Tiny reviews – JVIM Jan/Feb 2018

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by Deena Tiches, DVM, DACVIM (Neurology)
Originally posted on the NeuroWebVet website; modified and reprinted with permission.

Whoa! Lots to cover here! Neuro topics from the last 2 months of JVIM include:

Epidural response to IVD extrusion

Although the basic pathophysiology is the same in both cervical and thoracolumbar intervertebral disk (IVD) extrusions, researchers at the University of Bern evaluated the differences in epidural inflammatory response between the two. Clinical data and histopathologic variables were investigated. Associations between severity of epidural inflammation and clinical and pathologic variables, impact of chondrodystrophic phenotype, and localization (cervical versus thoracolumbar) were evaluated statistically. Dogs with cervical IVD extrusion were significantly older, had less severe and longer duration of neurologic signs, were more painful, and had a better outcome than dogs with a thoracolumbar IVD extrusion. On histopathology, cervical epidural material had less severe calcification and inflammation. No significant differences regarding chondrodystrophic phenotype were found. Comparing the extent of the inflammatory response, dogs with cervical IVD extrusion displayed significantly less intense inflammation than those with thoracolumbar IVD extrusion. The larger cervical epidural space may limit tissue injury and chemical irritation by the extruded nucleus pulposus (NP) within the vertebral canal, consequently provoking less inflammatory reaction. Notably, there was a significantly less severe epidural inflammatory response in the former, indicating a response of the innate immune system. This finding correlated positively with significantly less NP calcification in cervical extrusions indicating biochemical, metabolic, and biomechanical differences between the 2 locations, which remain to be characterized in future studies. Download article

Intracranial hypertension

Intracranial hypertension is defined as a continuous increase in intracranial pressure above the reference range. It can be caused by various intracranial diseases (eg, trauma, hemorrhage, infarction, ischemia, edema, masses, encephalopathy, status epilepticus). Intracranial hypertension can cause lethal damage to the brain as a result of decreased cerebral blood flow and mechanical compression of brain structures. Therefore, rapid diagnosis and appropriate treatment of intracranial hypertension are important. Transcranial Doppler ultrasound examination (TCD) is a rapid, noninvasive technique used to evaluate cerebral blood flow and is useful for the detection of intracranial hypertension in humans. Investigators at The Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University evaluated the association between the TCD variables and intracranial hypertension in dogs with intracranial diseases. Fifty-one client owned dogs with neurologic disease were studied. Dogs were classified into 3 groups based on MRI findings: no structural diseases (group I), structural disease without MRI evidence of intracranial hypertension (group II), and structural disease with MRI evidence of intracranial hypertension (group III). The TCD vascular resistance variables (resistive index [RI], pulsatility index [PI], and the ratio of systolic to diastolic mean velocity [Sm/Dm]) were measured. Fifteen, 22, and 13 dogs were classified into groups I, II, and III, respectively. Dogs in group III had significantly higher Sm/Dm (median, 1.78; range, 1.44-2.58) than those in group I (median, 1.63; range, 1.43-1.75) and group II (median, 1.62; range, 1.27-2.10). No significant differences in RI and PI were identified among groups. Our findings suggest that increased Sm/Dm is associated with MRI findings of suspected intracranial hypertension in dogs with intracranial diseases and that TCD could be a useful tool to help to diagnose intracranial hypertension. Download article

Meningoencephalomyelitis of unknown origin (MUO)

Meningoencephalomyelitis of unknown origin (MUO) is a common and life-threatening neuroinflammatory disease in dogs. Features of the disease are suggestive of an underlying immune-mediated process, but the association of this disease with a pathogen is still unknown. Colorado State University with collaboration between the Department of Microbiology, Immunology and Pathology and the Department of Clinical Sciences searched for a candidate etiologic agent associated with cases of MUO using next generation metagenomic sequencing. In metagenomic sequencing, total nucleic acids from a clinical or environmental sample are randomly sequenced and are taxonomically categorized by comparison to known sequences in public databases. They evaluated twenty-two dogs diagnosed with either MUO (11/22; 10 CSF and 3 brain), or noninflammatory CNS diseases inconsistent with MUO (11/22; 11 CSF and 2 brain) that served as negative controls. Fresh-frozen cerebrospinal fluid (CSF; 21) and brain (5) samples were collected and RNA and DNA were extracted separately for shotgun metagenomic sequencing. No candidate etiologic agents were identified in dogs with MUO. These results support, but do not prove, the hypothesis that MUO is not associated with infectious agents and might be an autoimmune disease. Download article

Chiari malformation syringomyelia

Characterizing the signs of CMSM (Chiari malformation syringomyelia) in Cavalier King Charles spaniels (CKCS) is challenging because of the difficulty of inferring signs of pain from behavior in dogs. It is crucial to have quantitative measures of chronic pain that are valid and reliable in clinical patients to enable development and testing of interventions (such as drugs or surgical procedures) designed to decrease such pain. Veterinarians at NCSU designed a study to develop a tool to capture owner-reported clinical signs for use in clinical trials and to examine the relationship among owner-reported signs, presence of pain on neurologic examination, and presence and severity of SM (syringomyelia) on MRI. They hypothesized that owner-reported signs would correlate moderately or highly with MRI findings. Fifty dogs were enrolled in the study. SM was present in 30 of 50 dogs, and lateralization of SM was present in 15 dogs. All dogs affected had SM located in the cervical spinal cord, and 24 also had SM in the cranial thoracic spinal cord. There was no relationship between the presence of owner-reported pain (yes or no) or scratching (yes or no) and the presence of SM. Likewise, the total scratch score and pain score were not significantly associated with the presence of SM. In conclusion, the full range of signs reported by owners of CKCS includes a variety of manifestations of pain, with phantom scratching as the most commonly reported sign followed by crying out when being lifted. Download article

