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Background: Autoimmune mechanisms represent a novel category for causes of seizures and epilepsies in humans, and LGI1‐antibody associated limbic encephalitis occurs in cats. Hypothesis/Objectives: To investigate the presence of neural antibodies in dogs with epilepsy or dyskinesia of unknown cause using human and murine assays modified for use in dogs. Animals: Fifty‐eight dogs with epilepsy of unknown cause or suspected dyskinesia and 57 control dogs. Methods: Serum and CSF samples were collected prospectively as part of the diagnostic work‐up. Clinical data including onset and seizure/episode type were retrieved from the medical records. Screening for neural antibodies was done with cell‐based assays transfected with human genes for typical autoimmune encephalitis antigens and tissue‐based immunofluorescence assays on mouse hippocampus slices in serum and CSF samples from affected dogs and controls. The commercial human und murine assays were modified with canine‐specific secondary antibody. Positive controls were from human samples. Results: The commercial assays used in this study did not provide unequivocal evidence for presence of neural antibodies in dogs including one dog with histopathologically proven limbic encephalitis. Low titer IgLON5 antibodies were present in serum from one dog from the epilepsy/dyskinesia group and in one dog from the control group. Conclusion and Clinical Importance: Specific neural antibodies were not detected using mouse and human target antigens in dogs with epilepsy and dyskinesia of unknown origin. These findings emphasize the need for canine‐specific assays and the importance of control groups. [ABSTRACT FROM AUTHOR]

Background: Blood‐brain barrier (BBB) permeability can be assessed quantitatively using advanced imaging analysis. Hypothesis/Objectives: Quantification and characterization of blood‐brain barrier dysfunction (BBBD) patterns in dogs with brain tumors can provide useful information about tumor biology and assist in distinguishing between gliomas and meningiomas. Animals: Seventy‐eight hospitalized dogs with brain tumors and 12 control dogs without brain tumors. Methods: In a 2‐arm study, images from a prospective dynamic contrast‐enhanced (DCE; n = 15) and a retrospective archived magnetic resonance imaging study (n = 63) were analyzed by DCE and subtraction enhancement analysis (SEA) to quantify BBB permeability in affected dogs relative to control dogs (n = 6 in each arm). For the SEA method, 2 ranges of postcontrast intensity differences, that is, high (HR) and low (LR), were evaluated as possible representations of 2 classes of BBB leakage. BBB score was calculated for each dog and was associated with clinical characteristics and tumor location and class. Permeability maps were generated, using the slope values (DCE) or intensity difference (SEA) of each voxel, and analyzed. Results: Distinctive patterns and distributions of BBBD were identified for intra‐ and extra‐axial tumors. At a cutoff of 0.1, LR/HR BBB score ratio yielded a sensitivity of 80% and specificity of 100% in differentiating gliomas from meningiomas. Conclusions and Clinical Importance: Blood‐brain barrier dysfunction quantification using advanced imaging analyses has the potential to be used for assessment of brain tumor characteristics and behavior and, particularly, to help differentiating gliomas from meningiomas. [ABSTRACT FROM AUTHOR]

Recent work identified anti‐GM2 and anti‐GalNAc‐GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain‐Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune‐mediated polyneuropathies. The sera from 41 cats clinically diagnosed with immune‐mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc‐GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide. A total of 29/41 IPN‐cats had either anti‐GM2 or anti‐GalNAc‐GD1a IgG antibodies, with 24/29 cats having both. Direct comparison of anti‐GM2 (sensitivity: 70.7%; specificity: 78.2%) and anti‐GalNAc‐GD1a (sensitivity: 70.7%; specificity: 70.9%) antibodies narrowly showed anti‐GM2 IgG antibodies to be the better marker for identifying IPN‐cats when compared to the combined ONM and CTRL groups (P =.049). Anti‐GA1 and/or anti‐sulphatide IgG antibodies were ubiquitously present across all sample groups, whereas antibodies against GM1, GD1a, GD1b, SGPG, LM1 and galactocerebroside were overall only rarely observed. Anti‐GM2 and anti‐GalNAc‐GD1a IgG antibodies may serve as serum biomarkers for immune‐mediated polyneuropathies in cats, as previously observed in dogs and humans. [ABSTRACT FROM AUTHOR]

Background: Increased cerebrospinal fluid (CSF) protein concentration is a common finding in neurological diseases of dogs. Distinguishing between intrathecally‐produced proteins and proteins that have passed the blood‐CSF barrier because of barrier disruption facilitates diagnosis. Albumin is a microprotein mainly produced extrathecally that can be used as a reference marker for blood‐CSF barrier dysfunction. Objectives: Develop a quotient graph based on the CSF/serum quotient of albumin and immunoglobulin A (IgA; Reibergram) to visualize intrathecal IgA synthesis and blood‐CSF barrier dysfunction. Animals and Methods: Retrospective single‐center cohort study. A hyperbolic function was developed using data from 6 healthy Beagles and 38 dogs with neurological diseases in which an isolated blood‐CSF barrier dysfunction was expected. The function was validated using data from 10 dogs with expected intrathecal IgA synthesis and was visualized as a quotient graph. Finally, the graph was used to evaluate data of 118 dogs with various neurological diseases. Results: Within the Reibergram, the function QLimIgA=0.13QAlb2+11.9·10−6−1.01·10−3 describes the upper values of physiological IgA quotients. It detects diseases with expected intrathecal IgA synthesis with higher sensitivity (85%) and specificity (89%) than the IgA index. The upper value of the physiological albumin quotient is 2.22 and detects diseases with expected blood‐CSF barrier dysfunction (sensitivity: 81%; specificity: 88%). Conclusion and Clinical Importance: The canine Reibergram can detect blood‐CSF barrier dysfunction and intrathecal IgA synthesis in the majority of cases. The graphical visualization simplifies data evaluation and makes it a feasible tool in routine CSF diagnostic testing. [ABSTRACT FROM AUTHOR]

