Ruminant Neurology 2

What is the phylogeny of rabies?

Family: Rhabdoviridae

Genus: Lysavirus

What is rabies made of?

RNA

What determines the incubation period for rabies?

Inoculation site

What is the incubation period for rabies?

30-90 days

What is the duration of C/S of rabies?

14 days

What are the 3 forms of rabies?

Furious (cerebral)

Brainstem (dumb)

Spinal cord (paralytic)

A rabid cow comes at you with aggression, hyperesthesia, vocalization, tenesmus, and seizures. What form do you think it is?

Cerebral

A rabid cow is somnolence, demented, stuporous, opisthotonos, pharyngeal paralysis, drooling, and ataxia. What form is it?

Brainstem

A rabid cow has progressive ascending paralysis, truncal and limb hyporeflexia, hypalgesia, priapism, and urinary incontinence what form is it?

Spinal cord

How can you diagnose rabies antemortem?

Nothing is definitive. Maybe mild mononuclear pleocytosis or mild-moderate protein elevation

How do you diagnose rabies postmortem?

Definitive with negri bodies in brain tissue or saliva. Direct or indirect IFA is done on brain tissue

What animals have a label for rabies?

Cattle and sheep

What animals do not have a labeled rabies vaccine?

Goats, pigs, llamas, or alpacas

What is the prevalence of rabies vaccination in livestock?

Not widespread, only used in areas with high likelihood of exposure

What is the etiology of pseudorabies?

Suid herpes virus type 1

What is mad itch?

Pseudorabies

What is the significance of pseudorabies or mad itch?

It is reportable and is only seen in feral swine populations

What is the reservoir for pseudorabies?

Pigs

What are the dead end hosts for pseudorabies?

Cattle, sheep, goats

What are the C/S of pseudorabies in piglets?

Ataxia, blindness, recumbency, death (fatal encephalitis)

What are the C/S of pseudorabies in adult pigs?

Mild respiratory disease

Encephalitis is transient or non-existent

What are C/S of pseudorabies in cattle, sheep, and goats?

Pruritus at sit of inoculation

Ataxia

Maniacal behavior

Death

What is the incubation period for pseudorabies?

3-7 days

How can you diagnose pseudorabies antemortem?

Pruritis on skin can be presumptive

How do you diagnose pseudorabies post-mortem?

Definitively with viral identification in tissues via PCR, virus isolation, IHC

What is PEM (polioencephalomalacia)?

Histologic description of neurologic disease resulting in necrosis and softening of the gray matter of the brain

What are the most common causes of PEM (polioencephalomalacia)?

Thiamine deficiency and sulfur toxicity

What are all the causes of PEM (polioencephalomalacia)?

Thiamine deficiency, sulfur toxicity, lead toxicity, salt toxicity or water deprivation

What are factors that promote cerebral edema?

Anything that changes osmotic forces like

• Cellular ability to maintain intracellular milieu

• Osmolality across BBB

What is required for the brain to have normal neuronal cell function?

Lots of energy and oxygen

What maintains intracellular osmolality in the brain?

Na/K ATP pump

What maintains extracellular fluid osmolality in the brain?

BBB

Serum/plasma osmolality

What is required for the production of thiamine in ruminants?

Healthy rumen microflora

What vitamin is thiamine?

Vitamin B1

What does thiamine do?

Co-factor for enzyme needed to make ATP

What is the MOA of thiamine deficiency?

Decreased thiamine causes decreased ATP

This leads to less activity of Na+/K+ pump and the accumulation of Na+ in the cell

H2O will follow Na and cause intraneuronal swelling

How does sulfur toxicity cause PEM?

Hydrogen sulfide gas impairs oxygen utilization affecting neuronal ATP production

What is the normal fate of hydrogen sulfide gas?

Detoxified

Eructated

Absorbed

What is the hallmark C/S of PEM?

Cortical blindless so, absent menace response and an intact PLR

What CN is affected with dorsomedial strabismus?

CN 4 or trochlear nerve

What are all the C/S of PEM?

Cortical blindness, dorsomedial strabismus, ataxia, tremor, seizure, opisthotonos, recumbency

When is lead toxicity most common?

Young stock recently placed on contaminated pasture

When is salt toxicity most common?

Secondary to a period of water deprivation followed by unrestricted water consumption

What are two other conditions that cause PEM?

Lead toxicity and salt toxicity

What is the pathophysiology of lead induced PEM?

1. Irreversible binds to RBCs

2. Other biological processes affected by Pb 

3. Deposition of lead into CNS

What happens when lead first enters the body?

Irreversible binds to RBCs causing shortened RBC half-life

Will also be deposited into tissues like bone, fat, milk, fetus

What biological processes are affected by lead?

Impairs heme synthesis, induces basophilic stippling, promotes microangiopathy 

What does the deposition of lead in the CNS cause?

Acute cerebral hemorrhage

Edema from capillary leakage

Cellular necrosis

Brain swelling

What are C/S in addition to cortical blindness with lead toxicity?

Hyperesthesia, muscular fasciculations, rapid spastic twitching of eyelids/facial muscles, ataxia, CP deficits, head pressing, odontoprisis, coma, convulsions, sudden death

What is the pathophysiology of salt toxicity?

