MRI staging using gadodiamide for soft-tissue tumors of the head and neck region. Results from a phase II trial and a 5-year clinical follow-up.

In order to document the safety, tolerability and efficacy of gadodiamide outside CNS, an open, non-drug comparative study was performed in patients with tumors of the head and neck region. Fifty adult patients were included and 48 patients received the contrast medium. The examinations were performed on a 1.5 T imager using transverse, non-enhanced T1- and PD-/T2-weighted conventional spin-echo sequences, followed by a contrast-enhanced transverse T1-weighted sequence. Post-contrast images provided more diagnostic information compared to unenhanced images in 33 of 48 patients (69%). This information was of significant help in four and of moderate help in 14 cases. Post-contrast images compared to non-enhanced T1-weighted showed improvement in lesion delineation for 29 of the 43 patients where a lesion was observed. Only in two patients was the diagnostic information lower post-contrast. A comparison between all pre-contrast images versus contrast medium enhanced showed post-contrast images to give more diagnostic information in 14 and less in nine patients. No patient experienced discomfort in relation to gadodiamide injection. Only one adverse event occurred which was described as thirst, being of moderate intensity. The 5-year clinical outcome was analyzed and compared with the pre-operative staging. The case-books of all patients were reviewed and in 44 patients all information could be found. Of those, 18 were still alive, one with active disease (AAD) and 17 with no evidence of disease (NED). Two of those four patients, where information was incomplete, showed NED and two had died. This trial showed that contrast-enhancement using gadodiamide for evaluation of soft tissue tumors in the head and neck region was safe and provided statistically significant more diagnostic information compared with unenhanced images. MRI, when compared with palpation/inspection, changed tumor staging in approximately 30% of all cases.

PCR diagnosis of primary herpesvirus type I in poliomyelitis-like paralysis and respiratory tract disease.

Successful and rapid recovery of HSV-1 DNA from the cerebrospinal fluid after amplification by polymerase chain reaction was obtained in a 7-year-old boy with subtotal and permanent upper extremity paralysis with rapid onset and magnetic resonance imaging evidence of cervical cord involvement. Early administration of intravenous acyclovir probably limited neuronal loss. The clinical course and outcome of this disorder best conformed with what has been described as poliomyelitis-like paralysis associated with respiratory tract infection (Hopkins syndrome).

Effects of radiopaque contrast media on calcium uptake and phosphatidylinositol metabolism in rat brain synaptosomes.

Radiographic contrast media (RCM) used in the subarachnoid space are associated with occasional adverse reactions. This study examines the possibility that RCM reactions are caused by interactions with the plasma membrane phosphatidylinositol (PI) second messenger system. Isolated nerve endings, known as synaptosomes, were produced from rat brain homogenates. The synaptosomes were then incubated with RCM to determine if 32Pi labeling of the PIs or the uptake of 45Ca were influenced in a manner consistent with known mechanisms. The RCM metrizamide, iopamidol, iodixanol, and iotrol (but not iohexol) increased the 32Pi labeling. Hyperosmolality produced large increases in phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4, 5,-bisphosphate (PIP2) labeling. In the non-depolarized state iodixanol, but not metrizamide or iohexol, caused a time-dependent increase in 45Ca uptake. Iodixanol, iohexol, and metrizamide also augmented the veratrine-stimulated uptake of calcium, but none of the RCM affected the uptake of Ca resulting from potassium depolarization. The increased 32Pi labeling of the PIs caused by RCM is not directly related to Ca uptake, because the direction of change is wrong. RCM perturbations of the plasma membrane may cause an inhibition of other membrane components and systems. Hyperosmolality also may cause inhibition of membrane components. It is not known if these effects are important in clinically observed RCM toxicity.

The effects of gadolinium-DTPA and -DOTA on neural tissue metabolism.

Gadolinium DTPA and DOTA are being used extensively for imaging blood-brain barrier lesions. This study was performed to determine clinically relevant blood, cerebrospinal fluid (CSF), and neural tissue concentrations of these agents, and to determine if they alter neural tissue glucose metabolism. Bolus injections of 0.2 mmol Gd-DTPA/kg were made in rabbits, and blood, CSF, and neural tissue Gd concentrations were measured using atomic emission. Rat hippocampus slices were incubated for 6 hours in solutions of Gd-DTPA and Gd-DOTA, and effects on the production of carbon-14-labeled CO2 from glucose determined. Plasma concentrations reached a peak of 2.46 mmol at 1 minute postinjection, and dropped to 50% of peak in 6 minutes. The highest CSF concentration observed was approximately 0.1 mmol, and the mean lumbar cord concentration was approximately 8.5 mumol/g. Gd-DTPA and Gd-DOTA concentrations greater than 1.0 mmol caused significant increases in CO2 production. In areas of blood-brain barrier lesions, Gd-DTPA and Gd-DOTA may cause changes in tissue metabolism; however, in other areas it is much less likely.

