Italian consensus recommendations for a biomarker-based aetiological diagnosis in mild cognitive impairment patients.

BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

Surgery after embolization of cerebral arterio-venous malformation: experience of 123 cases.

A group of 123 patients with large or critically located arterio-venous malformations (AVMs), operated on between 1990 and 2011 and who underwent preoperative embolization, was assessed in order to clarify the risks of this combined treatment. AVM location, volume, and Spetzler's grade were assessed in each case; AVM volume was over 20 cm(3) in 49 % of the cases; Spetzler's grade was 3 or above in 76 % of the cases (with 34 cases in grades 4-5). A mean of 2.3 embolization procedures per patient were carried out, using bucrylate and, more recently, Onyx and/or Glubran; a 4.5 % procedure-related complication rate was observed. Complications occurring after surgery were classified as hemorrhagic (16 cases, 8 requiring surgical evacuation) or ischemic (4 cases); hemorrhagic complications were more common for AVMs with volumes >20 cm(3) and/or deep feeders. Surgery-related unfavorable results (modified Rankin Score > 2) were observed in 6 % of patients in Spetzler's grade 3, and in 20-25 % of patients in grades 4-5. More recently, a triple treatment (radiosurgery + embolization + surgery) allowed for obtaining favorable results (mRS 0-2) in all patients. It has been concluded that a combined treatment with embolization and surgery constitutes a reasonable choice for complex cerebral AVMs; the association of radiosurgery may improve the patients outcome.

Endovascular treatment of brain arteriovenous malformations using a liquid embolic agent: results of a prospective, multicentre study (BRAVO).

OBJECTIVES: To evaluate the safety and efficacy of a new liquid embolic agent in brain arteriovenous malformation (bAVMs) embolisation. METHODS: A prospective, multicentre series was conducted at 11 interventional centres in Europe to evaluate embolisation of bAVMs with the new liquid embolic agent. Technical conditions, complications, clinical outcome and anatomical results were independently analysed. RESULTS: From December 2005 to December 2008, 117 patients (72 male; 45 female, aged 18-75 years) were included. Clinical presentation was mostly haemorrhage (34.2 %) and seizures (28.2 %). Most AVMs were located in the brain hemispheres (85.5 %). AVMs were <3 cm in 52.1 % of patients and ≥ 3 cm in 47.9 %. Morbidity was observed in 6/117 patients (5.1 %), related to haemorrhagic events in 2 cases and non-haemorrhagic complications in 4 cases. Five patients (4.3 %) died in relation to the treatment (bleeding in 4 patients and extensive venous thrombosis in 1). Complete occlusion of the AVM by embolisation alone was obtained in 23.5 % of patients. Complementary treatment was performed in 82.3 % of patients with partial AVM occlusion, mostly radiosurgery. CONCLUSIONS: In this prospective, multicentre, European, observational series, the new liquid embolic agent proved to be suitable for BAVM embolisation, with acceptable morbidity and mortality and good efficacy. KEY POINTS: • Numerous interventional techniques have been used to embolise brain arteriovenous malformations (AVMs). • This prospective multicentre study demonstrates the suitability of a liquid embolic agent. • The safety of treatment using Onyx is acceptable. • Such embolisation leads to complete AVM occlusion in 23.5 % of patients.

Neuroprotective role of neurophysiological monitoring during endovascular procedures in the brain and spinal cord.

