Download Stephanie Thomovsky, DVM, MS, DACVIM (Neurolo

IVMA 2017
Caudal Cervical Spondylomyelopathy – did that Great Dane just wobble?!
Stephanie Thomovsky, DVM, MS, DACVIM (Neurology), CCRP
Clinical Assistant Professor of Neurology and Neurosurgery at Purdue University
Director of Physical Rehabilitation at Purdue
Caudal Cervical Spondylomyelopathy – Wobbler Disease
I.
Caudal cervical spondylomyelopathy (CCSM)
A.
Aka Wobbler’s Disease, acquired vertebral malformation/malarticulation.
B.
This disease is relatively common; it is definitely one you will diagnose regularly in private
practice.
C.
The equine also suffers from Wobbler’s Disease. The equine version of the disease is
referred to as cervical stenotic myelopathy. This condition shares many similarities with the
canine form but there are also some differences.
D.
Patients with CCSM have a C6-T2 spinal cord neurolocalization, the vast majority of the
time. They therefore have a proprioceptive ataxia in all four limbs, reflex deficits in the thoracic
limbs and normal to hyper-reflexive pelvic limb reflexes.
1.
C6-T2 SC neurolocalization review
a)
All 4 limbs are neurologically abnormal. The pelvic limbs being often
more affected neurologically as compared to the thoracic limbs.
(1)
Tetraparesis
(a)
Paresis is often a term reserved to describe weakness in
an animal secondary to neurologic disease.
(b)
By definition it means a partial loss of voluntary
movement. The patient often has difficulty supporting weight
against gravity
(2)
Ataxia literally means “off axis.” This is a strictly neurologic term,
i.e. if you say that an animal is ataxic you are in effect saying that you
think it has an abnormality within the nervous system.
(a)
There are three main forms of ataxia (vestibular,
cerebellar and proprioceptive
(b)
Spinal ataxia is a type of proprioceptive ataxia. The term
spinal ataxia is reserved for cases with a proprioceptive ataxia
secondary to spinal cord disease.
(i)
Dragging or scuffing of limbs – these patients
traditionally drag their feet and scuff the tops of them.
They often have nail or hoof wear.
(ii)
There are two types of proprioceptive ataxia:
upper motor neuron (UMN) and lower motor neuron
(LMN). Clinically an UMN ataxia is far more
common/more obvious. LMN ataxia can also be
observed but usually is not as obvious.
(a)
UMN – long, loping stride. They look
like they are over-reaching with each step.
These patients look, to me, like ice skaters.
(b)
LMN – short, choppy stride. The LMN
that innervate the limbs are not functioning
appropriately, as a result, you end up with a
short stride as normal limb flexion and extension
is altered.
(c)
Two-engine gait is a type of
proprioceptive ataxia. Clinically this type of
ataxia is most commonly observed in CCSM
patients. This gait occurs in patients with an
UMN gait in the pelvic limbs (long and lopey)
while a LMN gait in the thoracic limbs (short and
choppy)
E.
There are 2 forms of this disease (refer to chart below)
1.
Young dog (Stenotic form)
a)
2.
This form is most common in the young adult Mastiff and Great Dane
Old dog (DJD)
a)
Most commonly affects adult black and tan dogs.
b)
Disc associated Wobblers is a type of old dog CCSM. This disease is
most common in the Doberman Pinscher. It is the descriptive term utilized for
CCSM in which a major component of compression is a protruding, type II disc.
3.
The diagnosis of CCSM is made via CT/myelogram or more commonly MRI.
Dynamic views are sometimes made. In the case of myelography this means taking
radiographs while the head and neck are flexed, extended and distracted. Dynamic MR
vies usually mean sagittal images taken in neutral, flexion and distraction.
a)
Dynamic views are performed to help aid in surgical planning.
b)
Compression of the spinal cord is observed (see chart below) on
imaging.
4.
Treatment options
a)
Medical management
(1)
Cage rest with controlled leash walks for 6-8 weeks to allow
inflammation to decrease.
(2)
Pain medications are prescribed if spinal hyperesthesia is a
component of the neurologic exam.
(3)
Steroids can be effective in these patients to both decrease
inflammation.
b)
Surgical management
(1)
Many surgical options exist. Options include: ventral slot, spinal
stabilization with implants, distraction with PMMA plug or artificial disc
implantation, dorsal laminectomy, hemilaminectomy or a combination of
any of the above procedures.
(2)
Surgical planning is based on imaging findings.
Type of CCSM
Breed
Young Form
Great Dane, Mastiff
(< 1 yr or just about 1 yr old at
presentation)
Old Form
Doberman, Rottweiler (middle-aged at
presentation)
Onset
• Acute onset
• Acute on chronic
• Chronic progressive
• Acute on chronic
Pathophysiology
• Osteochondrosis of caudal Cspine facet joints 
malarticulation/malformation
• Stenosis of vertebral canal
caudal to C2
• Osteochondrosis of caudal C-spine
facet joints 
malarticulation/malformation
• DJD in of caudal C-spine facet joints
• IVDD type II caudal C-spine
• Proliferation
•
Facet joint capsule+/-synovial
cyst
•
Ligamentum flavum
•
Dorsal longitudinal ligament
Diagnosis
•
•
•
•
•
•
•
•
•
Bulbous articular facets on
radiographs
MRI
Myelography
CT
All imaging +/- dynamic views
Treatment
Controversial: conservative vs. surgery
Miscellaneous
May be associated with high energy
MRI
Myelography
CT
All imaging +/- dynamic views
Controversial: conservative vs. surgery
2+
levels and high Ca levels in feed.
References
A Practical Guide to Canine and Feline Neurology. Curtis Dewey, 2
nd
ed., 2008
Small Animal Spinal Disorders Diagnosis and Surgery. Nicholas Sharp and Simon Wheeler, 2
nd
ed. 2005.
Veterinary Clinics of North America Small Animal Practice: Spinal Disease. Ronaldo da Costa, 20 (5);
2010.
rd
Veterinary Neuroanatomy and Clinical Neurology. Alexander de Lahunta and Eric Glass, 3 ed., 2009.
IVMA 2017
Cerebrovascular accidents in dogs – not always a stroke in the wrong direction!
Stephanie Thomovsky, DVM, MS, DACVIM (Neurology), CCRP
Clinical Assistant Professor of Neurology and Neurosurgery at Purdue University
Director of Physical Rehabilitation at Purdue
The term cerebrovascular accident (CVA) is synonymous with the more commonly used term, stroke.
The definition of stroke is a sudden onset of a nonprogressive focal brain signs secondary to
cerebrovascular disease. The basis of stroke is a compromise in blood supply. A thrombus or embolus
can occlude the lumen of a blood vessel supplying the brain, a vessel can rupture, and underlying disease
of the vessel wall can lead to leakage or the propensity for occlusion. Increased blood viscosity can also
lead to a compromised blood supply. Neurologic signs are dependent on the location of the occluded
vessel and the section of the brain affected by the vasculature compromise.
A CVA is by definition, a stroke whose clinical signs last longer than 24 hours in duration. A stroke, the
signs of which, resolve within 24 hours is referred to as a transient ischemic attack (TIA). Most human
TIA’s last, on average, 1 minute. There is usually no permanent brain damage in the case of TIAs. These
“mini-strokes” are considered in human medicine, the warning sign of stroke; 1/3 of humans who
experience a TIA will suffer a CVA within 1 year’s time.
There are two main categories of CVA: hemorrhagic and ischemic. The former is caused by rupture of a
blood vessel within or on the surface of the brain, while the latter is a sequela to occlusion of a vessel.
The most common type of stroke in both humans and dogs is the ischemic infarct. There are two main
subcategories of ischemic stroke: territorial infarct and lacunar infarct. Territorial infarcts are those in
which a large, major brain artery (rostral, middle or caudal cerebral or rostral or caudal cerebellar artery)
becomes occluded. The result is ischemia to a large territory of the brain. These more commonly occur in
the cerebral cortex or cerebellum. Lacunar infarcts occur secondary to occlusion of a small intraparenchymal brain artery (perforating arteries). More commonly these occur in the thalamus and
midbrain. The result of a lacunar infarct is a small region of brain damage.
At the cellular level, ischemia to a section of the central nervous system results in depletion of ATP and
subsequent dysfunction of the sodium/potassium ATPase pump on the neuronal cell wall. Intra-neuronal
sodium concentrations increase and water flows into the neuron resulting in cytotoxic edema. A depletion
of oxygen and glucose secondary to ischemia results in a significant increase in extracellular glutamate
levels. Glutamate is an excitatory neurotransmitter. The increase in glutamate results in increased
calcium transport within the neuron via NMDA and AMPA channels. The increase in intracellular
calcium sets off a chain reaction  increase in intracellular xanthine oxidase, nitrous oxide, lipid
peroxidation and phospholipase A2. These byproducts increase within the neuron and it depolarizes, free
radicals are produced and neuron cell apoptosis is the end result. Neuronal healing can take place if
oxygen and glucose delivery is reinstated.
