Neuro Flashcards
Relationship between equine herpesvirus-1 viremia and abortion or equine herpesvirus myeloencephalopathy in domesticated horses: A systematic review
Viremia as a Prerequisite
• Viremia consistently identified as a prerequisite for both abortion and EHM.
• The duration of viremia may influence risk, especially for neurological disease (EHM), but the magnitude of viremia had inconsistent associations with outcomes.
Neurological Disease (EHM)
• Inconsistent findings across studies regarding the relationship between the level of viremia and EHM:
• Some studies linked longer viremia duration to increased risk of ataxia.
• Others found no significant differences in viremia levels between horses with or without neurological signs.
• Peak viremia levels did not reliably predict EHM development, although viremic horses with neurological signs had higher viral loads than asymptomatic viremic horses in some studies.
Abortion
• Abortion rates were variable among studies and not consistently linked to the magnitude or duration of viremia.
• Pregnant mares with longer viremia durations appeared more likely to abort in some studies, but findings were inconclusive.
Methodological Challenges
• Heterogeneity in Study Design: Variability in virus strains, doses, challenge protocols, and diagnostic methods (e.g., PCR vs. plaque assays). Different methods of quantifying viremia (e.g., gene copies, cycle thresholds, TCID50) complicated comparisons.
• Reporting Gaps: Lack of raw individual horse data prevented robust statistical comparisons. Limited access to data on viremia duration and peak levels for both EHM and abortion outcomes.
• Small Sample Sizes: Low statistical power in many studies hindered conclusive analyses.
• Bias: Many studies lacked blinding of treatment groups or assessors, increasing the risk of bias.
• Monitoring viremia is essential for understanding EHV-1 pathogenesis and predicting disease outcomes, though current tools lack precision.
• Reducing viremia duration (e.g., via antiviral treatments) could theoretically lower risks of EHM and abortion.
Equine grass sickness is associated with major abnormalities in
the ultrastructure of skeletal neuromuscular junctions
EGS: Findings dissimilar to botulism. Evidence of accelerated SV exocytosis and depletion, acumulation of neurfilament like matierial and termial bouton degeneration in ICM and diaphragm. Consistent with an excitatory neurotoxin or reuptake inhibitor.
Sidewinder gait in horses
Neurologic Findings:
• leaning toward the affected side with contralateral pelvic limb abduction.
• Compressive Myelopathy: Caused by trauma, instability, or intervertebral disc disease.
• EPM: Confirmed in two cases and presumed in others; characterized by spinal cord or brainstem lesions.
• Ischemic Injury: Rare vascular events such as thrombosis, affecting motor and sensory tracts.
• Gliosis and Perivascular Cuffing: Suggestive of potential viral or inflammatory etiologies.
Musculoskeletal Findings:
• Advanced coxofemoral osteoarthritis.
• Multiple pelvic fractures.
• Severe myonecrosis of pelvic limb muscles (rare).
• Horses with musculoskeletal causes leaned contralateral to the most affected limb due to pain or mechanical limitations.
•Electromyography (EMG) was effective in distinguishing neurologic from non-neurologic causes and in localizing spinal cord lesions.
•Cerebrospinal fluid (CSF) centesis near the lesion site increased diagnostic yield but was not feasible in all cases.
• Supportive treatments included NSAIDs, antiprotozoals (e.g., ponazuril for EPM), and antioxidants, with minimal success in resolving the gait abnormality.
• Overall prognosis for recovery of function and quality of life is poor, with a high case fatality rate (79%).
• Remaining live horses showed persistent gait abnormalities despite treatment, precluding return to physical activity
Wobbler surgery: What is the evidence?
Comparison of Treatment Modalities:
• Surgical treatment offers better long-term outcomes compared to conservative methods in most cases.
• Conservative management may be effective for mild cases in young horses.
• Surgical correction is more reliable for addressing static or severe compressions, especially in older horses.
