Orthostatic Tremor in Dogs

How often do you hear "my dog's legs shake when s/he stands?" (Okay, perhaps not as often as I do...but I'm going to assume you hear it at least a LITTLE bit of the time!)

Etiology
Orthostatic tremors can be primary, meaning the tremor is the disease itself. This is suspected to originate from the cerebellum or brainstem but is still, as of now, unknown. The disease is progressive therefore neurodegenerative causes have been considered.
Tremors that are associated with another neurologic disease are termed OT-Plus and include an assortment of spinal cord compressive diseases such as Wobbler's or LS disc herniation. The tremors with OT-PLUS are therefore suspected to be associated with weakness driven from the primary myelopathy, not a disease process in its own right.

Description
When rising to stand, during standing, or occasionally when rising to sit, dogs will exhibit a fine, involuntary tremor in pelvic limbs (most commonly), all four limbs (second most commonly) or thoracic limbs only (rarely). These abate when recumbent, or in active motion (walking, running). Specific awake electrodiagnostic testing confirms the disease but the clinical suspicion is high with the history alone. Orthostatic tremor (OT) has been described in large or giant breed dogs only. Signs begin between 9 months and 2 years of age for OT, and a bit older for OT-plus. In fact, Retrievers and older age were associated factors with OT-plus in a recent retrospective study reporting on orthostatic tremors. (10.1111/jvim.16328.)

Treatment
Okay this is super interesting to me (and hopefully you)! This data is for primary OT, not OT-plus.

• Phenobarbital/primidone - 15/15obtained remission (2 lost to follow up)

• Gabapentin/pregabalin - 25/29obtained remission (3 lost to follow up)

• Clonazepam - 5/6 obtained remission (1 lost to follow up)

Improvement was more likely to be partial than complete resolution (7:3) but some improvement was noted. Interestingly, clonazepam is reported to be the drug of choice for human OT and yet the response to treatment is minimal compared to what we see with our canine patients.

Why do these treatments help? Unknown. It isn't a convulsive disorder therefore these medications are helping from a different angle. I'll keep you posted as we hear more!

Take away from this:
Young, large or giant breed dogs with tremors may have OT
Look for an underlying cause if signs onset at an older age, especially in a retriever breed
Try one of the treatments listed, let me know what you think!

As always, thanks for reading. Please let me know if you have any questions about OT, or any other case you are evaluating.

I appreciate your business and look forward to continuing to work with you and your team!

Managing a Pain in the Neck

Cervical pain can present with or without concurrent neurologic deficits and therefore maybe secondary to neurologic or non-neurologic disease.

Animals with neurologic deficits in addition to neck pain have a neuroanatomic lesion localization (C1-T2 myelopathy) which includes the region of pain.

Deficits noted in the C1-T2 lesion localization may include proprioceptive ataxia of all four limbs, tetraparesis (or plegia), reduced or absent postural reactions in all four limbs, +/- reflex deficits of the thoracic limbs. Postural reactions are often more severe in the pelvic limbs than thoracic limbs with a C1-T2 myelopathy therefore this finding should not dissuade you from this lesion localization. Rarely noted neurologic deficits may include unilateral Horner’s syndrome and unilaterally absent cutaneous trunci. With acute, peracute and severe cervical injury respiratory failure (lack of inspiration) can be seen secondary to damage to the phrenic nerve (driving diaphragmatic function) and/or damage to the upper motor neurons that regulate the intercostal innervation. A lesion localization of a C1-T2 myelopathy indicates neurologic damage, and therefore diseases affecting the nervous system should be considered for these patients. See the section below discussing differential diagnoses for animals with a C1-T2 myelopathy lesion localization.

Animals with cervical pain without neurologic deficits cannot have a neuroanatomic lesion localization because they do not necessarily have neurologic disease.

Therefore, the diagnosis written in the record should be “cervical pain”. These animals may have neurologic disease; however, diseases outside of the nervous system should also be included on a differential diagnoses list.

Differential Diagnoses (not a complete, textbook list...just the more common ones)
** Many differential diagnoses listed below may start with signs of neck pain ONLY, without evidence of a myelopathy and then may or may not progress to signs of a myelopathy.

Differential Diagnoses (not a complete, textbook list...just the more common ones)
** Many differential diagnoses listed below may start with signs of neck pain ONLY, without evidence of a myelopathy and then may or may not progress to signs of a myelopathy.

1. Acute/peracute onset clinical signs:

   1. C1-C2 subluxation (congenital or traumatic)

   2. Intervertebral disc herniation (type I)

   3. Traumatic fracture/subluxation non-C1-C2

   4. Meningomyelitis

   5. Discospondylitis/osteomyelitis

2. Slow/subacute onset clinical signs

   1. Discospondylitis

   2. Vertebral or neural neoplasia (note: intramedullary neoplasia is commonly non-painful. Any involvement of the meninges can result in cervical pain.)

   3. Intervertebral disc herniation type II

   4. Syringohydromyelia

   5. Cervical spondylomyelopathy (AKA Wobbler’s syndrome)

   6. Meningomyelitis

3. Acute, non-progressive clinical signs

   1. Fibrocartilagenous embolism (note: this may be painful in the first 24 hours, however most become non-painful after 24 hours.)

   2. Syringohydromyelia

What do you do?

First, a neurologic examination. If the animal has neurologic deficits, referable to the cervical region, localize the lesion. (Self promotion plug here....remember if you're not confident with a neurologic examination, please call for a consult!)

