Seizures are GOOD thing??

Brain tumors in adult dogs are relatively common. There are two primary brain tumor types in dogs: meningioma and glioma. Glial cell tumors are further divided into 3 subtypes varying from less aggressive to more aggressive in growth with rare metastasis. These tumors typically have a shorter long-term survival compared to meningiomas and are less surgically accessible. According to a recent study, dogs receiving palliative treatment have a median survival of about 1 month, compared to dogs receiving definitive treatment. Median survival for definitive treatment was almost 3 months.

This study looked at long-term survival using the new WHO classification scheme and found several interesting findings. The one that is most clinically applicable, and interesting to our pet population, is this:

Dogs with seizures as their first sign had a longer survival, regardless of histopathologic grade, than those with other neurologic signs at onset.

What does this mean? It means that, like in humans, seizures are like a warning shot, letting the rest of us know that something isn't right in the brain and we'd better take a look! If we proceed to MRI and make that diagnosis, dogs survive longer because of early onset palliative OR definitive therapy. This is yet another reason why we really should encourage clients to pursue a definitive diagnosis (i.e. brain MRI, spinal tap) even if they wouldn't consider definitive therapy such as surgery or radiation therapy. Early, aggressive, palliative medical care may actually prolong their dog's life beyond what we might get if we waited to "see what progressed".

I hope you have a good week and look forward to working with you, and your team, soon!

The full results of this study can be found at: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16199?campaign=wolearlyview

Hepatic Encephalopathy - UPDATE

Hepatic encephalopathy is caused by changes in hepatic metabolism that result in neuronal damage or swelling. Clinical signs can include neurological, gastrointestinal or urinary due to the abnormal metabolites or the formation of stones. As a neurologist, I see these patients when they have seizures, changes in mentation or behavior, or other neurological signs.

The preferred treatment is surgical correction with slow closing of the offending vessel. As many of us know, this doesn't always correct all clinical signs and some dogs require life-long treatment despite successful surgical closure.
Life-long medical management must provide a high quality protein source, but yet remain a low protein diet to avoid excessive amino acids.

There was an interesting article published recently (https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16135?campaign=woletoc) that outlined the changes in the different types of amino acids present in the body. There are two main types of amino acids that researchers watch: branched chain amino acids (BCAA) and aromatic amino acids (AAA). In normal animals, the ratio of BCAA to AAA is 3.0 to 4.0, whereas it is 1.5 in animals with a portosystemic shunt. The study goals were to evaluate what happened with the amino acids after shunt surgery.

Results

Interestingly, specific BCAA and AAA did not change a lot, nor were they all outside of the reference range to start. However, the ratio of BCAA to AAA did increase (improve) but did not return back to the normal range. Clinical improvement was noted in most of the dogs, however!

What does this mean? It means that functional recovery occurs faster than biochemical recovery and functional recovery may be more "complete". This also (probably) means that we still need to dig into the amino acids a bit more to see if there are specific amino acids to be more or less worried about.

Yes, I know, this was a very academic TidBit this week and I promised they would be clinically applicable...I'm sorry! I do try to keep it clinically relevant but every now and again I must deep dive into research with you. :)

Keep those consults coming! This has been a terrific few weeks, with interesting cases. I love working with you and your staff to help patients.

Thanks for reading and have a great week!

Idiopathic Head Tremor VS Seizures

Idiopathic Head Tremors vs. Focal Seizures

Wow, a lot of you have been seeing head tremors lately and sending them my way! I thought we could take this TidBit Tuesday to look more closely at Idiopathic Head Tremors and compare/contrast to seizures. Please read or skip to the end - there is a plea for data collection and I need your help!

What are Idiopathic Tremors?

Good question!

• Tremors are action-related in veterinary medicine.

• Two classes are: Postural (example is orthostatic tremor, idiopathic head tremors, and hypomyelination) and Kinetic (Intention tremors with cerebellar disease, others)

• Postural tremors happen NOT AT REST. Meaning, the body part isn't supported by the ground/bed/etc. If it is, the tremor stops.

• Further, idiopathic head tremors STOP WITH MOTION. Distract the dog, get it walking, eating, etc, the movement stops.

• Kinetic tremors DO NOT STOP WITH MOTION. They get worse. The classic example is a cat with cerebellar hypoplasia. As they move, the tremor becomes more obvious. This is a kinetic tremor.

So, what causes idiopathic head tremors? We...ahem...don't know. They are classified as a movement disorder but that means it could be from CNS or PNS lesion localization. Movement disorders are a huge box of diseases that are lumped together but may be anything associated with specific movements, or not. There is a really nice, recently published article by Dr. Mark Lowrie that outlines the different types of tremors if you'd like to read more.
(https://bvajournals.onlinelibrary.wiley.com/doi/epdf/10.1002/inpr.3)

How do you differentiate tremors from seizures?