• requires strict selection criteria: >/=50% narrowing of the dorsal myelo- graphic contrast column, grades 1–4 neurological horses of ages from 6 months to 24 years of age
•horses <1 year of age with evidence of kyphosis and/or stenosis of the cervical foramen require surgical fusion for a successful outcome
APJ pathology:
• Following intra-articular corticosteroid medication, 32% of horses have improved performance although in 50% of the improved cases the effect lasted only 1–6 months
• Older ataxic horses had a 60% improvement with an average 2 grades improvement of ataxia that was effective for 1–8 years (average 2 years)
• Horses with milder grades of ataxia (less than grade 3), normal MSD ratios and moderate APJ changes (grade 3a–4b) are good candidates for medication
Serum and cerebrospinal fluid phosphorylated neurofilament heavy protein concentrations in equine neurodegenerative diseases
Evaluated serum and CSF phosphorylated neurofilament heavy protein (pNfH) concentrations as biomarkers for neurodegenerative diseases in horses.
Diseases studied: equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM), cervical vertebral compressive myelopathy (CVCM), and Shivers.
• Serum pNfH concentrations >1 ng/mL were highly specific (99%) for eNAD/EDM but had poor sensitivity (12%).
• CSF pNfH concentrations >3 ng/mL were significantly associated with CVCM (P = .0002), but sensitivity was moderate (50%).
• Shivers did not show significant elevations in serum or CSF pNfH concentrations.
• Younger horses (<5 years) with eNAD/EDM or CVCM exhibited higher CSF pNfH concentrations, correlating with more severe axonal degeneration in early stages.
• Older horses with these conditions often had unremarkable CSF pNfH levels, potentially due to disease stabilisation or progression differences.
Disease-Specific Findings:
• Elevated CSF pNfH in CVCM likely reflects the severity of spinal cord compression.
• Serum pNfH >1 ng/mL indicated axonal damage in eNAD/EDM, but many cases fell below this threshold, limiting sensitivity.
• Shivers pathophysiology, limited to Purkinje cell axons in the cerebellum, does not significantly elevate pNfH levels.
• Serum and CSF pNfH combined offer higher diagnostic value for eNAD/EDM (AUC = 0.82).
• Elevated levels indicate axonal degeneration but are not disease-specific.
Computed tomographic findings in 101 horses presented for the investigation of headshaking
CT under standing sedation provided diagnoses in 3 of 101 horses, with a likely diagnosis in one additional case. Enabled detection of mild periapical infections and a paracondylar process fracture, which were not evident in clinical examinations or standard radiographs.
• Despite its low diagnostic yield, CT remains a valuable tool for identifying alternative causes of headshaking, especially when other diagnostic modalities are inconclusive.
• Standard radiography has moderate sensitivity (52–76%).
• no association between IOC compression and headshaking.
Optimisation and validation of immunohistochemical axonal markers for morphological and functional characterisation of equine peripheral nerves
• FFPE tissue with optimised protocols provided unambiguous detection of motor, sensory, and sympathetic axons.
RLN:
• Composed of large-diameter myelinated fibres (ChAT-positive motor axons) and unmyelinated fibres (predominantly sympathetic TH-positive and occasionally sensory CGRP-positive).
• Presence of ChAT-negative myelinated axons raises questions about their motor or sensory origin. ? Loss of ChAT expression could be an early indicator of motor neuron degeneration in RLN.
• Future studies on diseased horses could clarify if RLN selectively affects large-diameter motor axons or also involves sensory and unmyelinated fibres.
Phrenic Nerve Findings:
• Similar composition to RLN, containing myelinated motor axons, unmyelinated sympathetic, and sensory fibres.
• Extensive clustering of sympathetic fibres (TH-positive) within fascicles. Suggests that sympathetic fibres run parallel along the phrenic nerve, branching distally.
• Highlights the potential role of sympathetic fibres in regulating skeletal muscle blood vessel tonicity and intrafusal muscle spindle receptors.
Plantar Digital Nerve Observations:
• Did not contain myelinated motor axons (ChAT-negative).
• Myelinated fibres presumed to be sensory, while unmyelinated fibres were TH-positive (sympathetic) and CGRP-positive (sensory).
• CGRP-positive fibres likely contribute to vasodilation effects on digital arteries and veins.
