general Flashcards
ddx forebrain
Metabolic-toxic: hepatic, intestinal, equine leukoencephalomalacia (Fumosinin B1)
Neoplasia: cholesterinic granuloma, other
Inflammatory: EPM, WNV, EEE, WEE, VEE, rabies, EHV-1, Borna
Traumatic: pull injury
Vascular: intracarotid injection
What is the normal range for CSF proteins in horses?
0.5 – 1.0 g/L (up to 1.8 g/L in foals)
Remember that neonates of all species may have slightly xanthochromic CSF.
Moreover, with LS tap, we can have small particles swirl indicative of epidural fat and collagenous tissue which can increase CK measurements.
What is the most consistent sign of Horner’s syndrome in horses?
ptosis
Up to which level does sweating extend in case of a lesion
1/ in the region of the guttural pouch and cranial cervical ganglion?
2/ lesion involving the sympathetic trunk?
1/ Sweating of the face (most prominent at the base of the ear) and the cranial neck down to the level of C2
2/ Sweating of the face and neck extending down to the level of C3 to C4
Which are the bacteria, the toxin and the mechanism implicated in the leuko-encephalo-malacia in horses ?
Fusarium verticillioides (moniliforme)
Fumonisin B1 (in moldy corn)
Inhibit sphingolipids synthesis : accumulation of sphingolipids intermediates: increased ICP and oedema: liquefactive necrosis of subcortical WM (affect also liver and heart)
DDx vestibular dysfunction
Peripheral
Otitis media-interna
Temporohyoid osteopathy
Temporal bone fracture
Idiopathic vestibular disease
Central
EPM
Viral (rabies, WN, EHV1, EEV)
Abscess (Streptococcus equi, foals++)
Neoplasm
What is the most common genetic mutation associated with deafness in horses? Breeds? What is the frequency of this mutation in deaf population? What is the mechanism?
Gene: EDNRB, endothelin B receptor (autosomal semi-dominant)= Lethal white foal syndrome: ileocolonic aganglionosis (or aganglionic) megacolon
Frequency: ~91% of deaf and suspected deaf (mostly American Paint horses, Quarter Horse, Miniature horses, and rarely Thorougbred)
Mechanism: melanocytes contribute to the blood vessel-rich stria vascularis of the scala media of the inner ear. It normally regulates the chemical composition of the endolymph of the scala media within which the organ of Corti resides. A** lack of normal melanocytes** can alter the development and function of the stria vascularis, as well as the endolymph. This can lead to degeneration of cochlear hair cells and auditory nerve neurons.
What are the 3 pathophysiological mechanisms that can give rise to neonatal encephalopathy?
1/ Maladaptation to extrauterine life (better outcome, with 85% survival)
2/ Perinatal asphyxia (hypoxic-ischemic encephalopathy, outcome depends on the severity and duration of hypoxia)
-Dystocia
-Umbilical cord abnormalities (torsion, compression)
-Severe maternal disease
-Placental disease
3/ Metabolic derangements (outcome depends on the cause and consequences)
- Sepsis
- Kernicterus
- Electrolyte abnormalities (H/h Na, h Ca)
- Uremic encephalopathy
- Systemic illness
- Hypoglycemia
What is the indication for Madigan squeeze procedure? What is the benefit?
Foals with uncomplicated maladjustment, that is no signs of asphyxia or metabolic derangements, without respiratory depression or rib fracture
No benefit on overall outcome, but faster recovery
The purpose of this procedure is to simulate the pressure induced by parturition, thus resetting the hypopituitaric-pituitary-adrenal axis.
Give 2 non-infectious non-metabolic causes of behavioural changes.
eNAD/EMD: “bad” behavior
Leukoencephalomalacia (fumonisin B1): maniac
What is the major component that induce CNS depression in the fetus?
Allopregnanolone derived from progesterone metabolism
Which disease is associated with kernicterus in foals?
Neonatal isoerythrolysis
Antemortem diagnosis is achieved by the presence of appropriate clinical signs in the presence of total bilirubin concentrations greater than 19 mg/dL.
All reported cases of kernicterus in the veterinary literature are secondary to NI. The odds of developing kernicterus increased by 1.13 for each 1 mg/dL increase in maximum total bilirubin concentration.
Which toxin (and originating plant) can induce bilateral symmetrical vestibulocerebellar ataxia and tremors?
lolitrem B (perennial ryegrass)
At which age appear the normal menace response in horses?
2 weeks
What is the best surgical technique for temporohyoid osteoarthropathy? Why?
Ceratohyoidectomy
Lower rate of complications (22% against 33% for partial stylohyoid ostectomy) and favourable outcome
Complications include hemorrhage, dysphagia, dyspnea, and laryngeal collapse
What is the pathophysiology of THO? Why is CN VII affected?
Bony proliferation at the articulation of the stylohyoid bone with the petrous temporal bone can result from the spread of otitis media/interna or as a primary degenerative joint disease.
Both bone fuse and movement (chewing, opening of the jaw) can break the temporal bone and compress the facial nerve (and vestibulocochlearis), further it can lead to meningitis/encephalitis
Facial nerve is exiting at the stylomastoid foramen in close contact to the stylohyoid-petrous articulation.
Which breed is overrepresented in temporohyoid osteoarthropathy?
Quarterhorse and related breeds (52%)
What is the most common sign in horses with temporohyoid osteo-arthropathy ?
Loss of audition (100%)
50% unilateral (right > left); 50% bilateral
Followed by:
Vestibular and facial nerve dysfunction (83%)
Exposure ulcerative keratitis (71%)
Concurrent left laryngeal hemiparesis (61%)
The outcome for auditory loss is good with THO: true or false?
False
Short- and long-term follow-up revealed persistent auditory loss in all horses based on abnormal response to sound, and further confirmed through a BAER in 8 horses.
What are the most common causes of bilateral auditory loss?
Sensorineural deafness
THO
Multifocal brain disease
What are the most common causes of unilateral auditory loss?
temporo-hyoid osteopathy
otitis
What is the most common causes of BAER abnormalities?
Temporohyoid osteoarthropathy (20/57)
Followed by:
Congenital sensorineural deafness in Paint horses (17/57)
Multifocal brain disease (13/57)
Otitis media/interna (4/57)
Mainly bilateral because CSD are all bilateral.
What are the horse breeds described with cerebellar abiotrophy?
Arabian (TOE1, loss of Purkinje neurons, 20% of Arabian horses are carriers)
Gotland pony
Oldenburg horse breeds
aged less than 1 year and occurs most frequently in 1- to 6-month-old foals
Once affected Arabian foals reach maturity, the condition becomes static, although mild improvement has been observed. The cerebellar abiotrophy that occurs in Oldenburg horses is progressive and fatal with atypical
histologic lesions compared with the syndrome that occurs in Arabian foals.
Headshaking is not a seasonal disease: true or false?
Not true
Seasonality of clinical signs is reported in approximately 60% of HSK horses while the remainder exhibit constant or erratic episodes.
In a largely US population of HSK horses, the majority (91%) of horses with seasonal HSK developed signs in the spring and early summer and these ceased in late summer and fall.
The majority (43%) of UK horses with seasonal HSK are symptomatic in spring, summer and autumn, 39% in spring and summer.
Geldings consistently appear to be over-represented in headshaker population: true or false?
true
Increase in exercise intensity is not associated with precipitate clinical signs of idiopathic headshaking: true or false?
False
Increase in exercise intensity frequently precipitates clinical signs.
In which horse breed is known the mutation for cerebellar abiotrophy? What is the mutation?
Arabian
5-20% of Arabian horses are carriers
Also reported in Oldenburg, Gottland pony, and Eriskay pony
SNP in TOE1 gene (CFA 2)
In proximity with MUTYH on the antisense strand
Autosomal recessive
Which plant (and associated toxin) cause nigropallidal encephalomalacia?
Plant: Centaurea solstitialis (yellow star thistle) or Centaurea repens (Russian knapweed)
Neurotoxin: repin
What is the suspected mechanism of pituitary pars intermedia dysfunction?
Degeneration of dopaminergic neurons in the hypothalamus -> release of their inhibitory effect on pars intermedia of pituitary gland -> adenoma or hyperplasia
Which plant, toxin and mechanism cause swaisonine toxicosis ?