Background: Thoracolumbar intervertebral disc extrusion (TL‐IVDE) is the most common cause of acute paraparesis and paraplegia in dogs; however, guidelines on management of the condition are lacking. Objectives: To summarize the current literature as it relates to diagnosis and management of acute TL‐IVDE in dogs, and to formulate clinically relevant evidence‐based recommendations. Animals: None. Methods: A panel of 8 experts was convened to assess and summarize evidence from the peer‐reviewed literature in order to develop consensus clinical recommendations. Level of evidence available to support each recommendation was assessed and reported. Results: The majority of available literature described observational studies. Most recommendations made by the panel were supported by a low or moderate level of evidence, and several areas of high need for further study were identified. These include better understanding of the ideal timing for surgical decompression, expected surgical vs medical outcomes for more mildly affected dogs, impact of durotomy on locomotor outcome and development of progressive myelomalacia, and refining of postoperative care, and genetic and preventative care studies. Conclusions and Clinical Importance: Future efforts should build on current recommendations by conducting prospective studies and randomized controlled trials, where possible, to address identified gaps in knowledge and to develop cost effectiveness and number needed to treat studies supporting various aspects of diagnosis and treatment of TL‐IVDE. [ABSTRACT FROM AUTHOR]

Background: Reduced pelvic limb reflexes in dogs with spinal cord injury typically suggests a lesion of the L4‐S3 spinal cord segments. However, pelvic limb reflexes might also be reduced in dogs with a T3‐L3 myelopathy and concurrent spinal shock. Hypothesis/Objectives: We hypothesized that statistical models could be used to identify clinical variables associated with spinal shock in dogs with spinal cord injuries. Animals: Cohort of 59 dogs with T3‐L3 myelopathies and spinal shock and 13 dogs with L4‐S3 myelopathies. Methods: Data used for this study were prospectively entered by partner institutions into the International Canine Spinal Cord Injury observational registry between October 2016 and July 2019. Univariable logistic regression analyses were performed to assess the association between independent variables and the presence of spinal shock. Independent variables were selected for inclusion in a multivariable logistic regression model if they had a significant effect (P ≤.1) on the odds of spinal shock in univariable logistic regression. Results: The final multivariable model included the natural log of weight (kg), the natural log of duration of clinical signs (hours), severity (paresis vs paraplegia), and pelvic limb tone (normal vs decreased/absent). The odds of spinal shock decreased with increasing weight (odds ratio [OR] = 0.28, P =.09; confidence interval [CI] 0.07‐1.2), increasing duration (OR = 0.44, P =.02; CI 0.21‐0.9), decreased pelvic limb tone (OR = 0.04, P =.003; CI 0.01‐0.36), and increased in the presence of paraplegia (OR = 7.87, P =.04; CI 1.1‐56.62). Conclusions and Clinical Importance: A formula, as developed by the present study and after external validation, could be useful for assisting clinicians in determining the likelihood of spinal shock in various clinical scenarios and aid in diagnostic planning. [ABSTRACT FROM AUTHOR]

Objectives: A previous single‐country pilot study indicated serum anti‐GM2 and anti‐GA1 anti‐glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. Materials and Methods: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti‐glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti‐glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. Results: Anti‐GM2 anti‐glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti‐GalNAc‐GD1a anti‐glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti‐glycolipid antibodies were frequently present concomitantly. Anti‐GA1 anti‐glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti‐GM2 and anti‐GalNAc‐GD1a anti‐glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti‐GalNAc‐GD1a anti‐glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). Clinical Significance: Anti‐GM2 and anti‐GalNAc‐GD1a immunoglobulin G anti‐glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis. [ABSTRACT FROM AUTHOR]

Objectives: (1) To assess outcomes in children undergoing adenoidectomy for the treatment of mild obstructive sleep apnea (OSA). (2) To identify clinical factors that predict which children will have persistent obstruction following adenoidectomy. Study Design: Case series with chart review over a 10-year period. Setting: Tertiary children's hospital. Subjects and Methods: Children between 2 and 17 years old undergoing adenoidectomy for treatment of mild OSA (obstructive apnea-hypopnea index [AHI] between 1 and 5 on polysomnogram) were included. The need for additional medical or surgical intervention following adenoidectomy was recorded. When available, postoperative polysomnogram data were reviewed. Results: In total, 134 children with a mean age of 5.4 years were included. Fifty-three percent (n = 71) were female and 57% (n = 76) were black. The mean (SD) baseline AHI was 2.2 (1.09). Caregivers reported a moderate impact of sleep disturbance on quality of life with a mean (SD) preoperative total OSA–18 score of 64.1 (19.28). Postadenoidectomy outcomes were reported for 105 patients (78%) with a mean follow-up time of 6 months. Sixty-nine percent (n = 72) of children had resolution of obstructive symptoms. While 31% (n = 33) of children required additional intervention following adenoidectomy, only 6.8% (n = 9) underwent a subsequent tonsillectomy. Demographic factors such as age and baseline AHI did not predict which children required additional treatment following adenoidectomy. Conclusion: Adenoidectomy may be an effective treatment for mild OSA. A randomized trial comparing outcomes for adenoidectomy and adenotonsillectomy is needed to determine the ideal surgical treatment for nonsevere OSA in children. [ABSTRACT FROM AUTHOR]

Background: Retrospective research recently identified a possible relationship between duration of surgery and outcome in severely affected dogs treated surgically for acute thoracolumbar intervertebral disk herniation (TL‐IVDH). Hypothesis: That increased duration of surgery is associated with poorer outcome in dogs with absent pain perception treated surgically for TL‐IVDH. Animals Two hundred ninety‐seven paraplegic dogs with absent pain perception surgically treated for acute TL‐IVDH. Methods: Retrospective cohort study. Medical records of 5 institutions were reviewed. Inclusion criteria were paraplegia with absence of pain perception, surgical treatment of TL‐IVDH, and 1‐year postoperative outcome (ambulatory: yes or no). Canine data, outcome, and surgery and total anesthesia duration were retrieved. Results: In this study, 183/297 (61.6%) dogs were ambulatory within 1 year, 114 (38.4%) dogs failed to recover, including 74 dogs (24.9%) euthanized because of progressive myelomalacia. Median anesthesia duration in dogs that regained ambulation within 1 year of surgery (4.0 hours, interquartile range [IQR] 3.2‐5.1) was significantly shorter than those that did not (4.5 hours, IQR 3.7‐5.6, P =.01). Multivariable logistic regression demonstrated a significant negative association between both duration of surgery and total anesthesia time and ambulation at 1 year when controlling for body weight and number of disk spaces operated on. Conclusions and Clinical Importance: Findings support a negative association between increased duration of anesthesia and outcome in this group of dogs. However, the retrospective nature of the data does not imply a causal relationship. [ABSTRACT FROM AUTHOR]