Look for classic evidence of seizures such as autonomic signs, changes in mentation or a lack of stopping when moved, distracted or completely recumbent. Even the head must be recumbent for idiopathic head tremors to stop.

How do you diagnose idiopathic head tremors?

I'm sorry to say that we don't have any diagnostic tests available to make the diagnosis. Also, it is idiopathic, so even if we do brain MRI/CSF all testing is normal. There is a suspected genetic sire in Doberman dogs that idiopathic head tremors can be traced back to, but as of yet there isn't a genetic test available. Stay tuned.

Because we cannot reliably differentiate these from focal seizures AND seizure disorders can be progressive and life-limiting if left unchecked AND some movement disorders do respond to anticonvulsant drugs I always, always, recommend doing a trial of an anticonvulsant medication before simply stating that they are a movement disorder and ignoring them.

One of the tenants of idiopathic head tremors is that they don't respond to anticonvulsant medications but please read this line cautiously. Up to 30% of dogs and cats with seizure disorders do not respond to anticonvulsants (1 or multiple) either so a lack of response to anticonvulsant drugs still does not rule out a seizure disorder.

If the animal has autonomic signs (drooling, lacrimation, urination, defecation, vomiting) concurrent with the movement, they cannot be distracted easily from the movement OR it is present at rest consider this a seizure disorder and keep trying to treat. Or call your local, friendly, mobile neurologist.

DATA COLLECTION

I am looking into the seasonality of head tremors. If you have a case that you have seen with a postural tremor, such as a head tremor, (not cerebellar animals) please consider filling out the short form found online to contribute data to this study. It shouldn't take long to fill out. If you've sent me an email about a tremor, please consider filling out the online questionnaire so I have your permission to include your data. Thank you!!
Link:https://barnesveterinaryservices.com/head-tremor-database
Password: VET2021

I am here to help you, help your patients, live their best lives with neurologic disease. You don't need to be "good" at neurology - that's my job - you just need to be willing to advocate for your patient!

Stay safe. I look forward to working with you soon!

Are we any good at a neurologic exam when pets are vestibular?

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, 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).

My current work days are...well, all of them except Sundays. I'll post on FB or my website if I'm closed on a random day so feel free to check those spots if you're not sure. Otherwise, feel free to call, email or hop online to schedule a telephone, live or video consultation with me. Remember, all live consults are still curbside!

Anisocoria

** Credit for the amazing hand-drawn image goes to my good friend, and veterinarian Dr. Pam Boutilier.

Anisocoria

Anisocoria is defined as pupil asymmetry and may be seen with ocular or neurologic dysfunction. Malfunction of the sympathetic, parasympathetic, or visual system may result in anisocoria.

Neuroanatomy

Visual Pathway
When light enters the eye, it activates the light receptors in the retina. That information then travels along CN II, crosses in the optic chiasm, and terminates in the thalamus. Optic radiations relay the visual information from the thalamus to the visual cortex in the brain. This pathway can be tested using the menace response test and/or cotton ball testing.

Parasympathetic function: Pupil constriction
The parasympathetic pathway to the eye is a short, two neuron pathway which originates in the midbrain. The two, paired parasympathetic nuclei of CN III (PSNCNIII) send fibers along with the somatic nerves from CN III to the eye. The parasympathetic pathway is best assessed using PLR. When a bright light enters the eye, CN II activates and synapses on the PSNCNIII. The parasympathetic fibers transmit this information to the eye, using cranial nerve III as a conduit, resulting in pupillary constriction.

Sympathetic function: Pupil dilation
The opposing system is the sympathetic system, which causes pupillary dilation. The sympathetic pathway is a three neuron pathway and takes a longer course to the eye compared to the parasympathetic system. In general it goes from the thalamus, through the brainstem and cervical spinal cord to exit in the upper thoracic segments. Fibers then make a U turn and head back to the eye via the jugular groove (don't poke around too much when doing those jugular blood draws!), bulla (ear infection can = sympathetic dysfunction) and then hitches a ride with CN V to make the final leg to the eye. Malfunction anywhere along this pathway will result in a failure of iris dilation in a dark room and a comparatively miotic pupil, typically accompanied with enopthalmus and ptosis.

Putting it together

Let's put this new knowledge to work. If you see a case with anisocoria, how do you decide if it is a parasympathetic or sympathetic dysfunction?
1) Assess the pet in a dark room. Does the eye dilate? If yes --> The lesion is NOT due to sympathetic dysfunction.
2) Asses PLR. Does the eye constrict? If yes --> the lesion is NOT due to parasympathetic dysfunction.

