Neospora caninum and Ehrlichia canis co‐infection in a dog with meningoencephalitis

An 8‐year‐old mixed‐breed dog was presented for acute, progressive weakness and ataxia, inappetence, and weight loss. The patient was mentally normal, but nonambulatory, with a right head tilt, right positional ventral strabismus, and slight head tremors. A neurologic lesion was localized to the cerebellum and right brainstem. Cerebrospinal fluid (CSF) analysis showed a markedly increased protein concentration and mixed pleocytosis, with eosinophil predominance (44%), intracytoplasmic inclusions within eosinophils, consistent with Ehrlichia canis (E canis) morulae, and Toxoplasma gondii (T gondii) or Neospora caninum (N caninum) tachyzoites within eosinophils and monocytes. A serum indirect immunofluorescent antibody test was positive for N caninum (titer 1:12 800) and negative for T gondii. Both blood and CSF PCR results were N caninum‐ and E canis‐positive and T gondii‐ and Anaplasma phagocytophilum‐negative, and blood PCR, but not CSF PCR, was Hepatozoon canis‐positive. The dog was treated for 30 days with clindamycin, sulfamethoxazole‐trimethoprim, doxycycline, prednisone, and cephalosporin, but did not improve neurologically, and was euthanized. Brain histopathology showed moderate multifocal, subacute meningoencephalitis with necrosis and gliosis. The neurologic disease was mostly attributed to central nervous system (CNS) neosporosis, with the possible contribution of ehrlichiosis, which was likely a manifestation of blood‐brain barrier disruption. Hepatozoonosis was probably a result or cause of underlying immunosuppression. To our knowledge, this is the first report of CNSN caninum and E canis co‐infection detected by both CSF PCR and cytology and E canis morulae identified within CSF eosinophils.     

Surgical technique, postoperative complications and outcome in 14 dogs treated for hydrocephalus by ventriculoperitoneal shunting

Objective: To report frequency and type of complications, and outcome in dogs with severe neurologic signs secondary to internal, suspected obstructive hydrocephalus treated by ventriculoperitoneal (VP) shunting. Study Design: Case series. Animals: Dogs (n=14). Methods: Medical records (2001–2006) was reviewed for dogs that had VP shunting. Inclusion criteria were complete medical record, progressive forebrain signs unresponsive to medical treatment, normal metabolic profile, negative antibody titers and/or cerebrospinal PCR for Toxoplasma gondii, Neospora caninum, and canine distemper virus, magnetic resonance images of the brain, confirmed diagnosis of VP shunting, and follow‐up information. Results: Hydrocephalus was idiopathic in 5 dogs and acquired (interventricular tumors, intraventricular hemorrhage, inflammatory disease) in 9 dogs. Four dogs developed complications 1 week to 18 months postoperatively, including ventricular catheter migration, infection, shunt under‐drainage, kinking of the peritoneal catheter, valve fracture, and abdominal skin necrosis. Three of these dogs had 1 or more successful revision surgeries and 1 dog was successfully treated with antibiotics. All, but 1 dog, were discharged within 1 week of surgery, and had substantial neurologic improvement. Median survival time for all dogs was 320 days (1–2340 days), for dogs with idiopathic hydrocephalus, 274 (60–420) days and for dogs with secondary hydrocephalus, 365 (1–2340) days. Conclusions: VP shunting was successful in relieving neurologic signs in most dogs and postoperative complications occurred in 29%, but were resolved medically or surgically.     

Detection of Neospora caninum tachyzoites in cerebrospinal fluid of a dog following prednisone and cyclosporine therapy

Abstract: A 9‐year‐old female spayed Shetland Sheepdog was presented to the Kansas State University Veterinary Medical Teaching Hospital for evaluation following a 3‐week history of left rear limb lameness that had progressed to generalized ataxia. Multifocal or diffuse brain lesions were suspected based on physical examination findings. Cerebrospinal fluid (CSF) contained 52 nucleated cells/μL composed of mixed inflammatory cells. Treatment with prednisone and cyclosporine was initiated based on a presumptive diagnosis of granulomatous meningoencephalitis. Thirteen days later the dog was nonambulatory and mentally obtunded. Repeat CSF analysis revealed 298 nucleated cells/μL with 61% eosinophils. Rare protozoal tachyzoites consistent with Neospora caninum, Toxoplasma gondii, or Sarcocystis spp. were found extracellularly and within macrophages and an eosinophil. Despite cessation of prednisone and cyclosporine therapy and provision of supportive care, the dog died 6 days later. Examination of brain tissue sections revealed multifocally extensive, necrotizing, histiocytic, and lymphoplasmacytic meningoencephalitis with numerous protozoal zoites and cysts. Immunohistochemical analysis of brain tissue using a monoclonal antibody specific for N. caninum confirmed the diagnosis of neosporosis. Similar but less severe lesions were noted in the spinal cord, although organisms were not found. This case emphasizes the value of repeated CSF analysis when therapy is ineffective and the importance of excluding infectious causes of meningoencephalitis before commencement of immunosuppressive therapy.     