Background: Medium‐chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE). Objective: To evaluate the short‐term efficacy of MCTs administered as an add‐on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles. Animals Twenty‐eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used. Methods: A 6‐month multicenter, prospective, randomized, double‐blinded, placebo‐controlled crossover trial was completed, comparing an MCT‐DS with a control‐DS. A 9% metabolic energy‐based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study. Results: Seizure frequency (median 2.51/month [0‐6.67] versus 2.67/month [0‐10.45]; P =.02) and seizure‐day frequency were significantly (1.68/month [0‐5.60] versus 1.99/month [0‐7.42], P =.01) lower when dogs were fed MCT‐DS in comparison with the control‐DS. Two dogs were free of seizures, 3 had ≥50% and 12 had <50% reductions in seizure frequency, and 11 dogs showed no change or an increase in seizure frequency. Conclusions and Clinical Importance: These data show antiseizure properties of an MCT‐DS compared to a control oil and support former evidence for the efficacy of MCTs as a nutritive, management option for a subpopulation of drug‐resistant dogs with epilepsy. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether the neurological examination correctly distinguishes between central and peripheral vestibular lesions in dogs. Materials and Methods: Retrospective study on dogs with vestibular disease presenting to two referral clinics in Germany. Results: Ninety‐three dogs were included; neurological examination suggested central vestibular disease in 62 and a peripheral lesion in 31. MRI diagnosis was central vestibular disease in 68 dogs and peripheral in 25. Of the 62 dogs with a lesion localisation diagnosed as central vestibular by neurological exam, 61 were correctly identified (98.4%). Twenty‐four of the 31 dogs diagnosed with a peripheral lesion by neurological exam had a consistent lesion on MRI (77.4%). Clinical Significance: The neurological examination is efficient at identifying lesions in the central vestibular system but less so for peripheral lesions. Therefore it is prudent to recommend imaging in dogs that show signs of peripheral vestibular syndrome but do not rapidly respond to treatment. [ABSTRACT FROM AUTHOR]

Background: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. Objectives: To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. Animals: Client‐owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus. Methods: Randomized parallel group clinical trial. Patients were randomly allocated to the IN‐MDZ (n = 21) or IV‐MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for ≥10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at α < .05. Results: IN‐MDZ and IV‐MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P =.34). The median seizure cessation time was 33 and 64 seconds for IN‐MDZ and IV‐MDZ, respectively (P =.63). When the time to place an IV catheter was taken into account, IN‐MDZ (100 seconds) was superior (P =.04) to IV‐MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN‐MDZ and IV‐MDZ, respectively. Conclusions and Clinical Importance: Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account. [ABSTRACT FROM AUTHOR]

A 1‐year‐old dwarf rabbit was presented with sub‐acute progressive tetraparesis. Radiography, CT and MRI revealed compressive cervical myelopathy secondary to a complex atlanto‐axial malformation including partial aplasia of the atlantal dorsal arch, dens malformation, malarticulation and lateral atlanto‐occipital displacement. Owners decided against surgical treatment and elected conservative treatment including analgesia with non‐steroidal anti‐inflammatory drugs, cage rest and physiotherapy. Within 2 months clinical signs deteriorated and the owner elected euthanasia. Subsequent necropsy confirmed imaging findings. Similar cases described in humans and dogs suggest that partial aplasia of the dorsal arch of the atlas might often be an asymptomatic radiologic finding in these species. In contrast, this first description of a similarly affected rabbit demonstrates that complex atlanto‐axial malformations can cause severe clinical signs. [ABSTRACT FROM AUTHOR]

Background: Whether compressive cervical myelopathy caused by hydrated nucleus pulposus extrusion (HNPE) in dogs should be treated surgically or conservatively has been debated. Only 1 recent study has contradicted the former predominant reports of surgical treatment for HNPE. Hypothesis and method: Single center retrospective study to compare the outcome of client‐owned dogs with HNPE after decompressive surgery or conservative treatment. Animals Thirty‐six dogs diagnosed with HNPE confirmed by magnetic resonance imaging (MRI). Results: Eighteen of 36 dogs underwent surgery whereas 18 dogs were managed conservatively including cage rest and physiotherapy. The most common affected intervertebral disc space was C4‐5. In 3 dogs, HNPE was diagnosed at the level of T13‐L1. Median time to regain ambulation was 6.6 days (range, 0‐28 days) after surgery and 5.9 days (range, 0‐15 days) with conservative management (P = .37). Only the length of a potential intramedullary lesion in cervical HNPE detected by MRI had an influence on the prognosis to gain ambulatory status in a time period of ≤9 days (P = .0035) and on short‐term survival (P = .0011). Conclusions and clinical importance: Conservative management of HNPE in the cervical as well as in the thoracolumbar region represents a reasonable alternative to surgery, showing similar favorable outcome. [ABSTRACT FROM AUTHOR]

Background: Transcranial magnetic motor evoked potentials (TMMEP) are associated with severity of clinical signs and magnetic resonance imaging (MRI) findings in dogs with spinal cord disease. Hypothesis: That in initially paraplegic dogs with thoracolumbar intervertebral disc herniation (IVDH), MRI findings before surgery and TMMEPs obtained after decompressive surgery are associated with long-term neurological status and correlate with each other. Animals: Seventeen client-owned paraplegic dogs with acute thoracolumbar IVDH. Methods: Prospective observational study. TMMEPs were obtained from pelvic limbs and MRI (3T) of the spinal cord was performed at initial clinical presentation. Follow-up studies were performed ≤2 days after reappearance of motor function and 3 months later. Ratios of compression length, intramedullary hyperintensities'length (T2-weighted hyperintensity length ratio [T2WLR]), and lesion extension (T2- weighted-lesion extension ratio) in relation to the length of the 2nd lumbar vertebral bodywere calculated. Results: TMMEPs could be elicited in 10/17 (59%) dogs at 1st and in 16/17 (94%) dogs at 2nd follow-up. Comparison of TMMEPs of 1st and 2nd follow-up showed significantly increased amplitudes (median from 0.19 to 0.45 mV) and decreased latencies (from 69.38 to 40.26 ms; P=.01 and .001, respectively). At 2nd follow-up latencies were significantly associated with ambulatory status (P=.024). T2WLR obtained before surgery correlated with latencies at 2nd follow-up (P=.04). Conclusions: TMMEP reflect motor function recovery after severe spinal cord injury. [ABSTRACT FROM AUTHOR]

