Sofia Cerda-Gonzalez

Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy

OBJECTIVE To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled suspected idiopathic epilepsy. DESIGN Open-label, noncomparative clinical trial. ANIMALS 11 client-owned dogs suspected of having idiopathic epilepsy that was inadequately controlled with phenobarbital, potassium bromide, or a combination of these 2 drugs. PROCEDURES Dogs were treated with pregabalin (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 h) for 3 months. Number of generalized seizures in the 3 months before and after initiation of pregabalin treatment was recorded. Number of responders (>or= 50% reduction in seizure frequency) was recorded, and seizure frequency before and after initiation of pregabalin treatment was compared by use of a nonparametric Wilcoxon signed rank test. RESULTS Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration in the 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. Mean and median plasma pregabalin concentrations for all dogs were 6.4 and 7.3 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Pregabalin may hold promise as a safe and effective adjunct anticonvulsant drug for epileptic dogs poorly controlled with the standard drugs phenobarbital or potassium bromide. Adverse effects of pregabalin appeared to be mild. Additional studies with larger numbers of dogs and longer follow-up intervals are warranted.

Mycophenolate mofetil treatment in dogs with serologically diagnosed acquired myasthenia gravis: 27 cases (1999-2008).

OBJECTIVE-To compare clinical outcome in dogs with serologically diagnosed acquired myasthenia gravis (MG) treated with pyridostigmine bromide (PYR) with that of dogs treated with mycophenolate mofetil (MMF) and PYR (MMF + PYR). DESIGN-Retrospective case series. ANIMALS-27 dogs. PROCEDURES-Medical records from August 1999 through February 2008 were reviewed to identify dogs with serologically diagnosed acquired MG treated with PYR or MMF + PYR. Data collected for each dog included signalment, whether the dog had megaesophagus or pneumonia (or both), thyroid hormone concentration, remission, time to remission, and survival time. Rates for detection of clinical signs and survival time were compared. Survival time was estimated via the Kaplan-Meier method. Influence of drug treatment protocol on likelihood of remission, time to remission, and survival time was examined. Effects of MMF treatment, megaesophagus, pneumonia, and low serum thyroid hormone concentration on time to remission and survival time were also analyzed. RESULTS-12 dogs were treated with PYR, and 15 were treated with MMF + PYR. Mortality rates were 33% (PYR) and 40% (MMF + PYR). There was pharmacological remission in 5 and 6 dogs in the PYR and MMF + PYR groups, respectively. No significant differences were detected between treatment groups for remission rate, time to remission, or survival time. Megaesophagus, pneumonia, and low serum thyroid hormone concentration had no significant effect on time to remission or survival time for either treatment group. CONCLUSIONS AND CLINICAL RELEVANCE-The results did not support routine use of MMF for the treatment of dogs with acquired MG.

Congenital diseases of the craniocervical junction in the dog.

Craniocervical junction disorders are most frequently seen in toy and small-breed dogs. They can present a diagnostic challenge, as multiple anomalies can be present concurrently and share similar clinical manifestations. Some, such as Chiari-like malformations, may be present in asymptomatic dogs. A thorough evaluation of the entire craniocervical junction, frequently using more than 1 imaging modality, is necessary before making treatment decisions.

Prevalence of Urinary Tract Infection in Dogs after Surgery for Thoracolumbar Intervertebral Disc Extrusion

BACKGROUND Urinary tract infection (UTI) is a common complication in people with spinal cord injury (SCI). Dogs with acute intervertebral disc extrusion (IVDE) have similar risk factors for UTI when compared with human SCI patients and have a high perioperative prevalence of UTI. OBJECTIVES Determine the prevalence of UTI in dogs for 3 months after surgery for thoracolumbar IVDE and identify risk factors for development of UTI. ANIMALS Twenty-five dogs treated surgically for 26 acute disc extrusions. METHODS Prospective study. Urinalysis and urine culture were performed perioperatively. At home, owners monitored urine with dipsticks every 48 hours for 1 month then once a week until 3 months. Dogs returned for assessment of motor function, urinalysis, and urine culture at 1 and 3 months after surgery. Presence of UTI over the 3-month period was correlated to potential risk factors. RESULTS Ten dogs (38%) developed 12 UTIs over the 3-month period, with the majority occurring between weeks 1 and 6; 60% of the UTIs were occult. Hematuria in the absence of pyuria or UTI was a common finding in the perioperative period. Sex, breed, and ambulatory status influenced the risk of developing a UTI. CONCLUSIONS AND CLINICAL IMPORTANCE There is a high prevalence of UTIs, many of which are occult, in the 3 months after surgery for thoracolumbar IVDE. These dogs should be routinely monitored for UTI with urine culture regardless of urinalysis results.

Spinal cord nephroblastoma in dogs: 11 cases (1985-2007).

