Dystrophin-Deficient Muscular Dystrophy in Two Male Juvenile Brittanys.

A 6 mo old and a 7 mo old male intact Brittany were presented for progressive exercise intolerance, failure to grow, and dysphagia. Creatine kinase activity was markedly and persistently elevated in both dogs. Based on the neurological examination, clinical signs localized to the neuromuscular system. Electromyography revealed complex repetitive discharges in multiple muscle groups. Immunofluorescence of biopsies confirmed dystrophin-deficient muscular dystrophy. This is the first report describing dystrophin-deficient muscular dystrophy in the Brittany breed. Currently, no specific therapies are available for this form of myopathy. The presence of dystrophin deficiency in the two dogs suggests an inherited myopathy rather than a spontaneous mutation. The location of the dogs in the United States and Japan suggests a wide distribution of this dystrophy and should alert clinicians to the existence of this myopathy in the Brittany breed. A mutation in the DMD gene has not yet been identified.

Dog leukocyte antigen class II alleles and haplotypes associated with meningoencephalomyelitis of unknown origin in Chihuahuas.

Idiopathic non-infectious meningoencephalomyelitis (NIME), which is thought to be an immune-mediated disease, is a common inflammatory disease in dogs. Meningoencephalomyelitis of unknown origin (MUO), a subgroup of NIME, consists of necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis, and granulomatous meningoencephalomyelitis. Recent studies have shown associations between disease development and dog leukocyte antigen (DLA) class II genes in NME in Pugs and in NIME in Greyhounds. This study focused on Chihuahuas, which have a high incidence of MUO and are one of the most common dog breeds in Japan. Because the development of MUO seems to be associated with DLA class II genes, we aimed to evaluate the association between DLA class II genes and MUO development in Chihuahuas. Blood samples were obtained from 22 Chihuahuas with MUO (MUO group) and 46 without neurological diseases (control). The allele sequences of three DLA class II loci were determined, and haplotypes were estimated from these data. In total, 23 haplotypes were detected. The frequency of one haplotype (DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01) was significantly higher in the MUO group than in the control group (odds ratio, 7.11; 95% confidence interval, 1.37-36.81; P=0.0141). The results suggest that the development of MUO in Chihuahuas may be associated with DLA class II genes. Because the identified risk haplotypes differed from those of other breeds, the pathogenesis of NIME-related diseases may differ among dog breeds.

Neurosurgery in feline epilepsy, including clinicopathology of feline epilepsy syndromes.

Feline epilepsy is treated with antiseizure medications, which achieves fair to good seizure control. However, a small subset of feline patients with drug-resistant epilepsy requires alternative therapies. Furthermore, approximately 50 % of cats with epileptic seizures are diagnosed with structural epilepsy with or without hippocampal abnormality and may respond to surgical intervention. The presence of hippocampal pathology and intracranial tumors is a key point to consider for surgical treatment. This review describes feline epilepsy syndrome and epilepsy-related pathology, and discusses the indications for and availability of neurosurgery, including lesionectomy, temporal lobectomy with hippocampectomy, and corpus callosotomy, for cats with different epilepsy types.

Clinical characterization of epileptic seizures in Pomeranians with idiopathic epilepsy or epilepsy of unknown cause.

BACKGROUND: Focal epileptic motor seizures manifested by limb contraction have been recognized anecdotally in Pomeranians. OBJECTIVES: To investigate clinical features of idiopathic epilepsy (IE) and epilepsy of unknown cause (EUC) in Pomeranians as well as the ADAM23 haplotype frequency previously reported as a common risk haplotype for epilepsy in several breeds of dogs. ANIMALS: Twenty-eight Pomeranians, including 15 with IE and 13 with EUC. Nine Pomeranians with epilepsy and 8 control Pomeranians were used for ADAM23 risk haplotype analysis. METHODS: Case series study including both retrospectively and prospectively collected cases. The ADAM23 haplotype was determined by direct sequencing of PCR amplicons. Data were analyzed descriptively. RESULTS: Focal epileptic seizures (FS) were the predominant type of seizure in 22 of 28 dogs (78.6%). Among these, 12 of the IE dogs (80.0%) and 10 of the EUC dogs (76.9%) showed FS. Notably, 21 of 22 Pomeranians with FS (95.5%) showed limb contraction during ictal periods. Some dogs with FS also showed immobility, generalized tremors, difficulty walking or moving, autonomic signs, orofacial automatisms or some combination during ictal events. Ten dogs with FS and limb contraction had electroencephalography (EEG) performed, and interictal epileptiform discharges were identified in 9 dogs. The haplotype frequency of ADAM23 in cases was lower (27.8%) than that of the controls (56.3%). CONCLUSIONS AND CLINICAL IMPORTANCE: In our study, FS was the predominant type of seizure in Pomeranians, and almost all cases with FS showed limb contraction, regardless of whether having IE or EUC.

Intrathecal tripeptidyl-peptidase 1 reduces lysosomal storage in a canine model of late infantile neuronal ceroid lipofuscinosis.

