Infectious Neurologic Disease/Traumatic Brain Injury/Degenerative/Toxic

Question 1

What is the prevalence of EHV-1 in horses?

Answer 1

Fairly uncommon
- only found in 2.7% of samples submitted for PCR testing
- most horses (up to 80%) are latently infected with EHV-1 (though often do not shed the virus)

Question 2

What is EHV-1?

Answer 2

An alpha herpes virus that may cause respiratory disease, neurologic disease or abortion

Question 3

What are the two viral genotypes of EHV-1 recognized and what is the difference between the two?

Answer 3

D752: known as neuropathic

N752: known as wildtype

Both genotypes can result in either neuro, respiratory or abortion, though D752 is more likely to cause neuro disease and N752 more likely to cause respiratory disease

Question 4

How do horses acquire EHV-1?

Answer 4

They are exposed through direct contact, aerosolized viral particles, or through contaminated equipment or personnel
- the respiratory tract is the primary site of infection
- then the virus enters the local lymph nodes
- monocyte- associated viremia disseminates the virus
- incubation period of 2-10 days
- often occurs in association with shows - then can go home and spread to home farm
- viremia results in vasculitis which can then lead to edema or ischemic damage to the brain and spinal cord

Question 5

What are the main clinical signs of EHV-1? What are these signs a result of?

Answer 5

• neuro signs usually preceded by fever (not always observed)
• can also have signs of vasculitits–> distal limb edema
• often accompanied by weak hind end leading to a dog sitting appearance, also fecal and urinary incontinence (easily expressed bladder)
• obtundation, cranial nerve deficits, recumbency, seizures if the brain is affected

Signs are a result of ischemic damage due to virus induced alterations in the coagulation cascade–> thrombosis of small vessels, activation of platelets, increased tissue factor transcription by monocytes

Question 6

What can be seen histologically in cases of EHV Myelo encephalopathy?

Answer 6

Perivascular cuffing (white cells surrounding area of vasculitis)

Question 7

What is the best way to diagnose EHV-1?

Answer 7

Quantitative PCR to confirm infection- rayon nasal swab and EDTA of blood
- allows determination of viral load and genotype
- send to specialized lab

CSF Cytology- to determine if its the myeloencephalopathy form of disease
- can see xanthochromia (yellow coloration), increased protein
- mild mononuclear pleocytosis (around 20,000)

Question 8

Describe the morbidity and mortality often associated with EHM outbreaks

Answer 8

Morbidity around 90% for EHV, 40% of those developed EHM, mortality around 30%
- horses with temperature elevations <103.5 more likely to die
- recumbency is associated with non-survival

Question 9

What are the main goals of EHM treatment?

Answer 9

Antiviral treatment
- reduce vasculitits that results in neurologic signs
- supportive care

Question 10

What is the antiviral treatment often used in EHM cases?

Answer 10

Valacyclovir
- does not kill virus
- prevents viral replication

*works best if used before clinical evidence of disease- good in the face of an outbreaks

Question 11

What anti-vasculitis medications are indicated in EHM cases?

Answer 11

NSAIDS (banamine is the main one)

Heparin: prevents virus induced activation of coagulation cascade- limits clotting of small vessels that supply the brain and spinal cord with oxygen

Question 12

What other medications other than anti-vasculitis meds and antivirals may be helpful in EHM cases?

Answer 12

Steroids -most potent antiinflammatory and anti-vasculitis drug

Supportive care- fluids, nursing care, sling, urinary catheter + TMS (to prevent bladder infection)

Question 13

How can you prevent EHV-1 outbreaks?

Answer 13

-cannot prevent previously exposed horse from shedding
-practice good biosecurity at home and when away including quarantining new horses for at least 2 weeks, limiting nose-nose contract with unfamiliar horses at shows, and not allowing horses to use public food/water/wash areas
- if high risk- vaccinate every 6 months- does not prevent EHM but decreases viral shedding and may decrease disease severity
- make sure immune supplements contain zinc

Question 14

What are the 3 main equine encephalomyelitis viruses?

Answer 14

EEE: Eastern equine encephalitis
- mostly in south/southeast, but is being seen farther north every year
WEE: western equine encephalitis
- mostly in western/midwest states
VEE: Venezuelan equine encephalitis
- reportable foreign animal disease

All alphaviruses in family togaviridae

Question 15

How are encephalomyelitis viruses spread?

Answer 15

Via mosquitos
- birds and small mammals are the reservoir hosts
- horses are accidental hosts

ZOONOTIC- but horses are unlikely to amplify EEE and WEE enough to be infectious to other horses or humans, definitely with VEE however

Question 16

What clinical signs are associated with equine encephalomyelitis viruses?