OBJECTIVE To evaluate clinical features and outcome of dogs with a confirmed spinal cord nephroblastoma and to describe the use of Wilms tumor-1 (WT-1) immunohistochemical staining to confirm a diagnosis of nephroblastoma in dogs. DESIGN Retrospective case series. Animals-11 dogs with a spinal cord nephroblastoma. PROCEDURES Medical records of dogs with a spinal cord nephroblastoma were reviewed. Information extracted included signalment, history, clinical signs, results of diagnostic testing, tumor location, treatment, and outcome. The diagnosis was confirmed through histologic review and WT-1 immunohistochemical staining of a tumor sample. In dogs with negative results for staining with WT-1, staining for cytokeratin, vimentin, and glial fibrillar acidic protein was performed. RESULTS 11 dogs had a spinal cord tumor with a histologic appearance and immunohistochemical staining consistent with a nephroblastoma. Positive results for staining with WT-1 were detected in 9 of 11 dogs. Age at admission ranged from 5 to 48 months (median, 14 months). Nine dogs were female. All had progressive paraparesis, paraplegia, or ataxia. Duration of clinical signs ranged from 2 to 60 days (median, 14 days). Median survival time was 30 days from the time of diagnosis. Median survival time in dogs treated via surgical resection was 70.5 days. CONCLUSIONS AND CLINICAL RELEVANCE The prognosis for dogs with a spinal cord nephroblastoma appeared to be poor, although combined surgical resection and radiation therapy may provide a good functional outcome. Results for staining with WT-1 can be used to support a diagnosis of nephroblastoma.

Medullary Position at the Craniocervical Junction in Mature Cavalier King Charles Spaniels: Relationship with Neurologic Signs and Syringomyelia

Background Medullary elevation (ie, medullary kinking) at the craniocervical junction (CCJ) is reported in dogs with Chiari‐like malformations (CM), but its diagnostic criteria and clinical relevance are unclear. Objective To describe the position of the medulla at the CCJ in mature cavalier King Charles spaniels (CKCS), and evaluate its relationship with clinical status and the presence of syringomyelia. Animals Thirty‐six CKCS, 5–12 years of age, including 16 asymptomatic dogs. Methods Dogs were assigned a neurologic grade; magnetic resonance imaging (MRI) of the CCJ then was performed. The presence of a CM and syringomyelia was recorded and syringomyelia severity was quantified. Medullary position was quantified using the medullary kinking index, the elevation angle and obex position relative to the foramen magnum. The relationship between medullary position measures and presence and severity of neurologic signs and syringomyelia was investigated. Results Chiari‐like malformation was found in 33 dogs; 26 of them had syringomyelia. Mean medullary kinking index was 46.4% (SD, 10.3), elevation angle was 132° (SD, 12) and obex position was 3.5 mm (SD, 0.8). A higher medullary kinking index was associated with the presence of neurologic signs (P = .0368). Obex position was associated with the presence (P = .0018) and severity of syringomyelia (P = .0164). Conclusions and clinical importance There is a significant association between medullary elevation and clinical signs, whereas more caudal brainstem positions appear related to the presence of syringomyelia.

Dorsal Compressive Atlantoaxial Bands and the Craniocervical Junction Syndrome: Association with Clinical Signs and Syringomyelia in Mature Cavalier King Charles Spaniels

Background Dorsal compressive lesions at the atlantoaxial junction (ie, AA bands) occur in dogs with Chiari‐like malformations (CMs), but their clinical relevance is unclear. Objective Investigate the influence of AA bands on clinical status and syringomyelia (SM) in mature cavalier King Charles spaniels (CKCS). Animals Thirty‐six CKCS, 5–12 years of age, including 20 dogs with neuropathic pain. Methods Dogs were examined and assigned a neurologic grade. Magnetic resonance imaging (MRI) of the craniocervical junction was performed with the craniocervical junction extended and flexed (ie, normal standing position). Imaging studies were assessed for the presence of an AA band, CM, SM or some combination of these findings. Band and SM severity were quantified using an objective compression index and ordinal grading scale, respectively. Results Of 36 CKCS imaged, 34 had CM. Atlantoaxial bands were present in 31 dogs and were more prominent in extended than flexed positions. Syringomyelia was found in 26 dogs, 23 of which also had AA bands. Bands were associated with both the presence (P = .0031) and severity (P = .008) of clinical signs and SM (P = .0147, P = .0311, respectively). Higher compression indices were associated with more severe SM (P = .0137). Conclusions Prevalence of AA bands in older CKCS is high. Positioning of dogs in extension during MRI enhances the sensitivity of the study for detecting this important abnormality. There were significant associations among AA bands, clinical signs, and SM in dogs with CM; additional work is needed to understand whether or not this relationship is causal.

