Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritance. Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable. A muscle/nerve biopsy revealed a mild type II fiber predominant muscle atrophy. While treatment with phenobarbital, diazepam or levetiracetam did not alter the clinical course, treatment with a gluten-free, home-made fresh meat diet in three dogs or a tryptophan-rich, gluten-free, seafood-based diet, stress-reduction, and acetazolamide or zonisamide in the fourth dog correlated with a partial reduction in, or even a complete absence of, dystonic episodes. The genomes of two cases were sequenced and compared to 654 control genomes. The analysis revealed a case-specific missense variant, c.1658G>A or p.Arg553Gln, in the PCK2 gene encoding the mitochondrial phosphoenolpyruvate carboxykinase 2. Sanger sequencing confirmed that all four cases carried the mutant allele in a heterozygous state. The mutant allele was not found in 117 Shetland Sheepdog controls and more than 500 additionally genotyped dogs from various other breeds. The p.Arg553Gln substitution affects a highly conserved residue in close proximity to the GTP-binding site of PCK2. Taken together, we describe a new form of paroxysmal exercise-induced dyskinesia (PED) in dogs. The genetic findings suggest that PCK2:p.Arg553Gln should be further investigated as putative candidate causal variant.

The term “meningoencephalitis of unknown origin” (MUO) describes a group of different encephalitides in dogs in which no infectious agent can be identified and a multifactorial etiology is suspected. Among others, genetic factors and unknown triggers seem to be involved. Included are necrotizing leukoencephalitis (NLE), necrotizing meningoencephalitis (NME), and granulomatous meningoencephalitis (GME). In this case series, we describe the histopathological findings of four toy breed dogs with focal or multifocal necrotizing encephalitis and mainly lymphocytic perivascular infiltrates on histopathological examination. At the same time, however, in all dogs, focal or multifocal high-grade angiocentric granulomatous inflammatory lesions were evident with focal histiocytic perivascular infiltrates in the brain. The former changes are typical for NLE and NME. In contrast, the latter changes are indicative of GME. This case series shows that the boundaries between the necrotizing and granulomatous variants of MUO might be smooth and suggests that NLE, NME, and GME are not as distinct as previously described. This finding could be a crucial piece of the puzzle in the study of the pathogenesis of MUO as individual susceptibility and specific triggers could be responsible for the manifestation of the different MUO subtypes.

Meningoencephalitis of unknown origin (MUO) describes a group of meningoencephalitides in dogs with a hitherto unknown trigger. An infectious agent has been suggested as one possible trigger of MUO but has not been proven so far. A relatively new method to screen for viral RNA or DNA is next-generation sequencing (NGS) or deep sequencing. In this study, a metagenomics analysis of the virome in a sample is analyzed and scanned for known or unknown viruses. We examined fresh-frozen CSF of 6 dogs with MUO via NGS using a modified sequence-independent, single-primer amplification protocol to detect a possible infectious trigger. Analysis of sequencing reads obtained from the six CSF samples showed no evidence of a virus infection. The inability to detect a viral trigger which could be implicated in the development of MUO in the examined population of European dogs, suggests that the current techniques are not sufficiently sensitive to identify a possible virus infection, that the virus is already eliminated at the time-point of disease outbreak, the trigger might be non-infectious or that there is no external trigger responsible for initiating MUO in dogs.

Meningoencephalomyelitis of unknown origin (MUO) is an umbrella term describing inflammatory changes of the central nervous system (CNS) with suspected non-infectious etiology. Diagnosis of MUO mostly remains presumed in a clinical setting. Histopathological and immunohistochemical examination of CNS tissue represent additional tools for detection of inflammation and the exclusion of specific infectious agents. While MUO is well-described in canine patients, only little is known about MUO in cats. Previous reports of feline MUO involve either clinical findings or histopathological examination but not both. The present case series is the first report describing both clinical and histopathological findings of feline MUO: Four cats (age: 1.7–17.8 years) showed acute to chronic progressive neurological signs of encephalopathy or myelopathy. Three cats had extraneural signs (hyperthermia, weight loss, hyporexia, leukocytosis). Magnetic resonance imaging (MRI) showed multifocal intraparenchymal lesions in forebrain, brainstem or spinal cord with homogenous contrast enhancement (2/2). Cerebrospinal fluid (CSF) examination was normal or displayed albuminocytologic dissociation. Histopathology revealed a multifocal, lympho-histiocytic meningoencephalitis in three cases and a lympho-histiocytic myelitis in one case. Immunohistochemistry for feline parvovirus, feline coronavirus, feline herpesvirus, tick borne encephalitis virus, Borna disease virus, morbillivirus, rabies virus, suid herpesvirus-1, and Toxoplasma gondii were negative in all cases. This case series is the first one reporting both clinical and histopathological findings in cats with MUO. Feline MUO incorporates heterogeneous subtypes of sterile CNS inflammation.

Background Whether compressive cervical myelopathy caused by hydrated nucleus pulposus extrusion (HNPE) in dogs should be treated surgically or conservatively has been debated. Only 1 recent study has contradicted the former predominant reports of surgical treatment for HNPE. Hypothesis and method Single center retrospective study to compare the outcome of client‐owned dogs with HNPE after decompressive surgery or conservative treatment. Animals Thirty‐six dogs diagnosed with HNPE confirmed by magnetic resonance imaging (MRI). Results Eighteen of 36 dogs underwent surgery whereas 18 dogs were managed conservatively including cage rest and physiotherapy. The most common affected intervertebral disc space was C4‐5. In 3 dogs, HNPE was diagnosed at the level of T13‐L1. Median time to regain ambulation was 6.6 days (range, 0‐28 days) after surgery and 5.9 days (range, 0‐15 days) with conservative management (P = .37). Only the length of a potential intramedullary lesion in cervical HNPE detected by MRI had an influence on the prognosis to gain ambulatory status in a time period of ≤9 days (P = .0035) and on short‐term survival (P = .0011). Conclusions and clinical importance Conservative management of HNPE in the cervical as well as in the thoracolumbar region represents a reasonable alternative to surgery, showing similar favorable outcome.

ChatGPT and scientific papers in veterinary neurology; is the genie out of the bottle?