Radiographs are useful if trauma or subluxation is a primary differential diagnoses. Treatment should follow with your differential diagnoses list. If the pet is poorly or non-ambulatory a consultation or referral to a neurologist is recommended ASAP.

Thanks for reading! I hope you have a great start to 2022. Keep those consults coming!

Neospora Meningoencephalitis vs Immune Mediated Meningoencephalitis

Immune mediated meningoencephalitis (aka meningitis of unknown origin: MUO) is very common and is a cause of intracranial disease for many pets. Infectious meningoencephalitis accounts for only about 2% of the cases seen through a referral center and is, therefore, in the minority. Infectious meningitis may be secondary to fungal infection, protozoal (Toxoplasma or Neospora), viral, bacterial or in southern states, some tick borne diseases. Neospora infection is one of the more common causes of infectious meningoencephalitis we see in Wisconsin (probably second only to fungal) and therefore one of the main differential diagnoses for a pet with meningoencephalitis. The current way to diagnose Neospora is via serum titer elevation, evidence of encysted protozoa on biopsy or necropsy, or PCR on serum or CSF. All of these tests take a variable amount of time, depending on the laboratory, so some researchers in the UK came up with another idea. (https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16334)

Scientific Question: Can we differentiate between Protozoal meningoencephalitis and MUO using CK and AST values?

Rational: Protozoa (Toxoplasma and Neospora) are often found in muscle which would result in membrane disruption, thus elevating CK (and subsequently AST). Seizures, a common sign of MUO and protozoal meningoencephalitis, can also elevate CK so the researchers also aimed to evaluate the temporal relationship between seizures and CK elevation.

Methods: This was a retrospective study of 59 dogs diagnosed with MUO and 21 dogs diagnosed with Neospora (no dogs were diagnosed with Toxoplasma in this study).

Results: A significantly higher CK and AST value were identified in dogs with Neospora compared to those with MUO. Using a cutoff value of 458 U/L, there was a sensitivity of 95.24% and specificity of 96.61% for active Neospora meningoencephalitis and using a prevalence of 2.25% for active infection in the UK, there was a negative predictive value of 99%. This suggests that dogs with a CK less than 485 U/L are unlikely to have a diagnosis of Neospora infection associated with their intracranial signs. Twenty of 21 dogs with Neospora had CK higher than 485 U/L, and 2 dogs with MUO had CK > than 485 U/L in this study.

Things to remember: CK has a short half-life (22 hours) so if you test, do so within the acute phase of disease. CK and AST are not muscle specific and can be found in myocardium, intestine and AST in the liver also.

What do you do with this information? If you have a dog with suspected meningoencephalitis, consider running a CK and AST on initial blood work. If it is greater than 485 U/L, a Neospora titer should be performed.

Have a great week and thanks for reading!

Note about the holidays: I will be available for emergency cases on December 24, and 25th.

New Years Eve and Day, I will be spending time with my family building a colossal gingerbread house and stables. If I'm not baking, cutting and cooling gingerbread I will be making sticky frosting glue and won't be available for phone calls, texts or email. Thank you for your understanding!

Feline Orofacial Pain Syndrome

This is a little bit out of my wheelhouse, but it has come across my radar recently on a few cases so I thought I'd share with you what I know about FOPS.

What is it?

This is not a seizure, we don't think, and shouldn't be confused with orofacial seizures in cats. FOPS is a behavioral disorder in cats with evidence of oral discomfort and occasionally tongue, lip or gum mutilation. There is some suspicion that this is a neuropathy, or neuropathic pain disorder arising from the trigeminal nerve or the ganglion processing from CN V.

How does it present?

This disease is more common in Burmese cats, but can be seen in any breed at any age. Signs are often linked to dental work, tooth eruption or oral surgery. According to data from one study (link below), the median age was 7 years at first onset of signs, with the majority of cats having repeated or ongoing signs.

Can it be diagnosed?

It is a diagnosis of exclusion. Rule out underlying dental disease, oral pain, or diet-related causes for automatisms of the mouth following eating or other activities. Unfortunately no confirmatory test exists at this time.

How is it treated?

Not well.... oh wait, that is not what you mean, is it? Sadly, it is the truth. What treatments have been tried?

• Dental procedures: 35/53 cats improved following a dental procedure but it was not sustained in 9 cats.

• NSAIDS: 18 cats received NSAIDS of some variety. This was effective in 6 cats

• Corticosteroids: 7/17 cats had relief with steroid use.

• Antibiotics: 2/12 cats attained improvement with antibiotics (unknown type, dose)

• Combination treatment (anti-inflammatory and antibiotic): 9/21 this was effective

• Opioids: 4/14 these were effective

• Phenobarbital: 14/14 cats, effective (this was combined with a dental 2 cats)

• Diazepam oral: 13/14 cats this was effective (combined with a dental in 1 cat)

• Gabapentin: only used in 1 cat and was effective (my experience has been that this is not effective)

• Chlorpheniramine: 2/4 cats it was effective

Take Home Message

It is very important to read the numbers regarding treatment carefully. This data is reporting a subjective response to treatment, with variable doses and types of drugs within one class, in a small group of cats. This data is suggestive of efficacy with phenobarbital or diazepam use but other treatment choices may be effective. These medications are proposed to be effective because of their anti-allodynic effect, not anticonvulsant effects. Human patients with neuropathic pain that is reported to be burning in sensation find phenobarbital particularly effective. Remember that oral diazepam can cause idiosyncratic hepatic necrosis and therefore should be used with caution in cats.

Have a great week, and thanks for reading!

