Prevention of postmetrizamide myelographic seizures in dogs, using 5% dextrose solution

Diuresis by IV administration of 5% dextrose in a balanced electrolyte solution (BES) reduced the frequency of occurrence of postmyelographic seizures in dogs. In the first study, a single myelogram was obtained in 8 dogs without dextrose diuresis. Two of these dogs weighed greater than 15 kg and both had seizures after metrizamide myelography. The remaining 6 dogs weighed less than 15 kg and only 2 had seizures. Greater body weight may have increased the risk of postmyelographic convulsions. In a crossover study, myelograms were obtained in 12 dogs weighing 20 to 31 kg. Six dogs were given 5% dextrose in BES (20 ml/kg of body weight/hr [diuresed]) and 6 were given BES alone (10 ml/kg/hr [not diuresed]). When myelography was repeated 10 days later, the 6 dogs that had been given 5% dextrose in BES were given BES only and the 6 dogs that had been given BES alone were given 5% dextrose in BES. The frequency of convulsions after metrizamide myelography was lower when dogs were given dextrose (33%) than when they were not (100%).     

IOHEXOL AND IOPAMIDOL MYELOGRAPHY IN THE DOG: A CLINICAL TRIAL COMPARING ADVERSE EFFECTS AND MYELOGRAPHIC QUALITY

In a blind clinical trial, adverse effects after iohexol and iopamidol myelography were evaluated in 151 dogs. Eighty-one dogs were given iohexol (240 mgI/ml) and 70 dogs were given iopamidol (200 mgI/ml) by pre-determined assignment. Each dog was evaluated postmyelographically for seizures, hyperthermia, prolonged recovery from anesthesia and intensification of pre-existing neural signs. Myelographic quality was evaluated with a subjective scoring method. In comparing iohexol and iopamidol groups, there was not a statistically significant difference in the incidence of adverse effects or in myelographic quality. Iopamidol and iohexol appeared to be equally efficacious for routine canine myelography.     

Cerebrospinal fluid response following metrizamide myelography in normal dogs: effects of routine myelography and postmyelographic removal of contrast medium

The effect of metrizamide myelography on 90-minute postmyelographic cerebrospinal fluid (CSF) samples was evaluated in a paired crossover study in 16 normal dogs. Each dog received a routine cervical myelogram (nonwithdrawal myelography) and a myelogram followed by contrast medium removal via aspiration from the subarachnoid space (withdrawal myelogram). Following nonwithdrawal myelography, the CSF was characterized by mild inflammation with a mixed pleocytosis and increased protein concentration. Compared with the nonwithdrawal CSF samples, the postmyelographic CSF of the withdrawal dogs had a more severe inflammatory response with significant increases (p < 0.05) in absolute numbers of neutrophils, monocytoid cells, eosinophils, lymphocytes, and protein concentration. The withdrawal procedure may have contributed an additional mechanical effect on the leptomeninges producing the more severe inflammatory response in the withdrawal dogs. Although seizure data are not reported here, postmyelographic seizures were more frequent following non-withdrawal myelography as compared with withdrawal myelography (p < 0.05), suggesting a decrease in metrizamide-induced neurotoxicity for the withdrawal dogs.     

Neurotoxicologic effects of the nonionic contrast agent iopamidol on the leptomeninges of the dog

The effect of iopamidol on the leptomeninges was tested and compared with that of metrizamide and normal saline solution in 18 dogs. Pathologic and clinical effects were evaluated at 24 hours and 14 days after cisternal injection of iopamidol, metrizamide, or normal saline solution. Pathologic changes were evaluated by microscopic examination of serial CSF samples and of sections of brain and spinal cord with the leptomeninges intact. Clinical changes were subjectively evaluated. Electromyograms and EEG were performed on each dog after physical and neurologic examination. There were no changes seen in neurologic status, electromyogram, or EEG in any of the dogs immediately after subarachnoid injection nor at 24 hours or 14 days later. Pathologic changes were limited to mild, moderate, or severe patchy hemorrhagic leptomeningitis seen at 24 hours after iopamidol or metrizamide was injected. The severity of changes were judged to be similar with both these agents. The CSF analysis and histologic evaluation of brain and spinal cord sections revealed a neutrophilic response to iopamidol and a mononuclear response to metrizamide. These findings indicate that iopamidol has minimal neurotoxicologic effect on the leptomeninges and therefore has merit as a myelographic agent.     