Answer 16

-Fever up to 106
-non-specific signs: circling, head pressing, hyperesthesia, seizures, obtundation, aggression, somnolence, CP deficits
-history and fever will clue you into virus diagnosis

Question 17

What is the mortality associated with EEE, WEE and VEE?

Answer 17

EEE- 75-100%
WEE- 20-50%
VEE- 40-80%

Question 18

What is the treatment for the equine encephalomyelitis viruses?

Answer 18

• no real treatment
• try anti-inflammatories and supportive care

Question 19

How can you diagnose equine encephalomyelitis viruses?

Answer 19

CSF cytology: mononuclear pleocytosis, increased protein

Serology: IgM capture ELISA- to differentiate between vaccination or acute response to active infection
-can also do acute and convalence IgG serum titers (horse has to survive long enough)
-PCR of CSF- less sensitive

Question 20

How can you prevent against equine encephalomyelitis viruses?

Answer 20

Mosquito control
Vaccination:
- foals should get initial vaccine at 3-6 months, booster 4-6 weeks later and again at 12 months
- unvaccinated adults should get vaccine and booster in 4-6 weeks
- annual in spring thereafter/ maybe 6 months depending on location
-if one animal on farm is exposed or infected, consider booster in other animals on property

Question 21

What is west nile virus?

Answer 21

A flavivirus endemic in avian populations
- amplifies in birds and mosquitos throughout late summer and early fall

Question 22

What clinical signs are seen with west nile virus?

Answer 22

-+/- fever
-diffuse fine muscle fasciculations (often specific to muzzle)
-change in mentation and consciousness (often very sudden)
-cranial nerve abnormalities
- spinal ataxia +/- hypermetria

Question 23

What is the treatment for WNV?

Answer 23

Supportive care, anti-inflammatories
- WNV plasma if you have access to this - gives antibody for virus
- try to keep them standing

Question 24

How do you diagnose WNV?

Answer 24

IgM capture ELISA
- CSF- mononuclear pleocytosis/xanthochromia/normal

Question 25

What is the prognosis for WNV?

Answer 25

30-40% become recumbent, most recumbent horses fail to survive
- good with return to full function if they do not become recumbent

Question 26

How can you prevent against west nile virus?

Answer 26

-Vaccination: initial vaccine + booster 2-3 weeks later, booster annually in spring or every 6 mo if year-round mosquito season

Question 27

What is rabies?

Answer 27

Zoonotic Rhabdovirus
-transmitted by the bite of infected animal (skunk, fox, raccoon)

Question 28

What is the incubation period for rabies?

Answer 28

Anywhere from 9 days to 1 year
- virus infects and replicates in myocytes at the bite (incubation depends on how far from CNS initial bite is)
- it infects peripheral nerves and ascends to the CNS where it multiplies rapidly
- invariably fatal

Question 29

What are the clinical signs of rabies?

Answer 29

They are variable, fluctuating and confusing
- bite wound is usually not present due to long incubation period
- in the cerebral/furious form (rare in horses), you can see aggression, hyperesthesia, muscle tremors, hydrophobia
- in the brainstem/dumb version you can see obtundation, head tilt, pharyngeal paralysis
- in the spinal/paralytic form you can see shifting leg lameness +/- self mutilation, ataxia or paralysis

Question 30

How can you diagnose rabies?

Answer 30

-usually clinical signs
- CSF can be normal or can see a mononuclear pleocytosis
- post mortem testing is necessary for definitive diagnosis
- send 1/2 of the brain in formalin for histopathology (can see negri bodies- eosinophilic inclusions within neurons or ganglion cells)
- send 1/2 brain on ice to state lab for fluorescent antibody test, monoclonal antibody test, or mouse inoculation

Question 31

How do you prevent against rabies?

Answer 31

VACCINATION
- foals 3-6 months of age, booster in 4-6 weeks
- adults that are unvaccinated can give single primary dose
- booster annually
- post exposure, if previously vaccinated booster immediately, if unvaccinated per state health official

Question 32

What is bacterial meningitis? What are the 3 ways it can be caused?

Answer 32

Bacterial infection of CNS
Causes:
- hematogenous spread of bacteria
- trauma to the head extending into the brain
- extension of a paranasal sinus infection or mass

Question 33

What is the common signalment and history for hematogenous meningitis? What are the most common implicated organisms?

