PNS Flashcards
Which domestic species are more, and which less susceptible to botulism?
Dogs, cats, and pigs are the most resistant to botulism. In affected dogs, the type C neurotoxin is most commonly involved. Ruminants and horses are highly susceptible, and deaths are common. Cattle are most commonly affected by the type C and D neurotoxins and horses by types B and C.
Which domestic species are more, and which less susceptible to botulism?
Dogs, cats, and pigs are the most resistant to botulism. In affected dogs, the type C neurotoxin is most commonly involved. Ruminants and horses are highly susceptible, and deaths are common. Cattle are most commonly affected by the type C and D neurotoxins and horses by types B and C.
Three proposed methods of intoxication in botulism?
1) ingestion of a preformed neurotoxin in a feed source.
2) in young animals, especially foals, absorption of a neurotoxin that is produced within the gastrointestinal tract from spores that have been ingested from the environmental soil. This method is referred to as toxicoinfectious botulism.
3) circulation of toxin produced by organisms growing in the anaerobic environment of an infected wound. This is wound botulism.
What can be an exposure route for a individual dog with botulism?
dead birds (or other carcases)
Mechanism of action of the botulinum toxin?
at the neuromuscular junction the neurotoxin binds to receptors on the axon terminal. It translocates into the axon and interferes with the release of acetylcholine. Because this affects only neuromuscular junctions, all the clinical signs are limited to an LMN deficiency. No sensory system signs exist.
Clinical features to help distinguish botulism from polyradiculoneuritis?
Loss of external anal sphincter tone.
Megaesophagus.
Dysphagia.
Paresis of the facial, eyelid and tongue muscles.
CSF exam should be normal in botulism (and cytoalbuminergic diss in PRN)
Which breeds have a familial basis for acquired myasthenia gravis?
Newfoundland
great dane breeds
Which receptors are targets for acquired myasthenia gravis?
Nicotinic ACh receptors
(Once the antibody is bound to the acetylcholine receptor, the entire unit is internalized into the muscle and is no longer available; it must be replaced by the formation of a new receptor. )
Three forms of acquired myasthenia gravis?
(1) generalized,
(2) focal,
(3) fulminating.
Why do dogs develop megaoesophagus commonly in comparison to cats with myasthenia gravis?
the esophageal muscle in dogs is striated voluntary muscle innervated by GSE neurons, and these muscle cells have acetylcholine receptors identical to those in skeletal muscle. This is in contrast to cats, who have mostly smooth muscle in their esophagus.
Name 2 cat breeds with high incidence of acquired myasthenia gravis
Abyssinian
Somali
Name a cattle breed with congenital myashenia gravis
Brahman calves
What percentage of dogs and cats have thymoma associated MG?
5% dogs and 25% of cats
Neuro findings to differentiate fulminant MG from polyradiculoneuritis?
Megaoesophagus and regurg to be expected with MG as opposed to PRN.
Severe atonia and hypo-areflexia to be expected with PRN as opposed to MG.
CSF exam should be normal in botulism (and cytoalbuminergic diss in PRN)
How is the response to edrophonium test in fulminant MG
Usually no response (since all the ACh receptors are occupied and internalised)
Pathogenesis of tick paralysis?
Clinical signs may occur after having been bitten by a single female tick. The neurotoxin enters the circulation and gains access to the neuromuscular junctions, where the toxin interferes with the function of calcium in the release of acetylcholine from the axonal terminal.
Neuro signs in tick paralysis?
Clinical signs occur 5 to 9 days after the tick infestation, with a rapid onset of LMN paresis starting in the pelvic limbs and spreading to the thoracic limbs. Dogs may become recumbent in 24 to 72 hours. Spinal reflexes are depressed or absent. Nociception is normal, and hyperesthesia is absent. Cranial nerve LMN signs are uncommon except for severe cases. Megaesophagus is uncommon. Death may occur as the result of respiratory paralysis in 1 to 5 days if left untreated.
Name at least 3 infectious agents associated with polymyositis
- Toxoplasma gondii,
- Neospora caninum,
- Hepatozoon americanum,
- Leptospira icterohaemorrhagiae
Name 2 PNS disorders of dogs linked to hypothyroidism (De Lahunta)
myasthenia gravis
imune-mediated polymyositis
Which breed of dog is overrepresented with polymyositis and lymphoma?