Background: Epileptic seizures are a common cause for neurological evaluations in dogs. Hypothesis/Objectives: To determine the timing, frequency, and risk factors for early seizure recurrence (ESR) among dogs admitted to the hospital for seizure evaluation and to facilitate rapid decision making about whether dogs should be placed in the intensive care unit (ICU) or day ward. Animals: Nine‐hundred twenty‐two dogs referred for seizure investigation; 214 patients were included. Methods: Retrospective study. Medical records between 2000 and 2017 were reviewed to determine risk factors for ESR. Findings were compared among dogs diagnosed with idiopathic epilepsy (IE), structural epilepsy (StE) and reactive seizures (RS), as well as in all selected cases together. Results: Fifty percent of dogs had a seizure while hospitalized. In the group 53.1 and 52.2% in the StE group, whereas in the RS 40.44% had ESR. The average time to ESR was 7 hours. In IE group, abnormal postictal neurological examination with prosencephalon signs predicted ESR. In StE group, a single generalized or focal seizure 72 hours before hospital admission and abnormal neurologic examination predicted ESR. In the RS group, ERS was predicted by long‐term antiepileptic monotheraphy. When all dogs were analyzed together, abnormal neurological examination, the occurrence of cluster seizures, status epilepticus, or combination of them 72 hours before presentation predicted ESR. Conclusions and Clinical Importance: Epileptic seizures recurred in 50% of patients within a mean time of 7 hours. In general, when cluster seizures, status epilepticus or both occurred 72 hours before presentation and neurological examination was abnormal upon presentation, the dog should be placed in ICU for observation. [ABSTRACT FROM AUTHOR]

Myoclonic epilepsy in Rhodesian Ridgeback (RR) dogs is characterized by myoclonic seizures occurring mainly during relaxation periods, a juvenile age of onset and generalized tonic‐clonic seizures in one‐third of patients. An 8‐month‐old female intact RR was presented for myoclonic seizures and staring episodes that both started at 10 weeks of age. Testing for the DIRAS1 variant indicated a homozygous mutant genotype. Unsedated wireless video‐electroencephalography (EEG) identified frequent, bilaterally synchronous, generalized 4 Hz spike‐and‐wave complexes (SWC) during the staring episodes in addition to the characteristic myoclonic seizures with generalized 4–5 Hz SWC or 4–5 Hz slowing. Photic stimulation did not evoke a photoparoxysmal response. Repeat video‐EEG 2 months after initiation of levetiracetam treatment disclosed a >95% decrease in frequency of myoclonic seizures, and absence seizures were no longer evident. Absence seizures represent another seizure type in juvenile myoclonic epilepsy (JME) in RR dogs, which reinforces its parallels to JME in humans. [ABSTRACT FROM AUTHOR]

Background: Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. Objective: To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. Animals: Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). Methods: Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05. Results: IN-MDZ and R-DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. Conclusions and Clinical Importance: IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home. [ABSTRACT FROM AUTHOR]

Background Prognostic tools to predict early postoperative motor function recovery ( MFR) after thoracolumbar intervertebral disk herniation ( IVDH) in paraplegic dogs represent an opportunity to timely implement novel therapies that could shorten recovery times and diminish permanent neurological dysfunctions. Hypothesis Fractional anisotropy ( FA) values obtained using diffusion tensor imaging have a higher prognostic value than a lesion extension ratio in T2-weighted images (T2W- LER) and clinical assessment of deep pain perception ( DPP) for MFR. Animals Thirty-five paraplegic dogs with diagnosis of acute or subacute thoracolumbar IVDH. Methods Prospective, descriptive observational study. At admission, absence or presence of DPP, T2W- LER, and FA values was evaluated. MFR was assessed within 4 weeks after decompressive surgery. Values of T2W- LER and FA of dogs with and without MFR were compared using t-tests. All 3 methods were evaluated for their sensitivity and specificity as a prognostic factor. Results No differences were found between groups regarding T2W- LER. FA values differed statistically when measured caudally of lesion epicenter being higher in dogs without MFR compared to dogs with MFR ( P = .023). Logistic regression analysis revealed significance in FA values measured caudally of the lesion epicenter ( P = .033, area under the curve = 0.72). Using a cutoff value of FA = 0.660, the technique had a sensitivity of 80% and a specificity of 55%. Evaluation of DPP had a sensitivity of 73.3% and specificity of 75% ( P = .007). Conclusions and Clinical Importance Evaluation of DPP showed a similar sensitivity and a better specificity predicting early MFR than quantitative magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

O bjectives To investigate possible interactions visible on electroencephalogram recordings caused by concomitant administration of marbofloxacin and carprofen or cimicoxib in dogs without central nervous system disease. M ethods Totally 21 client-owned dogs undergoing different surgeries were included in a randomised, blinded, clinical study. Each dog was assigned to one of two groups treated with either carprofen or cimicoxib pre- and postoperatively. After anaesthetic induction both groups received marbofloxacin intravenously while recording an electroencephalogram. Offline electroencephalogram analysis included qualitative evaluation and Fast Fourier Transformation. Postoperative analgesia was evaluated for 24 hours and after 10 days with the short-form Glasgow Composite Measure Pain Scale. Statistical analysis included Wilcoxon signed rank test, Mann-Whitney U test and Student's t-test with α set at 5%. R esults Marbofloxacin injection caused no effects on quantitative and qualitative electroencephalogram parameters in both groups. No differences in postoperative pain scoring were found between treatment groups. C linical S ignificance Concurrent use of marbofloxacin with either cimicoxib or carprofen did not induce neuroexcitatory activities in dogs without CNS disease directly after administration. [ABSTRACT FROM AUTHOR]