According to the United States Stroke Association, 795,000 Americans suffer a new or recurrent stroke
each year and 129,000 Americans are killed each year by a CVA. Stroke is the number 5 cause of death
in America. As stated previously, hemorrhagic strokes are less common than ischemic stokes in humans,
with 13% of all strokes being secondary to hemorrhage. Ischemic strokes comprise 87% of all human
CVA’s, the leading cause of which is atherosclerosis. Traditionally diagnosis of stroke in humans is via
advanced imaging (CT scan +/- MR). Carotid ultrasounds are performed to look for a source of embolic
material. Treatment for strokes is dependent on time of arrival post stroke to a hospital. If a human is
treated within 3 hours, they are given intravenous tissue plasminogen activator (tPA). Interventional
procedures whose goal is to break down a thrombus or embolus are performed following tPA
administration.
At the core of the neurologic presentation for stroke is the vascular anatomy of the brain. The most
common vessel to stroke in the human is the middle cerebral artery; in the dog it is the rostral cerebellar
artery. Humans, therefore, more commonly present with forebrain signs while dogs present with central
vestibular/cerebellar signs. As a general rule, in both man and the canine, the basilar artery and internal
carotid artery are the major vessels that supply the Circle of Willis. The Circle of Willis is a vascular ring
that is located ventral to the brain and surrounds the pituitary. From this ring emanate the major cerebral
and cerebellar arteries. In cats the only vessel that supplies this vascular ring is the maxillary artery. The
basilar artery actually carries blood away from the circle in the cat. The rostral and middle portion of the
forebrain are supplied by the internal carotid artery, while the vertebral artery (via the basilar artery)
supplies the caudal forebrain and brainstem and cerebellum in both man and dogs. Strokes are thought to
be more common in humans as compared to dogs as there are less anastomotic vessels involved in the
arterial supply to the brain. Thus, it is easier to disrupt the blood supply to the brain with a single
embolism, for example. In dogs, however, there are many more anastomoses of brain vessels whose jobs
are to ensure that the brain has an adequate blood supply.
In our canine patients CVA’s are diagnosed based on history, neurologic findings and also MRI
characteristics. Historically the neurologic signs have an acute onset and are focal signs,
neurolocalization is to one specific side and location within the brain. Progressive signs are uncommon
occurring only over the first 24 hours following clot formation. Some neurologic improvement is
commonly seen in the first 24-72 hours following the onset of signs. A CVA is not a good differential
diagnosis for a dog with chronic progressive signs or a dog with multifocal CNS signs.
Several veterinary papers suggest that strokes are most commonly diagnosed in Cavalier King Charles
Spaniels and Greyhounds. Many veterinary studies would also suggest that Weimaraners may also be
overrepresented. Strokes are more common in dogs that are middle aged to older; several reports
indicating the median age at the time of neurologic signs to be 8 years. The size of infarct is inversely
proportional to the size of the patient; dogs less than 15 kgs more commonly suffer territorial infarcts
while those larger than 15 kg suffer lacunar infarcts.
MRI reveals clinical evidence of stroke formation within 12-24 hours of the onset of neurologic signs.
Stroke lesions typically do not cause an obvious mass effect. The observed lesion is secondary to
ischemia, cytotoxic edema and malacia. Hemorrhagic strokes are best imaged with a T2* or gradient
echo (GRE) MR scan. Ischemic strokes are best observed using T2-W, fluid attenuated inversion
recovery (FLAIR) imaging, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC)
imaging. Contrast enhancement is observed only after 7-10 days in a typical stroke as enhancement is
occurs secondary to regional reperfusion. A cerebrospinal fluid tap can also be performed but often only
reveals a mild protein elevation.
Following suspected stroke diagnosis on MR imaging, the next step is to determine the cause of stroke
formation. Hemorrhagic strokes in dogs are often secondary to trauma. Ischemic strokes are most
commonly a sequela to: chronic kidney disease, neoplasia, cardiac disease or endocrine disease such as
hyperadrenocorticism, diabetes mellitus, and hypothyroidism. Hypertension can precede stroke
formation. Hypertension is most commonly secondary to chronic kidney disease or
hyperadrenocorticism. The veterinary literature would indicate that in only 50% of cases is the cause of
stroke diagnosed at the time of MR despite extensive metabolic testing and diagnostic imaging.
Metabolic testing includes: CBC, chemistry panel, urinalysis, urine protein/creatinine ratio, anti-thrombin
3 levels, test for Cushing disease (low dose dexamethasone suppression test, ACTH stimulation test or
UCCR), thyroid testing (TSH/T4 or T4 by equilibrium dialysis), cardiac work-up (echocardiogram and
ECG and serial blood pressure measurements). Chest and abdominal imaging is also recommended in
order to look for neoplasia. Coagulation testing is also recommended including thromboelastography,
platelet aggregation testing, buccal mucosal bleeding time and clotting times (PT/PTT).
Treatment for CVA consists of time and physical therapy. Some neurologists also recommend the use of
anti-platelet medications such as clopidogrel or low dose aspirin. At this point, there is no proof in the
veterinary literature that would support the use of anti-platelet medications to prevent the recurrence of
stroke in dogs. The use of tPA in canine patients is not recommended as it carries significant side effects,
is expensive and because canine strokes are rarely diagnosed within 3 hours of the onset of clinical signs.
The long term outcome and prognosis of canine stroke in 33 dogs was recently studied by Garosi L et al
(2005). There was found to be no association between type of infarct or location of infarct and patient
outcome. Concurrent medical conditions as the suspected cause of stroke were recorded in 18 of the dogs
in this study, the most common conditions were chronic kidney disease and hyperadrenocorticism. A
shorter survival time was observed in patients which were diagnosed with a concurrent medical condition.
Dogs were followed for a minimum of 3 months post diagnosis of CVA. Twenty three dogs were
reported to be alive, 16 of those dogs were described as having a good or excellent prognosis. Seven dogs
were alive but reported to have a poor prognosis at a minimum of 3 months follow-up. Ten dogs were
dead at the completion of the study period. Five of these dogs were euthanized because of a lack of
neurologic improvement and 5 either died or were euthanized because of the severity of their concurrent
medical condition. This is the first veterinary report to assess recurrence of stroke in dogs. Five dogs
(15%) suffered a second infarct within 5-10 months of the first stroke event in this study. This infarct was
diagnosed either via clinical suspicion or repeat brain MR. Dogs suffering recurrence were more likely to
have been diagnosed with a concurrent disease at the time of the first CVA (80% of dogs).
In the last 15 year there has been a huge rise in the number of peered reviewed literature in veterinary
medicine regarding CVA’s. As more time goes on and the use of MR becomes more and more prevalent
hopefully more outcome studies will be published with the end goal of improved treatment for canine
stroke patients.
References:
Garosi LS. Cerebrovascular disease in dogs and cats. Vet Clin North Amer Sm Anim Prac 2010; 40: 6579.
Garosi LS and McConnell JF J Ischaemic stroke in dogs and humans: a comparative review. Sm Anim
Prac 2005; 46: 89-97.
Garosi LS, McConnell, Platt SR, et al. Results of diagnostic investigations and long-term outcome in 33
dogs with brain infarction (2000-2004). J Vet Int Med 2005; 19: 725-731.
King AS. Arterial supply to the central nervous system. In King AS (ed). Physiological and clinical
anatomy of the domestic mammals, volume 1. New York (NY); Oxford Press, 1987. 1-13.
www.strokeassociation.org
IVMA 2017
Marvelous micturition
Stephanie Thomovsky, DVM, MS, DACVIM (Neurology), CCRP
Clinical Assistant Professor of Neurology and Neurosurgery at Purdue University
Director of Physical Rehabilitation at Purdue
A.
Review of the CNS
1.
Somatic Nervous System
a)
This portion of the nervous system is involved with skeletal muscle
innervation. The term “soma” literally means “body.”
2.
Autonomic Nervous System
a)
The ANS is made up of two separate divisions. Both portions are
involved with smooth muscle innervation: they sympathetic and
parasympathetic nervous system.
b)
The ANS is a 2 neuron system. Meaning that there is a nerve cell body
within the CNS (preganglionic cell body) and a second cell body that is outside of
the PNS (postganglionic cell body). The term cell body means the same thing as
neuron (it is the cell body of the neuron). The axon from the preganglionic cell
body sends a signal directly to the postganglionic cell body. The axon from the
postganglionic cell body acts directly on what is referred to as an effector or
target organ.
