Prevalence of Idiopathic Epilepsy and Structural Epilepsy in Boxer Dogs

We have another interesting article to review this week! A group from Germany published a retrospective study of 74 Boxer dogs with epilepsy and, although the results aren’t surprising, I felt these were good statistics for us to have in our “conversation belt” when discussing seizures with owners of Boxer dogs. 
 
Before we dive into the results, a little refresher. Idiopathic epilepsy in the general (not exclusive to the Boxer dog) population occurs in about 53% of dogs with structural epilepsy occurring in about 45% of dogs. These numbers change a little bit with age qualifiers. Dogs between 6 months and 6 years of age were diagnosed with idiopathic epilepsy 75% of the time and structural epilepsy 45% of the time. Dogs greater than 6 years of age were diagnosed with idiopathic epilepsy only 34% of the time, with structural epilepsy taking a bigger chunk of the diagnoses at 64%. 

• 
  Now, let's compare these data to Boxer dogs. A recent retrospective study by Loncarica (August 2022...okay, recent is relative), looked at the prevalence of idiopathic epilepsy and structural epilepsy in Boxer dogs. They divided the groups into < 6 months old, 7 months and 6 years and > 6 years old. 
  Results
  < 6 months old - 2/74 dogs diagnosed with seizures: 1 had idiopathic epilepsy, 1 had a meningoencephalocele
  6 mo-6 years - 12/74 dogs diagnosed with seizures: 8/12 (66%) had neoplasia. Of these 8, 2 had a NORMAL neurologic examination. 
  > 6 years old - 60/74 dogs diagnosed with seizures. 58/60 (97%) were diagnosed with neoplasia. Of these 13.58 had a normal neurologic examination. 
  It is notable that only 11 of the dogs in the study had a histologic confirmation of neoplasia, the remainder were based on MRI characteristics. 
  
  Summary
  Is finding seizures in Boxer dogs earth shattering? No. It is noteworthy, I think, that boxer dogs had a MUCH higher prevalence of structural epilepsy, and probable neoplasia, than the average dog population. Is this novel? No, but now we have data to show what we have all been suspecting all these years. :)
  The other key point is that about 25% of dogs over 6 months of age had a normal neurologic examination with structural epilepsy. If a dog has an abnormal neurologic examination, with a seizure history, structural epilepsy is more common. A normal neurologic examination doesn't eliminate the possibility, however. 
  
  Thanks for reading! Please reach out if you have any questions. My schedule is quite limited over the next two weeks as I take a little vacation time with my family over the long Holiday weekend and then spend a few days at IVECCs speaking to an awesome bunch of criticalists, generalists and emergency docs. If you're planning to be there please stop in and say HI! (And come swim with me and my daughter in the water park!) If you have a case that should be seen sooner than later, and cannot find a suitable time on the scheduler, PLEASE REACH OUT. Thanks!
  

Global brain ischemia

A recent article by Dr. Harper Crawford and colleagues from the UK caught my attention. Global brain ischemia can be seen following minutes of poor blood flow including during cardiopulmonary arrest during general anesthesia, severe bite injuries and strangulation. It has also been associated with the use of mouth gags during dental procedures in cats. (Yikes! You probably knew this, but I was surprised by this!) This article was an enlightening review of global brain ischemia as well as a retrospective look at several cases with a focus on treatment, survival and prognosis. 

What is the consequence of failure?

The authors suggest that cerebral perfusion failure can simply be defined as failing to meet the energy demands of the brain and failure of adequate waste removal products. Simple, yes? Irreversible failure can start within minutes of ischemia through loss of ATP. After ATP is depleted, Na+ and K+ will influx intracellular dragging water with it and the neuron will depolarize. This is the start of cytotoxic edema. From there, a secondary release of excitatory neurotransmitters, particularly glutamate will be released which results in eventual mitochondrial dysfunction, lipid peroxidation and vascular injury. The final nail in the proverbial coffin is rising intracellular Ca++ which triggers cell death. The most sensitive cells are in the cerebral cortex, hippocampus and Purkinje neurons in the cerebellum.

Materials and Methods

Short term outcome was defined as survival (or not) for the first 72 hours. Long-erm was defined as the neurologic examination at the last follow-up examination available for review.
The study utilized an outcome scale as follows:
0: dead or euthanized due to severe neurologic deficits
1: poor recovery with severe persistent neurologic deficits
2: good recovery with mild persistent deficits
3: excellent recovery with normal function.

Results

10 animals were included: 8 dogs and cats with in hospital cardiopulmonary arrest and 2 dogs with out of hospital arrest (1 vehicular trauma, 1 asphyxiation from food). The duration of suspected arrest ranged from 1-5 minutes (median 3 minutes) for animals with in-hospital cardiopulmonary arrest and 10-22 minutes for the 2 animals with out of hospital cardiopulmonary arrest. The neurologic exam for the animals with in hospital cardiopulmonary arrest was reported at a median of 9 hours post insult. Median hospital duration was 7 days. Short term survival occurred in 8/10 cases including 1 case that did not survive to long-term. Seven animals survived to discharge and were re-evaluated at a median of 67 days. Outcome scale results:
Grade 0: 3
Grade 1: 1
Grade 2: 2
Grade 3: 4
The patients with an outcome score of 2 or 3 all showed consistent neurologic improvement in the first 48-72 hours. For the animals that experienced seizures during hospitalization (3), anti-epileptic medication was continued for between 2-8 months after starting. Levetiracetam was used in 1 cat and 1 dog, and phenobarbital was used in 1 dog. No additional seizures were reported in any pet following discharge.
This report demonstrated that although global ischemia can cause severe neurologic deficits, successful long-term outcomes are possible. Furthermore, they noted that an association with duration from onset of cardiopulmonary arrest to spontaneous breathing is a factor in recovery in rodent models and human studies, but this study was too small to draw those conclusions.

References: DOI: 10.1111/jvim.16790 Harper Crawford A, Beltran E, Danciu CG, Yaffy D. Clinical presentation, diagnosis, treatment and outcome in 8 dogs and 2 cats with global hypoxic-ischemic brain injury (2010-2022). JVIM 2023.
Thanks for reading! I hope you have a great week and I look forward to working with you soon!

