[COVID-19 and the central and peripheral nervous system]. / COVID-19: Auswirkungen auf das zentrale und periphere Nervensystem.

The health effects of coronavirus disease 2019 (COVID-19) caused by the infection of SARS-CoV­2 (severe acute respiratory syndrome coronavirus 2) are becoming increasingly clear as the pandemic spreads. In addition to the lungs, other organs are also affected, which can significantly influence morbidity and mortality. In particular, neurological symptoms involving the central nervous system can lead to acute or long-term consequences. The mechanisms of this neuropathogenesis of SARS-CoV­2 infection and its relation to acute and chronic neurological symptoms are the subject of current studies investigating a potential direct and indirect viral infection of the nervous system. The following review summarizes the current status of neuropathological manifestations, molecular pathogenesis, possible infection pathways in the nervous system, and systemic effects. In addition, an overview of the Germany-wide CNS-COVID19 registry and collaborations is presented, which should contribute to a better understanding of the neurological symptoms of COVID-19.

Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog.

Neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases that have been described in a variety of dog breeds, where they are caused by different mutations in different genes. However, the causative gene defect in the breed Alpenländische Dachsbracke remained unknown so far. Here we present two confirmed cases of NCL in Alpenländische Dachsbracke dogs from different litters of the same sire with a different dam harboring the same underlying novel mutation in the CLN8 gene. Case 1, a 2-year-old male Alpenländische Dachsbracke was presented with neurological signs including disorientation, character changes including anxiety states and aggressiveness, sudden blindness and reduction of food intake. Magnetic resonance imaging (MRI) scans showed cerebral atrophy with dilation of all cerebral ventricles, thinning of the intermediate mass of the thalamus and widening of the cerebral sulci. Postmortem examination of the central nervous system (CNS) showed neuronal loss in the cerebral cortex, cerebellum and spinal cord with massive intracellular deposits of ceroid pigment. Additional ceroid-lipofuscin deposits were observed in the enteric nervous system and in macrophages within spleen, lymph nodes and lung. Ultrastructural analyses confirmed NCL with the presence of osmiophilic membrane bounded lamellar-like structures. Case 2, a 1,5-year old female Alpenländische Dachsbracke was presented with progressive generalized forebrain disease including mental changes such as fearful reactions to various kinds of external stimuli and disorientation. The dog also displayed seizures, absence of menace reactions and negative cotton-ball test with normal pupillary light reactions. The clinical and post mortem examination yielded similar results in the brain as in Case 1. Whole genome sequencing of Case 1 and PCR results of both cases revealed a homozygous deletion encompassing the entire CLN8 gene as the most likely causative mutation for the NCL form observed in both cases. The deletion follows recessive inheritance since the dam and a healthy male littermate of Case 1 were tested as heterozygous carriers. This is the first detailed description of CLN8 gene associated NCL in Alpenländische Dachsbracke dogs and thus provides a novel canine CLN8 model for this lysosomal storage disease. The presence of ceroid lipofuscin in extracerebral tissues may help to confirm the diagnosis of NCL in vivo, especially in new dog breeds where the underlying mutation is not known.

Metastasizing Esthesioneuroblastoma in a Dog.

A 7-year-old Afghan hound presented with a history of disorientation, loss of vision, and seizures. Magnetic resonance imaging helped identify a mass at the level of the main olfactory bulb that compressed and displaced adjacent tissues in the cribriform plate into the nasal cavity and nasopharynx. Bony structures were osteolytic. After removing almost 80% of the mass, the tumor recurred a few months later. Due to severe respiratory distress and subsequent to an ultrasound diagnosis of a liver tumor, the dog was euthanized. In addition to the nasal mass, a single nodule in the liver and multiple nodules in the lung were present. All masses had similar cell morphology and were diagnosed as metastasizing esthesioneuroblastoma. The neoplastic cells expressed neuron-specific enolase and chromogranin A, and a few cells within the nasal mass were positive for cytokeratin. This is the first description of a canine esthesioneuroblastoma with distant metastases.

