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CASE DESCRIPTION A 9-month-old intact male domestic shorthair cat was evaluated for increasing frequency of generalized tonic-clonic seizures. CLINICAL FINDINGS The cat was reported to have had episodes of circling between the seizures. Upon examination, the cat had bilateral inconsistent menace response but otherwise normal physical and neurological examinations. DIAGNOSTICS Magnetic resonance imaging (MRI) of the brain identified multifocal, small, rounded intra-axial lesions within the subcortical white matter containing fluid with similar characteristics as cerebrospinal fluid. Evaluation of urine organic acids showed increased excretion of 2-hydroxyglutaric acid. An XM_023255678.2:c.397C>T nonsense variant in the L2HGDH gene encoding L-2-hydroxyglutarate dehydrogenase was identified using whole genome sequencing. TREATMENT AND OUTCOME Levetiracetam treatment was initiated at 20 mg/kg PO q8h, but the cat died after a seizure 10 days later. CLINICAL RELEVANCE We report the second pathogenic gene variant in L-2-hydroxyglutaric aciduria in cats and describe for the first time multicystic cerebral lesions on MRI.

BACKGROUND Some paroxysmal movement disorders remain without an identified genetic cause. OBJECTIVES The aim was to identify the causal genetic variant for a paroxysmal dystonia-ataxia syndrome in Weimaraner dogs. METHODS Clinical and diagnostic investigations were performed. Whole genome sequencing of one affected dog was used to identify private homozygous variants against 921 control genomes. RESULTS Four Weimaraners were presented for episodes of abnormal gait. Results of examinations and diagnostic investigations were unremarkable. Whole genome sequencing revealed a private frameshift variant in the TNR (tenascin-R) gene in an affected dog, XM_038542431.1:c.831dupC, which is predicted to truncate more than 75% of the open read frame. Genotypes in a cohort of 4 affected and 70 unaffected Weimaraners showed perfect association with the disease phenotype. CONCLUSIONS We report the association of a TNR variant with a paroxysmal dystonia-ataxia syndrome in Weimaraners. It might be relevant to include sequencing of this gene in diagnosing humans with unexplained paroxysmal movement disorders. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi-center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from seven veterinary centers were searched for cases of histologically confirmed IVL. Dogs were included if an MRI was performed. The MRI studies and histopathology samples were reviewed to compare the MRI changes with the histopathological findings. Twelve dogs met the inclusion criteria (12 brains and three spinal cords). Imaging of the brains revealed multifocal T2-weighted/FLAIR hyperintense and T1-weighted iso-hypointense lesions, with variable contrast enhancement; areas of abnormal diffusion both in arterial and venous territories in diffusion-weighted imaging; and meningeal enhancement. On gradient echo images (GRE), the changes comprised tubular susceptibility artifacts, consistent with the "susceptibility vessel sign", and additional variably sized/shaped intraparenchymal susceptibility artifacts. Spinal cord lesions presented as fusiform T2-weighted hyperintensities with scattered susceptibility artifacts on GRE and variable parenchymal and meningeal contrast enhancement. On histopathology, subarachnoid hemorrhages and neuroparenchymal areas of edema and necrosis, with or without hemorrhage, indicating ischemic and hemorrhagic infarctions, were found. These lesions were concurrent with severely dilated meningeal and parenchymal arteries and veins plugged by neoplastic lymphocytes and fibrin. Due to the unique angiocentric distribution of IVL, ischemic and hemorrhagic infarcts of variable chronicity affecting both the arterial and venous territories associated with thrombi formation can be detected on MRI.

The unpredictable nature of seizures is challenging for caregivers of epileptic dogs, which calls the need for other management strategies such as seizure detection devices. Seizure detection devices are systems that rely on non-electroencephalographic (non-EEG) ictal changes, designed to detect seizures. The aim for its use in dogs would be to provide owners with a more complete history of their dog's seizures and to help install prompt (and potentially life-saving) intervention. Although seizure detection via wearable intracranial EEG recordings is associated with a higher sensitivity in humans, there is robust evidence for reliable detection of generalized tonic-clonic seizures (GTCS) using non-EEG devices. Promising non-EEG changes described in epileptic humans, include heart rate variability (HRV), accelerometry (ACM), electrodermal activity (EDA), and electromyography (EMG). Their sensitivity and false detection rate to detect seizures vary, however direct comparison of studies is nearly impossible, as there are many differences in study design and standards for testing. A way to improve sensitivity and decrease false-positive alarms is to combine the different parameters thereby profiting from the strengths of each one. Given the challenges of using EEG in veterinary clinical practice, non-EEG ictal changes could be a promising alternative to monitor seizures more objectively. This review summarizes various seizure detection devices described in the human literature, discusses their potential use and limitations in veterinary medicine and describes what is currently known in the veterinary literature.