Neuronal-Visceral GM1 Gangliosidosis in Portuguese Water Dogs

Three female siblings in a litter of seven Portuguese Water dogs (PWDs) showed clinical signs of ataxia and/or lameness at 5 months of age. Signs of cerebellar dysfunction (intention tremors, ataxia, widebased stance, dysmetria, and/or nystagmus) and mild limb weakness developed rapidly. Results of hemograms (three dogs), blood chemistry profiles (two dogs), urinalyses (two dogs), electroencephalograms (two dogs), and radiographs of the limbs or pelvis (three dogs), vertebrae (two dogs), and skull (one dog) were unremarkable except for an absolute lymphocytosis in one dog. Routine cerebrospinal fluid (CSF) analyses were normal in all three dogs. However, the CSF creatine kinase concentration was elevated in the one dog in which it was measured. Mucopolysacchariduria was present in all three dogs. Due to the rapid progression of clinical signs and a poor prognosis, all three dogs were euthanatized between 6 and 7 months of age. Histopathologic and electron microscopic studies showed neuronal cytoplasmic inclusions, vacuolated hepatocytes, and vacuolated renal tubular epithelial cells, compatible with the diagnosis of a storage disease. Beta-galactosidase activities in leukocytes, serum, and brain homogenates were reduced when compared with that in normal dogs and the stored product was identified as GM1 ganglioside, confirming GM1 gangliosidosis.     

Protozoa1 encephalomyelitis of dogs involving Neosporum caninum and Toxoplasma gondii in New Zealand

In a retrospective study of 15 cases of encephalomyelitis in dogs, three cases of Neospora caninum and two cases of Toxoplasma gondii infection were identified using immunohistochemical staining of central nervous system sections. All cases of neosporosis showed ataxia and progressive hind limb paralysis due to multifocal non-suppurative meningoencephalomyelitis which was most severe in the spinal cord and base of the brain stem. Neospora tissue cysts could not be distinguished morphologically from those of T. gondii using light microscopy, but electron microscopy confirmed their characteristic features. Although Neospora abortion in cattle has only recently been recognised in New Zealand, this study has shown that neosporosis has been present in dogs since at least 1972.     

MAGNETIC RESONANCE IMAGING CHARACTERISTICS IN FOUR DOGS WITH CENTRAL NERVOUS SYSTEM NEOSPOROSIS

Neosporosis is a polysystemic disease that can affect dogs of any age and can cause inflammation of the central nervous system. Antemortem diagnosis can be challenging, as clinical and conventional laboratory test findings are often nonspecific. A previous report described cerebellar lesions in brain MRI studies of seven dogs and proposed that these may be characteristic for central nervous system Neosporosis. The purpose of this retrospective study was to describe MRI characteristics in another group of dogs with confirmed central nervous system neosporosis and compare them with the previous report. The hospital's database was searched for dogs with confirmed central nervous system neosporosis and four observers recorded findings from each dog's MRI studies. A total of four dogs met inclusion criteria. Neurologic examination was indicative of a forebrain and cerebellar lesion in dog 2 and multifocal central nervous system disease in dogs 1, 3, and 4. Magnetic resonance imaging showed mild bilateral and symmetrical cerebellar atrophy in three of four dogs (dogs 2, 3, 4), intramedullary spinal cord changes in two dogs (dogs 3, 4) and a mesencephalic and metencephalic lesion in one dog (dog 2). Multifocal brain lesions were recognized in two dogs (dogs 1, 4) and were present in the thalamus, lentiform nucleus, centrum semiovale, internal capsule, brainstem and cortical gray matter of the frontal, parietal or temporal lobe. Findings indicated that central nervous system neosporosis may be characterized by multifocal MRI lesions as well as cerebellar involvement in dogs.     