Plant: locoweeds (Oxytropis, Astralagus, Swainsona)
Toxin: swainsonine (indolizidine alkaloid)
Mechanism: inhibition of alpha-mannosidase -> lysosomal storage -> neuronal vacuolation and epithelial cells
What are the mechanism/localization of lesions in shivers?
The mechanism is a Purkinje cell (PC) axonal degeneration without a substantial impact on PC soma.
When compared with controls, calretinin-negative, calbindin-positive, glutamic acid decarboxylase-positive spheroids were increased 80-fold in Purkinje cell axons within the deep cerebellar nuclei of horses with shivers.
In horses with shivers, surface EMG (sEMG) show abnormalities only during backward walking: true or false?
False
During backward walking, hindlimb muscle activation patterns show sustained, elevated flexor and extensor muscle activation with loss of the precise agonist and antagonist firing patterns required for a normal gait.
Although a movement disorder was only obvious with backward walking during surface EMG studies, altered and elevated firing patterns were present even during forward walking and trotting.
Thus, signs of shivers arise from a lack of coordinated recruitment of hindlimb flexor and extensor muscles obvious during backward walking but present subclinically during forward walking.
What are the most affected deep cerebellar nuclei in horses with shivers?
Lateral nuclei (dentate and interpositus)
What is the gene associated with hydrocephalus in horse? In which breed?
B3GALNT2 (AR)
Friesian horse (+ 1 case of Belgian foal)
Give 3 treatments for idiopathic headshaking.
Nose nets / face mask
Cyproheptadine (antihistamine with additional anticholinergic, antiserotonergic, calcium channel blocking and local anaesthetic activity)
Carbamazepine (anticonvulsant which stabilises voltage-gated sodium channels)
Electrostimulation
Magnesium
Platinum coil compression
What is the EDX finding associated with headshaking?
Reduced threshold for nerve activation
What is the clinical presentation of shivers?
Shivers in horses is characterized by trembling or shivering of the tail and thigh muscles and a characteristic hindlimb posture initiated by specific movements.
By 7 years of age, walking backward is difficult for Shivers horses because of either fixed hyperflexed abducted hindlimbs or rigid hindlimb extension.
types: shivers hyperflex, shivers forward hyperflex, shivers hyperext, forelimb shivers
Signs associated with guttural pouch mycosis?
Most common clinical signs:
Non-exercise-associated epistaxis (ICA ± maxillary artery, suberficial temporal artery)
Dysphagia (CN X & IX)
Other clinical signs:
Laryngeal hemiplegia (CN X)
Horner (cranial cervical ganglion or ganglionic axons)
Facial nerve paresis
Tongue paresis (CN XII)
Dorsal displacement of the soft palate (tensor veli palatini, CN V.3; palatopharyngeus, palatinus, levator veli palatini, CN X.pharyngeal branch)
Rarely, vestibular signs (inflammation eroding tympanic cavity)
Rarely, sternocephalicus muscle atrophy (CN XI)
What are the 3 breeds predisposed to narcolepsy?
Shetland pony
American miniature horse
Suffolk draft horse
What is the unusual clinical sign associated with shivers when horses are walking backward?
Facial twitching (17%)
How to differentiate shivers from standing hyperflexion and stringhalt?
1/ Backing and forward walking:
Normal: standing hyperflexion (only present during picking up hoof)
Abnormal: shivers (consistent HE or HF) or stringhalt (consistent or variable HE).
Entrained forward walking (trotting, cantering)
Normal: shivers (walking can be impaired intermittently with shivers-forward hyperflexion)
Hyperflexion: stringhalt
During backward walking, what is the main difference between shivers-hyperflexion and stringhalt?
Shivers: abduction
Stringhalt: adduction
What is the main hypothesis for isolated unilateral trigeminal dysfunction in a horse?
EPM / Sarcocystis neurona
Causes of laryngeal paralysis in horses (9)
Idiopathic
Guttural pouch disease
Iatrogenic (perivascular injection of irritating substances)
Trauma
Organophosphate intoxication (bilateral!)
Lead poisoning
Thiamine deficiency
Toxic plants (chickpeas, Lathyrus)
Infectious : strangles, EPM
Optic fibers decussation at the optic chiasm in human, horses
Humans 50%, Horses 80-90%
Fluphenazine toxicosis and yellow star thistle encephalopathy affect motor/sensory function
motor
Icteric CSF is a normal finding in foals: true or false?
True
Up to 10 days of age
What are the 4 most common causes of facial neuropathy?
Trauma (31%)
CNS disease (25%)
Idiopathic (19%, including 6% of true idiopathic and 13% not investigated)
Temporohyoid osteopathy (16%)
What is the outcome of facial paralysis in horses?
53% had full resolution
25% were euthanized
11% partially improved
11% were unchanged or worse
How many horses with facial paralysis also have ocular pathology?
36%
How many horses with facial paralysis were diagnosed with temporohyoid osteoarthropathy?
16%
Which breeds were overrepresented in concomitant facial paralysis and temporohyoid osteoarthropathy?
Quarter Horses were 8.14 times more likely and Pony breeds were 40.71 times more likely to have a diagnosis of THO than Thoroughbreds
Complex central nervous system malformations in Dutch Warmblood foal is associated with poor prognosis: true or false?
false
What is the cause of stiff horse syndrome?
Antibodies directed against glutamic acid decarboxylase (GAD), which produces the active form of GABA in the central nervous system, have been identified in the CSF of confirmed cases.
EMG has shown increased motor unit firing in the absence of any limb movement, which seems to be due to a decrease in GABA.
Horses show an insidious onset of waxing and waning muscle stiffness progressing to acute painful muscle contractions often initially initiated by startling or touching.
Which breeds/age/sex seem predisposed for shivers?
Warmblood
Troughbreed
Draft horses
male
more than 7y
more than 17 hand tall
sometime unilat at begining, maj bilat
What is the pathological findings in stringhalt? What is the suspected mechanism for the clinical signs?
Histo: Wallerian-type distal axonopathy of the tibial, deep, and superficial peroneal as well as recurrent laryngeal nerves accompanied by myofiber atrophy in the muscles supplied by affected nerves.
EMG (hindlimb): increased insertional activity, Fibs, and PSW, consistent with denervation.
Mechanism: disruption of the afferent or efferent fibers supplying muscle spindles and golgi tendon organ. Disruption of these stretch or tension feedback loops could interfere with the muscle’s ability to gauge the number of motor units required for a normal smooth muscle contraction resulting in hypertonicity and hyperreflexia.
What is the plant responsible for plant-associated stringhalt?
Hypochaeris radicata (Australian dandelion)
Taraxacum officinale (European dandelion)
(commonly referred to as catsear, flatweed)
Complex central nervous system malformations in Dutch Warmblood foal is associated with seizures: true or false?
True
Horses have smooth muscles that innervate the eyelid, which dogs do not have. How are these called?
arrector ciliorum m
ptosis of upper eyelid is most probably associated with … in Horse
Most probably associated with Horner syndrome
and equine grass sickness
Epilespy in arabic foal: type of seizure, age of cessation, most common concurrent disease
Seizures are characterized by generalized tonic activity
Cessation of seizures can be expected by 1 year of age
Pneumonia is the most common concurrent disease
What is the muscle implied in eyelash angle?
What is the innervation?
In which species?
Which significant disease is associated with its dysfunction and how to test that?
Arrectores ciliorum
Sympathetic
Horses and cattle (not in humans and dogs)
Equine grass sickness / Horner syndrome
low-dose of topical phenylephrine (alpha-1 agonist, 0.5%)
resolve the upper eyelid ptosis (tarsal smooth muscle) and the lowered angle of the upper eyelashes
Which CN are affected in nigropalladial encephalomalacia?
Ingestion of yellow star thistle (Centaurea solstitialis) or Russian knapweed (Centaurea repens).
CN V
CN VII: hypertonicity of facial and lips muscles, with the upper lips often pulled over the teeth in a grimace
CN XII: tongue lolling and fail to move food into back of the throat but remain capable to withdraw the tongue (different from botulism): may attempt to drink by immersing their head, allowing water to reach pharynx
Magnesium sulfate is associated with decreased head-shaking behaviour: true or false?
True
Administration of MSS IV increased plasma total and ionized magnesium concentrations and significantly decreased head-shaking behavior in horses with trigeminal-mediated headshaking.
