Idiopathic Head Tremor VS Seizures

Idiopathic Head Tremors vs. Focal Seizures

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

What are Idiopathic Tremors?

Good question!

• Tremors are action-related in veterinary medicine.

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

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

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

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

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

How do you differentiate tremors from seizures?

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

How do you diagnose idiopathic head tremors?

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

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

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

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

DATA COLLECTION

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

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

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

Root Signature Sign: Neurologic Lameness

It's Wednesday morning and your first consult is a limping dog. You nod...you've got this. Upon examination you cannot find any evidence of joint pain, muscle or bone pain. Not deterred, you radiograph shoulder to foot. Nothing of interest is visible.

What if the lameness is neurologic in origin, you ask yourself?

The most common causes of neurologic lameness in dogs are cervical disc herniation and nerve sheath tumors. Most dogs have neurologic deficits along with their lameness so it is worth a close look at the neurologic examination. Deficits could include reflex deficits, postural reaction deficits and/or pain.
Side note: Did you know that lameness from a neurologic cause is called a root signature sign?

Cervical Disc Herniation
Cervical disc herniation with resulting nerve root impingement occurs from type I or type II disc herniation. Many dogs have cervical pain along with the root signature sign, but not all. Cervical radiographs are non-diagnostic for cervical disc herniations and therefore not often recommended. MRI or CT/myelogram are the diagnostic tests of choice with MRI providing greater detail. Treatment may be medical or surgical. My recommendations for medical management vary by pet, but typically include a NSAID, gabapentin and a muscle relaxant. Additional management with opioids can also be included. Best rest is often recommended for the first 3 weeks. Surgical management is recommended for medically resistant dogs, or if the MRI or clinical signs are severe.

Nerve Sheath Tumor
Nerve sheath tumors are typically slow growing, locally invasive (eventually into the spinal canal) tumors. These are best diagnosed with MRI. Definitive treatment is surgical removal. If surgical removal is not pursued, supportive care with pain management (NSAID or prednisone +/- opioid), muscle relaxant and gabapentin are recommended. Acupuncture may provide additional pain relief. The slow growing nature of nerve sheath tumors means that clinical signs may be present for months before the pain or debilitation becomes life limiting.

Not sure if the patient you are seeing has neurologic disease? This is one of the main functions of a traveling neurologist (me!). Sorting between orthopedic and neurologic causes of lameness can be challenging, especially if you're not comfortable doing the neurologic examination. Please reach out, you're not alone! You can find me on email, or schedule directly online using my website.

Okay, now that we got that out of the way, enjoy that Wednesday morning lameness evaluation!

Happy St. Patty's Day everyone. I have two kids that do Irish dancing so we're really missing the festivities this year, but we look forward to celebrating next year.

Stay safe, stay kind, and I look forward to working with you soon!

Paroxysmal Dyskinesia

These words are not uttered by many of us on a regular basis (unless you are studying for boards and talking in your sleep). So, why do you need to know what this is? So that we remember that not all things that twitch have seizures.

Paroxysmal dyskinesia's are one, of a group, of movement disorders characterized by abnormal muscle movements UNRELATED to epileptic discharges. If you take one thing away from this email it is this: movement disorders are not seizures. Not that I suggest you stop reading...

How do I identify a Paroxysmal Dyskinesia (PD)?

This group of movement disorders manifest as sudden cramping in muscles and limbs. It has been identified in several breeds, with increased incidence in Terrier breeds. Notably there is no loss of consciousness, no autonomic signs, and upon recovery from the cramping the dogs return to normal function immediately. These cramping episodes can be triggered with specific activities in some patients (activity or exercise is a common trigger) and may last for minutes to hours. When performed, no EEG abnormalities consistent with epileptic discharges are noted.

What diagnostic testing should I run?

Cramping syndromes may be triggered from metabolic causes as well as genetic causes. A CBC, serum biochemistry and urinalysis are a wonderful way to rule out metabolic causes. If normal, assessment of a video can determine if additional testing for seizure disorder should be pursued.

Are there any treatment options?