Comparison of total white blood cell count and total protein content of lumbar and cisternal cerebrospinal fluid of healthy dogs

Lumbar and cisternal CSF from 31 healthy dogs were analyzed and compared statistically. The mean total protein of the lumbar CSF samples was 28.68 mg/dl; the mean total protein of cisternal CSF was 13.97 mg/dl. The mean total WBC count of lumbar CSF was 0.55 cells/microliter; the mean WBC count of cisternal CSF was 1.45 cells/microliter. Statistical analysis indicated that the protein and WBC differences between the 2 types of CSF were significant (P = less than 0.001 and P = less than 0.01, respectively).     

Characterization of matrix metalloproteinase-2 and -9 in cerebrospinal fluid of clinically normal dogs

OBJECTIVE: To characterize matrix metalloproteinase (MMP)-2 and -9 in CSF of clinically normal dogs. SAMPLE POPULATION: Samples of CSF collected from 23 dogs. PROCEDURE: Dogs were anesthetized, CSF samples were collected, and dogs were then euthanatized. Each CSF sample was evaluated immediately for RBC count, WBC count, and protein and glucose concentrations, and cytologic examination also was performed. Samples were considered normal when protein concentration was < 25 mg/dL and CSF contained < 6WBCs/microL and < 25 RBCs/microL. Samples were stored at -70 degrees C. Sections of brain tissue were collected and processed for histologic examination. The MMPs were evaluated by use of gelatin zymography and a polyclonal antibody-based sandwich ELISA. RESULTS: Mean WBC count for CSF samples was < 1 WBC/microL (range, 0 to 3 WBCs/mL). Mean protein concentration was 12 mg/dL (range, 8 to 17 mg/dL). Mean RBC count was 3.65 RBCs/microL (range, 0 to 21 RBCs/microL). All CSF samples generated a clear band on zymography gels that corresponded to the human commercial standard of proenzyme MMP-2. Other major clear bands were not detected on zymography gels. Bands correlating to MMP-9 were not detected in any samples. The ELISA results revealed a mean +/- SD proenzyme MMP-2 concentration of 5.61 +/- 1.92 ng/mL (range, 3.36 to 10.83 ng/mL). CONCLUSIONS AND CLINICAL RELEVANCE: The proenzyme form of MMP-2 is detectable in CSF of clinically normal dogs, whereas MMP-9 is not detectable. Additional investigation of MMPs in CSF from dogs with various diseases of the nervous system is indicated.     

Transient leakage across the blood-cerebrospinal fluid barrier after intrathecal metrizamide administration to dogs

Cerebrospinal fluid samples from 9 dogs given 84 mg of metrizamide/kg of body weight intrathecally were collected at intervals from 3 hours to 30 days after treatment and were compared with CSF samples collected before metrizamide treatment (base line) and with samples taken at similar intervals from 2 nontreated control dogs. Increased CSF albumin (mean 19.2 mg/dl) and immunoglobulin (Ig) G (mean 5.91 mg/dl) concentrations occurred 1 day after myelography, compared with base-line concentrations (6.15 and 1.24 mg/dl, respectively) and with concentrations from controls. Immunoglobulin M and IgA concentrations also were increased in some of these samples. However, immediately after myelography (3 hours after treatment) CSF albumin and IgG concentrations were comparable with those of controls, and these values returned to base line within 5 days of myelography and remained so for 30 days. A high correlation between albumin and IgG concentrations of individual CSF samples indicated the likelihood that leakage across the blood-CSF barrier was the origin of the increased values. A transient increase in CSF leukocytes, consisting of mononuclear cells and neutrophils, was also noticed 1 day after treatment but not at other times and not in controls. Nonsuppurative, predominately histiocytic meningitis of decreasing intensity was noticed in dogs euthanatized at 1 or 5 days, but not in dogs euthanatized at 10, 20, or 30 days after treatment. The meningeal cells stained intensely with periodic acid-Schiff stain and intracellular contrast medium was ultrastructurally apparent in phagolysosomes. Control dogs killed after 30 days did not have these changes. The intrathecal administration of metrizamide resulted in transient leakage of serum components into CSF and an accompanying transient meningitis.     

Characteristics of cerebrospinal fluid associated with canine granulomatous meningoencephalomyelitis: a retrospective study