Cellular distribution of cannabinoid-related receptors in equine cervical dorsal root ganglia
Investigated cannabinoid-related receptors (TRPV1, PPARγ, GPR55, and GPR3) in equine cervical dorsal root ganglia (DRG).
• TRPV1: Widely expressed in sensory neurons and satellite glial cells (SGCs) of the DRG. desensitisated by cannabinoids like CBD
• PPARγ: Expressed in the nuclei of neurons, SGCs, and interneuronal cells. PPARγ ligands are known for anti-inflammatory and neuroprotective effects.
• GPR55: Found in neurons, SGCs, and macrophages in the DRG. Associated with inflammatory pain modulation and macrophage activity. CBD acts as a GPR55 antagonist,
• GPR3: Expressed in sensory neurons but absent in nerve fibres. Linked to neuropathic pain modulation and neuroprotection. Though CBD shows low potency at GPR3, it may contribute to pain relief in pathological conditions.
• Strong evidence of cannabinoid receptor-mediated interactions between neurons and SGCs. SGCs play a crucial role in pain modulation by releasing neurotransmitters and inflammatory mediators, influencing nociceptive pathways.
• Neuron-Glia-Macrophage Triad: GPR55 expression in macrophages highlights their role in inflammatory responses and pain hypersensitivity. Suggests a significant role for the neuron-glia-macrophage complex in managing nerve injuries and pain.
• Cannabinoids may regulate nociception, inflammation, and neuroprotection via TRPV1, PPARγ, and GPR55 receptors.
Vitamin E depletion is associated with subclinical axonal degeneration in juvenile horses
• Investigated the relationship between vitamin E deficiency and subclinical axonal degeneration in juvenile horses using phosphorylated neurofilament heavy (pNfH) as a biomarker. Up to 6 months of age. QH only. no histo
• Vitamin E depletion was associated with elevated cerebrospinal fluid (CSF) pNfH concentrations in otherwise healthy foals, indicating subclinical axonal damage.
• In eNAD-affected foals, CSF pNfH showed variability but ultimately increased by 6 months.
• Axonal damage occurred in foals without overt neurological symptoms, suggesting early subclinical degeneration due to vitamin E deficiency.
• Vitamin E supplementation mitigated the increase in CSF pNfH concentrations observed in vitamin E-depleted foals.
Diagnostic Implications:
• CSF pNfH could aid in diagnosing eNAD but should be interpreted alongside vitamin E levels to account for subclinical effects.
• Serum pNfH concentrations were unreliable due to detection limitations and potential interference, emphasizing CSF as the preferred diagnostic medium.
• CSF pNfH concentrations increased with age in vitamin E-depleted foals but remained stable in supplemented foals.
History, Rest and Exercise Score (HRE-S) for assessment of disease severity in horses with trigeminal-mediated headshaking
• The study validated the History, Rest and Exercise Score (HRE-S) for assessing the severity of trigeminal-mediated headshaking (TMHS) in horses.
• Addressed limitations of existing scoring systems by creating a tool that evaluates TMHS comprehensively, including history, resting signs, and exercise-related signs.
Advantages Over Existing Systems:
• Improves on subjective grading systems by integrating specific, measurable parameters.
• Includes chronicity and triggering environmental factors, which existing scores often overlook.
• Expresses results as percentages, increasing precision over categorical grades.
Key Findings:
• Excellent inter- and intraobserver reliability, even across observers with differing expertise levels. Reliability was highest for extreme scores (low or high severity).
• Strong convergent validity with Talbot’s score for exercise signs, though rest signs were not directly comparable.
• Discriminant validity confirmed by differentiating severity levels assessed by expert observers.
• Practicability: Generally rated as “easy” or “fast” to use, though more time-consuming than subjective scoring systems. Observers found it particularly effective in identifying subtle changes in clinical severity.
• Indicators of Disease Severity: Presence of “pain face” and “electric shock-like jerking” were strongly correlated with higher scores, highlighting their significance in TMHS evaluation.
• The HRE-S detected variability in severity between rest and exercise, underscoring the need for context-specific assessments.
