Large Animal Neurologic Diseases

Three large animal neuro diseases:

1.) Listeriosis

1.) Polioencephalomalacia (PEM)

3.) Parelaphostrongylus tenuis

Listeriosis

Bacterial disease caused by Listeria monocytogenes that commonly produces brainstem dysfunction

Listeria monocytogenes

causative agent of Listeria; gram positive bacteria that is zoonotic!

Primary neurologic location affected by listeriosis

Brainstem, particularly the caudal brainstem

Three major animal species affected by listeriosis

1) Sheep

2) Goats

3) Cattle

Which are more commonly affected by listeriosis, small ruminants or cattle?

Small ruminants

Three important environmental reservoirs of Listeria

1) Soil

2) Animal feces

3) Intestinal tracts of humans and animals

Four major risk factors for listeriosis

1) Poorly fermented or spoiled silage

2) Cold, wet weather

3) Housing or confinement

4) Environmental contamination

There are many forms of listeriosis, including...

1) Encephalitic

2) Ocular

3) Septicemic

4) Reproductive

5) Mastitis

6) Gastrointestinal

What can the ocular form of listeriosis cause?

Keratoconjunctivitis or uveitis, also called silage eye

Septicemic listeriosis

Systemic Listeria infection that is especially important in young animals and may cause rapid death

What can the reproductive form of listeriosis cause?

Late-term abortion

What can the GI form of listeriosis cause?

diarrhea

Most common form of listeriosis

Encephalitic listeriosis

Encephalitic listeriosis

Infection involving the CNS, particularly the brainstem

Listeriosis is considered a _________ disease. Why?

localizing; It commonly produces unilateral cranial nerve deficits that help identify the affected side of the brainstem

Lesions of listeriosis are often ___________ and involve _________ nerves

asymmetric; cranial

Primary proposed route by which Listeria enters the brainstem

Ascension through the trigeminal nerve following entry through oral tissues

Pathogenesis of Listeriosis (6)

1.) animal consumes contaminated feed or encounters the organism in its environment

2.) Listeria enters through small injuries in the oral cavity, oropharynx, or dental tissues

3.) The organism gains access to branches of the trigeminal nerve (CN V)

4.) It ascends the trigeminal nerve toward the brainstem

5.) The infection reaches the trigeminal nucleus and can spread into surrounding brainstem tissues

6.) Inflammation and tissue damage produce cranial nerve and other neurologic deficits

Listeria infection generally begins _______, explaining why clinical signs are often asymmetric

unilaterally

Seven important clinical findings associated with listeriosis

1) Cranial nerve deficits

2) Head tilt

3) Ear droop

4) Facial deviation

5) Exposure keratitis

6) Dysphagia and drooling

7) Metabolic acidosis

Three abnormal movement or postural signs associated with listeriosis

1) Compulsive circling

2) Head pressing

3) Leaning or falling

Which cranial nerves are commonly affected by encephalitic listeriosis?

CN V-XII

CN V deficits associated with listeriosis

Jaw drop, decreased jaw tone, difficulty eating, and decreased facial sensation

CN VI deficit associated with listeriosis

Medial strabismus on the affected side

strabismus

crossed eyes

CN VII deficits associated with listeriosis

Ear droop, ptosis, decreased lip tone, facial asymmetry, and impaired blinking, exposure keratitis

Why can CN VII dysfunction cause exposure keratitis?

Paralysis of orbicularis oculi prevents normal eyelid closure, leaving the cornea exposed to damage

Direction of nasal philtrum deviation with unilateral CN VII dysfunction

Away from the affected side

CN VIII deficits associated with listeriosis

-Head tilt toward the affected side

-Nystagmus

-Leaning, rolling, or falling toward the lesion

-Circling

-Abnormal eye position

CN IX-XII deficits associated with listeriosis

-Dysphagia

-Hypersalivation

-Abnormal swallowing

-Stertorous breathing

-Tongue paresis or paralysis

-Accumulation of feed in the mouth

Four major consequences of impaired swallowing in listeriosis

1) Inadequate water intake

2) Salivary loss

3) Dehydration

4) Metabolic acidosis

Why does listeriosis cause dehydration?

The animal cannot adequately drink or swallow saliva, resulting in fluid deficits

Why can excessive salivary loss cause metabolic acidosis?