ANS
Sympathetic nervous system
Parasympathetic nervous
system
Type of Receptor
Adrenergic
Cholinergic
Type of neurotransmitter
Epinephrine or norepinephrine
Acetylcholine (Ach)
Purpose
Fight or flight
Rest and digest
Location of preganglionic
nerve cell bodies
Thoracolumbar spine
Cranial or sacral
Preganglionic cell body
location
T1-L4(5)
Brainstem nuclei for cranial nerves
3, 7, 9, 10, 11 or
Sacral SC (S1-S3)
Length of the axon between
preganglionic cell body and
postganglionic cell body
Short
Long
Location of postganglionic
nerve cell bodies
Sympathetic chain ganglion (this
is a structure you guys would
have dissected in anatomy).
In very close proximity to the target
organ.
Length of the axon between
postganglionic cell body and
target organ
Long
Short
B.
CNS Control of Micturition
1.
There are several areas in the CNS that control micturition.
a)
The brain
(1)
Cerebral cortex – this controls the conscious component of
urination. For example, this is why, if you are not in a bathroom when
you have to urinate you hold it until you are in an appropriate location.
(2)
Brainstem- this is where the pontine micturition center is
located. This center is involved with storage and evacuation of urine, it
also received information from the SC and sends that information from
the brain via the reticulospinal tract to the bladder.
(3)
Cerebellum – In general the cerebellum, no matter, what we are
talking about sends out inhibitory signals. This is why, with cerebellar
disease, movements, for example are exaggerated and of increased rate
and range. Similarly, the cerebellum does have some control over
frequency of urination  with disease patients may have an increased
frequency of urination.
b)
Spinal cord
(1)
The reticulospinal tract descends from the reticular formation in
the brain (located throughout the brainstem) down the SC. It terminates
in the ventral gray matter within the SC and signals LMN that innervate
the bladder.
c)
In general, an easy way to remember how the ANS controls urination is
to remember that “S” is for Storage and Sympathetic control. While, “P” is for
Peeing and Parasympathetic.
C.
PNS Control of Micturition
1.
There are 3 main peripheral nerves that control micturition. These neuronal cell
bodies for this nerves are located with all LMN in the ventral gray horn of the SC.
D.
a)
Hypogastric nerve
b)
Pelvic nerve
c)
Pudendal nerve
Anatomy of the Urinary Bladder
1.
The bladder muscle wall is called the detrusor muscle. It is made of smooth
muscle. The internal urethral sphincter (IUS) is composed of smooth muscle and it not a
true sphincter in that is basically composed of redundant smooth muscle. The external
urethral sphincter (EUS) is the big gun (i.e. the strongest sphincter in the bladder); it is
composed of skeletal muscle and is, therefore, under conscious control.
E.
Neural Control of Micturition (look at figure below)
1.
As stated above, the type of receptors in the sympathetic nervous system are
adrenergic receptors and the neurotransmitters (NT) that binds to these receptors are
either norepinephrine or epinephrine. The hypogastric nerve is under sympathetic
control. The hypogastric nerve innervates the detrusor muscle and the IUS. Thus, the
receptor on the detrusor muscle which is the target organ for the hypogastric nerve is the
B1 receptor. The hypogastric nerve innervates the IUS via the alpha-1 receptor. The
neurotransmitter released at both the detrusor B1 receptor and the IUS alpha-1 receptor
is norepinephrine.
2.
The receptors for the parasympathetic NS are cholinergic and the NT that binds
to these receptors is acetylcholine (Ach). The pelvic nerve is under parasympathetic
control. The pelvic nerve innervates the detrusor muscle. Thus, the receptor on the
detrusor muscle which is the target organ for the pelvic nerve is a muscarinic receptor
and the NT is Ach. Sensory information related to bladder fullness also travels up this
nerve to the SC and then onto the brain. When you get the sensation that your bladder is
full it is because sensory signals have been sent via the pelvic nerve to your brain to tell
you to think about urinating soon.
3.
The receptors for the somatic nervous system are nicotinic and the NT that binds
these receptors is Ach. The pudendal nerve is under somatic control. This nerve
innervates the EUS. Thus the receptor on the EUS which is the target organ for the
pudendal nerve is the nicotinic receptor and the NT is Ach. When you are in an
appropriate location but get the urge to urinate and you hold your urine you are
consciously controlling this EUS via the pudendal nerve.
F.
Normal Bladder Filling
The bladder fills with urine  pelvic nerve sends sensory information to the SC  via reticulospinal
tract, the information is relayed to the cerebral cortex  if the patient is inside and it is not an
appropriate time to urinate  via the reticulospinal tract excitatory signals are sent to the hypogastric
nerve  relax the detrusor muscle and contract the IUS. Excitatory signals are also sent to the pudendal
nerve  contract the EUS. Inhibitory signals are sent to the pelvic nerve  inhibit contraction of the
detrusor muscle  store urine.
G.
Normal Bladder Evacuation
The bladder is full  tight junctions of the detrusor muscle stretch  pelvic nerve sends sensory
information to the SC  via reticulospinal tract, the information is relayed to the cerebral cortex  if the
patient is outside and it is an appropriate time to urinate  via the reticulospinal tract inhibitory signals are
sent to the hypogastric nerve  relaxing the IUS. Inhibitory signals are sent to the pudendal nerve 
relaxing the EUS. Excitatory signals are sent to the pelvic nerve  contract the detrusor muscle  urine
flows.
H.
Micturition and Spinal Cord Disease
1.
There are two kinds of urinary bladders associated with neurologic dysfunction:
UMN and LMN bladder. One key point to remember is that the bladder follows what is
going on in the pelvic limbs. Meaning, if a patient is unable to move their pelvic limbs you
can assume they are unable to consciously urinate. Conscious urination refers to what
we discussed earlier, the idea that the cerebral cortex is in control of where and when
you urinate. If there is disease of the SC, the reticulospinal tract will be unable to carry
sensory information to the brain from the bladder and similarly the brain will be unable to
send motor information via the reticulospinal tract to the SC.
2.
Along the same line, if you feel as though reflexes and tone in the pelvic limbs
are consistent with LMN disease then the bladder probably is a LMN bladder.
Meanwhile, if you feel as though the tone and reflexes in the pelvic limbs are consistent
with UMN disease, then the bladder is probably an UMN bladder.
Neurologic Urinary Bladder Type
UMN Bladder
LMN Bladder
Tone
Great tone
Poor tone
Feel on palpation
Firm
Like a floppy water balloon
Ease of Expression
Difficult
Easy
Type of SC lesion
T3-L3 SC (you can also see UMN
L4-S2 SC
bladder dysfunction with C1-C5 SC or
C6-T2 SC disease)
3.
UMN SC Lesion
a)
These patients are neurolocalized to L3 and cranial (most cases are T3L3 SC). Clinically these patients are paretic to plegic. They have increased
pelvic limb tone and increased to normal pelvic limb reflexes. They may have
disuse atrophy to the pelvic limbs. The bladder is firm and difficult to express.
Side note, as discussed earlier, most patients who have lost the ability to
consciously urine are plegic.
4.
Bladder Function in Cases of UMN SC Disease
a)
The UMN system, as a general rule, is a system that inhibits all of the
LMN that it communicates with. So, when there is disease of the spinal cord at
T3-L3 (and less commonly C1-C5 or C6-T2 SC) there is disease of the UMN 
this leads to lack of inhibition to the nerves that these UMN tracts communicate
with.
(1)
Parasympathetic Control: Lack of UMN inhibition of the pelvic
nerve  increased tone to detrusor muscle
(2)
Sympathetic Control: Lack of UMN inhibition of the hypogastric
nerve  tone to IUS. Remember, however, that the hypogastric nerve
cell bodies are housed within the spinal cord gray matter from L1-L4/5
SC so it is possible with a lesion in the T3-L3 spinal cord segments that
the cell bodies for the nerve itself could be affected leading to a
hypogastric nerve that is not totally functional. That being said most
diseases do not affect 4-5 spinal cord segments so some of the nerve
cell bodies should be unaffected directly by the disease process.
(3)
Somatic Control: Lack of UMN inhibition of the pudendal nerve
 increased tone to EUS sphincter
5.