Longitudinal Study of the Relationship among Craniocervical Morphology, Clinical Progression, and Syringomyelia in a Cohort of Cavalier King Charles Spaniels

Background Craniocervical junction (CCJ) anomalies and secondary syringomyelia are commonly diagnosed in Cavalier King Charles spaniel (CKCS). Familiarity with the natural history of these abnormalities is vital to understanding the disease syndrome. Objective To evaluate magnetic resonance imaging (MRI) predictors of worsening clinical signs, syringomyelia, and morphology in CKCS longitudinally. Animals Fifty‐four client‐owned CKCS, 5–13 years old; 50% currently symptomatic. Methods Longitudinal observational study. We enrolled CKCS with an MRI of the CCJ performed ≥3 years earlier. We used questionnaires and neurologic examinations to grade initial and current clinical status. Dogs that could be anesthetized were reimaged. Morphologic assessments included the presence and severity of: Chiari‐like malformations, medullary position, atlantooccipital overlapping (AOO), dorsal atlantoaxial bands, and syringomyelia. Cranial cavity volumes and foramen magnum height were measured. Results Clinical status was evaluated in 54 dogs; 36/54 were reimaged. Mean follow‐up was 71 months. Of initially asymptomatic dogs, 32% were symptomatic at re‐evaluation. Of initially symptomatic dogs, 56% had worsened; 13% had improved with medical management. The morphology of the CCJ at initial imaging did not predict development of either new or worsened signs or syringomyelia by the time of re‐evaluation. Conclusion Craniocervical junction anomalies assessed in this study did not appear predictive of future clinical status or syringomyelia in our cohort. The impacts of syringomyelia, AOO, and atlantoaxial bands on future clinical status merit further study in larger groups of CKCS. Clinical progression in our cohort of medically managed CKCS did not differ substantially from published reports of those treated surgically.

Pharmacokinetics of Single-Dose Rectal Zonisamide Administration in Normal Dogs

Background Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications. Hypothesis/Objectives To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and PO to dogs. Animals Eight healthy research dogs. Methods Randomized cross‐over design. Zonisamide, 10 mg/kg, was administered rectally in polyethylene glycol (PEG‐R), rectally in water (H2O‐R), and as an oral capsule. Plasma zonisamide concentrations were measured until 72 hours after administration. Zonisamide was quantitated by HPLC and plasma concentration versus time curve data was analyzed by using noncompartmental modeling. Results Mean maximum plasma zonisamide concentrations (μg/mL) were significantly higher after oral administration (11.56 ± 4.04) compared to H2O‐R (5.00 ± 1.83) (P = .004). Disappearance half‐life (hours) and mean time to maximum concentration (hours) were not significantly different between methods of administration. Mean relative bioavailability of PEG‐R (85 ± 69%) was significantly higher than that of H2O‐R (53 ± 37%) (P = .039). Dogs tolerated all dosing forms with no evidence of adverse effects. Conclusions and Clinical Importance The vehicle in which zonisamide is dissolved influences rectal bioavailability, with PEG preferred to H2O‐R. Because of the prolonged time to maximum concentration, rectal administration of zonisamide should not be used to treat status epilepticus in dogs. A dose higher than what was used in this study might be necessary, if currently recommended minimum therapeutic concentrations (10 μg/mL) are to be achieved with a single‐dose administration.

Questionnaire-based Analysis of Owner-reported Scratching and Pain Signs in Cavalier King Charles Spaniels Screened for Chiari-like Malformation and Syringomyelia

Background Chiari‐like malformation (CM) and syringomyelia (SM) cause a pain syndrome in Cavalier King Charles spaniels (CKCS). Clinical signs are not consistently apparent on neurologic examination, and owner reporting of signs provides vital clinical history. However, owner questionnaires for this disease are not well developed. Objectives To develop a tool to capture owner‐reported clinical signs for use in clinical trials and to compare owner‐reported signs with the presence of pain on neurologic examination and SM on magnetic resonance imaging (MRI). Animals Fifty client‐owned CKCS. Methods Owners completed a questionnaire and pain/scratch map. Each dog underwent a neurologic examination and craniocervical magnetic resonance imaging (MRI). Questionnaire responses were developed into scores, area of shading for pain/scratch maps was measured, and consistency of responses between these tools was assessed. Owner‐reported findings were compared with neurologic examination findings and presence and severity of SM on MRI. Results Thirty‐three dogs were symptomatic and 17 asymptomatic; 30 had SM. The most common sign of pain was crying out when lifted (n = 11). Extent of shaded areas on maps positively correlated with questionnaire scores for pain (r 2 = 0.213, P = 0.006) and scratch (r 2 = 0.104, P = 0.089). Owner‐reported findings were not significantly associated with presence or severity of SM or neurologic examination findings. Owner‐reported lateralization of signs was significantly associated with SM lateralization (P < 0.0001). Conclusions The questionnaire and maps may be useful for clinical trials. Lack of association of owner‐reported signs with SM highlights our lack of understanding of the pathophysiology of pain in this disease.