OBJECTIVES To describe relapse rates in steroid-responsive meningitis-arteritis and to describe clinical and laboratory parameters in dogs with and without relapses. METHODS Seventy-four dogs with steroid-responsive meningitis-arteritis were retrospectively identified and assigned to one of three groups: (1) without relapse; (2) at least one relapse and (3) unknown relapse status. The following parameters are reported for the first two groups: sex, age, breed, body weight, nucleated cell count, total protein concentration and percentage of neutrophils on initial cerebrospinal fluid analysis, immunoglobulin A in serum and initial cerebrospinal fluid analysis, nucleated cell count on cerebrospinal fluid analysis at 3-month re-evaluation, C-reactive protein in serum and initial cerebrospinal fluid analysis and at 3-month re-evaluation. RESULTS Relapses occurred in 32 · 4% of dogs (one relapse: 62 · 5%; two relapses: 25 · 0%; three relapses: 8 · 3%; four relapses: 4 · 2%), 55 · 4% were relapse-free and in 12 · 2% the relapse status was unknown. C-reactive protein in serum and cerebrospinal fluid on 3-month re-evaluation was normal in 80% and 75% of dogs with relapses, respectively. In dogs without relapse, C-reactive protein in serum and cerebrospinal fluid on 3-month re-evaluation was normal in 100% and 90% of dogs, respectively. CLINICAL SIGNIFICANCE Relapses are frequent but no reliable predictive indicator has emerged in this study. Nevertheless, elevated C-reactive protein in serum warrants continuing therapy; normal C-reactive protein in serum does not exclude future relapse. [ABSTRACT FROM AUTHOR]

The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs. [ABSTRACT FROM AUTHOR]

Background Peripheral nerve injuries are the most frequent neurologic disorder in cattle. So far, no physiologic values have been established for the motor nerve conduction velocity ( mNCV) in this precocial species. Objectives The electrophysiologic and morphometric reference values of peripheral nerves in calves were determined. It was hypothesized that these parameters would correlate to the high degree of maturity in the first days of life in this species compared to other species. Animals Twenty-six healthy calves were used in this study. Methods The mNCV of the radial and the sciatic/common peroneal nerve was measured in all 26 calves. Nerve biopsies from a group of 6 calves were taken to correlate the obtained electrophysiologic data with morphological parameters. Results The mean mNCV of the radial nerve was 48.3 ± 10.6 m/s, whereas the mean mNCV of the sciatic/peroneal nerve was with 83.8 ± 5.9 m/s significantly faster ( P < .0001). The average fiber diameter was 8.40 ± 2.80 μm (range, 1.98-17.90 μm) and the average g-ratio was 0.61 ± 0.04 SD. Conclusion and Clinical Importance The established reference values for mNCV in calves correlate well with the evaluated morphometric parameters. Attributable to their comparably fast mNCV and high fiber diameters, juvenile calves appear to be much more mature individuals than other mammals. Electrophysiologic characterization of peripheral nerve injury now is feasible in this species. [ABSTRACT FROM AUTHOR]

Purpose In humans, traumatic brain injury ( TBI) is one of the most common causes of acquired (symptomatic) epilepsy, but as yet there is no treatment to prevent the development of epilepsy after TBI. Animal models of posttraumatic epilepsy ( PTE) are important to characterize epileptogenic mechanisms of TBI and to identify clinically effective antiepileptogenic treatments. The prevalence and phenomenology of naturally occurring canine epilepsy are similar to those in human epilepsy. However, the risk of epilepsy after TBI has not been systemically studied in dogs. We therefore performed a large retrospective study in 1,000 dogs referred to our clinical department over a period of 11.5 years with the aim to determine the incidence of early and late seizures after head trauma in this species. Methods Two strategies were used: in group I (n = 392), we evaluated whether dogs referred for the treatment of a head trauma (group Ia) or other trauma (group Ib) developed seizures after the trauma, whereas in group II (n = 608) we evaluated whether dogs referred for the treatment of recurrent epileptic seizures had a history of head trauma. Data for this study were obtained from our clinical database, questionnaires sent to the dogs' owners, and owner interviews. Key Findings In group Ia, 6.6% of the dogs developed PTE, which was significantly different from group Ib (1.9%), indicating that head trauma increased the risk of developing epilepsy by a factor of 3.4. The risk of PTE increased with severity of TBI; 14.3% of the dogs with skull fracture developed PTE. In group II, 15.5% of the dogs with epilepsy had a history of head injury, which was significantly higher than the incidence of PTE determined for group Ia. Significance Our study indicates that head trauma in dogs is associated with a significant risk of developing epilepsy. Therefore, dogs with severe TBI are an interesting natural model of PTE that provides a novel translational platform for studies on human PTE. [ABSTRACT FROM AUTHOR]

Spinal cord injury ( SCI) represents a devastating central nervous system disease that still lacks sufficient therapies. Here, dogs are increasingly recognized as a preclinical animal model for the development of future therapies. The aim of this study was a detailed characterization of axonopathy in canine intervertebral disc disease, which produces a mixed contusive and compressive injury and functions as a spontaneous translational animal model for human SCI. The results revealed an early occurrence of ultrastructurally distinct axonal swelling. Immunohistochemically, enhanced axonal expression of β-amyloid precursor protein, non-phosphorylated neurofilament (n- NF) and growth-associated protein-43 was detected in the epicenter during acute canine SCI. Indicative of a progressive axonopathy, these changes showed a cranial and caudally accentuated spatial progression in the subacute disease phase. In canine spinal cord slice cultures, immunoreactivity of axons was confined to n- NF. Real-time quantitative polymerase chain reaction of naturally traumatized tissue and slice cultures revealed a temporally distinct dysregulation of the matrix metalloproteinases ( MMP)-2 and MMP-9 with a dominating expression of the latter. Contrasting to early axonopathy, diminished myelin basic protein immunoreactivity and phagocytosis were delayed. The results present a basis for assessing new therapies in the canine animal model for translational research that might allow partial extrapolation to human SCI. [ABSTRACT FROM AUTHOR]

M. Jafari, V. Haist, W. Baumgärtner, S. Wagner, V. M. Stein, A. Tipold, H. Wendt and H. Potschka (2012) Neuropathology and Applied Neurobiology 38, 647-664 Impact of Theiler's virus infection on hippocampal neuronal progenitor cells: differential effects in two mouse strains Aims: Disease-associated alterations in hippocampal neurogenesis are discussed as an important factor contributing to long-term consequences of central nervous system diseases. Therefore, the study aimed to determine the impact of Theiler's murine encephalomyelitis virus infection on hippocampal cell proliferation, neuronal progenitor cells and neurogenesis as well as the influence of microglia on respective disease-associated alterations. Methods: The impact of the infection was evaluated in two mouse strains which differ in the disease course, with an acute polioencephalitis followed by virus elimination in C57BL/6 mice and a chronic demyelinating disease in SJL/J mice. Results: Infection with the low neurovirulent BeAn strain did not exert significant acute effects regardless of the mouse strain. In the chronic phase, the number of neuronal progenitor cells and early postmitotic neurones was significantly reduced in infected SJL/J mice, whereas no long-term alterations were observed in C57BL/6 mice. A contrasting course of microglia activation was observed in the two mouse strains, with an early increase in the number of activated microglia cells in SJL/J mice and a delayed increase in C57BL/6 mice. Quantitative analysis did not confirm a correlation between the number of activated microglia and the number of neuronal progenitor cells and early postmitotic neurones. However, flow cytometric analyses revealed alterations in the functional state of microglial cells which might have affected the generation of neuronal progenitor cells. Conclusions: Theiler's murine encephalomyelitis virus infection can exert delayed effects on the hippocampal neuronal progenitor population with long-term alterations evident 3 months following infection. These alterations proved to depend on strain susceptibility and might contribute to detrimental consequences of virus encephalitis such as cognitive impairment. [ABSTRACT FROM AUTHOR]