To localize to the appropriate location beyond sympathetic or parasympathetic function requires a full neurologic examination. If you aren't comfortable performing or interpreting a neurologic examination please consider a neurology consultation! I am not comfortable doing a dental...we all have our limitations! :)
If you're interested in digging into anisocoria more deeply, or you have a case with anisocoria consider checking out the following article for a full discussion and more amazing images. Note: I do not receive any royalties or financial impact from this article.
* Barnes Heller H, Bentley E. The practitioner's guide to neurologic causes of canine anisocoria. Today's Veterinary Practice Jan/Feb 2016 pg. 77- 83.

Keep those consults coming; we all get to learn a little bit more with each consult. Have a great week!

20% of dogs receiving AEDs have dermatologic reactions??

Up to 20% of dogs taking AEDs may have a drug reaction that manifests as a dermatologic reaction.

Wow! That number is higher than I remember from residency; what's your experience?? I dug into this statistic this week after consulting on a case about a possible dermatologic drug reaction in a dog receiving an anti-epileptic drug (AED).

What signs are seen?

During a prospective study, 15 dogs (of 137 dogs) were identified as having a dermatologic condition after starting an AED. However, three may have had signs before starting the AED. All 15 were treated with phenobarbital!

9 dogs were seen by a dermatologist and the following signs were documented:

• Extensive erosions or epidermal necrosis leading to skin detachment (4 dogs)

• Papules, pustules, erythema, crusty lesions (8 dogs)

• Pruritus and/or alopecia (3 dogs)

How do they *know* it is related to the drug?

They utilized an index based assessment, which is used for drugs in which withdrawal or drug challenges may be unethical (AEDs!). The index is called the Naranjo intext. I'm not terribly familiar with the nuances of using this index, so forgive my lack of a more detailed explanation. When they applied this, they considered 6 dogs to have probable cutaneous drug reactions, possible drug reactions in 8 dogs and doubtful in 1 dog. We all know these indexes can be wrong, but those numbers sound pretty compelling, and concerning.

How was it managed?

The AED therapy was withdrawn in 7 cases and 5 subsequently resolved completely with 2 weeks. Another dog had partial improvement after withdrawal of the drug and the rest received supportive or directed treatment such as anti-inflammatory, antimicrobial topicals, ant parasitic agents, or systemic prednisolone. All dogs had resolution of signs with the above treatments, but improvement wasn't complete and appeared temporary.

Key Point: Do a thorough physical examination on your patients before starting any AED and document new dermatologic changes if they arise. Can they still be coincidental? Yes. But, maybe we're are missing some that are not.

Do you need help with an epileptic patient? I am especially fond of helping with seizure management so I'd love to help! Call, text or email. Please note that I respond to emails at night (most days) so if you have an urgent question please call or text.

*Reference: Koch T, Mueller BD, et al. Cutaneous adverse drug reactions in dogs treated with antiepileptic drugs. Frontiers in Veterinary Science 2016: 3: 1-10.

Meningitis...Encephalitis...?

Canine Meningitis...Encephalitis...Meningoencephalitis... oh bother...

Canine Meningitis...Encephalitis...Meningoencephalitis... oh bother...

Canine meningoencephalitis is a general term, used to collectively describe inflammation in the brain and meninges of dogs. Although infectious meningoencephalitis can occur, the majority of dogs have a non-infectious, inflammatory disease.

Remember the term GME? Well, that is only ONE type of non-infectious inflammatory meningoencephalitis! Note: to call it GME we need histopathology. Not surprisingly, many clients do not opt for brain biopsies so we cannot confirm if it is GME, or NME or NLE or another histologic subtype of inflammatory brain disease antemortem. That won't do!

IF I CANNOT CALL IT GME IN A LIVE PATIENT, WHAT DO I CALL IT?

We call the collection of non-infectious, inflammatory brain diseases Meningoencephalitis of Unknown Etiology (MUE). Or, if you're British it's MUA (aetiology). Or, sometimes its called MUO (origin). Shoot, we're back to alphabet soup again. 😒 When we settle on a term, I'll let you know, but for now the literature typically refers to non-infectious, inflammatory brain disease as MUE. (Not GME)

CLINICAL SIGNS
* Any age, breed or body condition. (cats too!)
* Chronic or acute progression of signs (I've diagnosed it in dogs with clinical signs for 6 months, and those with a 24 hour history of signs).
* Multifocal or focal neuroanatomic lesion localization.
* Unless the dog has SRMA (one form of non-infectious inflammatory brain disease), fever is NOT a common clinical sign.

DIAGNOSIS
MUE is a clinical diagnosis which must be supported by diagnostic investigation. Without diagnostic investigation the word presumptive is recommended, or simply include MUE in the listed differential diagnoses in the medical record.