Yes! Many movement disorders improve with anticonvulsant drugs such as the benzodiazepine class of drugs. One recent report (reference below) detailed successful treatment of a Welsh Terrier with levetiracetam (20 mg/kg PO q8h) to control signs.

Do you suspect you have a patient with a movement disorder? Please reach out for a consultation - I'm happy to help. I truly love working with you and your staff to help patients live their best lives, with neurologic disease. Keep up the good work!

Stay safe - it's almost spring time and we can make it!

Reference:
Green S, Olby N. Levetiracetam-responsive paroxysmal exertional dyskinesia in a Welsh Terrier. JVIM 2021: https://doi.org/10.1111/jvim.16068

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

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

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

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

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

A few more good reminders:

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

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

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

So, what does that mean for us?

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

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

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

Bromide!!

Bromide tablets received conditional FDA approval this month so I thought this was a good time for us to review Bromide and the do's and don'ts of this drug. 

What should clients (and vets) know about bromide?

Bromide is one of my favorite anticonvulsant drugs for dogs. Seizures happen when there is too much excitability or too little inhibition in the brain therefore neurons fire. Making neurons' less able to "fire" reduces seizures. Below are answers to common client questions about bromide.

How does it work?
This drug makes neurons more negative making it harder to fire a nerve. Less firing = fewer seizures. It does not eliminate seizures, nor does it "cure" an epileptic dog.

Has this drug been shown to be safe in dogs (or cats)?
This medication should ONLY be used for dogs. Cats do not tolerate bromide!

How long does it take to be effective?
Bromide has a long half-life, therefore it takes about 3 months to reach the point of maximal expected efficacy (steady-state). You may notice side effects, and clinical improvement sooner than 3 months however, it won't be fully stable (or fully effective) until at least 3 months. Furthermore, this means that when the dose is adjusted, it won't be fully realized until 3 months after the dose adjustment is made. Key point: Don't give up too soon on this drug. It is slooooowww.

Side note for vets: Please try to take a therapeutic serum concentration at 3 months even if the dog is doing well. This is valuable information should they loose that seizure control in the future.

What side effects are common?
Some pets do not demonstrate any clinical side effects. In those that do,sedation, ataxia, weakness, increased drinking, urinating, appetite and occasionally vomiting can be noted. It is important to understand that bromide and phenobarbital have very similar side effects so if the dog is already on phenobarbital and we're adding bromide, side effects may be additive! Don't blame the bromide! Vets: try reducing the phenobarbital a bit and often side effects will improve. We're adding bromide because we think it may help the dog so don't play with the dose too much (if at all) in the first 3 months.

What other life-style changes do I need to make for my dog?
Bromide must be given every day, at about the same time each day. It isn't as picky as some other anticonvulsant drugs so little adjustments in the administration time is usually okay. Vets: I prefer this medication is given 20 mg/kg PO q12h, but it can also be give as 40 mg/kg PO q24h.
Additionally, this drug will be confused with chloride during excretion through the kidney. This means that your dog must be maintained on a "stable" salt diet. Not restricted, just consistent. In other words, feed the same food, and if you must give "treats" give the same treats, every day. A sudden increase in salt consumption can result in a serious decrease in bromide in the body, resulting in seizures. (Think: 4th of July BBQ when the dog steals a hot dog from the table...)

Incidentally, "bromide" also means: a trite and unoriginal idea or remark, typically intended to soothe or placate. Hmmm, I wonder if I can put this in a sentence in everyday life? :)

For some of you, this was a repeat TidBit Tuesday from November 2019. This is one of those topics I think is worth repeating and I hope you agree.

Stay safe, stay warm and be healthy. I'm available Mon-Sat, if you have a question, or a case that needs evaluation.

Seizures vs Syncope

In honor of Valentine's day this past weekend, I thought we might discuss when the heart tries to act like the brain...known as syncope vs. seizures.