In a horse with diffuse prosencephalic signs, hepatic enzyme activities within normal limits, and marked hyperammonaemia, what would be your first hypothesis?
Intestinal encephalopathy
= primary hyperammonemia
Gastrointestinal upset, such as enteritis or colitis, occurs and a shift in intestinal flora results in overproduction of ammonia, potentially due to overgrowth of ** urease-producing bacteria**. This overproduction, frequently coupled **with intestinal inflammation and increased absorption of ammonia, leads to a high level of ammonia in the blood that overwhelms hepatic capacity for metabolism. Ammonia rapidly diffuses into the central nervous system and causes cerebral dysfunction.
In case of intestinal encephalopathy, blood works usually show hypo- or hyperglycemia?
hyper
What are the 3 main causes of hepatic encephalopathy in horses?
Theiler’s disease (virus)
Pyrrolizidine alkaloid toxicosis
Fall panicum hepatotoxicosis
DDx spinal cord
Degenerative: EDM/NAD
Neoplasia: melanoma
Inflammatory: EHV-1 myelopathy, equine protozoal myeloencephalitis (EPM), discospondylitis, WNV, (rabies)
Traumatic: cervical vertebrae stenotic myelopathy (CVSM), OAA malformation in Arabian, external injury
Vascular: FCEM
What should happen when you tap the skin over the brachiocephalic muscle with a closed tip of the hemostat from the cranial end of the neck to the back of the shoulder?
contraction of the brachiocephalicus and cutaneous colli muscles
Twitching of the facial muscles at the commisures of the lips
Mention the 2 most common spinal cord disease in horses
Cervical vertebral compressive myelomathy (CVCM), neuroaxonal dystrophy (NAD)
What are the genes involved in occipitoatlantoaxial malformation and in which breed?
HOXD3 (AR)
Arabian
Where can we see fractures of the neck most often in foals and adult horses?
Foals: fractures of atlas and axis, especially through the physis of the separate center of ossification of the dens
Adult: vertebral body or arch in the mid-neck region (3-6th vertebrae) or APJs of the more caudal vertebrae (5-7)
What is the unusual clinical sign associated with Parelaphostrongylus tenuis infestation in horses?
Acquired scoliosis due to dorsal gray matter segmental myelitis with reduced sensation over the affected side (convex curve)
leads to** loss of sensory afferent information on the affected side. Normal muscle tone requires sensory information; without it, the muscles become abnormally flaccid. Subsequent imbalance in cervical muscle tone (flaccid on affected side**, normal muscle tone on unaffected side) causes curvature of the neck toward the normal side.
What is the treatment of pasture associated stringhalt?
Spontaneous recovery, Phenytoin
Which mutation cause malignant hyperthermia?
+breed, other mut
RYR1 gene (ryanodine receptor), autosomal dominant.
Halter horses
In other species, description of Ca2+ voltage-gated channel mutation
What is the innervation of the thyrohyoideus muscle in horse?
First cervical (C1) nerve branches
What are the 3 causes of stringhalt?
Unipedal stringhalt: idiopathic, but often history of trauma to the dorsal metatarsus or hock
Pasture-associated stringhalt (PSH): grazing drought-affected, poor-quality pastures that contain the plant Hypochaeris radicata (commonly referred to as catsear, flatweed, and false dandelion); mainly affect mature and taller horses
Idiopathic bilateral stringhalt
What is the presentation and outcome of the 3 forms of stringhalt?
1/ Unipedal stringhalt
Unilateral hyperreflexive gait consistently present at a walk and trot
Function as trail horses and have been successful in jumping competitions; guarded after surgery (lateral digital extensor myotenotomy)
2/ Pasture-associated stringhalt (PSH)
Hyperflexion of both hindlimbs with some degree of asymmetry possible. Clinical signs vary in severity. Up to 20% of horses develop laryngeal hemiplegia.
Most horses recover over 6-18 months (spontaneously, or with phenytoin)
3/ Idiopathic bilateral stringhalt
Bilateral hyperflexion at a walk and trot that is not as extreme as that seen with PSH, and horses will back up and lift a hindleg normally
Which vertebral neoplasia has been reported in several horses of different breeds and ages? What would be your differential diagnoses?
Myeloma
Ddx: vertebral osteomyelitis or other primary metastatic neoplasia such as hemangiosarcoma, osteosarcoma, chrondrosarcoma, undifferentiated sarcoma and malignant melanoma.
Slap test can be detected from which age?
2 weeks
Efferent pathway of thoracolaryngeal reflex:
Contralateral vagal nucleus, vagal nerve, recurrent laryngeal nerve, larynx
Which infectious disease may cause nerve root lesions?
Borrelia burgdorferi
Post-anesthetic myelopathy is a condition of horses that affects primarily grey or white matter
grey
What is the minimal intravertebral ratio on horse?
C3-C6: 52%
C7: 56%
What is the minimal intervertebral ratio on horse?
50%
intervertebral MSD ratios were more accurate at determining site of compression than intravert but significant overlap between value
What change can be seen in C6 in normal horses? In which breeds?
Transposition of one or both ventral processes of C6 onto C5 or C7
Warmblood breeds
In a population of 100 horses, 24% had anomalous C6, with either asymmetric or symmetric absence of the ventral lamina of the transverse process.
What are the two main type of cervical vertebral stenotic myelopathy?
Type I: young horses with intensive training and rapid growth
Type II: older horses with osteoarthritic changes
What are the radiographic ratios used to diagnose CVSM?
Intra- and intervertebral ratio:
intra or intervertebral height of the vertebral canal
to maximal height of the caudal vertebral body
What are the myelographic ratios used to diagnose CVSM?
Minimal sagittal dural diameter to maximal one (cut-off 20%)
- or -
Minimal height of the dorsal contrast column to maximal one (cut-off 50%)
What is the most important prognostic factor for post-surgical improvement in CVSM?
Duration of clinical signs before surgery
What are the 2 genotypes of EHV-1?
DNA polymerase gene ORF30 -> single nucleotide polymorphism (SNP) at position 2254
Neuropathogenic causing EHM
Guanine: G2254 -> D752
neuropathogenic
Adenine: A2254 -> N752
reduced levels of viremia, viral shedding was similar between both virus mutants.
most EHV-1 viruses circulating in the field are of the N752 genotype
Both cause respiratory disease
most ofvthe reported EHM outbreaks showed D752 strain involvement.
Females are more susceptible than male during EHM outbreak: true or false?
true
Younger horses are more susceptible during EHM outbreak: true or false?
False
However, similar to the observations in experimental settings, foals and yearlings under natural outbreak conditions are only rarely affected by neurologic deficits, whereas adult/older horses are more susceptible and might show more severe clinical signs of EHM during an outbreak.
The most common findings on CSF in EHV infection are:
Xantochromia
Lymphocytic pleocytosis with increased protein
What test would you perform for EHV-1 antemortem diagnosis? At which timing?
PCR testing of whole blood (EDTA) and nasal secretions for universal gene (glycoprotein B) and virulence gene (ORF30)
Viremia classically occurs between 4 and 10 days after infection -> most suitable time to collect whole blood
Young horses are more at risk of EHM than adult/old horses: true or false?
False
Adult/old are more at risk
What is the pathogenesis of EHV-1 infection?
Respiratory epithelial cells (replicates within for up to 14 d)
-> Lymph node (1-2 d)
-> Leukocyte/PBMCs (circulate for up to 21 d) = cell-associated viremia
-> Cross into endothelial cell (CNS, uterus/testicles, eye)
-> Vasculitis with hemorrhage & thrombosis induces hypoxia and ischemia to adjacent CNS tissue
What are the risk factors for EHM? (11)
>3 yo
D752 strain (only 14-24% of EHM are N752)
G 2254
Late autumn, winter, spring
Stress
Pregnancy or foal at foot
Vaccination against EHV-1 5 weeks before
Past exposure with secondary fever
Crowding
Keep in stable
Presence of EHV-1
What is the proportion of EHV-1 viraemic horses that develop EHM?
10%
Attention: unlikely to occur in the absence of viremia
What is the major ocular lesion associated with EHV-1?
Chorioretinopathy
(shotgun lesions of the retina)
Occur in 50% of infected horses but in usually subclinical
EHV-1 is a neurotropic virus: true or false?
