Its a bird, it’s a plane…it’s Hyperesthesia Syndrome in Cats! <groan>
Brachial Plexus Avulsion: What Should You Know?
Midazolam vs. Diazepam...Which Drug is Better for At-Home Cluster Care?
Midazolam vs. Diazepam for At Home Seizure Care
History of Cluster Buster Protocols
In 1995 Dr. Michael Podell championed the idea of at-home, rectal diazepam use for canine cluster seizures. In that study, dogs that received rectal diazepam had fewer cluster seizures compared to those that didn't receive the drug. Since then, at home cluster care has become standard practice for many veterinarians.
According to human literature, benzodiazepine drugs (midazolam, diazepam and lorazepam) are the "best" first line anticonvulsant drugs to stop status epilepticus. As is typical, we simply adopted this idea in veterinary medicine without data to support it's use. But...the benzodiazepine drugs do show improved seizure cessation so...they probably help in some manner.
Which Benzodiazepine is Better?
Here is where the science gets a bit muddy. We've compared rectal diazepam to intranasal midazolam and intranasal midazolam was superior. We've compared intranasal midazolam to intravenous midazolam and intranasal midazolam stopped seizures faster. However, all of these studies involved few animals and ethically we cannot have a group of untreated animals to determine true efficacy.
What are the current recommendations?
At this time, intranasal midazolam at a dose of 0.2 mg/kg up to 3 times in 24 hours is my recommendation for dogs with a cluster or status epilepticus history. Do your best to use a nasal atomizer because this has been shown to be the superior technique compared to nasal-drop application. (I have found them at Midwest Vet:https://www.midwestvetsupply.com/products). Essentially nasal drop technique requires the client to drip the midazolam intranasal slowly during the active seizure while also avoiding getting bitten. The atomizer looks like a marshmallow that is attached to the end of the syringe and the client is then able to press the atomizer against the nare and dispense the dose in one "push". Not clear on this technique? Please ask me, I am happy to clarify! I do not have a financial incentive or disclosure for this product, or Midwest Vet Supply. :)
Hope you enjoyed the glorious weather a bit last week. I will be closed Friday October 16th, Saturday the 17th and Tuesday the 20th as we celebrate a collection of birthdays in my family. (Including mine!)
Have a good week!
Do Cats Have Seizures?
Do Cats Have Seizures?
You might be thinking "Has she lost her mind? Of course cats have seizures!" Naturally, we know this to be true (or half of my research is for nothing...eek!) A recent article published in the Journal of Veterinary Internal Medicine looked at a population of cats in the UK in the year 2013 to answer some questions about feline epilepsy. I have bulleted them below for ease of reading however this is an open access article so feel free to pull the entire article if you would like to know more!
The study aims: "To estimate the prevalence of recurrent seizure disorders (RSD) and epilepsy in the wider cat population under primary veterinary care int he UK and to evaluate demographic risk factors for their occurrence. A secondary aim was to explore risk factors associated with the diagnosis of epilepsy among the subset of cats."
1-year prevalence (2013) for recurrent seizure disorders (not called epilepsy): 0.16%
1-year prevalence for epilepsy: 0.04%
* Note these are lower than the listed prevalence for referral institutions (and mobile veterinary neurologists) for the obvious reason that referral hospitals have a different caseload!
Diagnosing epilepsy in cats is not defined, as it is in dogs, by the International Veterinary Epilepsy Task Force (IVETF). Many neurologists, myself included, extrapolate from the IVETF recommendations but also realize the limitations in data for cats.
The IVETF recommendations for dogs to diagnose epilepsy (Tier 1 - aka without diagnostic testing) are:
two or more seizures, at least 24 hours apart
Age 6 months - 6 years old
Normal (unremarkable) neurologic examination inter-ictal
No clinical abnormalities on CBC, serum biochemisry, urinalysis
A diagnosis of epilepsy was made in this study in 24.89% of the cats with recurrent seizure disorders. There was a disturbing sentence that I quote "It is conceivable that general veterinary practitioners may feel reluctant to formally diagnose epilepsy or idiopathic epilepsy in cats because of a combination of factors, including their limited confidence in performing a complete neurological examination in cats, the longstanding traditional belief that cats do not commonly have idiopathic epilepsy, and a believe that access to advanced imaging is essential to exclude other causes." This sentence is the reason I chose this article for our TidBit Tuesday this week. First, if you're not diagnosing a cat with epilepsy (and presumable starting appropriate care or recommending appropriate testing) because of a lack of confidence in the exam, know that you are not alone! Please call me for a neurologic examination with your feline patient - I too understand the limitations of cats in assisting with their own health care. (To put it mildly.) Let's not let a lack of confidence in the examination block us from doing what is right by the pet. Secondly, idiopathic epilepsy does occur and in this study it was almost 1/4 of the cases of recurrent seizures (if they diagnosed it correctly, of course). It has been reported that up to 12% of cats can have a normal neurologic examination and have structural disease, but that shouldn't stop us from attempting appropriate treatment. Please, let's remove this thought from our practices. Finally, you do NOT need access to advanced imaging to make a presumptive diagnosis of idiopathic epilepsy. The Tier I recommendations were designed expressly to meet the needs of making this diagnosis (in dogs) without MRI or spinal tap. Whew...okay, back on track.
Following multivariate analysis, the only variable that stood out as a risk factor for a diagnosis of epilepsy was age. Cats 3-6 years of age had a 3.32 times higher odds of developing epilepsy then cats less than 3 years of age.
Insurance was also a risk factor but that doesn't apply to the majority of the pets that I interact with so I have left that portion of the study out. Breed and sex were not associated risk factors.
*O'Neill, DG, Phillipps, SA, Egan, JR, Brodbelt, D, Church, DB, Volk, HA. Epidemiology of recurrent seizure disorders and epilepsy in cats under primary veterinary care in the United Kingdom. J Vet Intern Med. 2020; 1– 13. https://doi.org/10.1111/jvim.15881
I hope you are doing well and staying safe. I appreciate what you do to help clients and their pets. Let me know how I can help you manage your patients with neurologic disease.
