Pharmacokinetics of a commercially available product and a compounded formulation of extended-release levetiracetam after oral administration of a single dose in cats.

OBJECTIVE: To compare pharmacokinetics of levetiracetam in serum and CSF of cats after oral administration of extended-release (ER) levetiracetam. ANIMALS: 9 healthy cats. PROCEDURES: Cats received 1 dose of a commercially available ER levetiracetam product (500 mg, PO). Thirteen blood and 10 CSF samples were collected over a 24-hour period for pharmacokinetic analysis. After 1 week, cats received 1 dose of a compounded ER levetiracetam formulation (500 mg, PO), and samples were obtained at the same times for analysis. RESULTS: CSF concentrations of levetiracetam closely paralleled serum concentrations. There were significant differences between the commercially available product and the compounded formulation for mean ± SD serum maximum concentration (Cmax; 126 ± 33 µg/mL and 169 ± 51 µg/mL, respectively), Cmax corrected for dose (0.83 ± 0.10 µg/mL/mg and 1.10 ± 0.28 µg/mL/mg, respectively), and time to Cmax (5.1 ± 1.6 hours and 3.1 ± 1.5 hours, respectively). Half-life for the commercially available product and compounded formulation of ER levetiracetam was 4.3 ± 2.0 hours and 5.0 ± 1.6 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The commercially available product and compounded formulation of ER levetiracetam both maintained concentrations in healthy cats 12 hours after oral administration that have been found to be therapeutic in humans (ie, 5 µg/mL). Results of this study supported dosing intervals of 12 hours, and potentially 24 hours, for oral administration of ER levetiracetam to cats. Monitoring of serum concentrations of levetiracetam can be used as an accurate representation of levetiracetam concentrations in CSF of cats.

Intracranial magnetic resonance imaging artifacts and pseudolesions in dogs and cats.

Normal anatomic variation, study design, external factors, and tissue characteristics can all influence the manifestation of structures on magnetic resonance images (MRI). For the purpose of this review, imaging artifacts are considered to be nonpathologic abnormalities resulting from study design, intrinsic tissue characteristics, or external factors, while MRI pseudolesions are due to normal anatomic variation. Awareness of imaging artifacts and pseudolesions, as well as normal anatomic structures, is important when determining pathologic vs. normal or clinically insignificant abnormalities. The purpose of this report is to examine the literature to compile a review of selected artifacts and pseudolesions that are commonly encountered when imaging the canine and feline brain.

The function, composition and analysis of cerebrospinal fluid in companion animals: part I - function and composition.

Cerebrospinal fluid (CSF) is a clear, colourless ultrafiltrate of plasma with low protein content and few cells. The CSF is mainly produced by the choroid plexus, but also by the ependymal lining cells of the brain's ventricular system. CSF flows through the ventricular system and then into the subarachnoid space and it is subsequently absorbed through the subarachnoid villi into the venous system. CSF has several functions in the nervous system. It protects the brain during blood pressure fluctuations, regulates the chemical environment of the central nervous system and it is a vehicle for intracerebral transport. This two-part article reviews CSF function, physiology, analytical techniques and interpretations in disease states of companion animals. This first part will address the function and composition of CSF in companion animals.

Cerebrospinal fluid centesis at the cerebellomedullary cistern of kittens.

We needed an effective technique for obtaining cerebrospinal fluid (CSF) from young (2- to 18-week-old) kittens. Standard veterinary technique was not suitable, so we adapted a previously published technique for rats. We first established an effective isoflurane-only anesthetic protocol for young kittens. After inhalant anesthesia, the kittens were positioned on a supporting platform to gain flexion of the head and neck. A micromanipulator was used to hold and slowly advance the collection needle. At the time this report was written, we had collected a total of 33 samples from eight kittens without causing apparent neurologic deficits. Correct positioning of the animal and collection needle was critical for success. This procedure enabled the collection of approximately 0.5 ml CSF from kittens younger than 12 weeks and larger volumes from older kittens.

