Canine Distemper Causing Lameness?

An interesting case report came across my desk awhile ago so I thought I might share some key points with you this week. (Green L, Cook L, et al. Distemper encephalomyelitis Presenting with Lower Motor Neuron Signs in a Young Dog. JAAH 2020)

Signalment: 4 month old spayed female dog

History: The puppy was presented to the neurology service with a several day history of right thoracic limb monoparesis. Key findings in the neurologic examination included axial pain on palpation, thoracic limb lameness, weak withdrawal of the affected limb and a paw replacement deficit in that limb. Absent cutaneous trunci reflex was also noted on the right side. Other than the neurologic findings, the only other interesting finding on physical examination was a mildly febrile state of 102.7F) and crusting of the foot pads.

She was initially managed conservatively however signs progressed to inappropriate mentation which was suspected to be due to the fentanyl patch. This was removed and signs improved however the clients elected to proceed with additional testing at that time.

Neuroanatomic lesion localization? You tell me!! (see below when ready)

Differential diagnoses listed at this time included non-infectious inflammatory conditions (MUE), infectious meningomyelitis, and hemorrhage or trauma.

Diagnostic testing

• Spinal MRI: Abnormalities in the central spinal cord

• Brain MRI: Unremarkable

• CSF: Mild pleocytosis cell count 10/ul: reference < 5/ul) with normal protein and RBC.

• Infectious disease testing: Neospora IFA was negative however the Toxoplasma IgG was markedly elevated with a borderline IgM. Parvovirus testing and cryptococcus antigen testing was negative. PCR on CSF for distemper (CDV) was positive. A whole lot of other infectious diseases were tested for, and negative.
  

Treatment with clindamycin, sucralfate, gabapentin, tramadol, famotidine, metronidazole and a single dose of dexamethasone was started.

Progression: She was discharged 4 days later, but returned due to progressive mentation changes and worsening ambulation. During evaluation she had a focal seizure. (Now we have multifocal neuroanatomic lesion localization!). She was humanely euthanized and submitted for necropsy.

Necropsy: Findings consistent with CDV were found and in addition, immunohistochemistry of the C5 and lumbar spinal cord and strong nuclear and cytoplasmic brown staining for CDV and no staining for Toxoplasma.

What is so noteworthy about this case?

• She was partially vaccinated. Did you know that 40% of dogs with confirmed distemper infection, in one study, were vaccinated? (Tipold A: 1995).

• She had hyperesthesia associated with her neurologic signs. Pain is a very unusual finding for a distemper case and the authors suggest this is the first case report of confirmed CDV in a dog with limb pain.

• The progression from limb to brain is unusual but not unreported.

Take Home Message
A young dog, with multifocal neurologic findings, or findings of spinal pain in conjunction with neurologic findings, may have CDV. I suggest adding this disease to your ever-growing-list of infectious diseases that can cause spinal pain in dogs.

Neuroanatomic lesion localization answer: C6-T2 radiculopathy or neuropathy. There is no evidence of spinal cord involvement initially so a myelopathy is less likely.

As always, thanks for reading! I hope you have a NON-PAINFUL week, that isn't LAME! (Sorry...I just couldn't help myself.)

What do CBD and Phenobarbital Have in Common?

Phenobarbital and CBD are known to both use the Cytochrome P450 system for hepatic metabolism therefore it stands to reason that co-administration could result in altered metabolism of one or both of these drugs.

In a recent study by Doran et al (https://doi.org/10.2460/ajvr.21.08.0120), changes in CBD pharmacokinetics (PK) were discussed, in reference to phenobarbital. Interestingly, no apparent changes in PK of phenobarbital or CBD were noted when each drug was given ONCE (not chronic dosing).

Significant changes in serum ALP were noted during chronic (3 week) CBD dosing at 10 and 20 mg/kg/d. More dogs had a chance in serum ALP concentration at the higher dose, but the sample sizes were very small so it is difficult to extract too much information from that finding.

Also interesting, the maximal concentration of CBD was higher in fed animals, than in those fasted at the time of CBD administration. Food for thought...

What is the take away?
1. CBD alone can cause elevated ALP in dogs. Significance? Not addressed in this study.
2. We don't know how phenobarbital serum concentrations are affected by chronic or single dose exposure to CBD, because this wasn't studied as a separate question.
3. This study didn't tell us anything about dose escalations so if you are using CBD oil in your practice, please look elsewhere for dosing recommendations for efficacy!

**Disclaimer: the State of Wisconsin forbids prescribing or recommending CBD containing products by veterinarians. Please consider this TidBit informative and not a recommendation for treatment with CBD containing products for pets.**

Short and sweet this week! Have a great week and I hope to work with you soon!