On site consultation is available Monday through Saturday at variable times throughout the week. Email consults are completed in evenings.
Have a good week!
Tick Paralysis and Dogs
Tick Paralysis and Dogs
The ticks are still here but owners may have stopped applying topical treatments. So fall is the time to be on the look out for Tick Paralyses (okay, really anytime but now isn't a BAD time to be aware)!
What causes Tick Paralysis?
Salivary transfer from a Dermacentor (in America) and Ixodes (in Australia, for my Australian readers) will result in neuromuscular blockade. How it actually works is really pretty ingenious. (Skip this next part if you're in a hurry.) At the presynaptic terminal, acetylcholine packets must be released into the neuromuscular junction so they can then bind to the post synaptic (muscle) membrane receptors. The acetylcholine binds to the presynaptic membrane using specific proteins as well as calcium. The saliva from one of the aforementioned types of ticks will interfere with acetylcholine release at the presynaptic terminal by binding calcium. Amazing, really.
What are the common clinical signs?
If you cannot release acetylcholine from the presynaptic membrane at the neuromuscular junction, what can you do?
Exactly, nothing.
Therefore clinical signs are an ascending pelvic to thoracic limb flaccid paralysis. No reflexes, no motor, no paw replacement, nada. These signs begin 5-9 days after exposure to the tick saliva. Cranial nerves are RARELY affected. This is important because botulism more commonly affects cranial nerves and this can be one way to try to differentiate between these two diseases.
How do you make the diagnosis?
1. Find the tick.
2. Remove the tick.
2.5 (Apply Frontline/Bravecto/other)
3. Clinical improvement should begin 24-48 hours after tick removal.
No specific testing is available to confirm the diagnosis.
I once had to find a tick on an Old English Sheepdog waaaay back in the year 2000. Topical tick treatment wasn't as prevalent then as it is now, so our solution was to shave the dog. We found the tick between the dog's toes. (Insert eye rolling here!!) In 2020, I suggest applying Frontline/Bravecto (your choice of topical flea treatment) first then perform a non-invasive tick hunt and monitoring for clinical improvement. If ineffective after 48 hours you can either commence a thorough tick hunt, or search for other causes of flaccid paralysis. (Or, call me for a neurology consultation!)
How do you manage patients flaccid paralysis?
Flaccid paralysis means that the animal does not have reflexes, or voluntary motor. As such, these animals may be at risk of respiratory failure due to loss of intercostal muscle function. Therefore CO2 monitoring, respiratory watch and ventilatory support if needed can be very important in the early stages of disease. Due to the rapid recovery, most patients do not need long-term intensive nursing care or physical therapy.
I hope you are doing well and staying safe. I appreciate what you do to help clients and their pets. Let me know how I can help you manage your patients with neurologic disease.
On site consultation is available Monday through Saturday at variable times throughout the week. Email consults are completed in evenings.
Have a good week!
Metronidazole and Vestibular Signs
Today is the first day of Fall 2020!
In honor of this awesome season, I thought we'd talk about another type of fall...vestibular disease! :)
How Does Metronidazole Cause Vestibular Signs?
It is not 100% certain, but it appears that modulation of GABA at the level of the cerebellum is involved. Stay with me...!! GABA is an inhibitory neurotransmitter and there is LOADS of GABA in the cerebellum because it is a largely inhibitory part of the brain. (I like to think of the cerebellum as my mother. As a mother, my job is to "modulate" the activity of my children so they don't get hurt! When you take a step, I tell you how far, how wide, etc. so that you don't trip on a stair. See my point?) Okay, so if the cerebellum is inhibitory to movement, and you remove inhibition, movement gets exaggerated. (Hypermetria, intention tremors, truncal sway!) The cerebellum helps to keep balance in check as well via various mechanisms. Getting back to metronidazole, if we inhibit GABA, then actions become more exaggerated.
Signs of Metronidazole Toxicity
DOG: Signs of cerebellovestibular disease including head tilt, nystagmus, positional strabismus, truncal sway, hypermetria, intention tremor.
CAT: Okay, cat's don't play by the rules. They show forebrain signs such as seizures, blindness and mentation changes. Let's not talk about cats today, okay?
Diagnosis of Metronidazole Toxicity
This is both an easy one, and a hard one. There isn't a specific "test" used to make the diagnosis. However, with a history of ANY DOSE of metronidazole within the last 12 hours, one might consider metronidazole toxicity. I have seen several dogs that received metronidazole historically without trouble and developed signs of toxicity on subsequent dosing. I also have seen signs of toxicity at the first dosing sequence at standard doses. It is more likely at higher doses (60 mg/kg/day) but do not exclude the possibility at lower doses.
Treatment for Metronidazole Toxicity
Stop metronidazole administration! Additionally, you can administer diazepam at 0.1-0.5 mg/kg PO q8hr for several days. Why diazepam? I'm glad you asked! Diazepam is a GABA agonist, therefore it confers more inhibition to the cerebellum. Dogs receiving oral diazepam recovered in 1.5 days compared to untreated dogs that recovered in 11 days. (Evans J, et al. JVIM 2003; 17(3):304-310.) I routinely prescribe diazepam for pets with suspected metronidazole toxicity as a result of this study.
Whew it has been busy lately!! I hope you are doing well and staying safe. I appreciate what you do to help clients and their pets. Let me know how I can help you manage your patients with neurologic disease.
On site consultation is available Monday through Saturday at variable times throughout the week. Email consults are completed in evenings.
Have a good week!
Can the neurologic examination predict disease?
Age, the Neurologic Examination and Prediction of Disease
Age isn't a disease, right? But, disease is associated with age. The older pet, is more likely to have structural disease (i.e. idiopathic epilepsy vs CNS neoplasia), compared to the younger pet. But, none of us want to diagnose a terminal disease in an older patient simply because the patient is older!
How can the Neurologic Examination Help Vets with Old Patients?