Analysis of cerebrospinal fluid from dogs and cats after 24 and 48 hours of storage.

OBJECTIVE: To compare differential cell counts and cell characteristics of CSF samples analyzed immediately or after storage for 24 and 48 hours at 4 C with and without the addition of autologous serum. DESIGN: Prospective study. ANIMALS: 36 dogs and 6 cats. PROCEDURE: CSF samples were collected from the cerebellomedullary cistern and divided into 250-microliter aliquots. Slides of CSF samples were prepared by use of cytocentrifugation immediately and after 24 and 48 hours of storage with addition of autologous serum (final concentrations, 11 and 29%). Differential cell counts and number of unrecognizable cells were compared among preparations. RESULTS: Significant differences in the differential cell counts were not detected among samples analyzed before or after storage. Although the number of unrecognizable cells increased with storage time, this did not result in a significant effect on cell distribution or diagnosis. Cells in CSF samples stored with 11% serum more closely resembled cells in fresh samples than did cells in samples stored with 29% serum. CONCLUSIONS AND CLINICAL RELEVANCE: CSF samples collected at veterinary clinics remote from a diagnostic laboratory or during nonoperational hours may be preserved through the addition of autologous serum. Evaluation of such samples is likely to result in an accurate diagnosis for at least 48 hours after collection.

[Cells in the cerebrospinal fluid of dogs and cats. Part 2]. / Zellen im Liquor cerebrospinalis von Hund und Katze. Teil 2.

Three groups of cerebrospinal fluid (CSF) cells can be formed: 1. cells of the normal CSF, such as monocytes, small lymphocytes and occasionally cells of the ventricle system, 2. cells found in dogs and cats with neurologic disorders, such as reactive monocytes and lymphocytes, macrophages, neutrophils and eosinophils in addition to cells of the first group, 3. neoplastic cells. The different cells are introduced and their origin, function and occurrence are discussed. Mitotic figures, degenerated cells and artefacts are also mentioned.

[Experiences with a sedimentation technique for the enrichment of cerebrospinal fluid cells in the dog and cat. Part 1]. / Erfahrungen mit einem Sedimentier-verfahren zur Anreicherung von Liquorzellen bei Hund und Katze. Teil 1.

The differentiation of cells of the cerebrospinal fluid (CSF) gives valuable information about certain neurologic diseases. The sedimentation technique of Sayk modified by Kölmel is introduced and its application described. Cells of 300 samples of CSF from dogs and cats are evaluated. There were very good to reasonable results in 88% (263 of 300) of the samples. A comparison between cell number, morphology and protein content in 150 samples was performed. 90 CSF samples with normal cell count (less than or equal to 5/mm3, determined in the Fuchs-Rosenthal chamber) were compared with the cell yield after sedimentation. In 58% (52 of 90) of the samples more than 200 cells were found, in 13% (12 of 90) more than 800 could be differentiated. The results are compared with those of other methods mentioned in the literature.

Reference intervals for feline cerebrospinal fluid: cell counts and cytologic features.

Reference intervals for feline CSF cell counts and cytologic variables were determined. Values were derived from 58 adult cats that had normal neurologic examination findings and did not have histologic lesions of the CNS. Effect of age or gender was not apparent for any CSF variable, and no CSF variable was significantly correlated with its corresponding blood value. Total WBC count and neutrophil and eosinophil percentages were positively correlated with the CSF RBC count. Thus, proposed reference intervals for feline CSF were derived from 33 cats with CSF RBC count of less than 31 cells/ul. Data for CSF samples with range between 31 and 1,700 RBC/microliters were also determined. Erythrocyte count was not significantly different in CSF collected, using 20- or 22-gauge spinal needles.

Reference intervals for feline cerebrospinal fluid: biochemical and serologic variables, IgG concentration, and electrophoretic fractionation.