Canine cutaneous neosporosis in Brazil

The clinical signs of infection in dogs with Neospora caninum are usually associated with neurological disorders and are seen in young dogs. In this brief case report we observed multifocal ulcerative and exudative skin nodules on the neck and pelvic limbs of a 10‐year‐old cocker spaniel dog. Infection with N. caninum was diagnosed on the basis of cytology and examination of skin tissues by PCR. The dog initially responded to treatment with clindamycin and then relapsed; the dog died. Infection with N. caninum may have been due in part to immune suppression due to hyperadrenocorticism; which either allowed for the development of a primary infection or reactivation of a latent infection by N. caninum with the occurrence of skin lesions.     

Emergency presentations of 4 dogs with suspected neurologic toxoplasmosis

Objective: To review the signalment, clinical signs, abnormal laboratory data, therapeutics, and response to therapy of dogs with clinical signs consistent with toxoplasmosis infection. Series summary: A retrospective review was performed on the records of 4 dogs presented to the Animal Emergency Center between January 1998 and February 2000 exhibiting neurologic signs and having elevated titers for Toxoplasma gondii. A tentative diagnosis of toxoplasmosis was based upon one of the following criteria: (1) a serial 4‐fold or greater change in serum T. gondii IgG titers; 2) serially decreasing serum T. gondii IgM titers with concurrent increasing serum T. gondii IgG titers; or 3) positive cerebrospinal fluid (CSF) T. gondii titers. In addition, inclusion of cases was limited to dogs that showed improvement of neurologic signs following treatment with antiprotozoal drugs. Trimethoprim–sulfamethoxazole treatment was associated with successful elimination of clinical signs in all of the dogs. Two of the dogs developed side effects potentially attributed to the trimethoprim–sulfamethoxazole (TMS), and antiprotozoal treatment was continued using clindamycin. Unique information presented: Toxoplasmosis is an important differential diagnosis in any dog that presents as an emergency with central or peripheral neurologic signs. Affected dogs need not be immunocompromised for clinical signs of toxoplasmosis to occur. Appropriate treatment with TMS or clindamycin can lead to resolution of clinical signs.     

Listeria monocytogenes septicemia in an immunocompromised dog

An 11‐year‐old, male castrated, Boston Terrier was presented to the North Carolina State University College of Veterinary Medicine Small Animal Emergency Service with a 2‐day history of progressive ataxia, left‐sided head tilt, and anorexia. The dog had previously been diagnosed with chronic lymphoid leukemia and suspected immune‐mediated destruction of his bone marrow precursor cells, possibly due to therapy with immunosuppressive dosages of prednisone and azathioprine. During the physical examination, abnormal findings included an increased body temperature and horizontal nystagmus. Diagnostic investigations included a computed tomography (CT) scan, which confirmed bilateral otitis media, and a blood culture, which was positive for Listeria monocytogenes serotype 4b (epidemic clone 1). Upon treatment with ampicillin/sulbactam, enrofloxacin, and minocycline, the dog became normothermic and the neurologic signs improved. L monocytogenes serotype 4b (epidemic clone 1) has been associated with outbreaks of human listeriosis originating from food contamination. Although rare case reports of Listeria spp. infection in dogs exist, an actual infection with the epidemic clone 1 strain has never before been reported in a dog. It should be included in the differential diagnoses in immunocompromised dogs with clinical signs of septicemia.     

Distribution of Neospora caninum within the central nervous system and other tissues of six dogs with clinical neosporosis

Six cases of neosporosis in dogs were diagnosed on the basis of clinical signs, serology and immunohistochemistry. The brains and spinal cords, at several levels, and various other tissues were examined using anti-Neospora caninum serum by an immunoperoxidase technique. Parasite density varied markedly from case to case. Although found most consistently in the cerebrum, parasites were distributed throughout the central nervous system (CNS), both within the grey and white matter and within nerve roots. Clinical signs were not related to the position of parasites. Tissue cysts were found infrequently in all areas of the CNS, but not in other tissues. Parasite density was not related to the age of the dog or whether treatment had been given. However, with the exception of the only adult dog examined, more CNS parasites were found in dogs with a longer duration of illness and with higher antibody titres. Tachyzoites were present in skeletal muscles, in the muscularis of the oesophagus, in heart, lung and, less frequently, liver, and rarely in the adrenal gland, thyroid gland and uterus; no clinical signs were seen resulting from damage to these organs. Parasites were not observed in lymphoid tissue. In visceral organs, parasites were most widely distributed in peracute cases. For post mortem diagnosis of neosporosis, the CNS, particularly the cerebrum, is the optimum tissue to examine but parasites may also be found in many other tissues, especially in acute cases. Muscle biopsy of appropriate muscles (as suggested by the clinical signs) provides the possibility of a definitive pre-mortem diagnosis.     