LMN SC Lesion
a)
These patients are neurolocalized to L2-S2 SC. Clinically these patients
are paretic to plegic. They have decreased pelvic limb tone and decreased to
absent pelvic limb reflexes. They may have decreased to absent perineal reflex
and anal tone. They may have neurogenic atrophy to the pelvic limbs. The
bladder is floppy, and easy to express at the start. These bladders are difficult to
completely get all urine out of, however, because the bladder wall has such poor
tone. Side note, as discussed earlier, most patients who have lost the ability to
consciously urine are plegic.
6.
Bladder Function in Cases of LMN SC Disease
(1)
Parasympathetic Control: The nerve cell bodies for the pelvic
nerve are located from S1-S3 SC  decreased tone to detrusor muscle
 the bladder has poor tone on palpation.
(2)
Sympathetic Control: they hypogastric nerve cell bodies are
located from L1-L4/5 so this nerve is unaffected by a lesion from L4-S2
SC. They have normal IUS tone. The IUS is the only functional
sphincter in these cases. Because this sphincter is not as strong as the
EUS it provides little resistance to expression.
(3)
Somatic Control: The nerve cell bodies for the pudendal nerve
are located from S1-S3 SC  decreased tone to EUS  the bladder is
easy to express and has the propensity to leak.
7.
Reflex Micturition
a)
This condition develops only in cases of UMN disease and is not seen in
cases with LMN disease. IT develops days to weeks after an UMN SC lesion.
Basically a local reflex arc is set up between the bladder and the SC  the brain
is not involved. These are patients who have not improved neurologically from
initial injury, but who start “urinating on their own” weeks after UMN injury. It is
not a conscious urination and often they still to be expressed following urination
as these reflex urination patients rarely urinate the entire contents of their bladder
when they void.
b)
Pathophysiology of Reflex Micturition
(1)
The bladder fills with urine  the bladder tight junctions are
stretched  Sensory (afferent) signals are sent via the pelvic nerve to
the SC  sacral motor neurons are stimulated (efferent neurons) 
pelvic nerve stimulates the detrusor muscle to contract. There is
inhibition of the pudendal nerve  relaxation of the EUS  the patient
urinates. NO signal is every relayed up the reticulospinal tract to the
brain  thus, urination is unconscious!
I.
Neural Control of Defecation
1.
Defecation is controlled in a similar way to urination.
2.
Parasympathetic control to the descending colon and rectum is by way of the
Pelvic nerve (allowing expulsion of feces).
3.
Sympathetic control to the descending colon and rectum is inhibitory but it is
facilitory to the internal anal sphincter (allowing storage of feces). These sympathetic
nerves are the hypogastric, caudal mesenteric ganglion, caudal mesenteric plexus and
pelvic plexus.
4.
Somatic control to the external anal sphincter which is skeletal muscle is via a
branch of the Pudendal Nerve, the caudal rectal branch and also the sacral plexus.
5.
Just like with urination the reticulospinal tracts carry information from the rectum
and colon to and from the brain.
J.
Defecation and SC Disease
1.
To be honest, with small animal SC disease we do not worry too much about
defecation. It is very rare that anything has to manually be done to express the colon. I
can think of one patient I have had where the patient (and it was a cat) required
intermittent enemas. And also one (the same cat) who needs to have her colon
expressed every few days. The reason this is not an issue as it is with the urinary
bladder is because even in severe SC conditions that result in paraplegia involuntary
reflex fecal evacuation usually takes place  the colon it full  it stretches and a local
reflex arch results in relaxation of the anal sphincter and peristalsis of the colon.
2.
There are two main types of fecal incontinence: UMN and LMN fecal
incontinence.
a)
UMN fecal incontinence - clinically this is seen in two main instances,
one is just like we chatted about earlier with the bladder, where an animal has a
significant SC lesion cranial to L3 resulting in paraplegia and they are unaware
they are defecating – unconscious defecation. The colon is stretched but that
signal is blocked from getting to the brain via the SC  the patient is unaware
they are defecating and will common produce, formed feces but at inappropriate
times. The second time this can be seen is in patients who only have mild pelvic
limb neurologic deficits but they chief complaint is fecal incontinence. Usually
these patients have disease of the dorsal portion of the SC (such as
syringomyelia or a subarachnoid diverticula, for example). They realize they
have to defecate but too late or sometimes are completely unaware that they are
defecating.
b)
LMN fecal incontinence – this is just like we talked about with urination,
seen in SC disease where the patient is localized to L4-S2. If they are localized
to the all of the SC segments at L4-S2 then they have decreased pelvic limb
tone, reflexes and are severely paraparetic or plegic and have poor anal tone
and perineal reflex but they can also be localized to just S1-S3 (have poor anal
tone, perineal reflex and poor tail function and have normally functioning pelvic
limbs). These patients leak, often unformed stool often times constantly – fecal
scald is a large problem in these patients. The leaking is secondary to poor
external anal sphincter tone.
K.
Micturition Medications
1.
In our neurologic patients it is usually our goal to get our patients to urinate.
Thus, we use a combination of the first 5 drugs. We do not use phenylpropanolamine or
estrogen very often for this reason.
L.
Urinary Bladder Management
1.
Supportive care is key
a)
Keep patients clean and dry
b)
Bladder evacuation
(1)
Urinary catheterization (either intermittent or placement of an
indwelling urinary catheter system)
(2)
Urinary expression
(3)
There have been some good publications in the veterinary
literature addressing bladder management in our patients. A few are
listed below:
(a)
This article showed that there was no preferred method
of bladder management:
(i)
Bubenik L, Hosgood G. Urinary tract infection in
dogs with thoracolumbar intervertebral disc herniation
and urinary bladder dysfunction managed by manual
expression, indwelling catheterization or intermittent
catheterization. Vet Surg 2008; 37(8): 791-800.
(b)
This article showed low risk catheter-associated UTI if
indwelling catheters were not left in more than 3 days at a time:
(i)
Smarick SD, Haskins SC, Aldrich J, Foley JE,
Kass PH, Fudge M, Ling GV. Incidence of catheterassociated urinary tract infection among dogs in a small
animal intensive care unit. JAVMA 2004; 224(12):
1936-40.
(4)
Frequency of intermittent bladder evacuation
(a)
Every 6-8 hours
(b)
Something to be aware of is that in a normal dog (value
unknown for cats) after an animal properly urinates the dog will
have anywhere from 0.2-0.4 ml/kg of urine left remaining in the
bladder. This number becomes important in cases where you
think a dog has regained conscious urinary function after having
had SC disease.
2.
Bladder management is VERY important. The major seqelae to poor
management are:
a)
UTI – frequent urine cultures are important in patients who
neurologically are unable to void.
b)
Urine scald – to avoid this keep patients clean and dry. Also rotating
patients every 4 hours will prevent this as it allows wet, clean areas of the skin/fur
to dry. You can also get fecal scalding in our incontinent patients as well – just
another reason to keep them clean and dry.
The below picture is from a paraplegic patient we had last semester who
secondary to urine scald and licking her abdomen developed this wound in her
inguinal area.
c)
d)
Detrusor atony (this is a serious and often irreversible complication to
poor bladder management. The detrusor muscle contains tight junctions, if those
tight junctions are stretched there is the possibility that they will not be able to
heal and even though the patient regains neurologic function, in his limbs, for
example, the detrusor muscle will remain damaged and these patients commonly
will still be incontinent and unable to completely void their bladders).
3.
Important Thing to Remember
a)
**Just because an animal is laying in a large puddle of pee does
NOT mean they are consciously able to urinate  make sure they have not
overflowed  palpate the bladder and express them as needed**
References
A Practical Guide to Canine and Feline Neurology. Curtis Dewey, 2
nd
ed., 2008
rd
Veterinary Neuroanatomy and Clinical Neurology. Alexander de Lahunta and Eric Glass, 3 ed., 2009.
IVMA 2017
More Obscure Myelopathies
Stephanie Thomovsky, DVM, MS, DACVIM (Neurology), CCRP
Clinical Assistant Professor of Neurology and Neurosurgery at Purdue University
Director of Physical Rehabilitation at Purdue
1.
Myelopathies Besides Intervertebral Disc Disease and Wobbler Syndrome
1.
Degenerative Spinal Cord Conditions
a)
Lumbosacral disease (LS Disease)
(1)
This is a major cause of cauda equina syndrome. Cauda equina
syndrome refers to compression of the cauda equina and the associated
neurologic deficits that result when there is compression of these nerve
roots. The main nerve roots affected are those that supply the sciatic
nerve, pudendal and pelvic nerves.
(2)
LS disease is relatively common, it is definitely one you will
diagnose regularly in private practice.
(3)
LS disease refers to degenerative joint disease at the L7-S1
space. For all intents and purposes you can think of it as “wobblers of
the lumbosacral spine.” Meaning there is a combination of several
disease processes going on all at the LS space that contribute to cauda
equina compression in this area.