* Magnetic resonance imaging (MRI) focused to the area of neuroanatomic lesion localization
* Cerebrospinal fluid (CSF) analysis
* Negative geographically specific infectious disease testing
We cannot diagnose MUE with blood work, or on neurologic examination alone. (Sorry)

Extra tidbit - GME is not caused by vaccination or population density according to a recently completed study!*

TREATMENT
Standard treatment is immunosuppressive glucocorticoid therapy (1 mg/kg twice daily prednisone or prednisone equivalent dose) because of the ease of administration for owners, good penetration through the blood brain barrier and comparatively low cost. A slow taper over months is recommended, however some animals require medication for life. If glucocorticoid therapy is intolerable to dog or owner, other protocols could be considered.

PROGNOSIS
Survival to 3 months is the most reliable predictor of long-term survival.

What do I tell clients? Start treatment, and repeat a CSF tap at 1 month. If the pet is doing well, CSF tap is normal or normalizing, keep going. If all is going well by 3 months, consider repeating another CSF tap and continue to monitor life-long for relapse of clinical signs. The prognosis is based on the old saying, " if the dog is doing well, it's likely to do well." Sigh...just a sign that we have a lot more work to do sorting out this disease.

As a small business, I sincerely appreciate your business and your willingness to continue to support mobile neurology. I am the only mobile veterinary neurologist in Wisconsin and Illinois and, I appreciate your support!

Stay Safe, and Happy December Everyone!

*Barnes Heller HL, Granick M, Pinkerton M, Keuler NS. Case-control study of risk factors for granulomatous meningoencephalomyelitis in dogs. JAVMA 2019:254(7):7-10.

Tetanus and Animals

Tetanus and Animals

I saw a case of suspected tetanus this week in a cat so I thought we could take this opportunity to review this rare, but important, neurologic disease.

Tetanus is cased by the release of tetanus toxin by the Clostridium tetani bacterium. Once the toxin is produced in the wound, it travels via retrograde transportation from the peripheral nerve to the central nervous system where it attacks the real target: the inhibitory interneurons that regulate motor activity. So (you might ask), what is the lesion localization for tetanus? It is a CNS disease at the level of the spinal cord and brain NOT (as one might assume) a peripheral neuromuscular lesion localization!

Signs

The interneurons are focused on regulating muscle tone therefore a disruption of their function results spasticity. Remember, spasticity can occur in all skeletal muscles therefore diaphragm and intercostal muscles can be affected, resulting in respiratory paralysis. The spasticity can be stimulated by noise, touch and light. The incubation period for cats is 5-10 days with a longer suspected incubation period in dogs. According to a recent report about tetanus toxin, strychine intoxication is the only condition that exactly mimics the disease, however other myopathic diseases such as hypocalcemia can be included in the differential diagnoses in the early stages.

Treatment

Debridement of the wound(s) and antibiotics such as penicillin G and metronidazole are recommended to treat the infection but have no effect on the already-formed toxin circulating the body. Therefore, supportive nursing care is critical until a plateau in signs becomes evident. After this point, if the dog or cat can eat, drink, and void voluntarily, supportive care can be continued at home. Tetanus antitoxin is available for cases in which an early diagnosis is obtained however this has limited use in dogs and cats.

Prognosis

Recovery is expected for animals with appropriate supportive care. If respiratory paralysis occurs, ventilatory support may be needed, resulting in added expense and risk of secondary infections. However, a full recovery can be expected for dogs and cats affected by tetanus toxin with appropriate treatment and time.

A special shout out to the vets successfully managing this recent case. Keep it up and way to go!

Happy Thanksgiving! Stay safe, and keep those consults rolling.

Recent open access reference if you are interested: Popoff MR. Tetanus in animals. J Vet Diagn Invest. 2020 Mar;32(2):184-191. doi: 10.1177/1040638720906814. Epub 2020 Feb 18.

BREAKING NEWS: Phenobarbital causes side effects in cats!

Phenobarbital and Cats

It comes as no surprise that I'm a super fan of phenobarbital for seizure control in cats. My research at the University of Wisconsin started with the development of a novel transdermal phenobarbital product, and it ended (so far) with a novel oral formulation (not published yet). Phenobarbital works WELL and for many cats. But, it still has some misconceptions which I'll enumerate below.

Misconception.... TRUTH

1) Phenobarbital causes elevated ALP enzymes in cats.....IT DOES NOT. There was one study that reported a few elevations but NONE of the 77 cats in a recent study, nor any of the cats in a prior study my resident and I conducted had elevated ALP enzymes. Elevated ALP is a dog thing!

