What is the BEST tool in neurology?

Okay, perhaps you'd want to stop and have a cry if you were stranded on an island with 100 neurologic examinations to do. Hear me out...
Imagine this scenario instead: 2-year-old MC Labrador, with a history of 2 seizures in the last month. The owner is coming to see you and wants to know what is going on!? What do you do first?
Hopefully your answer is a...

THOROUGH NEUROLOGIC EXAMINATION!

What if you don't have the time, staff or patient patience to do a complete exam? If you focus on a few specific parts of the neurologic examination, you can get a good picture of what that pesky forebrain is up to. (The part of the brain that causes seizures.)

Okay, grab your pen (or what ever writing implement you use these days), here are the 4 things to focus on when you perform a neurologic examination on a patient with a history of seizures:

• Assess mentation: Signs of obtundation or stupor can indicate a lesion in the forebrain (but also the brainstem, so don't be narrow minded if the pet is mentally inappropriate. Do a full exam!)

• Menace response, paired with pupillary light reflex (PLR): A unilateral absent menace, with a normal PLR and blink reflex, indicates a CONTRA lateral forebrain lesion. 

• Gait assessment: Specifically, do you see circling? Unusual compulsion? If so, animals generally circle TOWARDS their lesion. E.g., circling left, I’d worry about a left forebrain lesion.

• Postural reactions:  Deficits will be CONTRA lateral to a lesion causing seizures. E.g. an animal with a left pelvic limb paw replacement deficit may have a deficit on the right forebrain. Note: the new name for CP is paw replacement deficit. Also, remember that those tracts for paw replacement can be abnormal with anticonvulsants, or from other neurologic diseases. When in doubt... do a full exam!

Beware! The neurologic examination may be abnormal after IV administration of anti-convulsant drugs, during the post ictal phase, or if the pet has received long-term anti-convulsant drugs.

Did you know that 90-95% of dogs with idiopathic epilepsy will have a normal inter-ictal neurologic examination??

Furthermore, dogs with an abnormal exam are 16x more likely to have structural brain disease than their normal counterparts! Seriously. The neurologic examination is one of the biggest tools used to predict a diagnosis in an epileptic dog (and I might add, cat). 

Statistics never predict an individual’s condition but by focusing the neurologic examination on these areas you can gain important insight into the health of your patient’s forebrain. Please note: if you find an abnormality, the entire neurologic exam should be performed to make sure that you're not missing multifocal disease. Ultimately guiding owners, helping dogs, and improving everyone’s quality of life is what we’re after, right?

Not feeling confident on the neurologic examination? I'd love to help. The vast majority of my business is identifying IF neurologic disease is present in a given pet so that we can build a reasonable differential diagnoses list.  

Some of you very astutely noted that my schedule went a bit wonky this week. For some reason, the calendar program decided that I didn't need to work until the end of January. (Perhaps AI is more advanced than we know??) As much as I'd love to hibernate, please note that the schedule is now fixed and appointments are now available on the schedule for the end of December and January. Thank you to the vets that reached out!! The only way I knew that something was amiss was because of you so please, please don't hesitate to reach out if you cannot find a suitable time for a consult. It might be because I'm super busy, but, lit might be for other, fixable, reasons, too! 

Have a great week and please fill up the schedule! :)

Epilepsy in Labradoodles

How many of us are old enough that a Labradoodle wasn’t labeled as such when we first started practice? The labradoodle was officially “started” in 1989 as a breed intended to have low shedding potential. They have gained in popularity over the years and are now extremely popular as a breed worldwide. They are not a recognized breed by the AKC as of 2024, but that hasn’t stopped many breeders from providing pedigrees. Although typically considered a mix of just a labrador and a poodle, they can also be mixed with Irish Water Spaniels, Curly Coated Retrievers and even Cocker Spaniels. One of the proclaimed benefits of a mixed breed dog is the perceived lower risk of health problems. Several studies have refuted this and certainly we see a similar incidence of seizures in Labradoodle dogs compared to Labrador dogs. Idiopathic epilepsy has a known genetic inheritance in the Labrador, and it is suspected in the Poodle. A recent study evaluated Labradoodle dogs with idiopathic epilepsy, presumptive epilepsy and those with epilepsy of unknown origin. They included 40 dogs in the study. Males were over represented in this study (supported in other studies) and most of the dogs were neutered before their first seizure.

Generalized seizures were noted in 25 of 40 dogs, 12 of 40 had focal and generalized seizures and three displayed only focal seizures. The average age of onset was 2.3 years +/- 1.3 years which is similar to the Labrador. Note that the study limited age as an inclusion factor so this could be slightly skewed. The average number of seizures per year in this cohort was 5.4 seizures +/- 6.5 seizures, also similar to the Labrador. Poodles tend to have fewer, less frequent seizures and rare status or clusters. There were similar numbers of seizures in the treated, and non-treated groups, but remember that we treat frequent seizures, and don’t tend to treat infrequent seizures!  Seizures were scored for severity on a 1-10 scale (1: not severe, 10 – very severe) and, although a subjective measure, was considered 6.9 on average +/- 2.0. About 33% of the dogs had cluster seizures (more than 1 seizure/24 hours) and the other remaining dogs had occasional clusters or no clusters.

This study utilized a questionnaire to determine the personality of the dog, and home setting. Eleven dogs were described as nervous/anxious dogs and the remainder were described as vivid, cheerful and stable. Although more seizures/year were noted in the anxious group, this was not statistically significant. No correlation was noted between tick/flea/food and vaccinations in this group of dogs. However, all owners thought that they identified precipitating factors that were all considered ‘stressors.’  Some examples provided included visits to the groomer, vet visits, home visitors and sounds. Both the ictal and post ictal phase were considered stressful for some of the owners, however more owners referred to the ictal phase as the most stressful part of the event. Owners scored their own and their pet’s QoL as fair to good for most of the study. However financial cost was considered a moderate problem (an average of 5.1 on a 10 point scale) for owners.