Seizures and syncope are both described as a temporary loss of consciousness. Clinical signs of seizures often include collapse, some form of somatic movement, and a display of autonomic activation (e.g. urination, defecation, salivation, pupillary dilation) but these signs can be subtle in some patients. Clinical signs of syncope may also include collapse with occasional loss of bladder or bowel function. However, the pathophysiology, differential diagnoses, diagnostic testing and treatment plans are markedly different therefore differentiation between seizures and syncope is critical! What are my top 5 ways to differentiate between seizures and syncope?

1. Autonomic signs: Loss of bladder control has been reported with syncope and is a common finding with seizures. Other autonomic changes such as loss of bowel function, salivation, lacrimation and dilation of pupils have not been reported with syncope and are regularly reported with seizure disorders.

2. Post ictal phase: blindness, disorientation and at times, aggression can be seen for minutes to hours following a seizure. Animals with syncope may appear momentarily disoriented but typically they are back to normal within seconds of a return to consciousness.

3. Timing of the event – It is more common for seizures to occur when the pet is at rest, and syncope to occur when the pet is in motion or accelerating. We know this doesn't apply 100% of the time but can be a very helpful to ask what the pet was doing immediately before it collapsed.

4. Evidence of metabolic disease: Evidence of metabolic diseases known to cause seizures such as hypoglycemia, hypocalcemia or hepatic failure concurrently identified in a patient with a history of acute collapsing episodes should lead the clinician to consider a seizure disorder. Without a doubt, patients with metabolic diseases can also have concurrent metabolic derangement however I will use this as a tool when trying to sort between seizures and syncope.

5. Neurologic examination abnormalities. This one is obvious. If the pet has neurologic abnormalities that localize to the prosencephalon (forebrain) it is reasonable to consider this lesion localization over syncope. You could turn this upside down and say that if the pet has evidence of a cardiac arrhythmia or cardiac disease, syncope may be considered more likely. I have seen several patients that have been unfortunate enough to have BOTH syncope and seizures but, thankfully, that is rare.

I hope this helps you differentiate between seizures and syncope. Let me know if you have any other ways to differentiate between seizures and syncope in your practice.

Thanks for reading and stay warm, my friends! Remember, if you're working with a dog or cat with neurologic disease, I'm an email or telephone call away! Better yet, schedule a consult and we can work through the case side-by-side.

Steroid Responsive Meningitis-Arteritis

It's a cold Tuesday morning and your first patient today is a painful, 6 month old Boxer dog. You dutifully run through the differential diagnoses in your head as you walk into the room. What you see when you arrive is a depressed, febrile Boxer puppy trying really hard not to move their head or neck and wincing when doing so.
After examination you find the dog has the following neurologic examination findings:
Mentation: QAR, especially for this normally hyperactive puppy
Cranial nerves: normal
Gait: stiff, stilted gait but no evidence of paresis, ataxia or lameness. (Although lameness and paresis CAN happen with steroid responsive meningitis-arteritis, a.k.a. SRMA)
Postural reactions: normal paw replacement in all four limbs
Reflexes: normal in all four limbs, normal c. trunci and perineal (you did a great job!)
Palpation: Oh how the dog winces with cervical palpation! (Don't do cervical ROM on this dog, okay?)

Neuroanatomic lesion localization: Well...technically the neurologic examination is all normal, right? So all you can say is "cervical pain" on the record. No neuroanatomic lesion localization when they are neurologically normal.

Differential diagnoses: Trauma, fracture, subluxation, muscle strain, infection/polyarthritis, and yes, SRMA.

What is SRMA?

It is an immune mediated disease that affects the vasculature of the meningitis, and sometimes the joints and it typically affects dogs < 2 years of age, with large breed dogs and beagle dogs over represented.

How do you diagnose it?

First, rule out other causes (radiographs, spinal MRI). Next, perform a spinal tap and identify a neutrophilic pleocytosis (often with a SUBSTANCIALLY increased cell count!). Third, rule out infectious diseases that cause meningitis in your area of practice. For most of us in Wisconsin, this is Neospora (toxoplasma if cat), fungi, and bacterial causes.

What is the recommended treatment?