False
Endotheliotropic
Respiratory signs are frequently present at the time EHM appear: true or false?
False
Outbreaks are characterized by a large number of horses affected with mild to moderate respiratory disease and a fever, with 10% to 40% of infected horses developing EHM.
BUT: clinical signs of EHM appear following the onset of viremia (1-3 days after resolution after fever), often following a secondary fever spike and in the absence of respiratory disease.
What is the prevalence of EHV-1 latently affected horses? What are the 2 breeds without described EHM outbreak?
80%
Arabian & Icelandic horses
Vaccine is usually effective to prevent EHM: true or false?
False
No vaccine have been shown to be effective in preventing EHM
What is the type of virus for: rabies, EEE, WEE, VEE, WNV, EHV-1? Which of this are transmitted via mosquito vectors?
Rabies: Lyssavirus
EEE/WEE/VEE: alphavirus – mosquito vector
WNV: flavivirus – mosquito vector
EHV-1: alpha herpesvirus
In which disease can we see Joest-Degen (intranuclear) inclusion bodies iand where?
Borna virus
in the hippocampus
Borna disease can affect which species? Which one is the most susceptible?
Equid, goat, sheep, dog, cat
Camelid are the most susceptible
For EEE/WEE/VEE/WNV serological testing, what type of immunoglobulin do you need to measure: IgM or IgG?
IgM because it is an acute response
Moreover, previous vaccination can modify IgG levels
What is the unusual CSF feature that can be associated with EEE?
Neutrophilic pleocytosis (viral encephalopathy)
In WNV, cerebral signs are more common than spinal cord signs: true or false?
False, it is the opposite
Compared to other viral diseases, which clinical signs are frequently observed in West Nile encephalitis?
Muscle fasciculation, tremors and behavioural change
Horses can transmit West Nile virus to humans: true or false?
False
Dead-end host with low viremia
WNV is frequently associated with neurological signs in horses: true or false?
False
< 10%
(overall, only 20% develop clinical signs with mainly fever)
What is the outcome with WNV encephalitis?
Mortality: 30% (22-44%)
Residual neurologic deficits: 10-40%
Recovery can take months
Relapse: 1/3
Vaccination is effective to protect against WNV: true or false?
True
Only include lineage 1 but cross-over protection against natural infections from lineage 2 strains
WM is more frequently affected than GM with WNV: true or false?
False
May even present central cord syndrome
Which structure is predominantly affected by WNV?
Hindbrain and spinal cord gray matter
Less frequently rostral brainstem and forebrain
*
Where are located the inclusion bodies in rabies? in borna disease?
Perikaryon (negri bodies)
Intranuclear eosinophilic inclusion bodies (Joest-Degen bodies)
Name main hosts and vectors of:
EEEV
WNV
Tick-borne encephalitis virus
Ehrichiosis
EEEV:
Hosts: passerine birds & small rodents
Vectors: mosquitos (Culex, Aedes)
WNV:
Hosts: birds
Vectors: mosquitos (Culex)
TBEV:
Hosts: small rodents
Vectors: tick Ixodes ricinus/persiculatus
Ehrichiosis:
Vectors: **Rhipicephalus sanguineus **in dogs; Ixodes spp. in horses
Antemortem diagnosis on WNV infection can be achieved by:
Serum IgM-capture ELISA
CSF IgM-capture ELISA
What are the 2 strongest risk factors for death with WNV infection? What is the major cause of death?
Risk factors:
Recumbency: 78 times more likely to die
Non-vaccination: 2 times more likely to die
Mortality rises with increasing age after 5 y
Cause of death: euthanasia (71-76%)
What unusual clinical sign is frequently associated with WNV (but is not pathognomonic)?
Tremors and fasciculation
(associated with forebrain disorder and ataxia)
What are the 2 viral diseases associated with xanthochromia?
West Nile virus
EHV-1
What is the main anatomical localization of WNV and EEE/WEE/VEE infection?
WNV: hindbrain + SC GM
EEE/WEE/VEE: forebrain
Equine TBEV is a tick-born flavivirus: true or false?
true
What are the 2 agents associated with equine protozoal myeloencephalitis? What is the definitive host for the most frequent agent?
Agent:
Sarcocystis neurona
Neospora hughesi
Definitive host: Opossum
What is the outcome for EPM?
60% improve (40% do not)
Only 15-20% return to “normal”
Relapse rate: up to 25%
Give an example of drug for treating EPM.
Sulfadiazine – pyrimethamine
Ponazuril
Nitazoxanide
Diclazuril
Is EPM a seasonal disease?
Yes
Fall > spring, summer > winter
What is the best diagnostic testing for EPM?
Use of SAG 2,4/3 ELISA
Ratio serum to CSF antibody titer to assess intrathecal antibody production (cut-off < 100)
Overall accuracy to 93-97%
What antemortem tests can be performed to diagnose EPM?
Western blot
Standard WB (sWB)
Modified WB (mWB)
Indirect fluorescent antibody test (IFAT)
Surface antigen (SAG) ELISAs
SAG 1
SAG 2, 4/3
SAG 1, 5, 6
All can be performed on serum or CSF
None considered a gold standard
Definitive and intermediate host of Sarcocystis neurona.
Definitive host: opossum
Intermediate host: cat, racoon, skunk, sea otter, armadillo
What areas are affected in NAD/EDM?
Medial and lateral cuneate nuclei, gracilis nuclei, thoracic nucleus, spinorecerebellar tracts
Onset age for EDM/NAD?
Few weeks – 3 yo (most 6-12 months)
What can be seen during fundoscopy in NAD/EDM horses?
Pigmented retinopathy (lipofuscinosis)
(only in Warmbloods?)
Which environmental factor seem to be involved in the pathophysiology of EDM/NAD?
Vitamin E deficiency (alpha-tocopherol) during the first year of life
What are the specificities for warmblood breeds concerning EDM?
More deficient in alpha-tocopherol
More severe ataxia
Pigment retinopathy (not in QH)
What is the heritability for EDM in QH?
70% -> incompletely penetrant autosomal dominant
What are the 2 conditions for EDM phenotype to develop in QH?
Genetic susceptibility
Temporal alpha-tocopherol deficiency
Faster metabolism of vit E in these horses?
High dose supplementation seems to prevent the clinical phenotype in genetically susceptible horses
Which pathological lesions are consistent with NAD and which with EDM?
1/ NAD: Histopathological lesions confined to brainstem, specifically the lateral cuneate nucleus, medial cuneate and gracilis nuclei; and the nucleus thoracicus
2/ EDM: Same + axonal necrosis and demyelination extending into the dorsal and ventral spinocerebellar tracts and **ventromedial funiculi **of the cervicothoracic spinal cord
Which breed has a familial component for eNAD?
Morgan horses
Quarter
Apaloosa
What is the most common clinical signs of eNAD/EDM?
Symmetric **ataxia **(more severe in PLs)
Abnormal base wide stance at rest
Proprioceptive deficits in all limbs
Abnormal (bad) behavior, usually at an age of 6-12 months
Which ancillary test can be used to oriented the diagnosis of EDM/NAD?
Phosphorylated neurofilament heavy chain (pNfH) in serum and CSF:
serum > 1 ng/mL and/or CSF > 3 ng/mL associated with EDM/NAD but need exclusion of other causes (also increased in CSF in CVSM
Serum pNfH: Se 12% Sp 99% -> negative result does not rule out NAD/EDM
can only be interpreted once infectious and traumatic causes for neurological disease have been excluded
What is the prognosis for NAD/EDM?
Poor, but can stabilize
No treatment when signs are already present…
The foals may still be mildly affected despite early supplementation.
In the CSF of horse, increased pNfH concentrations (>3 ng/mL) were observed with 2 diseases, which one ?
1/ Cervical Vertebral Compressive Myelopathy
2/ eNAD/EDM
CSF phosphorylated neurofilament heavy concentration is increased with age in healthy vitamin E depleted foals: true or false?
True
An effect that was not observed in healthy vitamin E supplemented foals.
We demonstrate that vitamin E depletion may elevate cerebrospinal fluid phosphorylated neurofilament heavy in otherwise healthy juvenile foals by 6 months of age
What is the bacteria responsible for tetanus and what are its characteristics?