What should we take away from this article? An awareness of the prevalence of idiopathic epilepsy in Labradoodles should be an important take away from this article. Secondly, it is helpful to note that generalized seizures are common, however focal seizures are also reported in Labradoodles. If you have a desire to read the remainder of the article it can be found here: https://doi.org/10.3389/fvets.2024.1459260

Thanks for reading! I hope you have a good week and stay warm!

Vestibular Disease in Cats

As we reflected on our familys, and leaned back in our chairs last week around the Thanksgiving table (sorry, Canadians, I know yours was last month) I thought - wait - vestibular disease in cats! (That, and why did I eat so much pie?) First, I have been asked "Do cats get vestibular disease?" The answer is: yes. They have the same anatomic structures and roughly the same neural pathways that influence the vestibular pathways as dogs do. Let's look at a case:

Signalment: 4 year old FS DSH
Neurologic Examination:
Mentation: normal
Cranial nerves: right head tilt, horizontal nystagmus FF left, positional strabismus OD, remainder of the cranial nerves are normal. 
Reflexes: normal
Postural reactions: normal tactile placing all four limbs
Gait: ambulatory with mild vestibular ataxia and staggering right when turning.
Palpation: Non-painful spinal palpation and cervical ROM

Peripheral Vestibular Disease

The basic players in the peripheral system are 1) The receptors, 2) cranial nerve VIII or vestibulocochlear nerve. Cats with peripheral nerve disease may have a head tilt, nystagmus, positional strabismus, vestibular ataxia and falling/rolling. The head tilt is towards the side of the lesion. The nystagmus are a bit trickier. In the old days we used to track the direction of the nystagmus as a localizer. Remember when we said horizontal nystagmus indicated peripheral disease, vertical nystagmus indicated central disease and rotary was either? Welllll..... that isn't strictly true anymore. While it is true that horizontal nystagmus are typically associated with peripheral disease, they can be seen with central disease, too. The same is true for vertical nystagmus. Nystagmus that develops only when the head is placed in a specific position (positional nystagmus) are more common with central disease, but unfortunately are no longer strictly associated with that neuroanatomic lesion localization. So how do we localize peripheral disease?? We localize based on the lack of specific findings on the neurologic examination. What they won't have is ipsilateral paw replacement deficits, ipsilateral hemiparesis and/or reduced mentation (obtunded, stupor, coma). These last three findings are identified with brainstem vestibular disease ONLY. 

Brainstem Vestibular Disease

The players in brainstem localization are the paired vestibular nuclei in the rostral medulla oblongata. The tracts for proprioceptive function, descending upper motor neuron and level of alertness (mentation) are also nearby. Therefore, if a disease in the brainstem is affecting vestibular function, it is also very likely to tick off one of those nearby pathways, therefore creating deficits. They don't need to have all 3 deficits, just one will do. So, a cat with a head tilt, nystagmus AND an ipsilateral tactile placing deficit is more likely to have a brainstem localization than peripheral disease. 

Cerebellar localization
The last group of neurons influencing or being influenced by the vestibular system are the cerebellar nerves. In the cerebellum there are "marionette" nerves that exert their influence on the brainstem vestibular system. By "pulling strings" the cerebellar influences the output from the vestibular nuclei.  Without this influence signs such as hypermetria, intention tremors and truncal swaying are noted. To localize to the cerebellum, signs of vestibular disease (head tilt, nystagmus, positional strabismus) are present PLUS hypermetria, truncal sway and intention tremors. When localizing to a specific side, follow the hypermetria. If an animal has hypermetria on the right front limb, the localization is right cerebellum. Occasionally delayed paw replacement is present, but this will be due to difficulty repositioning the limb rather than a solid paw replacement loss. 

Have you figured out the neuroanatomic lesion localization for the case? That's right - peripheral vestibular disease! Differentials for cats are very similar to dogs with the exception that we see more polyps in cats, and more PSOM in dogs. Therefore, I would consider otitis media/interna, polyps, neuritis (infectious or inflammatory), hypothyroidism (yes, in a cat!), diabetes, and peripheral neoplasia. These differential diagnoses are then tailored to the specific case based on the history. 

That wasn't too painful, was it? Let me know if you have a topic you think should be covered in a TidBit Tuesday!

Thank you!

In this week of Thanksgiving, I am remembering you and your staff.

• Thank you for trusting your patient's care to me. I am humbled by the kindness, consideration and feeling of welcome that I receive when I enter your clinic to help care for your patients.

• Thank you for having a room ready for me. 

• Thank you for having kind, knowledgeable staff to assist me.

• Thank you for giving up valuable floor space (rooms, hallways, office space or even bathrooms!) to allow me to fully examine the patient.

• Thank you for the insight, nuance and personal touch you add when talking about a client or patient. I love being a part of your team. 

• Thank you for being an advocate for your patient and for including me in their health care needs. 

• Thank you for following up with me, giving me feedback, patient updates and answering my emails when I check in. 

• Thank you for sharing new ideas for TidBit Tuesday topics...and then reading the emails!

Most of all, thank you for being you!

Many of you have become my friends over the years. I look forward to seeing you and your staff when I get that "ping" on my phone that signals a consult was scheduled. Keep up the good work. You are valuable and important.  