1. ECF: increased Na and increased osmolality 

2. ICF: increased production of idiogenic osmoles

3. Brain cell swelling

4. Increased intracranial pressure

5. Occlusion of venous blood flow leading to brain hypoxia

6. Acute encephalopathy

What C/S are seen in addition to cortical blindness with acute salt toxicity?

Mucohemorrhage diarrhea and colic, aggressiveness, hyperexcitability, seizures, ataxia, CP deficits, constant chewing, nystagmus, sudden tdeath

What C/S are seen in addition to cortical blindness with chronic salt toxicity?

Depressed and dehydrated

How do you diagnose Pb toxicity?

Elevated blood Pb and PEM findings

How do you diagnose salt toxicity?

Serum Na >160nM or CSF Na >160nM with PEM

How do you treat PEM?

Provide thiamine (vitamin B1)

Control cerebral edema

Supportive care

Correct hypernatremia with fluids

Chelator

How do you control cerebral edema?

Mannitol 20%, DMSO, or hypertonic saline (best)

What chelator is used for PEM treatment/

EDTA

How do we treat a Pb toxicity?

Start with PEM treatment

Administer chelator (Ca EDTA) however some people say just euthanize so depends on state

How do you treat acute H2O deprivation?

Administer hypotonic IV fluid and offer water

How do we treat chronic H2O deprivation if serum Na >170?

Do no decrease serum Na below 150 for 2 or 3 days

Decrease Na 0.5 mmol/h

What are the C/S of hypovitaminosis A?

Neurologic problems like retinal degeneration, thickening of dura and damage to optic nerve

What is required for hypovitaminosis A to occur?

Chronic deficiency for over 180 days

What does blinding with no menace, or PLR point you to in ruminants?

Hypovitaminosis A

What is bacterial meningitis?

Inflammation of any one of 3 layers of meninges (dura, arachnoid, pia mater)

What most commonly get bacterial meningitis?

Neonates

What bacteria are the cause of bacterial meningitis?

Gram - enteric pathogen like E. coli, Salmonella, Klebsiella

How do you get bacterial meningitis?

Hematogenous spread or local extension

What are the C/S of bacterial meningitis?

Abnormal mentation, depression, anorexia, reluctance to move neck (cervical pain), seizures, hyperesthesia, opisthotonos, death, fever

How do you diagnose bacterial meningitis?

Antemortem CSF analysis showing neutrophilic pleocytosis, elevated protein, hypoglycemia, organisms visualized (rare)

Can culture as well (rare)

How do you treat bacterial mengitis?

Good spectrum antibiotics that penetrate BBB and are bactericidal but nothing that can do that is legal (can try 3rd gen cephalosporin but legal doses are not high enough, ampicillin or florfenicol are used)

Anti-inflammatories

Anti-edema

Fluids

What is the prognosis of bacterial meningitis?

Poor to grave

What are the proposed mechanisms for altered thiamine metabolism?

Ruminal production of thiaminases

Ingestion of pre-formed thiaminases

Producing or ingesting thiamine analogs

Decreased intake by pre-ruminants

Impaired absorption/metabolism by rumen bacteria

Increased fecal excretion of thiamine

Decreased production of thiamine by rumen microbes

What is the signalment of PEM for cattle?

3wk-8 years old

What is the signalment of PEM in sheep?

3wk - 5 years old

What is the signalment of PEM in goats?

2 months - 2.5 years old

What is the prognosis of sub acute PEM animals?

Improvement within 24 hours of treatment

What is the prognosis of most animals with PEM?

Can take 3-7 days for improvement or can remain blind for weeks to months

What animals with PEM have a poor prognosis?

Acutely affected

What are risk factors for PEM?

High grain diets

Low roughage

High sulfur

Thiamine analog consumption

Exposure to lead

Water deprivation

How do we diagnose PEM antemortem?

History and cortical blindness present

Response to therapy (responds to thiamine supplement)

Why do we give all animals with PEM signs thiamine?

We are not sure if thiamine or sulfur is the cause, so treat everything with those signs as if it is thiamine deficient

What is on biochem for PEM?

Elevated sodium if salt toxicity

What is on CSF for PEM?

Pleocytosis and mild protein elevations but not very good for diagnosis

What can toxicology tell you when diagnosis PEM?

Can tell you high sulfur contents

How do you definitively diagnose PEM post-mortem?

Flattening of gyri, yellow discoloration, autofluorescence

Laminar necrosis

What commonly gets lead toxicity?

Young stock recently placed on contaminated pasture

What does lead toxicity present as?

PEM

What does salt toxicity present as?

PEM

What is the process of salt toxicity?

Secondary to a period of water deprivation followed by unrestricted water consumption

How do you treat salt toxicity/water deprivation with a moderate hypernatremia?

Slow removal of Na from CNS and CSF with frequent small amounts of water

How do you treat salt toxicity/water deprivation with a SEVERE hypernatremia?

Adult cattle: Slightly hypertonic saline IV and oral electrolytes

Calves: 1 L hypertonic saline IV and milk PO

How can you address brain edema from salt toxicity/water deprivation?

Mannitol