Recurrent Cervical Pain

Imagine with me that you are presented with a 10 kg small breed dog on Tuesday morning with a history of neck pain. This dog had a history of neck pain 1 year ago that underwent full work up, at your local University or specialty hospital, and was diagnosed with a disc herniation. The clients pursued surgery, and recovery was smooth and complete. The clients were thrilled...until yesterday. Now, they're angry.

How likely is it that this dog has herniated ANOTHER disc in it's neck?

It is a good question, and one that we have some recent data that might help answer this question. A study out of the UK looked at the recurrence rate of cervical pain in dogs that had a prior disc herniation diagnosed via advanced imaging.
119 dogs in the study, 36 dogs had signs of recurrent neck pain or a cervical myelopathy.

• 36/119 had medical management following diagnosis of IVDH

  • 13/36 (36%) had a recurrence of signs

  • Recurrence was more likely at the same intervertebral disc space

• 83/119 had surgical correction following diagnosis of IVDH
  

  • 27/83 (33%) had a recurrence of signs

  • Recurrence was more likely at neighboring intervertebral disc space to the original disc herniation

• Surgical correction did not decrease the odds of recurrence in this study. Important: We don't know if these dogs underwent surgical fenestration at the time of their first surgery, or not.

• Recurrence was within 2 years of the original diagnosis of a disc herniation for 80% of the dogs in this study. (Note: this means that 20% it was longer than 2 years!)

** We don't know that every one of the dogs had a second disc herniation but the few that did have work up did have a disc herniation confirmed.

The data reported in this study suggests that medical and surgical correction of cervical disc herniations does not change the risk of new onset cervical pain. Reported ranges in the literature for recurrence of cervical pain with surgical correction are between <10-30% (and probably more towards the 0-15% range in the cervical spine) so it is at the high end of reported recurrence. Reported recurrence with medical management is slightly more difficult to track but may be in the 30-40% range. Therefore, it is surprising that the authors saw a similar recurrence for medical vs surgical correction. This may come down to the surgical correction performed, which we don't know from this study. We do know that none of the dogs with surgical correction had a recurrence at the site of correction.

What should we tell the client before us? Surgical correction for a ruptured disc corrects the issue at that disc, but may not address degeneration at distant sites. Sadly, their pet may be faced with a recurrence of another disc herniation. If they're up for another workup and possible surgery, it's time to start the process for referral. If they'd like to give medical management a try, get started on some pain management and bed rest (avoid those steroids if you can in these cases!) and keep a close eye on the dog. Weekly neurologic exam would be recommended, if possible.

Link: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jsap.13480

This Tidbit took a slightly different approach than my usual updates. I typically try to pull 1-2 key points from an article that I find useful, and that I think you'll find useful. This time, I decided to represent a study that wasn't highly powered, that also didn't provide clear, convincing data to support a specific question. We all like black and white scientific data that we can read, digest and apply but honestly, that is a minority of what I read on a daily basis. This TidBit had more "waffling" in it because I wasn't fully convinced the data provided would change my practice. How did this report strike you? Did you find it useful, or not? As always, thanks for reading!

Have a great week and keep those consults rolling!

Status Epilepticus

Status epilepticus (SE) is defined as continuous seizure activity for more than 5 minutes or two seizures in which consciousness isn't resumed in between. SE has a potentially fatal outcome in dogs and humans and is devastating to watch, try to fix, and explain to clients. I wish it wasn't so.

A recent study out of the UK (see below) outlined risk factors for short term mortality (death during hospitalization for SE) and long-term recurrence of SE in dogs. Here are some key points but, as always, if you want more depth please read this open access article.

Short-term mortality:

• 124 cases included, 87 survived to discharge (70%)

• Increasing age, shorter duration of hospitalization, onset of SE before hospitalization and SE being caused by a potentially fatal etiology were related to mortality.

• Of the survivors - 42 had idiopathic epilepsy ( this was the first seizure in 6 dogs), 21 had structural epilepsy (first seizure in 12 of the dogs) and 8 had reactive seizures (first seizure in 10 of the dogs).

