Reactive seizures in cats: A retrospective study of 64 cases.

Epileptic seizures are a common indication for neurological evaluation. This retrospective study reviewed 789 cats referred for epileptic seizure evaluation to the Department of Small Animal Medicine and Surgery of the University of Veterinary Medicine in Hannover, between 1998 and 2017. The aim of this study was to determine common causes for reactive seizures (RS) in cats. Reactive seizures were diagnosed in 62 (7.9%) of 789 feline patients. The most common cause of RS was presumptive or confirmed intoxication (n=34/62; 54.8%). Toxins included permethrin (n=5/62; 8.1%), fipronil (n=1/62; 1.6%), and pesticide (n=1/62; 1.6%). Other common causes were hepatic and renal encephalopathy (n=6/62; 9.7% each), hypertension (n=5/62; 8.1%), hyperthyroidism (n=3/62; 4.8%), hypoglycaemia (n=3/62; 4.8%), and hyperglycaemia (n=1/62; 1.6%). Most commonly, cats with RS presented with generalised tonic-clonic seizures (n=25/62; 40.3%). A single status epilepticus was observed in 9.7% (n=6/62) and 4.8% (n=3/62) presented only with cluster seizures. Focal seizures were the only presenting sign in 3.2% (n=2/62) of cases, however in 4.8% (n=3/62) they were accompanied by tonic-clonic seizures. The mean age of all cats presented for RS was 10.8 years. In the intoxication group, the mean age was 2.9 years. Intoxication (confirmed or presumptive) was the most common cause of RS identified. Clinicians should suspect intoxication when other causes of RS are excluded; when there are appropriate historical findings; when the cat is frequently unobserved by the owner; when symptomatic treatment leads to cessation of epileptic seizures; and when seizures do not recur after treatment has been discontinued.

Absence Seizures as a Feature of Juvenile Myoclonic Epilepsy in Rhodesian Ridgeback Dogs.

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.

Comparison of Preoperative Quantitative Magnetic Resonance Imaging and Clinical Assessment of Deep Pain Perception as Prognostic Tools for Early Recovery of Motor Function in Paraplegic Dogs with Intervertebral Disk Herniations.

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.

Correlation between severity of clinical signs and transcranial magnetic motor evoked potentials in dogs with intervertebral disc herniation.

Transcranial magnetic motor evoked potentials (TMMEPs) can assess the functional integrity of the spinal cord descending motor pathways. In intervertebral disc herniation (IVDH), these pathways are compromised to varying degrees reflected by the severity of neurological deficits. The hypotheses of this study were as follows: (1) TMMEPs differ in dogs with IVDH and healthy control dogs; (2) TMMEPs reflect different severities of neurological signs; and (3) TMMEPs can document functional motor improvement and therefore monitor recovery of function. TMMEPs were recorded in 50 dogs with thoracolumbar IVDH. Clinical signs ranged from spinal hyperesthesia to non-ambulatory paraparesis in 19 dogs and paraplegia with/without deep pain sensation in 31 dogs. In these 31 paraplegic dogs, transcranial magnetic stimulation (TMS) was repeated during follow-up examinations. Ten healthy Beagle dogs served as controls. There was a significant increase in onset latency and decrease in peak-to-peak amplitude in the pelvic limb TMMEPs of dogs with spinal hyperesthesia to severe paraparesis compared to control dogs. Waveforms in dogs with IVDH were predominantly polyphasic in contrast to the biphasic waveforms of the control dogs. TMMEPs could not be generated in the pelvic limbs of paraplegic dogs. However, TMMEPs with markedly increased onset latencies and decreased peak-to-peak amplitudes reappeared in the pelvic limbs of dogs that were paraplegic before surgery and showed functional motor improvement during follow-up. The severity of neurological deficits was reflected by TMMEP findings, which could be used to document functional motor recovery in IVDH. TMS could therefore be used as an ancillary test to monitor response to therapy in dogs during rehabilitation.