Feline Hyperesthesia Syndrome

What is it?

Appropriately termed a ‘mystery disease’, feline hyperesthesia syndrome (FHS) has an unknown etiology to date. Clinical signs often include skin rippling over the dorsum, tail chasing and self-trauma, sudden jumping and running for no obvious reason and occasionally vocalization during episodes. Interestingly most cats are young (less than 1 year of age). The etiology has been proposed to be behavioral (due to the lack of identifiable organic disease), seizure disorder (due to the paroxysmal type clinical signs and directed motor activity), or a collection of multiple factors including behavioral and environmental.

How is it Diagnosed?

Obtaining a diagnosis is complex because as of yet, we don’t understand the etiology. <Groan> Therefore, as a neurologist I attempt to rule out organic CNS disease. This includes MRI, spinal tap, sometimes muscle biopsies and electrodiagnostic evaluation for peripheral neuropathy/myopathy. A recent retrospective study evaluated 7 cats with this clinical picture and did not identify any neurologic cause in these cats.1 Treatment with gabapentin, meloxicam, antibiotics, phenobarbital, prednisolone, and topiramate were tried in multiple cats. Clinical improvement was noted in 6 of 7 cats using gabapentin alone (2 cats), gabapentin, cyclosporine, and amitriptyline (1 cat), gabapentin, prednisolone, phenobarbital (1 cat) or gabapentin, topiramate and meloxicam (1 cat). Treatment in my practice consists of anticonvulsants to rule out/in epileptic activity, followed by pain management with gabapentin.  Referral to a behaviorist, dermatologist and/or internist is often made as well because of the complex and unknown nature of this mystery disease.

That's it for this week. Short and sweet because, honestly, I thought you could use a little less to read during summer!

Have a terrific week. Keep those consults coming! We've worked through some really interesting cases lately.

The Gut and The Brain

The gastrointestinal microbiota (GIM) is the new hot topic in neurology. This contractile organ, far distant from the brain is now considered a a possible source for drug resistant epilepsy in canine epilepsy research as well as a potential cause for behavioral disease in epileptic and non-epileptic dogs alike. A recent article by Watanangura et al highlighted the importance of the GIM in epilepsy.
The aim of their study was to investigate the effect of phenobarbital (monotherapy) on the composition of the GIM and to determine if it resulted in a change to behavior in a select group of dogs. To be included in this study, all dogs had to meet Tier II level of confidence for epilepsy (normal brain MRI, spinal tap, normal blood work and neurologic examination) and be naive on any anticonvulsant treatment. They had 12 dogs who meet these inclusion criteria. On day 1, they started phenobarbital at 2.5 mg/kg PO q12h and took fecal samples. The drug was continued without dose adjustment for 90 days at which time another fecal sample was taken. Behavioral questionnaires were submitted on day 1 and day 90 as well.

The results:

• Serum phenobarbital concentrations ranged from 19.8-18.1 mg/L (day 30 and day 90)

• Seven of 12 dogs were seizure free throughout the study and called responders.

• Five of 12 dogs were not seizure free and were called non-responders.

• Short chain fatty acids (SCFA) did increase significantly in the study, specifically propionate and butyrate.

• Butyrate was significantly higher in the responder group compared to the non-responder group. Butyrate is an anti-inflammatory fatty acid which may  benefit epileptic dogs, yielding better response to treatment. Perhaps this is due to the neuroprotective effects, or by providing an alternative energy source for the brain.

• The behavior survey showed a significant decrease in stranger-directed fear, and non-social fear with an increase in trainability! Phenobarbital has been used as an anxiolytic for humans and veterinary patients, supporting this finding. An idiosyncratic hyperexcitability and aggression has been reported with phenobarbital however it is rare. (More commonly seen with levetiracetam.)

• There was no difference in the bacterial taxa in this study except for a significant decrease in Clostridiales on day 90. The significance of this remains to be seen, however it may affect the distribution of MCFA and other products.

The Take Home Message
What do we do with this information? Well…we tuck it away in our heads and know that phenobarbital, or seizures themselves, might affect the GI microbiome and SCFA in the GI. Does this mean we should supplement? Not yet. I am not sure we know who, how and when to supplement based on this study. This was a critical step forward in our path towards understanding the GIM and I am excited to share additional information that comes forth in this area!
 
Have a wonderful week and enjoy what August has to offer us! I look forward to working with you soon.

The 5 Types of Disc Herniation (that we know of!)

The Five Types of Disc Herniation (that we know of!)

'Tis CE season so I thought it would be fun to pull up this old TidBit Tuesday from 2020 and refresh our memories about the different types of disc herniation that may be diagnosed in dogs. I hope you enjoy this light reading on your midsummers morning!

1. Dystrophic calcification secondary to chondroid degeneration of nucleus pulposus (NP), is called Hanson Type I. This causes mechanical stress on the outer annulus fibrosus (AF), leading to rupture of individual collagenous strands of AF and eventually full failure and extrusion.

2. Fibrous degeneration occurs when fibers of the disc split leading to accumulation of tissue fluid and plasma between the annular fibers. Over time the mechanical pressure exerted by NP causes thickening of the AF dorsally, causing protrusion. (Hanson Type II).

3. ANNPE (Acute noncompressive nucleus pulposus extrusion) - this is normal (probably) NP that is exploded into the canal, usually during high activity. Also called a traumatic disc herniation by some folks.

4. AHNPE (Acute hydrated nucleus pulposus extrusion) – An apparently normally hydrated NP that is compressive and often located ventral to the cord in the cervical spine.

   1. There may be significantly more neuro deficits and less signs of cervical pain with AHNPE compared to other causes of cervical myelopathy.

5. FCE (Fibrocartilaginous embolism): a piece of material histologically similar NP that becomes dislodged and finds its way into the vasculature surrounding the spinal cord. This can be into venous or arterial blood vessels. The end result is an acute shift in blood flow at the level of the spinal cord.