Recurrence of SE

• 74 of 87 dogs had follow-up information after discharge. Recurrence happened in 20 of 74 dogs.

• Pharmacoresistant epilepsy and having focal seizures were the only significant risk factor identified. .

• 50% of recurrence was within 2 months from discharge

What do we make of this?
Status epilepticus is a serious form of a seizure. We cannot fully prevent it, but we can counsel clients on the possibility if their animal has one of the predisposing factors identified above (advancing age, fatal etiology or focal seizures). Do not delay on treatment of seizures. Waiting and seeing can result in SE and avoidance is definitely the best policy for management of SE.

JVIM (2022): 36: 353-662.

Thanks for reading! Happy Easter and Passover to those of you that celebrate. Safe fast to those of you in the midst of Ramadan. I look forward to continuing to work with you and your staff to help pets with neurologic disease.

Spinal Trauma

We all know not all vertebra look the same, however did you know this means they don't behave the same way during trauma, too?
Let's look more closely at the cervical vertebra, for a moment.

C1-C2 are a common site of subluxation, especially in young small breed dogs. Congenital C1-C2 subluxation is not considered a traumatic subluxation in most situations. Traumatic C1-C2 subluxation does occur in developmentally normal dogs especially in circumstances when a collar may have resulted in a rapid deceleration of motion (hanging). Cervical vertebra are also "roomier" meaning that the ratio of cord to canal is smaller resulting in more fat in the epidural space compared to the thoracolumbar vertebra. This allows for a traumatic event to cause less clinical neurologic disease and may be a reason why dogs with cervical fractures and subluxations often recover well with medical management. Finally, cervical vertebra have more rotation and flexion or extension capacity compared to thoracolumbar vertebra therefore making them more resistant to fracture and subluxation.
Did you know that 5-10% of dogs have a site of a second spinal fracture/subluxation that is masked by a more cranial trauma? Please consider taking radiographs of the entire vertebral column in a post traumatic patient NOT just in the area of neuroanatomic lesion localization.

Three Column System of Stability
There is some debate about the validity of this system but I will mention it because many surgeons and neurologist ascribe to the principles. This system is used to determine the need to treat a fracture and does not base the need to treat solely on neurologic signs. (Although these are still important!) Instability is considered likely if 2 or more of the columns are affected.
Dorsal column: Dorsal process, dorsal laminal and dorsal ligaments
Middle column: Dorsal longitudinal ligament, dorsal anulus, middle, dorsal part of the vertebral body
Ventral column: Ventral longitudinal ligament, ventral anulus, and ventral body with lateral processes or rib heads.

How to use this information: Evaluate the fracture in two views, whenever possible. If two or more segments are affect, surgical correction should be entertained with the owner (and local surgeon/neurologist if you aren't correcting it yourself). If not (ex: fractured dorsal process), you may be able to avoid surgical correction. There are exceptions to every rule, so if you're unsure please reach out! (As a side note: I don't perform fracture reduction surgery but I am happy to help with the neurologic assessment, and to help facilitate referral.)

A few other notes about the difference between cervical and thoracolumbar vertebra:

• Fractures/subluxation in the C6-T2 region may carry a worse prognosis due to disruption of the LMN to the thoracic limbs.

• The paraspinal musculature of the thoracolumbar region is protective! Don't disrupt it if you don't need to.

• The lumbar vertebra have large articular processes, which protect them from subluxation.

Thanks for reading and I hope you have a great rest of the week! As a reminder - I'm off to Texas for the week so please email if you have any questions but calling/texting may be time delayed due to my lecture schedule.

Seizures in the Post Operative Period

Seizures in the immediate post operative period can indicate a poor prognosis for humans undergoing brain surgery. The same is suspected for dogs, but isn't known. A recent article (see below) recently discussed this question and I thought you might be interested in reading some key points from the article.

Key points:

• 88 dogs underwent 125 procedures. Most had either a brain biopsy or a brain surgery, but some had both.

• All included surgeries were rostro tentorial because caudal tentorial surgery and tumors have a very low incidence of seizures.

• Most dogs (72%) had seizures before brain surgery was performed, therefore diagnosed with structural epilepsy.