Boxer dogs
In some dogs, polymyositis may precede the development of a neoplasm
Which findings support a dignosis of snake envenoment (postsynaptic blockade of the neuromuscular junction) causing acute LMN tetraplegia and areflexia?
Hemolysis and hemoglobinuria
Pain swelling and erythema of the skin from the cellulitis at the site of the bite wound may be observed.
Name 2 organophosphates which could cause a LMN tetraplegia due to blockage of the acetylcholine receptor?
Chlorpyrifos and fenthion
Which drugs can be used to treat organophosphate toxicity?
atropine for the muscarinic signs
pralidoxime chloride for the nicotinic signs;
in some toxicities, diphenhydramine may help block the action of the toxin.
DDs for a generalised, fast progressing LMN tetraparesis
PRN
MG
Tick paralysis
Botulism
Polymyositis
Hypokalaemic myopathy
Organophosphate intox.
(snake envenoment)
Why do cats develop prominent dorsal displacement/protrusion of the scapula when the thoracic limb bears weight when walking in LMN disease?
presumably secondary to weakness of the serratus ventralis muscle
Spinal reflexes and postural reactions are normal or abnormal in animals with Hypokalaemic myopathy
usually normal
Which breed of cat has a recognised inherited hypokalemic myopathy?
Which gene has been implicated?
Burmese
WNK4 gene/chromosome E1
Feline hypokalemic periodic paralysis or Burmese hypokalemic periodic polymyopathy: most often with onset in 2- to 6-month-old Burmese kittens. Affected cats exhibit episodes of muscle paresis that may be diffuse, causing a crouched, short-strided gait, or localized to the cervical and proximal thoracic limb muscles.
Which drug can cause Hypokalemic myopathy in cattle?
mineralocorticoid drug isoflupredone (9-fluoroprednisolone acetate) for the treatment of ketosis or clostridial mastitis.
Name two inherited muscle disorders of labrador retrievers
1) Centronuclear (Type II Deficiency) Autosomal Recessive Polymyopathy (more common)
2) Dystrophinopathy, a Sex-Linked Recessive Muscular Dystrophy
What is a classical clinical sign of centronuclear Labrador polymyopathy?
The depressed or absent patellar reflex is a common clinical sign and may reflect involvement of the small striated intrafusal muscle cells in neuromuscular spindles that form the sensory component of the patellar reflex.
What is the prognosis of centronuclear Labrador polymyopathy?
This centronuclear Labrador retriever polymyopathy has a good prognosis for life because it is self-limiting. It rarely progresses beyond more than 9 or 10 months and rarely causes recumbency.
Neurological signs with dystrophinopathy?
The clinical signs vary considerably among affected dog breeds, according to the nature of the spontaneous mutation. In addition to the abnormal posture and gait (short-strided gait in all four limbs, the arched back, and the lowered head and neck position), a very early clinical sign is the decrease in range of mouth opening associated with prehension difficulties and sialosis. As the disease progresses, the tongue and pharyngeal muscles begin to feel enlarged between the mandibles. Although diffuse atrophy of most axial and appendicular muscles occurs, some of the caudal thigh muscles hypertrophy along with the diaphragm.
Ancillary tests to help differentiate centronuclear polymyopathy from dystrophinopathy?
marked elevation of serum muscle enzyme levels in dystrophinopathy (muscle fiber necrosis is usually severe, which results in the marked elevation of the serum enzymes CK, AST, and ALT)
What is the prognosis in dystrophinopathies?
It may be lethal in young puppies. Severely affected dogs have limited life spans and often develop complications associated with their cardiomyopathy.
Typical age of onset and breeds for exercise induced collapse (EIC)
Young adult (7 MO-2 Y)
Labrador Retriever +
Boykin Spaniel, Chesapeake Bay Retriever, Clumber Spaniel, Curly Coated Retriever, German Wire-haired Pointing Dog, , Old English Sheepdog, Pembroke Welsh Corgi
Clinical signs of EIC
collapse
hyperthermia (up to 42,5 C)
When the dog has collapsed, the pelvic limbs are flaccid and patellar reflexes are usually absent, but the withdrawal reflexes and nociception are normal. Dogs commonly get worse in the 3 to 5 minutes after exercise is halted, perhaps related to a progressive increase in their body temperature, and severe episodes of collapse sometimes progress to involve all four limbs.