Can we look at two of the most commonly performed tests on the neurologic examination and determine the sensitivity and specificity for the detection of a forebrain lesion? Actually, yes we can. The menace response and paw replacement (previously called conscious proprioception) testing both assess the forebrain and are some of the most commonly performed parts of the neurologic examination. Here is what a recent group from Australia found:
Menace response
Sensitivity: 72%
Specificity: 47%
Odds ratio: 2.26
Proprioception
Sensitivity: 54%
Specificity: 72%
Odds ratio: 3.08
If age is then factored into the analysis, dogs greater than or equal to 6 years of age are more likely to have a forebrain disease detected if they have a menace or proprioceptive deficit.
As a "field" neurologist (without a pocket MRI...yet) this tells me that I should encourage diagnostic imaging in patients with menace deficits and proprioceptive deficits. The chances (or Odds) of a patient having underlying forebrain disease is higher if they have these deficits than if they don't. Seems intuitive, but proprioceptive testing isn't as sensitive as assessing the menace response so by all means don't forget to do that on an older patient! :)
Hope this little study was insightful for you too.
Chan MK, Jull P. Accuracy of selected neurological clinical tests in diagnosing MRI-detectable forebrain lesion in dogs [published online ahead of print, 2020 Jul 15]. Aust Vet J. 2020;10.
Keep those consults coming! I'm continuing to answer email consults in the evenings but do my best to be available during working hours should you have a questions and wish to call or text me. On site consultation is available Monday through Saturday at variable times throughout the week.
Have a good week!
C Reactive Protein and Discospondylitis
C-Reactive Protein and Discospondylitis
What is C-Reactive Protein (CRP)?
It is an acute phase protein that has been used in other inflammatory conditions such as SRMA, IMPA or inflammatory bowel disease to support or monitor the clinical response to treatment.
Is it elevated with Discospondylitis?
Short answer: yes.
Long answer: It was elevated in most dogs in a recent study that were diagnosed with bacterial discospondylitis, but not all. In 8 dogs they measured it again 4-6 weeks into antibiotic treatment and it was normal in all 8 dogs.
What can we do with this information in practice?
When faced with a patient with discospondylitis you can use CRP to support the radiographic evidence of discospondylitis. I would NOT suggest using this as a disease monitoring tool for dogs with discospondylitis because, as the authors point out, the intervertebral disc is a very immune privileged area of the body therefore infection could persist that is not reflected in the CRP. One of the dogs, in the study quoted above, with normal CRP, had a recurrence of signs after stopping antibiotics. This suggests that CRP may not be a good long-term monitoring tool.
That's all for this week! Have a safe, happy week and keep those consults coming!
Nye G, Liebel FX, Harcourt-Brown T. C-reactive protein in dogs with suspected bacterial diskospondylitis: 16 cases (2010-2019). Vet Rec Open. 2020;7(1):e000386. Published 2020 Jul 20. doi:10.1136/vetreco-2019-000386
Neuroanatomic Lesion Localization Practice Case
Lesion Localization and Case Building Practice
Lesion localization is one of those things that can be lost, if not practiced. Don't lose it! You're welcome! :)
Maria, is a 13 year old FS Lab
History: Presented to me with a 24 hour history of acute onset difficulty walking.
Neurologic examination:
Mentation: BAR
Cranial nerves: right head tilt, rotary nystagmus, remainder normal.
Gait: Moderate vestibular ataxia, falling right. No hypermetria or intention tremors noted.
Postural reactions: absent right thoracic and right pelvic limbs, normal other limbs
Spinal reflexes: Normal all limbs, normal c. trunci and perineal
Palpation: non painful, normal cervical ROM
You know what you've got to do now, right?
What is the Neuroanatomic Lesion Localization?
There are several ways to go through lesion localization.
OPTION 1:
I like to make lists. Start by listing all of the abnormalities and ALL possible locations that could result in an abnormal finding. For example:
1) Right head tilt - peripheral CN 8 (right), medulla (right), cerebellum (right or left)
2) Rotary nystagmus - same as above
3) Vestibular ataxia - same as above
4) Reduced paw replacement right side - right C6-T2, right C-C5, right medulla, right pons, right or left midbrain, left prosencephalon.
Now, we start to eliminate some things. How do to differentiate peripheral vs. brainstem vs cerebellar disease? Well, for starters any animal with cerebellar disease is expected to have hypermetria and/or intention tremors and Maria did not. We can cross out cerebellar disease. What else? Animals with brainstem disease should have a) change in mentation and/or b)ipsilateral paw replacement deficits and/or c) hemiparesis. Maria has paw replacement deficits ipsilateral to the head tilt so she most likely has brainstem disease.
OPTION 2:
The other way to work through this is to identify the cranial nerve affected on the exam (in this case, cranial nerve 8), identify the brainstem segment associated with this cranial nerve (in this case, medulla) and then ask yourself if you can identify a,b, or c from above. If not, it is peripheral and if so, it is brainstem.
Differential Diagnoses
Brain stem vestibular disease in an elderly dog without an important prior medical history would suggest the following differential diagnoses:
Degenerative: none
Anomalous: none
Metabolic: Hypothyroidism
Neoplastic/nutritional: Neoplasia of the brainstem
Infectious/inflammatory/idiopathic: meningoencephalitis (infectious or inflammatory)
Trauma: no supportive history
Vascular: Cerebrovascular accident (stroke)
Diagnostic plan
CBC, serum biochemistry, T4, blood pressure, urinalysis. (Screen for causes of stroke and hypothyroidism). Brain MRI +/- CSF tap.
Final diagnosis: Cerebrovascular disease! She was lucky. We didn't find any underlying cause of disease therefore this was considered idiopathic vascular disease. She showed gradual improvement with the addition of meclizine over 3-4 days with a residual head tilt after 7 days. The head tilt is expected to be permanent but isn't always the case.
How did you do? The neurologic examination, when done thoroughly, can be your best diagnostic tool for patients with neurologic disease! Keep practicing.