Match the clinical sign with the type of disc herniation

A. Chronic, progressive ataxia progressing to paresis
B. Acute, non-progressive unilateral weakness affecting one leg, or one side (hemiparesis)
C. Acute, progressive, painful ataxia progressing to paresis in a chondrodystrophic dog
D. Acute non-progressive ataxia and paresis affecting both sides of the body (paraparesis or tetraparesis)
E. Acute, rapidly progressive tetraparesis and ataxia of all four limbs with minimal cervical pain

If you answered...
Type I: C
Type II: A
ANNPE: D
AHNPE: E
FCE: B

you are correct!

Based on the clinical picture, it can be very difficult to distinguish Type I from ANNPE, and AHNPE. Typically, type I is painful (but not always), and the other two are minimally to non-painful. 

Which of these require surgery?

Any disc herniation that results in compression of the spinal cord with associated clinical signs could be considered for surgical correction. This statement would then suggest that Type I, Type II and AHNPE could be surgically corrected. Therefore, any patient with signs of a progressive or painful myelopathy should be evaluated for diagnostic imaging (typically MRI) for possible surgical intervention whenever possible.


Thanks for reading! I hope you have a wonderful week. As always, reach out if I can help you, help your patients, with neurologic disease. 

Brain Herniation in Cats

Brain herniation is diagnosed when one part of the brain shifts to another part of the cranial vault. The four most common types of herniation include: 1) Midline falx herniation (from left to right side of the forebrain), 2) caudal transtentorial herniation (cerebrum herniations under the tentori cerebelli onto the cerebellum and brainstem, 3) rostral transtentorial herniation (cerebellum herniates rostrally into forebain and 4) foramen magnum herniation (cerebellum exits out the foramen magnum). Brain herniation may be acute, secondary to a sudden shift in intracranial pressure or gradual secondary to a chronic or slow rising intracranial pressure.

The most common cause of acute herniation is trauma, resulting in cytotoxic and vasogenic edema or hemorrhage with a subsequent sudden increase in intracranial pressure. Brain tumors account for the majority of cases with a gradual increase in intracranial pressure.

The Cushing's Reflex, identified by Dr. Harvey Cushing, describes a reflexive bradycardia and hypertension with a reduced level of consciousness, induced by increased intracranial pressure. Increased pressure can result in poor cerebral perfusion, and ultimately brain herniation. 
A recent article evaluated cats with brain herniation noted on MRI to cats with intracranial disease WITHOUT brain herniation for signs of the Cushing's Reflex, and other clinical factors that might predict the presence of herniation. They evaluated: age, weight, heart rate, respiratory rate, temperature, blood pressure, level of mentation, Glasgow Coma Scale gait assessment and brainstem reflexes. Can you guess what they found?

There was no significant difference in any of these factors between the two groups except as related to level of consciousness and age. Cats with brain herniation were significantly older, and had a reduced level of consciousness compared to cats with intracranial disease without evidence of herniation. Wow!

Why didn't we see a Cushing's Reflex? Well, one option is that the majority of cats were diagnosed with intracranial neoplasia which we know is a slow growing process. This may have provided ample time for compensatory mechanisms so that a significant difference couldn't be determined in this study. Another option is that clinical evidence of brain herniation is simply less obvious or prevalent in cats. One prior study of cats with normal brains found incidental herniation in up to 40% of the cats! 

What's the take away? Cats with brain herniation may present very similarly to cats without brain herniation . Therefore, any cat with an intracranial neuroanatomic lesion localization undergoing general anesthesia should be managed as if they have increased intracranial pressures. Do not administer anesthetic drugs that are known to markedly increased or decrease blood pressure as this may negatively affect the cerebral perfusion pressure. When in doubt, assume they have increased intracranial pressure. 

Thanks for reading! This week is the 4H Dane County Fair so if you need me I'll be watching horse shows and eating cotton candy! Feel free to text or email anytime, however my live consult availability is very limited due to my kid's show schedules. Have a great week!

The use of AI In Veterinary Medicine

At the recent ACVIM Forum in Philadelphia, a radiologist gave a very enlightening presentation about AI, and specifically ChatGPT. Have any of you messed around with this technology yet? Is anyone using it for work flow support? Although this TidBit Tuesday isn’t specifically about a neurology topic, I was so blow away by the ChatGPT lecture I decided to include it as a TidBit Tuesday. We’ll be back to our regularly scheduled neurology topics next week… 😊

To get us all on the same page, ChatGPT is a new artificial intelligence (AI) software developed by Microsoft engineers. The presenter at ACVIM (Dr. Eli Cohen, provided an example during his talk of a “conversation” he had with ChatGPT that terrified me. While reviewing a radiograph ChatGPT suggested that one of the differentials for this pet with clear lytic bone lesions on each side of an intervertebral disc space could be “sterile discospondylitis”. Dr. Cohen, like all of us in the audience, instantly worried that we had missed this diagnosis in our years of practice experience. STERILE disco? Is this real? How could I have missed this?? So, he asked ChatGPT to provide references for this statement. AND IT DID. Dozens of references popped up on the screen. They were from reputable journals like JAVMA, JVIM, and Vet Rad and Ultrasound. By real, live people, practicing veterinary neurologists and radiologists. Some of us were in the audience. The catch? None of these references were real. NOT ONE of the references was actually a reference for this imaginary disease. ChatGPT had taken names of people that may have written about “sterile” and “discospondylitis” separately and combined this into believable reference points. My take away from this was to make sure if and when I use ChatGPT for any work-related item, that I personally double check (dare I say vet?) all of the data points. Here is a perfect example. I fed ChatGPT the following question:

What is the neuroanatomic lesion localization for a dog with seizures?

Here is the answer:

Seizures in dogs can arise from various neuroanatomic locations. The specific neuroanatomic lesion localization for seizures depends on the underlying cause and can vary between individual cases. Here are a few examples of potential lesion locations associated with seizures in dogs…

WRONG. What is the correct neuroanatomic lesion localization for a dog with seizures? That’s right, forebrain or prosencephalon. There is only one neuroanatomic lesion localization for pets with seizures. The etiology varies widely from hypoglycemia to brain tumors, but all seizures come from one part.