My hours are changing December 20-January 30th. Please reach out via email or text if you cannot find a suitable time for a consult as I may have some flexibility outside of posted times.

Link to an article for additional information:https://doi.org/10.1016%2Fj.jfms.2010.03.005

What If We Could See a Seizure Focus?

Idiopathic epilepsy is something we all see on a regular basis. However, when we diagnose something by exclusion, I often wonder what we are missing. Currently idiopathic epilepsy is diagnosed if dogs meet the following criteria:

Tier I

• Normal neurologic examination

• Normal CBC, serum biochemistry and bile acid test

Tier II

• All of the above PLUS

• Normal brain MRI

• Normal CSF analysis results

(There is a Tier III, but it is rarely used.)

What if we could actually see a seizure focus?

This is the stuff of science-fiction, folks! A recent article in JVIM (https://doi.org/10.1111/jvim.16270) utilized an MRI technique that has been used in human epilepsy to try to visualize a seizure focus in dogs with idiopathic epilepsy. MRI works by affecting magnetic fields in the brain. With this new technique, neuronal currents are mapped with a specific oscillating magnetic field. This has been shown to be an effective mapping technique for humans with idiopathic epilepsy. The researchers applied the technique to a group of control dogs (those without seizures) and dogs diagnosed with idiopathic epilepsy with Tier II level confidence.

Results

There were three different frequencies used in the protocol however the authors combined the results from the different frequencies and found that 11 of 12 dogs with idiopathic epilepsy had a bright spot identified in their brain, with this technique. Even cooler, 4 of the 5 control dogs did NOT have any bright spots visualized in their brains. Perfect? No. Super cool? Yes!

Take Home Message

What does this mean for you and me? It means that as we test this new protocol a bit more we are one step closer to "seeing" the seizure focus in the brain. Who cares, you may ask? We all should!! If we can see it, we can remove it surgically (maybe), target it with radiation (already being done but this will improve accuracy), or start to identify different "types" of idiopathic epilepsy and assess how our drug protocols are affecting animals with specific forms of epilepsy. All of this allows us to target epilepsy much more specifically, and ultimately improve quality of life.

Thanks for reading! Hopefully you can use this new information to give your clients hope, when faced with a diagnosis of canine idiopathic epilepsy. Researchers (vets!) are working tirelessly to find a way to make life better for owners, and their pets with epilepsy.

Have a great week and be safe!

Metronidazole and Vestibular Disease in Dogs

'Tis the season of spinning tops in my home. In the spirit of the holidays, let's talk about another spinning...vestibular disease! (Gosh I hope you love these connections as much as I love making them up!) This one is an oldie but goodie from the TidBit Tuesday archives.

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.

In-Hospital consult days and times changing as we spin through the holiday season. Please check the website or Facebook for updates.
Happy Hannukah to those of you celebrating this week!

Thank You!

In this week of Thanksgiving, I am remembering you and your staff.

• Thank you for trusting your patient's care to me. I am humbled by the kindness, consideration and feeling of welcome that I receive when I enter your clinic to help care for your patients.

• Thank you for having a room ready for me.

• Thank you for having kind, knowledgeable staff to assist me.

• Thank you for giving up valuable floor space (rooms, hallways, office space or even bathrooms!) to allow me to fully examine the pet.

• Thank you for the insight, nuance and personal touch you add when talking about a client or patient. I love being a part of your team.

• Thank you for being an advocate for your patient and for including me in their health care needs.

• Thank you for following up with me, giving me feedback, patient updates and answering my emails when I check in.

Most of all, thank you for being you!

Many of you I now call friends. I look forward to seeing you and your staff when I get that "ping" on my phone that signals a consult was scheduled. Keep up the good work. You are valuable and important.

Happy Thanksgiving! May you have many of things to be thankful for in life. Thanks for reading. :)

PS - in case you're confused by the photo, it is an image of Turkey. Here is your TidBit of knowledge: Istanbul (which is not the capitol), spans two continents. It spans Asia and Europe, but only about 5% of the city is on the Europe side. What is the Capital of Turkey?

(Ankara) Now you can quiz your know-it-all Uncle on Thanksgiving.

Paroxysmal Movement Disorders

Welcome to another "what-if" TidBit Tuesday! Here we go...

It's Wednesday morning and on your schedule is a 6 month old MC Cavalier King Charles Spaniel to see you for a complaint of "seizures". Upon examination, you find the pet to be normal both physically and neurologically. The client proceeds to describe the events that they've noticed as follows:

"When she goes to jump up on me to greet me she will sometimes fall into a praying position with all four legs stiff. It lasts 2-3 minutes and then she gradually relaxes and is able to walk normally."

Upon further questioning you discover that the dog appears mentally appropriate without signs of drooling, urinating, defecating or vomiting before or after the event. The client provides you a video of the event and at the conclusion, the dog resumes wiggling and excited behavior without obvious change in mentation. Hmmm....no preictal phase, no postictal phase and a relatively long ictal phase. Maybe it isn't an ictus at all???

Hopefully by now you're starting to think this may not be a seizure at all, but in fact one of those "movement disorders" you've been hearing about. What are they, and what can we do?

Movement disorders are a large group of diseases that are non-epileptic changes in muscle tone that happen episodically. They can be triggered by environment, or not. The most common classification that we see in veterinary medicine is a paroxysmal dyskinesia (PD), with or without dystonia. (I'm sorry...say what?? Okay, sorry. Paroxysmal = sudden violent or periodic event; dyskinesia = involuntary, erratic movements of muscles, usually face or limbs; dystonia = sudden muscle contracture, usually of opposing muscle groups which results in a writhing or twisting movement.) There are breed-specific PD which can be found here (https://www.frontiersin.org/files/Articles/163467/fvets-02-00065-HTML/image_m/fvets-02-00065-t005.jpg). Many of these are known to be inherited and some form of genetic mutation has been identified but in some cases we aren't clear on the cause. In humans there are inherited and acquired causes and entire books written about the different forms of movement disorders and their appearance. We don't have that...yet.

