disease (HD). For further clarification of this issue we measured striatal and cerebellar rCMRGlc in 27 chorea-free subjects at risk of HD, 20 patients with manifest HD and 20 control subjects, using PET and18F-fluorodeoxyglucose. In 6 of the at-risk subjects cerebellar ratios of striatal rCMRGlc were decreased below the corresponding 99% confidence limit determined in the controls. This indicates that the PET measurement of rCMRGlc may, indeed, be valuable in establishing the diagnosis of incipient HD in presymptomatic at-risk subjects.

Progress in carotid artery surgery at the base of the skull

From 1977 to 1984, 752 reconstructions of the supra-aortic arteries were performed at our service. In a group of 31 patients presenting with transient ischemic attacks (13) or minor strokes (15), preoperative multiplane angiograms identified lesions from various causes in extremely high locations (fibromuscular dysplasia, 10; atherosclerosis, 6; traumatic changes, 10; spontaneous dissection, 3; and mycotic aneurysms and others, 4) in 34 internal carotid arteries (aneurysms, 10; and stenosis, 24). Surgery was performed on 30 patients. Flow restoration was achieved by resection and vein graft replacement (20), gradual dilatation (5), thromboendarterectomy (6), and tangential clip for exclusion of a lateral aneurysm (1). Only one patient was treated with an extracranial-intracranial anastomosis because the stenosis extended into the carotid siphon. One patient was treated with heparin. Exposure of the internal carotid artery (ICA) at the base of the skull required dissection of the digastric muscle, careful mobilization of the cranial nerves, and detachment of the styloid process in 29 patients. Partial resection of the mastoid process was helpful in two patients. The carotid bone canal was opened from the lateral side in four cases to allow the most distal anastomosis 1 cm within the carotid canal. Back-bleeding was controlled by a balloon catheter. A shunt was impossible to use and clamping time averaged 62 +/- 40 minutes. Except for one recurrent stroke and two transient ischemic attacks no other neurologic deficits occurred. Cranial nerve damage could not be avoided in 21 cases (nervus recurrens, 7; nervus glossopharyngeus, 16; and nervus facialis, 4) but disappeared clinically within a 1- to 6-month period in all but two. Each surgical patient underwent control angiography, which demonstrated 30 arteries to be patent, two became occluded, and one had an insignificant stenosis. We conclude that standard surgical techniques are unsuitable for repair of highly located lesions of the ICA. Although extracranial-intracranial anastomosis has been proposed in patients with planned ligation of the ICA, the anatomic reconstruction remains advantageous because flow is restored to normal and the source of emboli is eliminated. With the use of a special approach, graft replacement can be performed up to the base of the skull.

Selective MR angiography and intracranial collateral blood flow.

This study evaluates the usefulness of MR angiography (MRA) in analyzing the individual collateral flow dynamics and anatomy of the circle of Willis in patients with high-grade extracranial carotid stenosis or occlusion. Selective MRA of the carotid or vertebrobasilar territory was performed by means of presaturation of up to three of the brain-supplying arteries at the level of the middle or lower neck (angled presaturation slabs). Results obtained with selective and nonselective arterial MRA in 45 consecutive patients were compared with findings at transcranial Doppler ultrasonography and intraarterial angiography, the latter serving as the “gold standard.” Sensitivity of selective MRA in detecting intracranial collateral circulation via the anterior and posterior communicating artery was 95 and 97%, respectively; sensitivity in depicting extracranial to intracranial transorbital flow was lower (67%). Nonselective arterial MRA was 100% sensitive in detecting a nonfilling of the horizontal (A1) segment of the anterior cerebral artery and in identifying an origin of the posterior cerebral artery from the intracranial carotid artery. Visibility of the posterior communicating artery at MRA predicted for pathological collateral flow via this vessel in all cases. We conclude that selective and nonselective MRA of the cerebral arteries as used here is the most powerful noninvasive method to demonstrate collateral circulation via the basal communicating arteries and to identify hemodynamically relevant anatomic variants of the circle of Willis.

Local inflammation and devascularization — in vivo mechanisms of the “bystander effect” in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma

Somatic gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir (HSV-Tk/GCV) system and murine retroviral vector producer cells (VPCs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. The single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral VPC injection for HSV-Tk suicide gene therapy will be presented focused on findings of systematic and close MRI follow-up and a few histological specimens. The data indicate that hemorrhagic necrosis due to endothelial cell transfection mediated vessel necrosis and that local inflammatory immune response occurs frequently after gene therapy. These phenomena seem to be specific because none of the patients of a control group showed any similar features. The prognosis (time to progression, survival) of the patients with “bystander effects” after gene therapy was better, but compared to those patients without bystander effects, they were also privileged by a favorable constellation of prognostic factors. Therefore, the appearance of these neuroradiologic features cannot serve as an indicator for treatment effectiveness and outcome. Cancer Gene Therapy (2001) 8, 843–851

Bleeding Risk of Tirofiban, a Nonpeptide GPIIb/IIIa Platelet Receptor Antagonist in Progressive Stroke: An Open Pilot Study