Background:\ud As they have been seldomly described in the veterinary literature, the aims of this retrospective study were to describe the clinical presentation, MRI findings and long-term outcome after medical or surgical treatment of dogs presenting with foraminal and far lateral thoracolumbar intervertebral disc herniations.\ud \ud Methods:\ud Retrospective multicentre study of dogs diagnosed with foraminal and far lateral thoracolumbar intervertebral disc herniations between 2009 and 2020 in seven referral hospitals.\ud \ud Results:\ud Thirty-seven dogs were included. Dachshunds and mixed breeds were most affected. Median age at presentation and duration of clinical signs were 6 years and 14 days, respectively. Pain was the most frequent clinical finding (92%), particularly on spinal palpation and/or hip manipulation, followed by pelvic limb lameness (71%). Eighty-seven percent of herniations occurred at L5-L6 or L6-L7. A good to excellent outcome was seen in 95% of surgically and 90% of medically treated dogs.\ud \ud Conclusion:\ud Although much less frequently recognised than herniation affecting the vertebral canal, foraminal and far lateral thoracolumbar intervertebral disc herniations should be considered in the differential diagnosis list of chondrodystrophic dogs presenting with pain and pelvic limb lameness. Most dogs had a good to excellent outcome following medical or surgical treatment.

Background:\ud Status epilepticus (SE) is an emergency associated with serious consequences for both patient and owner. Data regarding risk factors for short-term mortality or recurrence in dogs with SE is limited.\ud \ud Objective:\ud Identify risk factors associated with short-term mortality (euthanasia or spontaneous death) and recurrence of SE in dogs.\ud \ud Animals:\ud One hundred twenty-four client-owned dogs that sustained an episode of SE.\ud \ud Methods:\ud Retrospective multicenter study using data collected from medical records of dogs presented in SE to the contributing institutions. Multivariable logistic regression analysis was performed using a manual backwards stepwise approach to identify risk factors associated with short-term mortality and recurrence of SE after discharge.\ud \ud Results:\ud Short-term mortality for affected dogs was 29.8%. Factors significantly associated with short-term mortality included increased patient age, shorter duration of hospitalization, development of SE before arrival, and SE caused by a potentially fatal etiology. Status epilepticus recurred in 27% of dogs that survived to discharge. Factors significantly associated with recurrence of SE included prior history of pharmacoresistant epilepsy and predominance of a focal seizure phenotype.\ud \ud Conclusions and Clinical Importance:\ud Our results may be used to inform clinicians and dog owners regarding risk factors for both short-term mortality and recurrence in dogs with SE.

Radiotherapy (RT) plays a fundamental role in the treatment of glioblastoma (GBM). GBM are notoriously invasive and harbor a subpopulation of cells with stem-like features which exhibit upregulation of the DNA damage response (DDR) and are radioresistant. High radiation doses are therefore delivered to large brain volumes and are known to extend survival but also cause delayed toxicity with 50%–90% of patients developing neurocognitive dysfunction. Emerging evidence identifies neuroinflammation as a critical mediator of the adverse effects of RT on cognitive function. In addition to its well-established role in promoting repair of radiation-induced DNA damage, activation of poly(ADP-ribose) polymerase (PARP) can exacerbate neuroinflammation by promoting secretion of inflammatory mediators. Therefore, PARP represents an intriguing mechanistic link between radiation-induced activation of the DDR and subsequent neuroinflammation. PARP inhibitors (PARPi) have emerged as promising new agents for GBM when given in combination with RT, with multiple preclinical studies demonstrating radiosensitizing effects and at least 3 compounds being evaluated in clinical trials. We propose that concomitant use of PARPi could reduce radiation-induced neuroinflammation and reduce the severity of radiation-induced cognitive dysfunction while at the same time improving tumor control by enhancing radiosensitivity.

Accurate knowledge of seizure frequency is key to optimising treatment. New methods for detecting epileptic seizures are currently investigated in humans, which rely on changes in biomarkers, also called seizure detection devices. Critical to device development, is understanding user needs and requirements. No information on this subject has been published in veterinary medicine. Many dog health collars are currently on the market, but none has proved to be a promising seizure detector. An online survey was created and consisted of 27 open, closed, and scaled questions divided over two parts: part one focused on general questions related to signalment and seizure semiology, the second part focused specifically on the use of seizure detection devices. Two hundred and thirty-one participants caring for a dog with idiopathic epilepsy, were included in the study. Open questions were coded using descriptive coding by two of the authors independently. Data was analysed using descriptive statistics and binary logistic regression. Our results showed that the unpredictability of seizures plays a major part in the management of canine epilepsy and dog owners have a strong desire to know when a seizure occurs. Nearly all dog owners made changes in their daily life, mainly focusing on intensifying supervision. Owners believed seizure detection devices would improve their dog's seizure management, including a better accuracy of seizure frequency and the ability to administer emergency drugs more readily. Owners that were already keeping track of their dog's seizures were 4.2 times more likely to show confidence in using seizure detection devices to manage their pet's seizures, highlighting the need for better monitoring systems. Our results show that there is a receptive market for wearable technology as a new management strategy in canine epilepsy and this topic should be further explored.