• All types of seizures were noted (35% generalized only, 29% focal and generalized and 17% focal only)

• Forty-one of 88 dogs (46%) had a normal interictal neurologic examination. This is MUCH higher than some other studies have shown and is worth noting in general practice. The neurologic examination can help guide you towards advanced diagnostic testing, or not. According to this study, almost 1/2 of the dogs had a normal exam and had a brain tumor!

• About 42% of dogs had an abnormal neurologic examination consistent with a focal lesion and 11% had examination findings consistent with multifocal disease.

What I learned from this article

This article was full of data, so if you're a practicing brain surgeon, it is worth a full read. That said, there were a few points that may benefit the non-neurosurgeons amongst us. I've summarized them below and included a link to the open access article at the bottom if you'd like to read more yourself.

• Early post-operative seizures in humans, are diagnosed in the first month after brain surgery. One of the hypotheses was that dogs receiving anticonvulsant drugs (ACD) would have a lower incidence of post-operative seizures. Interestingly, this article did not detect a difference in post operative seizures between dogs with or without ACD pre-operatively!

• Tumor location nor brain herniation were associated with the development of post operative seizures.

• Curative intent surgery carried a higher risk of post operative seizures when compared to biopsy procedures.

• Dogs with glioma had a higher incidence of seizures compared to other tumor types, except meningioma.

• Dogs with early post operative seizures were less likely to survive to discharge.

• Early post operative seizures occurred in the first 24 hours for all dogs, and were associated with longer hospitalization.

Take Away Message

What does this mean? It means that seizures are a small, but mighty way for the brain to express it's displeasure with human touch. Even the most careful surgeon risks causing seizures that could be life threatening for their patients. I still give ACD pre-operatively but am compelled, by this data, to consider stopping that practice. Why administer an ACD if it isn't associated with a lesser chance of seizures? For most of you, brain surgery is not a part of your daily practice, so I would suggest that the most important take away from this article might be that almost half of dogs had a normal neurologic exam and yet were diagnosed with a brain tumor. Also, if a client asks you about post operative seizures, you can refer to this article! Thank you, Science.

Thanks for reading all the way through! I hope you have a great week and look forward to working with you, and your patients, soon.

Article links: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16391

How reliable is the neurologic exam for patients with vestibular disease?

We (neurologists) like to think that the neurologic examination is the ultimate-be-all-end-all tool. But in dark corners, we talk about how incredibly hard it can be to do on patients with vestibular disease.
First, there are three parts that we need to consider for the lesion localization, correct?
1) Brainstem
2) Cerebellum
3) Peripheral CN 8
My rule of thumb is this: If the pet has ipsilateral hemiparesis/monoparesis, ipsilateral paw replacement deficits or decreased mentation (obtunded, stupor, coma) it is a brainstem lesion. If the pet has hypermetria, or intention tremors along with the vestibular signs, it is cerebellar in origin. Finally, in absence of those findings the lesion is localized peripherally.

An article out of Europe in 2019, dispelled our fears of the neurologic examination failing us and (thankfully) helped us sleep better at night when it was published that the neurologic examination correctly predicted if the vestibular signs were central (brainstem or cerebellum) or peripheral (cranial nerve 8) over 90% of the time.

Interestingly, central disease was more common in this study and, it was localized correctly MORE often than peripheral disease was localized correctly. In other words, dogs with central disease were more likely to be localized on the exam as having central disease compared to dogs with peripheral disease which were occasionally incorrectly localized with central disease.

A few more good reminders:

• Nystagmus are not a localizing sign! (E.g. 8 dogs with peripheral and 5 dogs with central disease had horizontal nystagmus.)

• The onset of disease does not predict it's lesion localization. (E.g. Acute and chronic onset of signs were not statistically different between the central and the peripheral groups.)

• They had a lot of French Bulldogs in the study! Huh..I'm not sure I've noticed an over representation of French Bulldogs in my clinical work. It's good to learn something new everyday.

So, what does that mean for us?