I hope you are well, and taking care of yourself. If you have a dog or cat with neurologic disease please reach out - I'd love to help.
Happy September 1st!
The Five Types of Disc Herniation
The Five Types of Disc Herniation (that we know of!)
Dystrophic calcification secondary to chondroid degeneration of nucleus pulposus (NP), called a Hanson Type I. This causes mechanical stress on the outer annulus fibrosus (AF), leading to rupture of individual collagenous strands of AF and eventually full failure.
Fibrous degeneration occurs when fibers of disc split leading to accumulation of tissue fluid and plasma between them. Over time the mechanical pressure exerted by NP causes thickening of the AF dorsally, causing protrusion. (Hanson Type II).
ANNPE (Acute noncompressive nucleus pulposus extrusion) - this is normal NP that is exploded into the canal, usually during activity. Also called a traumatic disc herniation.
AHNPE (Acute hydrated nucleus pulposus extrusion) – An apparently normally hydrated NP that is compressive and often located ventral to the cord, often in the neck.
Significantly more neuro deficits and less signs of cervical pain with AHNPE compared to other causes of cervical myelopathy.
FCE (Fibrocartilaginous embolism): a piece of NP that becomes dislodged and finds its way into the vasculature surrounding the spinal cord. This can be into venous or arterial blood vessels. The end result is an acute shift in blood flow at the level of the spinal cord.
Match the clinical sign with the type of disc herniation
A. Chronic, progressive ataxia progressing to paresis
B. Acute, non-progressive unilateral weakness affecting one leg, or one side (hemiparesis)
C. Acute, progressive, painful ataxia progressing to paresis in a chondrodystrophic dog
D. Acute non-progressive ataxia and paresis affecting both sides of the body (paraparesis or tetraparesis)
E. Acute, rapidly progressive tetraparesis and ataxia of all four limbs with minimal cervical pain
If you answered...
Type I: C
Type II: A
ANNPE: D
AHNPE: E
FCE: B
you are correct!
Based on the clinical picture, it can be very difficult to distinguish Type I from ANNPE, and AHNPE. Typically, type I is painful (but not always), and the other two are minimally to non-painful.
Which of these require surgery?
Any disc herniation that results in compression of the spinal cord with associated clinical signs could be considered for surgical correction. This statement would then suggest that Type I, Type II and AHNPE could be surgically corrected. Therefore, any patient with signs of a progressive or painful myelopathy should be evaluated for diagnostic imaging (typically MRI) for possible surgical intervention whenever possible.
Bonus question:
Can you name two diseases that are commonly diagnosed instead of a type I or type II disc herniation? Scroll to the bottom for the answer!
Change is coming! Starting in September I will have new fees, and new availability. I am happy to accommodate outside of these hours whenever possible so please reach out if you cannot find a suitable time using the online scheduler. ( https://barnesveterinaryservices.com/ )
New Hours (Starting September 8th)
Monday 11a-1p, 4-5p
Tuesday 3-4p
Wednesday 11a-1p, 2-4p
Thursday 2-4p
Friday 12-1p
Saturday 9-11a
Bonus Question Answer
Meningoencephalomyelitis (a.k.a meningitis), and neoplasia. Keep these two on your differential diagnoses list when you suspect a disc herniation!!
CBD oil and Canine Epilepsy
What is the Effect of CBD oil on Canine Seizures?
Yes, I'm opening a proverbial can of worms today! As a neurologist, vets often ask me if CBD can be used as an anti-epileptic drug (AED). As a practicing veterinarian in Wisconsin I say I cannot recommend or prescribe CBD containing products.
As a neurologist, I add the following…
In June 2019 a study was published that attempted to answer the question:
“What effect does CBD oil have on seizure control?”1
According to the authors:
CBD is metabolized through the cytochrome system in the liver in humans, and probably dogs. The ALP increased in all dogs receiving CBD oil in that study. What is the clinical significance? Unknown, currently.
There was no difference in seizure response between the CBD group or the placebo group (Response = dogs that had a 50% or greater reduction in seizures during the 12-week observation period.) Do we need a different dose? Different formulation? Or did it simply not work for this group of dogs?
Drugs that are metabolized through the liver (e.g. phenobarbital, zonisamide) may be affected by CBD. This means that the adverse clinical effects could be more pronounced in dogs concurrently receiving these drugs.
What adverse clinical effects does CBD have? We don't know yet. Several dogs in the CBD group developed ataxia, however they were concurrently on other anti-epileptic drugs. Was the ataxia due to CBD, or because of increased serum concentrations of concurrent AED?
So, although my response to clients remains that I don’t recommend it. My reasoning includes all of the reasons listed above in addition to the recommendations by the government officials in Wisconsin.
What if a client wants to give it anyway? As a veterinarian, I would thoroughly document the discussion, and then recommend monitoring at least liver values (ideally the entire biochemistry panel) every 4-6 months while the pet receives the product. It may be that CBD is the magical seizure potion we are searching for to help our drug-resistant seizure patients. However, history would tell us that the newest “catch all” tonic is typically not as universally perfect as we wish it to be. Be educated, be careful, and be observant when we walk into this yet uncharted territory of CBD oil and seizures.
1. McGrath S. et al Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy. JAVMA 2019; 254(11): 1301-1308.
Are you working with a patient with seizures and need some expert help? I'd love to! Please reach out via email, telephone or schedule an appointment online.
Microbiome and Epilepsy
Microbiotia-Gut-Brain axis...say what?
There has been growing evidence in human, and veterinary, medicine to suggest that what is in the gut can influence brain development, function and even the course of disease. Many clients have a firm belief that food plays a role in a dog's epilepsy however it has been less clear to me what this role may be. Is it the gluten in the diet (as with some Border Terriers)? Or, is it the microbiome? Maybe both? Maybe neither?
