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.

Treatment of acute basilar artery thrombosis with a combination of systemic alteplase and tirofiban, a nonpeptide platelet glycoprotein IIb/IIIa inhibitor: report of four cases.

In four patients with acute basilar artery thrombosis, complete arterial recanalization and good neurologic outcome were achieved with a treatment combining alteplase with tirofiban. In no cases were cerebral or extracerebral hemorrhagic complications observed. Combined fibrinolytic agents and glycoprotein IIb/IIIa inhibitors may have high potential in the treatment of acute cerebrovascular thrombosis.

MR imaging and single-photon emission CT findings after gene therapy for human glioblastoma.

BACKGROUND AND PURPOSE: Our goal was to evaluate MR imaging findings after local intracerebral gene therapy in patients with glioblastoma and differentiate postoperative contrast enhancement phenomena. METHODS: In all, 26 patients with supratentorial single lesion glioblastoma underwent tumor resection and intracerebral injection of murine retroviral vector-producer cells for gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir system. Serial contrast-enhanced MR studies were obtained before treatment and postoperatively on day 1 or 2; weeks 2, 4, 9, 13, 17, 25, and 33; and every 8 weeks thereafter. Iodomethyltyrosine single-photon emission CT (IMT-SPECT) investigations also were performed in selected cases. RESULTS: Twelve patients showed nontumorous enhancement of various intensities after treatment, arising within 18 to 72 hours and persisting at 3 to 10 months. It was characterized by a strong local enhancement up to 20 mm thick, which was initially nodular and later linear along the resection cavity wall and surrounded by massive perifocal edema. This "flare" enhancement had features that clearly differed from those of residual tumor enhancements and benign postsurgical enhancements. The IMT-SPECT investigations showed increased amino acid uptake in patients with enhancement from residual or relapsing tumor, but not in patients with flare. CONCLUSION: After local gene therapy, a unique dynamic, transient perifocal flare enhancement can occur on MR images. IMT-SPECT may help to differentiate between tumorous and nontumorous flare enhancements in patients with enhancing tissue on MR images after gene therapy for glioblastoma.

[Reversible multifocal encephalopathy in fulminant eclampsia]. / Reversible multifokale Enzephalopathie bei fulminanter Eklampsie.

Fulminant eclampsia characterised by the onset of focal neurological signs and convulsions is a rare complication of normal pregnancy in the third trimenon. We report on eight women (22-35 years old) with fulminant eclampsia who were admitted to our hospital due to seizures and central pareses. The patients presented with multifocal lesions involving grey and white matter preferentially of the occipital lobes, as evidenced by neuroimaging. Transcranial Doppler sonography revealed increased cerebral blood flow velocities. Treatment consisted of antihypertensive and anticonvulsive medication and operative termination of pregnancy. The patients normalised within 14 days. Our data show that fulminant eclampsia can induce a severe multifocal encephalopathy that can be reversible when treatment and termination of pregnancy are initiated immediately.

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.

Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy: serial quantitative MRI.

We describe serial studies of focal cortical dysplasia causing temporal lobe seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry of the temporal lobes showed significant left cortical thickening corresponding to an elevated amino-acid uptake in the left temporoparietal and inferior frontal cortex on SPECT using 3-[123I]iodo-alpha-methyl-L-tyrosine (IMT). After 1 year there was severe shrinkage of the left temporal lobe, possibly the result of recurrent complex partial seizures.

Surgical treatment of 50 carotid dissections: indications and results.