Steroids at 1-2 mg/kg PO q12h, depending on the literature. I start with 1 mg/kg PO q12h for 30 days and then reassess the CSF. Some studies suggest doing this dose, or a slightly tapered dose, for up to 3 months and then reassessing the CSF. When normal, a gradual taper over 3-6 months is common. Relapses can occur in up to 80% of the studies published but my experience has been a much lower recurrence rate.
A recent study by Giraud et al* found a lower relapse rate with the addition of azathioprine. They used 2 mg/kg PO q24h x 1 month and then tapered from there to an every other day dosing interval for 2 months for a total of 3 months of treatment. The authors suggested that the addition of azathioprine allowed them to reduce the prednisone dosage sooner and more rapidly, thus reducing long-term side effects. Over 80% of the dogs in this study were in clinical remission within the 2 year follow-up time without signs of relapse.
Azathioprine was also reported to have exceptionally long survival times when used in combination with steroids to treat meningitis of unknown etiology (MUE), another immune mediated CNS disease. So...perhaps we're on to something here! Interestingly, azathioprine was suspected not to cross the blood brain barrier initially. Hummm...

Key Points:

• SRMA is often treatable, but relapses do occur.

• A CSF tap is needed to confirm the diagnosis however MRI is often performed before CSF to rule out physical/structural abnormalities. This helps to decrease the risk of harm from a spinal tap.

• Steroids are the mainstay of treatment but azathioprine may be added to allow a more rapid reduction of steroids (thus reducing long-term side effects from steroids).

Have a great week and stay safe out there! It's been a snowy few weeks here in Wisconsin so drive safely if you're out and about!

Anisocoria

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

Anisocoria

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

Neuroanatomy

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

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

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

Putting it together

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

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

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

Neospora caninum: Update!

Medical Review: Neospora Myositis

You might be wondering why on Earth I'm talking about Neospora as a small animal vet. (Neospora causes abortion in cattle!) It infects dogs too!! Some of you have seen some positive cases with me throughout 2020 so, I thought it was worthwhile doing a mini-review so we could all brush up on it together.

Etiology: Toxoplasma gondii and Neospora caninum may cause myositis, peripheral neuritis or CNS meningoencephalitis.

Signalment:

Breed: any
Age: may be acquired in utero leading to signs at a very young age (months), or by consuming raw or under cooked meat causing signs at any age. **Adult onset is what I see most commonly. However, the dog pictured above was a puppy that presumably acquired it in utero.

Clinical signs: Stiff gait, muscle pain (myalgia), muscle atrophy. Note: Muscle atrophy can be anywhere including the muscles of mastication. I have been tricked into thinking a dog has MMM when in actuality it had Neospora myositis causing unilateral muscle atrophy in the masticatory muscles.

Diagnostic tests: IFA > 1:200 for Neospora caninum is consistent with an infection, however documentation with a repeated titer is recommended as a confirmatory test. Muscle biopsy showing the encysted organism is definitive but obviously the most invasive route.

Treatment options: Sulfadimethoxazine/ormetoprim (15 mg/kg PO q12h) or clindamycin (10 mg/kg PO q12h) twice daily is recommended for 4-6 weeks, possibly longer. Be aware that sulfa antibiotics can cause idiosyncratic myopathic drug reactions too!

Prognosis: Good, if treatment is started before severe muscle atrophy or fibrosis is present. Prognosis is poor if clinical signs are severe, or chronic.

Frequency: Uncommon, but not unheard of!

Voila! TidBit Tuesday-style update on Neospora caninum. 😊

Final question: When do I run the IFA? Answer: Any dog with a history of muscle pain, muscle atrophy (not explained by neuropathic disease) or an elevated CPK should have a Neospora titer performed. This disease is sneaky so I err on the side of caution and suggest running the test rather than getting caught unawares.

Be safe, be strong and keep those referrals coming!
Heads up for those of you in my referral area: I will be closed Thursday January 28th to celebrate my youngest kiddo turning 5 years old. My, how time flies! I apologize for any inconvenience this may cause and look forward to consulting with you on another day!