2) Phenobarbital does not have observable side effects....FALSE! Side effects occur in 46.7%of cats (Marsh et al). Sedation and ataxia were the most common side effects, but not the only ones.
Here are the side effects (called Type A adverse events), and percent of cats affected, as reported in Marsh's study:
a. Sedation 89%
b. Ataxia 53%
c.Polyphagia 22%
d. Polydipsia 6%
e. Polyuria 6%
f. Anorexia 6%
** Perhaps the last 4 are only notable to the observant owner, or in single cat households. Also of note, side effects in cats are reported less often compared with dogs.
Type B adverse events were extremely rare in the recent study, as well as in my experience. Bone marrow suppression did occur in 1 cat (as can be seen with dogs) and it resolved with removal of the phenobarbital. Lymphadenopathy has been linked to phenobarbital use as well.

3) Phenobarbital side effects happen randomly...FALSE! They are dose dependent and predictable. Higher serum concentrations (above 35 ug/ml) result in a higher odds ratio of developing a side effect. Additionally, 20 of the 36 cats in the study by Marsh had transient signs. The majority of side effects only occured in the first 4 weeks of treatment. This is a terrific point to make when discussing the use of this drug with clients.

What is the Take Away Message?

1) Start phenobarbital at a dosage targeted to reach 20-30 ug/ml. This typically means about 3 mg/kg (or a bit less) q12h.The goal is seizure control without concerning side effects.

2) Counsel clients that side effects occur in about 1/2 of cats, and of those, the majority occur within the first 4 weeks of administration AND resolve without any dose adjustments. If side effects are present beyond 4 weeks, consider a dose reduction.

Thanks for your business, especially in these unusual times. I truly enjoy working with you, and your staff. Please stay safe, stay healthy, and keep those consults coming!

*Marsh O, Corsini G, Van Dijk J, Gutierrez-Quintana R, De Risio L. Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Journal of Feline Medicine and Surgery. June 2020. doi:10.1177/1098612X20924925

*Finnerty K, Barnes Heller H, Mercier M, et al. Evaluation of therapeutic phenobarbital concentrations and application of a classification system for seizures in cats: 30 cases (2004 -2013). JAVMA 2014: 244(2):195-199.

Metronidazole and Vestibular Signs

Today is the first day of Fall 2020!
In honor of this awesome season, I thought we'd talk about another type of fall...vestibular disease! :) 

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. 

Whew it has been busy lately!! I hope you are doing well and staying safe. I appreciate what you do to help clients and their pets. Let me know how I can help you manage your patients with neurologic disease.

On site consultation is available Monday through Saturday at variable times throughout the week. Email consults are completed in evenings. 

Have a good week! 

CBD oil and Canine Epilepsy

What is the Effect of CBD oil on Canine Seizures?

Yes, I'm opening a proverbial can of worms today! As a neurologist, vets often ask me if CBD can be used as an anti-epileptic drug (AED). As a practicing veterinarian in Wisconsin I say I cannot recommend or prescribe CBD containing products.

As a neurologist, I add the following…

In June 2019 a study was published that attempted to answer the question:
“What effect does CBD oil have on seizure control?”1
 According to the authors:

• CBD is metabolized through the cytochrome system in the liver in humans, and probably dogs. The ALP increased in all dogs receiving CBD oil in that study. What is the clinical significance? Unknown, currently.

• There was no difference in seizure response between the CBD group or the placebo group (Response = dogs that had a 50% or greater reduction in seizures during the 12-week observation period.) Do we need a different dose? Different formulation? Or did it simply not work for this group of dogs?

• Drugs that are metabolized through the liver (e.g. phenobarbital, zonisamide) may be affected by CBD. This means that the adverse clinical effects could be more pronounced in dogs concurrently receiving these drugs.

• What adverse clinical effects does CBD have? We don't know yet. Several dogs in the CBD group developed ataxia, however they were concurrently on other anti-epileptic drugs. Was the ataxia due to CBD, or because of increased serum concentrations of concurrent AED?

So, although my response to clients remains that I don’t recommend it. My reasoning includes all of the reasons listed above in addition to the recommendations by the government officials in Wisconsin.

What if a client wants to give it anyway? As a veterinarian, I would thoroughly document the discussion, and then recommend monitoring at least liver values (ideally the entire biochemistry panel) every 4-6 months while the pet receives the product. It may be that CBD is the magical seizure potion we are searching for to help our drug-resistant seizure patients. However, history would tell us that the newest “catch all” tonic is typically not as universally perfect as we wish it to be. Be educated, be careful, and be observant when we walk into this yet uncharted territory of CBD oil and seizures.

1. McGrath S. et al Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy. JAVMA 2019; 254(11): 1301-1308.

 Are you working with a patient with seizures and need some expert help? I'd love to! Please reach out via email, telephone or schedule an appointment online.

Microbiome and Epilepsy

Microbiotia-Gut-Brain axis...say what?

There has been growing evidence in human, and veterinary, medicine to suggest that what is in the gut can influence brain development, function and even the course of disease. Many clients have a firm belief that food plays a role in a dog's epilepsy however it has been less clear to me what this role may be. Is it the gluten in the diet (as with some Border Terriers)? Or, is it the microbiome? Maybe both? Maybe neither?

