A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

A 3.5-month-old, intact male, miniature schnauzer was presented to the Boren Veterinary Medical Teaching Hospital at Oklahoma State University for ataxia that had lasted for 2 to 3 wk. The puppy fell over frequently, especially when leaning forward to drink water or posture to defecate. The owner had 2 other puppies from the same litter and noted that they were both normal. In comparison, the affected puppy was not as alert and slept more. The owner was unsure if the signs were progressive at that point. No history of trauma or any other illness was reported. At 3 wk of age, the puppy underwent cosmetic reconstruction of the pinnae. The referring veterinarian performed a complete blood cell count, serum biochemical profile, and fasting and postprandial bile acids analysis at age 3.5 mo; the results were normal. The puppy was on a normal schedule of puppy vaccinations and had been dewormed twice with pyrantel pamoate.

Upon presentation, the puppy was an appropriate size for his age. Physical examination revealed ataxia in all 4 limbs and a hypermetric gait that was more noticeable in the front limbs. He also had a mild truncal ataxia, head tremors, and a decreased menace reaction in the left eye. The pupillary light and palpebral responses were normal. Due to a lack of evidence of vision loss or optic nerve dysfunction, the decreased menace reaction was attributed to cerebellar dysfunction. A normal menace reaction develops at 9 to 10 wk of age. Conscious proprioceptive deficits (+11) were noted in the left front and hind limbs, suggesting a right forebrain, or left brain stem or cervical spinal cord lesion. The proprio ceptive deficits were only noted on neurologic examination and were not obvious on gait observation. With the exception of the decreased menace reaction in the left eye, examination of the cranial nerves yielded normal results. All spinal reflexes were normal.

The clinical signs, decreased menace reaction, truncal ataxia, and head tremors were most consistent with cerebellar dysfunction. The proprioceptive deficits could not be attributed to cerebellar dysfunction and could have been associated with a separate problem in the contralateral forebrain, ipsilateral brainstem, or cervical spinal cord. There were no other signs to help in differentiating these. Differential diagnoses included distemper virus, Toxoplasma gondii, Neospora canis, Ehrlichia canis, or Rickettsia rickettsii infection; cerebellar hypoplasia; cerebellar abiotrophy; storage diseases; toxins; or a previous hypoxic insult with permanent cerebellar damage. Serum was submitted for antibody titers against E. canis, and the puppy was discharged with doxycycline hyclate (generic; Mutual Pharmaceutical, Philadelphia, Pennsylvania, USA), 50 mg/kg body weight (BW), PO, 24 h for 14 d, empirically, because the neurologic manifestations could have been due to E. canis infection. Cerebrospinal fluid analysis and a computerized tomography (CT) scan of the brain were recommended. Magnetic resonance imaging was not readily available. The owner declined a more aggressive diagnostic or therapeutic plan at that time.

The puppy was returned 12 d later because of progression of the clinical signs, despite medical therapy. He was unable to stand for any period of time without falling over, continually hit his head on objects in the house, and fell down the stairs. He had difficulty eating due to his imbalance. His truncal ataxia was markedly worse. The proprioceptive deficits and decreased menace response noted on initial presentation were still present, but they had not progressed. Fundic examination revealed changes suggestive of bilateral retinal perivasculitis. The owners consented to a cisternal cerebrospinal fluid (CSF) tap, but declined a CT scan of the brain. Cerebrospinal fluid analysis was normal. Due to the small amount of CSF obtained, antibody titers against N. canis and T. gondii, but not against distemper virus, were determined. The puppy was discharged with med ication; clindamycin hydrochloride (Antirobe; Butler Company, Columbus, Ohio, USA), 12.5 mg/kg BW, PO, q12h for 14 d. After 3 d, the results of the CSF antibody titers were reported as negative. The puppy was then administered prednisolone (generic; Schein Pharmaceuticals, Florham Park, New Jersey, USA), 1 mg/kg BW, PO, q24h, in addition to the previously prescribed clindamycin, but showed no response to therapy after 10 d. The clinical signs of imbalance and falling over continued to progress. Due to the poor prognosis and progression of clinical signs, the owner elected to have the puppy euthanized and allowed a necropsy. He was euthanized at age 4.25 mo.

Specimens of brain, eyes, spinal cord, and multiple other organs were fixed in a neutral buffered 10% formalin solution for 72 h, processed, embedded in paraffin, sectioned at 5 μm, and stained with hematoxylin and eosin.

No significant gross postmortem changes were recognized in the brain or the eyes. Histologically, in the cerebellum, there was widespread loss of the Purkinje cell layer, with moderate attenuation and astrogliosis of the molecular cell layer. Astrocytes were hypertrophic and occasionally binucleated. Remaining Purkinje cells and neurons from the granular cell layer frequently exhibited central chromatolysis, with peripheral displacement of Nissl substance. Multifocally, scattered axonal spheroids were observed within the granular cell layer. There was vacuolation of the underlying cerebellar white matter. There were some digestion chambers, with accumulation of foamy macrophages and demyelination; axonal spheroids were seen occasionally. These discrete degenerative lesions extended along specific nerve tracts, were symmetrically distributed, and were traced from the cerebellum to the inferior aspect of the pons and rostral medulla, where the longitudinal fibers of the pons are located.