(4)
Compression is secondary to a combination of:
(a)
Type II IVDD at L7-S1
(b)
DJD of the articular facet joint at L7-S1
(c)
Bony proliferation  stenosis at L7-S1
(d)
Proliferation of two ligaments: the dorsal longitudinal
ligament and ligamentum flavum (yellow ligament). The former
is present dorsal to the disc while the latter is dorsal to the spinal
cord.
(5)
Signalment of dogs with LS disease
(a)
This is a disease of dogs and if seen in cats, is very rare.
It occurs in older, large breed dogs. It often occurs in working
dogs. So if you work with military dogs or service (police) dogs
you will definitely see LS disease on a fairly common basis.
(6)
Clinical Signs are secondary to compression of the cauda
equina. As we mentioned earlier, this means signs you would
associated with sciatic, pudendal and pelvic nerve disease.
(a)
* Fecal and urinary incontinence
(i)
This can become permanent if left untreated.
This is something very different about LS disease as
opposed to most other spinal cord diseases you will
study. Because this disease affects the cauda equina
rather than the spinal cord, per se, it is much less
common to have actual paresis and certainly paralysis
with disease back in this region. That being said
because the pudendal nerve innervates both the
external anal and external urethral sphincter
incontinence is a huge sequela to disease at the LS
space.
(ii)
If patients come in with LS disease and are
incontinent there is a poor to guarded prognosis for
return to function, and this is proportional to duration of
the incontinence. Key point, if you see a dog who you
suspect has LS disease that has fecal and urinary
incontinence, this is an emergency and should be
referred for further work up surgery. Time is important in
these cases.
(b)
Pain on L-S palpation
(c)
Paresis
(i)
Pelvic limbs
(ii)
Tail
(d)
+/- CP deficits in the pelvic limbs
(e)
+/- pelvic limb ataxia
(f)
Decreased reflexes
(i)
Decreased pelvic limb withdrawal reflexes
(ii)
Decreased perineal reflex
(iii)
Decreased anal tone
(g)
Difficulty lifting back feet when ambulating
(i)
(h)
Scuffs feet
Possible decreased step distance
(7)
Diagnosis of LS disease can be done with several diagnostic
modalities.
(a)
Survey spinal radiographs are quite effective in the
diagnosis of LS disease or at least, lend suspicion that there is
disease at this disc space.
(i)
Key things to look for are sclerosis of the caudal
vertebral endplate at L7 and cranial endplate at S1, DJD
of the facet joints at L7-S1, opacity within the
intervertebral foramina at L7-S1.
(b)
MRI – in this disease multiple studies show that MR and
CT both are adequate in the diagnosis of LS disease.
(c)
CT- in this disease multiple studies show that MR and
CT both are adequate in the diagnosis of LS disease.
(d)
Myelography- this is a disease condition where
myelogram is not as good as either MR or CT in the diagnosis of
disease at the LS space. It is mainly because myelography is
dependent on an intrathecal injection of contrast. Because nerve
root as opposed to spinal cord are present at the LS space,
compression is not as obviously seen after dye injection. Thus,
when myelography was our only option (before the days of MR
and CT) an epidurogram was done in these cases.
(i)
Epidural injection (epidurogram)- this is an
epidural injection (similar to what you would give as
analgesia before an orthopedic procedure involving the
pelvic limbs or to women at the time of labor) of contrast
agent. These are not pretty images and can be difficult
to interpret.
(8)
Treatment
(a)
Like all spinal disease two treatment options exist,
conservative vs. surgical management.
(i)
Conservative management is cage rest with
controlled physical therapy. PT is very important in
these cases as you want to maintain muscle mass and
joint mobility.
(ii)
Surgical management is a dorsal laminectomy at
L7-S1 with or without stabilization using a combination of
screw and PMMA, or a plating system of surgeon’s
choice. Surgical management should be strongly
encouraged in cases where pain is refractory to medical
management and certainly if there are signs of
incontinence (ideally before these signs are observed).
(9)
Prognosis is slightly different here than in other areas of the
spinal column. Deep pain is important, as always, except clinically with
LS disease we are usually talking about DP to the tail and perineum. If
this is absent the prognosis for recovery of this DP is poor. What makes
LS disease different is that prognosis is also, as stated earlier, affected
by incontinence. If the patient is incontinence (a LMN incontinence
secondary to pudendal nerve involvement) then return to function is often
poor.
2.
Degenerative Spinal Cord Diseases (continued)
a)
Degenerative myelopathy (DM)
(1)
This is a common neurologic condition. You will see this in
private practice.
(2)
Signalment
(a)
Older [>5 years of age (mean age = 9)]
(b)
Large breed dogs (except for the corgi!)
(i)
Most commonly, German Shepherd, Boxers,
Chesapeake Bay Retriever, Rhodesian Ridgeback,
Pembroke Welsh Corgis
(3)
Onset and progression of disease is key in this disease
(a)
Onset is slow, these patients have a chronic progressive
history of non-painful pelvic limb paraparesis and ataxia
(proprioceptive)
(4)
Clinical Signs
(a)
Early Signs (6-12 mths after onset)
(i)
Pelvic limb proprioceptive ataxia
(ii)
Can be asymmetric at start
(iii)
T3-L3 SC localization
(a)
(iv)
(b)
(UMN paresis)
Non-painful
Late Form (after 12 mths)
(i)
With time, signs become more symmetric
(ii)
Progression to LMN paraplegia
(iii)
Thoracic limbs start to become weak
(iv)
It can progress to flaccid tetraplegia and
brainstem signs
(v)
Patients are often euthanized prior many of
these late form signs developing.
(5)
Pathophysiology
(a)
Multisystem central and peripheral axonopathy
(b)
Degeneration of the white matter of SC
(i)
All funiculi affected
(ii)
Axon and associated myelin destroyed (this is
why signs are UMN at the start)
(iii)
Defects in cells that support axon maintenance
(i.e. astrocytes or oligodendrocytes) or defects in
axoplasmic flow
(6)
Genetics behind this condition have been elucidated and there is
genetic testing present for some breeds through the OFA.
(a)
Mutation in the superoxide dismutase 1 (SOD1) gene
(b)
This disease is similar to the human disease,
Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig Disease)
(c)
Homozygosity SOD1 mutation is a major risk factor for
canine DM. If genetic testing is pursued the results will indicate
if you are homozygous, heterozygous for the disease (i.e. a
carrier). Though the testing will tell you if the dog has the gene,
it will however, not tell you if you will express the gene.
(7)
Cats have been described as also having a form of degenerative
myelopathy, as well. But this condition is different from the canine form
and is uncommon.
(a)
It is associated with FeLV infections. Cats chronically
infected with this condition show signs of lethargy, behavior
changes, vocalization, hyperesthesia and urinary incontinence.
The most common sign, however, if pelvic limb paresis that can
progress to paralysis within 1 year.
(b)
These cats are older with a chronic progressive history
of paresis.
(c)
Histopathology shows white matter degeneration.
(8)
Diagnosis of canine DM – there is NO definitive ante-mortem
way to diagnose DM. It remains a diagnosis of exclusion. That being
said, the presumptive diagnosis of DM is made with a combination of
tests
(a)
Genetic testing through OFA.
(i)
(b)
Test for homozygosity of the SOD1 mutation
Neuro diagnostic results
(i)
Normal thoracic and lumbar MRI
(ii)
Normal CSF tap
(a)
Hence the idea of it being a diagnosis of
exclusion.
(9)
Treatment is supportive only
(a)
Intensive physiotherapy
(i)
Study showed improvement in survival time =
mean 255 days
(a)
days
Those that had moderate therapy = 130
(b)
days
Those that had no physiotherapy = 55
(ii)
Some bias is present in this study, however,
because those owners who are willing to do intensive PT
are probably also those willing to keep an animal alive
longer who is extremely weak in the pelvic limbs and
who requires bladder maintenance, for example.
(b)
Other treatments have been discussed including Nacetylcysteine and possibly aminocaproic acid but controlled
studies have yet to be performed.
3.
Congenital Malformations
a)
Caudal Occipital Malformation (COMS) and Syringomyelia (SM)
(a)
This refers to malformation of caudal fossa and
associated cerebellar overcrowding and herniation of the caudal
portion of the cerebellum through foramen magnum. In human
medicine COMS is synonymous with Chiari Type I.
(b)
Most commonly, the occipital bone is of abnormal shape
and is displaced rostrally. Additionally, there is some thought
that the caudal fossa is too small in size proportionally for the
brain size. This leads to herniation of the cerebellum and an
alteration in CSF flow at the level of the foramen magnum.