Cerebrospinal fluid of 22 dogs with histologically confirmed granulomatous meningoencephalomyelitis was analyzed, retrospectively. Seventeen dogs had cisternal CSF analysis, 4 dogs had lumbar CSF analysis, and 1 dog had both. For cisternal CSF, the mean +/- SEM total WBC count was 800.8 +/- 300.9 cells/microliter. The WBC differential count was predominantly lymphoplasmacytic cells, but 13 of the 18 cisternal CSF had polymorphonuclear (PMN) cells, and the mean +/- SEM PMN cell percentage was 18.6 +/- 5.3%. The mean +/- SEM total protein content of cisternal CSF was 255.8 +/- 98 mg/dl. Of 5 cisternal CSF pressures measured, 4 were within the normal range. The mean +/- SEM total WBC count and total protein content of lumbar CSF were 533.4 +/- 256.5 cells/mu/microliter and 163.2 +/- 25 mg of protein/dl, respectively. As with cisternal CSF, the WBC differential count of lumbar CSF was predominantly lymphoplasmacytic cells. Of 5 lumbar CSF, 4 contained PMN cells, but the percentage was less than the PMN cell percentage of cisternal CSF. Although variable, the general pattern of CSF abnormality associated with granulomatous meningoencephalomyelitis was different from the CSF abnormalities commonly seen with viral, bacterial, or mycotic encephalitides.     

Evaluation of the ADVIA 120 for analysis of canine cerebrospinal fluid

BACKGROUND: Conventional techniques for canine cerebrospinal fluid (CSF) analysis require large sample volumes and are labor intensive and subject to operator variability. Objective: The purpose of this study was to evaluate the ADVIA120 CSF assay for analysis of canine CSF samples. METHODS: CSF samples collected from 36 healthy control dogs and 17 dogs with neurologic disease were processed in parallel using the automated assay and established manual methods using a hemocytometer and cytocentrifugation. Results for WBC (total nucleated cell) count, RBC count, and differential nucleated cell percentages were compared using Spearman rank correlation coefficients and Bland-Altman bias plots. RESULTS: Correlation coefficients for WBC and RBC counts were 0.57 and 0.83 for controls, and 0.92 and 0.94 for ill dogs, respectively. Coefficients for the percentages of neutrophils, lymphocytes, and monocytes were 0.53, 0.26, and 0.12 for controls and 0.77, 0.92, and 0.70 for dogs with neurologic disease. When data were combined (n=53), correlation coefficients were 0.86 and 0.91 for WBC and RBC counts, and 0.63, 0.43, and 0.30 for neutrophil, lymphocyte, and monocyte percentages. A 9.5% positive bias and 7.0% negative bias were obtained for the ADVIA 120 CSF assay for lymphocytes and macrophages in dogs with neurologic disease with Bland-Altman analysis. A 12.2% positive bias was found for lymphocyte percentage in dogs with neurologic disease. CONCLUSIONS: Manual and automated CSF assays had moderate to excellent correlation for WBC and RBC concentrations, but results were more variable for differential cell percentages. The ADVIA assay may be more useful for assessment of canine CSF with adjustment of cell differentiation algorithms.     

A COMPARISON OF IOPAMIDOL AND METRIZAMIDE FOR CERVICAL MYELOGRAPHY IN THE DOG

Cervical myelography using iopamidol, a new nonionic contrast medium, was studied in nine dogs. Postmyelographic seizure activity, motor evoked potentials, and rectal temperatures were monitored, and myelographic quality was subjectively evaluated. The results were compared with data from eight dogs that had metrizamide myelography. The iopamidol group had fewer seizures ( p < 0.01) but exhibited no difference in motor evoked potential or rectal temperature recordings. Myelographic quality was similar for iopamidol and metrizamide. The study suggests that iopamidol was less neurotoxic than metrizamide for canine cervical myelography.     

Comparison of nonionic contrast agents iohexol and iotrolan for cisternal myelography in dogs

During this investigation, the use of iohexol was compared with iotrolan for canine cisternal myelography. Iohexol and iotrolan myelography was done in 6 dogs by cisternal puncture with a 6-week interval between both procedures; each dog served as its own control. Cerebrospinal fluid (CSF) was collected for baseline analysis from each dog immediately before the contrast agent was injected. Cerebrospinal fluid samples were obtained at 1, 3, 7, and 14 days after injection of each contrast medium for cytologic and chemical analysis. Total CSF leucocyte count and glucose concentration did not change significantly in comparison with baseline data in any of the samples. After the injection of iohexol, protein concentration increased significantly in the 24-hour sample, and lactate dehydrogenase activity increased significantly in the 3-day sample. Significant difference was not found between the different samples collected at 1, 3, 7, and 14 days, compared with both contrast media. None of the dogs had seizure activity during a 5-hour postmyelographic observation period. Pathologic changes were not found by gross or microscopic examination of the spinal cord. Although a degradation in time of radiographic quality of all myelograms took place, the average radiographic score decreased more rapidly with iohexol. The average score at 90 minutes with iotrolan was comparable with the score at 45 minutes with iohexol, and the average score at 150 minutes with iotrolan was better than the score at 90 minutes with iohexol. At 5 and 10 minutes after cisternal injection, no significant difference was observable between the myelograms, but from 45 minutes onward, myelograms with iotrolan were superior.     

