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.

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.

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.

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.

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.

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

Positron 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. Huntington's and Wilson's disease).

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.

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.

Stroke and dolichoectatic intracranial arteries.

During a 6-year-period, in 45 patients the diagnosis of dolichoectatic intracranial arteries was established. Dolichoectasia of the vertebrobasilar system was the most frequent finding (n = 39). Twenty-two patients presented with brain stem ischaemia, and 10 patients had ischaemic hemispheric events. Six patients had symptoms due to compression of cranial nerves. Hydrocephalus was observed once. Peak and mean flow velocities in 39 patients with dolichoectatic basilar arteries as revealed by transcranial Doppler ultrasound were significantly reduced (p less than 0.00001) when compared with an age-adjusted control group of 20 patients without evidence of vertebrobasilar dolichoectasia on angiogram. Non-invasive MR-angiography offered an excellent imaging of the vascular abnormality. The combined use of CT, TCD, MRI and MR-angiography allows reliable non-invasive diagnosis of dolichoectatic intracranial arteries. This condition seems to play an underestimated role in stroke patients, in particular with respect to the vertebrobasilar circulation.

Compensatory mechanisms in patients with asymptomatic carotid artery occlusion.

Twelve patients with asymptomatic occlusion of one (n = 8) or both (n = 4) internal carotid arteries were examined by positron emission tomography (PET) and transcranial Doppler ultrasound. PET measurements included the determination of the regional cerebral blood flow (rCBF), oxygen extraction ratio (rOER), cerebral metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose consumption (rCMRGlc). Transcranial Doppler ultrasound (TCD) was used to determine the pathways and efficacy of collateralization via the circle of Willis and included spectrum analysis of flow velocities within the middle and anterior cerebral arteries as well as vasoreactivity tests. In correspondence with ultrasound evidence of a haemodynamically effective intracranial collateral circulation no significant differences between patients and controls were observed for rOER, rCMRO2 and rCMRGlc, but rCBF was globally reduced. Furthermore, in all patients with unilateral carotid occlusion PET excluded side asymmetries of any parameter studied. In contrast, flow velocity parameters measured by TCD were significantly reduced ipsilateral and significantly increased contralateral to the carotid obstruction. Vasodilative capacities, however, remained preserved even in the territory of the occluded carotid system. These data indicate that patients with asymptomatic carotid occlusion compensate by haemodynamic and not by metabolic mechanisms in contrast to symptomatic patients.

[The use of computer tomography for radiation therapy of cerebral tumours (author's transl)]. / Der Einsatz der Computertomographie in der Strahlentherapie der Hirntumoren.

The application of computer tomography should be extended for indicating the need and choice of radiotherapy for cerebral tumours, and for observing the effects of treatment. In 26 patients it has been shown that CT is superior to conventional neuro-radiological methods in showing indications and in planning of radiation therapy. Forms of treatment can be suitably adapted where the histological type of the tumour is known. In most cerebral tumours, the beneficial effect of irradiation has been evident in our patients. Our criteria were based on the concept of "clinical malignancy", no attempt was made at a histological classification of the tumours.

[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.

[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.

[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.

[Subclavian-carotid transposition in the treatment of obstructive subclavian disease with steal syndrome]. / Subclavia-Carotis-Transposition zur Behandlung der Subclavia-Verschlusserkrankung mit Anzapfsyndrom.

Eleven patients with subclavian steal syndrome underwent end-to-side transposition of the subclavian into the common carotid artery. The post-operative evaluation was done in every case by neurological examination, brachial blood pressure measurement, transcutaneous Doppler examination and by angiography. The operative result of this reconstruction, which was performed mainly on high-risk patients, was excellent. The symptoms of subclavian steal disappeared. In all but one patient the brachial pressure raised to normal. After transposition a blood flow reduction of 20% was measured intraoperatively in the peripheral common carotid artery, while the vertebral blood flow reversed to its natural direction. The peripheral common carotid artery pressure measured simultaneously remained unchanged, and hemodynamic criteria of carotis steal were not detected. The blood flow quality at the anastomosis was measured by the turbulence index in patients with an ideal reconstruction. The amount of blood flow distortion caused by the anastomosis was negligible. Therefore a long patency is expected. In patients with occlusive disease of the proximal subclavian artery we like to recommend the transposition as the procedure of choice, because the method uses one single incision for the extrathoracic exposure and one anastomosis-only without any graft material.