Lactobacilli and the Influence on the Brain
Research suggests that Lactobacillus sp. can play a role on brain function in humans through it's anti-inflammatory properties and perhaps through the production of GABA, an inhibitory neurotransmitter. What about dogs with epilepsy? Dr. Karen Munana investigated Lactobacilli in fecal samples of dogs with epilepsy and compared them to fecal samples of dogs without epilepsy. (See reference below)
No difference in absolute ore relative numbers of Lactobacillus species were found in drug-free epileptic dogs compared to healthy dogs. Furthermore, Lactobacilli were not killed in culture when exposed to phenobarbital, potassium bromide, zonisamide and levetiracetam.
For now, this means we don't see a difference in this important bacterial species. This DOESN'T mean that we may not find a difference in the future, and it DOES NOT mean that gut health isn't linked to canine epilepsy. I will keep my ear to the ground on this one and keep you posted on any breaking news on GI health-brain health linking.
Stay safe, stay healthy, and keep me posted on how I can help you, help your patients with neurologic disease!
*Muñana KR, Jacob ME, Callahan BJ. Evaluation of fecal Lactobacillus populations in dogs with idiopathic epilepsy: a pilot study. Anim Microbiome. 2020;2(1):19.
What do you do with a missing reflex?
Cognitive Dysfunction Syndrome in Cats
What is Cognitive Dysfunction in Cats?
Sixteen years ago when I left my residency and started out as a newly minted neurologist, feline cognitive dysfunction syndrome (CDS) was not on my radar. That has changed. As we learn more about aging in cats, it has become a more widely recognized disease by yours truly, as well as many of you in practice. If you're like me and need a Tidbit-Tuesday style refresher...read on!
What is cognitive dysfunction syndrome?
Cognitive dysfunction syndrome (CDS) is a term used to describe deterioration of mental capabilities associated with age. Clinical signs referred to cognitive dysfunction can also be associated with other age-related illnesses (e.g. osteoarthritis, structural intracranial disease such as neoplasia, or cardiovascular disease). See table 1 for an outline of behavior changes seen in cats with CDS.
The underlying etiology of CDS is yet unknown. Causes such as oxidative stress/damage, neurodegeneration and vascular changes are among the leading hypothesis for human and canine CDS, and therefore suspected to be similar in feline CDS. Deposits of extracellular B-amyloid and intracellular accumulation of microtubule-associated protein tau have been seen in human patients with cognitive dysfunction. Similarly, B-amyloid deposits and increased tau have been detected in aged cats with cognitive decline, however the significance remains unclear.
What are the clinical signs of cognitive dysfunction in cats?
There is a handy article, recently published in the Veterinary Clinics of North America by Dr. Miele and associates that echos what others have been reporting in a very concise little table. (See reference at bottom) I have replicated this table, with a few modifications, here. Note: There are other signs such as decreased appetite or thirst, that don't usually drive an owner or veterinarian to seek consultation from a neurologist so I haven't included them here.
Table 1: Clinical behavioral changes associated with CDS in cats.Increased vocalization, especially at nightAltered social interaction and relationships, either with other or other pet. Altered sleep/wake patterHouse soilingSpatial Disorientation or confusion (i.e. forgetting the location of the litter box)Temporal disorientation (i.e. forgetting if they have been fed)Altered activity (i.e. aimless wandering)AnxietyLearning and memory dysfunction
How is CDS in cats diagnosed?
Oh, this is as tangled of a web as the tau proteins we chase. (A little CDS humor here...you see the tau proteins can cause the "tangles" seen in human CDS.). Currently, the diagnosis is made by ruling out structural brain disease and systemic causes for disease. This may include complete blood count, full biochemistry panel including thyroid screening, urinalysis, chest radiographs, blood pressure assessment, brain MRI and possibly spinal tap. Imaging changes associated with canine CDS include increased depth of the sulci, dilation of ventricles secondary to neuronal loss (called ex vacuo hydrocephalus) and a measurably small interthalamic adhesion. Exclude everything else, and it's probably CDS.
How can we help these cats age easier?
Currently, there are no proven treatments for feline CDS. The addition of antioxidants (B vitamins, vitamin C, other) as well as fish oil were evaluated for use in cats in one study and showed promise. The use of S-adenosyl-L-methionine (SAMe) has been recommended for cats based on a study that identified improved performance on cognitive testing. This study only found significant improvement in cognitive function testing in the least affected cats. In addition to medical management, environmental management with ready access to food, water, litter box and areas of comfort (beds, hiding spots) is recommended. Environmental stimulation with low impact toys, or bird feeders in which the cat can choose to ignore any activity if they do not feel inclined to engage, are recommended. Finally, focused veterinary visits can be important for cat owners to feel supported through the aging process. Focus your exam specifically evaluating body weight, urine production (to assess for signs of dehydration), behavior changes and mobility.This may help detect signs earlier in the course of disease and to identify concurrent morbidity that may contribute to, or be confused with, cognitive dysfunction.
Did I forget anything? Most of you treat and see this more than I do. What do you see in practice? What have you used (successfully, or not) for treatment? Please reach out - I want to hear your perspective!
Reference:
Miele A, Sordo L, Gunn-Moore DA. Feline Aging: Promoting Physiologic and Emotional Well-Being. Vet Clin North Am - Small Anim Pract. 2020;50(4):719-748.
What Do You Do With a Confused Cat?
What do you do with a confused cat?
Sigalment: 12 year old FS Domestic short-haired cat
History: 2-3 week history of seeming "confused", and a recent onset of circling right more than left. These very astute owners observed the cat seemed to walk into a room, forget why it entered, stand there, and then leave again. Additionally, she wasn't as bright as is typical for this indoor-outdoor Wisconsin cat. Birds would land on the feeder outside of the window and she appeared uninterested.
Physical examination: Normal TPR, normal exam. This was a remarkably fit cat for her age!
Neurologic examination:
Mentation: Obtunded
Cranial nerves: absent left menace response, normal PLR and normal menace response on the right. The cat was less responsive to facial stimulation on the left lip but did respond to hemostat pinch. All other cranial nerve exam findings were within normal limits.