Pathophysiology

What happens to cause this, if it isn't a seizure? That is a complex question that I will try to answer simply. Most movement disorders originate from the brain in an area of the basal nuclei. This is where one of the most famous movement disorders, Parkinson's disease, originates from. Pathophysiology is largely unknown for animal movement disorders but there is definitely something going on in the basal ganglia. Diagnostic testing including brain MRI/CSF and at times muscle/nerve biopsies are recommended to pursue an acquired cause. These tests are often negative because inherited causes are more common.

Treatment

Effecting the basal ganglia through the use of benzodiazepine drugs (clonazepam 0.5 mg/kg) or even acetazolamide has shown some improvement. Some dyskinesia respond favorably to zonisamide and potassium bromide as well which further complicates our ability to decide cage-side if this is a seizure disorder, or not. An EEG is valuable here to identify the lack of brain changes consistent with seizures. However interpretation and acquisition of an EEG is challenging making this less available and useful for veterinary patients.

Sometimes it is plain ol' not clear if this is a seizure disorder or a movement disorder and we must do a trial and error with medications. In either case, breeding pets with known or suspected movement disorder OR epilepsy is discouraged due to the likelihood of inheritance.

Do you have a case in which you suspect a movement disorder? Let me know if you want to work through the case together! (Group frustration is much more tolerable than beating your head against the wall - metaphorically speaking - alone!).

Thanks for reading and have a great week! Stay safe, stay well and let me know how I can help you.

Brachial Plexus Injury and Recovery

Brachial Plexus Injury and Recovery

Nerve injury can take 3 different forms, from least to most severe:
1) Neurapraxia: transient function loss (ex: conduction block) with no loss of nerve anatomy.
2) Axonotmesis: disruption of axons with some (mild) degree of myelin loss. Importantly the surrounding perineurium and epineurium are intact.
3) Neurotmesis: complete rupture of the nerve (axon, myelin and all surrounding structures).This injury does not lend itself well to recovery.
**Important, but trivial sounding, note: Nerve root avulsion is irreversible.

A recent study evaluated traumatic nerve injury and outlined their findings. The most clinically applicable key points are listed below:

• 226 animals were included (175 dogs, 51 cats)

• 46% were injured before age 2

• Horner's syndrome was seen in 68 animals (42%of dogs and 38% of cats) with miosis ipsilateral to the affected thoracic limb. Note: It should always be ipsilateral unless there is spinal cord damage.

• Cutaneous trunci reflex (which has it's motor origin between C8-T2) was lost in 81% of dogs, again ipsilateral to the affected limb. This reflex doesn't count in cats. :)

Prognostic factors in this study were largely related to electrodiagnostic studies, which are not clinically useful markers in practice. (Unless you have access to electrodiagnostic testing...which I don't, anymore!) That said, we know that animals with neurotmesis do not recover and prior studies have identified that animals with axonotmesis can recover but it may take awhile. Nerves may regrow 1 inch per month for a total of 8 inches. Therefore distal injuries resulting in axonotmesis may result in some functional recovery of the limb.
In the study referenced below, the only important clinical prognostic indicator from this study was the absence of cutaneous trunci reflex. When, absent, it was linked to a lesser chance of recovery, but no statistical analysis was performed to assess this trend. This study also reinforced the finding that electrodiagnostic testing is a valuable testing tool for providing a prognosis for dogs and cats following brachial plexus injury.

Do you have a patient with a traumatic limb injury with possible neurologic involvement? A neurologic examination may be able to better identify chances of recovery and direct treatment towards appropriate physical therapy, acupuncture and other management during the recovery phase. Reach out if I can help!

Have a great week and stay warm in this chilly turn towards fall!

Referenced article: https://doi.org/10.1111/jvim.16254

CBD, THC and Neurology

It doesn't matter how hard I try to avoid this question, it always comes up with clients. Perhaps you feel similarly? A group from Ontario, Canada recently published a study evaluating safety profiles of several CBD-oil, CBD/THC-oil and THC-oil containing products in a dose escalation study. The study evaluated 20 dogs in a blinded, placebo controlled (sunflower oil or MCT oil) multidose parallel study.

The following comparisons were made:
1. CBD oil or THC oil compared to MCT placebo
2. CBD/THC combined oil (ratio: 1.5) to sunflower oil

Results

This study contained a lot of data about adverse effects (AE: the new fancy word for side effects) that you might find interesting. The article is linked below. I will focus on the neurological and hepatic side effects.

Overall, they had mostly (n =401/505) mild adverse effects but a few moderate and severe adverse effects were seen. The oils containing THC had the most AE and were also the only groups to show severe AE. Neurologic AE that were noted included tremors and ataxia but AE categorized as "constitutional" included lethargy and hyperesthesia. I did not include the "constitutional" numbers below but could be persuaded that indeed those should have been considered neurological AE as well. Liver values were considered abnormal when they exceeded a 2-fold increase from normal.