(c)
This alteration in CSF flow leads to SM. Syringomyelia
refers to dilation of a section of the spinal cord with extracellular
fluid. Hydromyelia refers to dilation of the central canal. It is
difficult, other than on histopathology, to differentiate between
syringomyelia and hydromyelia. So, most of the time we refer to
them as syringo/hydromyelia or just refer to them both as SM
(syringomyelia) or a syrinx.
(i)
The pathophysiology behind syrinx formation is
not completely understood, although several theories
exist for its formation. (picture of hydromyelia below – it
is the cross section of the SC on the far left)
(d)
Signalment for COMS is
(i)
Young dogs who are 3 months – 5 yrs of age
(ii)
It is most common in toy or small breed dogs.
The poster child for this disease is King Charles Cavalier
Spaniels. It has also been described in the Maltese,
Brussels Griffon, Chihuahua, Poodle.
(e)
Onset/progression
(i)
Acute, chronic and possibly progressive.
(ii)
Most clinical signs occur in adulthood (though
this condition is present at birth, it is most common for
dogs to present with signs attributed to it after 1 year of
age.
(f)
Clinical Signs
(i)
Usually are a combination of brainstem and
cerebellar signs such as vestibular signs and head
tremors.
(ii)
They also display signs consistent with cervical
spinal cord disease (such as spinal hyperesthesia,
Scoliosis secondary to SM, CP deficits and paresis).
(iii)
Another common sign is scratching at the
shoulder, neck and ears. These patients common are
referred to dermatologists for this scratching.
(g)
Diagnosis
(i)
Made with MRI (+/- CSF tap). CSF tap is done
to rule out other diseases of small breed dogs such as
meningoencephalomyelitis. COMS cannot be diagnosed
with CT or myelogram. It is an MRI diagnosis.
(h)
Treatment consists of medical therapy versus surgical
treatment.
(i)
Medical
(a)
Pain medications, most commonly
gabapentin as the scratching most believe to be
secondary to neurogenic pain.
(b)
Medications to decreased CSF
production (omeprazole, carbonic anhydrase
inhibitors, furosemide). The goal of these
medications is to reduce CSF flow and in that
vein, reduce SM formation.
(ii)
Surgical
(a)
Foramen magnum decompression is the
surgery of choice. The goal is to decompress
the cerebellum and try to reduce/completely
reverse syrinx formation. Interestingly enough,
in human medicine the syrinx often goes away
with surgery. The same cannot be said in our
veterinary patients, more often than not, the
syrinx is unchanged by surgery. As the syrinx is
often the main cause of the patient’s clinical
signs, in vet med, we typically try medical
management first. We later pursue surgical
treatment only if medical management is not
helping the patient.
4.
Infectious/inflammatory Spinal Cord Disease
a)
Diskospondylitis (disko) - infection of the intervertebral disc and
adjacent vertebral endplate. This disease is completely different than
spondylosis aka spondylosis deformans. Disko is a very common disease and
one that can be confidently diagnosed with survey radiographs.
(1)
(2)
Signalment
(a)
Mostly, large, middle-aged dogs (uncommon in cats)
(b)
Male > female
(c)
Rare in cats
Clinical signs
(a)
#1 = spinal pain (> 80% of cases)
(b)
Neurologic signs are anything from ataxia to paralysis
(c)
Systemic signs of infection (30% of cases)
(i)
Fever, weight loss, inflammatory leukogram,
sometimes these patients present for just being ADR
(3)
Etiology
(a)
The most common cause of disko is a bacterial infection.
That being said the infection can also occur secondary to a
fungal infection of the vertebral endplate. The most common
type of bacterial infection is Staphylococcus. Infections can also
be secondary to E. coli, Brucella canis and streptococcus
organisms.
(b)
Fungal disko carries a worse prognosis than bacterial.
Aspergillus is the most common organism described.
(c)
Foreign bodies (grass awn migration) have also been
described as a cause.
(4)
Diagnosis
(a)
Survey spinal radiographs are the most common way
disko is definitely diagnosed. That being said, there can be
radiographic lag between onset of clinical signs and radiographic
evidence of disease.
(b)
The most common radiographic abnormalities are:
(i)
Irregularity of vertebral end plates
(ii)
Lysis of vertebral endplates
(iii)
Later, with chronic disko infections you will see
sclerosis of the endplates and osteophyte production
(iv)
Disko is most commonly diagnosed at the L7-S1
disc space (see picture below). However, it is fairly
common to have more than one set of vertebral
endplates that are infected. If you find disko in one site
we usually do full spinal rads to make sure there are not
multiple sites affected.
(c)
For cases wherein you cannot confidently use
radiographs to diagnose disko (i.e. when you are suspicious a
dog has disko, for example, there is definite back pain, but you
are concerned the radiographic lag is not allowing you to see it
on radiographs or when there is too much summation at the disc
space in question – this can happen with summation for the ilial
wing or the front limb) and you need a more sensitive modality to
diagnose disko you can use a CT scan, MRI or nuclear
scintingraphy.
(5)
Other diagnostics to pursue in cases of diskospondylitis
(a)
Urinalysis and urine culture this combination of
diagnostics is done in every case of disko because this is the
most common way to diagnose the infecting organism. Urine
culture is positive 25-50% of the time in cases of disko.
(b)
CBC you will see changes consistent with an
inflammatory leukogram.
(c)
Brucella serology (these are positive in 10% of disko
cases) is done in all dogs because of the zoonotic potential of
this infection. This is usually an infection most commonly seen
in breeding animals.
(d)
Blood cultures (these are positive in 45-75% of disko
cases)
(e)
+/- Echocardiogram – this diagnostic is pursued in cases
where there is an audible heart murmur. Because disko lesions
develop secondary to a period of bacteremia, for prognosis, it is
good to determine if endocarditis is present
(f)
Disko can lead to osteomyelitis and/or meningomyelitis,
for that reason, sometimes were pursue a CSF tap as a part of
the diagnostic protocol.
(g)
Sometimes we also pursue FNA of intervertebral disc
space. This is a bit of a risky procedure due to the potential for
pneumothorax in the T spine and the proximity of the aorta to the
IVD space in the lumbar spine. Sometimes we are able to, in
cases of L7-S1 disko do ultrasound guided FNA of the
surrounding soft tissues. This is especially successful if there is
a considerable amount of proliferation at the disc space. After
any FNA we culture the samples obtained.
(h)
Surgical biopsy is performed in rare cases for 1 of 2
reasons: the patient is unresponsive to empirical therapy, or
there is associated compression of the spinal cord in the area of
the disko lesion leading to significant neurologic deficits in the
patient.
(6)
Treatment is based on culture and sensitivity but there are times
when, despite our better efforts, we do not grow anything on urine, blood
or FNA cultures. At these times we have to empirically treat the
infection.
(a)
The choice of drug should be based on culture results,
that being said, if you are empirically treating you want to pick an
antibiotic that has good bone penetration and those that are
good against gram positive organisms as Staph infections are
most common. Such antibiotics include: cephalosporin’s such
as cephalexin, clavamox, clindamycin or enrofloxacin can also
be used. As for anti-fungals, if you are worried about CNS
penetration fluconazole is the best anti-fungal to choose, if you
think that the infection is solely in the intervertebral endplate then
ketoconazole or itraconazole can also be used.
(b)
Treatment for bacterial disko is usually 6 months to 1
year of continuous antibiotic therapy. These are infections of
bone and bone takes a long time to treat. Most patients if they
are treated appropriately will heal completely and have a good
prognosis.
(c)
Treatment for fungal disko can be much longer than 6-12
months. There has been a published paper of lifelong treatment
with antifungals for fungal disko (every time the dog was taken
off the drug signs came back). Prognosis with fungal disko is
guarded, contributing to this is that fungal disko is harder to
diagnose and so these patients probably are diagnosed and
started on anti-fungals much later than dogs with bacterial disko.
b)
Meningomyelitis is inflammation of the meninges and spinal cord. This
is an uncommon condition in either dogs or cats but often more quickly
progressive than meningoencephalitis as the spinal cord is smaller in diameter
than the brain, so it often takes less inflammation to cause more significant signs.
(1)
Onset is usually progressive although it can be acute.
(2)
Signalment in general
(a)
(3)
Young to middle aged dogs
Clinical Signs in general
(a)
Often causes multi-focal CNS signs involving the brain
and SC, but you can see pure myelitis which presents with just a
SC localization.
(b)
(4)
Spinal hyperesthesia to ataxia to paralysis
Diagnosis for all types of meningomyelitis
(a)
CSF tap – the main use of CSF is when it comes to CNS
inflammation. This is the main tool used to definitively diagnose
meningitis of any kind.