Neurogenesis in a young dog with epileptic seizures.

Epileptic seizures can lead to various reactions in the brain, ranging from neuronal necrosis and glial cell activation to focal structural disorganization. Furthermore, increased hippocampal neurogenesis has been documented in rodent models of acute convulsions. This is a report of hippocampal neurogenesis in a dog with spontaneous epileptic seizures. A 16-week-old epileptic German Shepherd Dog had marked neuronal cell proliferation (up to 5 mitotic figures per high-power field and increased immunohistochemical expression of proliferative cell nuclear antigen) in the dentate gyrus accompanied by microglial and astroglial activation. Some granule cells expressed doublecortin, a marker of immature neurons; mitotically active cells expressed neuronal nuclear antigen. No mitotic figures were found in the brain of age-matched control dogs. Whether increased neurogenesis represents a general reaction pattern of young epileptic dogs should be investigated.

Aprosencephaly with otocephaly in a lamb (Ovis aries).

Aprosencephaly is a rare condition in veterinary and human medicine characterized by the complete absence of telencephalon and diencephalon. Some cases are accompanied by a facial dysmorphism designated as otocephaly. A stillborn lamb had splanchnocranial anomalies that were classified by computed tomography, magnetic resonance imaging, and pathologic examination as aprosencephaly and otocephaly. The brain included parts of the cerebellum and brainstem but no telencephalon, diencephalon, or mesencephalon. The cerebellum had a structurally normal cortex with expression of neuronal nuclear antigen in the inner and doublecortin in the outer granular cell layers, as well as an irregularly situated nucleus dentatus. Aprosencephaly with otocephaly has been described in mice with heterozygous mutations in the Otx2 gene; however, no causative polymorphisms were detected in the Otx2 gene region of this lamb.

An in-depth diagnostic exploration of an inflammation and necrosis syndrome in a population of newborn piglets.

Inflammation and loss of tail integrity can be reasons for serious impairment of animal welfare and one of the major challenges facing modern pig farming. Evidence from practice increasingly suggests that tail lesions might be caused not only by tail biting but also by inflammation and necrosis, which can occur without any action from other pigs. Such changes are not limited to the tail but can also be observed in the ears, heels and soles, claw coronary bands, teats, navel, vulva and face. To describe inflammatory and necrotic manifestations in newborn piglets, all 146 piglets from 11 sows were clinically examined not later than 2 h after birth. In addition, the tail base of 30 randomly selected piglets out of the 146 was histo-pathologically examined as one of the most conspicuously affected body parts. Over 80% of the newborns showed affections in the tail base, claw wall and heels. In 65-87% of the animals, the coronary bands, teats, the face and the ears were affected. None of the 146 piglets was completely free from pathological manifestations. On average, the piglets were affected in six out of nine body parts simultaneously. Histological examinations showed that clear alterations in the skin were already manifested around the time of birth in all examined piglets. Alterations were characterised by the occurrence of numerous lymphocytes and granulocytes throughout the entire subepithelial connective tissue, predominantly in perivascular and perifollicular localisation but also within directly subepithelial glandular ducts and diffusely within the subepithelial connective tissue. In the majority of individuals, the epithelial structure was intact. This concurrence of symptoms in the newborns indicates a primarily endogenous aetiology of an inflammation and necrosis syndrome. Further studies in diverse herd contexts are necessary to establish the conditions for the emergence of such a syndrome and develop welfare indicators.

Leukoencephalopathy associated with parvovirus infection in Cretan hound puppies.