Vertebral and spinal dysplasia: A novel dominantly inherited congenital defect in Holstein cattle.

Monitoring and surveillance strategies are imperative for managing genetic defects in livestock populations in order to avoid detrimental effects on animal welfare and productivity. Recently, a number of previously unknown defects have been described in cattle, fostered by the huge progress in genome analysis and genomic selection. In response to reports about a potentially new defect in Holstein cattle, case-control studies were carried out to confirm a genetic background of the defect and to evaluate its phenotypic relevance. Eighty-five potentially affected offspring of a suspected carrier sire for the defect and 41 matched control calves were subjected to clinical and epidemiological monitoring on 39 farms. Forty-one animals, all offspring of the suspected carrier sire, showed pathognomonic tail malformations providing highly significant evidence for a congenital inherited defect, which was subsequently termed vertebral and spinal dysplasia (VSD). The defect is characterised by vertebral (specifically tail) deformities and neurological dysfunctions with gait abnormalities of the hind limbs. The deformities and neurological dysfunctions varied from very mild (only tail deformities) to severe (paraparesis). Detailed epidemiological monitoring provided no indication of environmental factors affecting VSD. The malformations and dysfunctions associated with VSD, as well as its mode of inheritance and the genotyping of the suspected carrier sire, indicated that VSD is a defect previously not described in cattle. VSD is inherited in a dominant mode, but shows incomplete penetrance of the phenotype, which impedes unequivocal identification of VSD carriers. A direct diagnostic genetic test for VSD is available.

Dynamic changes of Foxp3(+) regulatory T cells in spleen and brain of canine distemper virus-infected dogs.

Canine distemper virus (CDV) infection causes immunosuppression and demyelinating leukoencephalitis in dogs. In viral diseases, an ambiguous function of regulatory T cells (Treg), with both beneficial effects by reducing immunopathology and detrimental effects by inhibiting antiviral immunity, has been described. However, the role of Treg in the pathogenesis of canine distemper remains unknown. In order to determine the effect of CDV upon immune homeostasis, the amount of Foxp3(+) Treg in spleen and brain of naturally infected dogs has been determined by immunohistochemistry. In addition, splenic cytokine expression has been quantified by reverse transcriptase polymerase chain reaction. Splenic depletion of Foxp3(+) Treg was associated with an increased mRNA-expression of tumor necrosis factor and decreased transcription of interleukin-2 in the acute disease phase, indicative of disturbed immunological counter regulation in peripheral lymphoid organs. In the brain, a lack of Foxp3(+) Treg in predemyelinating and early demyelinating lesions and significantly increased infiltrations of Foxp3(+) Treg in chronic demyelinating lesions were observed. In conclusion, disturbed peripheral and CNS immune regulation associated with a reduction of Treg represents a potential prerequisite for excessive neuroinflammation and early lesion development in canine distemper leukoencephalitis.

An unusual case of spinal cord restricted mycobacteriosis in a European mink.

Granulomatous myelitis due to infection with Mycobacterium avium was diagnosed in a 4-year-old male neutered European mink (Mustela lutreola). The causative agent was detected by an acid-fast stain and further characterized by polymerase chain reaction and DNA sequencing of the PCR product. A thorough histological evaluation of the remaining organs revealed no granulomatous lesions or detectable acid-fast organisms. Although minks are generally highly susceptible for mycobacteria, localised infections, especially of the central nervous system, are unusual and may represent an atypical chronic form of the disease.

[Evaluation of decreased glucose levels in the cerebrospinal fluid of dogs]. / Untersuchungen zu erniedrigten Glukosewertenim Liquor cerebrospinalis des Hundes.