Happy Thanksgiving!  May you have many of things to be thankful for in life. As always, thanks for reading! :)

This email is a repeat from an earlier year but I just love the sentiment and, although I update it, the core still speaks to me. Appreciation has no expiration date! 

Phenobarbital and The Adverse Effects in Cats

Many of you know that Phenobarbital is one of the most effective anticonvulsant drugs (AED) that we use to help control feline seizure disorders. Data we published several years ago suggested that 93% of cats obtained seizure control with serum drug concentrations between 15-40 ug/ml, regardless of the etiology. Remember, control is either a 50% reduction in seizures or 1 or less seizures every 3 months. Despite its high accolades for control, phenobarbital can cause adverse effects in cats. Phenobarbital does undergo hepatic metabolism but, unlike in the dog, it does not result in an increase in ALP. So, what adverse effects can happen?

Clinical Adverse effects
Clinical adverse effects occur in 46.7%of cats in a 2021 study (Marsh et al). These may be described as Type I or Type A adverse effects because they are secondary to the drug properties and often dose dependent. Keep that in mind!  Sedation and ataxia were the most common side effects, but not the only ones. 
Here are the adverse effects, 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. Interestingly, 26 of the 36 cats with reported adverse effects had transient signs. The majority of these only occurred in the first 4 weeks of treatment and in cats receiving multiple anticonvulsants. Adverse effects were significantly more likely in this population of cats when more than 1 AED was being used.

Biochemical Adverse Effects
A more severe, and concerning type of adverse effect is Type B. These adverse effects 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. Biochemical adverse effects are much rarer in cats than in dogs. If a cat has an elevated ALP, as a general rule, find a reason other than phenobarbital administration. In both the study we published several years ago, and the study by Marsh et al, no cats showed an elevated ALP on laboratory results.
 
Take home message:

• Talk with owners about the common adverse clinical effects in the first 2-4 weeks of treatment. These should resolve but if not, consider reducing the dose.

• Recheck the CBC and biochemistry within 4 weeks of starting phenobarbital to monitor for those rare Type B adverse effects.

• Phenobarbital is useful, but imperfect, so always look at the cat in front of you when making decisions about seizure management. When in doubt -reach out!

Thanks for reading! I hope you have a good week and are appreciating the slow shift to cold pre-winter weather that we’ve been having. I look forward to working with you soon.

Brain-Gut-Epilepsy Link

This is exciting, folks! It has been well established that comorbidities such as anxiety, ADHD and fear-behavior are present for human and veterinary epileptics. Owners of dogs with epilepsy are frequently troubled by behavioral changes AND the seizures, especially when poorly controlled. Recently, the gut biome has been an area of focus as an area of possible therapeutics for these comorbidities in humans and animals. A group of colleagues from Europe and Asia recently published data looking into this question and... it’s pretty cool! Read on to learn what they learned. 

Material and Methods
Nine dogs with drug resistant epilepsy AND behavioral changes were included in the study. A fecal donor was a dog with epilepsy that did not have behavioral comorbidities and had responded well to phenobarbital. Fecal microbiota transplantation (FMT) was performed three times, two weeks apart. Questionnaires and behavioral tests were performed at 3 and 6 months after the FMT. This, along with urine testing of neurotransmitter concentrations and routine biochemistry and hematology. 

Results
There was a significant improvement in ADHD-like impulsivity, non-social fear and chasing behavior (questionnaire based), AND seizure severity and frequency. Not surprisingly, the care-giver anxiety concurrently decreased significantly. Even more interesting (to me), the excitatory neurotransmitters glutamate and aspartate decreased and GABA, an inhibitory neurotransmitter, increased. Only 1 dog had a partial seizure response (50% reduction in seizures), and several other dogs had a reduction in cluster days during the follow-up period. No dog was seizure-free after the FMT. 

Take Home Message
This was a pilot study, so it isn't clinically applicable yet. YET. But can you imagine having access to FMT to help manage comorbidities like these? I'm sure you can think of at least 1-2 patients right now that would benefit from a decrease in ADHD-like behavior, fear or anxiety behaviors! Although we cannot use this yet to change our patient's lives, keep your ears open for the future. However, as with all new treatments out there, there will be good and bad options as this comes out. Remember that there are a lot of factors that can affect FMT. Specifically, current or historic administration of medications (antibiotics, gastroprotection’s, NSAIDs, and possibly anticonvulsants). A donor with any of these medications in their past may have an altered gut biome that makes them an unfit donor for your specific patient. So, please don't just take any gut biome and assume it will work for another patient!

Thanks for reading. I hope you can feel my excitement oozing out as you read this week, and I hope you enjoyed reading this TidBit Tuesday as much as I enjoyed reading the article. If you wish to read more, please follow the link below. Have a great week!
Link: doi.org/10.3389/fvets.2024.1385469

Neospora in Adult Dogs

Neospora has become increasingly common in veterinary neurology, especially in the last few years. Neospora is an obligate intracellular parasite that causes notable complications in cattle but is not commonly diagnosed in dogs. Dogs are a definitive host, which means upon infection, they will not pass this infection along to other hosts (unless that new host consumes their meat). In other words, do not eat a dog infected with Neospora (!!).

How do dogs  get infected?

The most common transmission is transplacental or juvenile onset neosporosis. Dogs that develop clinical signs at greater than 12 months of age probably have adult onset or the newly acquired form. This form has fecal/oral transmission.

What are the clinical signs of Neosporosis in adult dogs?