(i)
Increased WBC (nucleated cells) (elevated
means more than 5 nucleated cells per microliter in the
dog and cat)
(ii)
Increased protein (increased means more than
30-35 mg/dL via a cysternal tap or more than 40-45
mg/dL if CSF is done via a lumbar tap)
(iii)
CSF culture (this is often a low yield, even in
cases where bacteria are seen on cytology of the CSF –
mainly because CSF is so low in protein, traditionally it is
difficult to isolate bacteria or fungal agents from it).
(b)
MRI
(i)
May show meningeal and SC enhancement with
contrast
(c)
Infectious disease titers are pursued to determine if the
meningomyelitis is infectious or non-infectious. More to come
below on this…
(5)
Two main categories of meningomyelitis. The same holds true
for meningoencephalitis.
(a)
Infectious
(i)
Viral such distemper or rabies, in cats FIP, FeLV
or FIV
(ii)
Bacterial
(iii)
Rickettsia sp. (Ehlichia or Rocky Mountain
Spotted Fever)
(iv)
Fungal such as aspergillus, cryptococcus,
coccidiodes, blastomycoses
(v)
Protozoal such as Toxoplasma gondii or
Neospora caninum
(vi)
Treatment and prognosis are variable depending
on the infecting agent.
(b)
Non-infectious
(i)
Sterile supporative meningitis aka canine
meningeal polyarteritis, steroid-responsive meningitisarteritis (SRMA)
(a)
Signalment –this disease is special in
that it is only seen in young, medium to large
breed dogs.
(i)
Young (< 2 yrs old)
(ii)
Medium-to-large breed dogs
(b)
Clinical Signs- also unique about this
disease is that it traditionally causes a fever and
only neck pain – no other neuro deficits
(i)
Fever
(ii)
Severe cervical pain (this is
usually the only neuro deficit)
(c)
Blood Work shows a neutrophilic
leukocytosis
(d)
Treatment is with immunosuppressive
doses of steroids. This condition is unique for
two other reasons, one is that these dogs can be
slowly tapered, over a few months, off steroids
and be cured (i.e. not require further
immunosuppressive therapy). The second
unique thing is that the prognosis for functional
recovery is good.
References
A Practical Guide to Canine and Feline Neurology. Curtis Dewey, 2
nd
ed., 2008
Small Animal Spinal Disorders Diagnosis and Surgery. Nicholas Sharp and Simon Wheeler, 2
nd
ed. 2005.
Veterinary Clinics of North America Small Animal Practice: Spinal Disease. Ronaldo da Costa, 20 (5);
2010.
rd
Veterinary Neuroanatomy and Clinical Neurology. Alexander de Lahunta and Eric Glass, 3 ed., 2009.
IVMA 2017
Neurologic manifestations of systemic disease
Stephanie Thomovsky, DVM, MS, DACVIM (Neurology), CCRP
Clinical Assistant Professor of Neurology and Neurosurgery at Purdue University
Director of Physical Rehabilitation at Purdue
Neurologic signs can be a sequela to many of the common systemic diseases seen in veterinary patients.
The purpose of today’s talk is to discuss the neurologic manifestations of common systemic diseases and
the pathophysiology associated with these neurologic signs. We will discuss thyroid disease, diabetes
mellitus, diseases of the adrenal gland and erythrocytosis.
Hyperthyroidism is a common disease of older felines. One of the main neurologic signs observed in this
disease is muscle weakness. This weakness is observed in 12-25% of cats with high thyroid hormone
levels. This muscle weakness is secondary to decreased action potential formation and decreased muscle
membrane excitability. A small number of cats, 1-3% cats, show ventral neck flexion as a sign of diffuse
muscular weakness. Seizures can also be associated with hyperthyroidism. The mechanism behind
seizure formation is not completely understood. It is thought that thyroid hormones may directly decrease
the electrical threshold of cerebral tissue, making it easier to depolarize and create an action potential
within cerebral neurons. Elevated thyroid hormones also alter neurotransmitter concentrations and
activity which can potentiate neuronal depolarization. Neurologic signs may also be secondary to thyroid
hormone’s effect on metabolism. Thyroid hormones increase the consumption of oxygen and glucose
within the brain, this can lead to neuronal cell death. Another possible cause of neurologic signs in
animals with hyperthyroidism is the fact that hypertension is often associated with hyperthyroidism.
Hypertension can alter brain vasculature and lead to cerebrovascular disease in humans and animals.
Unfortunately even one common treatment for hyperthyroidism, methimazole, can cause neurologic
signs. Methimazole is a thioureylene anti-thyroid medication. This medication is actively concentrated
within the thyroid gland; it inhibits thyroid peroxidase-catalyzed reactions, and binds to and alters the
structure of thyroglobulin and is used to reduce the amount of thyroid hormone. The use of methimazole
has been associated with neurologic signs, specifically myasthenia-like signs. Methimazole increases the
number of acetylcholine receptor antibodies, thus causing exercise intolerance, fatigue and muscle
weakness. This side effect of methimazole is normally observed 2-4 months following therapy initiation;
signs are resolved with withdrawal of the medication.
Hypothyroidism is also associated with neurologic signs. Hypothyroidism has been proven to cause both
peripheral (PNS) and central nervous system (CNS) signs. CNS manifestations of hypothyroidism
include central vestibular signs, myxedema coma and CVA. The mechanism of action as to how low
thyroid levels can cause central vestibular signs is unknown, however, it is thought that these neurologic
signs may be secondary to atherosclerosis and subsequent ischemic stroke formation, or central nervous
system demyelination. In one report by Higgins et al (2006) up to 70% of dogs with central vestibular
signs secondary to hypothyroidism had no other extra-neural clinical evidence of low thyroid levels (no
alopecia, or weight gain). So even in cases where a dog may not “look hypothyroid” it should still be
tested if the patient has central vestibular signs. Myxedema coma is also a sequela to a severe form of
hypothyroidism. This disease results in mental obtundation and stupor secondary to reduced oxygen
delivery and glucose utilization by brain tissues and altered cerebral blood flow. Hyponatremia can also
be a result of this extreme form of hypothyroidism and can affect neurons, neuronal action potential
formation and propagation. In addition to stupor these patients often have a non-pitting edema of the skin
secondary to accumulation of hyaluronic acid within the dermis, hypothermia, lack of shivering reflex,
bradycardia and weakness. This same hyaluronic acid deposition is also associated with PNS signs, as
discussed in the next paragraph. Cerebrovascular disease is also a sequela to hypothyroidism as it can
lead to atherosclerosis and/or hyperlipidemia.
In addition to CNS signs, hypothyroidism can also cause PNS signs (a mononeuropathy or diffuse
polyneuropathy). It is thought that low thyroid hormones levels can cause demyelination of peripheral
nerves. In extreme forms, myxomatous disease secondary to deposition of hyaluronic acid within the
dermis and surrounding soft tissues can also cause peripheral nerve compression. Most commonly,
hypothyroidism has been reported to affect the peripheral portion of several cranial nerves including
cranial nerve 5, 7, 8 and 10 (including its branch, the recurrent laryngeal nerve). Patients can therefore
present with peripheral vestibular signs, laryngeal paralysis, and megaesophagus.
Another manifestation of hypothyroidism is a diffuse polyneuropathy. These patients present with diffuse
lower motor neuron weakness. Reflexes are diminished-to-absent in all four limbs. The mechanism of
action behind the lower motor neuron signs is believed to be related to disruption of the
sodium/potassium ATPase pump on the neuronal cell membrane. A build-up of intraneuronal sodium
leads to cytoxic edema, slowed axonal transport and slowed neuronal firing and muscle contraction.
Rossmeisl JH et al (2010) studied the neurologic manifestations of hypothyroidism in a group of dogs.
He studied 18 female dogs; 9 control dogs and in 9 dogs in which hypothyroidism was induced via iodine
131 treatment. Neurologic and physical exams were performed in addition to electrophysiology testing.
The result of the study, however, were very interesting. He found no clinical evidence of neuropathy on
serial examinations in any of the dogs in his study. On electrophysiology testing he found some changes
on electromyogram (EMG) but all other electrophysiology testing was normal in both groups.
Rossmeisl’s findings seemed to indicate that hypothyroidism may NOT in fact cause peripheral nerve
signs. The author conjectured that perhaps his findings were related to the fact that he ablated the thyroid
gland in order to induce low thyroid in his study dogs. Naturally occurring hypothyroidism in the dog is
secondary to immune mediated thyroiditis. He conjectured that, perhaps it is the immune system’s role in
the naturally occurring hypothyroid animals that directly affects the peripheral nerve and its myelin rather
than simply the low serum thyroid levels.