OBJECTIVE: The aim of the study was to evaluate the glucose ratio (glucose level in the cerebrospinal fluid [CSF]/blood glucose level) as a quickly available marker for detecting bacterial meningoencephalomyelitis (BM). MATERIAL AND METHODS: Blood and CSF samples of 328 dogs were reviewed and evaluated retrospectively. Following the neurological diagnosis, the dogs were assigned to seven different groups: steroid-responsive meningitis-arteritis (SRMA), intervertebral disc disease (IVDD), neoplasia of the central nervous system (N), idiopathic epilepsy (IE), bacterial meningoencephalomyelitis (BM), meningoencephalomyelitis of other origin (ME) and healthy dogs. RESULTS: The median of the CSF-glucose level (mmol/l) and the median of the glucose ratio in the SRMA group displayed the lowest values and differed significantly from the CSF-glucose levels of dogs in the groups IVDD, N, IE and healthy dogs (CSF-glucose level: p<0.01; glucose ratio: p<0.05). In the BM group, both parameters did not differ significant- ly from other groups, but displayed similar low levels as in the SRMA group. There was a negative correlation between the CSF cell count and the CSF-glucose ratio (Spearman correlation coefficient -0.322, p=0.01, R²=0.108). CONCLUSION: The CSF-glucose concentration cannot be used as a distinct marker to differentiate BM from other inflammatory CNS-diseases, especially from SRMA usually accompanied by severe pleocytosis. Low CSF-glucose levels appear to be caused by elevated CSF cell counts rather than by bacterial metabolism. CLINICAL RELEVANCE: For a definitive diagnosis of bacterial meningoencephalomyelitis in dogs, the detection of microorganisms remains necessary.

Suspected primary glioblastoma multiforme in the canine spinal cord.

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.

Hereditary polyneuropathy in the Alaskan Malamute.

OBJECTIVE: To prove the hypothesis that a polyneuropathy in Alaskan Malamutes has a genetic background. MATERIAL AND METHODS: Pedigrees of 131 related Alaskan Malamutes were included in the current study. Neurological examination, electrodiagnosis as well as muscle and nerve biopsies could be performed in 10 dogs. Information about the disease status of the other 121 Alaskan Malamutes were supplied by referring veterinarians, breeders and owners. Segregation analysis using four different models (monogenic, polygenic, mixed monogenic-polygenic and the phenotypic model) was performed on 71 dogs to test the different mechanisms of genetic transmission. RESULTS: In seven clinically affected dogs abnormal electromyographic findings and reduced nerve conduction velocity were detected. Suspected diagnosis of polyneuropathy was confirmed by nerve biopsy results, characterized by axonal degeneration and hypomyelination. Muscle specimens revealed signs of neurogenic myopathy. Three related clinically normal Alaskan Malamutes also displayed moderate neuromuscular changes in histopathology. In the segregation analysis the polygenic model proved as best suitable to explain the observed segregation pattern among all other models tested. CONCLUSION: The current study could demonstrate that polyneuropathy in Alaskan Malamutes is a hereditary disease with variable phenotypic expression ranging from severely affected to subclinical forms, which has to be considered in future gene analysis studies.

Pathogenetic factors for excessive IgA production: Th2-dominated immune response in canine steroid-responsive meningitis-arteritis.

Canine steroid-responsive meningitis-arteritis (SRMA) is a systemic inflammatory disease with a predominant manifestation within the cervical meninges, increased immunoglobulin A (IgA) levels in serum and cerebrospinal fluid (CSF), and a shift of the B:T cell ratio towards a higher percentage of B cells. A Th2-dominated immune response associated with SRMA was therefore hypothesised. Pellets of peripheral blood mononuclear cells (PBMNCs) and CSF white blood cells (CSF WBCs) from dogs in the acute phase of SRMA (n=16) and under glucocorticoid treatment for SRMA (n=16) were investigated for interleukin (IL)-2, interferon (IFN)-γ, IL-4, IL-5 and IL-10 mRNA expression by means of reverse-transcriptase real-time polymerase chain reaction. Results were compared with those of dogs with other inflammatory (n=9) and neoplastic disorders (n=10) of the central nervous system. A tendency towards low levels of Th1 response related cytokines (IL-2, IFN-γ) and high IL-4 expression was observed indicating a Th2-skewed immune response. The pronounced IL-4 production may be an important pathogenetic factor for excessive IgA production in the acute phase of SRMA and for those cases under glucocorticoid treatment.