This was a wonderful reminder to me how important the grasp of words, terms and phrases is when we communicate in veterinary medicine. I, probably similar to you, will be using AI in my veterinary career in the future. I think it is probably inevitable. However, we must remember to double check what we put in is using the correct terminology, and that the produced answer is in line with our knowledge and understanding.

I’d love to hear if you use AI in your personal or professional life and how it has affected you. I hope you had a safe and happy 1st or 4th of July and I look forward to seeing you, without robots, in the future!

CBD Treatment for Resistant Epilepsy in Dogs

Use of CBD Oil for Refractory Epileptic Dogs

It's baaaack! At the ACVIM conference a few weeks ago I had the pleasure of listening to researchers from Colorado State University present data from a recent double blinded, placebo controlled prospective study evaluating CBD oil in resistant epileptic dogs. 

How the Study Worked

51 client owned dogs, taking at least 1 ACD (anticonvulsant drug) and continuing to have 2 or more seizures every month, were included. Resistant epileptics are already the hardest subset to manage so this was a really tough crowd for the researchers to target. The dogs were given either placebo or CBD oil for 3 months and then switched and given the other compound for 3 months. Initially, they dosed at 2.5 mg/kg PO q12h but no effect was noted so after 12 dogs the dose was increased to 4.5 mg/kg PO q12h. 

Key Points

• ALP and ALT were elevated in this study. This is the first study to document elevated ALT during CBD administration in dogs. The researchers aren't sure why this happened but hepatocellular damage of some sort was suspected. Bile acids were normal in all dogs except 2.

• No significant difference in response (response = a > 50% reduction in seizures) was noted between the placebo and CBD administrations group.

• Total number of seizures/month and seizure days/month was reduced in the CBD group compared to the placebo group BUT over all seizures went UP with both groups

Should we use CBD to manage seizures for resistant epilepsy?

Sorry, not based on this study. It's not compelling enough to suggest that we should be using this drug PLUS it showed evidence of liver enzyme changes that could be concerning AND phenobarbital serum concentration went by 11% when the dogs were on CBD. That said, they targeted resistant epileptic dogs so could this be effective in "easier" to control dogs? Maybe. Could this increased phenobarbital concentration mean that we could lower the dose of phenobarbital in these pets? Maybe. Do we need to check out different doses? Maybe - but at least with this question I am cautious because of the new elevation of ALT at this higher dose. Can we safely increase the CBD dose? Unknown. 

This is a good step forward but alas, we still don't have enough compelling evidence to say CBD should be a part of seizure therapy and at what dose.

Keep up the good work managing epileptic dogs! I'm available if you have questions about a case or need a second opinion. Have a great week!

What is Temporal Lobe Epilepsy?

Temporal lobe epilepsy (TLE) is a newly emerging term in feline seizure discussions and one worth becoming acquainted with. TLE is not an etiology, but rather a specific seizure phenotype (appearance) caused by epileptic seizures in a specific part of the brain (hippocampus) resulting from multitudes of causes.

What does TLE look like?

Cats with TLE have 6 specific stages or appearances. Not all cats go through all 6 stages, nor are all 6 stages apparent. The stages are:

Stage 1: looking around, sniffing, attention

Stage 2: Immobility and staring (arrest)

Stage 3:Orofacial automatism (lip smacking, facial twitching, swallowing, blinking) hypersalivation, mydraisis

Stage 4: Masticatory movement, facial twitching

Stage 5: Head turning, head nodding

Stage 6: Generalized convulsive tonic-clonic seizure

Most cats are observed in stage 2 or 3, and may progress to stage 4 and 5 but stage 6 is rarely observed.

What causes TLE?

Because TLE is not an etiology, but a description of a seizure syndrome located in one part of the brain, any cause of non-TLE seizures can cause TLE seizures as well. This list could include vascular causes, neoplasia, meningoencephalitis (infectious or non-infectious), or idiopathic.

How is TLE diagnosed?

When orofacial automatisms are observed, TLE should be suspected. To confirm TLE, an MRI with changes in the hippocampus is needed. There may be evidence of the seizure etiology such as neoplasia, or vascular disease as well, but the hippocampus must show specific MRI changes. Histopathology can reveal hippocampal sclerosis or necrosis. Some authors think sclerosis precedes necrosis but this sequence isn’t fully established. I won’t bore you with the detailed differences between sclerosis and necrosis, especially since the difference is detected on necropsy.

Can we treat TLE?

Yes! Treat seizures with antiepileptic drugs (AED) as you would any feline or canine seizure disorder. Any 1 seizure more than every 3 months, or longer than 3 minutes warrants a discussion of starting AEDs. Recently, hippocampectomy (removal of part of the hippocampus) has bene published in a cat as a treatment for TLE. This is a well-established treatment for human TLE (a common form of AED-resistant epilepsy in humans) and it carries an extremely high success rate for seizure elimination. Unfortunately, the procedure in cats needs a bit more work before we start considering it standard treatment. The hippocampus is the memory storehouse therefore loss of the hippocampus can cause difficulty with motivation, spatial memory, and learned behavior. Some researchers have described the effect to be similar to feline cognitive disorder in geriatric cats. Hippocampectomy was extensively performed in the 1960s during the time of rapid, although sometimes perhaps unethical, knowledge acquisition of how the brain works in animals and humans. We must acknowledge this work, even if we might find it ethically repulsive today.

Key Points

·         Temporal lobe epilepsy is a syndrome, resulting in damage to the hippocampus and a classic seizure presentation.

·         Temporal lobe epilepsy can be treated, but may be progressive and unresponsive to treatment once the necrosis stage has been reached. How do we know we reached this stage? No one knows antemortem….stay tuned!

·         Cats should take phenobarbital or levetiracetam. These are currently (2023) the only two drugs with enough literature to support their use and predict a reasonable efficacy. (Sorry my zonisamide-using friends.)

Intervertebral Disc Herniation in Yorkshire Terriers

Yorkies are a popular, and common dog breed in the USA and I (we?) see them quite a bit in neurology referral practice. That said, I had never read that they were officially considered a chondrodystrophic breed. Apparently, they are! 