Answer 33

Occurs more commonly in foals due to FPT and subsequent sepsis
- immunocompromise is a prerequisite

In adults it can be a result of common variable immunodeficiency, lymphoma, or transient IgM deficiency (1-6 years old) resulting in hypogammaglobulinemia +/- poorly functioning lymphocytes

Causative organisms: strep (most common), actinobacillus, actinomyces, E coli, staphylococcus

Question 34

What are the clinical signs of bacterial meningitis?

Answer 34

Fever
- multifocal brain signs, seizures
- may progress to being comatose

Question 35

How do you diagnose bacterial meningitis?

Answer 35

CSF cytology- NEUTROPHILIC pleocytosis, elevated protein, glucose <50 (due to bacterial consumption)
-submit CSF for culture
-inflammatory leukogram, elevated acute phase proteins

Question 36

What is the treatment for bacterial meningitis?

Answer 36

Broad spectrum antimicrobials IV initial
- CRI of time dependent antibiotics (ampicillin, K penicillin, 3rd or 4th gen cephalosporins)
-oxytet
- aminoglycosides (don’t penetrate intact BBB well- but fine in the first 48 hours)
- enrofloxacin in adults, marbofloxacin in foals

Also add on NSAIDs, plasma, supportive care and seizure care

Question 37

What is lyme disease caused by?

Answer 37

Borrelia burgdorferi
- gram negative spirochete
- most common tick borne disease in humans
- ixodes scapularis is the principle vector

Question 38

What are the clinical signs associated with lyme disease in horses? What makes them misleading?

Answer 38

In confirms cases
- Back and neck pain, hyperesthesia
- cranial nerve signs, ataxia, obtundation
- fever
- uveitis

Suspect cases
- ADR, weight loss
- shifting leg lameness
- mild neurologic signs

*Cant cause these signs with infection during studies however

Question 39

What testing is available for lyme disease? Why is it problematic?

Answer 39

Only have antibody testing right now (not evidence of actual disease)
- lyme multiplex is the most comprehensive
- SNAP test also available- doesnt tell you if acute or chronic

Seroprevalence is high- not necessarily sick
- titers do not change with/without treatment

Dont test on pre-purchase exam or in absence of clinical signs

If you suspect neuroborelliosis, should do CSF testing (will see neutrophilic pleocytosis)
- antibody testing is not the best option, but we dont have other options

Question 40

What antibiotics are recommended with Lyme disease diagnosis?

Answer 40

Oxytet or minocycline (better CSF penetration compared to doxy)
- continue to treat - reassess in a week or two and reassess if there is no response

Question 41

Describe otitis media/interna

Answer 41

Infection of the middle or inner ear
- may occur with THO or in isolation

Clinical signs: include head shaking, ear rubbing, aural discharge, CN VII +/- CN VIII deficits

Diagnosis: radiographs or CT (definitive)

Treatment: long term antibiotics, aural endoscopy and lavage

Question 42

Describe traumatic brain and spinal cord injury in horses

Answer 42

-accounts for 22-24% of neuro disease in horses
-flipping over backwards, falls and collisions most common findings

Question 43

What should you be sure to check on examination of a horse with suspect TBI?

Answer 43

-perform a concise physical and complete neuro exam
-special care should be used on palpation of the head and neck
- check for otorrhea (clear or bloody liquid out of ear could be CSF), swelling and creptitus
- pain can confuse a neuro diagnosis- repeat neuro exam in 24 hours to distinguish between the two

Question 44

Describe the pathophysiology of traumatic brain injury

Answer 44

There is often both a primary and secondary injury:
1. Primary is caused by direct trauma of CNS and blood vessels within skull/vertebral canal
- coup is injury on side of trauma, contrecoup is injury opposite side of trauma due to brain displacement

2. Secondary injury- due to increased intracranial pressure, hemorrhage, and ischemia which causes a cascade of excitotoxicity, ischemia and inflammatory cytokines
   - can result in ATP depletion, ROS, intracellular calcium accumulation and cerebral lactic acidosis
   - These lead to edema, neuronal and axonal injury and cellular death

Question 45

How should you diagnose a TBI?

Answer 45

Neuro exam and hydration/blood pressure status assessment are most important
- more definitive diagnosis comes from diagnostic imaging- orthogonal radiographs or CT

Question 46

What are the main treatment goals in cases of TBI?

Answer 46

-decreasing intracranial pressure while maintaining adequate cerebral blood flow (through hypertonic saline and judicious fluid therapy)
- feed elevated
- decrease inflammation and pain (flunixin, gabapentin, acetominophen)
- prevent sepsis if open fracture or large injury (oxytet is a good option)
- maintain them standing
- treat seizures if they occur
- corticosteroids? (only if clinical signs are worsening, not indicated with open wounds), DMSO?, Progesterone derived neurosteroids (not available yet)

Question 47

How do you prevent, and treat seizures?