Age-dependent decline of blood-brain barrier P-glycoprotein expression in the canine brain.

The efflux transporter P-glycoprotein serves as a major molecular gatekeeper at the blood-brain barrier. It has been suggested that a reduction of P-glycoprotein activity with aging might enhance exposure of brain tissue to exogenous and endogenous compounds thereby contributing to the development of neurodegenerative diseases. Brain tissue from owner-kept dogs renders an excellent tool to study the impact of aging on the background of variable environmental and genetic influencing factors. Therefore, we determined expression rates of P-glycoprotein in canine post-mortem tissue from 23 non-laboratory dogs. P-glycoprotein expression in the parahippocampal cortex exhibited a negative correlation with age. Analysis of the area labeled for P-glycoprotein in dogs aged >100 months revealed a 72% drop in P-glycoprotein expression as compared to young adults aged 23-36 months. Respective data from the dentate hilus and dentate gyrus indicated an earlier drop with a reduction by 77 and 80% in dogs aged 37-99 months in comparison with younger individuals. In contrast to the decline observed with aging in dogs without plaques, P-glycoprotein expression rates rather tended to increase with further aging in dogs with plaque formation. In conclusion, the thorough analysis of P-glycoprotein expression rates in non-laboratory dogs revealed a significant decline with aging. The data strongly support the concept that age-dependent changes might predispose to neurodegenerative diseases. In the early pathogenesis of Alzheimer's disease which is modelled by diffuse plaques in the canine brain, an up-regulation of P-glycoprotein might act as a compensatory mechanism to enhance Abeta efflux from the brain. Future studies are necessary to further evaluate the correlation between Abeta deposits and P-glycoprotein expression in different phases of the disease.

Marked MMP-2 transcriptional up-regulation in mononuclear leukocytes invading the subarachnoidal space in aseptic suppurative steroid-responsive meningitis-arteritis in dogs.

Canine Steroid-Responsive Meningitis-Arteritis (SRMA) is a suitable animal model for studies on the development of neutrophilic pleocytosis in aseptic meningitis. Samples of dogs in the acute phase of SRMA (n=16) were examined for gene expression of matrix metalloproteinases (MMP)-2 and -9 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2. Results were compared to those of dogs under glucocorticosteroid treatment for SRMA (n=16) and dogs with other inflammatory and neoplastic diseases of the central nervous system (CNS) (n=19). Samples included mononuclear (PBMCs) and polymorphonuclear cells (PBPMNs) of peripheral blood and cerebrospinal fluid white blood cells (CSF WBCs). In the acute phase of SRMA CSF WBCs showed mRNA expression for MMP-2 and -9 and TIMP-1 and -2, highlighting a contribution of these cells to the overall content of MMPs and TIMPs in CSF. MMP-2 mRNA levels in CSF WBCs were significantly up-regulated in comparison to PBMC expression levels, suggesting that MMP-2 is relevant for PBMC invasion into the subarachnoidal space and that the expression is influenced by migratory activity through the blood-CSF-barrier.

Barbiturate intoxication in two dogs confirmed by toxicological urinalysis.

Two dogs were presented within 24 hours to the Department of Small Animal Medicine and Surgery at the University of Veterinary Medicine Hannover for investigation of the sudden onset of neurological abnormalities following a walk in the same park. One dog was observed ingesting a piece of meat. Analysis of urine by gas chromatography-mass spectrometry from each of the dogs identified the presence of barbiturates. Both dogs recovered with supportive treatment. This is the first report to describe the use of toxicological urinalysis with gas chromatography-mass spectrometry for the diagnosis of barbiturate intoxication in dogs.

Two dogs with iatrogenic discospondylitis caused by meticillin-resistant Staphylococcus aureus.

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 beta-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.

Concentrations of acute-phase proteins in dogs with steroid responsive meningitis-arteritis.