Prognostic Indicators for Acute Myelopathy

Acute Paraplegia: When to ship for surgery, treat medically or consider euthanasia

It happens to all of us (perhaps to me, more than you). Monday morning, 9 am, we are presented with a dachshund (Shih Tzu, Corgi...pick your top chondrodystrophic breed) after the dog became acutely non-ambulatory over night.

You perform a neurologic examination (self high-five!) and determine that the dog has a T3-L3 myelopathy with spinal pain at the TL junction.

What do you do next?

To be clear, a T3-L3 myelopathy does NOT equal a type I disc herniation. It means the dog may have a type I disc herniation or it could have a fibrocartilaginous embolic myelopathy (FCEM), acute non-compressive nucleus pulposus extrusion (ANNPE) or in rare cases meningomyelitis. (Yes, even dachshunds can get meningomyelitis!)
If we play the odds, that chondrodystrophic dog likely has a disc herniation. What, if any, prognostic indicators can you provide to the client?

Thankfully, an article out of Frontiers in Veterinary Science entitled "Prognostic Factors in Canine Acute Intervertebral Disc Disease" was published in November 2020 for just this purpose! (1) Here are some key points from the article. (The entire article is available as an open access article if you wish to read it in it's entirety. I highly recommend doing so if you are in the habit of seeing paraplegic dogs.)

Prognostic Indicator Key Points:

• Recovery following medical management (only) for dogs with paraplegia (loss of all voluntary motor) and loss of deep pain perception (DPP) is about 22.4%.

• Recovery following medical management (only) for dogs with paraplegia and intact DPP is 56%.

• Recovery following surgical management for dogs with paraplegia and loss of DPP is about 61%.

  • 25% recovered at 2 weeks

  • 42% recovered by 4-6 weeks

  • 53% recovered by 12 weeks

• Recovery following surgical management for dogs with paraplegia and intact DPP is about 93%.

*** Did you catch that?? DPP is a prognostic indicator! Dogs without DPP do worse long-term compared to dogs with intact DPP. They are also have a 10x higher likelihood of developing progressive myelomalacia which is a fatal secondary outcome from acute spinal cord injury.

What exactly does "recovery" mean? It means walking without support but it DOESN'T mean walking normally or complete continence. Dogs may (and often do) have fecal or urinary incontinence consistently or occasionally following severe spinal cord injury.

Other Key Points:

• Spinal shock can be more commonly associated with long-term fecal incontinence but does not seem to affect the ability to recover ambulation.

• Age, breed and weight are not associated with prognosis...mostly. Some studies have found heavier dogs have a worse prognosis, other's haven't. My take - bigger dogs are harder to care for but that doesn't mean they cannot recover.

• Reduced pelvic limb reflexes due to a L4-S3 lesion (not associated with spinal shock) has a higher likelihood of incontinence long-term.

When do you send a dog for surgery?

1) if the dog is non-ambulatory or paraplegic and the clients have a desire and financial ability to pursue surgery. Surgery with imaging costs $2000-5000 USD, depending on the specialty referral center.
2) Rapidly progressive signs (E.g.: dog was walking at 8 am, and is paraplegic at 10 am, with loss of deep pain by noon) and clients wish to pursue surgical intervention if indicated after imaging.

My plea...

Please don't send clients several hours to a specialist for surgery only to discover that the cost is prohibitively expensive. It is heart breaking for everyone and unnecessarily stressful for the dog. Call me and I'll happily talk with you about consult/medical management choices or sadly advocate humane euthanasia for the dog, if it is the best option.

Stay Safe, Keep Keeping On and Have A Good Week!

(1) Olby Natasha J., da Costa Ronaldo C., Levine Jon M., Stein Veronika M. Prognostic Factors in Canine Acute Intervertebral Disc Disease; Frontiers in Veterinary Science. 2020:7 p 913.

Monoparesis following Vehicular Trauma

How do you sort out a cat or dog with thoracic limb monoparesis following trauma?