There are two forms of disease, which may occur separately or concurrently. First, we can see neuromuscular disease. Signs may include a strict myopathy (difficulty opening the jaw, tetraparesis with normal reflexes), neuromyopathy (myopathy signs plus patchy reduced reflexes) to a full neuropathy (reduced reflexes in multiple limbs along with clinical weakness). The other option is CNS signs, for which cerebellar signs and seizures predominate.

How is it diagnosed?

Adult onset, or acquired neosporosis, is diagnosed via IFA titer. Different papers have listed different “positive” IFA titers. A recent article from Sydney Australia by Kennedy et al(DOI: 10.1111/jvim.17219), listed the positive IFA titer as 1:800. Previous studies have listed anything from 1:200 to 1:800 as the positive titer rate. I typically recommend retesting if you get anything over 1:200. If it goes UP or remains above 1:400 it is likely clinically active and warrants treatment (if clinical signs are present). PCR inconsistently diagnosed Neospora in the recently published study.

How is it treated and do relapses occur?

The first line treatment for most studies is clindamycin (median dose 15 mg/kg PO q12h) x 12-17 weeks. Sulfa antibiotics are the second line of treatment, and several dogs received both drugs in the recently published study. Prednisone is important during active CNS disease to minimize the secondary inflammatory reaction during protozoal die-off. The dose and duration of prednisone is variable, but immunosuppression should be avoided. Relapses were common in the most recent study (9 relapses occurred in 4 dogs) highlighting the need for either longer treatment, or prompt treatment if signs recur. All signs were similar to the initial presenting signs except for one dog.

Take home message?

Remember to test for Neospora caninum when presented with a dog with CNS signs, myopathy, or neuromuscular signs. A simple titer using IFA is the best step, followed by consultation with your local neurologist.

Thanks for reading! I hope you have a wonderful start to November and look forward to working with you soon.

What do you do when you cannot elicit the cutaneous trunci reflex in a cat?

Okay, first let's talk about this reflex. The cutaneous trunci reflex (CTR) is used in dogs to evaluate the viability of the thoracolumbar spinal cord. It is a really LOOOONG reflex pathway. As with all reflexes there is a sensory and a motor component to CTR. The sensory input is each segmental spinal nerve from T1 to L6 and the motor output is via the lateral thoracic nerve found at C8-T1. Sensory and motor innervation is bilateral however stimulation of one side can result in a contraction bilaterally. 

How do you perform the CTR?

Simulate the hairs or the skin paraspinal between T1 and L6. I use my fingers, hemostats or in rare cases a needle to gently poke the skin. The sensory information goes through the spinal nerve, ascends the spinal cord to synapse on the nucleus of the lateral thoracic nerve found C8-T1. After synapses the motor efferent lateral thoracic nerve contacts the panniculus or cutaneous trunci muscle and you see a visual twitch. The effect may be bilateral, even if you stimulate unilaterally. 

What is the significance of the CTR in dogs?

When present and complete to L6, it carries no significance. Dogs can have severe spinal cord injury and still have a present CTR bilaterally. HOWEVER, if it is reduced cranial to L6, especially unilaterally, this can help focus your lesion localization in the T3-L3 segment. For example - CTR is absent between L1 and L6 on the left, the lesion will be 1-2 segments cranial to L1, or the T12-T13 region. What is better than precision?? Tracking lesions! If we take a dog to surgery and remove a herniated disc at T13-L1 and the CTR was cranially advanced to L1 preoperative, I can monitor the CTR for caudal decent to suggest spinal cord healing, or cranial decent to suggest myelomalacia. Perhaps you have seen some of your patients return from spinal surgery with sharpie marks on their back? This is likely because we were tracking the CTR.

Terrific, but what about cats?

Cats are well, different, aren't they? To start, the CTR is unreliable. In some cats it is present, in other cats it is not. A recent study published in the Journal of Feline Medicine and Surgery confirmed what most of us suspected clinically: the CTR has no significance in a neurologically abnormal cat. It cannot be used reliably to localize a lesion and it may, or may not, be present regardless of neuroanatomic lesion localization. One more way cats make us smile...

**Paushter AM, Hague DW, Foss KD, Sander WE. Assessment of the cutaneous trunci muscle reflex in neurologically abnormal cats. J Feline Med Surg. 2020.

This TidBit was a repeat from the archives but, I suggest, still makes for good discussion. I hope you enjoy your week and look forward to working with you soon!

CPs, postural reactions, paw replacement, oh my!

What we previously called CPs (conscious proprioception) we now call the paw replacement test. Yes, if you haven't heard,CP is now the "old fashioned" term and has been replaced with the much less sexy term "paw replacement test". Why?? (You might ask.) The reason is simple: we were lying when we said we were evaluating just the conscious proprioception pathway! When the paw goes on the dorsum, conscious, unconscious and even a bit of motor pathways are involved in righting it to the correct position.  Sometimes the truth isn't sexy, but alas, here we are. 

What parts of the nervous system must work for the paw replacement test to work?

An abnormal paw replacement test almost always indicates a neurological problem however the lesion may be located anywhere along the pathway involved. The pathway is: peripheral nerve --> ipsilateral spinal cord -->ipsilateral medulla and pons --> cross in midbrain --> end in prosencephalon. Some branches also go: peripheral nerve --> ipsilateral spinal cord --> ipsilateral medulla --> ipsilateral cerebellum. You can see that a LOT is involved with this pathway so you really need to put together the remainder of the neurologic exam to appropriately utilize this test. The paw replacement test is one of several ways to test the proprioceptive pathways and they are often collectively referred to as "postural reactions".

What are postural reactions?