The changes in the cerebellum, cerebellar white matter, pons, and medulla most likely occurred as a result of neuronal death and degeneration, primarily of the Purkinje cells, followed by axonal degeneration, spheroid formation, invasion of macrophages, formation of digestion chambers, and subsequent demyelination. In the normal adult cerebellum, the molecular layer is composed of stellate cells and basket cells. These stellate cells, which lie at the outermost level of the molecular layer, were absent in this dog's cerebellum. The cell types identified consisted primarily of basket cells, hyper trophic astrocytes, and capillary endothelium (Figures 1 and 2). Golgi cells were noted at the junction of the molecular and granular cell layers, with a few remaining Purkinje cells in between. Some of these Purkinje cells had swollen axons (axonal spheroids) within the mole cular layer. No evidence of retinal perivasculitis was observed microscopically. Based on the clinical signs and microscopic lesions identified, a diagnosis of cerebellar abiotrophy was made.

The hallmark of abiotrophy, which literally means the loss of a vital nutritive factor, is the premature demise of discrete and often functionally related populations of neurons (1). In veterinary medicine, the progressive degeneration and loss of cerebellar cortical neurons usually results in clinical presentation of the patient early in life. Cerebellar cortical abiotrophies have been described in most of the domestic animals, including cattle, horses, sheep, cats, and dogs (1). They have also been described in nonhuman primates, laboratory mice, and the Shaker rat (1). Where sufficient numbers of affected animals have been studied, an inherited basis has been demonstrable. Canine cerebellar abiotrophy was first reported in the Kerry blue terrier and has since been characterized as an autosomal recessive heritable disease in that breed (2). Other canine breeds proven to have heritable cerebellar abiotrophy include the Gordon setter, rough-coated collie, and Australian kelpie (3,4,5).

Cerebellar abiotrophy has also been identified in the beagle, Airedale terrier, Finnish harrier, Bernese mountain dog, miniature poodle, Brittany spaniel, Cairn terrier, cocker spaniel, Labrador retriever, golden retriever, Great Dane, and border collie breeds (2,6,7,8,9). Previously, this disease has not been recognized in a purebred miniature schnauzer, although it has been reported in a mixed-breed schnauzer (2). Age of onset of clinical signs is variable, with 3 general categories identified. Some dogs, like the beagle, miniature poodle, and rough-coated collie, have early onset of clinical signs, and may show signs of cerebellar ataxia at birth or as early as 3 to 4 wk of age (2,4,6,10). Most breeds, including the Kerry blue terrier, border collie, Australian kelpie, and Labrador retriever, fall into the next category and show clinical signs from 6 to 16 wk of age (2,5,8,9). Gordon setters and Brittany spaniels have been identified with onset of clinical signs occurring from 6 to 30 mo and 7 to 13 y of age, respectively (3,7).

The cause of cerebellar abiotrophy is currently unknown, but is presumed to be an intrinsic metabolic defect. One hypothesis revolves around excitotoxic degeneration of neurons that have glutamate receptors and receive axon terminals utilizing glutamate as the excitatory transmitter (2,10). Excessive glutamate stimulation could cause degeneration of the neuron. Possible explanations for excessive glutamate stimulation include excessive glutamate release, decreased glutamate uptake and clearance, or increased glutamate receptor sensitivity. These abnormalities could be due to inherent defects in the metabolism of glutamate, but could also be caused by damage associated with hypoxia or hypoglycemia (10).

The terms cerebellar abiotrophy and cerebellar atrophy have been used interchangeably. The use of the term atrophy is correct but lacks specificity. Abiotrophy specifically relates to a loss of nutritive factor, while atrophy can result from many things. In abiotrophy, the organ is affected after it has developed its full cellular complement. Thus, clinically, the animal affected is normal at birth and develops progressive cerebellar deficits during the postnatal period.

Some authors have made the distinction between cerebellar abiotrophy and cerebellar cortical degeneration (CCD), with abiotrophy defined as an inherited disease. It is believed that most cases of CCD are indeed abiotrophies that have yet to be proven heritable due to the low numbers of clinical cases that have been identified (2,8). Due to the lack of an identifiable etiology and the similarity to other breeds with heritable cerebellar abiotrophy in age of onset, progression of clinical signs, and histologic lesions, we believe that this miniature schnauzer is such a case. The sire and bitch of this litter were clinically normal at the time of this writing, as were all other puppies from this litter.

In an effort to keep purebred lines of dogs free of heritable abnormalities, reporting all possible defects, such as this case of cerebellar abiotrophy, is important. To our knowledge, this is the first reported case of cerebellar abiotrophy to be reported in the purebred miniature schnauzer dog. Additional cases are necessary to prove heritability.CVJ