EXPERIMENTAL ARACHNOID FIBROSIS PRODUCED BY METRIZAMIDE IN THE DOG*

The short-term neurologic and long-term leptomeningeal effects of repeated subarachnoid administration of metrizamide at concentrations of 170 mg I/ml and 300 mg I/ml were investigated in dogs. After two months, arachnoid fibrosis of varying degrees was present in all dogs that had received metrizamide at the higher concentration. The higher concentration of met-rizamide was more epileptogenic than the concentration of 170 mg I/ml. The presence of subarachnoid hemorrhage was not considered to play a role in the development of the arachnoid fibrosis. Veterinary Radiology Vol. 21, No. 2, 1980; pp 78–81.     

Composition of cerebrospinal fluid in clinically normal adult ferrets

OBJECTIVE: To determine the protein and cellular composition of CSF in healthy adult ferrets. ANIMALS: 42 clinically normal adult ferrets. PROCEDURE: CSF samples were collected from the cerebellomedullary cistern of anesthetized ferrets by use of disposable 25-gauge, 1.6-cm-long hypodermic needles. Samples were processed within 20 minutes after collection. The number of WBCs and RBCs per microliter of CSF was counted by use of a hemacytometer. The total protein concentration was determined by use of an automated chemistry analyzer. RESULTS: Total WBC counts (range, 0 to 8 cells/microL; mean, 1.59 cells/microL) in CSF of ferrets were similar to reference range values obtained for CSF from other species. Twenty-seven CSF samples had <100 RBCs/microL (mean, 20.3 RBCs/microL). A small but significant effect of blood contamination on WBC counts was found between the 27 CSF samples with <100 RBCs/microL and the remaining samples. Protein concentrations in CSF of ferrets (range, 28.0 to 68.0 mg/dL; mean, 31.4 mg/dL) were higher than has been reported for the CSF of dogs and cats. A significant effect of blood contamination on the CSF protein concentration was not found. CONCLUSION AND CLINICAL RELEVANCE: We have established reference range values for WBC counts and protein concentrations in CSF from healthy adult ferrets that may be useful in the clinical investigation of CNS disease. Results of our study indicate that the WBC count is significantly affected by blood contamination of the CSF sample.     

Comparison of metrizamide and iohexol for cisternal myelographic examination of dogs

A double-blind study, using metrizamide, iohexol, or Ringer's solution (control) as cisternal myelographic agents, was performed on 25 dogs. Before myelographic examination was done, each dog was subjected to physical, clinical pathologic, and neurologic examinations, as well as examinations by electroencephalography and computerized tomography. These were repeated 24 hours after completion of the myelographic examination. The group of dogs given metrizamide (group II) had a significantly greater occurrence of seizure activity (6 of 10) than did the control dogs (group I; 0 of 5) or dogs given iohexol (group III; 0 of 10; P less than 0.003). In group II, the CSF microprotein concentration was significantly greater 24 hours after myelography was done than were the values in groups I and III (P less than 0.003). Myelograms of the group II dogs (metrizamide) and group III dogs (iohexol) had similar diagnostic qualities. At 24 hours after myelographic examination was done, computerized tomography scan revealed that each dog given metrizamide and iohexol had myelographic contrast material in the brain and cervical spinal cord parenchyma. Seemingly, iohexol has good diagnostic quality, but is less epileptogenic than metrizamide when used in cervical myelographic examinations of dogs.     

EFFECTS OF METRIZAMIDE MYELOGRAPHY ON CEREBROSPINAL FLUID ANALYSIS IN THE DOG

The effect of metrizamide myelography on the composition of cerebrospinal fluid (CSF) was studied. Seven dogs received an intracisternal injection of metrizamide. An intracisternal puncture was performed in three additional dogs that did not receive metrizamide. CSF was collected before myelography and 24, 72, and 144 hours after myelography from all dogs. A significant increase in the percentage of neutrophils (p<0.05) and a pleocytosis noted 24 hours after myelography (p<0.02) were attributed to the effect of metrizamide. Significant increases in total protein concentration (p<0.001) and erythrocyte count (p<0.05), and a decrease in the percentage of small mononuclear cells (p<0.01) were attributed to repeated intracisternal puncture. No significant changes were observed for CSF creatine phosphokinase activity or the percentage of large mononuclear cells.     