• Paw replacement test: While providing support, and on stable footing, turn a paw upside down and place it on the dorsum. The animal should right the paw to the normal position with minimal to no delay, or scuffing. Want to brush up on your technique? See my YouTube channel with this link:  https://youtu.be/vEFEVvO4TCQ  

• Placing (visual or tactile): A useful test for cats. The animal is blinded and advanced towards a horizontal surface such that the paw gently touches the surface. A correct response occurs when the animal places the limb on the surface.  Want to see a video? Check out: https://youtu.be/VDyaL2kHNV8

• Hopping: One leg is on the ground; the other 3 legs are removed from support. Gently, the animal is pushed in the lateral  direction from the direction of the leg on the ground and the animal should hop.

Learning to perform postural reactions can take years...lots of practice...and seeing lots of different animals with different diseases. Paw replacement deficits are critical for localizing many parts of the CNS so, in my opinion, it is worth it to get this test right! If you want to get comfortable with these tests consider performing one or more of them on every patient you evaluate.

Thanks for reading! I hope you have a wonderful week. I will have limited service next week so please plan ahead if you have a case needing to be seen. Thanks!

The Nuts and Bolts of Anticonvulsant Drug Monitoring

The following information is contained in these two tables:
1. What drugs can I run therapeutic drug monitoring levels?
2. Where do I submit samples?
3. When do I draw blood for sampling?
4. What is the standard reference interval?
5. What is MY (i.e. Dr. Heidi Barnes Heller's) recommended reference range
6. How should I collect this sample? Note - all samples for therapeutic drug monitoring should be spun and separated into a plain red top tube. Do not use serum separator tubes! Plasma can be used for some samples also. Please separate the plasma into a plain red top tube as well.
7. What time of the day should I collect the sample?
*** The format became a little messy with the mailer so email me directly if you want a printable PDF of these tables and the mailer doesn't suffice. 

What is not contained in these tables? 
How do I use this information obtained from a drug serum concentration?? Stay tuned for that in a separate TidBit Tuesday! :)

DrugWhere to submitWhen to submitStandard reference range (may vary a little by lab)PhenobarbitalAny commercial lab. Unless you regularly run QC, in-house phenobarbital analyzers aren’t recommendedAfter 14 days on the same dose15-40ug/ml (dog)
Extrapolated for cats: 15-40ug/mlLevetiracetamAuburn University
https://www.vetmed.auburn.edu/ veterinarians/clinical-labs/After 3 days on the same doseNONE verified for dogs or cats. Human range is 5-40, but target may be closer to 20 for “resistant” humans.ZonisamideCornell Animal Health Diagnostic Center https://www.vet.cornell.edu/animal-health-diagnostic-center/testing/protocols/zonisamide
After 14 days on the same dose10-40 ug/ml (human) extrapolated to dogs and catsBromideAny commercial lab.After 12 weeks on the same dose, and/or after completion of a loading dose1-3 mg/dl

DrugMy recommended reference range (pet dependent of course) Other notesCollection timePhenobarbital25-30 ug/ml dog and cat (cat is extrapolated from dog)Plain red top, serum only.Any, if on longer than 14 days of medicationLevetiracetamNone. Use this sample as an internal reference. Not sure what I mean?? Please email me for additional details.Separate serum (or plasma) into a plain red top2-4 hr. post pillZonisamideNone. I don’t think we actually know the range for dogs and cats yet!Separate the serum or plasma and store in refrigeratorJust before the next dose (i.e., trough level)BromideSolo: 2-2.5 ug/dl
Combination with phenobarbital: variable but usually around 2.0 ug/dl.NoneAny time, if at steady-state

Thanks for reading! I hope you're getting in the fall spirit and enjoying all things pumpkin, cinnamon and apple-y! Please reach out over the next few weeks if you need a consult and cannot find a suitable time on the scheduler. I have a lot of days blocked off for family events but may be able to squeeze in a consult or two as needed. 

Episodic Head Tremor in Doberman Pinscher Dogs

We have talked recently (and historically) about idiopathic head tremors (IHT) common in bulldog breeds. There is another head and neck tremor that has been less well described in the Doberman Pinscher dog termed “episodic head tremor syndrome”. This isn’t new, but a recent case made me realize that we hadn’t discussed this form of head tremors in a TidBit Tuesday before. It is high time.

I’m going to refer back to one of my favorite articles (reference: movement disorders, vol 26, No 13, 2011) as we talk about episodic head tremors of Doberman Pinscher dogs. (EHT-DPD) because I think it’s an oldie but a goodie.

What are episodic head tremors in Doberman dogs?

This is an inherited, idiopathic, paroxysmal movement disorder of Doberman dogs. The signs were traced back to 1 sire in the previously referenced study, strongly suggesting inheritance. Episodic head tremors could be a seizure disorder, just like dogs with presumed IHT may actually have a seizure disorder, but for the moment we still classify it as a movement disorder. Movement disorders do not typically associate with autonomic signs (drooling, vomiting, urinating, defecating) or reduced mentation (loss of consciousness) and should not occur during sleep or when the head is fully supported (like lateral recumbence). Those phenotypic descriptions can guide you in the direction of a movement disorder vs a seizure disorder however, as I tell clients, the best way to “know” is to have an EEG performed. That said, EEGs can be misleading, difficult to interpret or so full of background noise that they are uninterpretable. So, we do the best we can, but sometimes it comes down to our best guess for this diagnosis over a seizure. Although idiopathic, EHT-DPD in the referenced study, appeared frequently with concurrent stress. That could include pregnancy, heat, medications and surgery or illness. That doesn’t mean that stress causes this but may unmask it.

What do the tremors look like?

They are rapid, often intermittent, horizontal or vertical head shaking episodes. The oscillations are RAPID, not slow head swinging movements. There is a congenital form, occurring in dogs less than 1 year of age, and a later onset version.