How to Use Phenobarbital Serum Concentrations

The 5 year old Golden Retriever

The set up...
Decker presented to me with a history of 3 seizures in the preceding 2 weeks. The seizures were consistent with generalized, tonic-clonic seizures of a duration about 30 seconds to 2 minutes (depending on the parent reporting the seizure). Decker was a very big boy. Not fat...just one of those super large Goldens that we occasionally see. He had a pretty healthy history prior to the seizures other than occasional ear and skin issues that the primary veterinarian had addressed. He wasn't taking any current treatment, was up to date on vaccines, hadn't traveled out of Wisconsin in the last 6 months, did not have a history of head trauma and wasn't a working dog. Yes, I do ask all of those questions during a seizure consult, every time. Unless I forget. But I try not to forget.

The Exam...
Decker's exam was normal. Normal physical (other than his giant, wonderful self) and a normal neurologic examination. So his lesion localization was... (you fill in this blank. Look at the bottom to check your answer).

The Plan...
Decker needed anticonvulsants. More than 1 seizure every 3 months is a good reason to start anticonvulsant therapy according to the IVETF. So, we did! We started phenobarbital at about 4 mg/kg PO q12h and requested a serum phenobarbital concentration in 14 days.

The Serum Concentration...
14 days after starting phenobarbital the serum phenobarbital concentration was 22 ug/ml (reference range: 15-40 ug/ml)

What do you do with this information?
Well, to answer that question you must first ask yourself why you took the serum phenobarbital concentration in the first place? Was it...
1. To document that it was therapeutic for Decker?
2. To ensure it wasn't toxic?
3. To show if the client wasn't giving it right?
4. To document if the serum concentration was too low?

How do you know if the dose was appropriate for Decker? You look at the seizure calendar, which we cannot do until Decker has been on phenobarbital for at least 3 "seizure cycles". What is a seizure cycle? It is the interval between seizures. In his case, it is less than 2 weeks (3 seizures within 2 weeks). So, we must evaluate efficacy by looking at about a 6 week interval of time.

Toxicity is seen by clinical adverse effects in the pet, which we cannot truly evaluate until the drug reaches steady-state. Steady-state is about 14 days in dogs, therefore signs of toxicity (or that the dose is too HIGH) should be assessed at the 14 day visit, or shortly thereafter. If adverse clinical effects are problematic after 14 days, the dose may be too high.

If the client isn't giving the drug, the serum concentration will be lower, but how much lower really depends on how often they miss a dose. This is not an appropriate way to ensure the client is giving the drug, in my opinion.

So, why take a serum concentration at all?? I do it to determine if the dose is too LOW. Serum concentrations below 15 ug/ml are outside of the accepted canine therapeutic range and therefore the dose should be increased. I would argue that serum concentrations below 25 ug/ml are clinically less desirable and typically advocate a dose increase for many pets (depending on clinical adverse effects).

What is the take away message?
Take the serum concentration to ensure it is not too low, use the dog to determine if the side effects are too high, and use the seizure calendar to determine if the dose is effective.

Thanks for reading! If reading this makes you groan, please reach out! I'm happy to help you manage your patients and love doing seizure consults. (Yes, for real!)

I am on vacation until Friday February 18th and ask for your patience if you reach out this week. I will reply but it probably won't be as quickly as you are used to!

Predicting Spinal Shock

When things go bump in the spine...

So many interesting cases happened this past week! Please join me today as we evaluate a 4 year old FS Mixed breed 10 kg dog, together. Her presenting complaint was acute onset difficulty walking in the last 24 hours.

Neurologic Examination:
Mentation: BAR
Cranial nerves: all normall
Gait: Paraplegia (no voluntary movement)
Reflexes: reduced withdrawal in both pelvic limbs, poor anal tone, and reduced cutaneous trunci reflex to T13 bilaterally. All remaining reflexes normal.
Postural reactions: Absent both pelvic limbs, normal both thoracic limbs
Palpation: Painful at T12-T13, remainder non painful.
Other: Absent nociception in both medial and lateral toes of both pelvic limbs.

Neuroanatomic lesion localization: Hmmmm....let's take a moment and think this through.
1) Does this dog have neurologic disease? Yes!
2) Are forelimbs and intracranial structures normal? I'd say, yes. Okay, the lesion is caudal to T2.
3) Our choices for lesion localization are, T3-L3, L4-S3 or neuromuscular at this point.
4) Are reflexes affected? Yes. Therefore the lesion must be L4-S3 or neuromuscular. But wait! What about that back pain and reduced c. trunci reflex? The cutaneous trunci reflex reflects a T3-L3 myelopathy and the back pain certainly supports that but could be from non-neural causes. Is this multifocal spinal cord?
5) Hold the phone, Barnes. Tell me why this isn't neuromuscular? Okay, I'll tell you. Sensory neuropathies are extremely rare and are usually congenital. Therefore, to have a loss of deep pain this animal needs to have a spinal cord lesion. Moving on then....

Neuroanatomic Lesion localization: Folks, this is an example of multifocal neuroanatomic lesion localization of T3-L3 and L4-S3 spinal cord. Primary differentials would include acute diseases affecting the spinal cord (such as FCE, disc herniation, trauma) plus spinal shock, or a true multifocal spinal cord disease (such as meningomyelitis).

What is Spinal Shock?