A PROSPECTIVE CLINICAL TRIAL COMPARING METRIZAMIDE AND IOHEXOL FOR EQUINE MYELOGRAPHY

A prospective clinical trial comparing adverse postmyelographic effects and myelographic quality of metrizamide and iohexol was conducted. Using a predetermined, randomized assignment, 24 horses exhibiting neurologic signs were administered either metrizamide (180 mgl/ml) or iohexol (180 mgl/ml) via cerebellomedullary puncture. Each horse was evaluated postmyelographically for adverse effects. Myelographic quality was assessed by a numerical scoring method. Adverse effects were observed more frequently with metrizamide (21) compared with iohexol (6) myelography (p < 0.05). Seizures, intensification of preexisting neurologic signs and prolonged anesthetic recovery were the most common complications after myelography. There was no difference in myelographic quality (p > 0.05). We conclude that iohexol is safer than metrizamide for equine myelography and that quality myelograms can be obtained with either contrast medium.     

Iohexol myelography in the horse

Iohexol, a water soluble non-ionic contrast agent, was evaluated for myelography in the horse. Both 300 and 350 mg iodine/ml iohexol gave diagnostic cervical myelograms. Pathological changes were limited to extradural oedema and an increase in the number of white blood cells and specific gravity in the cerebrospinal fluid two days after myelography. This increase in white blood cells in the cerebrospinal fluid was, however, much less than that recorded by other authors using metrizamide and iopamidol contrast media. These findings indicate that iohexol is a less irritant myelographic contrast agent than those previously evaluated in the horse.     

EFFECTS OF POSTMYELOGRAPHIC REMOVAL OF METRIZAMIDE IN DOGS

Using a paired crossover trial, the effects of postmyelographic removal of metrizamide injected via the cerebellomedullary cistern were studied in 16 normal dogs. Each animal received a routine and a withdrawal myelogram. Seizure activity, changes in spinal evoked motor potentials and body temperature were measured following each myelogram. The amount of metrizamide removed was determined by densitometrically analyzing radiographs of cerebrospinal fluid/metrizamide aliquots recovered during the withdrawal procedure. There was a significant decrease in the number of seizures for withdrawal versus nonwithdrawal myelography (p < 0.01). The mean amount of metrizamide withdrawn per dog was 29% of the total injected.     

Investigation of diagnostic importance of platelet closure times measured by Platelet Function Analyzer--PFA 100 in dogs with endotoxemia

This study was performed to evaluate the diagnostic importance of the platelet closure times measured by the Platelet Function Analyzer (PFA-100) in dogs with endotoxemia. E. coli endotoxin was given intravenously once, at the dose of 0.02 mg/kg or 1 mg/kg in groups I (n=9) and II (n=8), respectively. Normal saline (0.1 ml/kg) was injected in group III (n=8).The dogs were monitored for 48 h, and venous blood samples were collected prior to (baseline) and at intervals of 0.5, 1, 2, 4, 6, 8, 12, 24 and 48 h subsequent to the treatments. The white blood cell (WBC), platelet counts, and hematocrit (Hct) values were recorded. Platelet closure times were determined, using collagen/epinephrine (CEPI) and collagen/adenosine diphosphate (CADP) cartridges. Within 0.5 h after the endotoxin application baseline WBC and platelet counts (mean +/-SD) decreased significantly (p<0.001) to 2000 +/- 500 and 1850 +/- 200 cells/microl or 69.000 +/- 12.500 and 27.000 +/- 6.400 cells/microl in groups I and II, respectively. Platelet counts remained low during the first 1-48 h, but the WBC count was high at the 8th-48th h, in groups I and II, compared with baselines (p<0.001). After the application of the endotoxin, Hct values increased from baseline values of 37 +/- 3 or 39 +/- 2% to 48 +/- 2 or 51 +/- 3%, within 1 h (p<0.001), in groups I and II, respectively. Hct values in group II were notably higher (p<0.001) than those of group I, during the 2nd-48th h. Hematological parameters and closure times did not differ significantly throughout the study in group III. Baseline closure time ranged from 79 +/- 5 seconds (s) to 86 +/- 5 s for CADP and 144 +/- 13 s to 159 +/- 14 s for CEPI in all dogs (n=25). At 0.5 h after the endotoxin, the closure times of CADP as well as CEPI declined to 62 +/- 6 s and 76 +/- 8 s in group I (p<0.001) and 57 +/- 5 s and 75 +/- 6 s in group II (p<0.001). Afterwards, closure time prolonged to the levels of 280 +/- 8 s (CADP) and 294 +/- 5 s (CEPI) by 48 h (p<0.001) in group II, but returned to the baseline limit in group I. In conclusion, our results show that the shortened closure times may serve as a very early diagnostic sign of endotoxemia, prolonged closure times however may be used as an index for the severity of endotoxemia.