Local glucose utilization changes caused by subarachnoid contrast media in the rabbit.

The glucose metabolism effects of six hour exposures to subarachnoid injections of metrizamide, iohexol, iodixanol and control solutions were studied in vivo in 18 rabbits. The brain tissue uptake of intravenously injected 14C labelled deoxyglucose was measured using autoradiographic techniques. Metrizamide and iodixanol caused significant (p less than 0.05) decreases in deoxyglucose uptake in the outer cortical areas where the contrast medium concentrations were highest. Iohexol and the control CSF solution did not cause significant effects. The results appear to indicate that iohexol has less effect on brain tissue glucose metabolism than either metrizamide or the new non-ionic dimer iodixanol.

Iotrol, iodixanol, and 2-deoxy-D-glucose effects on neural tissue CO2 production.

In vivo and in vitro experiments have demonstrated that the myelographic agent metrizamide decreases neural tissue glucose metabolism whereas iohexol and iopamidol do not. This study compares the changes in slices of rat hippocampus CO2 production caused by the nonionic dimers iotrol and iodixanol with the effects of metrizamide and 2-deoxy-D-glucose. After 6-hr incubations, 70-mmol/l concentrations of iotrol and iodixanol increased CO2 production by 11 +/- 20% and 31 +/- 35%, respectively, as compared with the artificial CSF control medium. Metrizamide at 70 mmol/l and 2-deoxy-D-glucose at 35 mmol/l decreased CO2 production by 32 +/- 13% and 96 +/- 1%, respectively. The increases in CO2 production with iotrol and iodixanol appear to indicate that these molecules have some effect on cell metabolism. The mechanism for the increase in CO2 production could involve an effect on the glucose metabolic pathway or could be indirect via a mechanism that increases cell energy utilization. These in vitro effects have not been verified with in vivo experiments.

Effects of contrast media on neural tissue glucose uptake in vitro.

The authors previously showed that metrizamide causes an inhibition in CO2 production in rat neural tissue. The purposes of this work were to test if this inhibition was the result of a competitive inhibition of metrizamide with the D-glucose transport system and to test the effect of other contrast media. Deoxyglucose was used as a marker for glucose. The first cellular system using rat hippocampus slices was designed to examine the effect of 15 mM and 80 mM metrizamide on deoxyglucose uptake. The second cell-free system, using isolated rat brain synaptosomes, was designed to evaluate more accurately the mechanism and kinetics of metrizamide's inhibitory effect on the uptake of deoxyglucose and to compare metrizamide to other nonionic contrast media (iohexol, iopamidol, iotrol, and iodixanol). These experiments demonstrate that there is inhibition of D-glucose uptake only in hippocampus slices and that the inhibition is dependent on the concentration of metrizamide. This does not, however, appear to be a competitive inhibitory effect on the carrier such as that between D-glucose and 2-deoxy-D-glucose. In synaptosomes, none of the contrast media had a significant effect on the uptake of 2-deoxyglucose.

In vitro models for testing the metabolic effects of myelographic contrast media.

Water-soluble nonionic x-ray contrast media have greatly improved the quality and safety of myelography. Toxic side effects are still observed however. The side effects are generally worse with the first nonionic agent, metrizamide, which has a glucoselike side group. Two in vitro models were developed to examine the effects of contrast media on glucose metabolism. Using rat hippocampus slices, the authors observed significant depression of carbon dioxide production by metrizamide and by deoxyglucose, a known metabolic inhibitor. Iohexol and iopamidol did not cause significant depressions. In rat brain synaptosomes the authors did not observe a depression of the uptake of deoxyglucose 14C by any media tested. These studies indicate that metrizamide can create metabolic depression but that it does not compete with glucose for the membrane glucose carrier.

Observations on cerebral computed tomography in patients having carotid endarterectomy.