Leukoencephalopathies in dogs encompass presumably inherited conditions such as leukodystrophies, hypomyelination or spongiform degeneration, but other causes, such as virus infections and toxic or nutritional factors, might also play a contributory role. In this report, we provide evidence of parvovirus infection and replication in the brains of five 6-week-old Cretan hound puppies suffering from a puppy shaker syndrome and leukoencephalopathy. Although these puppies belonged to two different litters, they were closely related, tracing back two generations to the same sire. Histologically, a mild to moderate lymphohistiocytic meningitis, with focal lymphohistiocytic leukoencephalitis in two animals, and a mild to moderate vacuolation with myelin loss, mainly in the white matter of the cerebellum was detected. Vacuolation was also found in the corpus callosum, fimbria hippocampi, mesencephalon, capsula interna, basal ganglia, and hypothalamus. By immunohistology and in situ hybridization, either parvoviral antigen, DNA, mRNA, or replicative intermediate DNA were detected in the cerebellum, hippocampus, periventricular areas, corpus callosum, cerebral cortex, medulla oblongata, and spinal cord. Parvovirus antigen, DNA, and mRNA were present in cells of the outer granular layer of the cerebellum and in periventricular cells, most likely representing spongioblasts, glial cells, neurons, endothelial cells, occasional macrophages, and ependymal cells. Sequencing revealed canine parvovirus type 2 stretches. Thus, an association of parvovirus infection with the leukoencephalopathy seems likely, possibly facilitated by a genetic predisposition due to the mode of inbreeding in this particular dog breed.

Anencephaly in a german shepherd dog.

Anencephaly results from defects in neural tube closure early in gestation and, to the authors' knowledge, has not been reported in dogs. In this case, the canine fetus was stillborn at the 62nd day of gestation and had a hypoplastic calvarium, with flattened base of the skull and shallow orbits, causing protrusion of the eyes. Macroscopically, the brain was completely missing. Histologically, well-differentiated nerve fibers, fragments of cerebellar folia, and ganglia with large neurons and glial cells were detected in a loose stroma in sections through the cranial bone and adjacent soft tissue in the rudimentary cranial cavity. Immunohistochemically, single cells within the stroma expressed NeuN, consistent with mature neurons, whereas intracranial ganglion cells and nerves had mild expression of doublecortin. The presence of many immature, and only a few mature, neurons in the rudimentary nerve tissue in this case indicates a failure of physiological brain development and differentiation.

Proposing the term purkinjeoma: protein gene product 9.5 expression in 2 porcine cardiac rhabdomyomas indicates possible purkinje fiber cell origin.

Rhabdomyomas, defined as rare benign tumors of striated muscle, predominantly occur in the myocardium. In veterinary medicine, cardiac rhabdomyomas have rarely been reported but most frequently in pigs as an incidental finding. In the present case report, multiple circumscribed nodules found in the myocardium of 2 pigs were composed of large, vacuolated, glycogen-loaded cells. They expressed vimentin and desmin, neuron-specific enolase, and atrial natriuretic peptide. In addition, these cells expressed protein gene product 9.5, a marker for neuronal tissue and Purkinje fiber cells, in contrast to adjacent myocytes. The present findings-especially, the protein gene product 9.5 immunoreactivity-provide further evidence for the Purkinje fiber cell origin of the porcine myocardial proliferation. Therefore, the term purkinjeoma or purkinjeomatosis is proposed for cardiac rhabdomyoma in pigs.

Fatal cowpox virus infection in captive banded mongooses (Mungos mungo).

Cowpox virus infections have been described in various domestic and exotic animal species. This report is the first on an outbreak of fatal generalized cowpox virus infection among captive banded mongooses (Mungos mungo, suborder Feliformia). All animals of a colony of 8 mongooses showed a fulminant course of disease. The whole population died (n=7) or was euthanized (n=1) within 11 days. Postmortem examinations were performed on 4 animals. All animals showed extensive necrotizing inflammation of retropharyngeal lymph nodes, typical poxviral skin lesions, and multiple necrotic foci in liver and spleen. Three animals exhibited an ulcerating stomatitis. Pulmonary lesions, a common feature of fatal cowpox virus infections in other feliform species, were not obvious. Histopathologically, characteristic cytoplasmic inclusion bodies were detected in all affected organs but the spleen. Based on transmission electron microscopy and cell culture, Orthopoxvirus was identified as the etiology. The virus was further characterized by polymerase chain reaction and sequence analysis, identifying it as cowpox virus. A survey in the habitat suggests wild brown rats (Rattus norvegicus) as the most likely source of infection.