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.
 

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

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

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

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

A few more good reminders:

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

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

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

So, what does that mean for us?

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

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

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

Levetiracetam vs. Phenobarbital for Neonatal Seizures

Thankfully, neonatal seizures are not something that we identify frequently in veterinary medicine. Unfortunately, neonatal seizures are one of the most common reasons for presentation to the ER in human medicine. Among full term infants, seizures account for 1-3.5% of the cases for infant presentation to ER. To date, phenobarbital (PB) has been the anti-epileptic drug (AED) of choice, however levetiracetam (LEV) was evaluated in a meta-analysis in 202. (REF) The findings are interesting…read on to learn more!
 
Some Background
Human infants with seizures generally have a good prognosis. Phenobarbital has been reported to control 43-80% of electrical seizures, with the added benefit of reducing brain metabolism. The downside is that it has been shown to cause neuronal apoptosis in animal models (aka our patients). LEV has a seizure control rate of 35-86% for neonatal seizures and has been shown to have a neuroprotective effect without evidence of neuronal apoptosis or synaptic development. As we well know, LEV also has a lower side effect profile in our patients. This is true for human infants however the adverse effects monitored are slightly different. In this population, blood pressure and respiratory depression are more significant and are what are reported in studies evaluating adverse effects.

The Results
Most studies reported no significant difference in efficacy between LEV and PB however 1 study showed that LEV was more effective for clinical seizures (seizures we can see) and not significantly different with electrical seizures (those we can only see on EEG). Another study reported that high dose (20-40 mg/kg/d) PB was more effective than LEV, but regular dose (20-30 mg/kg/d) was inferior to LEV. The seizure control rate in 1 study was 86% with LEV, and 62% with PB. However, the meta-analysis identified that overall, no significant difference was found between the two drugs.
Levetiracetam was the winner in terms of adverse effects! In most studies, LEV had a lower incidence of hypotension and respiratory depression than PB. Neurodevelopment scores (motor, cognitive and language scores) were similar among the two groups with a slightly higher language score in infants that had been treated with PB.
Despite all of this, PB is still the first-line treatment for neonatal seizures according to the WHO (2021) because it controls most seizures, from most etiology, and also decreases the metabolic rate. This might seem trivial, but reduced metabolic rate can improve outcome fairly strongly due to a lack of “work” that the brain must do during the post ictal phase.
 
What do I think? Based on this data, I would favor intravenous LEV at 30-60 mg/kg single dose for neonatal seizures in our patients FIRST, followed by diazepam + phenobarbital second if seizures aren’t controlled.
Thanks for reading! I hope you have a wonderful week and I look forward to working with you soon.

Age, The Neurologic Examination and Seizures

Age isn't a disease, right? No, it isn't but disease is associated with age. The older pet with seizures is more likely to have structural disease (i.e. neoplasia instead of idiopathic epilepsy), compared to the younger pet. That said, none of us want to diagnose a terminal disease in an older patient simply because the patient is older!

Can the Neurologic Examination Help Vets differentiate disease in Older Patients?
Let's look at the two most commonly performed parts of the neurologic examination and see how they related to disease. The menace response and paw replacement testing (previously called conscious proprioception) both assess the forebrain and are some of the most commonly performed parts of the neurologic examination. Here is what a recent group from Australia found in reference to finding evidence of forebrain disease on MRI:

Menace response
Sensitivity: 72%
Specificity: 47%
Odds ratio:  2.26

Proprioception
Sensitivity: 54%
Specificity: 72%
Odds ratio: 3.08

If age is then factored into the analysis, dogs greater than or equal to 6 years of age were more likely to have a forebrain disease detected by MRI if they had a menace or proprioceptive deficit. 

As a "field" neurologist (without a pocket MRI...yet) this tells me that I should encourage diagnostic imaging in patients with menace deficits, and possibly for those with proprioceptive deficits depending on concurrent findings. The chances (or Odds) of a patient having underlying forebrain disease is higher if they have these deficits than if they don't. Seems intuitive, but proprioceptive testing isn't as sensitive as assessing the menace response.
What's the take-away message here? If you have an older pet with seizures, and the neurologic examination is NORMAL, you might miss underlying structural brain disease if you do an MRI but, then again, you might now. If you have an older pet with seizures and a menace or proprioceptive deficit is noted you'll LIKELY MISS a structural brain disease if you skip the MRI. 

Although this TidBit is a repeat from 2020, I liked this study and thought it was worth repeating...again. 

Chan MK, Jull P. Accuracy of selected neurological clinical tests in diagnosing MRI-detectable forebrain lesion in dogs [published online ahead of print, 2020 Jul 15]. Aust Vet J. 2020;10.

Thanks for reading! I look forward to working with you soon. Have a great week!

Myasthenia Gravis in Cats

What is myasthenia gravis?

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

What is the clinical presentation?

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

What causes the acquired form of myasthenia gravis?

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

How should I diagnose myasthenia gravis?

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

What is the ideal treatment?

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

What is the long-term prognosis?

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

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

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

What Role Does the BBB Play in Epileptogenisis?