The goal of endovascular neurosurgery is to occlude aneurysms and arteriovenous malformations (AVMs) or to reduce the vascular supply to hypervascularized tumors, while preserving function in the normal neural tissue. However, the intra-arterial injection of embolizing materials into the cerebral or spinal circulation exposes to the risk of ischemic complications. Under general anesthesia, unless a wake-up test is performed, the only way to assess the functional integrity of sensory and motor pathways is to use neurophysiological monitoring. Somatosensory (SEPs) and muscle motor evoked potentials (mMEPs) can be used in combination with pharmacological provocative tests (PTs) to predict the effects of embolization. Amytal blocks neuronal activity, while lidocaine blocks axonal conduction. Therefore, a positive Amytal or lidocaine test (i.e. more than 50% decrease in SEP amplitude and/or mMEP disappearance) indicates that the vessel distal to the tip of the microcatheter supplies the functional gray or white matter of the spinal-cord respectively and cannot be embolized. Brain and spinal-cord vascularization and hemodynamics are extremely complex and even more unpredictable in the presence of a vascular malformation, but using a combined SEPs, MEPs and PTs protocol, morbidity related to endovascular procedures is very low. Given the high sensitivity of peripheral recordings to spinal-cord ischemia, experimental and clinical studies support the concept that whenever the mechanism of spinal-cord injury is purely ischemic, recording mMEPs may suffice. Reports on the use of PTs and neurophysiological monitoring during embolization of brain AVMs in critical areas are more anecdotal and mainly limited to the use of short-acting barbiturates. Our preliminary experience using lidocaine and combining SEP and mMEP monitoring is encouraging, since no false negative results were observed. Finally, if the sensitivity of this method is very high, its specificity has not been tested because embolization is abandoned whenever PTs are consistently positive. Accordingly, the possibility of false positive results cannot be excluded.

Ependymoma with diffuse signet-ring features: report of a case and review of the literature.

Signet-ring cell ependymoma is a rare variant of ependymoma with only seven cases described in literature. Biological behavior and prognosis of this entity are not well-known until now. We present a case of a 49-year-old female with a history of headache and gait instability. Magnetic resonance imaging showed an upper cervical tumor with cystic component and mural nodule. The patient underwent surgery. Microscopically some cells displayed an eccentric nucleus compressed to the periphery by vacuolated cytoplasm. Perivascular pseudorosettes and ependymal rosettes were seen only focally. The cells were positive for glial fibrillary acidic protein and epithelial membrane antigen. The diagnosis was ependymoma with diffuse signet-ring features, grade II according to the World Health Organization. It may be difficult to diagnose this unusual variant of ependymoma especially on small biopsies or frozen sections. A complete examination of the specimen is recommended with immunohistochemical confirmation to rule out potential morphologic mimics, such as metastatic adenocarcinomas and gliomas in the differential diagnosis.

Hippocampus and entorhinal cortex in frontotemporal dementia and Alzheimer's disease: a morphometric MRI study.

BACKGROUND: Magnetic resonance imaging (MRI) of hippocampal atrophy is a sensitive but not specific method to support the clinical diagnosis of early Alzheimer's disease (AD). We recently described our findings that atrophy of the entorhinal cortex (ERC) in frontotemporal dementia (FTD) is equal to that found in AD but that hippocampal atrophy in FTD is less than that found in AD. The MRI volumes of these structures provide a topographic representation of the region of interest. We hypothesized that two different dementias with distinct histopathologic and clinical features might, in addition to quantitative patterns, display topographically different patterns of atrophy. METHODS: We adopted a morphometric approach to monitor the pattern of atrophy of the hippocampus and the ERC by computing two-dimensional profiles from MRI volumes of the structures in control subjects and patients with FTD and AD. RESULTS: Compared with control subjects, atrophy of the hippocampus in patients with AD was diffuse. In patients with FTD, atrophy of the hippocampus was localized predominantly in the anterior hippocampus, suggesting a different pattern of hippocampal atrophy in FTD compared with AD. The amount and pattern of atrophy of the entorhinal cortex was virtually equal in both demented groups. CONCLUSIONS: This study provides novel data on the nature of medial temporal lobe atrophy in FTD. Morphometric MRI may be a useful technique for characterizing different patterns of atrophy in primary degenerative dementias in vivo.

Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease.