Correlation between severity of clinical signs and motor evoked potentials after transcranial magnetic stimulation in large-breed dogs with cervical spinal cord disease

OBJECTIVE: To evaluate use of transcranial magnetic motor evoked potentials for assessment of the functional integrity of the cervical spinal cord in large-breed dogs with cervical spinal cord disease. DESIGN: Randomized, controlled, masked study. ANIMALS: 10 healthy large-breed control dogs and 25 large-breed dogs with cervical spinal cord diseases. PROCEDURE: Affected dogs were allocated to 3 groups on the basis of neurologic status: signs of neck pain alone, ambulatory with ataxia in all limbs, or nonambulatory. Transcranial magnetic stimulation was performed on each dog with the same standard technique. Motor evoked potentials (MEP) were recorded from electrodes inserted in the tibialis cranialis muscle. Following the procedure, each dog was anesthetized and cervical radiography, CSF analysis, and cervical myelography were performed. The MEP latencies and amplitudes were correlated with neurologic status of the dogs after correction for neuronal path length. RESULTS: Mean MEP latencies and amplitudes were significantly different between control dogs and dogs in each of the 3 neurologic categories, but were not significantly different among dogs in the 3 neurologic categories. A linear association was evident between MEP latencies and amplitudes and severity of neurologic deficits; the more severe the neurologic deficits, the more prolonged the latencies and the more decreased the amplitudes. CONCLUSIONS AND CLINICAL RELEVANCE: Transcranial magnetic MEP are useful to assess severity of cervical spinal cord disease in large-breed dogs. Impairment of the functional integrity of the cervical spinal cord was found even in dogs with neck pain alone.     

Systemic neosporosis in a dog treated for immune‐mediated thrombocytopenia and hemolytic anemia

A 4‐year‐old male Toy Poodle was presented to the Small Animal Veterinary Hospital of the Faculty of Veterinary Medicine of the Autonomous University of Mexico (FMVZ, UNAM) because of depression, lethargy, and hemorrhages involving several areas of the skin and around the eyes. Hematology data and a bone marrow analysis suggested hemolytic anemia and immune‐mediated thrombocytopenia. The dog was treated with prednisone, and after one month the hematology variables improved. However, the dog's clinical condition inexplicably worsened and it was euthanized. On necropsy, there were no relevant findings. However, in histology, multifocal lymphoplasmacytic and histiocytic meningoencephalitis and necrosis, and a protozoan cyst in the cerebellum were identified. In addition, moderate multifocal lymphoplasmacytic and necrotizing pancreatitis, hepatitis, myocarditis, and diffuse lymphoplasmacytic enteritis were observed. Immunohistochemistry of the cerebellum, liver, pancreas, and intestine with a specific antibody against Neospora caninum confirmed the diagnosis of systemic neosporosis. The systemic neosporosis in this dog was most likely caused by reactivation of latent parasites due to prednisone administration during the one month of treatment. It should be kept in mind that in dogs being treated with immunosuppressants for immune‐mediated conditions, opportunistic parasites, such as Toxoplasma gondii and N caninum, can be reactivated from a latent state, as it probably happened in the present case.     

Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs

Neuroaxonal dystrophy (NAD) was examined in two Papillon dogs and a mix breed dog between Papillon and Chihuahua. In addition, cerebellar cortical abiotrophy (CCA) in a Papillon dog, which had similar clinical and magnetic resonance imaging (MRI) features to those of NAD, was also investigated. The common clinical symptoms of all dogs affected with NAD and CCA, were pelvic limb ataxia and cerebellar ataxia including intention tremor, head tremor, and hypermetria in the early onset. These clinical signs were progressed rapidly, and two dogs with NAD were euthanized by owner's request and the other two died by aspiration pneumonia. MRI examinations and gross observations at necropsy revealed moderate to severe cerebellar atrophy in all cases of NAD and CCA. The most typical histological change of NAD was severe axonal degeneration with marked spheroid-formation in the dorsal horn of the spinal cords, the nuclei gracilis, cuneatus, olivalis and its circumference in the medulla oblongata. The spheroids were characterized as large eosinophilic or granular globes within the enlarged myelin sheaths, sometimes accompanied by moderate accumulation of microglias and/or macrophages. In contrast, such spheroid formation was minimal in the brain of CCA. In the cerebellum, mild to moderate loss of the Purkinje and granular cells were recognized in three dogs with NAD, whereas these changes were more prominent in a dog with CCA. Although the clinical signs and MRI findings relatively resembled between NAD and CCA, the histopathological features considered to be quite differ, suggesting distinct pathogenesis and etiology. Since both NAD and CCA are proposed as the autosomal recessive hereditary disorders, careful considerations might be needed for the breeding of Papillon and Chihuahua dogs.     

Signs consistent with syringobulbia may be detected in dogs undergoing MRI

Syringobulbia is a pathologic condition characterized by one or more fluid‐filled cavities within the brainstem. This retrospective case series describes observations in eight dogs with syringobulbia diagnosed during MRI. All dogs were adult, small‐breed dogs with concurrent syringomyelia and neurologic deficits localized to sites rostral to the spinal cord, which cannot be explained by syringomyelia (eg, six dogs had vestibular signs). On MRI, the fluid‐filled cavities had signal intensity characteristics like cerebrospinal fluid, were in the medulla oblongata, and were solitary in each dog. Initially, the shape of the cavity was a slit in five dogs and bulbous in two dogs. Magnetic resonance imaging was repeated in five dogs (6‐55 months of age). One dog had progression of syringobulbia from slit‐like to bulbous, and four dogs had unchanged slit‐like syringobulbia. One dog developed slit‐like syringobulbia after cranioplasty. A variety of medical and surgical treatments were performed with improvement of some but not all clinical signs. One dog died following surgery due to cardiopulmonary failure and the other seven dogs were alive at least 1 year after the initial diagnosis, which was the least time of follow‐up. One surviving dog developed a unilateral hypoglossal nerve deficit 2 months after the initial diagnosis and megaesophagus 14 months later. In conclusion, detecting a fluid‐filled cavity in the medulla oblongata consistent with syringobulbia is possible in dogs undergoing MRI. The cavity is likely acquired, slit‐like or bulbous, progressive, or static, and might be associated with breed size and neurologic signs localized to the medulla oblongata.     

Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis

A 10‐month‐old spayed female Cane Corso dog was evaluated after a 2‐month history of progressive blindness, ataxia, and lethargy. Neurologic examination abnormalities indicated a multifocal lesion with primarily cerebral and cerebellar signs. Clinical worsening resulted in humane euthanasia. On necropsy, there was marked astrogliosis throughout white matter tracts of the cerebrum, most prominently in the corpus callosum. In the cerebral cortex and midbrain, most neurons contained large amounts of autofluorescent storage material in the perinuclear area of the cells. Cerebellar storage material was present in the Purkinje cells, granular cell layer, and perinuclear regions of neurons in the deep nuclei. Neuronal ceroid lipofuscinosis (NCL) was diagnosed. Whole genome sequencing identified a PPT1c.124 + 1G>A splice donor mutation. This nonreference assembly allele was homozygous in the affected dog, has not previously been reported in dbSNP, and was absent from the whole genome sequences of 45 control dogs and 31 unaffected Cane Corsos. Our findings indicate a novel mutation causing the CLN1 form of NCL in a previously unreported dog breed. A canine model for CLN1 disease could provide an opportunity for therapeutic advancement, benefiting both humans and dogs with this disorder.     

Association of cerebrospinal fluid analysis findings with clinical signs and outcome in acute nonambulatory thoracolumbar disc disease in dogs