This is an important question. First, let's review the innervation to the front leg. (Get back here - it's not that bad!) There are two important nerves that guide weight bearing and movement in the front leg:
1) Musculocutaneous - exits spinal cord segments C6-8. Important innervation is biceps muscle but it does a few others. The important action is flexion of the elbow and extension of the shoulder
2) Radial - exits spinal cord segments C7-T1 +/- 2. Innervates triceps and the muscles on the cranial distal limb that extend the carpus. The important action is extension of the elbow and carpus for weight-bearing.

So, to weight bear there must be an intact radial nerve. To move the limb forward there must be an intact musculocutaneous nerve. The other nerves (supra and subscapular, axillary, median and ulnar) are important too, but not as important. If you want to remember only two nerves, remember radial and musculocutaneous.

Now that we have that over with, let's put this to practice. Here is the scenario: You are presented with a 1 year old cat with a history of vehicular trauma a few days ago. The cat is presented dragging the left thoracic limb, unable to bear weight. When you watch it walk you can see advancement of the shoulder and elbow but it is minimal.
Question: What nerve is affected MOST?
Answer: Radial
Question: What spinal cord segment does the radial nerve arise from?
Answer: C8-T1 or 2.

Really good question: What is this cat's lesion localization?
Answer: Let's do a neurologic examination! :)

Neurologic exam:
Mentation: BAR
Cranial nerves: normal (note Horner's can be seen with thoracic limb injuries but isn't seen in this cat).
Reflexes: Absent triceps, absent withdrawal of the left thoracic limb. Unable to detect bicep or extensor carpi reflex (hey, it's a cat, give me a break!). All other limbs have normal withdrawal and pelvic limbs have normal patellar reflexes.
Palpation: non painful
Proprioceptive testing: absent tactile placing left thoracic limb, absent tactile placing left PELVIC limb, normal entire right side.
Gait: left thoracic limb monoparesis as previously described.

Now you can properly answer the previous question.
With absent radial nerve and diminished musculocutaneous innervation to the left leg, we KNOW the lesion must involve C6-T2, correct? (It's absent because of the missing withdrawal reflex - mediated through largely the radial nerve but also musculocutaneous too.) The real question here is this: is the injury in the plexus only or is there evidence of spinal cord involvement? To answer that question, you must look downstream from the affected segment. This means, look at the left pelvic limb. This limb has absent tactile placement so there has been disruption to the spinal cord tract going from the brain to the left pelvic limb, and back again.
Answer: This cat has a C8-T2 spinal cord lesion.

The differential list must now include things that affect the spinal cord such as avulsion and a disc herniation, hematoma or hemorrhage. Your diagnostic plan would include advanced imaging of the spinal cord. If the lesion localization had been peripheral plexus (not spinal cord) you would consider a brachial plexus avulsion only and advanced imaging would not be indicated. Knowing the lesion localization can markedly change your differential diagnoses, diagnostic plan and ultimately treatment and recovery!

Not sure about this case? Feel free to email me! This TidBit Tuesday is a slightly altered version of a real case seen recently. Keep those consults coming so we can share the knowledge folks! Please email/call/text me to schedule a consult or hop on my website and utilize the online scheduler to find the best time.

Have a good week!

Midazolam as a Constant Rate Infusion (CRI)

We Tell Clients: Seizures Should Be Stopped ASAP. But...Why?

1. Prevent brain damage

2. Prevent secondary systemic problems such as hypoperfusion, acidosis and possibly hypoglycemia if prolonged.

Okay, fine that's reasonable. But how, and when do I use a CRI?

My rule of thumb for dogs and cats with seizures is to recommend hospitalization with placement of an IV catheter and initiation of a constant rate infusion if a pet has more than 3 seizures in 24 hours. (At home cluster buster care is another TidBit Tuesday.) Once seizure control has failed at home, it is time for hospitalization.
Diazepam is the mainstay drug intervention however diazepam shortages and a growing recognition of phlebitis secondary to IV diazepam has lead to a greater use of midazolam. Full disclosure, I have used midazolam without hesitation for more than 12 years but...sigh...we didn't have scientific literature to support it's use, until now!
A study out of North Carolina State University by Dr. Bray and colleagues (two of whom were my resident mates way back...) described the use and safety of midazolam CRIs in dogs with status epilepticus and cluster seizures.