Answer 47

Prevention: gaba or phenytoin
During seizure: diazepam or midazolam
Maintenance: levetiracetams (keppra) or phenobarbital

Question 48

When should you pursue surgical stabilization in TBI cases?

Answer 48

If there is a depressed skull fracture- unless easily accessible you should probably leave fragments where they are
- vertebral fractures: consider surgical management, medical management may be sufficient

*ideal patient for surgery has no neuro deficits- lots of risk associated with these surgeries

Question 49

What is the prognosis for TBI cases?

Answer 49

Depends on the trauma involved
- basilar fractures have worse prognosis
- recumbency has worse prognosis

Question 50

What is eNAD &EDM?

Answer 50

-equine neuroaxonal dystrophy and equine degenerative myeloencephalopathy
-inherited neurodegenerative disorder linked to vit E metabolism

Question 51

What are the clinical signs associated with eNAD &EDM?

Answer 51

-symmetric ataxia and conscious proprioceptive deficits in all limbs
- abnormal stance at rest
- thoracic and pelvic limbs both weak and spastic (pelvic limbs may be worse)
- excessive hypermetria when head is elevated

*looks a lot like spinal ataxia

-ataxia develops within the first 1-2 years of life, but may not be recognized until put into training
- variably reported signs: decreased menace, lack of fight/flight (esp in QHs)

Question 52

How is eNAD &EDM diagnosed?

Answer 52

Post mortem
- on histopath see spheroids, axonal loss and demyelination within the caudal brainstem and spinal cord (primary damage in afferent proprioceptive tracts in spinal cord and nucleus of dorsal spinocerebellar tracts)

eNAD- lesions confined to caudal medulla oblongata
EDM- lesions more widespread and include demyelination within the ascending tracts of cord (worse clinical signs)

Question 53

What is the prevalence of eNAD &EDM?

Answer 53

Fairly common- more common than was once thought

Question 54

Describe the inheritance pattern of eNAD &EDM?

Answer 54

Autosomal dominate- incomplete penetrance
- if a mare has it she will pass it on to her foal
- foal will be clinically affected, unless environmental modifications are made that keep it from expressing the trait

Question 55

What causes expression of the oxidative phenotype in eNAD &EDM?

Answer 55

Oxidative damage causes it
- vitamin E is a potent antioxidant
- risk increased with application of insecticide to pasture, exposure to wood preservative, housing in dirt lots, Low vit E environment

Question 56

T/F: vitamin E supplementation of genetically susceptible horses lowers sensitivity and incidence of eNAD &EDM

Answer 56

True
-however low vitamin E is not consistently present in all cases
- QHs have increased rate of vit E metabolism
- it will not improve neuro deficits, but halts progression of disease

Question 57

What are some differentials for eNAD &EDM?

Answer 57

CVCM, EPM, EHV-1, WNV

Question 58

What should be your target serum vit E in eNAD &EDM cases?

Answer 58

> 3 ug/mL
- must give them water soluble/natural/rrr- alpha tocopherol
- for those at risk give 10 IU/kg/day
- for those without access to forage but have no predisposing factors- give 1 IU/kg/day

Question 59

What is Equine Motor Neuron Disease?

Answer 59

-caused by vit E deficiency
- may occur alone or in conjunction with eNAD &EDM
- affects the motor neurons in spinal cord and brainstem resulting in a generalized neuromuscular weakness and muscle atrophy

Question 60

What are the clinical manifestations of EMND?

Answer 60

Subacute: symmetrical muscle atrophy, muscle fasciculations, weight shifting, toe dragging/weakness
- standing on a ball type stance common
Chronic: poor performance, failure to gain weight, symmetric muscle atrophy

-30% of horses will develop pigment retinopathy
- mosaic/reticulated pattern of brown pigment that does not compromise vision

Question 61

How can you obtain a definitive diagnosis for EMND?

Answer 61

Biopsy of the sacrocaudalis dorsalis muscle
- will see denervation atrophy of type I muscle fibers and scattered muscle necrosis
- Low vitamin E is supportive of a diagnosis of EMND (may be normal in horses that have been recently supplemented)

Question 62

What is the treatment for EMND?

Answer 62

Same as with eNAD &EDM
- 10 IU/kg/day

Question 63

What is Equine Dysautonomia?