Clostridium tetani
Spore-forming
Gram positive
Anaerobic
Rod
Which ocular sign is frequently seen in horse tetanus?
Flashing of the nictitans membrane
What are the 3 toxins release by C. tetani? What is the toxin that induce clinical signs and on which protein does it act?
Tetanospasmin + tetanolysine + non spasmogenic toxin
Tetanospasmin acting on synaptobrevin in Renshaw cells
What is the mechanism of TeNT?
Tetanospasmin immediately cleaved by host proteases into heavy and light chain
Diffuse into the vasculature
Spreads hematogenously before binding to ganglia (ANS) and neuromuscular junctions
Once bound, the toxin becomes internalized by endocytosis and is carried along the axon in a retrograde fashion (75-250 mm/day)
Enters the CNS, reaching the neuronal cell body
Crosses the synaptic cleft and enters the inhibitory interneuron (Renshaw) cells.
Active light chain acts on synaptobrevin (vesicle-associated membrane protein = VAMP) in the Renshaw cells to irreversibly impede the release of glycine and GABA
Release from inhibition -> spastic muscle contractions and muscular rigidity
What is the risk associated with tetanus antitoxin?
Hepatitis (theiler’s disease) due to unknown virus (parvovirus suspected) 45-90 d after administration
What is the treatment of tetanus?
- Supportive care: quiet environment, cotton in ears, sedation, nutritional and hydration support, …
- Muscular relaxation: acepromazine, methocarbamol, barbiturates, diazepam
- Treatment of infection: debride the wound, penicillin (or metronidazole)
- Neutralization of unbound toxin: antitoxin (any route)
- Establish active immunity: vaccination
Does horse that recover from tetanus need to be vaccinated?
Yes, because natural infection does not provide immunity
What are the cranial signs of tetanus in horse?
Erect, caudally directed ears
Elevated upper eyelid
Spasmodically protruding 3rd Eyelid
Flared nostrils
Retracted lips
Trismus
What is the differentials of tetanus in horse?
Strychnine
Electrolytes (hypoCa, hyperK, hypoMg)
Acute laminitis
Myopathies
Meningitis
Colic
EMND
Shivers
Severe neck pain (stiffness)
What is the bacteria responsible for botulism and what are its characteristics?
Clostridium botulinum
Spore-forming
Gram positive
Anaerobic
Rod
What are the 3 route of intoxication for botulism?
Ingestion of preformed BoNT (food-borne, adult)
Ingestion of spores (toxicoinfectious, foals, colonisation of GI tract by C. botulinum producing BoNT)
Wound infection
What is the target of the BoNT?
Neurotoxin acts on presynaptic motor neuron and cleaves fusion proteins (SNARE proteins), thus preventing release of Ach
Specific proteins affected depend on neurotoxin type
What are the 5 diagnostic tests for botulism in horses?
Clinical: exclusion of other diseases, consumption of 250 mL/8 Oz in < 2 min
Mouse bioassay: lack of sensitivity (32%)
ELISA: lack of sensitivity, not in vaccinated
PCR (A, B, C): Se 88% Sp 98%
Identification of spores or BoNT in faeces, but low yield
What are the clinical signs associated with botulism?
+ onset
Progressive, symmetrical, flaccid paralysis by generalized muscle weakness with low carriage of head and neck
Decreased suckle and drooling milk when suckling
Slow eating
Dysphagia (may be the earliest sign)
Dysphonia
Decreased eyelid, tongue, tail, anal tone
Mydriasis with decreased PLR
Exercise intolerance (in severe forms, death by respiratory failure)
Constipation & ileus
Onset: 12h – 7d following exposure, depending on dose
What nerve can be used for RNS for botulism testing in horse?
Common peroneal nerve
BoNT can cross BBB: true or false?
False
Botulism can induce miosis: true or false?
False
Mydriasis and slow PLR
Contrary to tetanus, antitoxin can neutralize bound botulism neurotoxin: true or false?
False
Does NOT neutralized bound toxin -> does not reverse signs, which might progress for > 24 hours
Is vaccination against botulism possible?
Yes but only for type B
What are the target of the different types of BoNT?
- A, E: SNAP-25
- C: SNAP-25 + syntaxin 1
- B, D, F, G: VAMP-2
The vaccination against botulism is not protective in horses: true or false?
False
Protective in adults
Passive transfer of Ab from vaccinated dams significantly reduced botulism in foals
But, lack of cross-protection between types
What are the clinical signs associated with equine grass sickness?
Dullness
Anorexia (indifference to food)
Dysphagia
Drooling of saliva
Tachycardia
Ptosis (bilateral)
Patchy sweating
Muscle fasciculations / tremors
Rhinitis sicca
Nasogastric reflux
Abdominal pain (colic signs)
Weight loss / cachexia
Progressive myasthenia
Dry, mucous-covered faeces within rectum
The outcome for botulism is poor in foals: true or false?
False
Survival rate up to 96%
Better management of recumbency and mechanical ventilation
Which structures can be biopsied for equine grass sickness diagnosis without laparotomy?
Cranial cervical ganglion
Foliate papillae (tongue)
Rectal mucosa
What is the agent believed to be associated with equine grass sickness?
Toxins of Clostridium botulinum type C
In equine grass sickness, what are the risk factors associated with an increased odds of occurrence?
(10)
Grazing (98% of cases)
2-7 years (decreased risk after 10 y)
Good body condition
Increased sun hours and frost days
Recent cool, dry weather and irregular ground frosts
Recent movement within 2 wks
Change in feed type/quantity within 2 wks
Grazing in premises with previous occurence, high soil nitrogen content, pasture disturbance, high number of horses, high soil titanium
In equine grass sickness, what are the risk factors associated with a decreased odds of occurrence?
Higher average maximal temperatures
Contact with previous cases (acquired immunity?)
Feeding of supplementary hay/haylage
In equine grass sickness, what are the risk factors associated with an increased odds of recurrence? (4)
Presence of younger animals
Loam and sandy soil
Rearing of domestic birds
Mechanical removal of feces from pasture
In equine grass sickness, what are the risk factors associated with a decreased odds of recurrence?
Cograzing with ruminant
Grass cutting
Manual removal of feces from pasture
Chalk soil
Which antemortem non-invasive test can be performed to support the diagnosis of equine grass sickness?
Phenylephrine 0.5% applied to the eye
temporally reverse ptosis
More invasive:
Oesophagal endoscopy (dysmotility, ulcers)
EMG (denervation: fibs, psw, doublets to neuromyotonic discharges, increased MUAP duration with polyphasia)
In equine grass sickness, what are the risk factors associated with non-survival? (6)
+ treatment
Acute & subacute presentations (in these cases, euthanasia is recommended)
Severity of dysphagia (ability to drink and swallow feed)
Severity of loss of appetite & thirst (willingness to attempt to drink and swallow feed)
Continuous moderate to severe signs of colic
Severity of rhinitis
Greater BW loss (rapidity and magnitude were equally predictive)
In chronic cases, 40% may survive.
Cisapridemay decrease mortality.
Which specific ileal cell type seems relatively spared in equine grass sickness?
Interstitial cells of Cajal in muscularis externa
What are the factors supportive for C. botulinum intoxination in EGS?
Higher mucosal IgA against BoNT/C and D in patients with acute ED vs control animals
Reportedly successful historic botulinum vaccine trial (1922 and 1923)
Significantly greater prevalence of intestinal C botulinum bacteria and/or toxin in patients with ED vs control animals
Risk factors supportive of involvement of a soil-borne agent
Inverse association between disease risk and systemic concentration of antibodies against C botulinum bacteria and toxin
What are the factors refutative for C. botulinum intoxination in EGS?
Disease phenotypic differences between ED and neuroparalytic botulism
Neuropathology apparently inconsistent with action of C botulinum neurotoxins
SNARE protein expression in ED ganglion and enteric neurons inconsistent with action of C botulinum neurotoxins
Greater prevalence of other (non–C botulinum) clostridial species in intestinal tract of patients with ED vs controls (possibly reflecting generalized clostridial overgrowth)
Lack of evidence of temporal and geographic clustering of ED and neuroparalytic botulism cases
DDx neuromuscular
Metabolic-toxic: equine motor neuron disease (EMND), equine grass sickness, atypical myopathy, PSSM 1 & 2, MYH1, HYPP
Inflammatory: tetanus, botulism
Examples of glycogenosis
Polysaccharide storage myopathy in horses
Myophosphorylase deficiency in cattle
Glycogen branching enzyme deficiency in Quarter horse foals
In which disease can we see circulating antibodies to P2 myelin protein?
