Bacterial Meningitis in Dogs

Bacterial meningitis or meningoencephalitis is rare in dogs. A recent study evaluated clinical presentation, treatment and outcome in a group of 24 dogs. It is good to note that these 24 dogs were accrued over 10 years from 5 different referral clinics, reflecting the rare nature of this disease. That said, when I suggest meningitis as a differential diagnoses to clients, many of them assume I mean bacterial meningitis. Immune mediated meningitis makes up about 98% of the cases of dog meningitis we see however, infectious meningitis is still possible! I thought we could review bacterial meningitis in light of this recent publication from the UK. 

What is a typical presentation for bacterial meningitis?

For humans, pyrexia, cervical hyperpathia and altered mentation are the three signs often attributed to bacterial meningitis. About 20-45% of people present with all three signs and most of these are older people. In the recent study (https://doi.org/10.1111/jvim.16605), only 2 dogs (8%) had all 3 signs, 4 dogs (17%) had only 2 signs and 12 dogs (50%) had 1 of these signs. The remaining 6 dogs did not have any of those three signs. Almost 1/2 of the dogs presented with vestibular signs and were diagnosed with bacterial meningitis secondary to otitis media/interna. The conclusion of the authors was that an absence of these signs should not exclude a diagnosis of bacterial meningitis. I would add to this that the presence of those three signs is not pathognomonic for bacterial meningitis either!

How is it diagnosed?

Positive CSF culture, observation of intracellular bacteria on CSF analysis or (in rare cases) positive outcome with antibiotic treatment only were the diagnostic criteria for the aforementioned study. Less than 40% of CSF cultures were positive! Culturing CSF has always been incredibly low yield which is why we don't do it very often in veterinary medicine. Urine and blood cultures were all negative in this study. Most often, intracellular bacteria were noted on CSF evaluation. A combination of MRI or CT and cerebrospinal fluid analysis resulted in the diagnoses for most of the patients in this report. The few dogs were diagnosed with bacterial meningitis without intracellular bacteria, and without a positive culture, but with a positive response to antibiotics. This last group *probably* had bacterial meningitis but I feel a little unsure including it a published study. 

Treatment and Outcome

The median duration of antibiotic therapy was 8 weeks but there as no real standardized treatment. In humans, treatment times range from 1-4 weeks. The antibiotic chosen seemed clinician dependent and ranged from amoxicillin to cephalosporines, second generation fluroquinolones. About 75% of dogs received a glucocorticoid before referral or at the referral center. Glucocorticoid use is controversial but has been shown to be useful in human medicine to reduce inflammation in the acute stage of disease. The current study was too small to make any conclusions about the utility of glucocorticoid steroids in bacterial meningitis with dogs. Outcome was favorable in the dogs in this study. Survival data for longer than 21 days suggested that about 1/2 of the patients had residual deficits, the remainder did not. The majority (19 of 24) survived to 21 days. 

Although rare, bacterial meningitis or meningoencephalitis is a complicated and potentially life-threatening CNS infection that is worth keeping on our radar. Although immune mediated forms are much more common, we always check for infectious meningitis before instituting immunosuppressive doses of steroids whenever possible for this reason!

Have a great week! I'm back to my usual schedule so if you cannot find a suitable time spot please email me; I'm sure we can work something out!

Case Based Practice

Lesion localization is one of those things that can be lost, if not practiced. This week, we’re going to work out those muscles.

Maria, is a 13 year old FS Lab
History: Presented to me with a 24 hour history of acute onset difficulty walking. 

Neurologic examination:
Mentation: BAR
Cranial nerves: right head tilt, rotary nystagmus, remainder normal.
Gait: Moderate vestibular ataxia, falling right. No hypermetria or intention tremors noted. 
Postural reactions: absent right thoracic and right pelvic limbs, normal other limbs
Spinal reflexes: Normal all limbs, normal c. trunci and perineal
Palpation: non painful, normal cervical ROM

You know what you've got to do now, right?

What is the Neuroanatomic Lesion Localization?

There are several ways to go through lesion localization.

OPTION 1:
I like to make lists. Start by listing all of the abnormalities and ALL possible locations that could result in an abnormal finding. For example:
1) Right head tilt - peripheral CN 8 (right), medulla (right), cerebellum (right or left)
2) Rotary nystagmus - same as above
3) Vestibular ataxia - same as above
4) Reduced paw replacement right side - right C6-T2, right C-C5, right medulla, right pons, right or left midbrain, left prosencephalon.

Now, we start to clump things. Well, for starters any animal with cerebellar disease is expected to have hypermetria and/or intention tremors and Maria did not. We can cross out cerebellar disease. What else? What is the one spot where all of the signs can be explained? That's right - medulla on the right! Voila, lesion localization. 

OPTION 2:
The other way to work through this is to identify the cranial nerve affected on the exam (in this case, cranial nerve 8), identify the brainstem segment associated with this cranial nerve (in this case, medulla) and then ask yourself if you can identify if she has a) paw replacement deficits b) hemiparesis and/or c) mentation changes. . If not, it is peripheral and if so, it is brainstem. 

Differential Diagnoses

Brain stem vestibular disease in an elderly dog without an important prior medical history would suggest the following differential diagnoses:
Degenerative: none
Anomalous: none
Metabolic: Hypothyroidism
Neoplastic/nutritional: Neoplasia of the brainstem
Infectious/inflammatory/idiopathic: meningoencephalitis (infectious or inflammatory)
Trauma: no supportive history
Vascular: Cerebrovascular accident (stroke)

Final diagnosis: cerebrovascular accident (stroke). 

Please reach out if you have a case that is troubling you, a client that needs reassurance that you're doing all you can, or simply have a question. I hope you have a great week!

Idiopathic Geriatric Vestibular Disease of Dogs

Idiopathic Geriatric Vestibular Disease

If I had a dime for every time a client told me their dog had a stroke (usually "several years ago") and that they suddenly were dizzy, and then, suddenly got better, I'd be rich. Or at least I could by myself a soda. :)

Idiopathic Geriatric Vestibular Disease is Not Caused by a Stroke

Human strokes happen suddenly, and can cause signs such as hemiparesis, hemifacial weakness, and often resolve over time so it is reasonable that a stroke would be confused with the canine idiopathic geriatric vestibular disease (IGVD). But they are different! Strokes occur at the level of the brain, brainstem, or cerebellum, and IGVD localizes to the peripheral vestibular system. 

What is Idiopathic Geriatric Vestibular Disease?

As the name implies, we have yet to find the etiology. Several proposed causes have been postulated but none confirmed. Clinical signs include:
1) Acute onset vestibular signs (head tilt, nystagmus, vestibular ataxia, positional strabismus)
2) NO evidence of ipsilateral hemiparesis (weakness on the same side as the head tilt)
3) NO evidence of ipsilateral paw replacement deficits. Some older dogs have unrelated or preexisting paw replacement deficits. If the deficit involves both pelvic limbs, equally, or a contralateral limb to the head tilt, the odds are strong that the deficit is unrelated to the vestibular signs. 
4) NO mentation changes (obtunded, stupor, coma).
5) NO evidence of hypothyroidism, otitis media/interna, neuritis or peripheral/ear neoplasia 

Options 2-4 above help you localize the lesion to the peripheral system, but that is just a localization. Options 1 and 5 help you eliminate the other differential diagnoses that could also cause peripheral vestibular disease and thus, narrow the diagnosis to idiopathic geriatric vestibular disease. 

Treatment

Treatment for IGVD is supportive. Steroids, antibiotics and NSAIDs do not improve clinical signs. Signs typically begin to resolve within 48 hours of the onset, and have reached a state of stability by 30 days. The most marked improvement typically occurs in the first 14 days. Supportive care with anxiolytics (diazepam, trazodone, other), antivertigo drugs (meclizine, ondansetron), and nutritional support may allow the animal to be more comfortable during the recovery process. Clean, dry bedding with frequent comfort checks are important for non-ambulatory dogs to minimize bed sores and other complications. 

Prognosis

Dogs with IGVD have some of the most severe clinical signs but have a very good long-term prognosis! Intensive supportive care is important in the first few days. Most dogs will recover to a functional state within 1 week and return to baseline within 30 days. Importantly, the head tilt is often permanent!! Please be sure to inform clients of this, otherwise they may think the dog is still clinically affected months and years after the signs have otherwise resolved. 

Please let me know if you have a dog with vestibular disease that you feel would benefit from an evaluation. I look forward to working with you soon.  Have a great week!

Levetiracetam use in Cats

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

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

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

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

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

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

Have a great week!

Rabies: It's Still Out There

Last week, the CDC announced the death of a 7 year old Texas boy from Rabies virus infection. I was saddened for his family, and thought this would be a good time to remind ourselves about this virus. As of October, 14 cases of rabies had been identified in the State of Wisconsin; all 14 were in bats. It's still infecting animals, and therefore a risk to humans, too. 

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). 

Once neurologic signs are present, progression is rapid, and most animals will be dead within several days. The CDC report says that the boy was bitten by a bat 2 months prior to onset of signs and that he became deceased after 22 days of clinical signs. 

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 other rabid, or wild, animals.

Diagnostic Tests

  Key point: 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. Due to the neurotropic nature of rabies it can remain undetected by the immune system and therefore cause a negative (false negative) RFFIT antibiotic result.

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! Rabies virus infection is something I think about daily and is one of the more daunting zoonotic diseases we are faced with. Please reach out if you have any questions!

Please note: If you use my services for live or video neurology consultations, fees are changing January 1, 2023. Please email for an updated fee schedule.

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

Thank You and Happy New Year!

This final week of 2022, I am thinking of you and your staff.

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

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

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

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

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

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

Most of all, thank you for being you!

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

If you missed a TidBit Tuesday, or misplaced an email, you can always find them on the blog at https://barnesveterinaryservices.com/new-blog. I'm always happy to add new subscribers so don't forget to sign up new vets in your practice!

Happy New Year and thanks for reading. :)

Myoclonus - what does it mean?

Myoclonus is defined as a sudden onset jerking motion. How is this different from a tremor? Tremors tend to have a creshendo, decreshendo appearance where as myoclonus has been described as "square form" impulse with sudden, rapid onset, sustained contraction, and sudden stop. Okay, fine, it's not a tremor. How do I diagnose myoclonus? 

There are four common types:
1) Physiologic - the classic example is hiccups.
2) Epileptic- occur with or around epileptic seizures
3) Idiopathic - unknown origin or cause (rare in veterinary medicine...or we're just missing it.)
4) Symptomatic - due to an underlying pathology. For example, distemper virus. 

Neuroanatomic lesion localization:
1) Cortical - usually associated with myoclonic seizures. 
2) Subcortical (brainstem) - "falling asleep" myotonia. In this case, people or animals will suddenly "jerk" just as they fall asleep. Classically, this has been thought to occur because the cortical functions "turn off" before the brainstem functions but this may not be the complete story. 
3) Peripheral - an example is hemifacial spasms, or ocular spasms (have you ever had your eyelid  twitch annoyingly and you cannot stop it?)

Veterinary neurologists are often consulted for symptomatic and epileptic myoclonus. Although there is a population with idiopathic myoclonus, it is rare. Symptomatic myoclonus occurs at rest, asleep, or during motion. Symptomatic myoclonus does not stop with sleep! The animal may appear aware or unaware of the twitch. If the contraction is happening in a body part used for walking or eating it may be life limiting. If not, animals may live with a myoclonus with minimal disruption. Epileptic myoclonus occurs around a time of seizure activity and is therefore often managed with anticonvulsant management.

Distemper virus is a common cause of canine myoclonus and CNS infections (various causes) have been cited as causes of feline myoclonus. There is no treatment available for distemper virus therefore, patients are monitored for progressive neurologic signs (mentation changes, gait changes, seizures, other) and euthanized if signs are progressive. If the signs are not progressive, usually myoclonus is not a reason for euthanasia. 
That's all I have for you today! I hope you enjoyed this TidBit about myoclonus and feel better prepared when you see it in your exam room. :)

Thank you for reading! May you have a wonderful, twitch-free holiday week! 

Neuroanatomic Lesion Localization Practice book!

It's Here! The Small Animal Neuroanatomic Lesion Localization Practice Book by yours truly!

It's always hard to self promote, so instead I wish to draw your attention to the many neurologists that contributed cases that made this little workbook the workhorse that it is.
1. Dr. Helena Rylander (UW-VC neurologist)
2. Dr. Joy Delamaide-Gasper (MVS neurologist)
3. Dr. Kari Foss (U of I neurologist, and former student)
4. Dr. Devon Hague (U of I neurologist)
5. Dr. Julien Guevar (Swiss neurologist and former UW-VC Neurologist)
6. Dr. Susan Arnold (U of Minnesota Neurologist and UW- VC graduate)
7. Dr. Sam Long (Australian neurologist and all around amazing guy)
8. Dr. Simon Platt (Forum UGA neurologist and ACVIM-Neurology past president)

The Small Animal Neuroanatomic Lesion Localization Practice Book is just that - a practice book - geared for general practitioners, students, and interns who are interested in brushing up or dusting off their neuroanatomic lesion localization skills. This little ditty has 7 chapters, with many cases in each chapter for you to try your hand at neuroanatomic lesion localization.

Not enticed enough?? If you get stuck - you know the author of the book and can email me directly for help! (yay for connections!)

Still not enticed?? Check out this link to see more: https://www.cabidigitallibrary.org/doi/10.1079/9781789247947.0000
Cost $65 USD

Note: I don't get any notifications of who buys a book, but if you suddenly stop consulting I'll assume you bought the book and learned it all and no longer need me. I really should stop trying to teach myself out of a job.... :)

That's it for this week. Not a typical TidBit per se, but hopefully you don't mind so much. Thanks for reading!
Have a great week!

Bruxism and Forebrain Disease

Bruxism is defined, in human medicine, as repetitive, involuntary, masticatory muscle activity, often appears as grinding teeth, bracing or thrusting of the mandible. There are two types: awake and asleep. Asleep bruxism is quite commonly reported in humans and can be triggered by stress or anxiety. Awake bruxism, or uncontrolled bruxism during awake states, is a very different thing. Awake bruxism (AB) can be broken into pathologic or physiologic causes. Physiologic causes don't apply to veterinary medicine so let's dig deeper into pathologic, awake bruxism. Within the pathologic group there are idiopathic causes and symptomatic causes. Neurologic diseases such as inflammatory conditions, traumatic or congenital disease, epilepsy and a host of other causes have been reported to be associated with awake bruxism in humans. A recent article, published in the JVIM, noted that bruxism secondary to a neurologic cause is most commonly awake bruxism.

Have you seen a dog with Bruxism? The recent article by Liatis T, et al, evaluated AB in 4 dogs over a span of 11 years so don't feel badly if you've not seen one! A link to the entire report is found at the bottom. Although previously reported in dogs with congenital storage disorders, it is rare in mature adult dogs. In this study, two dogs were presented by the owners with a complaint of AB, along with other clinical signs of neurologic disease. AB was noted in the second two dogs by the attending clinicians during evaluation. AB was episodic in all four dogs, occurring throughout the day and always stopped when distracted. No post ictal signs were noted and no autonomic signs were seen during or after the event. All four dogs had forebrain lesions!

Take away: If you evaluate a dog for awake bruxism, or if you note it during the exam while evaluating the pet for other neurologic abnormalities, consider it abnormal. It is not pathognomonic for forebrain disease but, at least according to this report, is strongly supportive of a forebrain lesion. This may be an indication to get a neurology consultation and advanced imaging.

Link: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16570?campaign=wolearlyview

Thanks for reading! I look forward to working with you again soon.

Exercise and Seizure Control

Last year we talked about a temporal relationship between seizures and exercise. It has been shown that seizures rarely occur DURING exercise.

Recently, I was involved in a study, performed at the University of Wisconsin, evaluating increased activity and it's relationship to seizure development. In this study, dogs were tracked using a FitBark(tm) exercise tracker for 3 months and then prescribed a 20% increase in activity over the next 3 months. Seizure frequency and "seizure days' (the number of days that a dog has a seizure) per month were evaluated. Unfortunately, many of the dogs did not actually do the exercise increase as prescribed (ugh!) but even accounting for that, exercise was not associated with a statistically significant reduced seizure frequency or number of seizure days during the study period.

Why didn't this work? There are many possible reasons why prescribed exercise didn't change the seizure frequency. The most obvious reason is that not enough pets made the change to show a statistical difference. The other, more concerning option, is that exercise really doesn't have an effect on overall seizure performance. There are mixed results in the human epilepsy studies. Although it is rare to have seizures during activity, it can happen. Furthermore, some studies showed a lower seizure frequency when exercise was added to a treatment plan and other studies did not.

What is the take home message? Increased activity cannot (yet) be used as an adjunctive treatment for seizure management. It is still a healthy choice, and should be encouraged in all pets but especially our dogs with epilepsy but not, sadly, as a means to seizure control. This was a small study, so my hope is that future studies will yield more robust results.

Thanks for reading! If you want to read the whole study you can find it here: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jsap.13568

Have a great week. Happy Thanksgiving! Enjoy exercising with your pets, friends, and family this holiday week!

Dogs Fall in the Fall

Today, you're presented with a 4 year old German Short-Haired Pointer with a history of rapidly progressive difficulty walking. Although your heart rate may be going up when you read this on your schedule, you're calm, cool and collected as you pick up your pleximeter and head into the room.

Your technician has provided the following history for you: The pet was out hunting last weekend with the owner and no unusual circumstances occurred. He did run away two days ago and came back with a small bite wound on his muzzle. The pet is up-to-date on vaccination (including rabies) and has not had any change in voiding habits prior to the last 24 hours. The dog is fed a mixture of a commercial kibble diet and raw meat. There is no reported prior medical history. 

Physical exam: Unremarkable other than the bite wound. It is healing, not infected (visual inspection only) and does not appear to be bothering him. He is his typical, high strung, friendly self!

Neurologic examination:

Mentation: BAR

Cranial nerves: normal

Postural reactions: Absent in 3 of four limbs, reduced in right front limb only. 

Reflexes: Absent patellar reflexes bilaterally, absent withdrawal reflexes in both pelvic limbs (but he howled pitifully when you tried to do it!) reduced withdrawal in both thoracic limbs, more notable on the left thoracic limb than the right. Absent cutaneous trunci reflex to T6 on the left, and reduced to T/L junction on right. 

Palpation: non-painful on palpation but hyperesthetic when trying to do reflexes. This is unusual for him as he doesn't typically mind his feet touched or even flinch during vaccinations. 

 Gait: Non-ambulatory tetraparetic with paraplegic (no motor observed in PL), marked paresis in both thoracic limbs, more noted in left than right. 

Neuroanatomic lesion localization:

First, decide if this is brain or spinal cord.

1. Brain: With reduced reflexes, it isn't a brain problem.

2. Spinal cord: It could be a spinal cord problem, but then it must be localized to BOTH C6-T2 and L4-S3 (entire plexi for both sites) and, although possible, it is highly unusual. If that is where we localize the problem, how do we account for the c. trunci reflex? Based on the findings, it should suggest a lesion mid thoracic lesion (1-2 segments cranial to the cranial most reflex) and that doesn't fit in either C6-T2 or L4-S3 segments, does it? No. Therefore, this isn't a spinal cord problem either. This is neuromuscular, my friends!

Neuromuscular neuroanatomic lesion localization.

We can narrow it down further within the neuromuscular localization. You have 3 choices: 1) Muscle 2) neuromuscular junction and 3) nerve. Dogs with myopathies (muscle disease) have normal reflexes (and he doesn't) so it isn't a myopathy. Dogs with disease of the neuromuscular junction have absent reflexes (and he does), so it could be this. Dogs with a peripheral neuropathy often have patchy loss of reflexes (and he does) so it could be this. Therefore, you would suspect either a neuromuscular junctionopathy or peripheral neuropathy in this dog. 

Differential diagnoses:

1. Junctionopathy - botulism, tick paralysis, coral snake envenomation, Ca blockers, acute myasthenia gravis (rare).

2. Acute peripheral neuropathy - hypothyroid crisis, polyradiculoneuropathy (APN), autoimmune (rare). 

Of these, the most likely is APN (Coonhound paralysis) based on the dog's history, neurologic exam and signalment. 

Although an ELISA test does exist (Developed at UW-Vet School), it has a long turn around time and therefore isn't terribly useful for the initial diagnosis. I find it helpful to rule out the other causes rather than focusing on diagnosis this cause. I suggest applying a tick repellant (rule out tick paralysis), submitting a myasthenia titer, checking CBC, serum biochemistry for signs of biochemical imbalance (calcium specifically) and a T4. If all of this is normal, we're likely back to acute polyradiculoneuropathy (APN). 

Treatment is purely supportive. This disease is caused by an autoimmune attack against the nerve roots triggered by many things, including racoon saliva. Yes, saliva. Interestingly, a report in 2019 found an association with the consumption of raw meat contaminated with Campylobacter jejunii within 7 days of the development of APN. Antibodies are available and can be administered in the early phase but may not be available in your area. Supportive care includes ventilatory monitoring and mechanical ventilation as needed (they can loose the ability to contract the intercostal muscles and therefore cannot inhale), nutritional support (they can eat, drink and void voluntarily but need to do so sternal and be cleaned frequently to avoid bedsores), and nursing care (see prior). Signs reach peak severity within 10 days for most dogs. Signs typically improve within 3 months (12 weeks).  Please note that this disease is very recoverable with appropriate nursing care but it takes long, and intensive, at home nursing care. