Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: a pilot study of a novel therapeutic approach.

Introduction: Anxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy. Methods: Nine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification. Results: Following FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged. Discussion: Behavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT's potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.

A retrospective case series of clinical signs in 28 Beagles with Lafora disease.

BACKGROUND: Clinical signs and their progression in Beagles with Lafora disease are poorly described. OBJECTIVES: To describe clinical signs in Beagles with Lafora disease. ANIMALS: Twenty-eight Beagles with Lafora disease confirmed by genetic testing or histopathology. METHODS: Retrospective multicenter case series. Data regarding signalment, clinical signs, diagnostic tests and treatment were retrieved from hospital data files. A questionnaire was sent to owners asking about neurological deficits, changes in cognitive functions, behavioral changes, response to treatment and survival time. RESULTS: Onset of clinical signs was 8.3 years (mean; range, 6.3-13.3). All dogs had myoclonic episodes as an initial clinical sign with tonic-clonic seizures in n = 11/28 (39%) and n = 12/28 (43%) later developing tonic-clonic seizures. Deficits of coordination (n = 21/25; 84%), impaired vision (n = 15/26; 58%), and impaired hearing (n = 13/26; 50%) developed later. Mental decline was observed as loss of house training (urination; n = 8/25; 32%), difficulties performing learned tasks (n = 9/25; 36%), and difficulties learning new tasks (n = 7/23; 30%). Common behavioral changes were: increased photosensitivity (n = 20/26; 77%), staring into space (n = 16/25; 64%), reduced stress resistance (n = 15/26; 58%), increased noise sensitivity (n = 14/26; 54%), and separation anxiety (n = 11/25; 44%). Twenty-one dogs were alive (median age 11.9 years; range, 9.8-18.6), and 7 dogs were dead (mean age 12.1 years; SD: 1.3; range, 10.5-12.6) at time of writing. CONCLUSIONS AND CLINICAL IMPORTANCE: Lafora disease in Beagles causes significant behavioral changes, and mental decline as well as neurological deficits in addition to myoclonic episodes and generalized tonic-clonic seizures. Nevertheless, a relatively normal life span can be expected.

Comparison of surgical and conservative treatment of hydrated nucleus pulposus extrusion in dogs.

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.

Quantitative magnetic resonance imaging characteristics: evaluation of prognostic value in the dog as a translational model for spinal cord injury.

SUMMARY OF BACKGROUND DATA: The mechanisms of injury in spinal cord injury in dogs are similar to those in human patients and the dog is considered to be a valuable translational model for new treatment modalities. Studies regarding the quantitative characteristics of magnetic resonance imaging (MRI) findings in spinal cord injury in a uniform cohort of patients are lacking. OBJECTIVE AND STUDY DESIGN: The aim of this retrospective study was to evaluate the quantitative MRI signal characteristics of the spinal cord in T2-weighted (T2W) sequences, degree of spinal cord compression, and functional outcome in paraplegic dogs with thoracolumbar disk herniation proving the usefulness of imaging before treatment studies. METHODS: MR images of 63 paraplegic dogs with intact or absent deep pain perception due to thoracolumbar disk herniation examined between January 2005 and June 2009 were reviewed blinded to clinical information. The presence and degree of spinal cord compression, and the presence and length of an intramedullary hyperintensity on T2W images were correlated to clinical signs and outcome. RESULTS: A statistically significant correlation was seen between the neurological status before surgery and the presence and extent of the intramedullary hyperintensity adjacent to the disk herniation in T2W sequences. In dogs with a longer duration of clinical signs, the degree of spinal cord compression was statistically significantly higher. The extent of hyperintensity and the degree of spinal cord compression presented a positive correlation, whereas improvement in the neurological score for each grade was faster with no or a smaller size of T2W intramedullary hyperintensity. CONCLUSIONS: In conclusion, a direct correlation between neurological status and MRI signal intensity and extent was proven. Moreover, the presence and extent of T2W hyperintensity can help determine the prognosis before surgery and to decide, whether new therapeutical strategies in dogs as a translational model should be evaluated.

Genetically modified canine Schwann cells--In vitro and in vivo evaluation of their suitability for peripheral nerve tissue engineering.

After peripheral nerve injury, Schwann cells (SC) guarantee for a regeneration-promoting milieu and are crucially involved in axonal regeneration. For extended nerve defects, bridging with an autologous nerve transplant is the gold standard therapy. Artificial biohybrid nerve transplants which combine a synthetic conduit with autologous SC genetically modified to express regeneration-promoting proteins may provide an alternative therapy to autotransplantation. The dog seems to be an ideal translational animal model for new treatment strategies. In the present study, utilizing a new transfection protocol, we transplanted enhanced green fluorescent protein (EGFP)-expressing adult canine SC (cSC) into a 5mm epineural pouch in the sciatic nerve of adult rats (n=9). The epineurial pouch technique serves as proof of principle to follow the fate of the transplanted cSC for up to 14 days after surgery. Fluorescence microscopy and immunohistochemistry revealed survival and integration of EGFP-expressing cSC into the regenerating host nerve tissue. We demonstrate that transplanted cSC contribute to the formation of bands of Büngner and are located in close vicinity to growth-associated protein-43 (GAP-43) expressing regenerating nerve fibers. This provides first evidence that transplanted genetically modified Schwann cells do successfully integrate into the host tissue where they could actively contribute to the regeneration process.