Spinal shock occurs when there is "reverberation" and a change of the local environment that results in temporary cessation of reflexes downstream from the injury. In most models, the injury is at the TL junction so the pelvic limb spinal reflexes are temporarily lost. This is transient! For most animals, the reflexes return in 1-3 days if not shorter. It is important to note that there is NO pathology in the pelvic plexus.

Predictive Models

How do you know when you have a pet with spinal shock or a pet with a multifocal disease when you have multifocal spinal cord lesion localization? The honest truth is you don't know until you do an MRI and show that only one lesion is present. However, there was a predictive model recently published (https://onlinelibrary.wiley.com/doi/10.1111/jvim.16352) that showed smaller breeds, with a history of less than 24 hours, are more likely to have spinal shock. As with all predictive models, this isn't fool proof, but it is a start. For the case above, I would strongly consider spinal shock with a T3-L3 myelopathy. Indeed this is what we had; we had an FCE at T12-L1 on MRI and no additional lesions in the L4-S3 segment.

Hope this TidBit was helpful to your practice! Please reach out if you have a case I can help with, or if you have an idea for a TidBit Tuesday mailer. Happy February!

The Weak Lab

Here is the scene: You're evaluating a 10 year old MC Labrador retriever for a 6 month history of progressive difficulty walking. Signs were first noted in the pelvic limbs but have recently been noted in the thoracic limns. As an astute vet, you also discover that the dog has become hoarse, too. (Nice job!)

Physical examination: Unremarkable other that OA in the stifles from prior CCL injury and surgery .

Neurologic examination:
Mentation: BAR
Cranial nerves: Hoarse voice and harsh breathing consistent with laryngeal paralysis. Remaining cranial nerve examination normal.
Gait: ambulatory, slapping limb gait when walking, especially in the pelvic limbs. The dog appears to walk like he is wearing clown shoes.
Postural reactions: Absent paw replacement testing all four limbs

Reflexes: Absent femoral reflex (bilateral), reduced gastroc reflexes (bilateral), reduced distal withdrawal of all four limbs but most notable distal to the hock bilaterally, unable to obtain bicep reflexes (bilateral). Intact perineal, and reduced (but present) C. trunci throughout the entire TL region.
Palpation: Non painful spinal palpation, normal cervical ROM

Holy cow! What is this? (You might be wondering) This neurologic exam is all over the place!! I need help. (It's okay to stop here and call me or setup a consult.) However, since we're on a learning track today let's talk though this one together. I am willing to bet you can get this.

How to lesion localize this case if you lived inside of my brain:

1. First, we don't see any evidence of forebrain or brainstem disease, correct? (No CN deficits, no seizures, no mentation changes.) Okay, cross that off.

2. Secondly, all four limbs are involved. This cannot be T3-L3, or L4-S3 because ONLY the pelvic limbs would be affected. (See, we're getting somewhere!) Cross those off.

3. This leaves us C1-C5 or C6-T2 myelopathy, if this is spinal in origin. You might be tempted to say C6-T2 myelopathy because of the reflex deficits in the thoracic limbs but remember that we have reflex deficits in all four limbs and that just isn't possible with a C6-T2 myelopathy. You must have a lesion in the spinal cord plexus (C6-T2, L4-S3), or the nerve, or the neuromuscular junction to have a reflex deficit. Cross off C1-C5, and C6-T2.
   

4. Okay, big breath. This is NOT spinal cord in origin. It cannot be. It doesn't line up! We have ourselves a neuromuscular disease

What to do next, if you suspect neuromuscular disease

1. Neuropathy – reduced reflexes in multiple limbs, and/or limbs and head. Postural reactions may be reduced or absent. Pain is not noted on palpation. NO ataxia!

2. Junctionopathy – absent reflexes, non-ambulatory paresis or exercise induced non-ambulatory paresis. Depending on the severity, these animals may have a range reduced to absent postural reactions. (Myasthenia gravis is the exception. It is a junctionopathy but acts like a myopathy.)

3. Myopathy – Classically, these animals have a normal neurologic examination. (Think muscle disease, not neurologic disease) They are paretic (ranging from poorly ambulatory to ambulatory with fatigue) without any postural deficits or reflex deficits. Muscle pain, stiffness and pain on palpation may fool you into thinking they have spinal pain.

This case fits with a neuropathy, doesn't it? In fact, this is an example of a neuropathy. This dog has a neurodegenerative neuropathy common in Labrador retrievers. It is suspected to be genetic. The diagnosis is confirmed with muscle and nerve biopsy. (Yes, I can do these for you.)

Sadly, we do not have treatment available to reverse or slow down progression therefore treatment is supportive. Slings when needed, good solid footing such as rugs/carpet or yoga mats, and physical therapy are the mainstay of treatment. Supportive care with acupuncture has also been beneficial for some dogs.

Thanks for reading! Have a wonderful week and stay warm! I will be closed on January 28-29th. I appreciate your patience and look forward to connecting with you on Monday January 31st with any cases or questions you may have.

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.