Lactobacilli and the Influence on the Brain

Research suggests that Lactobacillus sp. can play a role on brain function in humans through it's anti-inflammatory properties and perhaps through the production of GABA, an inhibitory neurotransmitter. What about dogs with epilepsy? Dr. Karen Munana investigated Lactobacilli in fecal samples of dogs with epilepsy and compared them to fecal samples of dogs without epilepsy. (See reference below)

No difference in absolute ore relative numbers of Lactobacillus species were found in drug-free epileptic dogs compared to healthy dogs. Furthermore, Lactobacilli were not killed in culture when exposed to phenobarbital, potassium bromide, zonisamide and levetiracetam. 

For now, this means we don't see a difference in this important bacterial species. This DOESN'T mean that we may not find a difference in the future, and it DOES NOT mean that gut health isn't linked to canine epilepsy. I will keep my ear to the ground on this one and keep you posted on any breaking news on GI health-brain health linking.

Stay safe, stay healthy, and keep me posted on how I can help you, help your patients with neurologic disease!

*Muñana KR, Jacob ME, Callahan BJ. Evaluation of fecal Lactobacillus populations in dogs with idiopathic epilepsy: a pilot study. Anim Microbiome. 2020;2(1):19. 

Cognitive Dysfunction Syndrome in Cats

What is Cognitive Dysfunction in Cats?

Sixteen years ago when I left my residency and started out as a newly minted neurologist, feline cognitive dysfunction syndrome (CDS) was not on my radar. That has changed. As we learn more about aging in cats, it has become a more widely recognized disease by yours truly, as well as many of you in practice. If you're like me and need a Tidbit-Tuesday style refresher...read on!

What is cognitive dysfunction syndrome?
Cognitive dysfunction syndrome (CDS) is a term used to describe deterioration of mental capabilities associated with age.  Clinical signs referred to cognitive dysfunction can also be associated with other age-related illnesses (e.g. osteoarthritis, structural intracranial disease such as neoplasia, or cardiovascular disease). See table 1 for an outline of behavior changes seen in cats with CDS.
The underlying etiology of CDS is yet unknown. Causes such as oxidative stress/damage, neurodegeneration  and vascular changes are among the leading hypothesis for human and canine CDS, and therefore suspected to be similar in feline CDS.  Deposits of extracellular B-amyloid and intracellular accumulation of microtubule-associated protein tau have been seen in human patients with cognitive dysfunction. Similarly,  B-amyloid deposits and increased tau have been detected in aged cats with cognitive decline, however the significance remains unclear. 

What are the clinical signs of cognitive dysfunction in cats?
There is a handy article, recently published in the Veterinary Clinics of North America by Dr. Miele and associates that echos what others have been reporting in a very concise little table. (See reference at bottom) I have replicated this table, with a few modifications, here. Note: There are other signs such as decreased appetite or thirst, that don't usually drive an owner or veterinarian to seek consultation from a neurologist so I haven't included them here. 

Table 1: Clinical behavioral changes associated with CDS in cats.Increased vocalization, especially at nightAltered social interaction and relationships, either with other or other pet. Altered sleep/wake patterHouse soilingSpatial Disorientation or confusion (i.e. forgetting the location of the litter box)Temporal disorientation (i.e. forgetting if they have been fed)Altered activity (i.e. aimless wandering)AnxietyLearning and memory dysfunction
How is CDS in cats diagnosed?
Oh, this is as tangled of a web as the tau proteins we chase. (A little CDS humor here...you see the tau proteins can cause the "tangles" seen in human CDS.). Currently, the diagnosis is made by ruling out structural brain disease and systemic causes for disease. This may include complete blood count, full biochemistry panel including thyroid screening, urinalysis, chest radiographs, blood pressure assessment, brain MRI and possibly spinal tap. Imaging changes associated with canine CDS include increased depth of the sulci, dilation of ventricles secondary to neuronal loss (called ex vacuo hydrocephalus) and a measurably small interthalamic adhesion. Exclude everything else, and it's probably CDS.

How can we help these cats age easier?
Currently, there are no proven treatments for feline CDS.  The addition of antioxidants (B vitamins, vitamin C, other) as well as fish oil were evaluated for use in cats in one study and showed promise. The use of S-adenosyl-L-methionine (SAMe) has been recommended for cats based on a study that identified improved performance on cognitive testing. This study only found significant improvement in cognitive function testing in the least affected cats. In addition to medical management, environmental management with ready access to food, water, litter box and areas of comfort (beds, hiding spots) is recommended. Environmental stimulation with low impact toys, or bird feeders in which the cat can choose to ignore any activity if they do not feel inclined to engage, are recommended. Finally, focused veterinary visits can be important for cat owners to feel supported through the aging process. Focus your exam specifically evaluating body weight, urine production (to assess for signs of dehydration), behavior changes and mobility.This may help detect signs earlier in the course of disease and to identify concurrent morbidity that may contribute to, or be confused with, cognitive dysfunction.

