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.

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.

[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.

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.

Transcranial Doppler ultrasonography versus arteriography for assessment of the vertebrobasilar circulation.

The investigation of the vertebrobasilar arterial system by transcranial Doppler (TCD) ultrasonography is difficult due to the numerous anatomical variations in the posterior circulation. To test the validity of TCD, we compared topographic measurements from vertebrobasilar angiograms and corresponding TCD findings in 58 patients with cerebrovascular diseases (N = 37, 21 affecting the vertebrobasilar system), brain tumors (N = 8), and other neurological diseases (N = 13). Normal TCD recordings of the vertebrobasilar system were confirmed by the angiograms in 25 patients, although the noninvasive method failed to separate morphologic variants (N = 15). In patients with pathological conditions of the vertebrobasilar system revealed by either method (N = 17), the combined use of both hemodynamic and radiomorphologic methods improved the diagnostic validity in 24%. We conclude that TCD examination of the posterior fossa circulation provides unambiguous results only if used in combination with cerebral arteriography.

Doppler color flow imaging of carotid body tumors.

Doppler color flow imaging is a new ultrasound method for the simultaneous spatial display of tissue and vessel morphology (B-mode echotomograms) and of color-coded blood flow velocity information (Doppler-mode analysis). This new method is particularly useful in the neck, not only for the assessment of brain arteries but also for the safe and valid identification of carotid paragangliomas compared with other neck tumors. Early clinical detection of carotid paragangliomas is difficult since these lesions often occur sporadically and the patients remain symptom-free until the tumor becomes noticeable. Doppler color flow imaging allows the diagnosis of even small paragangliomas, which may improve management because of existing complications of surgical therapy.

Absorbable polydioxanone suture for venous anastomoses: experimental studies using venography and transluminal angioscopy.

Because of their increased tendency to stenosis and spasm and thrombosis, results after venous anastomoses are often unsatisfactory. Nonabsorbable sutures and a continuous suture technique have been suggested to have a negative effect on the compliance of vascular anastomoses. Eighty venous anastomoses were performed with either an interrupted or continuous suture technique, using polypropylene or polydioxanone (PDS) sutures, according to a randomised experimental model. The anastomoses were divided in four groups: (1) Nonabsorbable suture material, continuous suture technique; (2) Nonabsorbable suture material, interrupted suture technique; (3) Absorbable suture material, continuous suture technique; and (4) Absorbable suture material, interrupted suture technique. The morphology of the anastomoses was controlled by venography directly after closure of the wound and at weekly intervals for 2 months and monthly intervals thereafter until 2 years had passed. In 10 cases venography was followed by transluminal angioscopy in the early postoperative period and after 1, 2, 4, 8 and 12 weeks. In the first 2 months moderate and high degree stenoses were found in all 4 groups by venography. After 8 weeks there was a significant decrease in the incidence of stenosis in all groups with the exception of the group, in which continuous nonabsorbable suture had been used. Using angioscopy a marked swelling of the intima at the site of the anastomoses could be detected in the early postoperative period in all experimental groups. After 2 months no significant narrowing could be identified in groups 2, 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

[CT follow-up of neurocysticercosis treated with praziquantel]. / CT-Verlaufsbeobachtungen bei Neurocysticerkose unter Praziquanteltherapie.

Praziquantel therapy has produced a much better prognosis in neurocysticercosis since 1980. The computed tomographic findings and follow-up study in 4 patients with neurocysticercosis before and after praziquantel therapy are described. The special difficulties of differential diagnosis and further diagnostic procedures are discussed in cases in which calcifications are absent and only solitary foci can be found.

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)

Percutaneous transluminal angioscopy. A new imaging technique for diagnosis of extracranial arterial disease.

Angiography and ultrasound techniques are well established methods for the detection of extracranial vascular disease, but they only allow indirect demonstration of changes in the vessel wall. The development of an ultra-thin fiberscope allows direct demonstration of the pathogenic process in the vessel lumina by angioscopy. The percutaneous transfemoral approach for carotid angiography enables the combination of both methods. After development of an appropriate catheter system we investigated the value of this method producing definite lesions by vascular surgery in adult dogs followed by repeated examinations using angioscopy. Vessel wall alterations such as stalagmite-shaped lesions, subintimal bleeding and thrombotic layers, plaques, ulcerations and postoperative intimal bridging or ablation, which could not be identified by angiography have been analysed with high resolution of details using angioscopy with a video monitoring technique.

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.