Lecture 5: Toxic and Nutritional Neuropathies Flashcards
What does malacia mean
Necrosis
What does polioencephalomalacia mean
Necrosis of the gray matter within the brain
What does poliomyelomalacia
Necrosis of the gray matter of the spinal cord
What is leukoencephalomalacia
Necrosis of the white matter of the brain
What is leukomyelomalacia
Necrosis of the white matter of the spinal cord
Describe what you are seeing and what caused this
loss of vacuolation of tissue with minimal inflammation
Macrophages (gitter cells) influx to clean up necrotic neuroparenchyma
Malacia
What diseases are associated with Multifocal, bilaterally symmetric malacia
- Yellow star thistle
- Clostridium perfringes type D
What diseases are associated with laminar malacia
- Poliencephalomalacia
- Leukoencephalomalacia
What species typically gets nigropallidal encephalomalacia
Horses
What causes nigropallidal encephalomalacia
Yellow star thistle
What is the pathogenesis for nigropallidal encephalomalacia
- Prolonged ingestion of yellow star thistle
- Repin neurotoxin
- Oxidative damage
- Neuronal cell death
What are the gross findings associated with nigropallidal encephalomalacia
Bilaterally symmetric malacia of globus pallidus and substantia nigra
White and gray matter affected
Horse brain- what wrong and cause
Nigropallidal encephalomalacia caused by yellow star thistle toxicosis
What species typically get C. Perfringes type D epsilon toxicosis
Small ruminants
What is pathogensis of C. Perfringens type D Epislon toxicosis
- Excess grains
- Promotes C. Perfringes type D overgrowth in the intestine
- Epislon toxin permeates into circulation
- Endothelial damage and increased vascular permeability
- Brain edema
Histology from sheep brain who recently ate an entire bag of grain. What does histo show and what is cause
histo: brain edema
C. Perfringes Type D epsilon toxicosis
What are the gross findings associated with C. Perfringes type D epsilon toxicosis
Bilaterally symmetric malacia of basal ganglia and brainstem
White and gray matter affected
Goat brain- what wrong and what cause
Encephalomalacia of basal ganglia caused by C. Perfringes type D epsilon toxicosis
What are some causes of polioencephalomalacia
Thiamine deficiency, salt toxicity, sulfur toxicity, lead toxicity, severe hypoglycemia, anoxia/hypoxia
How do areas with polioencephalomalacia appear
Gray matter is yellow-tan glistening layer that fluoresces under UV light
Cerebral edema which presents as flattening of gyri
What does polioencephalomalacia histology look like
Necrosis of cortical neurons
What happening in histo and what wrong
Cortical neuron necrosis
Cause: polioencephalomalacia
What wrong
polioencephalomalacia- flattening of gyri
How does thiamine deficiency cause polioencephalomalacia
Thiamine is produced by bacteria in the rumen and decreased when you ingest thiaminases like bracken fern or thiamine analogs
Decreased production by rumen microbes typically associated with increased grain intake
What species is thiamine deficiency most common in
Ruminants- cattle, goats, sheep
How does sulfur toxicosis cause polioencephalomalacia
- Excess sulfur in food or water
- Rumen microbes produce too much hydrogen sulfide which is absorbed into circulation
- Interferes with energy production
- Neurons need a lot of energy and lack of leads to cortical neuronal necrosis
How does lead toxicity lead to polioencephalomalacia
- Lead enters circulation
- Mimicking Ca2+ it is able to cross BBB and enter neurons
- Oxidative stress
- Neuronal necrosis
What species is typically affected by salt toxicity
Swine
How does salt toxicity lead to polioencephalomalacia
- Decrease water
- Dehydration
- Na+ retention
- Accumulation Na+ in CSF
- Rapid water intake
- Rapid water influx into brain- edema—> cortical necrosis (water follows salt)
What histological presentation is classic with salt toxicity in pigs
Eosinophilic inflammation
Owner notices water troughs for pigs have been frozen over for days, he breaks it open and suddenly a lot of bigs die. The following histo was taken from the brain- what does it show and what caused this
histo: eosinophilic inflammation
Cause: salt toxicity leading to polioencephalomalacia
How does hypoglycemia cause polioencephalomalacia
Brain needs high levels of glucose, so when low glucose—> lack ATP production—> cell death
What are some causes of severe hypoglycemia
- Malnutrition/ anorexia
- Xylitol toxicity
- Excess insulin
- Juvenile hypoglycemia
Moldy corn ingestion causes ___ in ___
Leukoencephalomalacia in horses
What is pathogenesis of moldy corn ingestion causing leukoencephalomalacia in horses
- Prolonged ingestion of moldy corn with fumonosin spp
- Produces fumoisin B1
- Inhibits normal lipid synthesis in the brain leading to accumulation of sphingosine (toxic to white matter)
- Leukoencephalomalacia
Horse ate lots of corn- then died, what happened
Moldy corn ingestion causing leukoencephalomalacia
How are lysosomal storage neuropathies induced
Ingested plant toxins that inhibit lysosomal enzymes
What does induced lysosomal storage neuropathies lead to
Abnormal accumulation of materials within neurons which disrupts their function
Describe histo and what wrong
Abnormal neuron with vacuolated cytoplasm
Cause: lysosomal storage neuropathies
What is an example of a disease that causes induced lysosomal storage neuropathy in horses
Locoweed (swainsonine) toxicosis
How does locoweed toxicosis cause lysosomal storage neuropathy
Prolonged ingestion of swainsonine inhibits lysosomal enzymes
Copper deficiency is common in what species
Young, small ruminants
Vitamin E deficiencies are common in what species
Horses
What is the purpose of vitamin E and copper and what does deficiency affect brain
Protect from oxidative stress, without increase oxidative stress-> neuronal cell death
What does neonatal copper deficiency cause
Progressive central neurological signs with ascending hind limb paralysis
What is the most common cause of neonatal copper deficiency
Secondary- reduced intestinal absorption due to other GI pathology or availability due to ingestion of copper antagonists
What are some copper antagonists
Molybdenum, sulfate, iron, calcium
Goat presents with ascending hindlimb paralysis. What nutritional deficiency can cause this
copper deficiency
___is the primary source of vitamin E in equine diets
Green gas’s
What two diseases can vitamin E deficiency cause in horses
- Equine degenerative myeloencephalopathy
- Equine motor neuron disease
Vitamin E deficiencies inn horses can cause lesions in ___ and ___
Brain and spinal cord
What is one of the top causes of spinal ataxia in young horses
Equine degenerative myeloencephalopathy due to vitamin E deficiency
What horses get EDM
Young horses 6-24 months
What breeds might have genetic disposition to EDM
Morgans, appaloosas, Lusitanos
How do horses with EDM present
Symmetrical ataxia
T or F: EDM horses have gross CNS lesions
False
Who is affected by equine motor neuron disease
Adult horse >2yrs because requires prolonged deficiency
What happens in equine motor neuron disease
Lower motor neurons targeted which are nerves that innervate muscles—> denervation atrophy
What muscles are most commonly affected by equine motor neuron disease
Triceps brachii and vastus lateralis