Reference intervals are reported for feline CSF biochemical and serologic variables, IgG concentration, and electrophoretic fractionation, derived from 58 clinically normal adult cats that did not have histologic lesions of the CNS. There was no apparent effect of age on any variable. The CSF total protein concentration was significantly (P = 0.012) greater in males than in females, but all other variables were unaffected by gender. The only variable that had a statistically significant correlation with its corresponding blood concentration was IgG. Blood contamination of the CSF affected the following CSF variables: total protein concentration, activities of lactate dehydrogenase and creatine kinase, IgG ratio, and gamma-globulin percentage. The reference intervals proposed for feline CSF were derived from 33 cats with CSF RBC count less than 31 cells/microliters. Reference limits for CSF with 31 to 1,700 RBC/microliters also are reported.

Cerebrospinal fluid constituents of cat vary with susceptibility to motion sickness.

Six female cats, varying in susceptibility to motion sickness, were implanted with chronic cannulae in the rostral portion of the fourth ventricle. The cats were then challenged with a motion sickness-inducing stimulus. Samples of cerebrospinal fluid were withdrawn before and after emesis or 30 min of motion if emesis did not occur and again on control (no motion) days. The samples were analyzed by HPLC with an array of 16 coulometric detectors. Thirty-six compounds were identified in the samples. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not become motion sick. None of the identified compounds varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.

Cerebrospinal fluid.

It is hoped that we have demonstrated that collection, handling, and limited analysis of CSF samples from the dog and cat are relatively simple. No special equipment or handling is required, and the procedures are within the capabilities of any veterinarian interested in performing them. In addition, although this article was not intended to present a detailed discussion on the interpretation of the analysis of CSF, we have demonstrated some very practical interpretations to the various aspects of a routine CSF analysis. When combined with a signalment, complete history, and thorough general physical and neurologic examination, CSF analysis can prove invaluable in the workup of an animal with a neurologic disorder. Relatively simple laboratory procedures can be helpful in differentiating peripheral blood contamination from true intrathecal hemorrhage, in identifying an active inflammatory process, in potentially characterizing an etiologic agent, and, on rare occasions, in identifying primary or metastatic neoplastic disease involving the CNS. In many cases, the above is not directly possible, because the changes observed in our routine analysis are nonspecific. Yet, documenting and following these "nonspecific" alterations are helpful in determining if there is progression or regression of the disease process. In turn, these changes or lack of changes are helpful in identifying if the proper therapy has been instituted and if additional or different therapy is required.

[The phenomenon of the replication of ontogenetic immaturity in adult cats caused by the cerebrospinal fluid of kittens]. / Fenomen vosproizvedeniia ontogeneticheskoi nezrelosti u koshek, vyzvannyi likvorom kotiat.

Studies have been made on the electrical activity of muscles in the hindlimbs in kittens and adult cats before and after injection the liquor from 10-, 21-day and 1-month kittens into the lumbar part of the spinal cord. Analysis was made of the EMG at rest and that of the evoked reactions. It was shown that EMG of adult cats after injection of kitten liquor attained the pattern typical of the donor. The data obtained indicate the presence in kitten liquor of biologically active substances which account for the level of regulatory relationships. Transfer of these substances to adult animals results in the formation of a new level of coordinations of movements which corresponds to immature organism.

Effects of blood contamination on cerebrospinal fluid analysis.

Data were obtained from 190 cerebrospinal fluid samples collected from both clinically normal and diseased dogs, cats, cows, and horses. Red blood cells, indicating blood contamination, were identified in 115 samples. White blood cells were a rare finding in normal animals. Blood contamination appeared to have little effect on white blood cell numbers even though, in several samples, thousands of red blood cells were identified. An accepted formula to correct for blood contamination was found to be an unreliable method to determine "uncontaminated" values for white blood cells, total protein, or creatine phosphokinase.