Hypothyroidism also causes a myopathic disease, specifically muscle weakness and exercise intolerance.
Thyroid hormone contributes to skeletal muscle stores of free carnitine. Carnitine is integral in
transportation of fatty acids into the mitochondria of the myocyte. Once in the mitochondria, fatty acids
go through beta-oxidation and energy is produced. Eighty percent of humans with hypothyroidism report
problems associated with skeletal muscle dysfunction and 40% have clinical manifestations of skeletal
muscle weakness at the time of diagnosis.
Rossmeisl JH et al (2009) studied the effects of hypothyroidism on skeletal muscle. He studied 9 total
dogs, 3 control dogs and 6 dogs in which he induced hypothyroidism via iodine 131 treatment. Similar to
his nerve study, he performed monthly physical and neurologic examination, electrophysiology testing,
but he also assessed CK, ALT, AST, lactate and LDH levels in addition to skeletal muscle biopsies and
muscle carnitine concentrations in these dogs. Significant increases in CK, AST and LDH were recorded
in affected dogs. There was also a significant depletion of skeletal muscle free carnitine in affected dogs.
Muscle biopsy revealed nemaline rod inclusions, decreased mean type II fiber area and increase in the
predominance of type 1 myofibers. There were accumulations of abnormal mitochondrial within the
muscles biopsied and myofiber degeneration. In conclusion, the changes both in blood work and also
muscle biopsy were consistent with altered muscle energy metabolism and skeletal muscle carnitine.
That being said, all myopathic changes were subclinical, all physical and neurologic exams were normal
between dogs studied. It could be that clinical evidence of muscle weakness was not observed due to
abbreviated length of the study period.
Diabetes mellitus is perhaps one of the more common endocrinopathies that veterinarians associate with
neurologic manifestations. Patients can have PNS and CNS signs. The most common neurologic signs
observed is a plantigrade stance secondary to a peripheral neuropathy. This stance is more commonly
observed in diabetic cats as compared to dogs. In the grand scheme of animals who are diagnosed with
diabetes mellitus, neurologic signs are not very common; 8% of cats have peripheral neuropathy signs at
the time of diabetes mellitus diagnosis. Cats present with a history of progressive paresis and muscle
atrophy, especially evident in the distal pelvic limbs. Pelvic limb reflexes are decreased, especially the
ability of the patient to withdrawal his limb at the level of the hock. The neurologic signs are normally
symmetric. This neuropathy is a mixed neuropathy with the disease affecting both the sensory and motor
nerves. Human type II diabetic patients are affected by neuropathy roughly 50% of the time.
There are several theories as to why these patients develop a plantigrade stance secondary to a peripheral
neuropathy. These theories include: reduction of the sodium/potassium ATPase pump, deficiencies in
growth factor, glycosylation of the structural protein in myelin and tubulin, abnormalities within the
vasculature and alterations in the polyol pathway. The latter is the most researched and most accepted
explanation for neuropathy signs in these patients. Normally glucose is converted to sorbitol and then to
fructose in the polyol pathway. Aldose reductase converts glucose to sorbitol; for this to occur, NADPH
is converted to NADP+. Sorbitol dehydrogenase converts sorbitol into fructose. In the presence of
hyperglycemia there is excessive production of aldose reductase leading to an excessive production of
NADP+. The production of NADP+ leads to decreased glutathione levels and increased free radical
formation. It is thought that these excessive levels of free radicals affect the axon and its myelin.
Electrophysiological testing in diabetic patients with peripheral nerve signs include electromyogram
(EMG) and motor (MNCV) and sensory nerve conduction velocity (SNCV) testing, F wave and cord
dorsum potentials (CDP). EMG shows spontaneous activity, positive sharp waves and fibrillation
potentials in distal pelvic limb musculature. MNCV and SNCV show reduced velocities. The latency of
CDP and F waves are prolonged. Polyphasia and temporal dispersion are also observed. The
electrophysiological findings are supportive of demyelination. Demyelination leads to slowed action
potential propagation and peripheral neuropathy signs. That being said, with these signs can often be
reversed or significantly improved with appropriate blood glucose regulation.
The CNS sign most commonly associated with diabetes mellitus is cerebrovascular disease.
Cerebrovascular disease is most common in diabetic who are also hyperosmolar. Viscous blood is
associated with a more turbulent flow within vasculature and can lead to ischemia.
Adrenal diseases are also associated with neurologic signs. Canine patients with hyperadrenocorticism
can present with either PNS or CNS signs. The most common PNS manifestation of Cushing’s disease is
Cushing’s myopathy, however Cushing’s mytonia can also occur. Cushing’s myopathy is term used to
describe generalized muscle atrophy observed in patients with Cushing’s disease. This muscle atrophy is
seen in roughly 35% of canine patients with hyperadrenocorticism. Muscle weakness has been reported
in between 14-57% of cases. Though observed, this muscle atrophy and weakness is often subclinical and
creatinine kinase (CK) can sometimes be mildly elevated in these cases. Cats with Cushing’s disease do
not typically have a distinct myopathy but they can have muscle atrophy.
Cushing’s myotonia is a more rare and serious sequela to hyperadrenocorticism; it occurs in 0.6% of
dogs with Cushing’s disease. This myotonia is often referred to as a pseudomyotonia. Cushing’s
myotonia is more common observed in dogs suffering from untreated Cushing’s disease for a prolonged
period of time. These patients present with severe limb stiffness and hypertrophy of the proximal
appendicular musculature. Electrodiagnostic testing in these patients reveals spontaneous discharges on
EMG. These discharges are referred to as pseudomyotonia and are considered a type of complex
repetitive discharge. Unlike true myotonic discharges which wax and wane, pseudomyotonia discharges
have an abrupt stop and start to them when they are heard. Muscle biopsy performed in patients with
Cushing’s disease reveals atrophy of the fast twitch type 2 muscle fibers. Muscle atrophy occurs
secondary to fibrosis of the perimysium and endomysium. In cases of Cushing’s myotonia muscle
hypertrophy is the result of fat deposition within the perimysium and endomysium.
Hyperadrenocorticism can also cause CNS signs. These signs are most commonly secondary to
cerebrovascular disease. In one study, 6/33 dogs with CVA’s were diagnosed with Cushing’s disease at
the time stroke. The exact pathophysiology behind stroke formation in these patients is not completely
understood, however, hypercoagulability is thought to play a key role. Cushing’s patients are in a
hypercoagulable state for one of two reasons: an increase in pro-coagulant factors or a decrease in antithrombin levels. The decrease in anti-thrombin is thought to be related to glomerular disease. The
glomerulus becomes damaged secondary to hypertension and/or a delay in immune complex clearance
and subsequent immune complex deposition at the glomerulus. Excessive glucocorticoid serum levels
lead to diminished Immune complex clearance. Glomerular damage results in loss of anti-thrombin 3 in
the urine, proteinuria and a resultant increased propensity for thrombus formation. The increase
coagulation observed in Cushing’s disease is also related to an increase in the number of certain clotting
factors within the blood stream. Humans with hyperadrenocorticism have increased numbers of clotting
factors 2, 5 and 7-12, while dogs with Cushing’s disease have increased number of factors 2, 5, 7, 9, 10
and 12.
Hypoadrenocorticism results in diffuse muscular weakness, shivering and muscle tremors. Some patients
also have weakness of the pharyngeal and esophageal muscles; they can present with dysphagia. If
weakness is severe patients can also show signs consistent with a lower motor neuron tetraparesis.
Appendicular reflexes are reduced and dysphagia can be observed. It is thought that with
mineralocorticoid deficiency alterations in sodium and potassium concentrations lead to alterations in
muscle membrane potential and poor muscle membrane excitability and alterations in the Na/K+ ATPase
activity. In extreme cases hyponatremia can cause cerebral edema secondary to dysfunction of the
neuronal Na/K ATPase pump. Glucocorticoid deficiency Addisonians have decreased gluconeogenesis
and glycogenolysis. Decreased glucose concentrations directly affect the brain and neuronal activity as
neurons are dependent on whole body glucose stores. Decreased glucose leads to decreased ATP
production, decreased neuronal energy and neuronal apoptosis.
Polycythemia or erythrocytosis is can also be associated with central nervous system signs. The increased
number of red blood cells in the bloodstream increase the viscosity and turbulence of blood flow. This
turbulence leads to cerebrovascular disease and thrombosis formation. Neurologic signs are secondary to
ischemia and would depend on the location within the CNS of the ischemia.
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