Intervertebral disc herniation (IVDH) occurs with high frequency in chondrodystrophic dogs, but how often do we see it in Yorkies? According to a recent article, about 10% of Yorkshire Terriers with neurologic disease are diagnosed with IVDH and undergo surgical intervention. 

How do Yorkies present with IVDH?

• Cervical hyperesthesia only 5/60 (8.3%)

• Ambulatory tetraparesis with or without neck pain (grade 2):  26/60 (43.3%)

• Non-ambulatory tetraparesis or plegia with or without neck pain: 29/60 (48.4%)

No association with recovery and presence or absence of ambulation was found in this study. This is inline with other studies that have not found voluntary motor to be a prognostic indicator. 

• Acute signs in 80% of dogs

• Chronic signs in the remaining 20%

Yorkies with IVDH instead of another neurologic disease were statistically heavier and older

How do Yorkies do with surgery?

Thankfully, quite well, according to this report. In this study, the majority (82%) had one IVDH, 15% had two and 3% had 3 IVDH site repaired. In my experience, Yorkies far exceed dachshunds for having multiple IVDH requiring surgery at the time of diagnosis. Could this be a difference in genetic pool (this study was conduced in Czechia, Slovakia and Hong Kong)? In this study, all dogs returned to ambulation at some point, post operative. Most were walking by hospital discharge, but not all. This is comparable to dachshunds. 

Key Points

• Yorkshire Terriers are chondrodystrophic and therefore predisposed to type I IVDH

• Surgical intervention is likely to improve ambulation

• Approximately 50% of Yorkies will be ambulatory, and 50% will not at the initial diagnosis. 

Thanks for reading! I am leaving for ACVIM today (Tuesday June 13th) and will be out for the remainder of the week. I'm so excited to collaborate with colleagues and bring new knowledge back to the patients we share! If you need me, email is preferred but texting is also fine. I will have limited ability to answer the phone but will do my best to return your call in a timely manner. Please excuse any unusual delays! Have a great week!
 

Immune-mediated Polyneuropathy in cats

Riddle me this: a 10 month old cat is brought into your exam room by a very concerned owner. They report that the cat has had a rapid, progressive weakness develop over the past 2 weeks. Being the astute veterinarian that you are, you notice that the cat takes 3-4 steps and then sits. There doesn't appear to be any ataxia...just paresis (weakness). 

Neurologic examination:
Mentation: BAR
Cranial nerves: all normal (about 11% of cats will have facial nerve paralysis with this disease)
Gait: Ambulatory tetraparesis, worse in the pelvic limbs
Reflexes: reduced withdrawal all limbs, absent patellar reflexes bilaterally. 
Postural reactions: reduced to absent tactile placing in both pelvic limbs, reduced tactile placing in both thoracic limbs. 
Palpation: non-painful

The remainder of the physical examination is unremarkable.

What is the neuroanatomic lesion localization?

Start at the very beginning. Are there any signs of seizures, mentation changes or cranial nerve deficits? No. Therefore this cannot be intracranial lesion localization. We have all four limbs affected therefore if this is a spinal neuroanatomic lesion localization it must be cranial to the front legs. This means C1-C5 or C6-T2 myelopathy. (If the lesion was T3-L3 or L4-S3, the thoracic limbs should be normal.) To narrow it down between C1-C5 or C6-T2, we look at reflexes. Reflexes are reduced in the thoracic limbs therefore this would suggest a C6-T2 myelopathy. BUT WAIT!! The reflexes in the pelvic limb are also reduced to absent and that cannot happen with a C6-T2 spinal cord lesion. The reflexes in the pelvic limbs should be normal with a C6-T2 spinal cord lesion. Is this a multifocal lesion, affecting two spinal cord segements (C6-T2 and L4-S3)? Although possible, you would expect a proprioceptive ataxia with a spinal cord lesion therefore this is very unlikely to be a spinal cord lesion at all, even a multifocal spinal cord lesion. There, we must assume this is not spinal cord or intracranial lesion. What does that leave us? Neuromuscular disease, that's right! Your options are: 1) peripheral nerve, 2) neuromuscular junction or 3) muscle. Animals with muscle disease should have normal reflexes (and do, except with myasthenia gravis), so it isn't that. This is either a neuromuscular or peripheral neuropathy localization. 

Our differential diagnosis would include diseases such as: toxoplasma or fungal neuropathy, myasthenia gravis (yes, I know this localizes to the muscle but clinical signs look like a junctionopathy at times!), and immune mediated neuropathy. 

Diagnostic testing for this patient

CBC, serum biochemistry (including CK!) is normal. Toxoplasma testing was negative, as is the myasthenia gravis titer. Occasionally we will see an elevated CSF WBC or protein count with this mystery disease, but it isn't common. 

Muscle and nerve biopsy results

Diffuse variability in muscle fiber size is expected on biopsy. Nerves are almost all missing from the muscle biopsy sections. The nerve biopsy is markedly abnormal, with inflammatory cells infiltrating the axon, nodes of Ranvier and Schwann cells. 

Diagnosis: Immune mediated polyneuropathy!

This is a very interesting disease for many reasons but most notably, most cats can achieve a complete recovery without any treatment at all. In a recent study (see below), 10/11 cats that received no treatment obtained full recovery with a median time of 4 weeks. Nine of 12 cats that received glucocorticoids and 18/20 cats that received L-carnitine supplementation recovered as well. Relapses are reported and can occur months or years after resolution of signs. Overall, all except 1 cat improved regardless of treatment in this study. This same study found a predominance in males but did not find a breed association. 

So there you go! A self resolving, relapsing remitting polyneuropathy of young cats. 

Article: DOI: 10.1111/jvim.16701

I hope you have a great week and look forward to working with you soon!

Long-term infection and monitoring of Brucella suis in dogs

B.suis, you say? Why do I need t know about a swine variant of Brucella?? Did you know that B. suis can be pathologic in dogs, as well as swine, and is also zoonotic? You're welcome :)

A recently published article detailed the clinical signs, blood work, imaging (when available), serologic progression over time, and body fluid levels of organism over an 18 month period in 27 dogs from 17 households. The study population was located in Australia where naturally occurring B. canis is not found. Exposure to feral pigs was considered an important source of disease acquisition and may be a stand alone reason to test. (1 in 10 pigs are positive in Australia.) Although B. suis is not as commonly noted in our US canine population, we are a global veterinary profession now with lots of dogs traveling or being adopted from international locations. I felt this article was a nice reminder that B. suis exists, and is pathologic in dogs as well as having zoonotic potential, like B. canis. 