Loss of bicarbonate-rich saliva contributes to systemic bicarbonate depletion

Three major components of diagnosing listeriosis:

1) History

2) Characteristic neurologic signs

3) CSF analysis

Three important historical findings supporting listeriosis:

1) Silage consumption

2) Seasonal exposure

3) Relevant housing or management conditions

Characteristic neurologic pattern of listeriosis

Asymmetric brainstem dysfunction with unilateral cranial nerve deficits

Three characteristic CSF findings in listeriosis:

1) Increased protein

2) Increased nucleated cells

3) Predominantly mononuclear inflammation

What CSF cell type may predominate in young small ruminants with listeriosis?

Neutrophils

Why are CBC and chemistry profiles useful in listeriosis?

They help assess dehydration and acid-base disturbances but are not diagnostic for Listeria

How can refrigeration assist with postmortem diagnosis of listeriosis?

Refrigeration of nervous tissue at 4°C can enrich Listeria organisms

Two important methods of definitive Listeria postmortem diagnosis:

1) Gross and histologic examination

2) Listeria-specific immunohistochemistry

Polioencephalomalacia (PEM)

Neurologic disorder characterized by softening and necrosis of cerebral cortical gray matter

Primary neurologic location affected by Polioencephalomalacia

Gray matter of the.cerebral cortex

Are neurologic signs of Polioencephalomalacia symmetric or asymmetric?

symmetric

Unlike listeriosis, PEM is not caused by a single _______. How?

agent; multiple metabolic, nutritional, and toxic disturbances can produce the condition

Four major consequences of impaired cerebral metabolism in Polioencephalomalacia

1) Cerebral edema

2) Increased intracranial pressure

3) Neuronal dysfunction

4) Cortical necrosis

Why is the brain particularly vulnerable to swelling?

The rigid skull limits the amount of space available for brain expansion

What cellular pump is important for maintaining fluid balance in the brain?

Na⁺/K⁺-ATPase

Since the Na⁺/K⁺ is fueled through ATP, what effects can ATP depletion have on the brain?

Impaired ion regulation that allows intracellular sodium and water accumulation --> neuronal injury

Thiamine

Vitamin B1, an essential cofactor involved in cellular energy metabolism

Thiamine important for normal cerebral _________. Why?

function; it supports metabolic pathways required for normal cellular energy metabolism

Where do ruminants get their thiamine?

Rumen microorganisms

How can thiamine deficiency contribute to Polioencephalomalacia?

Impaired energy metabolism can disrupt cellular ion regulation, contributing to swelling and neuronal injury

Seven major causes of Polioencephalomalacia

1) Thiamine deficiency

2) Thiaminases

3) Grain engorgement and rumen acidosis

4) Amprolium

5) Sulfur intoxication

6) Salt poisoning/water intoxication

7) Lead toxicity

thiaminases

enzymes that destroy thiamin

Three plants associated with thiaminases

1) Bracken fern

2) Horsetail

3) Nardoo fern

How can grain engorgement contribute to Polioencephalomalacia?

Rumen acidosis alters microbial populations, potentially decreasing thiamine synthesis and increasing degradation

Amprolium

Thiamine analogue used to prevent and treat coccidiosis

How can amprolium contribute to Polioencephalomalacia?

It interferes with normal thiamine utilization

How can sulfur intoxication contribute to Polioencephalomalacia?

Excess sulfur exposure can interfere with normal cellular metabolism and cause cerebral injury

What gas may be produced from excess sulfur compounds in the rumen?

Hydrogen sulfide

How can salt poisoning or water intoxication cause cerebral dysfunction?

Changes in sodium concentration and osmolality alter fluid movement within the brain

How can lead toxicity contribute to Polioencephalomalacia-like disease?

Lead can cause cerebral dysfunction and swelling

Why might thiamine administration fail to resolve Polioencephalomalacia?