The blood-brain-barrier is an important player in epilepsy, even if it is an unsung hero. You may (or perhaps may not) recall from veterinary school that there are 3 parts to the BBB. 1) the tight junction (TJ) proteins between endothelial cells 2) the highly specialized and restrictive transport system in the cellular walls and 3) the capillary wall which utilizes a basement membrane, astrocyte feet (I love that they have feet) and little pericytes. The BBB is one of the best bouncers in the system and it takes extreme caution allowing molecules to pass. Over the years we have learned that the BBB plays an important role in epilepsy. For example, disruption of the TJ proteins, most notably upregulation of MMP9 (if you want to know everyone’s full name, please refer to the article) has contributed to the generation of seizures. Conversely, stabilization of the BBB can prevent seizures in experimental models. Leakage of serum albumin, through a dysfunctional BBB, has been shown to bind to TGF-beta on astrocytes and cause astrogliosis (an increase in astrocytes, or upregulation of their function). The development of astrogliosis, followed by some changes in the extracellular matrix causes a DECREASE in the inhibitory protein GABA and INCREASE in excitatory synapses in the brain. Decreasing the inhibitors and increasing the excitatory proteins. Yikes! Bring on the seizures. 

A study was published outlining some novel ways to look at the BBB using MRI (Hanael E, et al from Israel. JVIM 2024). There are parts of that article that I will be skipping for this TidBit Tuesday because they aren't applicable unless an MRI is part of your practice. However, the parts that I think are good for general discussion relate to the location in the brain. Seizures are frequently generated in the piriform lobe, so the researchers looked at that lobe using MRI, histopathology and CSF. They found a significant increase in albumin and MMP9 proteins in the piriform lobe in dogs with idiopathic epilepsy, along with evidence of damage to the BBB on MRI in this region. CSF albumin was increased AND serum MMP9 activity was increased in dogs as well. All of this supports evidence that we are finding damage to the BBB, causing consequences to the brain (specifically the piriform cortex) which is then manifested physically as a recurrent seizure disorder (epilepsy). Perhaps the future will hold some therapies directed at "patching" the BBB as a treatment modality - you'll have to stay tuned!

This week's TidBit Tuesday was a bit heavy on the sciences so I hope you'll forgive me on this first full week of summer. Epilepsy is an ever changing area of study that I find fascinating and hope you don't mind coming along for the ride with me sometimes. Have a terrific week and I hope you can get out and enjoy the sunshine!

Zonisamide Use in Dogs

Guess what? Another study evaluating zonisamide was published recently (this one out of Japan: Saito et al. JVIM 2024). A historical paucity of data about zonisamide has made me hesitant to use this antiepileptic drug (AED) so I’m pleased that times are a changing!
On to the important stuff… This was a prospective multicenter, open-label uncontrolled study in 56 dogs. Several dogs dropped out, so the end result was that 53 dogs were assessed for efficacy and 56 dogs were included for evaluation of tolerability.

Results

To determine an appropriate dose and the target plasma concentrations, many researchers will calculate the mean drug dose and concentration for 50%, 90% and 100% of the responders. They found the following:
50%: dose range was 2.7-4.9 mg/kg PO q12h; no mean trough plasma concentration provided.
90%: mean dose 4.8 mg/kg PO q12h; mean trough plasma concentration 18.9 ug/ml
100%: mean dose 5.5 mg/kg PO q12h; mean trough plasma concentration 21.9 ug/ml
Putting all of this together, the starting dose recommendation by the authors was 2.5-5.5 mg/kg PO q12h for most dogs (reduce this for dogs with renal disease). The recommended therapeutic range is 10-40 ug/ml. However, there are a couple of things to be aware of when using this therapeutic range. First, the study design stated that the dose would be increased incrementally every 1-2 weeks for dogs with persistent seizures until adverse effects were noted OR they reached 15 mg/kg dosing. They did not exceed 15 mg/kg which could affect what is considered an appropriate therapeutic range. Secondly, the dose did not predict the serum concentration, suggesting non-linear PK. What this means is that if you start a dog on zonisamide at 5 mg/kg PO q12h, you cannot necessarily predict the plasma drug concentration. Phenobarbital in cats has predictable PK, but it doesn’t in dogs, for example. Because of this, it’s not completely clear what an “acceptable” starting dose may be for a given individual. How do you decide? It is recommended that you start with the given dose, measure drug concentrations and evaluate adverse effects. If the animal is displaying unwanted adverse effects, the dose is probably too high (regardless of drug concentration). If the animal is continuing to have seizures at an undesirable frequency, without adverse effects, the dose is likely too low. We know that adverse effects happen at higher concentrations AND that organ disease is more likely to occur at higher drug concentrations so do be cautious above 40 ug/ml plasma concentration.
Adverse effects noted in this study were minimal. They reported at least 1 adverse effect in 7 of the 56 dogs. Several dogs were withdrawn from the study due to perceived poor efficacy and adverse effects as well. Adverse effects noted include reduced activity, reduced appetite, vomiting, pelvic limb weakness, soft stools and constipation. All were mild and transient. No elevation in liver values were noted. Remember that this drug is a sulfa derivative so a patient with known sulfa sensitivity should avoid zonisamide. No renal disease or renal tubular acidosis was noted however it has been reported in other dogs receiving zonisamide. 
Seizure control was obtained in 76% of the 53 dogs. A further 55% of dogs obtained seizure freedom. These results are better than the prior study evaluating zonisamide in which about 60% of the dogs were reported to obtain seizure control. The improved results are possibly due to different dosing, or a different genetic epileptic population.

Take home message:
Zonisamide is a viable alternative for dogs either as a primary or as an add-on AED. Start at 2.5 – 5.5 mg/kg PO q12h and measure plasma drug concentrations (yay!!) at 2 weeks.
 
Thanks for reading! I hope you have a great week. Remember to check FB for last minute updates to my schedule through out the summer. Happy Father’s day to all of the dads, dads-to-be and pet-dads out there!