Idiopathic and structural episodic nonintentional head tremor in dogs: 100 cases (2004-2022).

BACKGROUND: Although idiopathic episodic head tremor (IEHT) in dogs is well-known, little is known about structural brain lesions causing structural episodic head tremor (SEHT). HYPOTHESIS/OBJECTIVES: Describe semiology, magnetic resonance imaging (MRI) findings and outcome of dogs with IEHT or SEHT. We hypothesized that structural lesions affecting the middle cranial fossa or mesencephalic aqueduct could lead to SEHT. ANIMALS: One hundred dogs with IEHT (n = 71) or SEHT (n = 29). METHODS: Retrospective, multicenter, study of dogs with episodic (nonintentional) head tremor and brain MRI between 2004 and 2022. RESULTS: Lesions on MRI in SEHT dogs were localized to the middle cranial fossa (15/29), cerebrocortex (3/29), brainstem (2/29), fourth ventricle (1/29) or multifocal (8/29) with thalamus involvement (6/8). Secondary compression of the mesencephalic aqueduct (19/29), third ventricle or interthalamic adhesion or both (14/29) was common. The most common underlying condition in dogs with SEHT was a pituitary mass. Dogs with SEHT were older, had additional neurological signs and were more likely to be euthanized after diagnosis (P < .001 for all) compared to IEHT dogs. Two SEHT dogs had only tremor. In IEHT dogs, 8/10 owners reported that the tremor decreased or abated over time (range, 106-2315 days) without treatment. Tremor remission occurred in SEHT dogs treated for underlying meningoencephalitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Presence of additional neurological signs and older age may indicate an underlying structural cause for episodic (nonintentional) head tremor involving the mesencephalic aqueduct, third ventricle, interthalamic adhesion or some combination of these. An intracranial structural abnormality cannot be excluded in dogs with normal neurological examination.

Complications associated with cerebrospinal fluid collection in dogs.

BACKGROUND: This study aimed to identify complications associated with cerebrospinal fluid (CSF) collection in dogs. METHODS: This was a prospective, observational multicentre study using data collected from 102 dogs undergoing CSF collection for the investigation of neurological disease. CSF was collected from the cerebellomedullary cistern (CMC), lumbar subarachnoid space (LSAS) or both sites. Pre-, intra- and postprocedural data were collected. Descriptive statistics were performed to outline complications associated with CSF collection. RESULTS: CSF sampling was attempted on 108 occasions, and CSF was acquired on 100 occasions (92.6%). Collection from the CMC was more likely to be successful than that from the LSAS. No dogs exhibited neurologic deterioration following CSF collection. There was no significant difference between pre- and post-CSF collection short-form Glasgow composite measure pain scores in ambulatory dogs (p = 0.13). LIMITATIONS: The scarcity of complications limited the ability to quantify the incidence of some potential complications reported elsewhere. CONCLUSIONS: Our results may be used to inform clinicians and owners that CSF sampling is associated with a low frequency of complications when performed by trained personnel.

Bruxism in awake dogs as a clinical sign of forebrain disease: 4 cases.

BACKGROUND: Bruxism is a repetitive masticatory muscle activity characterized by clenching or grinding of the teeth, or by bracing or thrusting of the mandible, or both. OBJECTIVES: To investigate whether bruxism in awake dogs could be associated with brain lesions. ANIMALS: Four dogs with episodic bruxism in the awake state. METHODS: Observational retrospective single-center case series. Inclusion criteria were dogs examined between 2010 and 2021 with episodic bruxism as a presenting complaint or observed during the examination or hospitalization, complete medical records and magnetic resonance imaging or computed tomography of the brain. Bruxism during epileptic seizures as oroalimentary automatism was an exclusion criterion. RESULTS: Four dogs met the inclusion criteria. Two dogs had bruxism while awake as a presenting complaint, whereas in the remaining 2 it was a clinical finding. All dogs had neuroanatomical localization consistent with a forebrain lesion, with diencephalic involvement in 3/4. The diagnostic evaluation was consistent with neoplasia (n = 2) and meningoencephalitis of unknown origin (n = 2), in 1 case accompanied by corpus callosum abnormality affecting the forebrain, in 3 dogs advanced imaging findings were suggestive of increased intracranial pressure. All dogs were euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that the presence of bruxism in the awake state associated with other neurological deficits might indicate a forebrain lesion.

Dissolution of Mn-bearing dolomite drives elevated Cr(VI) occurrence in a Permian redbed aquifer.

Municipalities in central Oklahoma, U.S.A. increasingly rely on water drawn from the Central Oklahoma Aquifer (COA) as surface water resources have not grown in proportion to population and current water demands. However, water drawn from certain regions of the COA frequently contains elevated levels of naturally occurring hexavalent chromium. Rock samples from the Norman Arsenic Test Hole Core (NATHC) were investigated to identify the mineralogic host(s) of Cr and mechanisms of Cr(VI) release via bulk mineralogy and chemistry measurements, selective chemical extractions, and microscale elemental analyses. Results demonstrate most COA Cr is contained in Fe oxides and clays as isomorphic substitutions for Fe(III). Analyses of regional groundwater data, including hierarchical clustering methods and GIS, demonstrate the most intense Cr(VI) occurrence is linked to cation exchange with Na-clays at depth. Cation exchange allows dissolution of Mn-bearing dolomite, which in turn produces Mn oxides in otherwise dolomite-saturated groundwaters. Mn oxides in turn are known to oxidize Cr(III) to Cr(VI). In general, co-occurrence of Mn-bearing carbonates and exchangeable clays in any aquifer, particularly those with Cr(III) present in iron oxide cements, serve as ingredients for groundwater occurrences of oxidizable trace metals.