History score: weater, activity, location, seasonality, duration
Resting score: vertical, horizontal, rotating, vertical head and neck, ear shaking, other, lip/ tongue movement, pain face- and duration up to >3min
Exercise score- the same as rest, defined as number/ round.
The prevalence of headshaking in horses with primary and secondary dental sinusitis and computed tomographic evidence of infraorbital canal pathology
headshaking may be casued by IOC pathology but not all IOC pathology causes headshaking
• IOC pathology was common in horses with dental sinusitis (65 out of 66 cases) but did not consistently correlate with headshaking.
• Only 5 out of 48 horses with follow-up exhibited headshaking behaviour, despite widespread IOC abnormalities.
• Most IOC changes included hyperostosis, periosteal proliferation, and osteolysis, yet these were present in both headshaking and non-headshaking horses.
Significance of IOC Pathology:
• Hyperostosis was the most frequent abnormality, often involving both the IOC and supporting bone structures.
• In 43 cases, hyperostosis extended to surrounding structures, yet only 5 showed clinical headshaking, indicating hyperostosis may be incidental in many cases.
• In horses exhibiting headshaking, the behaviours often coincided with advanced IOC pathology or ongoing dental inflammatory processes (e.g., oroantral fistulas or periapical osteitis).
• Resolution of inflammatory conditions (e.g., fistula debridement) reduced or eliminated headshaking in some cases.
Detection of equine herpesvirus-1 (EHV-1) in urine samples during outbreaks of equine herpesvirus myeloencephalopathy
• Confirmed the presence of EHV-1 DNA in urine, particularly during later stages of viraemia, suggesting a diagnostic role for urine samples.
• EHV-1 DNA persisted longer in urine compared to blood (buffy coat, BC) and had similar duration but lower concentrations compared to nasal swabs (NS).
Clinical Implications:
• Urine sampling offers a less invasive diagnostic alternative
• potential use in monitoring EHV-1 infection and ensuring biosecurity measures during outbreaks.
Differences in Detection Patterns:
• In the 2021 outbreak: BC samples were positive for shorter periods (up to 13 days post-onset of fever) compared to urine (up to 18 days). Urine samples showed higher EHV-1 DNA concentrations than BC towards the end of viraemia.
• In the 2023 outbreak: NS samples had higher positivity rates and DNA concentrations compared to urine. Urine samples were positive for shorter periods (up to 8 days).
Significance of Findings:
• The urinary bladder may serve as a site for EHV-1 persistence or replication, although further studies are needed to confirm this.
• Urinary shedding of EHV-1 could potentially contribute to viral transmission, though this requires investigation.
Equine herpesvirus-1 genotype did not significantly affect clinical signs and disease outcome in 65 horses diagnosed with equine herpesvirus-1 myeloencephalopathy
• No significant difference in clinical signs (fever, lethargy, ataxia) or disease outcomes (survival vs. non-survival) between horses infected with D752 and N752 genotypes.
• Urinary incontinence was significantly more common in horses infected with the D752 genotype (P = 0.04).
• The distribution of EHV-1 genotypes among horses with EHM (46% N752, 54% D752) showed no genotype frequency bias.
Clinical Observations:
• Ataxia was the most common clinical sign (97%), with similar severity levels across genotypes.
• Urinary incontinence, linked to D752, may reflect neuroanatomical tropism or severity of EHV-1-mediated vasculitis in the central nervous system.
• The study findings challenge earlier research suggesting D752 is more commonly associated with severe clinical signs.
Computed tomography findings in horses presented with signs of head-shaking
• Found CT to be useful, identifying abnormalities in 94 out of 103 cases (91.3%).
• In 22 cases (21.4%), treatable conditions were identified, leading to resolution of head-shaking.
• Trigeminal nerve-mediated head-shaking (TNMH): Most common diagnosis (60.2%, 62 horses). Diagnosis was by exclusion when no CT abnormalities accounted for clinical signs or when structural abnormalities were treated unsuccessfully.
Primary Treatable Conditions:
• Dental fractures, sinusitis, temporomandibular joint (TMJ) arthritis, and otitis externa were among the conditions leading to resolution of head-shaking after treatment.