OBJECTIVE: To describe atrophic changes of the hippocampus and entorhinal cortex in frontotemporal dementia (FTD) and compare them with those of AD. BACKGROUND: The medial temporal lobe shows atrophic changes early in the course of AD, but whether these changes are specific to AD or occur in other degenerative dementias, and to what extent, is unclear. METHODS: The authors measured the volumes of the left and right hippocampus and entorhinal cortex from MR images (1.5 T, 2-mm-thick slices) in 12 patients with FTD, 30 with AD, and 30 elderly control subjects. RESULTS: In FTD patients, the left and right hippocampus (16% and 21% tissue loss) and the entorhinal cortex (28% and 27% loss) were more atrophic than the control subjects. Atrophy of the hippocampus in FTD was less severe than in AD, but atrophy of the entorhinal cortex was equally severe. Greater hippocampal and entorhinal cortex atrophy was present in the most severe patients in both groups (as high as a 49% tissue loss). The sensitivity of the hippocampus and the entorhinal cortex to discriminate FTD patients from control subjects was low (49% and 52%, respectively; specificity set at 90%), whereas hippocampal volumes could better differentiate AD patients from control subjects (80% sensitivity). CONCLUSIONS: At variance with AD, detectable in vivo atrophy of the hippocampus might not be an early event in FTD. Differential patterns of atrophy might help in the diagnostic process of the degenerative dementias.

APOE-epsilon4 is associated with less frontal and more medial temporal lobe atrophy in AD.

OBJECTIVE: To test the hypothesis that the e4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD. METHODS: Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (-/-), 9 were heterozygous (e4/-), and 5 were homozygous (e4/4) for the e4 allele. Dementia severity was similar across the three AD groups. RESULTS: Smaller volumes were found with increasing dose of the e4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from -15.3 to -22.7% in the -/- AD group, from -26.2 to -36.0% in the e4/- group, and from -24.0 to -48.0% in the e4/4 group (p < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing e4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the e4/- group, and -1.4% in the e4/4 group (p = 0.03). CONCLUSIONS: We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE-e4 gene dose in AD patients. These data suggest a region-specific biological effect of the e4 allele in the brains of AD patients.

Paradoxically greater interhemispheric transfer deficits in partial than complete callosal agenesis.

Symptoms of interhemispheric disconnection are typically much less severe in callosal agenesis than after surgical section of the corpus callosum. Sperry [Sperry, R. W., Plasticity of neural maturation. Developmental Biology, 1968, 2 (Suppl.), 306-327.] has attributed this difference to two interconnected factors: (1) the callosal section is usually performed after the brain has lost the maximal degree of functional plasticity associated with the early stages of development and (2) the removal of an already formed structure is more disruptive for functional brain organization than the failure of the same structure to develop. It has been suggested that functional compensation is less efficient if callosal agenesis is partial rather than complete [Dennis, M., Impaired sensory and motor differentiation with corpus callosum agenesis: A lack of callosal inhibition during ontogeny? Neuropsychologia, 1976, 14, 455-469.]. This suggestion is supported by the present findings of partial left-hand anomia, partial left-field alexia and poor tactile cross-localization in a subject with a congenital absence of the posterior part of the corpus callosum due to an arteriovenous malformation. In agreement with many previous studies, similar, though more severe, symptoms of interhemispheric disconnection were found in a subject with a complete section of the corpus callosum, but not in a subject with complete callosal agenesis. Praxic control of the left hand on verbal commands was severely deficient in the callosotomy subject, but it was normal in the subject with callosal hypogenesis. The lesser degree of compensation in partial compared to complete callosal agenesis may be explained by a reduced pressure to develop extracallosal means of interhemispheric communication, contingent on the partial existence of callosal connections, as well as by the later occurrence in development of the causes of callosal hypogenesis compared to those of total callosal agenesis.

APOE and modulation of Alzheimer's and frontotemporal dementia.