Polyneuritis equi
Which antemortem examination can be done for suspicion of polyneuritis equi? Histological lesions ?
Muscular biopsy of sacrocaudalis dorsalis ± ultrasound
Granulomatous inflammation of cauda equina ± spinal nerves ± cranial nerves
Demyelination with subsequent axonal degeneration, thickening of epi/peri/endoneurium, fibrosis
Which drugs can act/interfere at the NMJ function in horses and thus, need to be avoid with NM disease? (5)
Tetracyclines
Aminoglycosides
Metronidazole
Procaine
Lidocaine
Hyperkaliemic periodic paralysis is due to mutation of which channel? What is the mode of inheritance?
Sodium (SCN4A)
Autosomal codominant
What is the main differential diagnosis for hypocalcemia in horses? How to differentiate them?
Tetanus
Diaphragmatic flutter in hypoCa
Eyeball contraction and protrusion of 3rd eyelid in tetanus
What is the mutation associated with polysaccharide storage myopathy?
Glycogen synthetase 1 (GYS1)
Autosomal dominant
PSSM1 – gain of function
What are the 2 molecules for organosphosphate intoxication treatment?
Atropine sulfate
Pralidoxime hydrochloride
GBE1 mutation is dominant: true or false? Which disease is associated with this mutation?
False
Recessive –** glycogen branching enzyme deficiency**
What is the cause of bilateral masticatory myopathy in horses?
Vitamin E and selenium deficiency
What is the mutation associated with myotonia congenita?
Chloride channel 1 (CLCN1)
Autosomal recessive
Mexiletine (Na channels)
What can be seen in muscular biopsies from PSSM1 horse?
Numerous subsarcolemmal vacuoles
and dense, crystalline PAS-positive, amylase-resistant inclusions
in fast fibers (type II).
What are the main differences between PSSM1 and PSSM2?
Cause
PSSM1: GYS1 mutation (autosomal dominant)
PSSM2: unknown
Breeds
PSSM1: numerous breeds, especially Belgian draft and halter horses; but no Warmblood/Arabians
PSSM2: Warmbloods/Arabians
Muscle biopsy
PSSM1: anguloid atrophy, macrophage infiltration, subsarcolemmal vacuoles, cytoplasmic polysaccharide PAS+ amylase-resistant inclusions in type II fibers
PSSM2: less structural modifications, polysaccharides inclusions (PAS+) are usually amylase-sensitive (but can also be resistant)
What is the cause of EMND? By which mechanism?
Vitamin E deficiency: usually when horse has little/no access to pasture and poor-quality hay for prolonged period (17 months)
Increased CNS oxidative stress -> increased permeability of BBB-> degeneration of LMN -> muscle denervation and weakness
What is the management for HYPP?
Corn-syrup or grain to stimulate insulin-mediated movement of K+ into cells
Epinephrine
Dextrose
What is the treatment of malignant hyperthermia crisis?
Dantrolene -> binds to RYR1 and inhibit Ca2+ release -> until CK decline
Which muscular fibers are primarily involved in EMND?
Type 1 (postural, slow-twitch)
Which toxin is responsible for atypical myopathy? By which mechanism
HypoGlycine A (HGA)-containing
sycamore maple tree seeds
Acquired multiple acyl-CoA dehydrogenase deficiency
Give 5 diseases that induce non-exertional rhabdomyolysis and associated mutation for genetic diseases.
1/ Atypical myopathy
2/ Myosin heavy chain myopathy (MYHM): myosin-heavy chain 1 gene (MYH1)
-> 2 variants: non-exertional rhabdomyolysis and immune-mediated myositis
3/ Polysaccharide storage myopathy 1 (PSSM1): glycogen synthase 1 (GYS1)
4/ Polysaccharide storage myopathy 2 (PSSM2)
5/ Malignant hyperthermia (MH): ryanodine receptor 1 (RYR1)
What is the lavender foal syndrome gene? In which breed?
MYO5A(AR)
Introduces premature stop codon
Arabian foals
What is the percentage of Egyptian Arabian foals carriers for lavender foal syndrom?
10%
What is the prognostic factor for immune-mediated myositis in horse?
Fever
glycogen branching enzyme deficient horses can survive few years: true or false?
False
All affected foals have died by 18 weeks
What are the causes of chronic exertional myopathy in horses?
Polysaccharide storage myopathy (types 1 & 2)
Myofibrillar myopathy
Maligant hyperthermia
Reccurent exertional rhabdomyolysis
Which disease(s) in horse can be associated with lipofuscin deposition in the retina?
EMND, EDM/NAD
Which biopsies can be performed to diagnose EMND? Which findings?
Sacrocaudalis dorsalis medialis muscle: neurogenic atrophy of slow twitch muscle fibers + axonal depletion of IM nerve branches
Ventral branch of the spinal accessory nerve in chronic cases
Which cranial nerves are affected in EMND?
All motor nerves except occulomotors: CN V, VII, IX, X, XI, XII
PSSM1 can be associated with which other genetic myopathies?
GYS1 + RYR1 (MH)
GYS1 + GBE1 (GBED)
GYS1 + SCN4A (HYPP)
GYS1 + SCN4A (HYPP) + GBE1 (GBED)
What are the main neuromuscular causes of generalized muscular atrophy in horses?
PSSM
MYHM – immune-mediated myositis
EMND
Vitamin E deficient myopathy
Which muscle is usually recommended for biopsy in generalized muscular atrophy in horse? Why?
Sacrocaudalis dorsalis medialis
It is usually the only muscle with lesion in vitamin E and EMND
What is the prevalence of atrophy and rhabdomyolysis associated with an MYH1E321G mutation in Quarter Horses?
Approximately 20% of My/N QH develop rapid atrophy.
Atrophy is more common (80%) in homozygous My/My QH and less likely to resolve.
Which vaccine need to be avoided in MYT1 muted horses?
Strangles
To avoid immune-mediated polymyositis development
There is always an inciting cause in muscle atrophy and rhabdomyolysis associated with an MYH1 mutation in Quarter Horses: true or false?
False
Inciting causes such as vaccination and infection are inapparent in over half of cases.
What is the treatment of systemic calcinosis?
IV sodium thiosulfate to reverse calcium-phosphate precipitation in soft tissue
PO aluminum hydroxide to decrease intestinal phosphorus absorption and serum phosphorus concentration
(findings: increased CK, hyperPhosph, increased calcium-phosphorus product, hypoPT, inflammatory leukogram, multiform ventricular tachyarrhythmia)
Which CN are most commonly affected with polyneuritis equi?
V, VII, VIII > III, IX, X XII
Polyneuritis equi is usually associated with analgesia of the prepuce: true or false?
False
Analgesia of the penis: sacral plexus
But not the prepuce: genitofemoral nerve L3-4
Slap test can be detected from which age?
At which age is menace response present in foals and calves?
2 weeks
several days
gene associated with ability of Icelandic horses to perform the gait ‘pace’
DMRT3
RELN and STAU2
def movement disorder
involuntary movements that are not due to a painful stimulus and that are not associated with changes in consciousness or proprioception
diff stringhalt/shivers
- bilateral hindlimb hoof pain (stringhalt)
- upward fixation of the patella (string + shiv, period of hyperextension before hyperflexion)
- fibrotic myopathy (restricts forward movement and causes protraction of the hoof before placement on the ground at the walk. Stringhalt or shivers-forward hyperflexion have a much more pronounced degree of hyperflexion than observed with fibrotic myopathy)
- Neuropathies in horses can produce a stringhalt-like gait. Causes include Scandinavian knuckling disease, idiopathic polyneuropathy, equine protozoal myelitis, and vitamin E deficiency. These causes can be distinguished clinically by evaluating horses for evidence of muscle atrophy, proprioceptive or cranial nerve deficits, and
weakness as well as by performing ancillary diagnostic tests. - Lathyrism toxicity can cause a spastic gait abnormality in horses without evidence of proprioceptive deficits. Unlike stringhalt or shivers, gait deficits with lathyrism tend to worsen with increased exercise duration and speed. In addition, the stride length of all limbs is short, asymmetry is particularly apparent in hindlimbs, and the coordination between limbs is inappropriate with lathyrism. grass pea (Lathyrus sativus)
causes of standing hyperflexion
gelding, 12y, unilat
- pain
- early onset shivers (young, geld, tall)
- hyperactive reflex arc
remain stable except for shivers (7y)
etiology of Shivers
lack coordinated recruitement flex/ext muscles
disatl axonal degen Purkinge cells
degen lat (dentate, interpositus) cerebellar nuclei
prognosis/treatment Shivers
70% agravation
treat: removal precipitating factor, regular exercise, limited time in stall, balanced diet, low stress, +/- vit E/phenitoin
EMG in stringhalt
electromyography of hindlimb muscles reveals
increased insertional activity, fibrillation potentials, and positive sharp waves, consistent with denervation.
histopath lesion stringhalt
a Wallerian-type distal axonopathy of the tibial, deep, and superficial peroneal as well as recurrent laryngeal nerves accompanied by myofiber atrophy in
the muscles supplied by affected nerves.