Clinical Signs of B. suis

Ten dogs had clinical signs attributed to brucellosis. Clinical signs included pyrexia with orchitis and epididymitits (4/10), lymphadenopathy (1/10), spinal pain (3/10), abortion or dystocia ( 1/10), and athritis (2/10). The remaining 17 dogs were assymptomatic throughout the entire 18 month period!

Serology and PCR

Titers did not correlate with severity of signs. Postive results were deemed positive if a Rose Bengal rapid plate test (RBRPT) yielded a positive result along with a complement fixation test (CFT) greater than or equal to 8. Only 2 dogs had seronegative results after 18 months and both had low baseline serology. Brucella DNA was not detected by PCR in blood, urine, saliva or preputial swabs in any dog at any time in the study. Notably, they weren't swabbed weekly or daily, so it is possible that some shedding occurred without detection on the sporadic testing. Only 3 positive PCR tests were found and this occurred in 1 bitch post whelping (vaginal fluid), as well as milk at 3 and 7 weeks post whelping as well as a lymph node at necropsy on a puppy that died. Although culture may be the gold standard diagnostic test for some countries, the RBRPT and CFT were considered safter to personnel performing the test and were preferred in this study. 

Diagnostic Imaging Results

Fifteen dogs had some sort of radiograph taken during the study period. Two of 15 had joint siease, 3/15 had vertebral lesions and 2 of 15 had lymphadenopathy. The dogs with radiographic changes had spondylosis, which we know can be a normal finding, therefore I question the inclusion of this as a clinical sign of brucellosis. 

Treatment Response

Six dogs were treated with doxycycline and rifampicin (one dog relapsed and was treated twice. It was generally well tolerated with one case of marked hepatitis. There is no standardized treatment for brucella and many dogs are considered to harbor the bacteria long-term, with or without clinical signs, with intermittent bacteremia. The zoonotic risk to humans, therefore remains present with dogs with a current or historic positive Brucella test. Euthanasia is the recommended treatment for positive livestock, however this causes emotional conflict for veterinarians and owners of companion animals. Check with your local veterinary health directors to determine the legal requirements in your state or country. This is a reportable disease in the USA. 

If you'd like to read more about this study you can find it here: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16678

In honor of Memorial Day yesterday, I wish to thank all of you that have served or have friends or family members that have been lost during military service. We honor you!

Have a wonderful week! My schedule has changed for summer so please reach out if you cannot find a suitable time for a consult online - I may have additional flexibility that isn't listed. 

Seizures, Quality of Life and Side Effects, oh my!

A study published in JAVMA (Gristina BR et al. JAVMA 2023)  just recently caught my eye and I thought, perhaps it might interest you as well. The study evaluated 100 dogs with , with Tier I or Tier II level confidence of idiopathic epilepsy and assessed owner satisfaction, seizure control and adverse effects (the fancy name for side effects) of various drugs. 
*Tier I = normal CBC, serum biochemistry, neurologic examination and bile acid test
* Tier II = all of tier I plus normal brain MRI and CSF analysis

How was the Seizure Control?

Improvement in seizure control was reported in 86% of dogs with phenobarbital, 76% in the levetiracetam and 65% in the zonisamide group. Treatment failure, due to inadequate seizure control, was 48% for phenobarbital, 32% for  levetiracetam and 35% for zonisamide. Importantly, they didn't corelate seizure control with serum drug concentrations because we don't have target serum concentrations for levetiracetam and zonisamide. HTerefore, some dogs could have been under medicated, and thus poorly controlled. Interestingly, 88% of dogs were still on their original antiepileptic drug (AED) at the time this study was performed. Mean daily doses for phenobarbital, levetiracetam and zonisamide were 4.9  mg/kg, 53.8 mg/kg and 12.4 mg/kg, respectively. 

What side effects made a splash?

Phenobarbital had the highest reported adverse effects at 77%, followed by levetiracetam at 59% and zonisamide at 39% of dogs. The most common adverse effects are listed below for each drug:

• Phenobarbital: polyphagia, polydipsia, ataxia, sedation and polyuria

• Zonisamide: sedation, ataxia, hyporexia

• Levetiracetam: Sedation, ataxia, hyporexia, diarrhea, behavioral changes.

What was the perceived Quality if Life?

Owners perceived a significant improvement in quality of life, regardless of the anticonvulsant used, between pre and post treatment assessment. This is important for us to realize: clients can tolerate adverse effects if they perceive improved seizure control and quality of life! Although this retrospective, owner-perception study has limitations (all studies do), I felt it was worth repeating a bit of the information for you to add to your knowledge when addressing seizure management with your clients. 

Have a wonderful week! Remember, early bird registration ends May 31st for the July CE event so register soon if you are planning to do so! Details are available on my website. 

Reference: doi.org/10.2460/javma.22.10.0469

How to Question an Owner

Careful questioning of the owner is required to determine if the episodes described ARE seizures. Syncope, vestibular signs, neck pain, and movement disorders (think Scottie cramp) have episodic presentations with similarities to seizures. Nothing is fool proof, even an EEG, but here are some tips to get you going in the right direction. 

Describe the event, please!

Discrete episodes, with a finite start and stop, combined with autonomic signs often indicate a seizure. Level of mentation can be confusing and difficult to determine (especially for those pesky night time seizures) so don't spend too much time grilling an owner on this one. Videos can be priceless. I have evaluated many dogs and cats for seizures that actually have something else after reviewing the video. Neck pain, movement disorders, and syncope are the most common pretenders that I've seen. Finally, ask how long the events are lasting. This question is subject to tremendous bias, but if the owner says "all day" I start wondering about other non-seizure events. 

How often have the events occurred?

