A 2-month-old female Holstein Friesian calf was admitted to the Veterinary Teaching Hospital, University of Berne, Switzerland for evaluation of ataxia, weakness and stunted growth. On physical examination the animal was underweight with generalized muscle atrophy. Neurological examination showed generalized ataxia, propioceptive deficits, decreased menace response and superficial sensibility. Temperature, heart and breathing rates were at normal range. Cerebrospinal fluid analysis, blood and serum biochemical analyses including liver enzymes were also within normal limits. Electromyographic (EMG) examination revealed isolated spontaneous activity such as fibrillation potentials in the proximal musculature of front and hind limbs, which indicated a nonspecific denervating neuropathic or myopathic disease. The calf was treated during hospitalization with penicillin (40,000 IU/kg iv), dexamethasone (0.03 mg/kg iv; Boehringer Ingelheim, Germany) and thiamine (4.5 mg/kg; Vétoquinol, France) for 7 days. The animal recovered and was therefore taken home. Two months later it was returned to the Veterinary Hospital with a rapidly progressing debilitation. The animal was in left lateral recumbency, and dyspneic. Although the rectal temperature was normal (38.2℃), the heart and respiratory rates were relatively high at 128/beats per min and 80/breaths per min, respectively (normal ranges are 80 to 100 beats per min and 24 to 36 breaths per min) [12]. The general condition of the calf deteriorated rapidly with progression to stupor and coma. After poor prognosis was established, the calf was humanely euthanized.

Subsequently, a complete necropsy was performed, the analysis of which identified a poor staturoponderal development considering the age and the breed of the animal (measured weight 82 kg, normal weight 136 kg). The general body condition was reduced with generalized muscle atrophy. No other macroscopical lesion was observed. Representative tissue samples were fixed in 10% neutral buffered formalin, processed by routine methods in ascending grades of alcohol and embedded in paraffin wax. Sections were cut (4 µm) and stained with hematoxylin and eosin. Selected brain and spinal cord tissue samples were additionally stained with Luxol fast blue. Immunohisto chemistry was performed on brain and spinal cord sections with a streptavidin-biotin method using an anti-bovine glial fibrillary acid protein (GFAP) antibody (1:1,000 DAKO, Denmark). Paraffin wax-embedded brain and spinal cord tissues of one normal age-matched calf was used as control.

Histological examination of the CNS revealed an intense and widespread bilateral-symmetric spongy degeneration, primarily affecting the white matter with involvement of transitional areas between grey and white matter (Fig. 2). The lesion was diffusely distributed throughout the cerebrum, midbrain, cerebellum, brainstem and spinal cord. Spinal cord lesions were seen along the whole spinal cord involving primarily the myelinated fibers in the grey matter (Fig. 3). In the cerebral cortex and in the adjacent white matter, Alzheimer type II cells were observed as isolated clusters. Luxol fast blue staining of spinal cord tissue did not reveal any changes in myelin compound. Immunohistochemically, GFAP staining did not show any obvious differences in staining intensity in comparison with a normal control calf.

Microscopically, the hepatic portal triads presented numerous prominent proliferating small arterioles, hypoplastic to absent portal veins, proliferation of bile ducts and often ectasia of lymphatic vessels (Fig. 4). In cross-sections, skeletal muscles revealed diffusely atrophic myofibers (up to 30 µm in diameter) with occasionally single group of angular and shrunken atrophic myofibers. Peripheral nerves were histologically unremarkable.

The pathomorphological lesions described herein are compatible with a hepatic encephalomyelopathy due to a CPSS with secondary generalized muscle atrophy. HE is described in association with hepatic failure and consists of bilateral symmetric spongy degeneration of white matter and the presence of single or small groups of Alzheimer type II cells [11]. Hepatic myelopathy is rarely described in veterinary medicine. A similar myelopathy as decribed in this case has only been described in experimentally induced hyperammonemic calves [1]. In human medicine, hepatic myelopathy is defined as a neurological complication of hepatic cirrhosis [5] with portal hypertension, usually characterized by symmetrical demyelination of the corticospinal tracts [5]. In this case, the most pronounced spinal cord changes were restricted to the nerve fibers in the spinal cord grey matter without obvious demyelination which differs significantly to that found in human patients.

Hepatic atrophy and intra- or extra-hepatic vascular anomalies are the main gross findings reported in large animal species with CPSS [4,13]. Ascites, due to persistent portal hypertension, is commonly associated with acquired portosystemic shunts, and is absent in congenital portosystemic shunts [14]. The histological findings of the liver together with the absence of ascites, multiple tortuous shunted vessels or hepatic changes were compatible with a CPSS, similarly to previous reports [9].

Due to the absence of clinicopathological evidence of hepatic dysfunction in this calf and to the unspecific clinical signs, a portosystemic shunt with secondary hepatic encephalopathy was not included in the differential diagnosis. However, total serum bile acid concentration, total blood ammonia values and sulfobromophthalein retention time tests, normally increased in CPSS, were not measured. The clinical signs observed in this reported calf (ataxia, depression, stupor and coma) could be explained by the hepatic encephalomyelopathy. However, clinical signs were far unspecific which led to a erroneous diagnosis. The muscle atrophy in this calf was most likely related to the CPSS, as severe liver disease are known to induce protein metabolic perturbations and secondary muscle atrophy [14]. Although EMG results suggested a peripheral nervous system involvement, peripheral nerves did not reveal any histopathological changes. However, the presence of single group of atrophic myofibers in histology suggested a mild neurogenic atrophy, probably correlated to the severe spongy changes in adjacent areas of the motor neurons in the grey matter. The possible explanation for the initial recovery after antibiotic administration may be that ureaseproducing intestinal bacteria were temporarily reduced in the intestinal tract, hence long-term medical management using oral antibiotics has been described in small animals to inhibit both the production and absorption of potential gut derived CNS toxins [7].

Congenital portosystemic shunt with secondary hepatic encephalomyelopathy has rarely been described in calves. However, hepatic encephalomyelopathy due to CPSS might have heterogeneous manifestations. Because of the nonspecific associated clinical signs, it is likely that CPSS is often under-diagnosed. Hence, it should be considered in the differential diagnostic list in young animals exhibiting stunted growth and history of intermittent neurological deficits.