Stiff horse syndrome
spasms are often initially induced by startling or excitement. This syndrome can resemble shivers hyperextension, except that spasms occur with stiff horse syndrome during periods of inactivity.
Antibodies directed against glutamic acid decarboxylase (GAD), which produces the active form of GABA in the central nervous system, have been identified in the cerebrospinal fluid of confirmed cases.
treat: prednisolone immunosup, recurrence can require reinstitution of treatment. The prognosis is guarded,
and cases may progress to become very painful and debilitating.
breed with congenital myoclonus
Peruvian Paso foals
environmental stimuli that results in prolonged myoclonic muscle contractions and stiff extended limbs
difficulty rising but can stand when assisted
40% to 60% deficit in spinal glycine receptors
breed with suposed genetic predisposition to THO
genetic predisposition in quarter horses (more than 50% have bilateral disease)
definitive deficit in THO
auditory loss
toxicity of gentamycin in horse
7/10 had auditory loss: maj partial unilateral. sensorineural auditory loss was suspected. Auditory dysfunction was reversible in 4 of 7 horses.
1 case of suspected vestibulotox
Causes of auditory loss in foals
congenital sensorineural deafness,
hypoxic ischemic encephalopathy,
bilirubin encephalopathy,
prematurity,
sepsis,
brainstem disease,
trauma,
otitis
parasitic encephalitis in horse
Halicephalobus gingivalis
breed with pigmented retinopathy in NAD/EDM
in young **Warmbloods **
no evidence of lipofuscin deposits and electroretinograms
were unremarkable in QHs
breed with significant significant familial component dor NAD/EDM
Morgan
cholesterol metb in NAD/EDM
In the SC, targeted markers of cholesterol oxidation (oxysterols) were significantly increased in horses with eNAD/EDM.
including 7-ketocholesterol, 7- hydroxycholesterol, and 7-keto-27-hydroxycholesterol,
upregulation of specific genes targeted by a nuclear transcription factor, the liver X receptor (LXR)
Unfortunately, these biomarkers were not altered in serum or CSF with eNAD/EDM, precluding their use as diagnostic tests.
metabolism of vit E in horse with NAD/EDM
Metabolic rate of α-tocopherol was increased in eNAD/EDM horses, with no difference in the metabolic rate of γ-tocopherol.
Horses with eNAD/EDM had increased expression of the CYP4F2 equine orthologue but no differences in copy number.
prevention NAD/EDM in susceptible foal
prevented in genetically susceptible foals by supplementing dams with high doses of water-soluble RRR-α-tocopherol (10 IU/kg PO once daily), a form of vitE, during the last trimester of gestation and supplementing foals through the first 2 years of life
fresh pasture
biologic marker for NAD/EDM
pNfH
using serum, overall sensitivity is low
breed specific, with Quarter Horses more likely to have increased serum pNfH concentrations than Warmbloods.
risk factors associated with the development of EDM
use of insecticide (insect repellent) applied to foals,
exposure of foals to wood preservatives/sealers (creosote,
oil-based stain)
foals spending time on dirt lots while outside
immunohisto marker for NAD/EDM
calretinin as an immunohistochemical marker of axonal swellings, or spheroids
differenical diagnosis of NAD/EDM
spinal cord compression due to cervical vertebral stenotic myelopathy
spinal cord inflammation: EPM
neck pain -> more likely to have CVSM
asymmetrical ataxia or concurrent focal muscle atrophy -> more likely to have EPM.
unpredictable or aberrant behavior -> eNAD/EDM
breed with normal serum pNfH concentrations in NAD/EDM
Warmblood
equine neuro congenit diseases with known mutation
lethal white foal syndrome: breed, mut, transm
= Ileocolonic aganglionosis
American Paint horses, Quarter horses, Miniature horse, (rarely) Thoroughbred
often all white or have nearly an all-white coat and often have blue irides +/- hearing deficits
colic, progressive abdominal distension and failure to pass feces, ileus
mut endothelin receptor B gene (EDNRB), autosomal semidominant. abnormal development of enteric ganglia and melanocytes within the embryologic neural crest
heterozygous: maj frame overo phenotype
human equivalent of white letal foal syndrome
Hirschsprung disease, where children are born with aganglionic
megacolon
lavender syndrom in foal
affects **Egyptian lineage Arabian **
tetanic episodes with opisthotonus,
paddling, and extensor rigidity from birth
**anomalous choroid plexus and vacuolization of CNS neurons **
mut myosin Va (MYO5A), autosomal recessive
impairs binding of myosin Va to organelles with appropriate receptors, which leads to the loss of vesicle traffic (melanosomes and dendritic cargo) and interferes with the function of melanocytes and neurons.
prevalence lavender foal syndrome
Preliminary carrier frequencies were estimated to be 10.3% in Egyptian Arabian and 1.8% in non-Arabians
Arabians in South Africa 11.7%.
human equivalent of lavender foal syndrome
Griscelli syndrome,
although the mutations of MYO5A that have been associated with Griscelli syndrome in humans are often due to changes in a single amino acid rather than loss of a large portion of the transcript.
The clinical signs observed in foals with LFS are more severe than those observed in humans
cerebellar abiotrophy
Arabian, Gotland, Oldenberd, Eriskay
affected horses may stabilize with time
degenerative Purkinje cells, Mineralized cell bodies have been reported in the thalamus of affected cases
autosomal recessive, mut TOE1, not high level in cerebellum, involved in cell-cycle regulation.
MUTYH, which is located on the opposite strand, is highly expressed in the cerebellum and encodes for a DNA glycosylase involved in postreplicative repair in the nuclei of rapidly proliferating Purkinje cells as well as DNA repair due to oxidative damage of mitochondrial genomes
2 genes associated with cerebellar abiotrophy and roles
TOE1 and MUTYH were not differentially expressed in CA-affected horses.
However, genes involved in calcium homeostasis and specifically expressed in Purkinje cells were downregulated in CA affected cerebella, whereas markers for microglial phagocytosis were found to upregulated.
specific MUTYH isoforms are differentially expressed in the equine cerebellum. Expression of isoforms 1 and 2 were significantly increased in CA-affected cerebella compared with healthy controls.
CA-associated SNP results in loss of methylation in the MUTYH promoter, which causes binding of a unique transcription factor, myelin transcription factor-1-like protein (MYT1L)
MUTYH gene expression corresponds to differential localization in the Purkinje (mitochondrial) and granular neurons (nuclear) of the cerebellum as well as the spectrum of onset and severity of disease.