To investigate the difference in the morphologic expression of frontotemporal dementia (FTD) and Alzheimer's disease (AD) in patients carrying and not carrying the epsilon4 allele of APOE, MR images of 26 controls, 18 AD patients (11 carrying the epsilon4 allele, seven non-carriers), and eight FTD (two carriers, six non-carriers) were compared using voxel by voxel analysis. Greater atrophy was found in the disease-specific regions of the epsilon4 carriers vs the non-carriers at P < 0.05 corrected: medial temporal atrophy was greater in the AD carrying the epsilon4 allele, right ventral striatal atrophy in the FTD carrying the allele. The non-carriers did not have atrophic regions compared to the carriers. The epsilon4 allele of the APOE might modulate the expression of degenerative dementias by enhancing the specific effects of neurodegenerative diseases on the brain.

Fossa navicularis magna.

A notchlike bone defect in the basiocciput due to a prominent fossa navicularis was incidentally discovered in a patient referred for radiologic evaluation of sinusitis. MR images showed that the osseous defect was filled with lymphoid tissue of the pharyngeal tonsil. The occurrence of this anatomic variant is discussed, with reference to ancient anatomic works.

Linear measures of atrophy in mild Alzheimer disease.

PURPOSE: To assess the sensitivity of linear measures of brain atrophy in the diagnosis of Alzheimer disease (AD) in the early stages. METHODS: Linear measures of regional frontal (Bifrontal index, interhemispheric fissure width), medial temporal lobe (interuncal distance, minimum thickness of the medial temporal lobe), and hippocampal (hippocampal height, width of the choroid fissure, width of the temporal horn) atrophy were made on magnified MR images obtained in 46 patients with AD (33 with mild severity and 13 with moderate severity) and in 31 control subjects. Gaussian modeling was used to compute sensitivity with specificity set at 95%. Discriminant analysis was used to identify measures independently contributing to the ability to discriminate AD patients from control subjects. RESULTS: The measure with the best sensitivity in discriminating AD patients from control subjects was the width of the temporal horn. A compound measure of width of the temporal horn, width of the choroid fissure, height of the hippocampus, and interuncal distance could discriminate patients with mild AD from control subjects with 86% sensitivity. Cross validation in patients with moderate AD confirmed the usefulness of the model (81% sensitivity). Measures of hippocampal atrophy alone could discriminate patients with mild AD from control subjects with 83% sensitivity; in patients with moderate AD, cross validation produced 87% sensitivity. CONCLUSIONS: Linear measures of hippocampal atrophy can be a useful adjunct in the routine diagnosis of AD, even in its early stages.

Preoperative embolization of arteriovenous malformations with polylene threads: techniques with wing microcatheter and pathologic results.

The technique with a wing microcatheter system and the pathologic aspects of 11 cerebral arteriovenous malformations (AVMs) surgically resected after embolization with polylene threads are reported. Embolization was performed once in eight patients and twice in three patients. Resected AVMs were submitted both to routine hematoxylineosin examination and to immunohistochemical workup in order to detect the type of immunologic response to thread emboli. In nine cases, 50% or more of the nidus was obliterated by the embolization. After embolization two patients developed reversible neurologic deficits. Pathologic specimens of resected AVMs demonstrated no vascular necrosis; however, a moderate inflammatory response could be seen, characterized by the presence of both mononuclear cells and foreign-body giant cells, associated with the absence of polymorphonuclear infiltrates. A granulomatous fibrotic process was identified that was present from the first month after embolization. Immunohistochemistry indicated that the immunologic response to thread emboli was cell-mediated, not humoral. Embolization with the wing microcatheter with the use of polylene threads proved to be a safe and efficient system of embolization, as a preoperative procedure. Polylene threads are a nontoxic and biocompatible material that can be used as an embolic agent for brain AVMs.

Hemodynamic effects of preoperative embolization in cerebral arteriovenous malformations: evaluation with transcranial Doppler sonography.