PURPOSE: This article analyzes the course of 48 patients with 49 chronic carotid dissections (who were treated surgically at our institution after a median anticoagulation period of 9 months because of a persistent high-grade stenosis or an aneurysm) and the course of one additional patient with acute carotid dissection (who underwent early operative reconstruction 12 hours after onset because of fluctuating neurologic symptoms). METHODS: All medical and surgical records and imaging studies were reviewed retrospectively. All histologic specimens were reevaluated by a single pathologist to assess the cause of dissection. Follow-up of 41 patients (85%) after 70 months (range, 1-190 months) consisted of an examination of the extracranial vessels in the neck by Doppler ultrasound scanning and a questionnaire about the patients' medical history and their personal appraisals of cranial nerve function. RESULTS: Seventy percent of the dissections had developed spontaneously; 18% were caused by trauma; 12% of all patients (22% of the women) had a fibromuscular dysplasia. Indication for surgery was a high-grade persisting stenosis and a persisting or newly developed aneurysm. Flow restoration was achieved by resection and vein graft replacement in 40 cases (80%) and thromboendarterectomy and patch angioplasty in three cases (6%). Gradual dilatation was performed and effective in two cases (4%). Five internal carotid arteries (10%) had to be clipped because dissection extended into the skull base. One patient died of intracranial bleeding. Five patients (10%) experienced the development of a recurrent minor stroke (ipsilateral, 4 patients; contralateral, 1 patient). Cranial nerve damage could not be avoided in 29 cases (58%) but were transient in most of the cases. During follow-up, one patient died of unrelated reasons, and only one patient had experienced the development of a neurologic event of unknown cause. CONCLUSION: Chronic carotid dissection can be effectively treated by surgical reconstruction to prevent further ischemic or thromboembolic complications, if medical treatment for 6 months with anticoagulation failed or if carotid aneurysms and/or high-grade carotid stenosis persisted or have newly developed.

Incidentally discovered pituitary lesions: high frequency of macroadenomas and hormone-secreting adenomas - results of a prospective study.

OBJECTIVE: With increasing use of computed tomography and magnetic resonance imaging, pituitary adenomas are being discovered incidentally with increasing frequency. However, limited data are available concerning the clinical importance and natural history of such 'incicentalomas'. We have undertaken a prospective study to investigate changes in adenoma size and endocrine and visual function in patients with incidentally discovered intrasellar masses. PATIENTS AND METHODS: Our study included 67 patients with incidentalomas of the pituitary gland during a 5-year period (1992-96). 50 of these patients were followed up prospectively over a mean period of 2.7 years. Initially, all patients underwent endocrine testing and ophthalmological examinations as well as magnetic resonance imaging or computed tomography scans. These investigations were repeated after 3 months and then annually. RESULTS: 42 (62.7%) out of 67 patients with incidentalomas had microadenomas whereas 37.3% had macroadenomas. Macroadenomas were found more frequently in men (52.2%). Visual field defects could be documented in 4.5% of the patients. Partial deficiency of anterior pituitary function was present in 14.9%. Eight patients (11.9%) had prolactinomas. An increase in adenoma size was detected in 3.2% of the microadenomas and in 26.3% of the macroadenomas within the follow-up period. CONCLUSION: Macroadenomas and hormone secreting adenomas are not uncommon in patients with pituitary incidentalomas. Macroadenomas should be closely monitored for tumour enlargement. All patients should undergo biochemical assessment and ophthalmological examination, since endocrine dysfunction or visual field defects may be present at the time a pituitary incidentaloma is detected.

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.

Triple spontaneous cervical artery dissection.

A 39-year-old healthy man had several transient ischaemic attacks suggesting left internal carotid artery (ICA) occlusion. There were no vascular risk factors and no preceding trauma. Colour-coded duplex sonography suggested a pseudo-occlusion of the left ICA, and cerebral angiography demonstrated dissection of the left ICA and both vertebral arteries. Angiography 6 months later was completely normal. This underlines the importance of four vessel angiography in young patients with dissections of cervical arteries.

[Iatrogenic arteriovenous fistulas of the vertebral artery after venipuncture of the neck. Vascular surgery treatment and long-term outcome]. / Iatrogene arteriovenöse Fisteln der Arteria vertebralis nach Venenpunktion am Hals. Gefässchirurgische Therapie und Langzeitergebnisse.

Direct puncture of the vertebral artery for angiography has been abandoned since the introduction of angiography catheters. Nowadays puncture of jugular veins for intravenous nutrition or monitoring is the predominant cause of accidental arteriovenous vertebral artery fistulas. We describe the history of four patients with such fistulas and the long-term results after surgical repair.