Background:Glycoprotein (gp) IIb/IIIa-receptor antagonists are highly effective antiplatelet agents with proven efficacy in the treatment of acute coronary and experimental cerebral ischemia. In this study we examined the rate of hemorrhagic transformation and major bleedings in patients with acute stroke treated with tirofiban, a nonpeptide gpIIb/IIIa antagonist. Methods: Eighteen patients with progressively deteriorating acute ischemic stroke were treated with body-weight adjusted intravenous tirofiban for a mean period of 46 h and compared with a matched group of 17 acute ischemic clinically stable stroke patients. Cerebral hemorrhage was assessed by cranial imaging 6–10 days after symptom onset. Results: No major intracranial hemorrhage was observed in either group. Clinically asymptomatic hemorrhagic infarctions type I/II/III were detected in 4/2/0 controls and in 4/1/1 patients of the tirofiban group, respectively (OR = 0.92; 95% CI 0.4–2.5). Clinical outcome scores were not different in both groups (p = 0.18). Conclusions: Tirofiban was not associated with a significantly increased cerebral bleeding rate in acute ischemic stroke. Randomized multicenter studies are needed to further evaluate the safety and efficacy of tirofiban in the treatment of acute stroke.

The role of subclavian-carotid transposition in surgery for supra-aortic occlusive disease

From 1977 through 1985, 1043 patients underwent operation for supra-aortic occlusive disease. One hundred thirty-four of these patients (13%) with 146 lesions of the aortic arch branches (innominate, 25; subclavian, 103; and multiple, 10) had one or more symptoms of subclavian steal (78%), transient ischemic attacks (37%), arm ischemia (37%), and others (7%). However, according to results of a critical prospective neurologic examination, the classic steal syndrome appeared in only 13 patients (10%), vertebrobasilar insufficiency in 32 patients (24%), and hemispheric symptoms in 48 patients (36%). Symptomatic and/or significant internal carotid occlusive disease was present, ipsilateral in 28% and contralateral in 31% of the patients. Other supra-aortic vessels were involved in 49% of the patients. During the same period 192 patients with supra-aortic occlusive disease were treated without surgical intervention for various reasons. Fifty-five patients (27%) were completely asymptomatic except for the presence of reversed flow within the vertebral artery. The surgical approach in 138 operations was extrathoracic (ET) in 71% of patients (innominate artery, 2; subclavian artery, 95; and arch syndrome, 1) and transthoracic (TT) in 29% of patients (innominate artery, 23; subclavian artery, 8; and arch syndrome, 9). Generally, bypass procedures were preferred, but for 72 (71%) of the subclavian lesions subclavian-carotid transposition (SCT) was performed. Three patients had been referred for complications of previous carotid-subclavian bypass. The grafts were removed and vertebral and arm circulation restored by SCT. Carotid end-arterectomy was performed simultaneously (20%) or staged (3%) in 8% of the innominate procedures and 25% of the subclavian reconstructive procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal striatal glucose consumption in two patients with benign hereditary chorea as measured by positron emission tomography.

SummaryPositron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) was used to investigate the regional cerebral metabolic rate of glucose consumption (rCMRGlc) in two patients with benign hereditary chorea (BHC) and 21 normal subjects. Relative and absolute values of cerebellar, striatal, thalamic, and cortical rCMRGlc were within normal limits for both patients with BHC, indicating that the choreic movement disorder encountered in these two patients was not caused by a decrease of energy metabolism in the striatum such as that found regularly in most patients with other forms of chorea (e.g. Huntingtons and Wilsons disease).

Regional Cerebral Glucose Consumption Measured by Positron Emission Tomography in Patients with Unilateral Thalamic Infarction

Regional cerebral glucose consumption (rCMRGlc) was measured in 7 patients with unilateral and isolated thalamic infarctions and 19 normal subjects using 18F-fluorodeoxyglucose and positron

Focal brain lesions in patients with AIDS : aetiologies and corresponding radiological patterns in a prospective study

We report the results of a hospital-based study of 188 consecutive patients seropositive for the human immune deficiency virus type 1 (HIV-1) who presented in a 4-year period (1988–1991) with possible signs or symptoms of first-ever central nervous system disease. Confirmed diagnoses were cerebral toxoplasmosis in 47 patients (25.0%), HIV-1 encephalopathy in 19 (10.1%), progressive multifocal leucoencephalopathy (PML) in 9 (4.8%), cerebral lymphoma in 1 (0.5%), and other conditions in 9 patients (4.8%). Seventy-three subjects (38.8%) showed focal brain lesions on initial computed tomography or magnetic resonance imaging, which were assessed prospectively. Positive predictivity for toxoplasmosis was 100% if multiple lesions occurred in combination with mass effect or contrast enhancement (23 patients), or if at least one space-occupying or enhancing lesion was located in the basal ganglia or the thalamus (26 patients). Solitary lesions with mass effect or contrast enhancement were seen in 26 patients and were caused by cerebral toxoplasmosis in 22 (84.6%). Eight of the 9 PML patients presented with one or more non-enhancing, non-mass lesions, although the predictive value of this pattern was low (47.1% for PML). Thus, in our epidemiological context, certain imaging findings in HIV-1-seropositive patients were highly predictive of cerebral toxoplasmosis. This may differ from findings from other parts of the world where cerebral toxoplasmosis may be less prevalent among HIV-1-infected individuals.