An eight-year-old mixed-breed dog was presented with progressive paraparesis. Neurological examination revealed a painful diffuse lesion between spinal cord segments T3 and L3. Magnetic resonance images displayed multi-focal contrast enhancing spinal cord and meningeal lesions. Cytology of these lesions revealed a malignant tumour prompting euthanasia of the dog. Histopathology confirmed the cytological diagnosis and a final diagnosis of a glioblastoma multiforme was made based on immunohistochemistry. [ABSTRACT FROM AUTHOR]

E.-L. von Rüden, J. Avemary, C. Zellinger, D. Algermissen, P. Bock, A. Beineke, W. Baumgärtner, V. M. Stein, A. Tipold and H. Potschka (2012) Neuropathology and Applied Neurobiology 38, 426-442 Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis Aims: Despite knowledge about the impact of brain inflammation on hippocampal neurogenesis, data on the influence of virus encephalitis on dentate granule cell neurogenesis are so far limited. Canine distemper is considered an interesting model of virus encephalitis, which can be associated with a chronic progressing disease course and can cause symptomatic seizures. Methods: To determine the impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we compared post-mortem tissue from dogs with infection with and without seizures, from epileptic dogs with non-viral aetiology and from dogs without central nervous system diseases. Results: The majority of animals with infection and with epilepsy of non-viral aetiology exhibited neuronal progenitor numbers below the age average in controls. Virus infection with and without seizures significantly decreased the mean number of neuronal progenitor cells by 43% and 76% as compared to age-matched controls. Ki-67 labelling demonstrated that hippocampal cell proliferation was neither affected by infection nor by epilepsy of non-viral aetiology. Analysis of CDV infection in cells expressing caspase-3, doublecortin or Ki-67 indicated that infection of neuronal progenitor cells is extremely rare and suggests that infection might damage non-differentiated progenitor cells, hamper neuronal differentiation and promote glial differentiation. A high inter-individual variance in the number of lectin-reactive microglial cells was evident in dogs with distemper infection. Statistical analyses did not reveal a correlation between the number of lectin-reactive microglia cells and neuronal progenitor cells. Conclusions: Our data demonstrate that virus encephalitis with and without seizures can exert detrimental effects on hippocampal neurogenesis, which might contribute to long-term consequences of the disease. The lack of a significant impact of distemper virus on Ki-67-labelled cells indicates that the infection affected neuronal differentiation and survival of newborn cells rather than hippocampal cell proliferation. [ABSTRACT FROM AUTHOR]

The current study evaluated the diagnostic value of electroencephalographic recordings (EEG) in cats with epilepsy under special consideration of photic stimulation and hyperventilation. EEGs in six healthy cats were recorded under light (mean dose of 0.23 mg/kg/min) and deep (mean dose of 0.7 mg/kg/min) propofol anaesthesia, whereas EEGs in 13 diseased cats were recorded under a propofol anaesthesia which was kept as light as possible (mean dose of 0.39 mg/kg/min). Paroxysmal discharges were detected in six of 13 cats suffering from seizures (two cats with idiopathic epilepsy and four cats with symptomatic epilepsy). Activation techniques did not enhance the diagnostic value of the EEGs. Photic driving was detected in one of six healthy cats under light, in five of six healthy cats under deep propofol anaesthesia and in 11 of 13 cats with seizures. Systematic use of activation techniques does not seem to increase the diagnostic yield of the recorded EEGs and should not be used in a clinical setting until future studies indicate value. Further investigations into the origin of photic driving under propofol anaesthesia are needed and could lead to the development of a reliable animal model to research into drug effects on the EEG. [ABSTRACT FROM AUTHOR]

Background Idiopathic epilepsy ( IE) in Australian Shepherds ( ASs) occurs worldwide but there is a lack of description of the epilepsy syndrome in this breed. The ABCB1-1Δ mutation is more prevalent in ASs than in many other dog breeds. Hypothesis Australian Shepherds suffer from a poorly controlled IE syndrome with prevailing severe courses. Seizure control and ABCB1-1Δ mutation might be related in this breed. Animals Fifty ASs diagnosed with IE and 50 unaffected ASs. Methods Predominant study design is a longitudinal cohort study. Pedigrees, medical records, seizure, and treatment data of ASs with IE were analyzed descriptively. Sex, color, and the ABCB1-1Δ genotype were compared between case and control groups and ASs with poorly or well-controlled seizures. Differences in survival times were assessed by logrank tests and Cox regression analysis. Results Idiopathic epilepsy in ASs is dominated by moderate and severe clinical courses with the occurrence of cluster seizures and status epilepticus and a high seizure frequency. Poor seizure control and a high initial seizure frequency (≥10 seizure days/first 6 months) are associated with shorter survival times ( P < .05). Poor seizure control, unrelated to the ABCB1( MDR1) genotype, is evident in 56% of epileptic ASs. Pedigree analysis suggests a genetic basis. Conclusion and Clinical Importance Frequent severe clinical courses, poor seizure control unrelated to the ABCB1( MDR1) genotype, and a young age at death compromise animal welfare and warrant further genetic studies to unravel the underlaying molecular mechanisms of IE and seizure control in the breed. [ABSTRACT FROM AUTHOR]

The article describes the case of an 8-week-old female German-Holstein calf that developed spinal cord infarction following aortic catheter implantation. The calf was subjected to aortic catherization in order to regulate arterial access for continuous monitoring of blood pressure and serial arterial blood sampling. Results of a pathological examination indicated a mild to moderate, focal subacute hematoma with necrosis.