1. CBD oil (80 AE): 13 were neurologic; 1 dog had elevated ALP (2.9-fold)
2. THC oil (206 AE): 89 were neurologic*
3. THC/CBD oil (115 AE): 56 were neurologic*; 1 dog had an elevated ALP (3.6-fold)
4. Placebo: 27 AE, 13 were neurologic (!)
* The proportion of GI to neurologic side effects were higher in the groups containing THC compared to placebo or CBD oil only groups.

Moderate side effects were not noted in the CBD oil group and accounted for 22 or 505 AE in the THC and CBD/THC group with also a few dogs in the placebo group.

Severe side effects were noted in 3 dogs - one in the THC only group and 2 dogs in the CBD/THC group. Signs were transient and resolved in 9-28 hours.

A reminder about hepatic metabolism

The elevation of ALP due to CBD results from activation of the p-450 system in the liver. This should sound familiar because it is the workhorse for drug metabolism for drugs such as phenobarbital or zonisamide. Co-administration of CBD and phenobarbital (and probably zonisamide but not in published data for dogs) can affect the metabolism of phenobarbital.

Take away message: What is the big picture here?

My take away from this article was that THC containing products have more neurological side effects compared to CBD containing products and CBD containing products affect liver metabolism. You may be thinking "but I wouldn't recommend THC products for my patients!" and I would support that. And yet, remember production oversight and regulation of these products, especially for animal consumption, isn't robust therefore contamination of THC may be possible. Please note that the State of Wisconsin continues to prohibit prescribing CBD products by vets with clients unless under specific situations. (https://datcp.wi.gov/Documents/VEBCannabis.pdf) therefore this TidBit Tuesday in no way supports or advocates for the use of CBD oil containing products for veterinary patients.

Article link: https://www.frontiersin.org/articles/10.3389/fvets.2020.00051/full#B21

Thanks for reading! Have a great day, and keep those consults coming!

Is Age a Disease?

Age, The Neurologic Examination and Prediction of Disease

Age isn't a disease, right? No, it isn't but disease is associated with age. The older pet is more likely to have structural disease (i.e. neoplasia instead of idiopathic epilepsy), compared to the younger pet. That said, none of us want to diagnose a terminal disease in an older patient simply because the patient is older!

Can the Neurologic Examination Help Vets with Older Patients?

Let's look at the two most commonly performed parts of the neurologic examination and see how they related to disease. The menace response and paw replacement testing (previously called conscious proprioception) 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 in reference to finding evidence of forebrain disease on MRI:

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 by MRI 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 possibly for those with proprioceptive deficits depending on concurrent findings. 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.


Although this TidBit is a repeat from 2020, I liked this study and thought it was worth repeating.
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! It has been a hectic week (for all of us, I think!) so remember to breathe, eat and hydrate. Have a great week!

How to Diagnose Idiopathic Epilepsy in the Exam Room

In 2015, the International Veterinary Epilepsy Task Force (IVETF) published a list of criteria to diagnose idiopathic epilepsy in dogs (not cats). The IVETF consisted of a group of veterinary neurologists, neuropathologists, and epileptologists. If you wish to see all of the resulting publications, just let me know! (They are available open access.)

The IVETF listed several ways to make a diagnosis of idiopathic epilepsy, starting with the lowest level of confidence (Tier I) and rising to the top with the most confidence in the diagnosis (Tier III). When using this information in your daily practice, consider writing "diagnosis: idiopathic epilepsy with Tier 1 confidence" in the medical record when a patient meets the criteria for a Tier I diagnosis of idiopathic epilepsy.

Please note, idiopathic epilepsy does not mean, any seizure disorder. Idiopathic epilepsy is a specific disease, that causes repeated seizures. ANY animal with repeated seizures can be diagnosed with epilepsy, but idiopathic epilepsy is ONE form of epilepsy. Make sense?

Tier I:

A dog must have:

• A history of 2 or more seizures at least 24 hours apart

• Have the age at onset between 6 months and 6 years

• Demonstrate a normal inter-ictal physical and neurologic examination

• A normal CBC, and serum biochemistry (the IVETF lists what they consider to be standard in a serum biochemistry analysis. Let me know if you want/need this list.)

• A normal fasting bile acids and/or ammonia

• A normal urinalysis

• A familial history of IE is supportive, but not required

Tier II:

To diagnose idiopathic epilepsy with Tier II level confidence a dog must have:

• All of Tier I plus...

• A normal brain MRI

• A normal CSF analysis

• Normal fasting and post-prandial bile acids

Tier III:

• All of Tier II plus...
  

• Identification of ictal or inter-ictal EEG abnormalities suggestive of seizure disorders.

So, if a patient meets Tier I level confidence, when should MRI be performed?

• Anytime a client wishes to confirm a diagnosis of intracranial disease. (This includes idiopathic epilepsy which is diagnosed by exclusion of other causes)

• If a dog has a seizure onset of < 1 year or > 7 years of age (according to the IVETF)

• If neurologic abnormalities reflective of the prosencephalon/forebrain are identified on the neurologic examination regardless of age, breed or a familial history of seizures.

In summary, it is always worthwhile to inform clients of the option of MRI when their dog (or cat) has seizures however, if the Tier I criteria are met and MRI has a high likelihood of normal results, it is very reasonable to skip this test and begin treatment for idiopathic epilepsy.

I try to remember that MRI abnormalities were identified in 22% of dogs with a normal neurologic exam and 90% of dogs with an abnormal neurologic examination in one study.

What about CSF analysis, you ask? I'm glad you asked! Some dogs with meningitis will have a normal MRI, therefore an MRI PLUS CSF tap is often my recommendation to ensure we don't overlook those patients inappropriately by just performing an MRI.