• Less common findings included nuchal bursitis, musculoskeletal pathologies, infraorbital nerve mass, and basisphenoid bone fracture.
Incidental Findings:
• Common incidental findings included gas within the infundibula, nuchal ligament enthesopathy, and minor infraorbital canal changes.
•Limitation: Difficulty in distinguishing incidental findings from clinically significant abnormalities.
Genome-wide association study for host genetic factors associated with equine herpesvirus type-1 induced myeloencephalopathy
• No significant SNPs, haplotypes, or runs of homozygosity (ROH) were identified as associated with the development of EHM.
• The study did not confirm a previously reported association of a specific SNP (BIEC2-946397 on chromosome 6) with EHM.
• Findings exclude the involvement of a recessive genetic factor in susceptibility to EHM but could not rule out other genetic contributions, such as dominant, additive, or complex inheritance patterns.
Limitations:
•Small number of cases (27) and controls (67) limited the statistical power to detect associations, particularly for complex traits.
•The inclusion of diverse breeds may have introduced variability, complicating the detection of breed-specific genetic influences.
•The phenotype used (development of EHM) likely encompasses a variety of genetic and environmental factors, reducing the likelihood of identifying simple genetic markers.
Computed tomographic myelography for assessment of the cervical spinal cord in ataxic warmblood horses
• CTM effectively identified sites and causes of spinal cord compression, quantified compression severity, and detailed the direction of compression.
• No association was found between AP joint size and degree of compression, suggesting other factors contribute to compression severity.
Partial ceratohyoidectomy as surgical treatment for horses with temporohyoid osteoarthropathy: 10 cases (2010-2021)
• Similar clinical outcomes compared to complete ceratohyoidectomy were observed.
• Two horses experienced complete resolution of clinical signs.
• Nine out of ten horses returned to their previous work level, indicating a high success rate for functional recovery.
• Minimal complications in planned partial ceratohyoidectomy cases, with no instances of intraoperative hemorrhage or postoperative neuropathy.
• Complications were more frequent when surgeries were transitioned from planned complete ceratohyoidectomy to partial due to complications during dissection (e.g., hemorrhage, tongue mobility issues).
• All complications resolved before discharge, with no long-term adverse effects.
• Partial ceratohyoidectomy had fewer intraoperative complications compared to complete ceratohyoidectomy, likely due to avoiding deep dissection near neurovascular structures.
• Return-to-performance rates (90% in this study) were comparable or better than previous reports of complete ceratohyoidectomy.
Other Sx options include sytlohyoidectomy/ full ceratohyoidectomy
Caudal cervical vertebral morphological variation is not associated with clinical signs in Warmblood horses
• Morphologic variation of C6 and C7 was detected in 28.6% of horses, consistent with previous studies.
• Variations were more frequently found in control horses (38%) compared to case horses with clinical signs (23.7%).
• Morphologic variation did not correlate with clinical signs such as ataxia, cervical pain, or lameness, suggesting no direct pathological impact.
• Multivariate analysis confirmed the lack of association between morphologic variations and clinical signs, even after adjusting for age and breed.
• The presence of morphologic variations should not be assumed to indicate clinical relevance or pathology in Warmblood horses.
• Contradicts earlier hypotheses suggesting variations could predispose to pain or dysfunction due to altered biomechanics.
The safety and efficacy of neuromodulation using percutaneous electrical nerve stimulation for the management of trigeminal-mediated headshaking in 168 horses
• Approximately 53% of horses experienced remission after the initial three-procedure course.
• Median remission duration was 9.5 weeks, with a range of 2 days to 156 weeks (ongoing).
• Follow-up revealed that horses with longer remission periods (>56 weeks) often remained in remission for years.
• Horses were more likely to achieve remission by the third procedure if they responded to the first and/or second procedure.
• Horses that relapsed often regained remission after additional procedures, with subsequent remission durations generally increasing.
• Complication rate was 8.8% across 530 procedures, mostly mild and transient (e.g., suspected neuritis, haematomas, minor compliance issues).
• No placebo or control group; reliance on owner-reported outcomes introduces a potential bias,