After a period of 10 to 20 minutes of rest, these dogs recover completely.
Gene mutation for EIC?
DNM1 (Dynamin-1)
Dynamin-1 (DNM1) is a protein that plays a key role in repackaging neurotransmitters into synaptic vesicles for release in the brain and spinal cord. DNM1 is not required for neurotransmission during low-level neurologic stimulation, but when a heightened stimulus such as intense exercise, excitement, or hyperthermia creates an increased demand for release of CNS neurotransmitters, DNM1 becomes essential for sustained synaptic transmission
Treatment and prognosis of EIC?
No specific treatment is available for d-EIC, but the disorder is not progressive. Affected dogs generally lead healthy lives as long as their participation in activities that trigger collapse is limited. Several dogs have died during severe episodes of collapse, so exercise should be stopped and attempts made to cool the affected dogs at the first hint of an abnormal gait.
It has been observed that affected dogs are less likely to collapse when they are exercised in water or in cold weather.
DDs for exercise-induced fatigue in dogs
(1) dogs that are normal on examination and
(2) those that are abnormal.
1:
cataplexy, syncope, focal seizure, movement disorder, or a nonneurological disorder (i.e., cardiac dysfunction)
myasthenia gravis, hypoglycemia, hyperkalemia, hypokalemia, muscular dystrophy, and, in Labrador retrievers, EIC
2:
myasthenia gravis, polymyopathy, muscular dystrophy, polymyositis, hypoglycemia, hyperkalemia, and hypokalemia.
Pathogenesis of congenital motor neuron disease (spinal muscular atrophy)?
abiotrophy of GSE neurons in the spinal cord ventral gray horn and brainstem nuclei.
(Neuronal abiotrophy most commonly affects Purkinje neurons in the cerebellum and GSE neurons in the spinal cord and brainstem. Often, multiple neuronal systems are affected. Clinical signs usually reflect the loss of those neurons most important for the animal’s ability to support weight and to generate a coordinated gait)
Breeds with canine and feline congenital motor neuron disease (hereditary spinal muscular atrophy)?
What about bovine?
Dogs:
Spinal muscular atrophy - Brittany Spaniels
Focal spinal muscular atrophy - German Shepherds
Motor neuron disease - Rottweilers
Multisystem chromatolytic neuronal degeneration - Cairn Terrier
Multisystem neuronal abiotrophy - Swedish Lapland dogs
Cats:
spinal muscular atrophy - Maine Coon
Bovine:
Bovine spinal muscular atrophy (BSMA) - Brown Swiss cattle, Holstein, Friesian, and Red Danish breed - genetic mutation of the FVT1 gene
Blonde d’Aquitaine calves (not associated with FVT1 mutation)
3 forms of ongenital motor neuron disease (hereditary spinal muscular atrophy) in Brittany spaniel?
The puppies that are homozygous for the dominant gene have an accelerated form that results in clinical signs by 6 to 8 weeks of age with tetraparesis, difficult prehension, and dysphagia. By 3 to 4 months of age, the tetraparesis may progress to tetraplegia, along with severe neurogenic atrophy and associated limb deformities.
Two phenotypes are seen in the heterozygote dogs.
The intermediate form shows clinical signs of LMN tetraparesis at 6 to 12 months of age, and it slowly progresses to the inability to walk by 2 to 3 years of age.
The chronic form consists of a subtle paresis that is not observed until a few years of age and is accompanied by mild neurogenic atrophy.
What causes Equine motor neuron disease (EMND)
acquired disorder of adult horses that is strongly associated with an inadequate amount of vitamin E in the diet
Which receptors can be targeted in canine MG?
AChR
MUSK (muscle specific kinase)
(Cats no musk ab reported)
Proposed current classification of MG in dogs/cats
A photomicgrograph of a retina of a hors with weakness while standing is shown. What is shown in the image and what is the most likely DD?