What about cats? The IVETF recommendations do not specifically apply to cats however many neurologists, including me, extrapolate this information to cats in practice. My fingers and toes are crossed for science driven cat-specific recommendations in the near future.

Have a great week! As always stay safe, and let me know how I can help you, help your patients, with neurologic disease.

Rabies Awareness

Etiology

Rabies is neurotropic rhabdovirus that causes fatal infection in dogs, cats and humans. Usually infection is transmitted by inoculation with saliva by means of a bite. The virus then spreads into the CNS via peripheral nerves. Once the brain is infected, the virus spreads out through peripheral nerves to the salivary glands among other targets – at this point, the animal can transmit rabies.

Signalment
Any dog, cat, horse, cow, HUMAN

Clinical Signs

Two syndromes are described:

• Furious syndrome (forebrain signs)

• Paralytic syndrome (lower motor neuron signs ascending from the site of the bite).

Once neurologic signs are present, progression is rapid, and most animals will be dead within several days. Rabies should be considered as a differential diagnosis in any animal with acute onset, rapidly progressive neurologic disease especially if there is a poor vaccination history or exposure to other rabid animals.

Diagnostic Tests

Key point: Definitive diagnosis can only be achieved postmortem, and requires fluorescent antibody staining of brain tissue to demonstrate rabies antigen. A serum RFFIT (Rapid fluorescent foci inhibition test) can be performed to evaluate for evidence of previous vaccination however it should NOT be used to make a diagnosis of active rabies infection. Due to the neurotropic nature of rabies it can remain undetected by the immune system and therefore cause a negative (false negative) RFFIT antibiotic result.

Further reading
If you're interested in reading about a real case of Rabies virus infection please check out this article. https://doi.org/10.5326/0390547 I saw this case a number of years ago, but the disease hasn't changed much in 20 years! Furthermore, a rabies positive bat was identified on a sidewalk in Dane county just this week. Although fewer Rabies positive bats have apparently been identified this year (so far) the virus is still around and therefore still something we should be talking about!

Thanks for reading! Rabies virus infection is something I think about daily, given the cases that I see, and is one of the more daunting diseases we are faced with. Please reach out if you have any questions!

Other good resources:
The Wisconsin Rabies Algorithm: (for exposure or sick animals) https://www.dhs.wisconsin.gov/rabies/algorithm/algorithmcategories.htm
Illinois Rabies information: https://www.ilga.gov/commission/jcar/admincode/008/00800030sections.html

Temporalis and Masseter Muscle Atrophy

It's Tuesday at 10 am and you're about to see a 7 year old dog with unilateral temporalis and/or masseter muscle atrophy. What parts of the neurologic system could be involved?

1. Muscle: A problem with muscle function, termed a myopathy, can result in muscle atrophy. The most common cause of temporalis and masseter muscle atrophy in dogs is masticatory muscle myositis (MMM), which is caused from an immune mediated attack against the muscle fiber. This is a UNIQUE form of muscle inflammation because the proteins on these muscles are embryologically unique (2M fiber type, if you must ask) from all other muscles in the body. We care about that because it means that we can have a an antibody (AB) test that we can run that is highly specific AND sensitive! The second myopathic disease of the head muscles, that I see commonly, is myositis due to neospora or toxoplasma infection. Simply put, the protozoa get into the muscle, set up a secondary inflammation (myositis) and sometimes you can see a mild positive on the aforementioned MMM AB titer test. However, if you concurrently test for neospora and toxoplasma (serum titers) you can catch this "false" positive, and treat the correct disease.

Treatment for MMM: Immunosuppressive steroids for 30+ days
Treatment for infectious myositis: clindamycin or sulfa antibiotics until negative or stable titers.

2. Cranial nerve 5: A dysfunction of CN 5 can result in denervation atrophy of one (or both) temporalis muscles. On the exam, look closely for concurrent signs of a sensory neuropathy to the face and if present, a CN 5 dysfunction should be suspected. The differential diagnoses list is much bigger but typically centers around a few common causes (neoplasia, neuritis, hypothyroidism, and trauma). To diagnose a CN 5 neuropathy the best approach is a brain MRI followed by a spinal tap, along with titers for infectious diseases, thyroid panel and routine CBC, serum biochemistry. Not all of those tests are needed for each patient so pick and choose as appropriate for your case.

Treatment for CN 5 deficits: this varies widely and is dependent on the underlying cause. It is a bit hard to summarize TidBit Tuesday-style. :) Stay tuned for another email detailing all of the possible causes and treatments for cranial neuropathies.

I hope this TidBit Tuesday helps you focus your exam, and thoughts, when faced with a case of unilateral atrophy of the muscles of the head. This report was stimulated from recent conversations about this presentation so please reach out if you have a case, or questions about a case, with unilateral muscle atrophy. The more we talk with each other, the more we learn from each other!

Have a great week!

Traumatic Brain Injury And Blood Glucose

We're approaching the month of October - known for scary costumes and sugar overload. Why not look at a recent study about glucose to kick up our adrenaline? Okay, so this is a study in dogs and cats, specifically about traumatic brain injury and relationship between glucose and prognosis but don't shame me for trying to make a link to "current events"!

Background

This was a retrospective study (Cameron S, et al. JVECCs, 2021) looking at 131 dogs and 81 cats that were presented to one of two teaching hospitals following trauma and were diagnosed with traumatic brain injury (TBI). (TBI is the new term for head trauma, in case you're wondering.) At admission, glucose and a modified Glasgow Coma Scale, among other tests, were evaluated from the record and correlated to outcome. The animals were termed "survivors" if they lived to be discharged from the hospital and they were termed "non-survivors" if they, well, didn't.