Gait: Ambulatory with mild proprioceptive ataxia and occasional circling right
Postural reactions: absent tactile placing left pelvic limb, intermittent on left thoracic limb, normal on right thoracic and pelvic limbs.
Spinal reflexes: normal all limbs, and c. trunci
Okay..take a moment and put all of that together in your mind. I'll take this moment to remind you that my next Webinar is on Wednesday July 15th (TOMORROW) and we'll be talking about lesion localization. If you're interested in joining me to practice on cases just like this please go to https://barnesveterinaryservices.com/ce-opportunities and sign up!
Back to this case. How did you do? Here is how I would talk myself through this one...
1. The cat has a change in mentation..the problem MUST be intracranial.
2. There is a menace deficit - the affected parts could be cranial nerve 2, forebrain or cranial nerve 7.
2a. PLR is normal (this is cranial nerve 2, midbrain and cranial nerve 3) so we can eliminate cranial nerve 2 as a possible cause of the menace deficit.
2b. The cat did not have any noted change to motor of the face (run by cranial nerve 7), so we can eliminate cranial nerve 7 as a cause for the menace deficit.
2c. Finally, one must remember that the menace response crosses and enters the opposite side forebrain so, since we have narrowed the problem down to the forebrain we then must comment that it is the RIGHT forebrain we are concerned about
3. Circling is either a vestibular or forebrain sign. This cat did not have evidence of vestibular disease so we could consider this another forebrain sign. Animals circle towards their lesion, thus supporting a RIGHT forebrain lesion.
So far, so good?
4. Tactile placing goes from the toes, up the ipsilateral spinal cord, brain stem (crossing at the midbrain) and enters the opposite side forebrain. Voila! We don't have any evidence of spinal cord disease, or brain stem disease in this cat (no cranial nerve deficits) so this also suggests a RIGHT forebrain lesion.
What about that sensory deficit on the cranial nerve exam? This actually suggests a proprioceptive change to the face! This finding might be the only finding we didn't routinely teach in veterinary school because it's an oddity. But, it is a crossing tract and reflects forebrain disease.
So, what lesion localization did you come up with? Scroll to the bottom to see if you are correct.
Diagnosis
We diagnosed a brain tumor on MRI (see image above) and took this kitty to surgery. The mass was removed entirely, and was eventually diagnosed as a meningioma. Meningiomas are locally invasive, rarely spreading, intracranial tumors in cats. With complete surgical resection no additional treatment is needed! The cat went back to her normal personality, stopped circling, and regained vision in the left eye post operative (by the 1 month recheck...not immediately). Pretty cool stuff, huh!?
I hope you have a safe and fun week. Keep those consults coming and I hope to see you at the Webinar tomorrow!
Answer: RIGHT forebrain.
What drug, route and dose should you use for at home acute seizure management?
I hope you had a wonderful and safe 1st and 4th of July (my American and Canadian friends)! Enjoy this week's TidBit Tuesday...
What drug, route and dose do you use for at home acute seizure management?
For most of us, benzodiazepine drugs (diazepam, midazolam, lorazepam) are our first choice drugs for acute seizure cessation.
Not all benzodiazepine drugs are equal!
What routes can you give the drugs? What routes shouldn’t you give the drugs?
Benzodiazepine drugs were introduced in the 1960s for human status epilepticus. A 2015 human meta-analysis identified that benzodiazepines are the “best” first line IV drugs. To date, there have not been any veterinary studies identifying which drug is ‘best’ for acute seizure management. We’ve just always used benzodiazepines so we continue to do so. Furthermore, limited data regarding efficacy is available for veterinary patients. So, what do we know?? The table below outlines the approved routes for each of the common benzodiazepine drugs. This should be printable.
DiazepamSafe for dogs ☒Safe for cats ☒ Okay if given:IV ☒IM ☐ Not recommended!Rectal ☒ Preferred drug!Intranasal ☒MidazolamSafe for dogs ☒Safe for cats ☒ Okay if given:IV ☒IM ☒Rectal ☐ (nope).Intranasal ☒ Preferred drug!LorazepamSafe for dogs ☒Safe for cats ☒ Okay if given:IV ☒IM ☐ No dataRectal ☐ Nope, not absorbedIntranasal ☒
In 2017 a randomized veterinary clinical trial determined that intranasal midazolam was superior to rectal diazepam for controlling seizures in some dogs. As such, intranasal midazolam (0.2 mg/kg intranasal) is currently my treatment recommendation for at home anti-convulsant care. Guess what? It works great in hospital too when you cannot access a vein fast enough.
My current recommendations for at home care are:
1) Intranasal midazolam at 0.2 mg/kg IN up to 3x in 24 hours. Use a nasal atomizer - it's a game changer.
2) Rectal diazepam at 1 mg/kg PR up to 3x in 24 hours. Make sure to prescribe the BOTTLE, this drug is light sensitive so dosing it in a syringe makes it useful for up to 30 minutes and then it may loose potency.
Other choices, such as rectal or IV levetiracetam, have been evaluated for acute seizure management too. We have more data about benzodiazepine drugs, and I'm more accustomed to using them (over the past 20 years!) therefore they are still my preference. I'll keep you posted if data surfaces suggesting we should change to using levetiracetam, or another drug, instead of the benzodiazepine class.
Stay safe and keep those consults coming! For July my days of operation should remain Monday-Saturday. The schedule will change at the end of August once we sort out what kind of schooling we will be doing for the kiddos - I will keep you posted or you can always check the website or Facebook. Thanks for reading!
Portosystemic Shunts and Their Effect on the Nervous System
Portosystemic Shunts and Their Effect on the Nervous System
Portosystemic shunts (PSS) are common in small breed dogs and surgical correction is commonly recommended. However, there is concern about neurologic signs peri-operative for these patients. Some develop seizures, mentation changes, and other neurologic signs before shunt attenuation while others do not show signs until after shunt attenuation. Sadly, the presence of neurologic signs is a poor prognostic indicator according to many studies. One recent study looked for prognostic indicators in dogs that develop seizures post attenuation (PAS) within 7 days of surgery. I hope you'll find the study as interesting as I did!