Verapamil add-on treatment has been suggested as a novel therapeutic concept for overcoming transporter-mediated pharmacoresistance. Efficacy data have been limited so far to case reports in individual epileptic patients. Therefore, we aimed to thoroughly evaluate the efficacy and tolerability of verapamil add-on treatment. In a prestudy in healthy Beagle dogs the tolerability of verapamil add-on treatment was investigated. The efficacy of verapamil was then evaluated in 11 dogs with phenobarbital-resistant epilepsy. Verapamil add-on treatment (6.2-7.3 mg/kg) did not affect phenobarbital concentrations in plasma or cerebrospinal fluid. Side effects observed in healthy as well as in epileptic dogs comprised bradycardia and a decrease in blood pressure. Therefore, we had to limit the dosage to 1-1.5 mg/kg in the main study. In phenobarbital nonresponders, verapamil failed to improve seizure control. Verapamil treatment was discontinued prematurely in five animals due to worsening of seizure control or lack of an effect. In the remaining animals, seizure frequency tended to increase during the verapamil add-on phase, reaching a mean of two seizures per month compared to the pre-verapamil phase with phenobarbital monotherapy (mean of 1.4 seizures per month). In view of the detrimental effects in the majority of the dogs, the study had to be discontinued and no further animals were enrolled. The failure of the maximum tolerated dosage to improve seizure control in dogs with phenobarbital-resistant epilepsy argues against the suitability of verapamil add-on treatment to overcome pharmacoresistance. Deterioration of seizure control in some individual animals suggests that verapamil might also exert unfavorable effects on seizure thresholds or its spread. [ABSTRACT FROM AUTHOR]

Steroid responsive meningitis-arteriitis (SRMA) is an immunemediated disorder commonly recognised in dogs in small animal practice. Two different forms of SRMA may occur. The typical, acute form of SRMA is characterised by cervical rigidity, pain, pyrexia and a polymorphonuclear pleocytosis of the cerebrospinal fluid (CSF). In a less common, chronic form of SRMA, additional neurological deficits consistent with a spinal cord or a multi-focal neurological disorder may be present, often accompanied by a mononuclear CSF pleocytosis. The prognosis for young dogs in the acute stage of SRMA is relatively good with early and aggressive anti-inflammatory or immunosuppressive therapy. In more protracted, relapsing cases of SRMA the prognosis is guarded, and therapy requires more aggressive, long term immunosuppression. The complete etiopathogenesis of SRMA is unknown; however, an aberrant immune response directed against the central nervous system (CNS) is most likely. Neutrophilic pleocytosis in SRMA seems to be facilitated by chemotactic factors in the CSF and upregulation of integrins and metalloproteinases that disrupt the blood brain barrier. Upregulation of IgA, induced by a Th2 immune response, also plays a central role in the pathogenesis of SRMA. [ABSTRACT FROM AUTHOR]

The article describes the case of a 3-month-old female Icelandic foal with idiopathic narcolepsy. Nacrolepsy was diagnosed using the atropine test wherein atropine sulfate was administered. Radioimmunoassay of the cerebrospinal fluid (CSF) collected from the cerebellomedullary cistern revealed the presence of hypocretin-1. The pathophysiology and genetic basis of narcolepsy are discussed.

Two dogs developed discospondylitis caused by meticillin-resistant Staphylococcus aureus following thoracolumbar hemilaminectomy. Diagnoses were established by magnetic resonance imaging and radiography, respectively, in conjunction with culturing of microbial swabs. Treatment with β-lactam antibiotics was first initiated. As soon as culturing results, confirming meticillin-resistant Staphylococcus aureus infection, and antibiograms became available, antimicrobial therapy was changed to gentamicin and trimethoprim/sulphadiazine. One dog, however, deteriorated further and was euthanased. The other dog improved on appropriate therapy. The first attempt to discontinue drug therapy four months after surgery led to a relapse. Antimicrobial therapy with chloramphenicol was then initiated and maintained for an additional four months. This dog is free of any relapses for 2·5 years. The veterinary surgeon should be aware of the possible involvement of meticillin-resistant Staphylococcus aureus in postsurgical discospondylitis when choosing an antibiotic for initial antimicrobial therapy while culturing results are still pending. [ABSTRACT FROM AUTHOR]

Demyelination is the prominent histopathological hallmark in the acute stage of canine distemper virus infection. Magnetic resonance imaging is an important diagnostic tool in human beings to determine demyelination in the brain, for example in multiple sclerosis. Five young dogs with clinically suspected canine distemper virus infection were subjected to magnetic resonance imaging of the brain and histopathological and immunohistochemical examinations. Hyperintense lesions and loss of contrast between grey and white matter were detected in T2-weighted images in the cerebellum and/or in the brainstem of three dogs, which correlated with demyelination demonstrated in histopathological examination. Furthermore, increased signal intensities in T2-weighted images were seen in the temporal lobe of four dogs with no evidence of demyelination. Magnetic resonance imaging seems to be a sensitive tool for the visualisation of in vivo myelination defects in dogs with acute canine distemper virus infection. Postictal oedema and accumulation of antigen positive cells have to be considered an important differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Measurement of concentrations of acute-phase proteins (APPs) is used as an aid in the diagnosis of a variety of diseases in animals. Objective: To determine the concentration of APPs in dogs with steroid responsive meningitis-arteritis (SRMA) and other neurologic diseases. Animals: One hundred and thirty-three dogs with neurologic diseases, 6 dogs with sepsis, and 8 healthy dogs were included in the study. Thirty-six dogs had SRMA (31 of which had monitoring), 14 dogs had other meningoencephalitides (ME), 32 had disk disease (IVDD/DLSS), 26 had tumors affecting the central nervous system (TCNS), and 25 had idiopathic epilepsy (IE). Methods: Prospective, observational study: C-reactive protein (CRP), α2-macroglobulin (AMG), and albumin concentrations were determined in the serum or plasma. CRP was also measured in the cerebrospinal fluid. Results: Serum CRP was significantly higher in dogs with SRMA ( = 142 μg/mL ± 75) and sepsis ( = 114 μg/mL ± 67) in comparison with dogs with other neurologic diseases ( = 2.3–21 μg/mL; P < .001). There was no significant difference detected in AMG between groups. Serum albumin concentration was significantly lower ( P < .01) in dogs with SRMA ( = 3.2 g/dL ± 0.41) than in other groups ( = 3.6–3.9 g/dL). Serum CRP concentration of SRMA dogs correlated with alkaline phosphatase levels ( r= 0.515, P= .003). Conclusions and Clinical Importance: CRP concentrations in serum are useful in diagnosis of dogs with SRMA. Serum CRP could be used as a monitoring parameter in treatment management of these dogs. [ABSTRACT FROM AUTHOR]