EMND
Retina of a horse with equine motor neuron disease showing a mild excessive accumulation of lipofuscin in the pigment epithelium of the retina and in the space between that layer and the photosensitive layer.
Most likely diagnosis?
5 YO Dachshund, non tetraplegia which started as pelvic limb weakness 3 days prior.
Dorsal view of the entire spinal cord of a 4-year-old dachshund with ascending-descending myelomalacia.
Which disease could cause a skipping type gait and with a posture evident in the image (lexed posture of the tarsus and the severe atrophy of the caudal crural muscles)
Dancing doberman disease
(Inherited neuropathy/myopathy of Doberman Pinschers)
Which disease could cause a skipping type gait and this posture in a Leonberger?
Leonberger inherited neuropathy (distal polyneuropathy)
Which disease could cause a posture like this in this breed? (Tibetan mastiff)
hypertrophic neuropathy affecting the tibial nerves.
DDs for this posture?
An 8-year-old doberman pinscher with an overflexed left tarsus caused by rupture of the tendon of insertion of the gastrocnemius muscle at the calcaneus. Note the flexion of the digits from the stress placed on the intact superficial digital flexor tendon.
What causes this type of gait in horses?
Stringhalt
a hyperactivity of flexors of hips, stifle, tarsus, and digit aided by the reciprocal apparatus. It involves a disorder of the central pattern generators of spinal cord segments L4 through S2, their roots, spinal nerves, spinal ganglia, femoral, sciatic, fibular, and tibial nerves.
Aetiology of “stiff lamb syndrome”?
The most common muscle disorder in young ruminants and foals is the myopathy and rhabdomyolysis associated with vitamin E and selenium deficiency.
Which nucleus houses the GSE bodies of the CN III?
motor nucleus of the oculomotor nerve in the rostral mesencephalon at the level of the rostral colliculi.
The nucleus is adjacent to the midline within the ventral portion of the central grey substance that surrounds the mesencephalic aqueduct. This nucleus is rostral to the motor nucleus of the trochlear nerve and caudal to the parasympathetic nucleus of the oculomotor nerve.
Where are the GSE cell bodies of the CN IV located?
motor nucleus of the trochlear nerve is adjacent to the midline in the ventral portion of the central gray substance that surrounds the mesencephalic aqueduct at the level of the caudal colliculi.
It is caudal to the larger motor nucleus of the oculomotor nerve.
Where are the GSE cell bodies of the CN VI located?
Motor nucleus of the abducent nerve in the rostral medulla.
This is a small nucleus at the level of the medulla where the caudal cerebellar peduncle merges with the cerebellum. It is adjacent to the midline and floor of the fourth ventricle.
Which diseases most commonly cause CN IV dysfunction in cats and which in horses/cattle? What about dogs?
Cats: vertical pupils -> lateral deviation of the pupils.
Otitis media-interna.
Cattle/horses: horisontal pupils, dorsomedial strabismus.
Polioencephalomalacia (thiamin deficiency).
Dogs: round pupils so the rotation of the eyeball can not be appreciated except with a fundic exam.
Dysfunction of which CN is shown in the image?
Trochlear nerve CN IV
What is the cavernous sinus syndrome?
Also called the middle cranial fossa syndrome. Clinical signs of neoplasms or other disease processes that cause a mass effect located here that affect cranial nerves III, IV, and VI and the ophthalmic and maxillary nerves from cranial nerve V
Which nucleus houses the cell bodies of the GSE CN V?
Motor nucleus of CN V (pons)
This nucleus is found at the level of the middle and rostral cerebellar peduncles, just rostral to where all three cerebellar peduncles merge with the cerebellum.
Name on disease of ruminants one for horses which causes encephalitis that involves the motor nuclei of the trigeminal nerve bilaterally causes paresis or paralysis of the muscles of mastication that results in an open mouth that cannot be closed to prehend food
Listeria monocytogenes in ruminants
Sarcocystis neurona in horses
Dysfunction of which nerve is shown here?
complete R CN VII (ear, nose)
Dysfunction of which nerve is shown here?
R buccal branches of CN VII
paralysis limited to the right nose and lip muscles caused by compression of the buccal branches of the facial nerve at the ramus of the mandible after prolonged lateral recumbency for surgery