Okay sorry, I need to harp on this one. My pet peeve is hearing "about once a month" as an answer! This is an easy one and something we should encourage ALL clients with seizure pets to do. Keep a calendar! Tell owners to write it down, put it in a spreadsheet, mark it on their phone, keep a list - the choices are as varied as the seizures they record! You will NEED this to be in place to help you direct treatment. The single biggest reason to change treatment is that the seizures do not meet the seizure goals for epileptic pets. What are the seizure goals? Animals should have 1 seizure or less every 3 months. 

Your second goal here is to learn about cluster seizures. If the animal has 2 or more seizures in 24 hours that is defined as cluster seizures. Cluster seizures need at home cluster seizure management (another topic for another day). Furthermore, some drugs work better for dogs with cluster seizures than those with single seizures. I personally believe that bromide is a terrific option for cluster seizures and will readily use it for patients with this type of pattern. 

How long is each seizure? 

This question is utilized to learn about status epilepticus. Any seizure longer than 3-5 minutes (people argue about what is the correct time) is considered status. Status warrants emergency management with injectable solutions (intranasal, intravenous, other). Untreated status can set an animal up for systemic side effects as well as increase the risk of permanent brain damage. 

What does the animal do after the event is finished?

Your goal here is to evaluate the post ictal phase so that you can decide if a change in treatment is needed. Based on the rules outlined by the International Veterinary Epilepsy Task Force, severe post ictal changes (such as aggression) warrant treatment even if the other parameters for treatment haven't been met. I also use this question to determine how the owner is feeling about the event. Answers such as "he was fine" or "he paced and paced and seemed really upset" give me a window into how they feel about as much as how the dog did. Helping owners cope with seizures is also part of our job!

Do you have a seizure case that isn't meeting your seizure goals? Let me know! My favorite part of neurology is long-term seizure management so I'd love to help you, help your patients!

I'm headed to Chicago Vet Conference on Friday for a few talks on seizures, the neuro exam and lesion localization. I'd love to see you if you're at the conference so stop by and say "hi" if you have time!

Pituitary Apoplexy in Dogs

Pituitary Apoplexy in Dogs

What is Pituitary Apoplexy and What Does It Look Like?
Pituitary apoplexy is a clinical diagnosis caused by acute hemorrhage or infarction of the pituitary gland. The hemorrhage occurs secondary to neoplasia (benign or malignant). The hemorrhage is thought to occur because the tumor grew faster than the blood flow, or because of compression of the very sensitive blood vessels in the area of the pituitary gland.  Apoplexy isn’t common with pituitary neoplasia, and rarely fatal, but remains an important possibility for patients with pituitary gland neoplasia. Clinical signs described on presentation for dogs with pituitary apoplexy include acute onset mentation changes (obtunded, stupor, coma:62%), cranial nerve deficits (65%), gastrointestinal signs such as vomiting or nausea (54%), gait changes such as circling, weakness/paresis, ataxia (85%), and hyperthermia (31%). Other signs such as bradycardia, and cervical hyperpathia were noted but less commonly. The GI signs are critical, and unique, and shouldn’t be ignored. They could be due to vestibular signs (present in about 15% of dogs), but also could indicate a rapid rise in intracranial pressure.
Do all Dogs with Pituitary Apoplexy have Endocrinopathy?
No! According to a recent study by Woelfel et al, only 50% of dogs with pituitary apoplexy diagnosed on either post mortem exam or presumptively diagnosed on MRI had an endocrinopathy. A further 12% had signs suggestive of an endocrinopathy but did not undergo workup. This means that 38% of dogs did not have clinical or biochemical evidence of an endocrinopathy. The endocrinopathies could be the obvious one (Cushing’s disease), or the less obvious (central diabetes insipidus, hypothyroidism).
Treatment and Survival
Dogs receiving radiation therapy survived longer than those medically managed. There is probably a bit of bias, however, because the severity of clinical signs likely steered clients or veterinarians towards or away from treatment. The use of hyperosmolar solutions (mannitol, hypertonic saline) was associated with a poorer survival. Again, this may be due to the severity of signs of those patients receiving this treatment rather than the treatment itself. No clinically useful markers were identified to predict survival in this study but that doesn’t mean they don’t exist; just stay tuned!
Take home message: Acute onset mentation changes with vomiting? Get those dogs to a neurologist (or get a consult!!) as soon as you can.

I hope you have a wonderful week! I look forward to seeing you soon!
 

Reference: https://doi.org/10.1111/jvim.16703

Trace Minerals and Canine Epilepsy

Trace elements are the micronutrients found throughout live animals that are essential for organ function and brain health. They keep mitochondria running smoothly, improve neurotransmission and aid with enzyme function. Deficiency or excess has been linked to multiple neurologic diseases including neurodegenerative diseases, behavior diseases and inflammation in humans and animal species. A recent study evaluated the levels of several trace elements in hair samples of dogs with epilepsy and compared them to dogs without seizures.
 

What Trace Elements were Abnormal?

In this study, by Rosendahl et al, there were 10 epileptic dogs without any treatment, 53 epileptic dogs currently undergoing treatment for epilepsy, and 42 control dogs (no seizure history).

• Phosphorus: lower in epileptic dogs

• Copper: Higher in epileptic dogs

• Zinc: higher in epileptic dogs

• Copper/zinc ratio: higher in epileptic dogs. Specifically, higher in dogs treated with phenobarbital, in one previous study. Studies have shown that copper homeostasis is an important preventative for some neurodegenerative diseases. More work needs to be done in veterinary species to determine if this holds true for our patients, too.

• Selenium: higher in epileptic dogs

• Arsenic: higher in epileptic dogs but also much higher in dogs receiving potassium bromide!

Some of these findings were significant, some were significant only when comparing control dogs with either treated, or untreated dogs, and others were significant for both subgroups of epileptic dogs.

This study is likely to be a stepping stone for either this group, or others, studying trace minerals and their relationship to seizures. It was important work to identify differences, but the clinical significance remains unknown. Treatment, or correction of these deficits or elevations of trace minerals has not been evaluated in epileptic dogs. Stay tuned!
 

Thanks for reading! I hope you have a great week and enjoy what I hope is our final push out of winter, into spring, weather.