Answer 63

Acquired degenerative polyneuropathy that predominately affects neurons of the autonomic and enteric nervous systems
- has been identified mainly in UK and northern europe
- Botulinum toxin is suspected
- risk factors include full time turnout, young age, recent movement to new pasture, highest incidence in spring/summer

Question 64

What are the clinical forms of Equine Dysautonomia?

Answer 64

Acute (0-48 hrs): develop dysphagia, bilateral ptosis
- acute and severe gastrointestinal ileus resulting in distended SI and LC impaction
- moderate to severe abdominal pain
- hypovolemia may result in heart failure
- patchy sweating and muscle fasciculations

Subacute 3-7 days: similar to acute form but less severe

Chronic (weeks to months): dysphagia, ptosis and severe weight loss, sweating muscle tremors, base narrow stance, leaning against walls, rhinitis sicca (dry nose) and piloerecetion

Question 65

How do you diagnose Equine Dysautonomia?

Answer 65

Clinical signs
- phenylephrine eye challenge (reverses ptosis temporarily)
- histopathology necessary for definitive diagnosis- reduction in interstitial cells of cajal in ileum

Question 66

What is the treatment for Equine Dysautonomia?

Answer 66

Acute and subacute require euthanasia
- recovery from chronic is possible but rare with nasogastric tube feedings, and intensive care

Question 67

What is the typical history and signalment for THO cases?

Answer 67

Signalment: adult horse of any breed
History: facial nerve paralysis (chronic ulcers, decreased lacrimation, ear droop, lip droop), vestibular disease (head tilt, nystagmus, strabismus, base wide ataxia), difficulty chewing
-might also have hearing loss

Question 68

What are some differential diagnoses for THO?

Answer 68

Gutteral pouch disease in lateral compartment
-traumatic injury to skull base
- otitis media/interna
- EPM
- extracranial mass

Question 69

What is THO?

Answer 69

Bony proliferation of the stylohyoid and petrous temporal bone causing inflammation and compression of CN VII and or VIII
- repetitive trauma/motion and extension of infection are possible underlying causes, but in most cases cause is not found

Question 70

How do you diagnose THO?

Answer 70

Radiographs (least sensitive), guttural pouch endoscopy or CT (most sensitive)

Question 71

What are the treatment options for THO?

Answer 71

Ceratohyoidectomy- removal or ceratohyoid releases pressure and eliminates movement of the joint where the nerves course
- can also disarticulate in some cases
-majority of cases experience immediate improvement in signs

There are options for medical management too with tarsorrhopathy, antibiotics or anti-inflammatories (steroids)
- if you can take horse to surgery, DO IT

Question 72

What causes hyperammonemia?

Answer 72

Failure of the liver to remove ammonia and other toxic metabolites from the blood

OR

Overproduction of ammonia and amino acids by products by intestinal bacteria

Question 73

What does hyperammonemia cause?

Answer 73

Inhibition of ATP production and disturbance of cell energy production –> increased glutamine which causes cell edema and increased ICP
- increased concentration of excitatory neurotransmitter glutamate
- induction of ROS and NO

All of these result in bilateral forebrain dysfunction which can cause behavioral changes, circling, head pressing, central blindness, stertorous breathing and seizures
- may be permanent in chronic cases
- often have concurrent signs of hepatic insufficiency or enterocolitis

Question 74

How do you diagnose Hyperammonemia?

Answer 74

-clinical signs with evidence of hepatic insufficiency or enterocolitis
- elevated plasma or CSF ammonia (ammonia is labile and should be run immediately)

Question 75

What is the treatment for hyperammonemia?

Answer 75

Lactulose- acidifies GI contents converting ammonia into a form that cannot be absorbed
-tracheostomy for laryngeal collapse
- manage seizures
- anti-inflammatories hypertonic saline, fluid therapy, supportive care
- treat underlying cause

Prognosis not great for either cause

Question 76

What is equine leukoencephalomalacia?

Answer 76

Moldy corn disease
- caused by ingestion of Fusarium moniliforme
- interferes with sphingolipid metabolism
- results in liquefactive necrosis and malacia of WHITE MATTER

Occurs when corn becomes contaminated during a wet harvest season- toxicity is dose dependent
- clinical signs start 3-4 weeks after ingestion

Question 77

What is seen clinically in cases of ELEM?

Answer 77

Multifocal brain signs: circling, ataxia, blindness, seizures
Hepatic disease: icterus, petechiae, increased liver enzymes

Diagnosis based on diet history, number of horses affected
- can test feed for fusarum
- on CSF can see increased protein, hemorrhage and TNCC

Question 78

What is the treatment for ELEM?

Answer 78

Supportive care, gastric lavage and charcoal, anti-inflammatories, mannitol

<10% survival