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), alpha(2)-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 (x=142 microg/mL+/-75) and sepsis (x=114 microg/mL+/-67) in comparison with dogs with other neurologic diseases (x=2.3-21 microg/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 (x=3.2 g/dL+/-0.41) than in other groups (x=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.

[Chronic inflammatory demyelinating polyradiculoneuropathy with hypertrophy of cervico-thoracal nerve roots in a dog]. / Chronische entzündliche demyelinisierende Polyradikuloneuropathie mit Hypertrophie zerviko-thorakaler Nervenwurzeln beim Hund.

A case of chronic inflammatory demyelinating polyradiculoneuropathy in a Magyar Vizsla dame, 7 months of age, is described. The neurological deficits such as movement disorders, hyporeflexia and muscle atrophy, were limited to the front legs. The hypertrophied cervico-thoracal nerve roots could be shown by magnetic resonance imaging. The diagnosis was additionally based on clinical findings, the relapsing course, the good response to therapy with prednisolone, the results of electrodiagnostic workup and muscle and nerve biopsy.

[Case-report. Malignant nerve sheath tumor in a cow with symptoms of suspected BSE]. / Fallbericht: Maligner Nervenscheidentumor bei einer Kuh mit BSE-verdächtiger Symptomatik.

We report here on a 3 1/2-year-old mother cow with a malignant perineural tumour near the pontine angle of the cerebellum, but which first drew attention because of clinical signs of BSE. Neurological symptoms that manifested during the course of the disease included disturbances in behaviour, movement and aesthesia, as described by BRAUN et al. (2001) in cases of BSE. Inconsistent with a diagnosis of BSE were focal neurological disturbances (head held aslant to the right, tendency to fall to the right, right-sided facial weakness, left-sided nystagmus and ventral strabismus). Following euthanasia, magnetic resonance imaging (MRI) revealed a tumour in the cerebellopontine angle. Histological findings describe a malignant peripheral nerve tumour of the vagal nerve with rhabdoid differentiation (a so-called Triton tumour) with an intracranial and an extracranial part.

Correlation between the clinical course of granulomatous meningoencephalomyelitis in dogs and the extent of mast cell infiltration.

The data from 20 dogs with histopathologically confirmed granulomatous meningoencephalomyelitis were reviewed in an attempt to identify clinical signs and morphological and cellular parameters, particularly the infiltration of mast cells, which might be associated with the clinical course of the disease. Thirteen of the dogs had the acute form of the disease and seven had the chronic form. Young to middle-aged, small breed female dogs were over-represented. Central vestibular signs were observed in six of the dogs with the acute disease. Analyses of cerebrospinal fluid revealed moderate to severe pleocytosis and high protein concentrations in all cases. Histopathological investigations revealed disseminated perivascular cuffs, large confluent granulomata, tissue necrosis, infiltration with neutrophils and a large number of mitotic cells in the dogs with either of the clinical forms of the disease. Tryptase-positive mast cells were observed in all the cases, but there were significantly larger numbers in the dogs with the acute form.

Presumed immune-mediated cerebellar granuloprival degeneration in the Coton de Tuléar breed.

An unusual form of cerebellar granuloprival degeneration was observed in three male Coton de Tuléar puppies between 12 and 14 weeks of age from different litters showing progressive cerebellar signs beginning at 8 weeks after birth. Pathological examinations revealed a shrunken cerebellum. Histopathologically the granular cells were diminished or almost completely absent, some 'torpedos' of Purkinje cells were present. There was a marked gliosis, and occasionally small inflammatory foci were present. A marked diffuse T cell infiltration (CD3(+) cells) occurred in the lesions, B cells did not appear. CD18 staining showed an upregulation of microglial cells at the lesion site. Histopathologically the lesions resembled paraneoplastic cerebellar degeneration which is caused by an autoimmune mediated T cell reaction. This congenital condition in the Coton de Tuléar dog breed could be based on a genetically defined immune defect leading to autoimmune destruction of the granular cells.