Did I forget anything? Most of you treat and see this more than I do. What do you see in practice? What have you used (successfully, or not) for treatment? Please reach out - I want to hear your perspective!

Reference:
Miele A, Sordo L, Gunn-Moore DA. Feline Aging: Promoting Physiologic and Emotional Well-Being. Vet Clin North Am - Small Anim Pract. 2020;50(4):719-748. 

What Do You Do With a Confused Cat?

What do you do with a confused cat?

Sigalment: 12 year old FS Domestic short-haired cat
History: 2-3 week history of seeming "confused", and a recent onset of circling right more than left. These very astute owners observed the cat seemed to walk into a room, forget why it entered, stand there, and then leave again. Additionally, she wasn't as bright as is typical for this indoor-outdoor Wisconsin cat. Birds would land on the feeder outside of the window and she appeared uninterested. 
Physical examination: Normal TPR, normal exam. This was a remarkably fit cat for her age!
Neurologic examination:
Mentation: Obtunded
Cranial nerves: absent left menace response, normal PLR and normal menace response on the right. The cat was less responsive to facial stimulation on the left lip but did respond to hemostat pinch. All other cranial nerve exam findings were within normal limits. 
Gait: Ambulatory with mild proprioceptive ataxia and occasional circling right
Postural reactions: absent tactile placing left pelvic limb, intermittent on left thoracic limb, normal on right thoracic and pelvic limbs. 
Spinal reflexes: normal all limbs, and c. trunci

Okay..take a moment and put all of that together in your mind. I'll take this moment to remind you that my next Webinar is on Wednesday July 15th (TOMORROW) and we'll be talking about lesion localization. If you're interested in joining me to practice on cases just like this please go to https://barnesveterinaryservices.com/ce-opportunities and sign up!

Back to this case. How did you do? Here is how I would talk myself through this one...
1. The cat has a change in mentation..the problem MUST be intracranial.
2. There is a menace deficit - the affected parts could be cranial nerve 2, forebrain or cranial nerve 7. 

• 2a. PLR is normal (this is cranial nerve 2, midbrain and cranial nerve 3) so we can eliminate cranial nerve 2 as a possible cause of the menace deficit. 

• 2b. The cat did not have any noted change to motor of the face (run by cranial nerve 7), so we can eliminate cranial nerve 7 as a cause for the menace deficit. 

• 2c. Finally, one must remember that the menace response crosses and enters the opposite side forebrain so, since we have narrowed the problem down to the forebrain we then must comment that it is the RIGHT forebrain we are concerned about

3. Circling is either a vestibular or forebrain sign. This cat did not have evidence of vestibular disease so we could consider this another forebrain sign. Animals circle towards their lesion, thus supporting a RIGHT forebrain lesion. 

So far, so good?

4. Tactile placing goes from the toes, up the ipsilateral spinal cord, brain stem (crossing at the midbrain) and enters the opposite side forebrain. Voila! We don't have any evidence of spinal cord disease, or brain stem disease in this cat (no cranial nerve deficits) so this also suggests a RIGHT forebrain lesion. 

What about that sensory deficit on the cranial nerve exam? This actually suggests a proprioceptive change to the face! This finding might be the only finding we didn't routinely teach in veterinary school because it's an oddity. But, it is a crossing tract and reflects forebrain disease. 

So, what lesion localization did you come up with? Scroll to the bottom to see if you are correct.

Diagnosis
We diagnosed a brain tumor on MRI (see image above) and took this kitty to surgery. The mass was removed entirely, and was eventually diagnosed as a meningioma. Meningiomas are locally invasive, rarely spreading, intracranial tumors in cats. With complete surgical resection no additional treatment is needed! The cat went back to her normal personality, stopped circling, and regained vision in the left eye post operative (by the 1 month recheck...not immediately). Pretty cool stuff, huh!?

I hope you have a safe and fun week. Keep those consults coming and I hope to see you at the Webinar tomorrow!

Answer: RIGHT forebrain. 

Portosystemic Shunts and Their Effect on the Nervous System

Portosystemic Shunts and Their Effect on the Nervous System

Portosystemic shunts (PSS) are common in small breed dogs and surgical correction is commonly recommended. However, there is concern about neurologic signs peri-operative for these patients. Some develop seizures, mentation changes, and other neurologic signs before shunt attenuation while others do not show signs until after shunt attenuation. Sadly, the presence of neurologic signs is a poor prognostic indicator according to many studies. One recent study looked for prognostic indicators in dogs that develop seizures post attenuation (PAS) within 7 days of surgery.  I hope you'll find the study as interesting as I did!