6 classes of Familial Occipitoatlantoaxial Malformation of Arabians
- Familial occipitalization of the atlas with atlantalization of the axis in Arabian horses
- Congenital asymmetrical OAAM (non-arabian: Standartbreed, Morgan, Miniature)
- Asymmetric atlantooccipital fusion
- Duplication of the axis and/or atlas (Arabian)
- Symmetric OAAM in non-Arabian horses (Appaloosa, Quarter horse, Friesian, Miniature horse)
- Subluxation of the atlantooccipital joint, fusion of the atlas and axis with lateral deviation of the atlantoaxial joint, and rotation of the atlas (Half-Arabian)
mutation for familial OAAAM
Arabian
HOXD3 (homeobox gene involved in the devt of the axial and appendicular squeleton)
autosomal recessive
mutation for hydrocephalus
Friesian
autosomal recessive
B3GALNT2, involved in glycosylation of dystroglycans, which are present in skeletal muscle but also in many tissues as the brain where it affects morphogenesis and early development.
estimated allele frequency in Friesian was determined to be 8.5%
a communicative hydrocephalus, leading to decreased cerebrospinal fluid (CSF) absorption secondary to a distorted jugular foramen
age of onset of juvenile epilepsy
median 2 m, 2d-6m
resolve by 1 to 2 years of age
autosomal dominant in Egypsean Arabian foal
seizure description in juvenile epil
In the preictal phase, there may be no clinical signs or mild behavior changes.
During the ictal phase, tonic seizures are followed by clonic motor activity in severe cases or focal head twitches and nystagmus in milder cases.
During the postictal phase, blindness, lethargy, and obtundation are observed
EEG: with spikes, sharp waves, spike and wave discharges, or multiple spike complexes
Sensory Deafness in American Paint Horses
extensive white facial markings (also often in legs) and one or more blue irides
splashed white overo and frame-splashed white overo blends.
EDNRB + other mutation
susceptibility to EPN in horses
a defective IFNgamma response
a large inoculum (10^5–10^6 sporocysts)
case where The Goldmann–Witmer coefficient (C-value) and the antigen-specific antibody index (AI) are recomanded instead of a simple ratio of serum:CSF S. neurona titers in EPM
uncompelling ELISA titer results (ie, the serum:CSF ratio equals the cut-off) and/or abnormally high CSF albumin concentration (including conditions associated with a “leaky” BBB).
prophilactic treatment EPM
intermittent treatment with
low doses of the triazine drugs might be an effective prophylactic
for reducing parasite infection and the risk of EPM.
diagnostic value of transcranial electrical stimulation (TES) to assess neuronal functional integrity in horses
TES-MEP latencies are highly sensitive to detect impairment of spinal cord motor functions for mild-to-severe ataxia (grades 2–4).
TES-MEP amplitudes were the least discriminative between healthy and ataxic horses.
Rooney types of Cervical Vertebral Stenotic Myelopathy
type I: , the vertebral column is fixed in flexed position at the site of malarticulation/malformation, which generally occurs at C2–C3, less common and often presents at birth.
type II: symmetric overgrowth of the articular processes causes spinal cord compression during flexion of the neck. foals and weanlings and are generally found in the mid-cervical region.
type III: asymmetrical overgrowth of one articular process that leads to compression of the spinal cord either directly by bony proliferation or indirectly by associated soft tissue hypertrophy. mature horses but can begin as early as 1 to 3 years of age. This lesion most often affects C5– C6 and C6–C7.
CVSM has been divided into two broad categories or classes of horses: one is affecting young horses (Type I, which correlates with Rooney’s Type II) and one is affecting older horses (Type II, which correlates with Rooney’s Type III)
breed predisposed to type 1/all types CVSM
Type1: Thoroughbred, multifactoriel disease (gender, inherence, diet, trauma, rate of grown)
CVSM affect 1.3% to 2% of Thoroughbred horses
All type: Thoughbred, Quarter, Warmblood, tenessee walking horse
Arabians and Standardbred were underrepresented
male/female and age predisposition to CVSM
Male horses are more likely to be affected than female horses with a ratio of 3:1
horses less than 7 years of age are more likely to be diagnosed with CVCM than horses 10 years or older
five characteristic bony malformations of the cervical vertebrae in horses with CVSM
abnormal ossification of the articular processes
degenerative joint disease of the articular processes
malalignment between adjacent vertebrae
extension of the dorsal laminae
“flare” of the caudal vertebral epiphysis of the vertebral body
most common site of static/dynamic compression in CVSM
static stenosis:
C5–C6 and C6–C7
Dynamic compression:
in flexed views, C3–C4 and C4–C5
myelographic evidence of compression in CVSM
complete attenuation of the ventral contrast column with 50% attenuation of the dorsal contrast column
minimal sagittal dural diameter, which is the sagittal diameter of the dural space measured intervertebrally greater than 20% smaller than the largest dural diameter measured within the cranial vertebra
medical treat recomandation for horse <1yo with CVSM
restricting protein and carbohydrates to 65% to 75% National Research Council (NRC) recommendations,
maintaining balanced vitamin and mineral intake (minimum 100% NRC requirements),
supplementing vitamins A and E at three times NRC recommendations,
and supplementing selenium to 0.3 ppm.
factor associated with post surg prognosis in horse with CVSM
shorter duration of clinical signs before intervention was positively associated with neurologic improvement and return to function, whereas age and number of compressive lesions did not affect outcome.
risk factor for resp/EHM/abortion with EHV1
gender associated with higher risk of EHM
female
antemortmen diagnosis of EHM is supported by
(i) ruling out other neurologic conditions,
(ii) demonstrating xanthochromia and an elevated cerebrospinal fluid (CSF) protein concentration,
(iii) identifying or isolating EHV-1 from the respiratory tract, buffy-coat, or CSF,
(iii) demonstrating a fourfold increase in antibodies using serum neutralizing, complement fixation, or enzyme-linked immunosorbent assays performed on acute and convalescent serum from affected or in-contact horses 7 to 21 days apart
PCR recomandation for EHM diagnosis
use a diagnostic laboratory that offers both testing for a universal gene (glycoprotein B gene) and a virulence gene (ORF 30).
quantitative PCR
14% and 24% of EHV-1 isolates from horses with EHM do not have this neuropathogenic marker
detection of a neurotropic strain -> valacyclovir
% latent infected horses with herpesvirus
15-27% maj in trigeminal ganglia >lymphoreticulr system
affection associated with MND at post mortem exam
eosinophilic enteritis
MND: type 1 oxidative fiber
which exam is recommanded for headshaking cause identif
CT (6% clinical relevant abnom)
sensory nerve threshold sens/spe for headshaking
minimal SNCT <= 10mA
spe 100%, sensit 41%
seasonal effect headshaking
60%
spring/sumer +/- autumn
human equivalent headshaking
trigem neuralgia: unilat, demyelin trigem nerve root, focal compression by blood vessels
sex predisposition headshaking
gelding overrepresented
electrical nerve stim mechanism
substancia gelatinosa modulate synaptic transmission of n impulse from periferal fibers to CNS
-> is stim by small nocic Adelta and C fiber
large mecanorecept Abeta inhib pain transm (higher act threshold in nociceptfiber)
+ descend inhib pathway by periaq grey => released endogenous opioids and alt sec serot, norad, GABA, ach, substance P, adenosisn
clinical variables associated with prognosis in EHV1 caused by A2254/N752 strains
urinary complications
systemic signs of vasculitis
% retouring exercice in horse with EHM + prognostic factor
68% chance of returning to exercise, and 53% were able to achieve their preoutbreak performance level.
Horses with an ataxia grade at admission ≥4/5 had an increased fatality rate and 10% chance of reaching their preoutbreak performance level.
None of the horses with both vascular and urinary complications returned to their previous performance level.
Finally, horses vaccinated against EHV-1 and those with urinary complications had a 71.4% and 43.7% fatality rate, respectively.
caudal neck pathology in warmblood horses
Focal caudal cervical muscle atrophy (47.9%), hypoesthesia ( 39.6%), patchy sweating (16.7%), hyperesthesia (11.5%), and pain upon firm pressure applied over the caudal cervical articular process joints and transverse processes (60.4%) were only observed in cases.
Sideways flexion of the neck was restricted in a higher proportion of cases (49%) compared with controls (32%).
Hopping-type thoracic limb lameness was only observed in cases, (31.6%).
Deterioration in lameness after diagnostic anesthesia occurred in 13/31 (42%) cases.
novel spinocerebellar neurological disease in juvenile Quarter Horses
median of 16 d of age, acute onset of neurological deficits. asymmetrical spinal ataxia, with pelvic limbs more severely affected.
high serum activity of gamma-glutamyl transferase and hyperglycemia.
All foals became recumbent (median, 3 days: [0–18 days]), which necessitated humane euthanasia
dilated myelin sheaths and digestion chambers within the spinal cord, maj the dorsal spinocerebellar tracts.
likely autosomal recessive mode of inheritance.