GM2-gangliosidosis

GM2-gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β-hexosaminidase A (Hex-A) and β-hexosaminidase B (Hex-B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency. Researchers at the University of Pennsylvania School of Veterinary Medicine sought to characterize the phenotype and genotype of GM2-gangliosidosis disease in an affected dog. A 14-month-old, female Shiba Inu presented with clinical signs resembling GM2-gangliosidosis in humans and GM1-gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog’s brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex-A and Hex-B activities in both tissues. Genetic analysis identified a homozygous, 3-base pair deletion in the HEXB gene (c.618-620delCCT). Clinical, biochemical, and molecular features were characterized in a Shiba Inu with GM2-gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2-gangliosidosis seen in this dog is the Sandhoff type. Because GM1-gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1- and GM2-gangliosidosis should be considered to make a definitive diagnosis. Download article

Extended-release levetiracetam in cats

Repeated PO dosing of anti-epileptic drugs may contribute to poor compliance in treated cats. Intermediate-release levetiracetam has been used safely in cats, but must be given q8h to maintain serum concentrations in the therapeutic interval for humans (5-45 μg/mL). Approved extended-release levetiracetam (XRL) for human use may require less frequent dosing, but the large dosing unit has limited its use in cats. Researchers at the University of Wisconsin and Auburn University hypothesized that, in healthy cats, serum levetiracetam concentration will remain above 5 μg/mL for at least 24 hours after administration of a single dose of 500 mg XRL PO and will be well tolerated. They found that the median dosage of 86.2 mg/kg, (range, 80-94.3) achieved a mean maximum concentration (Cmax) of 89.8 ± 25.8 μg/mL at 4.9 ±1.57 hours. Serum levetiracetam was >5 μg/mL in all cats by 90 minutes. Mean concentrations were 43.7 ± 18.4 and 4.9 ± 3.4 μg/mL at 12 and 24 hours, respectively. The half-life was 4.1 ± 1.0 hours. The drug was well tolerated. They concluded that a single 500 mg PO dose of XRL safely maintained serum levetiracetam concentration ≥5 μg/mL in healthy cats for at least 21 hours. Clinical efficacy studies in epileptic cats receiving XRL are indicated; however, monitoring should be implemented for individual cats. Download article

Acute polyradiculoneuritis

Acute polyradiculoneuritis (APN) is an immune-mediated peripheral nerve disorder in dogs that shares many similarities with Guillain-Barré syndrome (GBS) in humans, in which the bacterial pathogen Campylobacter spp. now is considered to be a major triggering agent. Little information is available concerning the relationship between APN and Campylobacter spp. in dogs. Dr. Martinez-Anton et al investigated the association between Campylobacter spp. infection and APN. Associations with additional potential risk factors also were investigated, particularly consumption of raw chicken. Twenty-seven client-owned dogs suffering from suspected APN and 47 healthy dogs, client-owned or owned by staff members were selected. Fecal samples were collected from each enrolled animal to perform direct culture, DNA extraction, and polymerase chain reaction (PCR) for detection of Campylobacter spp. In some cases, species identification was performed by sequence analysis of the amplicon. Data were obtained from the medical records and owner questionnaires in both groups. In cases in which the fecal sample was collected within 7 days from onset of clinical signs, APN cases were 9.4 times more likely to be positive for Campylobacter spp. compared to control dogs (P < 0.001). In addition, a significant association was detected between dogs affected by APN and the consumption of raw chicken (96% of APN cases; 26% of control dogs). The most common Campylobacter spp. identified was Campylobacter upsaliensis. Raw chicken consumption is a risk factor in dogs for the development of APN, which potentially is mediated by infection with Campylobacter spp. Download article

Ischemic optic neuropathy

A case report of ischemic optic neuropathy in a dog with acute bilateral blindness and primary systemic hypertension was presented by the Centre for Small Animal Studies, Animal Health Trust. A 6-year-old neutered female Jack Russell terrier was investigated for sudden onset prechiasmatic bilateral blindness, left circling, reduced proprioception in the right pelvic limb and right facial allodynia. Electroretinography was normal. Magnetic resonance imaging (MRI) examination revealed that the right optic nerve and the optic chiasm were hyperintense on diffusion weighted imaging and hypointense on apparent diffusion coefficient map consistent with ischemic optic neuropathy. A concurrent lacunar infarct was detected in the left rostral colliculus. Primary systemic hypertension was diagnosed based on blood pressure measurement and no detectable abnormalities on hematology, comprehensive serum biochemistry, urinalysis including protein/creatinine and cortisol/creatinine ratios and thoracic/abdominal imaging. Prednisolone for 10 days and amlodipine long-term were administered. Vision was not recovered after 7 months. Repeat MRI supported the diagnosis of ischemic lesions and revealed a recent striatocapsular infarct. Ischemic optic neuropathy is a well-recognized cause of blindness in humans and should be included as a differential diagnosis for acute prechiasmatic blindness in dogs. Download article

Juvenile myoclonic epilepsy with absence seizures

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. Researchers at the Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany, and the Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany described an 8-month-old female intact RR presenting 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. Download article