A series of 83 patients with cerebral arteriovenous malformations is presented. All patients were evaluated with transcranial Doppler sonography. Thirty-two patients were treated with staged embolization and surgery: 19 of these patients were operated on within 4 weeks of the last embolization, and the remaining 13 patients underwent surgery 6 months or more from embolization. Transcranial Doppler sonography performed 1 day after embolization showed a significant (> 60%) reduction of main feeder flow velocity in 72% of patients after the first embolization and in 45% of patients after the second embolization. In no case did such a significant reduction occur after the third embolization. A flow redistribution in the basal vessels (defined as an increase in flow velocity of at least 30% of the initial value) occurred only in patients after the first embolization (64%). On delayed post-embolization studies, complete recovery of flow velocity in the embolized vessel occurred in 46% of patients, and sonographic recruitment of new feeders occurred in the remaining 54%. When main feeder flow velocity (mean) was higher than 120 cm/s after embolization and before surgery, the incidence of postoperative hyperemic complications (cerebral edema and/or intracerebral hematoma) was significantly higher than in patients with a mean flow velocity under 120 cm/s. It is concluded that transcranial Doppler sonography is a valuable method for a noninvasive hemodynamic assessment of shunt flow in arteriovenous malformations, and it permits a physiological monitoring of hemodynamic changes after embolization and allows more precise indications regarding further stages of embolization and timing of surgery after embolization.

Treatment of cerebral arteriovenous malformations with a combination of preoperative embolization and surgery.

Forty-nine patients with cerebral arteriovenous malformations (AVMs) were treated with preoperative embolization followed by resection using a microsurgical approach. In 27 patients, the AVM was located in an eloquent area; in 32 patients, the volume of the AVM was over 20 cm3. Preoperatively, flow-directed embolization was performed in 10 patients (28 procedures), selective embolization with threads was performed in 35 patients (46 procedures), and a combination of flow-directed and selective embolization was performed in 4 patients (12 procedures). The percentage of reduction of the AVM volume averaged 36% after embolization. Five minor complications (transient neurological deficits, in 2 cases associated with ischemic areas on the CT scan) were observed after embolization. The interval between the last embolization and surgery was as follows: within 10 days in 7 patients; between 11 and 20 days in 3 patients; between 21 and 30 days in 10 patients; between 31 and 60 days in 11 patients; and 2 months later in 18 patients. The efficacy of this combined treatment (embolization plus surgery) was evaluated by the incidence of hyperemic complications and the clinical outcome. Hyperemic complications occurred more frequently in patients with an AVM volume greater than 20 cm3. When compared with flow-directed embolization, selective embolization was linked with decreased bleeding during surgery; postoperatively, the incidence of cerebral edema was also lower. Clinical outcome was better after selective embolization, with no occurrence of major deficits and no mortality. When the percentage of reduction of the AVM volume after embolization was 40% or more, the incidence of intraoperative hyperemic complications was lower; moreover, new permanent deficits were never observed in patients with this volume reduction. A retrospective clinical comparison of two groups of patients with similar AVM volumes (greater than 20 cm3)--those given combined treatment (n = 32) versus those treated by direct surgery alone (n = 27)--showed that intraoperative bleeding appeared to decrease in patients treated by embolization; the incidence of postoperative hyperemic complications was not different in the two groups. New major deficits and deaths were less frequent in patients treated by embolization (P = 0.05 for the incidence of major deficits); postoperative epilepsy was also less common in these patients. In conclusion, combined treatment with selective preoperative embolization and direct surgery may help the neurosurgeon in the treatment of large, high-flow AVMs, reducing the risks connected with their surgical removal.

Treatment of posttraumatic carotid-cavernous fistula using a detachable balloon catheter.

Five cases of posttraumatic carotid-cavernous fistula are reported. The fistulas were occluded by intravascular detachable balloons, as described by Serbinenko and later modified by Debrun. The good results obtained in three of these patients illustrate the value of this procedure, as it allows a direct obliteration of the fistula with preservation of the internal carotid blood flow.