 
Reference: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16698?campaign=wolearlyview

Neurologic signs of Hypertension in Cats

Hypertension is common in cats. It can be associated with a predisposing disease such as chronic kidney disease or hyperthyroidism, or idiopathic. Idiopathic hypertension is diagnosed when all predisposing causes have been eliminated (and hypertension is documented on 2 separate occasions)  and accounts for less than 1/2 of the cats diagnosed with hypertension (about 40%). 

Target organs for hypertension are the CNS, kidneys and cardiovascular system. Despite under recognition by clients, several studies have suggested that hypertensive encephalopathy might be present in 30-40% of cats. 

Neurologic manifestations of hypertension in cats

Seizures, mentation changes, vestibular signs (central), behavioral changes (disorientation), tremors, sudden collapse, cervical ventroflexion, paraparesis, cerebellar ataxia with hypermetria, cranial nerve deficits and cortical blindness (not retinal blindness). That's quite a list, isn't it?? It's amazing that these signs are the reason for presentation to a vet in only 10-20% of cats! 

A small study was recently published in the Journal of Feline Medicine and Surgery that aimed to identify the clinical occurrence of hypertensive encephalopathy in cats. In this study, 31 of 56 cats were diagnosed with neurologic signs associated with hypertension. Retinal lesion were identified in 28 of the 30 cats that under went fundoscopy. 

Cats with neurologic signs presented most often with proprioceptive ataxia, some with vestibular ataxia. Additional signs included hiding, disorientation, sleeping in unusual locations, increased and inappropriate vocalization, and increased appetite. Three of the 31 cats had seizures. Neuroanatomic lesion localization was predominantly prosencephalon, second most commonly vestibular signs and lastly spinal cord signs. Many cats had multifocal neurologic signs. 

Treatment and Outcome

Amlodipine was used in 22/31 cats. Telmisartan was used in 4/31 cats. The remaining cats received combination therapy. Follow-up was available for 25 of 31 cats. Fifteen cats had complete recovery after starting antihypertensive medications including one cat with severe seizures. Partial improvement was noted in 8/25 cats with residual ataxia or seizures manifesting most commonly. No initial response to treatment was noted in 2 cats with subsequent euthanasia within 1 week of treatment initiation. 

Key points:

• Feline hypertension is common (they enrolled 56 cats in less than 2 years!)

• Neurologic and behavioral signs occurred in more than 1/2 of the cats in this study but clients weren't aware of the significance!

• Treatment with antihypertensive medication can result in improvement

• Routine monitoring for hypertension is recommended in at risk cats, especially those with neurologic signs!

Reference: https://doi.org/10.1177/1098612X231153357

Thanks for reading! Have a terrific week; I look forward to working with you soon. Remember to sign up for the July CE if you are planning on attending because space is limited!

Unilateral Masticatory Muscle Atrophy

It's a Wednesday morning and you see on your schedule a 7 year old dog with unilateral temporalis and/or masseter muscle atrophy. What parts of the neurologic system could be involved?

1. Muscle: A problem with muscle function, termed a myopathy, can result in muscle atrophy. The most common cause of temporalis and masseter muscle atrophy in dogs is masticatory muscle myositis (MMM), which is caused from an immune mediated attack against the muscle fiber. This is a UNIQUE form of muscle inflammation because the proteins on these muscles are embryologically unique (2M fiber type) from all other muscles in the body. We care about that because it means that we can identify an antibody (AB) test that we can run that is highly specific AND sensitive! What else should we consider? Infectious myositis, secondary to neospora or toxoplasma infection would be my second choice differential for many dogs with this clinical presentation. In this scenario, the protozoa get into the muscle, set up a secondary inflammation (myositis) and muscle atrophy results. Sometimes you can see a mild positive on the aforementioned MMM AB titer test, but it is low, if positive at all. However, if you concurrently test for neospora and toxoplasma (serum titers) you can catch this "false" positive, and treat the correct disease.

Treatment for MMM: Immunosuppressive steroids for 30+ days, followed by a taper protocol.
Treatment for infectious myositis: clindamycin or sulfa antibiotics until negative or stable titers. This is often MONTHS of treatment!

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

Treatment for CN 5 deficits: this varies and is dependent on the underlying cause. It is a bit hard to summarize TidBit Tuesday-style. :) 

These cases can be puzzling to sort out so please reach out if you feel a neurologic examination is helpful for your patient. Have a great week!

Cervical Disc Herniation Associated Myoclonus in Dogs

Intervertebral disc herniation (IVDH) is the most common cause of cervical pain in small breed dogs. The most common clinical presentation is cervical pain with a normal neurologic examination, however in a few dogs gait deficits, paw replacement deficits, or reflex deficits can seen. Myoclonus, or a sudden onset, repetitive muscle contraction is seen in about 4% of dogs in a recent study from France. This muscle contraction is frequently confused for seizure behavior by clients so be on the look out for it! The classic presentation is a small breed dog that stops an activity, demonstrates myoclonus, and then resumes it's activity. Other signs of cervical pain (yelping, low head carriage, reduced range of motion) are often present when clients are questioned, so be sure to ask! 

What is the Significance of Cervical Myoclonus with IVDH?

The presence of myoclonus did not change the prognosis or outcome for the 20 patients in the recent study (JAVMA 2023: 261:4: 511-516.). Surgical correction resulted in less recurrence of signs, and immediate resolution in the post operative period compared to medical management. Approximately 25% of of medically treated dogs experienced another episode of myoclonus considered to be distinct from the original presentation. Medical management consisted of NSAIDs, gabapentin and, for some, tramadol. 

What is the Take Away?

• Myoclonus can occur with mechanical or chemical irritation of cervical nerve roots 

• Myoclonus does not affect prognosis

• Surgical management remains the recommended treatment for rapid resolution of signs of pain and reduction in relapse/recurrance

• French Bulldogs were over represented in this study!! (Again - See TidBit Tuesday in March for the list of Frenchie spinal cord diseases

As always, thank you for reading! I am thrilled to see the lovely weather on the horizon this week and hope you have a chance to enjoy some of it, too.