Use of 3D Printing Technology to Create a Canine Simulator for Cerebrospinal Fluid Sampling at the Lumbar Subarachnoid Space.

Cerebrospinal fluid (CSF) sampling at the lumbar subarachnoid space (LSS) is technically challenging to learn. Currently, training relies on cadaver availability or performance in a clinical scenario. This study aims to develop and validate a low-cost, high-fidelity simulator to train in this technique. Using three-dimensional printing technology, a model of a healthy adult dog's lumbosacral vertebral column was produced. The model was augmented with synthetic materials and a fluidic system to replicate all procedural steps and permit successful CSF collection. The simulator was validated by four experts, who rated it highly across multiple criteria. Final-year veterinary students were recruited to take part in practical sessions using either the simulator (n = 16) or a cadaver (n = 16). Performance was recorded for each student, and feedback was obtained using an anonymous online survey. Student performance was similar between groups (p = .2), with 87.5% and 68.75% of students in the simulator and cadaver group, respectively, successfully placing the needle into the LSS. All successful students in the simulator group were able to obtain a CSF sample, versus none in the cadaver group. No difference in the number of attempts was detected between groups (p > .99), with most students taking more than three attempts. User experience was similar between groups, with 93.8% of students in each group rating the session as a positive learning experience. In summary, we demonstrate the validity of a novel, low-cost, and anatomically precise simulator that can be used for teaching CSF sampling at the LSS.

Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth.

Myelination of axons by oligodendrocytes enables fast saltatory conduction. Oligodendrocytes are responsive to neuronal activity, which has been shown to induce changes to myelin sheaths, potentially to optimize conduction and neural circuit function. However, the cellular bases of activity-regulated myelination in vivo are unclear, partly due to the difficulty of analyzing individual myelinated axons over time. Activity-regulated myelination occurs in specific neuronal subtypes and can be mediated by synaptic vesicle fusion, but several questions remain: it is unclear whether vesicular fusion occurs stochastically along axons or in discrete hotspots during myelination and whether vesicular fusion regulates myelin targeting, formation, and/or growth. It is also unclear why some neurons, but not others, exhibit activity-regulated myelination. Here, we imaged synaptic vesicle fusion in individual neurons in living zebrafish and documented robust vesicular fusion along axons during myelination. Surprisingly, we found that axonal vesicular fusion increased upon and required myelination. We found that axonal vesicular fusion was enriched in hotspots, namely the heminodal non-myelinated domains into which sheaths grew. Blocking vesicular fusion reduced the stable formation and growth of myelin sheaths, and chemogenetically stimulating neuronal activity promoted sheath growth. Finally, we observed high levels of axonal vesicular fusion only in neuronal subtypes that exhibit activity-regulated myelination. Our results identify a novel "feedforward" mechanism whereby the process of myelination promotes the neuronal activity-regulated signal, vesicular fusion that, in turn, consolidates sheath growth along specific axons selected for myelination.

Dietary management and major clinical events in patients with long-chain fatty acid oxidation disorders enrolled in a phase 2 triheptanoin study.

BACKGROUND & AIMS: Long-chain fatty acid oxidation disorders (LC-FAOD) are rare, life-threatening, autosomal recessive disorders that lead to energy depletion and major clinical events (MCEs), such as acute metabolic crises of hypoglycemia, cardiomyopathy, and rhabdomyolysis. The aim of this study was to report a post hoc analysis of diet diary data from the phase 2 UX007-CL201 study (NCT01886378). METHODS: In the single-arm, open-label, phase 2 UX007-CL201 study, the safety and efficacy of 78 weeks of treatment with triheptanoin, an odd-carbon, medium-chain triglyceride consisting of three 7-carbon fatty acids on a glycerol backbone, was investigated in subjects with LC-FAOD versus a retrospective 78-week period when subjects were optimally managed under published dietary guidelines. Subject dietary reports were collected to analyze the relationship between diet, triheptanoin treatment, and MCEs. Referring metabolic physicians completed a survey on patient management and clinical outcomes before and after initiation of triheptanoin. Before initiating triheptanoin, subjects received a mean daily caloric intake (DCI) of 17.4% from medium-chain triglycerides (MCT). During the study, subjects received a mean of 27.5% DCI from triheptanoin. Protein (13.7% vs 14.5% DCI), long-chain fat (13.1% vs 10.5% DCI), and carbohydrate (55.3% vs 47.1% DCI) intake were consistent between the pre-triheptanoin and triheptanoin treatment periods, respectively. RESULTS: Following 78 weeks of treatment, mean annualized MCE rate decreased by 48.1% (p = 0.021) and mean annualized MCE event-day rate decreased by 50.3% (p = 0.028). A weak association existed between improvement in annualized MCE rate and change in percent DCI from MCT (Spearman rank correlation: r = -0.38; 95% CI: -0.675, 0.016). However, there was large variability in the association and no specific pattern of change for larger or smaller changes in dose. Seventy-two percent of physicians reported that triheptanoin had a clinically meaningful benefit on medical management of their patients. CONCLUSIONS: Treatment with triheptanoin at the protocol-specified dose decreased the rate of MCEs in patients with LC-FAOD independently from other dietary changes between the pre-triheptanoin and triheptanoin treatment periods. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01886378.