The underlying cause may be unrelated to thiamine deficiency or irreversible cerebral injury may already be present

Three general categories of Polioencephalomalacia clinical signs

1) Early signs

2) Progressive signs

3) Severe signs

Five early clinical signs of Polioencephalomalacia

1) Separation from herd

2) Depression

3) Anorexia

4) Hypersensitivity to touch

5) Incoordination

Seven progressive clinical signs of Polioencephalomalacia

1) Cortical blindness

2) Head pressing

3) Stargazing

4) Tremors

5) Ear twitching

6) Nystagmus

7) Papilledema

stargazing

Abnormal upward positioning of the head and neck

Four severe clinical signs of Polioencephalomalacia

1) Opisthotonus

2) Seizures

3) Extensor rigidity

4) Lateral recumbency

opisthotonus

Severe extension of the head and neck

What is a particularly important clinical sign of Polioencephalomalacia?

Cortical blindness!

Cortical blindness

Loss of vision caused by cerebral cortical dysfunction rather than primary ocular disease

What happens to the menace response with cortical blindness?

What about PLR?

Menace response: absent

PLR: intact

Why can an animal with cortical blindness have an intact PLR?

The PLR uses a subcortical pathway that does not require visual processing by the cerebral cortex

Four major components of Polioencephalomalacia diagnosis:

1) Clinical signs and history

2) Response to thiamine

3) CSF analysis

4) Investigation of underlying causes

Characteristic neurologic pattern of Polioencephalomalacia

Bilaterally symmetric cerebral dysfunction, particularly cortical blindness and abnormal mentation

Why is thiamine often administered empirically when Polioencephalomalacia is suspected?

Early treatment may improve thiamine-responsive disease and support the clinical suspicion

Typical CSF findings in Polioencephalomalacia

Normal cell count and cellular morphology

Why is CSF analysis useful in suspected Polioencephalomalacia?

It helps exclude inflammatory or infectious conditions such as listeriosis and bacterial meningitis

Three important laboratory measurements when investigating Polioencephalomalacia

1) Rumen gas sulfur

2) Blood lead

3) Blood sodium

What odor may raise suspicion for excessive hydrogen sulfide in rumen gas?

Rotten eggs

Four characteristic postmortem findings in Polioencephalomalacia:

1) Cortical gray matter necrosis

2) Cerebral softening

3) Flattened cerebral gyri

4) Cerebral swelling

What type of brain tissue undergoes necrosis in Polioencephalomalacia?

Cerebral cortical gray matter

How may necrotic cerebral tissue appear under UV light?

Characteristic fluorescence

Parelaphostrongylus tenuis

aka brain worm; parasitic nematode that can cause severe neurologic disease through abnormal migration within the CNS

Definitive host of P tenuis

White-tailed deer

Intermediate hosts of P tenuis

Snails and slugs

Five aberrant hosts of P tenuis

1) Alpacas

2) Llamas

3) Sheep

4) Goats

5) Cattle

Aberrant host

Host in which a parasite cannot successfully complete its normal life cycle

Primary neurologic location affected by P tenuis in aberrant hosts

Spinal cord

Four major stages of the P tenuis life cycle:

1) Adult worms in deer

2) Larval shedding in feces

3) Development in snail or slug

4) Infection of susceptible hosts

Stages of P tenuis life cycle:

1.) adult worm develops in the subarachnoid space in the bae of deer skulls

2.) Females produce eggs that hatch into larvae

3.) larvae travel to the respiratory tract, are coughed up, swallowed, then passed through feces (gross!)

4.) Once in the environment, larvae are taken up by snails and slugs where they develop

5.) Susceptible livestock become infected through ingestion of of infective larvae associated with snails or slugs

Infective stage of P tenuis

L3 larvae

Five steps in the pathogenesis of P tenuis in aberrant hosts

1) L3 ingestion

2) Entry into GI tract

3) Abnormal migration

4) CNS invasion

5) Inflammation and neurologic injury

Why does P tenuis cause neurologic disease in aberrant hosts?

Abnormal larval migration produces inflammation and direct damage to nervous tissue

What portion of the spinal cord is particularly important in P tenuis disease?

Caudal lumbar spinal cord

Approximate time between P tenuis infection and development of clinical signs

4-8 weeks

Three general categories of P tenuis clinical signs:

1) Mild to moderate gait abnormalities

2) Progressive weakness

3) Severe neurologic dysfunction

Six common clinical signs of P tenuis

1) Wide-based pelvic limb stance

2) Short, stilted gait

3) Foot dragging

4) Ataxia

5) Pelvic limb weakness

6) Difficulty walking backwards