Myasthenia Gravis in Cats

What is myasthenia gravis?

Myasthenia gravis (MG)  has two forms: 1) congenital and 2) acquired. Acquired myasthenia gravis is more common and results from the development of antibodies against the nicotinic acetylcholine receptors on the muscle membrane. 

What is the clinical presentation?

Cats present commonly with the generalized form which includes a wide variety of clinical signs and progressions. This may include weakness (the "floppy cat"), cervical ventroflexion, or pharyngeal weakness. Signs may be slowly or rapidly progression and even result in waxing-waning clinical signs. 

What causes the acquired form of myasthenia gravis?

Most cats have an idiopathic MG however up to 30-50% of cats will develop paraneoplastic MG for which thymoma are commonly implicated. Spontaneous remission of idiopathic MG within 6-8 months is common in dogs, but was previously thought to be uncommon in cats. A 2019 article found remission within 6 months in ALL 8 cats evaluated. (Mignan T, et al. JVIM Nov 2019) Remission even occurred in several cats that didn't have any form of immunosuppression or acetylcholinesterase inhibitors prescribed (see treatment below). 

How should I diagnose myasthenia gravis?

1. A thorough neurologic exam for appropriate lesion localization (yay!), and
2. An acetylcholine receptor (Ach-R) antibody titer through a reputable lab. Here in the states, I recommend Dr. Shelton's lab (http://vetneuromuscular.ucsd.edu/). This titer can be repeated to document biochemical remission along with the neurologic exam to document clinical remission. 

What is the ideal treatment?

Oh, the million dollar question! Based on experience I'd say cats respond less favorably to acetylcholinesterase inhibitors (think pyridostigmine or edrophonium) and therefore immunosuppressive steroids have been my go-to treatment. Having seen the data on spontaneous remission, I might consider no treatment in a minimally affected cat.

What is the long-term prognosis?

Idiopathic myasthenia gravis carries a good prognosis in cats. Should pharyngeal weakness become a clinical problem, aspiration pneumonia may result in increased morbidity or mortality. The 2019 study by Mignan et al reported a 100% survival at 6 months, without signs of relapse up to 4 years after treatment. Cats with paraneoplastic myasthenia gravis have a poorer short and long-term prognosis. 

Key Points:
1. Cervical ventroflexion, or a "floppy" cat on examination should prompt an Ach-R antibody titer for myasthenia gravis diagnosis. (Maybe even a neurology consult!)
2. Treatment could be immunosuppressive steroids OR no treatment at all if clinically mild
3. Prognosis is good if a thymoma or other neoplastic process is not identified. 

Thanks for reading! Happy 4th of July to US folks reading and Happy July 1st to Canadian folks! The rest of ya - hope you're having a good week!
Also, I'm looking for a location that can hold up to 20 people for a possible CE event in February 2025 in the middle of the state (Portage/Dells/Stevens Point). Do you have a hospital conference room I could rent or do you have a reocmmenation for a conference center that you thought did a good job in that area? Please reach out if you do!

How Effective is Zonisamide in Cats?

Seizures are a common reason for me to evaluate cats and therefore (I assume) something you encounter frequently. Seizures originate from the forebrain (prosencephalon) and can be secondary to idiopathic epilepsy, structural epilepsy (such as congenital disease, neoplasia, meningoencephalitis, cerebrovascular events, head trauma, and on goes the list), or metabolic seizures (hypoglycemia, thiamine deficiency, etc.).

The mainstay treatment for cats has been phenobarbital for many years and not without good reason. Phenobarbital controls seizures in over 90% of cats, regardless of the etiology, and has predictable clinical side effects. When cats cannot tolerate phenobarbital, or have seizures in excess while on phenobarbital, other antiepileptic drugs (AED) are added; one of those is zonisamide. Very little data has been published to date about zonisamide use in cats. A recent study out of UW (go Bucky) was published recently. I thought it was worth a quick summary, TT style.

How many cats were enrolled in this retrospective, multicenter study? 57

The median age of seizure onset was 7 years (range 0.17-22) and the median age of onset for cats diagnosed with idiopathic epilepsy was 8 years. Note the difference between cats and dogs! Dogs have a lower median age at onset! Importantly, note that 30 cats did not have advanced diagnostics (52%) which means a final diagnosis was not reached and therefore their disease may have affected their response to zonisamide (but we don’t know!).
How did the cats on zonisamide respond to treatment?

• There was a significant decrease in seizures/month AND seizures/day after starting zonisamide. Note: we don’t know how long the seizures were monitored before starting zonisamide.

• 70% of cats responded to zonisamide monotherapy (had less than 1 seizure per 3 months)

• 56% of cats responded to zonisamide as add-on therapy

• Almost 70% of cats diagnosed with idiopathic epilepsy responded to zonisamide but it isn’t clear if these cats were on monotherapy or add-on therapy.