A review was undertaken of all patients seen in our institution between January 1978 and March 1987 in whom a cerebral CT scan was obtained in association with elective carotid endarterectomy. Three hundred fifty-nine such patients were identified. In a subgroup of 89 patients who were neurologically normal after carotid endarterectomy, scans were performed at least 48 hours after surgery to quantitate the incidence of silent postoperative infarction. These scans were interpreted by one neuroradiologist. Preoperative cerebral CT scans showed ipsilateral infarction in 146 of 359 patients (40.6%). Ipsilateral infarction was most common in patients with stroke (76%) but was also seen in 32.8% of patients with transient ischemic attacks, in 9 of 40 patients (22.5%) with nonhemispheric symptoms, and in 9 of 45 patients (20%) with asymptomatic hemodynamically significant carotid stenosis. The postoperative stroke rate was not significantly increased by the presence of infarct on preoperative cerebral CT scan (2.6% vs 1.9%). New infarcts were seen on cerebral CT scanning after carotid endarterectomy in 2 of 89 patients with no detectable neurologic abnormality (2.3%). This study demonstrates a high frequency of ipsilateral infarction in patients having elective carotid endarterectomy, even in those patients with clinical symptom complexes thought by many physicians to be relatively benign (i.e., transient cerebral ischemia, nonhemispheric ischemia, and asymptomatic carotid stenoses).(ABSTRACT TRUNCATED AT 250 WORDS)

Local blood-brain barrier penetration following systemic contrast medium administration. A case report and an experimental study.

The present study was initiated by a severe complication in a patient with renal dysfunction who developed cortical blindness and weakness of her left extremities 30 hours following renal and abdominal angiography. To evaluate the impact of prolonged high serum concentrations of contrast medium (CM) this clinical situation was simulated in a laboratory model using sheep with elevated serum levels of contrast medium maintained for 48 hours. The experimental data did not support the theory that the prolonged exposure to high circulating levels of contrast medium (4 ml/kg body weight of meglumine diatrizoate 60%) is sufficient alone to cause penetration of the blood-brain barrier.

MR of the cauda equina.

To define the anatomy of the cauda equina nerve roots by MR imaging, the lower spine of 14 normal volunteers was imaged using a high-field surface-coil technique. A total of 56 sagittal and 56 axial MR sections (eight selected slices from each case) were correlated with undistorted anatomic sections from cadaver spine specimens, and the visualization of the nerve roots was assessed. In addition, MR images of three patients with infiltrating or seeding tumors affecting the cauda equina were analyzed. Seventy-eight percent of the MR sections from normal cases clearly showed the anatomy of the cauda equina nerve roots. The nerve roots were fairly shown in 17% of the sections; and false findings (presumably caused by CSF pulsation) were observed in the remaining 5%. Coronal imaging provided excellent anatomic views of the nerve roots within the intervertebral foramina. Morphologic alterations in the pathologic cases were correctly shown when both T1- and T2-weighted imaging were used. In conclusion, MR proved efficient in viewing the cauda equina region.

High-dose iohexol myelography.

Lumbar myelography was performed with high volumes of iohexol (15-24 ml) at a concentration of 180 mgI/ml (average dose, 20 ml) in 48 patients. In 44 patients receiving more than the currently recommended upper dose limit of 17 ml, the frequency of headache (41%), nausea (14%), and vomiting (9%) was comparable to results for routine-dose lumbar metrizamide myelography. Overall, adverse reactions were more frequent, particularly at the highest dose levels, than reported for conventional-dose iohexol myelography. However, there were no occurrences of neuropsychiatric disorder, encephalopathy, or seizure. High-dose technique allows superior visualization of upper lumbar and conus detail and may be advantageous in patients with large subarachnoid spaces and in multi-level examinations. This study supports the results of previous trials that suggested the relative safety of iohexol as a contrast agent and extends those observations to a higher dose range. Because of the increased rate of adverse reactions at the highest dose levels (despite the absence of major adverse reactions), iohexol should continue to be used conservatively, with doses carefully tailored to each examination.

Further support for the glucose hypothesis of metrizamide toxicity. The effect of metrizamide and glucose analogue-free contrast media on hexokinase.

Metrizamide neurotoxicity has been hypothesized to be caused by an inhibitory effect of the drug on glucose metabolism. Metrizamide contains a glucose side chain, and glucose analogues including metrizamide have been shown to be inhibitors of hexokinase, an enzyme that is central to cerebral glucose metabolism. We studied the effect of the nonionic contrast agents iohexol, iotrol, and iopamidol, and the ionic contrast meglumine diatrizoate, on hexokinase in vitro. Although metrizamide reproducibly caused competitive inhibition of the reaction, the nonglucose contrast agents had no significant effect on the enzyme. These results add further support for the glucose hypothesis of metrizamide neurotoxicity.

Postoperative radiographic appearance of intracranial hemostatic gelatin sponge.