Study Design

This was a retrospective study including 93 dogs from 14 different institutions. 53% of dogs received prophylactic levetiracetam. There were lots of different small breeds with a median age of 34 months (range 5-124 months). 

Results

• 17.3% of the dogs had experienced at least 1 seizure prior to surgery.

• Interestingly, 78% of the dogs had exhibited neurologic abnormalities including those with seizures.

• Only 30% of dogs with PAS survived to 30 days. Yikes.

• More often those with focal seizures survived, compared to dogs with generalized seizures.

• Sadly, the most common reason for euthanasia following the shunt was the presence of uncontrolled seizures. 

Key Points

According to their multivariate analysis the only two factors associated with short term survival were 1) having a history of seizures PRIOR to shunt correction (p=.004) and 2) the development of focal PAS (p=.0003). That's it! 

So, what do we tell our clients? Well, for starters..they need to know that these pets are are risk of developing seizures even if they DON'T have surgery. But, according to this study if they do elect surgery, the development of generalized seizures is a poor prognostic indicator. 

This article was packed with other data so if you want to read the entire thing please reach out and let me know. 

Reference:
Mullins RA, Sanchez Villamil C, Selmic LE, et al. Prognostic factors for short term survival of dogs that experience post attenuation seizures after surgical correction of single congenital extrahepatic portosystemic shunts: 93 cases (2005-2018) Vet Surg.2020; 49:958-970.


That's it for now! I'm maintaining curbside service for the summer and am starting to widen my travel radius again. Please reach out if I can asist with a case. Stay safe, stay healthy!

Prevalence of Idiopathic Epilepsy in Dogs

Idiopathic Epilepsy Update!

A recent article out of the Vet Record by Dr. Rachel Hall and colleagues outlines the prevalence of idiopathic epilepsy and structural epilepsy in dogs.* I found this a very interesting read, packed with useful information so I thought I'd pass along a bit (get it?) of it to you!

Study Design and Points Worth Noting

• This is a retrospective study based out of the UK. 

• 900 cases with MRI, a neurologic examination and medical record history were included. (wow!)

• Structural epilepsy is defined as a seizure disorder secondary to an identifiable structural cause. Examples include neoplasia, meningoencephalitis, hydrocephalus, etc.

• Idiopathic epilepsy is defined as the lack of identification of a structural abnormality in a pet with 2 or more discrete seizures. 

• Small (< 10 kg), medium (10-20 kg) and large breed (>20 kg) dogs were represented in approximately the same percentage in this study.

Results of Interest (there are a lot of interesting results in this study!)

• About 50% of the dogs were between 6 months and 6 years old, and 50% were > 6 years old. 

• About half of the dogs had structural epilepsy based on abnormal MRI findings

• The other half of dogs had no significant findings on MRI and the majority were classified as having idiopathic epilepsy. (The others had toxin and metabolic disease diagnosed).

  • Prevalence of idiopathic epilepsy in dogs in the UK? 50%!

Okay, fine (you might think) how does knowing the prevalence of idiopathic epilepsy in dogs in the UK help me?

I'm glad you asked...

• Idiopathic epilepsy was the leading diagnosis for dogs between 7 months and 6 years old. Inflammatory brain disease was second.

  • Take away point? Meningoencephalitis is NOT rare! Oh, and idiopathic epilepsy is most common in the group of dogs we thought it would be most common.  

• Idiopathic epilepsy was also the leading single diagnosis (34%) for dogs over 6 years of age. HOWEVER when they combined all types of neoplasia together into one group they found 43% of dogs over 6 years of age had neoplasia making it the leading singe diagnosis in this group.

  • Take away point? Read that sentence above again! I considered making this TidBit Tuesday a one line update because it's so critical to make sure we don't forget that "old" dogs can actually have idiopathic epilepsy!

  • Also, dogs over 6 years of age had structural epilepsy more often than idiopathic epilepsy if all causes for structural epilepsy were combined. (Not surprising, I know.)

What do you do with this information?

Do a neuro exam on every patient with a seizure history!

• If the exam is NORMAL, include idiopathic epilepsy on the differential diagnoses list, regardless of age. 

• If the exam is ABNORMAL, include causes for structural epilepsy on your differential diagnoses list, regardless of age.

Thanks for reading - I hope you have a great week!

Reminder! Upcoming Webinar "The Neurologic Exam for the Busy Vet" on Wednesday May 27th 12-1pm and repeated 7-8 pm.
Check out my website at www.barnesveterinaryservices.com for details and registration.

* Hall R, et al. Estimation of the prevalence of idiopathic epilepsy and structural epilepsy in a general population of 900 dogs undergoing MRI for epileptic seizures. Vet Record 2020.