• The median dose was 7.5 mg/kg/day with about 1/3 of the cats receiving the drug once daily and 2/3 receiving it twice daily.

• More cats obtained seizure control on twice daily dosing than once daily dosing but the side effects were more profound on twice daily dosing.

• Side effects were noted in 15/57  cats and they included inappetence (10 cats), sedation, ataxia and vomiting for most reports. The duration of the side effects was up to 4 weeks after starting the medication. This is surprising and warrants further investigation. Anorexia has been the side effect I note more commonly but

• No clinically significant CBC or biochemistry changes were noted on the cats in this study

So what’s the take home message? Would I use zonisamide in a cat? A qualified, yes. Phenobarbital still has a better reported seizure control compared to this cohort of cats on zonisamide. BUT it is worth a try if the cat fails treatment with phenobarbital and the don’t have a history of a sulfa drug reaction (zonisamide is a sulfa derivative). Starting dose should be less than 10 mg/kg daily, and side effects appear dose dependent…but last awhile!

Thanks for reading this week’s, TidBit Tuesday! I hope you learned a little something – I know I did! Keep those consults rolling. Have a great week and stay warm and safe out there.
 
 Reference: https://doi.org/10.1111/jvim.16984

Status Epilepticus in Cats

Last week we looked at the ACVIM consensus statement for the treatment of status epilepticus and focused on the different stages, and the treatment algorithm outlined by the committee. This week, I thought we should look at this statement through the lens of cat care. Please refer to the article for more details - it's a good one! (DOI 10.111/jvim.16928)
As a reminder, all available literature was reviewed and classified according to it's level of evidence. Studies with a high level of confidence for or against a specific treatment included treatments in which 2 or more clinical studies with a high quality score (more about that in a minute) evaluated this specific intervention. Moderate level of evidence for a treatment needed 2 or more studies with moderate quality score or 1 study with high quality score. A label of low evidence for a specific intervention was used in situations where 2 or more studies with low-quality score were reviewed or 1 with a moderate quality score without any high quality score articles identified. A label of conflicting evidence was used when 2 or more studies, usually with a high quality score, were reviewed and found to have results in conflict. Finally, the label "absence of evidence" is pretty self explanatory. The quality scores were numeric scores assigned each study based on clearly defined criteria such as EEG or clinical confirmation of seizure cessation for each study reviewed. 

Definitions
The definitions are the same for cats as they are for dogs. Any seizure longer than 5 minutes is considered status epilepticus (SE). Similarly, cluster seizures are 2 or more seizures within 24 hours in which consciousness is regained between the seizures. Okay, off to a good start. 

Antiseizure Therapy for Cats
Figure 3, in the aforementioned article, is a pyramid of hierarchy for therapy recommendations for cats in status epilepticus. Sadly, there are no studies with a high level of confidence for any intervention. This means that no high quality studies, evaluating seizure cessation in cats, were identified. We need to fix this! Intravenous bolus or CRI of midazolam, intravenous bolus of diazepam, intravenous levetiracetam, intravenous phenobarbital and inhalant anesthetics were considered to have moderate level of confidence for cats. This suggests that there is at least clinical evidence (if not EEG evidence) that supports these treatments for SE management in cats. Oral levetiracetam, intravenous bolus or CRI of phenobarbital and propofol had low level of evidence suggesting that giving these drugs, via these routes, to cats with seizures is not supported by the literature. Oral midazolam, intravenous CRI, oral or endotracheal diazepam were not supported by the literature. Not surprisingly, there were many drugs that were withheld from analysis due to a lack of evidence for cats. 

As I mentioned last week, the authors made the following statement:
"Although both benzodiazepine drugs are potent and safe for the management of SE in dogs and cats, midazolam may be considered a more potent or safer benzodiazepine drug than diazepam."
Based on this, and my own clinical impression, if you aren't carrying injectable midazolam yet, now is a good time to consider adding this to your cabinet!

The authors also specifically addressed CRI reduction and recommended reducing by 25-50% every 4-6 hours after a cat (or dog) has been seizure free for at least 12 hours, preferred 24 hours. It is always preferred to taper the medication, not stop abruptly, whenever feasible. 


I think that is enough for today. I hope you had a good holiday, didn't go too crazy on Black Friday, and I look forward to working with you soon!

As always, the holidays bring many challenges. If you cannot find a suitable time for a consult using my online scheduler please reach out to me via email. I will always try to accommodate your request if I can. 

Levetiracetam use in Cats

We all know cats are not small dogs, so how does levetiracetam (leh-vuh-tr-A-suh-tam) differ between species?

Metabolism
The mechanism of action (modification of the SV2A receptor) is the same for cats and dogs. This mechanism of action (MOA) is unique to levetiracetam and different that the MOA for phenobarbital. 