Results

Here are the key points, and the interesting bits!

Dogs:

• The MGCS was significantly lower in non-survivors compared to survivors.

• Blood glucose concentration was significantly higher in non-survivors compared to survivors.

• A cut off of 148 had a sensitivity of 73% and specificity of 76% for a poor outcome (non-survivor)

Cats:

• The MGCS was the ONLY significant predictor of outcome

• Glucose was not significantly related to outcome!

Take home message:
When presented with a post-traumatic patient, perform a serum blood glucose concentration and a neurologic examination (to get a MGCS). Both of those may be able to help you predict the outcome for a DOG (not cat) and guide the clients towards or away from referral if they are considering humane euthanasia. Naturally, we must account for co-morbidity, financial impact and prior medical conditions of the pet when faced with a post-traumatic patient but hopefully these two little points will further improve your ability to help the patient.

Thanks for reading! I hope you have a nice week and keep those consults coming!
New hours are in effect so please use the online scheduler whenever possible to schedule a consult or email/text me if you cannot find a suitable time. Thanks!

Cluster Seizure Management

What is a cluster seizure?

Cluster seizures are defined as 2 or more discrete seizures within a 24 hour period.1 Cluster seizures are different than status epilepticus (any one seizure lasting for an extended period of time, or 2 seizures in which poor recovery occurred between seizures). Cluster seizures pose a special concern for seizure patients because of they have been linked with poorer outcomes compared to dogs without a history of cluster seizures.

The goal with cluster seizure management is to minimize the number and duration of seizures. A secondary goal is to reduce the need for hospital visit or stay thus reducing the financial burden to the client.

When should I provide a cluster seizure plan to a client?

• If a patient has a history of 2 or more times when they had cluster seizures

• If the patient has a history of status epilepticus

What drug choices, routes of administration and doses can I offer?

Levetiracetam

1. Rectal administration – 40 mg/kg PR at the time of seizure, repeated once if needed within 24 hours. Results suggest an improvement in seizure management in the medium term using rectal levetiracetam AND standard anticonvulsant therapy in one stud

2. Oral administration – start 20-30 mg/kg PO q8hr (NOT Extended release) levetiracetam after a pet experiences the first seizure and has recovered enough to eat and continue q8hr dosing for 2 days beyond the pet’s last seizure. The levetiracetam is then stopped, and standard anticonvulsant therapy is continued long-term. Clinical experience suggests this approach will reduce clinic visits, number of seizures during the cluster event. However, clinical side effects such as sedation or ataxia may be present during the dosing period. Note: This approach should NOT be used if levetiracetam is part of a patient’s standard oral therapy for long-term seizure control. Suddenly discontinuing an anticonvulsant medication can lead to breakthrough seizures or status epilepticus.

Benzodiazepine
Diazepam has been the main acute anticonvulsant treatment for veterinary patients.4–7

1. Rectal - Be sure to target the rectum, not colon, to avoid hepatic metabolism. Start 1-2 mg/kg per rectum.10 Compounded suppository formulations of diazepam have not demonstrated reliable serum diazepam concentrations in dogs therefore compounded suppositories are not currently recommended.9

2. Intranasal – preferred by some due to the ease of administration, and avoidance of the first pass effect of metabolism. Start with 0.5 mg/kg intranasal.

Midazolam

1. Intranasal – this is my preferred route and drug for at home benzodiazepine administration. Additionally, it was reported to be favorable compared to intravenous midazolam in 44 dogs. 11 Start with 0.2 mg/kg intranasal.

2. Intramuscular – this route is favored by some but is not my recommended route of administration for clients at home in emergency situations. In a clinical situation, intramuscular administration can be effective when intravenous access is limited. Starting dose of 0.2 mg/kg is recommended.

3. Rectal – do not use midazolam rectally due to erratic and unpredictable plasma concentrations at standard doses.

Phenobarbital
Patients receiving daily phenobarbital administration can benefit from an increase, or pulse, of phenobarbital therapy during a cluster event.

1. Oral increase – in my clinical practice we regularly recommend increasing a dog from q12h dosing to q8h dosing for 2 days beyond the last seizure. An example of this would be if a dog had a seizure Saturday morning. Upon recovery from the seizure an additional oral dose of phenobarbital (at the same oral dose administered) is recommended followed by q8hr dosing Sunday and Monday. Tuesday the dog would return to the standard twice daily dosing interval. This approach provides a slight increase of serum phenobarbital concentrations which may protect against further cluster seizures. Clinical adverse effects such as increased sedation, ataxia, polyuria, polydipsia, and polyphagia may become evident during the increased dosing period.

Summary
Providing options at home for cluster seizure care can reduce the need for hospitalization, or clinic visits. Additionally, any of the above treatments can be provided in hospital during seizure observation should that be needed. All the treatment choices discussed above are targeted for dogs and are rarely used in cats. Although the medications discussed have been evaluated for safety for use in cats, the specific protocols do not have clinical trial data, and minimal clinical experience.

This week I spoke to a wonderful group of vets at IVECCs about cluster buster protocols and it reminded me that we haven't read about this in awhile on our TidBit Tuesdays. We're all learning together!
(references available upon request)

Canine Cognitive Dysfunction

Cognitive Dysfunction Syndrome in Dogs

Canine cognitive dysfunction syndrome (CDS) is reported to be a progressive disorder with specific characteristics. Many authors group canine CDS signs into specific categories such as:

• disorientation

• social interactions

• sleep-wake cycles

• house soiling, learning and memory

• activity and anxiety

There is a scoring system called the DISHAA Cognitive Dysfunction Evaluation Tool that utilizes these categories in forming a score, that has been shown by some to correlate to the level of impairment of the dog.