Reversible brain MRI changes in acyclovir neurotoxicity.

This case report shows reversible brain MRI changes probably associated with acyclovir toxicity. So far, neuroimaging in acyclovir toxicity had been negative or uninformative. A 12-year-old girl developed focal secondary generalizing epileptic fits following 4 weeks of prophylactic administration of acyclovir (3 x 10 mg/kg body weight/day i.v.) on day +22 after allogeneic peripheral blood stem cell transplantation for CML. Infective causes were excluded. Brain MRI demonstrated multiple gadolinium-enhancing areas with impairment of the blood-brain barrier in cortical and subcortical regions. Clinical symptoms and neuroimaging pathology resolved completely within 9 days of acyclovir withdrawal.

Pseudo- and segmental occlusion of the internal carotid artery: a new classification, surgical treatment and results.

OBJECTIVES: Occluded internal carotid arteries imply a high risk of ischaemic complications, but an "occluded" carotid artery is not always totally occluded. Pseudo- and segmental occlusions can be detected angiographically, and increasingly non-invasively, and include a variety of morphologic findings. METHODS AND MATERIALS: 128 patients with pseudo- or segmental occlusion were treated in a 13 year period. Three different types of pseudo- or segmental occlusion were identified. In most cases a subtotal stenosis (near-occlusion) at the carotid bifurcation is the underlying lesion (type I). In approximately 35% the internal carotid artery is totally occluded at the bifurcation, but collaterals prevent downstream occlusion (type II), or retrograde flow from the circle of Willis and ophthalmic artery preserves a patent petrous part and siphon (type III). RESULTS: In 79% patency of the arteries could be restored. Three patients (2.3%) died perioperatively, nine (7%) developed ischaemic stroke (7 ipsilateral, 2 contralateral), one intracerebral haemorrhage. The combined stroke-mortality rate was 8.6%. During follow-up (41 +/- 29.9 months) four patients (4.5%) experienced a stroke (3 ipsilateral, 1 contralateral), one an intracranial (1.1%) haemorrhage and six transient ischaemic attacks (6.7%). The annual ipsilateral stroke rate was 0.9%, the cumulative patency rate of the entire series 78% after 73 months. CONCLUSIONS: Although the surgical management carries an increased risk of complications (stroke, transient ischaemic attacks) compared to conventional carotid endarterectomy it is likely that the stroke risk can be reduced at least for symptomatic patients. Symptomatic internal carotid artery occlusion diagnosed non-invasively should be confirmed angiographically to exclude pseudo- or segmental occlusion.

Intracranial stenoocclusive disease: MR angiography with magnetization transfer and variable flip angle.

PURPOSE: To assess time-of-flight MR angiography that uses magnetization transfer contrast (MTC) pulses, tilted optimized nonsaturating excitation (TONE), and a 256 x 512 image matrix for the detection of small intracranial arteries and for the detection and quantification of intracranial arterial stenoocclusive disease. METHODS: To assess anatomic sensitivity, six interpreters, in a blinded fashion, reviewed the MTC/TONE MR angiograms and selective intraarterial angiograms obtained in 70 patients within a mean interval of 5.5 days (SD, 1.5). In addition, all intracranial angiograms were evaluated with regard to presence and degree of arterial stenosis and anatomic variants. RESULTS: Interobserver correlations for determining vessel length were comparably high for both methods. A strong correlation was found between measurements obtained on MR angiograms and those obtained on intraarterial angiograms. The mean vascular length averaged across all arteries was 34.8 mm (SD, 28.1) on MR angiograms and 53.2 mm (SD, 36.8) on intraarterial angiograms. Forty-one stenoses and occlusions and 30 anatomic variants were identified with intraarterial angiography. All arterial variants and 100% of occluded vessels were graded correctly. Moreover, 80% of stenoses greater than 70% and 88% of stenoses less than 70% were quantified correctly at MR angiography. Specificity for identifying stenotic disease was 99%. CONCLUSION: Despite inferior display of vessel length, MTC/TONE MR angiography with increased spatial resolution was able to show the vast majority of high grade lesions visible at selective intraarterial angiography and may suffice for clinical decision making in many patients.