What causes it?
It is idiopathic based on normal EEG, MRI, infectious disease screening, metabolic screening, and CSF analysis in the study mentioned above.

Should it be treated?

No, not usually. It doesn’t appear to be progressive in a negative manner. Breeding is not recommended for dogs exhibiting signs of EHT due to the suspected inherited manner.

Have you seen a case of EHT in your practice? How did it progress? Thanks for reading! I hope you have a good week. Stay tuned for more fun reading next week.

Tetanus in Cats

Tetanus is caused by the action of the Clostridium tetani neurotoxin causing generalized muscle stiffness. This clever neurotoxin gains access to the CNS via retrograde transport up a peripheral nerve to the spinal cord, or brainstem (if it goes up a cranial nerve). Once in the spinal cord, it will irreversibly inhibit the inhibitory interneurons in the spinal cord thus resulting in generalized or partial muscle stiffness and spasm. Cats are more resistant to tetanus neurotoxin compared to humans or dogs, but they can still get the signs. Let’s talk about how to recognize this rare disease, in cats!

A recent retrospective study out of Europe (11 referral centers) was published in 2024 outlining signalment, clinical and neurologic findings, treatment and outcome. In this report, they cite that cats are thought to be 12 to 2400x more resistant to the toxin than humans or dogs. WOW!
This study described tetanus in 27 cats. Not surprisingly, this was mostly reported in the warmer months of spring, summer and fall with few cases in winter. It is interesting to note that this is not the case with dogs. More tetanus is reported in dogs in winter in Europe. The source of the infection was thought to be a wound in most cases; however, 5 cats had a recent history of sterilization.

The initial clinical signs were lameness or stiffness in a limb in 17/26 cats. This was noted as a difficulty manually flexing the joints in one or more limb on evaluation. Progression was noted in most of the cases, peaking at about 4 days from onset of signs. Two cats demonstrated tonic clonic seizures with loss of consciousness. Marked hyperthermia was noted in 10 cats. Unlike humans or dogs, generalized tetanus was less common in cats. Autonomic signs were rarely reported in cats but are more common in humans or dogs and may result in an increased mortality. Signs might include hypertension, hyperthermia, tachycardia, arrhythmias, profuse sweating and bradycardia. Three cases had wound cultures performed and all 3 were positive for Clostridium tetani.

Treatment

Hospitalization occurred in 21/27 cases with a mean hospitalization time of 7 days. Wound debridement was mentioned in 9/27 cats, along with antibiotics (26/27). Metronidazole was the most common antibiotic recommended, followed by Clavamox. The duration of antibiotic treatment was difficult to determine for many of the cats, but the authors report median treatment duration of 15 days (range 7-28). Muscle relaxation was facilitated with oral diazepam (21/27 cats) monotherapy or combined with methocarbamol, alfuzosin or magnesium sulfate (1 cat). Equine tetanus antitoxin was administered in 6/27 cats and no side effects were reported. The most common adverse effects reported included hyperthermia, urinary retention, dysphagia and osteoarticular disease (fractures due to muscle contractures or osteomyelitis). The more severe cases were noted to have adverse effects more commonly.

Outcome

Outcome was available for 25/27 cats. Of these, 23/25 (92%) regained independent motor within a median period of 25 days (range 11-42). The two cats that did not regain appropriate motor ultimately had limb amputation due to osteomyelitis.
 
What’s Take Away?
Even though more resistant, cats can get tetanus just like dogs. If you are presented with a cat with inappropriate focal stiffness and a wound, consider tetanus. Culturing the wound may aid in making a diagnosis. Metronidazole appears to successfully eliminate the infection, however due to the irreversible binding of the toxin the clinical signs may take longer to abate. When in doubt – refer for a consult!

 Thanks for reading! I hope you have a wonderful week and enjoy this summer-like fall weather that we're having. 
 
Reference: https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1425917/full

Mydriasis in a Cat

It’s time for another case! This time, we’re going to talk about cat eyes – it’s almost Halloween, right? This case was taken from a case report presented in Vet Record August 2024 (https://doi.org/10.1002/vrc2.956). I thought it was interesting, and quite similar to another case I worked with one of you on…with the exception that we haven’t made it to MRI yet.

Signalment: 12 year old MC DSH.
History: 3 month history of mydriasis, photophobia and avoidance of jumping.

On examination, the cat had an unremarkable PE. Neurologic exam was as follows:
Mentation: normal
CN: Dilated pupils OU, no PLR (direct or indirect) OU, remainder normal. (Yes, even oculocephalic reflex!)
Gait: normal
Reflexes: not reported but assumed normal.
Postural reactions: normal

Lesion localization?

Let’s take a step back and remember that the parasympathetic innervation to the eye comes from midbrain (Parasympathetic nuclei of CN III), piggybacks with CN III to the eye where it then enters the iris muscles, causing constriction (normally). A lesion in the brainstem (midbrain in this case) should produce a change in mentation, paw replacement deficits, and/or hemiparesis along with the CN deficit. Bilateral peripheral parasympathetic damage hadn't been reported yet, but it would stand to reason that damage to CN III should result in strabismus and a loss of oculocephalic reflex (physiologic nystagmus). These somatic changes would/should be in conjunction with the parasympathetic changes expected. 

This case was localized to bilateral peripheral parasympathetic nerves because there wasn’t evidence of a brainstem lesion. This is reasonable!
MRI and CSF, along with bloodwork were normal. Unfortunately, they could not collect enough blood for infectious disease testing. Based on these findings, the cat was diagnosed with an idiopathic bilateral peripheral neuropathy of the parasympathetic nerves. So cool! No signs of progression have been noted over 9 months.
 