CD45, also called leucocyte common antigen is a transmembrane protein tyrosine phosphatase on the surface of nearly all white blood cells and has a functional role in signal transduction. In the brain, the expression of CD45 can be used to distinguish microglial cells with a characteristic phenotype of CD11b/c+ and CD45low from other central nervous system (CNS) macrophages which show an expression of CD11b/c+ and CD45high. In the course of pathological changes in the CNS, microglia in rodents is known to readily upregulate expression of various surface molecules, such as CD45. Understanding the mechanisms that regulate expression of surface molecules is essential to study the pathogenesis of CNS diseases. In the present study, the expression of CD45 on microglia of 42 dogs was examined ex vivo by means of flow cytometry. The dogs were classified in two groups according to the histopathological diagnosis in the CNS. All dogs without changes in the CNS (group I; n = 22) only showed low percentages of CD45+ microglial cells. In group II consisting of 20 dogs with different intracranial diseases varying results were obtained. Thirteen dogs showed a low percentage of CD45+ microglial cells whereas seven dogs exhibited high percentages of microglial cells expressing CD45. Evaluation of expression intensity in these seven dogs revealed two subpopulations of CD45+ microglial cells: a large subpopulation with CD45low and a small subpopulation with CD45high. The expression intensity of CD45high was comparable with that of canine monocytes. It was attempted to correlate these findings to age of the animals, underlying disease, duration of clinical signs, medical treatment, occurrence of seizure activity and the expression of other surface molecules. It appeared that dogs with high percentages of CD45+ suffered from long-lasting CNS disease with seizures. In future studies, the reason and consequences for upregulated CD45 in long-lasting CNS diseases has to be further evaluated. [ABSTRACT FROM AUTHOR]

Objectives: Investigation of the efficacy of zonisamide as an add-on therapy in dogs with refractory epilepsy. Methods: Thirteen dogs fulfilled the inclusion criteria of poor seizure control despite adequate serum levels of phenobarbital, potassium bromide or both. One further dog was treated with zonisamide as monotherapy because of severe blood dyscrasia due to phenobarbital treatment. Various seizure parameters were evaluated retrospectively for a four month period without zonisamide and prospectively for the same time period under zonisamide add-on therapy. The study time period was extended by up to 17 months to evaluate long-term outcome. Results: Data of 11 dogs could be evaluated: nine of them were responders. The median reduction of seizure frequency of all dogs on zonisamide add-on therapy was 70 per cent (range 14 to 100 per cent). Only transient central nervous system side effects were reported. No further increase of liver enzymes occurred. In three of the responder dogs, seizure control subsided after individual time periods (between 69 days and seven months). Clinical Significance: In dogs with refractory epilepsy, zonisamide may have a beneficial effect on seizure control. In three responder dogs, seizure activity relapsed possibly because of an induction of tolerance. Limiting factors are the high costs. [ABSTRACT FROM AUTHOR]

Purpose: Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, loss of efficacy (tolerance), development of dependence, and the potential for drug abuse limit the clinical use of benzodiazepines (BZDs) for long-term treatment of epilepsy or anxiety. BZD ligands that are in current use act as full allosteric modulators of γ-aminobutyric acid (GABA)-gated chloride channels and, on long-term administration, trigger a functional uncoupling between the GABAA and BZD recognition sites. Partial allosteric modulators, which have a low intrinsic activity at the BZD recognition site of the GABAA receptor, might eventually overcome the limitations of full agonists such as diazepam (DZP). Methods: In the present study, the new low-affinity partial BZD-receptor agonist ELB 138 [former name AWD 131–138; 1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one] was evaluated in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures. Results: ELB 138 was shown to increase potently the pentylenetetrazole (PTZ) seizure threshold in dogs. Prolonged oral administration with twice-daily dosing of ELB 138 with either 5 or 40 mg/kg over a 5-week period was not associated with loss of anticonvulsant efficacy in the PTZ dog model. To study whether physical dependence developed during long-term treatment, the BZD antagonist flumazenil was injected after 5 weeks of treatment with ELB 138. Compared with prolonged treatment with DZP, only relatively mild abstinence symptoms were precipitated in dogs treated with ELB 138, particularly at the lower dosage (5 mg/kg, b.i.d.). In a prospective trial in dogs with newly diagnosed epilepsy, ELB 138 markedly reduced seizure frequency and severity without significant difference to standard treatments (phenobarbital or primidone) but was much better tolerated than the standard drugs, in dogs with chronic epilepsy, most dogs exhibited a reduction in seizure frequency and severity during add-on treatment with ELB 138. Conclusions: The data demonstrate that the partial BZD receptor agonist ELB 138 exerts significant anticonvulsant efficacy without tolerance in a dog seizure model as well as in epileptic dogs with spontaneously recurrent seizures. These data thus substantiate that partial agonism at the BZD site of GABAA receptors offers advantages versus full agonism and constitutes a valuable approach for treatment of seizures. [ABSTRACT FROM AUTHOR]

Two wirehaired dachshund puppies were presented with generalized tremor and gait abnormalities characterized by mild ataxia, tetraparesis and slightly abnormal proprioception. Neurological examination led to the suspicion of a diffuse generalized white matter lesion. Computerized tomography and pathological examination revealed a remarkable unilateral dilatation of the lateral ventricles in each dog. Histopathological examination showed a severe reduction of stainable myelin, widespread mild perineuronal oedema with vacuolations and multifocal reactive astrocytosis affecting the subcortical and deep periventricular white, and to a lesser degree, grey matter of the cerebral hemispheres, most prominently at the level of the optic chiasm. Axons showed a moderately reduced packing density; some axons were irregularly shaped and slightly thickened. There was no evidence of myelin breakdown products and neurones appeared to be well preserved. Brain stem, cerebellum and spinal cord were normal, as was the peripheral nervous system. This leukoencephalopathy in two dachshund puppies most closely resembles human periventricular leukomalacia caused by pre- or perinatal hypoxia-ischaemia. [ABSTRACT FROM AUTHOR]