Cerebral microembolism in patients with Sneddon's syndrome.

BACKGROUND: The pathogenesis of Sneddon's syndrome is unclear. This study addresses the question whether cerebral thromboembolism may be involved in the pathogenesis of the neurologic complications of the disorder. The study consisted of 13 patients with Sneddon's syndrome defined by both generalized livedo reticularis and a history of one or more cerebrovascular ischemic events; none had clinical or Doppler ultrasonographic evidence of atherosclerosis. METHODS: Transcranial Doppler microembolic monitoring of the middle cerebral artery; blood screening for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies). RESULTS: Five patients (38%) showed clinically silent microembolism at transcranial Doppler monitoring, with individual microembolic event rates of the middle cerebral artery between 2 per hour and 33 per hour. In this group, the time since the last ischemic symptom was significantly shorter than in the eight patients without microemboli. Antiphospholipid antibodies were detected in three patients (23%), all of whom belonged to the microemboli-positive group. CONCLUSIONS: These data suggest that the detectability of both clinically silent cerebral microembolism and antiphospholipid antibodies may provide paraclinical evidence of active disease in patients with Sneddon's syndrome. The results support the notion that an immune-mediated prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization, and/or triggering in situ thrombosis of cerebral vessels, plays a pathogenetic role in the neurologic manifestations of this disorder.

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.

[The hemodynamics and anatomy of the circle of Willis. The technic and clinical value of selective MR angiography]. / Hämodynamik und Anatomie des Circulus Willisi. Technik und klinische Wertigkeit der selektiven MR-Angiographie.

This study evaluates the usefulness of MR angiography in analysing the individual collateral flow dynamics and anatomy of the circle of Willis in 56 patients with high-grade extracranial carotid stenosis or occlusion. Selective MRA of the carotid or vertebrobasilar area was performed by means of presaturation up to the brain-supplying arteries at the level of the middle neck (angled presaturation slabs). Results obtained with selective and non-selective MRA in 56 consecutive patients were compared with the findings at transcranial Doppler ultrasonography and arterial angiography. Ischaemic cerebral infarctions were classified by computerized tomography and correlated with the results of collateral flow analysis: Sensitivity of selective MRA in detecting intracranial collateral flow via anterior or posterior communicating artery was 96 and 97%, respectively; sensitivity in depicting extracranial transorbital flow was lower (71%). Non-selective MRA was 100% sensitive in detecting a non-filling 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. Slow flow infarctions occurred more frequently in patients with transorbital and posterior-to-anterior collateral flow than in patients with collateral flow via anterior communicating artery.

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 Huntington's 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 and 18F-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.

[Quantification of extracranial carotid stenosis. Magnetic resonance angiography and Doppler sonography versus intra-arterial angiography]. / Quantifizierung extrakranieller Karotisstenosen. Magnetresonanzangiographie und Doppler-Sonographie versus intraarterielle Angiographie.

UNLABELLED: To assess various non-invasive techniques for quantifying internal carotid artery CA stenosis, per cent luminal diameter reduction on intraarterial angiograms (IAA) was measured in 63 patients with ICA stenosis or occlusion. These data were compared with independent measurements based on MR-angiography, continuous-wave (cw) Doppler ultrasonography, systolic peak flow velocity and colour Doppler assisted duplex imaging. Correlations with IAA were equally strong for MR angiography, cw Doppler and colour Doppler analysis (0.95; 0.92; 0.92). Positive predictive values for > or = 70% ICA stenosis were lower and negative predictive values were higher for cw Doppler (0.85; 0.92) and colour duplex analysis (0.81; 0.94) than for MR angiography (0.86; 0.88). Statistical analysis showed non-linear correlations between percentage of lumen diameter narrowing and the length of the zone of signal intensity loss (0.72) and maximum systolic peak flow velocity (0.77). CONCLUSION: Several non-invasive methods do compare with IAA in identifying and quantifying high-grade ICA stenosis and may suffice for decisions on treatment.