Study Design
This was a retrospective study including 93 dogs from 14 different institutions. 53% of dogs received prophylactic levetiracetam. There were lots of different small breeds with a median age of 34 months (range 5-124 months).
Results
17.3% of the dogs had experienced at least 1 seizure prior to surgery.
Interestingly, 78% of the dogs had exhibited neurologic abnormalities including those with seizures.
Only 30% of dogs with PAS survived to 30 days. Yikes.
More often those with focal seizures survived, compared to dogs with generalized seizures.
Sadly, the most common reason for euthanasia following the shunt was the presence of uncontrolled seizures.
Key Points
According to their multivariate analysis the only two factors associated with short term survival were 1) having a history of seizures PRIOR to shunt correction (p=.004) and 2) the development of focal PAS (p=.0003). That's it!
So, what do we tell our clients? Well, for starters..they need to know that these pets are are risk of developing seizures even if they DON'T have surgery. But, according to this study if they do elect surgery, the development of generalized seizures is a poor prognostic indicator.
This article was packed with other data so if you want to read the entire thing please reach out and let me know.
Reference:
Mullins RA, Sanchez Villamil C, Selmic LE, et al. Prognostic factors for short term survival of dogs that experience post attenuation seizures after surgical correction of single congenital extrahepatic portosystemic shunts: 93 cases (2005-2018) Vet Surg.2020; 49:958-970.
That's it for now! I'm maintaining curbside service for the summer and am starting to widen my travel radius again. Please reach out if I can asist with a case. Stay safe, stay healthy!
Help! My patient sustained head trauma!
Help! My Patient Sustained Head Trauma!
Traumatic brain injury (TBI) in dogs and cats is a dynamic process. The outcome depends not only on the severity of the primary injury, but also on the resulting secondary effects. Primary injury is defined as injury that occurs at the moment of impact and results in physical disruption of tissues (fracture, etc.). Secondary injury is defined as the physiologic alterations that occur hours to days after the primary injury. Medical therapy is aimed at affecting secondary injury. Animals with TBI frequently have serious injuries elsewhere and shock, hemorrhage, airway obstruction, pneumothorax, and traumatic cardiac arrhythmias should be detected and treated timely.
Pathophysiology
Following TBI local vascular disruption can cause hemorrhage, which results in deposition of iron, free radical formation and mass effect. The effects on the vascular system contribute to vasogenic edema. Cytotoxic edema is the other type of edema that can occur in head trauma. Cytotoxic edema forms when excessive neurotransmitters are released by surrounding cells, which cause overstimulation of neurotransmitter-dependent channels, causing excessive intracellular accumulation of sodium and calcium. Increased intracellular sodium results in an osmotic draw of water into the cell, causing swelling and possibly apoptosis.
Cerebral Perfusion and the Cushing's Reflex
Cerebral perfusion is the driving force behind cerebral blood flow and cerebral blood flow is reduced in the first 24 hours following traumatic brain injury. Reductions in cerebral blood flow can result in poor delivery of oxygen and metabolic substrates and inadequate removal of waste and CO2. CO2 is a potent vasodilator, therefore excessive local CO2 may result in local (or global if severe enough) vasodilation. Maintaining cerebral perfusion, and therefore cerebral blood flow is critical in the head injured patient. There are several equations that are commonly used in TBI and they include:
CPP = MAP – ICP1
CBF = CPP/CVR
CPP = cerebral perfusion pressureCBF = cerebral blood flowMAP = mean arterial blood pressureCVR = cerebral vascular resistanceICP = intracranial pressure
Animals with TBI may develop focal or global increases in CO2 as cerebral blood flow decreases, which result in vasodilation and therefore causes worsening CBF. Following TBI, the brain’s intrinsic ability to manage cerebral blood flow and perfusion pressure becomes altered. Vasomotor centers in the brain may detect increased CO2 and attempt to vasoconstrict through increase in sympathetic function. Systemic hypertension then occurs, which is noted clinically as an increase in MAP. This increase is detected by baroreceptors and a reflexive bradycardia ensues. Animals with decreased mentation, hypertension and bradycardia are at increased risk of having or eminently developing increased ICP. This triad of abnormalities (bradycardia, hypertension and altered mentation) in a post-traumatic patient is called the Cushing’s reflex. The end result of excessive increased ICP is brain herniation.
Management of the Head Trauma Patient
1) Get oxygen to the brain: A clear airway must be established, oxygen and CO2 status should be determined. If oxygen supplementation is required, an oxygen cage or mask may be used. Remember to avoid nasal canula as sneezing can increase ICP. Also, oxygen supplementation will correct hypoxemia, but will not prevent hypercarbia in a hypoventilating animal. Tracheal intubation and mechanical ventilation is indicated in animals that are apneic or hypoventilating.
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2) Monitor blood pressure and heart rate: Head-injured patients require maintenance of systemic and cerebral hemodynamics. The two most important goals are preservation of CPP and maintenance of systemic oxygen availability. Ideally mean arterial blood should be constantly monitored in these patients. Hemodynamic goals include a MAP>80-90 mm Hg and <115-120 mm Hg. Fluid restriction is NOT encouraged in the post-traumatic patient because of the risks to systemic health and the minimal benefit to reducing cerebral edema. Colloidal support may improve blood flow (and perfusion) however, the 2007 SAFE study in human TBI demonstrated an increased mortality in patients receiving albumin compared to those receiving saline rehydration. It remains unknown if all colloidal support would have the same outcome.3
3) Manage Increasing intracranial pressure: Mannitol (1 gm/kg slow IV over 20-30 minutes) has become a cornerstone in the management of increased ICP. There are several proposed mechanisms of action by which mannitol decreases ICP. 1) It expands circulating volume, decreases blood viscosity and therefore increases cerebral blood flow and cerebral oxygen delivery. 2) Reduction of CSF production 3) free radical scavenger 4) Delayed effect: osmotic action: transfer of extravascular edema fluid (in neurons) into the intravascular space: occurs 15-30 minutes after administration when gradients are established between plasma and cells. The effects of mannitol persist for a variable period ranging from 1 to 3 hours depending on clinical conditions. Mannitol can be administered as repeated boluses, or continuous infusion. Due to a rebound effect, risk of hypernatremia and hyperosmolarity, mannitol should not be administered more often than 3 times over a 24 hour period. Dangers of repeated dosage are related to effects on blood volume and electrolytes rather than specific toxicity and the patient's blood volume status should be closely observed. Hypertonic saline may also be used instead of mannitol and is considered equivalent by most neurologists for most patients. Hypertonic saline (4 mL/kg of 7.5% or 5.4 mL/kg of 3%) has the added advantage of rapidly restoring volume by causing an osmotic shift from extracellular to intravascular space. Due to the high sodium level, salt toxicity is possible therefore; serum sodium levels should be frequently monitored. The exception may be patients that are volume depleted; these patients may benefit from hypertonic saline more than mannitol. For a favorable prognosis, a response to medical therapy should be seen within 4 to 6 hours following commencement of treatment. An animal should be assessed every 30 minutes until stabilized.
Glucocorticoids are contraindicated in TBI due to the exacerbation of hyperglycemia. The majority of available evidence indicate that glucocorticoids do not lower ICP, or improve outcome in severely head-injured patients.
Monitoring of TBI patients
1) respiratory status, pupil size (and PLR) and level of mentation. In a very simplistic sense, inspiration and expiration are initiated in the medulla, and the rate and pattern is driven from the midbrain/pontine centers. Feedback loops, largely responsive to blood levels of CO and oxygen are present in the prosencephalon as well. Damage to specific areas of the brain will result in specific respiratory patterns.
2) Monitoring pupil size can help with formulating a prognosis (see below) and aid in initial lesion localization. Sympathetic function to the eye originates in the thalamus, descends through all parts of the brainstem and exits the spinal cord T1-T3. Damage to this tract will result in an inability to dilate the eye, or miosis. This most often occurs with damage to the thalamus (prosencephalon) or medulla. Parasympathetic innervation to the eye starts in the midbrain and goes to the eye by traveling along with the somatic fibers of cranial nerve 3. Damage to the midbrain would result in an inability to constrict the eye, or a dilated fixed pupil. If both the sympathetic and parasympathetic fibers are damaged the eye will appear fixed and midrange.
3) Monitor mentation changes are described as obtunded, stupor or coma. Obtunded animals have diminished responsiveness to the environment but will respond to tactile, visual or verbal stimuli. Animals with stupor will only respond to firm tactile stimuli (not visual or verbal) and animals in a coma will not respond to sharp tactile stimuli such as pinching with a hemostat. Body posture can also help one lesion localize the problem. Decerebrate rigidity occurs with damage to the descending corticospinal tracts, usually at the level of the midbrain. Animals have increased extensor tone to all limbs and severely decreased mentation, usually coma. This indicates a poor prognosis. Decerebellate posture occurs with damage to the cerebellar peduncles and typically has a fair to good prognosis. Patients demonstrate forelimb extension, variable pelvic limb positioning and normal mental awareness.
Prognosis
Both the modified Glasgow coma scale (MGCS) and animal trauma triage (ATT) score have been used to provide estimated, objective assessments for prognostication in animals. For the MGCS, motor activity, brainstem function and level of consciousness are scored and then compared to a graph to determine the relative survival probability.5 For the MGCS, the LOWER the number, the LOWER the probability of survival. Remember to perform 2-3 GCS before considering the number reliable if the animal is in the immediate post-traumatic period. This scale is useful for adjusting the prognosis on a daily basis, as the patient progresses through treatment.
Unlike the MGCS, the animal trauma triage score accounts for more than just intracranial trauma. Scores are summed for each of the following six categories: perfusion, cardiac, respiratory, eye/muscle/integument, skeletal and neurological. Scores are 0-3 for each category resulting in a maximum score of 18. The LOWER the number the HIGHER the probability of survival. 6 For each increase in 1 point, there is a 2-2.6x decrease in survival.7 One recent study compared the two scoring systems for animals with head trauma and identified the ATT as a more predictive and reliable scoring system.7
References:
1. Kuo KW, Bacek LM, Taylor AR. Head Trauma. Vet Clin NA Small Anim Pract. 2018;48(1):111-128.
2. Van Beek J, Mushkudiani N, Steyerber E, et al. Prognostic value of admission laboratory parameters in traumatic brain injury: Results from the IMPACT study. J Neurotrauma. 2007;24(2):315-328.
3. SAFE study I, Australian and New Zealand Intensive Care Society Clinical Trials G, Australian Red Cross Blood S, George Institute for International H, Myburg J, Cooper D. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med. 2007;357(9):874-884.
4. Hayes GM. Severe seizures associated with traumatic brain injury managed by controlled hypothermia, pharmacologic coma, and mechanical ventilation in a dog: Case report. J Vet Emerg Crit Care. 2009;19(6):629-634.
5. Platt SR, Radaelli ST, McDonnell JJ. The prognostic value of the modified Glasgow Coma scale in head trauma in dogs. J Vet Intern Med. 2001;15(6):581-584.
6. Rockar RA, Drobatz KS, Shofer FS. Development of a scoring system for the veterinary trauma patient. J Vet Emerg Crit Care. 1994;4(2):77-83.
7. Ash K, Hayes GM, Goggs R, Sumner JP. Performance evaluation and validation of the animal trauma triage score and modified Glasgow Coma Scale with suggested category adjustment in dogs: A VetCOT registry study. J Vet Emerg Crit Care. 2018;28(3):192-200.
That's it for now! I'm maintaining curbside servcie for the summer and am starting to widen my travel radius again. Please reach out if I can assit with a case. Stay safe, stay healthy!