Formulations
There are two formulations available 1) standard release (SRL) and 2) extended release (XRL). The dosage of 20 mg/kg PO q8h for the SRL formulation, comes from pharmacokinetic analysis of this drug in a cohort of healthy cats. A therapeutic range has not yet been developed for cats therefore if seizure control is poor, the dosage is often increased until signs of toxicity are noted and then reduced to the highest effective dose with minimal side effects. When doing that, the prescriber is using the individual animal as a guide for toxicity rather than an established therapeutic range. Reported side effects include hypersalivation (mild, transient), inappetence and mild lethargy. There are very few efficacy studies for cats, however in 2008, a single study reported a greater than 50% reduction in seizures  in 7 of 10 cats when levetiracetam was added to phenobarbital. Liquid formulations are readily available through compounding pharmacies and can be used interchangeably with the 250 mg size tablets. Use caution when prescribing the liquid formulation to ensure it does not have xylitol as an added ingredient. 

Extended release levetiracetam is available in 500 mg and 750 mg size tablets. Historically, this has limited its use in cats. In 2017, I decided it was high time we changed that thinking so we evaluated the pharmacokinetics of a single dose of 500 mg XRL in healthy cats and found that it was well tolerated with minimal side effects. Furthermore, we identified that a reduce dosing interval from q8hr (SRL) to q24h when using XRL was appropriate for cats! The serum levetiracetam concentrations were really high therefore we subsequently evaluated the use of levetiracetam over 10 days to monitor for drug accumulation. Thankfully, none was identified! No efficacy studies have been performed using 500 mg PO XRL q24h in cats, to date, however I do recommend this dosage for cats, when levetiracetam is needed and q8h dosing isn't an option.

The story doesn't end there! Medicating cats is such a terrible thing to do to a cat (and horrifying for some owners) that I then explored the idea of transdermal levetiracetam (TD).The dosage of 20 mg/kg transdermal q8h resulted in serum concentrations similar to those of the oral route with minimal side effects. We have not evaluated TD levetiracetam long-term so efficacy remains unknown. Do I use TD levetiracetam? Yes. I ensure that the clients know that this is cutting edge research and therefore long-term efficacy studies have not been performed; purely that it is well tolerated. 

That's all for now! Please reach out with any suggested topics and stay tuned for a super fun neurology CE event coming this summer. Shhhh...it's still in the planning stages! 

Have a great week!

Intervertebral Disc Herniation in Cats

Intervertebral disc herniation (IVDH) does occur in cats but is reported at a much lower prevalence than dogs. Is this because the disease is less prevalent or because owners are less likely to pursue advanced diagnostic imaging to obtain a diagnosis? I don't know the answer, however a recently published article reported on 35 cases of feline TL IVDH over 21 years. That sounds like a lot fewer cases than we see for dogs!

Clinical Presentation

Like dogs, the most common presenting complaint is difficulty walking and/or pain. In this study, They found 2 cats had grade I, 20 cats were grade II, 7 cats were grade III, 3 cats were grade IV and 3 cats were grade V on presentation. (Grading scale listed at the bottom). There was no significant difference between outcome at discharge or follow up and initial presenting grade. Does that mean that we shouldn't rush to get cat's seen, imaged, and cut? Probably not. Of the 3 grade V cats (the ones that we would consider a surgical emergency), one improved, one was static and the other was lost to follow-up. What was the timeline for surgery? Unknown. Dogs have a 50% chance of improvement if they are grade V and undergo surgery within 24 hours. This is debated amongst neurosurgeons but as a general rule I subscribe to the plan of cut ASAP whenever possible if deep pain is absent.

Location of the Offending Disc

In the referenced study, thoracolumbar disc herniation was most common at L6-7. This is slightly different from the previous reports in which L7-S1 was reported to be most common, but not far off. I think it is safe to say that cats are more likely to have low lumbar disc herniation than T11-L2 disc herniation, like dogs. Why? Cats are SO MUCH more flexible than most dogs (especially the chondrodystrophic type) that the vertebral dynamics are different as well. Previous reports suggest obesity is more common in cats with IVDH (and in my experience, too) but this cannot be the entire answer. It remains to be seen, why cats are more likely to have a low lumbar disc herniation than TL. When someone knows...I'll tell you!

Key Points:

• Intervertebral disc herniation does occur in cats

• The most common presenting sign is weakness or lumbar pain

• Surgery can be done and SHOULD be done (when appropriate for the patient)

If you have a cat patient with lumbar or lumbosacral pain, reach out. I'd love to see them! Schedule a consult using my online scheduler (for veterinary use only) and let's get your patients feeling better, soon!

Grading scale:
Grade I: normal gait with hyperpathia
Grade II: ambulatory paraparesis
Grade III: non-ambulatory paraparesis
Grade IV: paraplegia with intact nociception
Grade V: paraplegia with absent nociception

Reference: https://journals.sagepub.com/doi/pdf/10.1177/1098612X211028031

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