I hope you enjoyed reading about this interesting case report. If you have any questions about the lesion localization, or anything else, please let me know! Have a great week!

Idiopathic Head Tremors

Wow, a lot of you have been seeing head tremors lately! I thought we could use this TidBit Tuesday to look more closely at Idiopathic Head Tremors and compare/contrast to seizures. 

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, if the body part that is tremoring is supported, 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. 

We're going to focus on postural tremors, and specifically head tremors. There are structural head tremors and idiopathic head tremors. Structural tremors are caused by something we see on MRI or CSF. These cases often involve pituitary lesions and are typically older pets, with neurologic deficits on neurologic exam. Contrast this with idiopathic head tremor. Animals with idiopathic head tremor can be of any age but are typically younger dogs, with a normal neurologic examination and normal MRI/CSF. 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, slightly older 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. 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 usually 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. Furthermore, rapid head movement in a bulldog is a COMMON presentation for a focal seizure so don't just disregard the information. Do a neurologic exam!! 

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 for a consult :)

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!

Rabies : It's still out there

I read some sobering data recently, produced by the CDC, pertaining to Rabies. They published a table of Human Rabies virus infections in the USA and Puerto Rico between 2000-2022. No cases were reported in 2022. Over the remaining 21 years, 57 cases were identified ranging in age from 7 to 87 years old. The source of infection was listed as "contact", "bite", "unknown" or "organ transplant" (Yeah, this one was unexpected to me!). One individual survived but the remaining 56 cases were, not surprisingly, all fatal. Reading this table reminded me that we haven't talked about Rabies on TidBit Tuesdays for awhile (actually since 2022!). As your friendly neighborhood neurologist, I feel strongly that we should have this conversation so please read on. 

Etiology

Rabies is a neurotropic rhabdovirus that causes fatal infection in dogs, cats and (usually) humans. Infection is caused by inoculation from saliva by means of a bite.  The virus then spreads into the CNS via peripheral nerves.  Once the brain is infected, the virus spreads back out through peripheral nerves to the salivary glands – at this point, the animal can transmit rabies.

Signalment
Any dog, cat, horse, cow, HUMAN

Clinical Signs

Two syndromes are described:

• Furious syndrome (forebrain signs)

• Paralytic syndrome (lower motor neuron signs ascending from the site of the bite). This means a paraplegic dog could be considered for rabies observation if they are NOT vaccinated. Be aware! 

Once neurologic signs are present, progression is rapid, and most animals will be dead within several days. Most of the individuals on the CDC table were deceased within 3 weeks of their noted infection date. 

Rabies should be considered as a differential diagnosis in any animal with acute onset, rapidly progressive neurologic disease especially if there is a poor vaccination history or exposure to wild animals.

Diagnostic Tests

  Key point: A definitive diagnosis can only be achieved postmortem, and requires fluorescent antibody staining of brain tissue to demonstrate rabies antigen. A serum RFFIT (Rapid fluorescent foci inhibition test) can be performed to evaluate for evidence of previous vaccination however it should NOT be used to make a diagnosis of active rabies infection. One of the cases I evaluated had a negative RFFIT test and was confirmed to have the rabies virus on necropsy. Due to the neurotropic nature of rabies it can remain undetected by the immune system and therefore cause a negative (false negative) RFFIT result.

What do you do if you've been exposed? Contact your local heath department immediately. 
What do you do if you have a patient that you suspect has a rabies virus infection? Contact the State Veterinarian (Dr. Yvonne Belay at 608-516-2664)

Further reading
If you're interested in reading about a case of Rabies virus infection please check out this article. https://doi.org/10.5326/0390547. I saw this case a number of years ago, but the disease hasn't changed much in 20 years!

Thanks for reading! A rabies virus infection is something worry about for those of you out there on the front lines. Be aware, be cautious, and when in doubt - put on PPE!! Please reach out if you have any questions.

Other good resources:
The Wisconsin Rabies Algorithm: (for exposure or sick animals) https://www.dhs.wisconsin.gov/rabies/algorithm/algorithmcategories.htm
Illinois Rabies information: https://www.ilga.gov/commission/jcar/admincode/008/00800030sections.html

Can Paraplegic Dogs walk?

What do we know about the natural progression of thoracolumbar intervertebral disc extrusion (TL-IVDE) in dogs? We have been taught when a dog stops having voluntary movement of their pelvic limbs (paraplegia) they need surgery to recover the ability to walk, right? What about those that have lost deep pain? What if we didn’t do surgery – what happens to those dogs? A study was published in JVIM this year that looked at the natural progression of medically managed TL-IVDE in non-ambulatory dogs and evaluated not only the recovery rate, but also what the discs “did” on sequential MRI 3 months after starting medical management.

Results

Sixty-seven dogs met the inclusion criteria – 51 with deep pain, 21 without deep pain, 5 with signs of myelomalacia at presentation.

Treatment consisted of NSAIDs (steroids were discontinued and replaced with NSAIDs if started), pain management and physiotherapy.

·         Recovery

·         Dogs with deep pain: 96% regained walking and voluntary urination (49/51)

o   Median time to recovery 11 days (7-21 days IQR).

·         Dogs without deep pain: 63% regained walking and voluntary urination (10/21).

All dogs (regardless of ambulatory status on recheck) did not have signs of back pain on evaluation 3 months after enrollment in the study.

The change in compression on MRI was interesting. In some patients, the compression almost completely resolved, and for others there was less than a 5% change. This wasn’t correlated with clinical signs but looking at the figures it does not appear to have a direct relationship.