Hemostatic gelatin sponges were placed in hemispheric defects created in four dogs which were then periodically scanned by computed tomography to determine the postoperative appearance of the sponges. The hemostatic sponges appeared as low attenuation regions for 7-10 days. The attenuation value of these Gelfoam cavities was intermediate between fat and air. Subsequently, clinical cases were selected in which the location of gelatin sponges were known to demonstrate the appearance of the material in patients. In addition to enhancing the accuracy of computed tomographic interpretation, we have found that the gelatin sponge can be useful as a transient computed tomography marker for localization of surgical activity.

Iopamidol and neural tissue metabolism. A comparative in vitro study.

Metrizamide was the first water-soluble contrast medium with a neurotoxicity low enough to allow it to be used routinely in the entire subarachnoid space. However, neurologic complications are still observed in some patients following the use of metrizamide. The cause of this toxicity has not been established, but existing evidence suggests an interference with glucose metabolism. In previous studies, a depression in CO2 production in neural tissue slices was demonstrated when isotonic metrizamide was added but not isotonic iohexol. In addition to iohexol, there is another new, nonionic, monomeric, water-soluble CM, iopamidol, soon to be released for clinical use in the United States. Iopamidol, like iohexol, has shown fewer adverse reactions and seems to be safer for myelography than metrizamide. Direct comparative studies of iopamidol and iohexol are sparse and the cause of their toxicity is not yet understood. This study was performed to determine the effect of iopamidol on neural tissue glucose metabolism as compared with the effects of iohexol and metrizamide. Metrizamide decreased CO2 production in neural tissue slices by 23%. Iopamidol and iohexol did not produce significant depression. Moreover, this model could not demonstrate any significant difference between iopamidol and iohexol in direct comparisons. The new monomeric contrast media, iopamidol and iohexol, thus do not appear to interfere with glucose metabolism. Adverse reactions to these new media are most likely caused by other mechanisms.

Neurologic complications in diabetics after metrizamide lumbar myelography.

Recognized risk factors for metrizamide myelography are seizure disorder, seizure-threshold-lowering drugs, dehydration, and possibly age. After observing serious neurologic complications in diabetic patients after routine metrizamide myelography, a retrospective study was conducted to determine if diabetes should be considered another independent and important risk factor. Forty-one diabetic patients who had lumbar metrizamide myelograms were compared with a control group of 110 nondiabetic patients. A significantly higher incidence was found of severe vomiting (15% vs. 3%, p less than 0.01) and neurologic complications (20% vs. 2%, p less than 0.001) in the diabetic population. Neurologic complications included one case each of seizure, severe encephalopathy, auditory and visual hallucinations, and prolonged somnolence and four cases of confusion-anxiety. Four of the diabetic patients had major transient elevations of blood pressure. These findings suggest that diabetics are a high-risk population for metrizamide myelography. The dose of metrizamide should be minimized, whenever possible. The new nonionic myelographic agents may prove to be safer in this population, but caution and careful follow-up should be exercised in the initial trials with these patients.

Angiographic and pathologic correlates in carotid artery disease.

Eighty-four consecutive intact atheromata from the carotid bifurcation were examined macroscopically and by standard microscopic techniques. Preoperative angiograms of these cases were reviewed by a single radiologist with special attention to detecting the presence of ulceration. Pathologic and angiographic findings were compared and correlated with the patient's clinical presentation. Macroscopic findings of ulceration were present in 43 cases (51%). Thirty-four specimens contained intramural hemorrhage and 27 showed evidence of mural thrombus. Mural thrombus was significantly associated with evidence of ulceration (p less than 0.01). Intramural hemorrhage was commonly associated with ulceration (25/34) but was also seen in nonulcerated plaques (p greater than 0.05). Angiographic diagnosis of ulceration was made in 54 cases (64%). While angiography identified 78% of macroscopic ulcers (34/43; p = 0.05), seven typical ulcerations were missed angiographically and there were 18 angiographic false positive results (18/54:33%). Macroscopic ulcerations were most common in patients with symptoms of hemispheric ischemia (p less than 0.1). The angiographic diagnosis of ulceration did not correlate with the patient's clinical presentation (i.e., hemispheric ischemia, nonhemispheric ischemia, or asymptomatic stenosis). These results support the thesis that macroscopic ulceration is an important cause of hemispheric ischemia. Angiography does not reliably predict the presence of macroscopic ulceration and this limitation should be kept in mind when patients with hemispheric symptoms are evaluated. Such patients should not be denied consideration for endarterectomy simply because the angiogram fails to demonstrate ulceration.