The findings, in a nutshell:

• 106 dogs including 40 with idiopathic epilepsy, 16 unknown seizure etiology, 43 structural epilepsy and 7 with reactive seizures. --> I suggest that this heterogenous population provides us challenges with efficacy studies but at least we have something!

• Median start dose was 0.25 mg/kg/hr., range 0.1-0.75 mg/kg/hr. (Remember it has a 20% higher binding affinity than diazepam)

• Seizure control was obtained in 82 dogs (77% of the population) including 49 in which no dose adjustment was needed and 25 in which dose escalation was required to control signs and a further 8 in which 1 single additional seizure occurred but they still considered it control. (Hmmm, this group doesn't meet their criteria very well.)

• Adverse effects were reported in only 24 dogs (22.6%) which included sedation, vomiting/diarrhea, hyperexcitability, ataxia and polyphagia. No reports of phlebitis, as expected.

• Median time to control was 13 hours and CRI duration was 25 hours.

The main limitation to the study, from my point of view, is the heterogenous population. We suspect poorer seizure control in dogs with structural epilepsy than those with idiopathic epilepsy. This was also noted in the study wherein control was obtained in 85% of dogs with idiopathic epilepsy and 74% of dogs with structural epilepsy. This difference, however was not statistically significant.

Take Home Message

• Continue to use midazolam, with a starting dose of 0.2 mg/kg/hr. (Now with data to support it's use!!)

• Expect success in most patients, regardless of the underlying cause

• Plan to use it for at least 12 hours, but possibly longer

• Phlebitis is not expected, unlike with diazepam!

Want more? The full article can be found online (open access):
Bray, KY, Mariani, CL, Early, PJ, Muñana, KR, Olby, NJ. Continuous rate infusion of midazolam as emergent treatment for seizures in dogs. J Vet Intern Med. 2020; 1– 9. https://doi.org/10.1111/jvim.15993

Welcome to 2021!! I look forward to continuing to work with you, and your staff.

Seizure management is my passion - please call/email or have me out for a consult if you have a seizure case!

Happy New Year!

Happy New Year!
Good bye 2020 and hello 2021!

This year I have learned:

1. I'm more resilient then I thought.

2. My kids are fragile, and yet stronger than I gave them credit for.

3. I love working, especially as your "pocket neurologist"!

Things I am looking forward to in 2021:

1. Going swimming in a swimming pool (not a lake). I'm tired of seaweed...

2. Playing with my children at parks without fear of their (and my) exposure to a potentially deadly disease.

3. Traveling to a city in Wisconsin or Illinois that I haven't yet been to (come on Northern Woods vets!!).

4. Hugging!!

5. Continuing to work with all of you wonderful, dedicate, kind, strong and resilient veterinarians and veterinary staff. YOU are whom I look forward to when I go to work!
   

Wishing all of us a happy, safe and prosperous New Year!

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.

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! :)

As always, please stay safe, and mentally and physically healthy out there. I love working with you and look forward to continuing to do so.

Please note that I am performing consults through December 25th and then I will be modifying my schedule through January 16th because of my concern for increasing COVID numbers following the holidays. As many of you know, I have an at risk kiddo so I am super-duper cautious. If you need a consult between December 25th and January 16th please email me to discuss options.

Happy Hanukkah to those of you also celebrating!

20% of dogs receiving AEDs have dermatologic reactions??

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

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

What signs are seen?

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

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

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

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

• Pruritus and/or alopecia (3 dogs)

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

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

How was it managed?

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

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

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

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

Meningitis...Encephalitis...?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Stay Safe, and Happy December Everyone!

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

Tetanus and Animals

Tetanus and Animals

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

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

Signs

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

Treatment

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

Prognosis

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

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

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

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

BREAKING NEWS: Phenobarbital causes side effects in cats!

Phenobarbital and Cats

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

Misconception.... TRUTH

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

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

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

What is the Take Away Message?

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

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

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

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

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