Key point:

If you have a patient presenting with acute, non-ambulatory paraparesis or plegia, surgery is a very reasonable first step. However, it isn’t the only option! Don’t euthanize unless myelomalacia is present!! Consider conservative treatment because we may end up with an ambulatory patient after 3 months! Just because an owner cannot afford an MRI or surgery, doesn’t mean we should do a neurology consult, either. 😊

Thanks for reading! I hope you’re having a good week and look forward to working with you soon.

Shock Index and Head Trauma

How many of you see pets with head trauma in your practice? Okay, that’s good. There are several ways to look at prognosis following head trauma but the key feature of any of the measurements is serial evaluations. One singular measurement doesn’t seem to correlate well with prognosis in such a dynamic disease. A recent retrospective study evaluated the shock index (heart rate divided by systolic BP) to determine the correlation with mortality in a population of dogs with head trauma. A second part of the study was to determine if it was predictive of survival to discharge or improvement in signs during hospitalization.

Results

 A total of 86 cases and an unknown number of control dogs (normal dogs) were included. There was quite a list of possible ways these poor dogs were traumatized and an even longer list of breeds affected. See the study for full details on that.  The mean SI for the control group was 0.75 (range 0.62-0.92 with not normal distribution). The mean SI for dogs with head trauma was 0.91 (range 0.34-3.33, also not normally distributed). SI was significantly (0.0014) higher in the trauma group compared to the control group. However, the SI was not significantly different between dogs that diet or were euthanized compared to those that lived until discharge. There was also no significant difference in SI between dogs with a normal neurologic examination at discharge and those that were improved or static, but not normal, at discharge.

So, what does this tell us? My take away is that the SI is higher in dogs with head trauma, but it doesn’t prognosticate (using the data from this cohort of dogs) regarding survival or neurologic outcome. Why is SI higher in pets with head trauma? Following trauma, if the intracranial pressure (ICP) goes UP (hemorrhage, edema) the mean arterial BP goes up to keep blood flowing to the brain. The HR will concurrently drop due to a feedback loop. This SHOULD result in a lower SI (HR/systolic BP). The authors noted that in one case they had a dog with significant hypovolemia at the initial evaluation which resulted in a very high SI but due to a swing in pressure dynamics in the brain, the dog oscillated between hypo and hypertension over time. The authors suggest that SI may be an unreliable measurement in post-head trauma patients for this reason. So, I return to all of you smart people out there. Why is the SI higher in head trauma than in control dogs? This has also been reported in humans post head trauma so there must be a very good reason, but I can’t figure it out and would love your thoughts!

Thanks for reading this TidBit Tuesday! I hope you have a wonderful week and look forward to seeing you soon!

Reference: McConnell BM, Cortes Y, Bailey D. Retrospective evaluation of shock index and mortality in dogs with head trauma (2015-2020): 86 cases. DOI: 10.1111/vec.13411

How do MRI lesions affect survival for MUE?

 
A study was published this week that looked at the survival times between dogs with and dogs without MRI lesions and diagnosed with meningoencephalomyelitis of unknown etiology (MUE). MUE is diagnosed if a dog has evidence of CNS inflammation (meningitis, encephalitis, myelitis or a combination of these) without evidence of infectious etiology. Signs can be focal or multifocal, and age is irrelevant. To make this diagnosis an MRI, CSF tap, and infectious disease testing are performed. There is a subset of dogs that are diagnosed with immune mediated CNS disease that do not show evidence of disease on MRI but have all of the other markers of MUE. The purpose of this paper was to determine if there is a difference in survival between the two groups of dogs.
Results
A total of 73 dogs with MUE were included in the study. This included 19 dogs with a normal MRI and 54 with an abnormal MRI. The survival time was >107 months in both groups with a significantly longer survival in the normal MRI group. Neither group reached median survival in Kaplan-Meier survival, however. Death was secondary to MUE in 1/19 dogs with a normal MRI, and 18/54 in dogs with an abnormal MRI.
Below is the breakdown comparison between the two groups:

• Remission – 68% of the normal MRI group; 53% of the abnormal MRI group.

• Death within 3 months due to disease – 5% in the normal MRI group and 13% in the abnormal MRI group.

No difference was found between dog groups regarding remission, disease-free interval, or relapse while on prednisone. The two groups received similar treatment protocol, for which corticosteroids were included in all dogs and a variation of additional immunosuppression. The total nucleated cell count (TNCC) was higher in the dogs with the abnormal MRI however this did not correlate with higher rates of death after multivariate analysis. The only significant factor associated with death was the presence of an abnormal MRI.

Why don’t they have lesions on MRI?

Perhaps we’re catching these cases early in the course of disease. This would stand to reason why they might have a lower death rate than those with more progressive disease at the time of diagnosis. Another option is that this is a different form of inflammatory brain disease. MUE is a “catch all” for inflammatory brain disease that isn’t infectious, or a specific form such as SRMA or EME. It likely includes all of the previously diagnosed cases of GME and NME.
Take away: If you have a dog with spinal pain, seizures, vestibular signs or multifocal CNS signs remember MUE! This disease can cause all of those signs, and a collection of other signs, in dogs. Early detection may = improved outcomes. So, if your patient is showing neurologic signs, please reach out to get a consult ASAP and to proceed with additional testing when able. We might just save their life!

Thanks for reading! I hope you are scratching out the very best that summer has to offer. I look forward to working with you soon!

Reference: Survival in dogs with meningoencephalomyelitis of unknown etiology with and without lesions detected by magnetic resonance imaging. Ostrager A, Bently, TR, Lewis MJ, Moore GE.