A recent study out of The Ohio State University by Dr. O'Brian et al, published in JAVMA (Sept 15, 2021), described the use of an educational 50 minute weekly class, as a means to controlling clinical progression of CDS. This is a case-control study with about 20 owner/dog pairs completing the class and 66 owner/dog pairs used as control. Scoring was performed at entrance to the study, as well as at 3, 6 and 12 months. During class the instructor spent part of the time informing the clients about a specific aspect of CDS, and the remainder of the time working on an interactive activity with the dog/owner pair geared towards cognitive enrichment and new learned tasks. The owners were asked to practice outside of class as well as in class. The most notable finding was a significant progression of clinical score, using the DISHAA scoring system, in the control group and a lack of progression in the class group. The only exception to this was the disorientation scores. These appeared to increase in the class group which, as the authors suggested, may be due to increased owner awareness by attending the class. The authors suggest that owner information, and structured interaction with the dog, is what slowed progression of all of the other markers of CDS.

What is the take away?

Well...maybe an information session (zoom or live) once monthly for all of your dogs over age 8 could increase awareness by clients and alert them to seek medical attention should signs arise. Or, maybe a senior class in your area (lead by a veterinarian or a trainer) might be the best answer for your clientele.

I hope you have a wonderful week! Please remember that I will be closed Monday-Thursday next week, with limited hours on Friday September 10th. Have a safe and happy Labor Day and Happy New Year, if you celebrate!

Canine Distemper

Etiology

Viral replication initially begins in lymphoid tissue and induces marked immunosuppression. Virus then reaches the CNS through the choroid plexus, ependymal cells and perivascular spaces 1-3 weeks after infection by virus infected lymphocytes and monocytes. What is the significance here? Neurologic signs often follow GI and respiratory signs.

Signalment

Distemper should be strongly suspected in an unvaccinated young dog with neurologic signs and with a history of recent GI and/or respiratory disease. Myoclonus, a repetitive twitching of muscles, is a common indication of current or previous distemper infection. Distemper can also be present – and a diagnostic challenge – in older, vaccinated dogs with no history of systemic disease prior to neurologic signs. Older dogs typically have a demyelination, with chronic, slowly progressive, signs of a myelopathy.

Clinical Signs

Respiratory and GI signs occur 1-3 weeks prior to CNS signs. The presence and pattern of illness depend primarily on the viral strain and the age and the immunocompetence of the patient. (Different strains but only one serotype means that exposure to one strain protects dogs against any subsequent strain.) There are 3 different scenarios:

• Dogs that develop an early, effective immunological response recover from mild or no neurological signs. Approximately 50% of dogs have a subclinical neurologic course

• Dogs that are unable to mount an immunological response suffer severe systemic illness, including acute encephalitis, leading to death within about 3 weeks of exposure. These dogs will have seizures, blindness, and other signs of grey matter disease.

• Dogs with delayed immunologic response don’t develop acute illness but may develop a chronic, persistent infection, characterized by chronic encephalitis or myelitis.

In acute disease, infection of neurons and microglia and astrocytes leads to mostly grey matter damage. In chronic infection, the immune response to persistent viral infection leads to inflammation and demyelination. Vaccine induced distemper is associated with a mild encephalitis in dogs vaccinated with modified live vaccines.

Diagnostic Tests

• Active or inactive chorioretinitis may be evident on ophthalmoscopic examination.

• CSF varies from normal to having increased protein and lymphocytic pleocytosis during active infection

• Distemper antibody titers or PCR in CSF, blood and urine can be helpful. False positive urine and blood PCR results may occur within 3 weeks of vaccination.

• PCR on CSF is the most diagnostic test for active infection, however myoclonus, demyelination and seizures can be residual neurologic signs after the acute infection has been cleared. Therefore, a negative PCR on CSF does not suggest that the pet NEVER had distemper, it merely suggests that there isn't detectable virus at that point in time. CSF titers (IgG/IgM) can be quite useful in this situation when compared to the serum titers. That said...what do we do with this information?
  

• Immuno-histochemistry on hyperkeratotic foot pad, conjunctiva, respiratory epithelium or CSF WBC can be diagnostic.

Treatment

Supportive care is important. Anticonvulsant drugs should be employed if seizures are present. Quality of life may be limited and poor if seizures are present and progressive. Myoclonus does not necessitate euthanasia (and should be differentiated from seizures) but it may negatively affect the quality of life depending on the muscles involved. I have personally seen distemper cause myoclonus of the jaw with repeated opening and closing (it looks like a pet gasping for air), flexion of the lips (with resultant wear of the teeth due to grinding) and abdominal contraction (like a hyperactive cutaneous trunci reflex) in dogs with confirmed distemper. No treatment resolves myoclonus at this time.

Although this is a rare disease due to vaccination, we have had a resurgence in our area due, I suspect, to an increase in pet adoptions from endemic areas such as the southeastern USA. Vaccination can prevent infection for most pets!

Have you treated distemper? How did it go? Reach out and let me know if you have any questions or comments on this disease.

For those of you in my referral zone - please note that I will be closed and not responsive to email or telephone Monday-Thursday September 6-9th as we celebrate Rosh Hashanah (Jewish New Year). I apologize for any delayed responses during this time and, as always, appreciate your patience!