It means if you do a thorough neurologic exam, you'll be correct about 90% of the time when you guide a client towards an MRI and spinal tap (for central disease) or treat for idiopathic or otitis (for peripheral disease). If you're unsure, err on the side of it being a central lesion and recommend a full work up. (Or contact me for a consult!) Oh, and 68% of dogs diagnosed with peripheral vestibular were idiopathic! Idiopathic disease means we have a lot more to learn...so let's get back to it!

(Bongartz U, et al. Vestibular Disease in dogs: association between neurological examination, MRI lesion localization and outcome. JSAP 2019).

Thanks for reading! This was an oldie, but a goodie and I hope you enjoyed revisiting it along with me. Please reach out if you have any questions. Have a great week

The Case of the Shrinking Head

Signalment: 4.5 year old MC Shepherd Mix

Clinical history: The dog had a 3 week history of left unilateral temporalis muscle atrophy when I met him. Hyporexia and nasal hemorrhage from the right nostril were noted when the signs first started, but they had improved by our consult. The atrophy, however, continued to progress.

Physical and Neurologic Examination:
The physical exam was normal.

Mentation: BAR
Cranial nerves: moderate left temporalis muscle atrophy, otherwise normal. No sensory abnormalities noted.
Gait: Ambulatory, no evidence of lameness, weakness or ataxia
Reflexes: normal all limbs
Postural reactions: Normal all limbs
Palpation: Non-painful spinal palpation and normal CROM

Neuroanatomic Lesion Localization?
Let's walk this through. First, what nerve innervates the temporalis muscles? (CN 5: trigeminal) So, our problem is a) peripheral trigeminal b) brainstem at the trigeminal motor nucleus or c) muscle. How do you sort between these? Right! Let's rule out the easy one first. Signs of brainstem disease include changes in mentation, paw replacement deficits (ipsilateral to the atrophy) and/or hemiparesis. Any one of these three abnormalities is present and voila! it is a brainstem lesion until otherwise discovered. We ruled out brainstem disease in this dog. Is this, then, peripheral trigeminal nerve (motor portion) or muscle? This differentiation can be hard on the neurologic examination so I actually included both of these possibilities on this dog's final neuroanatomic lesion localization. However, without a sensory deficit (he didn't have one) a trigeminal neuropathy is less likely. That said, if the CK is normal, it's hard to make a story for a myopathy. His was normal. So...I left both on the final list. You could have said "neuromuscular" and you would have been correct because that localization includes peripheral neuropathy, neuromuscular junction and myopathy.

Differential Diagnoses?
Neuropathy: Neoplasia, neuritis (infectious or non-infectious), hypothyroidism and trauma.

Myopathy: Masticatory muscle myositis (3M), infectious myositis (toxoplasma and Neospora caninum are most common causes of infectious myositis.)

Diagnostic Results
CBC, serum biochemistry: unremarkable.
T4: normal
Neospora antibody M titer: > 1:200 (positive!)
Toxoplasma IgG/IgM titer: Negative
3M antibody titer: < 1:100 (negative)

Conclusion
This patient was diagnosed with a Neospora myositis based on positive titers. We placed him on sulfa antibiotics and tracked the titers. Clindamycin is also an acceptable antibiotic choice for fighting protozoa myositis.
2 months later: 1:200
4 months later: 1:100
1.5 months later: negative.

Unfortunately, this patient developed an adverse reaction from the sulfa that included blood dyscrasias and hypothyroidism 5.5 months from the original diagnosis. The sulfa-based antibiotic was discontinued and clindamycin was started. My goal is to have 2 negative Neospora titers before discontinuing antibiotics but we will have to see if we get to meet that goal with this guy!

Key Points:
1. Muscle atrophy (especially unilateral) should prompt a toxoplasma (cat) and toxoplasma and Neospora titer (dog). This is a lesser known infection in Wisconsin dogs!
2. Treat with either a sulfa antibiotic or clindamycin to the point of two consecutive negative titers to ensure clearance of the infection. Titers are typically checked every 4-8 weeks.

This was a very interesting case and a great one to remind us all about protozoal infections in house pets. Remember - when we work together, we all learn!

I look forward to working with you soon.

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!