Background: Cerebrospinal fluid (CSF) pleocytosis recently was associated with the severity of neurologic signs in dogs with intervertebral disc disease (IVDD). Hypothesis/Objectives: To look for an association among CSF cell counts, total protein concentration, and severity of neurologic signs at presentation with outcome in dogs with acute thoracolumbar IVDD. Our hypothesis was that CSF total nucleated cell count (TNCC) and percentage cell types would be associated with the severity of spinal cord damage and therefore with both the presenting clinical signs and the prognosis of affected dogs. Animals: Fifty‐four dogs with acute nonambulatory thoracolumbar IVDD were evaluated. Methods: Retrospective study. Signalment, neurologic grade, CSF TNCC, protein concentration, red blood cells count and differential cell percentages, and short‐ and long‐term outcomes were evaluated. Results: CSF pleocytosis (>5 cells/μL) was present in 54% of dogs and was positively associated with neurologic grade at presentation and with postoperative time to regaining ambulation. Neutrophils were observed most frequently. The percentage of CSF macrophages and macrophage to monocyte ratio were higher (P= .001, for both) in dogs presented without deep pain sensation (DPS) that did not regain ambulation. Receiver operator characteristics curve analysis yielded a cut‐off point of 13% macrophages with a sensitivity and specificity of 100 and 83%, respectively, for prediction of a negative outcome. Conclusions and Clinical Importance: CSF pleocytosis is positively associated with the severity of spinal cord damage in dogs with thoracolumbar IVDD. The percentage of CSF macrophages can be used as a prognostic indicator for regaining ambulation in dogs that have lost DPS.     

IMAGING DIAGNOSIS—SPINAL CORD HISTIOCYTIC SARCOMA IN A DOG

A 12‐year‐old mixed breed dog was presented for evaluation of progressive paraparesis and ataxia. Magnetic resonance (MR) imaging was performed and identified multifocal intradural spinal cord mass lesions. The lesions were hyperintense in T2‐weighted sequences, isointense to mildly hyperintense in T1‐weighted sequences with strong contrast enhancement of the intradural lesions and spinal cord meninges. Spinal cord neoplasia was suspected. A diagnosis of intramedullary spinal cord histiocytic sarcoma, confined to the central nervous system, was confirmed histopathologically. Spinal cord histiocytic sarcoma is a rare neoplasm, but should be included in the differential diagnosis for dogs with clinical signs of myelopathy.     

Cytologic detection of Toxoplasma gondii in the cerebrospinal fluid of a dog and in vitro isolation of a unique mouse-virulent recombinant strain

Parasites resembling Neospora caninum or Toxoplasma gondii were detected by cytologic examination of cerebrospinal fluid (CSF) from a dog with neurologic disease. The dog became severely ill and was euthanized. Canine tissue homogenates were used for direct parasite isolation in cell culture, bioassay in 2 mouse lineages, and PCR. T. gondii was isolated in monkey kidney cells, and species identity was confirmed by PCR. Inoculated parasites were highly virulent for mice, which developed clinical signs and were euthanized immediately. PCR-RFLP for T. gondii using the cultured isolate (TgDgBA22) was conducted with 12 genetic markers, and a unique recombinant strain was identified. Detection of T. gondii by CSF cytology, although described in humans, had not been reported previously in dogs, to our knowledge, and was crucial for the diagnosis of toxoplasmosis in the examined dog.     

A truncated retrotransposon disrupts the GRM1 coding sequence in Coton de Tulear dogs with Bandera's neonatal ataxia

Background: Bandera's neonatal ataxia (BNAt) is an autosomal recessive cerebellar ataxia that affects members of the Coton de Tulear dog breed. Objective: To identify the mutation that causes BNAt. Animals: The study involved DNA from 112 Cotons de Tulear (including 15 puppies with signs of BNAt) and 87 DNA samples from dogs of 12 other breeds. Methods: The BNAt locus was mapped with a genome‐wide association study (GWAS). The coding exons of positional candidate gene GRM1, which encodes metabotropic glutamate receptor 1, were polymerase chain reaction (PCR)‐amplified and resequenced. A 3‐primer PCR assay was used to genotype individual dogs for a truncated retrotransposon inserted into exon 8 of GRM1. Results: The GWAS indicated that the BNAt locus was in a canine chromosome 1 region that contained candidate gene GRM1. Resequencing this gene from BNAt‐affected puppies indicated that exon 8 was interrupted by the insertion of a 5′‐truncated retrotransposon. All 15 BNAt‐affected puppies were homozygous for the insert, whereas all other Cotons de Tulear were heterozygotes (n = 43) or homozygous (n = 54) for the ancestral allele. None of the 87 dogs from 12 other breeds had the insertion allele. Conclusions and Clinical Importance: BNAt is caused by a retrotransposon inserted into exon 8 of GRM1. A DNA test for the GRM1 retrotransposon insert can be used for genetic counseling and to confirm the diagnosis of BNAt.