Postoperative Wound Healing

Introduction

Three related litters (all parents had a common ancestor) of the German Shepherd breed with 11 affected puppies (9 males and 2 females) are described here. Two litters were born in Germany and one in Finland. The affected dogs exhibited coarse tremors of the head and trunk from side to side that disrupted normal aimed movements and disappeared at rest. Symptoms were observed shortly after birth.

Puppy Examination

At the age of 7 weeks, clinical and neurological examinations, laboratory tests, and imaging examinations (brain MRI in 4 puppies, spinal MRI in 1 puppy, CT angiography in 1 puppy) were performed. Two siblings (males) were raised to adulthood, allowing monitoring of the disease's progression until the age of 3 years. One of them underwent repeated brain MRIs (at 15, 27, and 69 weeks). Euthanasia was performed on 9 puppies, and an autopsy was subsequently conducted on 1 affected puppy from each litter (at the ages of 3, 5, and 7 weeks). The breeder also provided videos of the puppies.

Laboratory evaluation included routine hematology and biochemistry, serum electrolyte concentration, creatine kinase activity, ammonia concentration in blood fasting and postprandially, ammonia tolerance test, bile acids concentration, blood gas analysis, lactate concentration in blood, serum cobalamin concentration, urine analysis, and screening for hereditary neurometabolic disorders (urine organic acids, oligosaccharides, and mucopolysaccharides, plasma amino acids). All laboratory results were normal, except for borderline increased ammonia concentrations in affected puppies, which normalized in adult dogs. 

Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging revealed a homogeneous hyperintense signal of the entire subcortical white matter in 3 affected 7-week-old dogs and a hypointense signal in a presumably unaffected sibling. In repeated MRI examinations at 15 and 27 weeks, the subcortical white matter appeared abnormally isointense to gray matter. The abnormal white matter signal with disrupted display of normal gray and white matter contrast persisted into adulthood. The cerebellar branch-like pattern vermis (arbor vitae) was not visible at any time. Clinical symptoms, MRI findings, and pathological examinations suggested hypomyelinating leukodystrophy.

Genetics

Genetic testing failed to identify a causal gene variant, and previously reported pathogenic variants in the PLP1 and FNIP2 genes were not found in the affected German Shepherds. The pedigree of the puppies corresponds to a model of autosomal recessive inheritance.

Clinical Course of the Disease

The breeder first noticed neurological symptoms in the puppies at 11 days old. At this time, there was no size or weight difference between affected and unaffected puppies. All puppies were only able to crawl and roll, and all would fall during their attempts to move. The affected dogs (males) exhibited a coarse side-to-side tremor spreading from the hindquarters to the neck and head.

At 17 days of age, the difference between affected and unaffected puppies was apparent. Three affected puppies were only able to crawl, exhibiting a marked coarse tremor of the hind limbs from side to side and a coarse tremor of the head and neck. There was no difference in size or severity of clinical symptoms between affected males and females. At 4 months old, the dogs could only walk a few meters and displayed severe hypermetric ataxia of the pelvic limbs and paresis. Adult dogs walked with residual pelvic limb ataxia. One dog developed epilepsy with tonic-clonic seizures at 15 months old.

Summary and Conclusion

Repeated conventional brain MRI examination was useful in characterizing abnormal maturation of subcortical and cerebellar white matter. The clinical course was non-progressive, and adult dogs walked with residual pelvic limb ataxia. The disease is presumed to be genetic with an autosomal recessive inheritance pattern. Therapy is supportive and symptomatic only.

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Source: Quitt P. R., Brühschwein A., Matiasek K. et al. A hypomyelinating leukodystrophy in German Shepherd dogs. J Vet Intern Med 2021 May-Jun; 35 (3): 1455−1465, doi: 10.1111/jvim.16085.