Magnetic resonance and single-photon emission tomography findings in a pair of twins discordant for Alzheimer's disease.

The value of functional and morphological neuroimaging in the early diagnosis of Alzheimer's disease (AD) is still debated. Described here are cerebral perfusion and linear measures of medial temporal lobe atrophy in 2 monozygotic twins discordant for AD who were investigated with technetium 99m-hexamethylpropy-leneamineoxime single-photon emission tomography (SPET) and magnetic resonance (MR) imaging. Both showed pathological cortical perfusion findings on SPET, while medical temporal lobe atrophy was present only in the affected twin. MR measures of medial temporal lobe atrophy have greater agreement with clinical data than do SPET measures of cerebral perfusion. Evaluation of atrophy may be useful in the early diagnosis of AD.

CNS trauma: head injuries.

Head injuries are a common cause of death and permanent disability, particularly in the first decades of life. The high mortality and morbidity associated with head trauma is due mostly to the severity of the injury itself but also in part to the possible events that could aggravate the primary brain damage. This also occurs in patients with an initially mild head trauma. This article reviews imaging procedures, complications of head trauma, and the order of diagnostic evaluation.

Irreversible respiratory failure in an achondroplastic child: the importance of an early cervicomedullary decompression, and a review of the literature.

The authors report the case of a girl with achondroplasia suffering from a progressively worsening hypotonic quadriparesis. CT scan showed slight dilatation of ventricular and subarachnoid spaces, with well-defined evidence of cortical sulci and gyri. This aspect was compatible with the diagnosis of macrocrania and megalencephaly (CP being 51 cm). The foramen magnum was narrowed, the transverse diameter measuring 15 mm and the 50th percentile being, for age, 26 mm. Somatosensory evoked potentials (SEPs) revealed bilaterally prolonged interpeak latencies Erb-N13, slowing of central conduction time N13-N20 from right median nerve stimulation, and block from left median nerve. The suspicion of cervicomedullary compression was confirmed by MRI, showing a very marked stenosis with compression exerted by the odontoid process. Further, a stenotic cervical canal and optic nerves verticalization were manifest. The patient underwent neurosurgical decompression by suboccipital craniectomy and cervical-C1 laminectomy. In spite of treatment, both neurologic and respiratory problems (rapid, shallow and almost abdominal breathing) were unchanged. The girl died 4 1/2 months later. The authors emphasize the important role of SEPs in detection of cervicomedullary compression in achondroplastic children and also stress the necessity of an early surgical treatment as the only condition for possible clinical improvement and/or full recovery.

Double-blind comparison of safety and efficacy of iomeprol and iopamidol in carotid digital subtraction angiography.

Iomeprol is a nonionic monomer which provides injectable formulations with the lowest osmolalities and the lowest viscosities among the currently available low-osmolar radiographic contrast agents of the same category. These favourable physico-chemical characteristics, together with high water solubility and low molecular toxicity, make this agent particularly suitable for carotid angiography, a procedure in which contrast-induced blood-brain barrier damage is maximal. This single-centre, randomised, double-blind, parallel-group study aimed at comparing the safety, tolerance and efficacy of 200 mgI/ml solutions of iomeprol and iopamidol in 100 consenting adult inpatients undergoing carotid intra-arterial digital subtraction angiography (IA-DSA). Both agents appeared to be safe and well tolerated. Only minor and transient adverse events occurred throughout the study. Electroencephalographic and neurological examinations performed pre- and post-contrast showed no abnormality induced by the test compounds. Vessel opacification was good or excellent in the vast majority of technically adequate examinations. Information provided by the angiographic examination was useful for subsequent patient management in almost all cases. It is concluded that iomeprol-200 and iopamidol-200 are safe and effective contrast media when used for carotid IA-DSA, an examination which proves useful not only for the diagnosis of vascular lesions, but also to best direct the management of patients scheduled for surgery of intracranial tumors.