Late infantile neuronal ceroid lipofuscinosis (LINCL) is caused by mutations in the gene encoding tripeptidyl-peptidase 1 (TPP1). LINCL patients accumulate lysosomal storage materials in the CNS accompanied by neurodegeneration, blindness, and functional decline. Dachshunds homozygous for a null mutation in the TPP1 gene recapitulate many symptoms of the human disease. The objectives of this study were to determine whether intrathecal (IT) TPP1 treatment attenuates storage accumulation and functional decline in TPP1-/- Dachshunds and to characterize the CNS distribution of TPP1 activity. TPP1 was administered to one TPP1-/- and one homozygous wild-type (WT) dog. An additional TPP1-/- and WT dog received vehicle. Four IT administrations of 32 mg TPP1 formulated in 2.3 mL of artificial cerebrospinal fluid (aCSF) or vehicle were administered monthly via the cerebellomedullary cistern from four to seven months of age. Functional decline was assessed by physical and neurological examinations, electrophysiology, and T-maze performance. Neural tissues were collected 48 h after the fourth administration and analyzed for TPP1 activity and autofluorescent storage material. TPP1 was distributed at greater than WT levels in many areas of the CNS of the TPP1-/- dog administered TPP1. The amount of autofluorescent storage was decreased in this dog relative to the vehicle-treated affected control. No improvement in overall function was observed in this dog compared to the vehicle-treated TPP1-/- littermate control. These results demonstrate for the first time in a large animal model of LINCL widespread delivery of biochemically active TPP1 to the brain after IT administration along with a decrease in lysosomal storage material. Further studies with this model will be necessary to optimize the dosing route and regimen to attenuate functional decline.

Abnormal Behavior Episodes Associated With Zonisamide in Three Dogs: A Case Report.

Psychiatric adverse effect associated with anti-seizure drugs has been well-recognized in human medicine. This case report describes three dogs with presumptive idiopathic epilepsy presented for abnormal behavior episodes. Abnormal behavior episodes included sudden rage and aggression to the family members, insomnia, restlessness, and/or constant attention-seeking behavior. MRI study and cerebrospinal fluid analysis in two dogs were unremarkable. The abnormal behavior episodes deteriorated along with gradual dose increment of zonisamide and these episodes almost completely disappeared within 5 days after discontinuation of zonisamide. The exact same episodes relapsed within days after re-administration of zonisamide and disappeared again shortly after discontinuation of zonisamide. Dose adjustments of other anti-seizure medications in case 2 did not result in significant changes in these behavior episodes. Although psychiatric adverse effects including aggressive behavior associated with zonisamide are widely recognized in humans, this is the first report in dogs in the clinical setting.

Case Report: Corpus Callosotomy in a Cat With Drug-Resistant Epilepsy of Unknown Cause.

A 2-month-old, intact male domestic shorthair cat with dullness, bilateral central blindness, and recurrent epileptic seizures was presented to a local clinic. Seizures were the generalized myoclonic and tonic-clonic type. Phenobarbital was initiated and maintained; however, seizures were not controlled. Other anti-seizure drugs, including levetiracetam, zonisamide, and diazepam, also provided insufficient seizure control with seizures occurring hourly to daily. By 8 months of age, the cat displayed non-ambulatory tetraparesis and deep somnolence. Magnetic resonance imaging (MRI), cerebrospinal fluid analysis, and pre- and post-prandial total bile acid analyses were unremarkable. Scalp electroencephalography (EEG) revealed central dominant but generally synchronized spikes and multiple spikes. The cat was diagnosed with drug-resistant epilepsy of unknown cause and was included in a clinical trial of epilepsy surgery. Given the unremarkable MRI and bilateral synchronized EEG abnormalities, a corpus callosotomy was performed at 12 months of age, and partial desynchronization of spikes was confirmed on EEG. Incomplete transection was found in the genu of the corpus callosum on postoperative MRI. After surgery, the mental status and ambulation clearly improved, and seizure frequency and duration were remarkably reduced. Recheck with follow-up EEG and MRI were performed at 3, 6, and 12 months after surgery. Scores of activities of daily living and visual analog scales including cat's and owner's quality of life had also improved considerably. This case report is the first documentation of the one-year clinical outcome of corpus callosotomy in a clinical feline case with drug-resistant epilepsy.

Unilateral hydronephrosis and partial ureteral obstruction by entrapment in a granuloma in a spayed dog.

A 6-year-old, spayed female dog had hydronephrosis and incomplete ureteral occlusion on the left side. An end-to-side ureteral anastomosis was performed. The incomplete ureteral occlusion was determined to be related to an ovarian pedicle granuloma formation and was presumably related to a reaction to the suture material used for ovariohysterectomy (OVH) performed 5 years prior to presentation. Azotemia and hydronephrosis were dramatically improved after surgery, and renal function has been well maintained for 3 years. To the authors' knowledge, a chronic partial ureteral occlusion associated with an ovarian pedicle granuloma from an OVH has not been reported.

Epidural idiopathic sterile pyogranulomatous inflammation causing spinal cord compressive injury in five Miniature Dachshunds.

OBJECTIVE: To characterize the clinical signs, diagnostic and surgical findings, and outcome of dogs with idiopathic sterile pyogranulomatous inflammation (ISP) of epidural fat causing spinal cord compression. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n=5). METHODS: Dogs with epidural ISP (2002-2006) were identified retrospectively. Inclusion criteria were neurologic examination, myelography, and definitive diagnosis of ISP confirmed by surgery and histopathologic examination of epidural spinal cord compressive tissue. RESULTS: The most common clinical sign was paraparesis/paraplegia. No abnormalities were detected by laboratory testing or survey spine radiographs. On myelography, extradural spinal cord compressions were focal (dogs 1, 3, and 5) or multifocal (dogs 2 and 4). Surgical decompression of the spinal cord was completed by hemilaminectomy. Epidural fat collected surgically had pyogranulomatous inflammation of unknown cause and was histologically similar to subcutaneous ISP. All dogs had good long-term neurologic outcome (10-45 months follow-up). Some dogs had episodes of ISP at other sites before or after surgical treatment of epidural ISP, suggesting there may be a systemic form of ISP. CONCLUSION: Epidural ISP may cause a spinal cord compressive lesion in Miniature Dachshunds, which can be treated by surgical decompression of the spinal cord with or without administration of adjunctive steroids. CLINICAL RELEVANCE: Epidural ISP should be considered as a possible cause of thoracolumbar myelopathy for Miniature Dachshunds.

Vertebral stabilization using positively threaded profile pins and polymethylmethacrylate, with or without laminectomy, for spinal canal stenosis and vertebral instability caused by congenital thoracic vertebral anomalies.

OBJECTIVE: To describe diagnostic findings, surgical technique, and outcome in dogs with thoracic spinal canal stenosis and vertebral instability secondary to congenital vertebral anomalies. STUDY DESIGN: Retrospective clinical study. ANIMALS: Dogs (n=9) with thoracic spinal canal stenosis. METHODS: Medical records (1995-1996; 2000-2006) of 9 dogs with a myelographic diagnosis of spinal canal stenosis and/or vertebral instability secondary to congenital vertebral anomaly that were surgically managed by vertebral stabilization with or without laminectomy were reviewed. Data on pre- and postoperative neurologic status, diagnostic findings, surgical techniques, and outcomes were retrieved. Follow-up evaluations were performed at 1, 2, and 6 months. Long-term outcome was assessed by means of clinical examination or owner telephone interviews. RESULTS: Spinal cord compression was confirmed by myelography, and in 2 dogs, dynamic compression by stress myelography. Eight dogs regained the ability to ambulate postoperatively. One dog with a partial recovery regained voluntary movement but did not become ambulatory. CONCLUSIONS: Spinal cord injury secondary to congenital vertebral anomaly may have a good outcome when treated by vertebral stabilization with or without laminectomy. Adequate stabilization of the vertebrae and improved neurologic outcome were achieved in most dogs. CLINICAL RELEVANCE: Vertebral stabilization using positively threaded profile pins and polymethylmethacrylate with or without laminectomy is an effective treatment for spinal canal stenosis and vertebral instability secondary to congenital thoracic vertebral anomalies.

Long-term neurologic outcome of hemilaminectomy and disk fenestration for treatment of dogs with thoracolumbar intervertebral disk herniation: 831 cases (2000-2007).

OBJECTIVE: To determine the proportion of dogs with thoracolumbar intervertebral disk herniation (IVDH) that successfully recovered following hemilaminectomy and fenestration, the time to ambulation (TTA) in affected dogs after surgery, and the frequency of urinary and fecal incontinence in recovered dogs and to document long-term complications. DESIGN: Retrospective case series. ANIMALS: 831 dogs with thoracolumbar IVDH treated by hemilaminectomy and concomitant disk fenestration by the same surgeon. PROCEDURES: For all dogs, neurologic deficits before surgery had been assessed with a modified grading system. Dogs were reexamined after surgery over a period of 3 to 6 months, and follow-up evaluation was performed at > 12 months. The proportion of dogs that neurologically improved after surgery, TTA, and incidence of fecal or urinary incontinence in recovered dogs were compared among dogs with various grades of neurologic dysfunction before surgery. RESULTS: Of 831 dogs, 122 had unsuccessful outcomes and 709 had successful outcomes. Of 620 dogs with intact deep nociception before surgery, 606 (97.7%) were ambulatory after surgery. Despite maintaining the ability to walk, 7 dogs were judged to have an unsuccessful outcome because the severity of ataxia did not improve. Of 211 paraplegic dogs with loss of deep nociception, 110 (52.1%) dogs became ambulatory after surgery. Long-term complications included incontinence, permanent neurologic deterioration, and self-mutilation. Dogs with paraplegia before surgery had a higher frequency of urinary or fecal incontinence, compared with dogs that were ambulatory. CONCLUSIONS AND CLINICAL RELEVANCE: Prognosis for dogs with thoracolumbar IVDH that retain deep nociception in at least 1 of the pelvic limbs or tail before surgery was good.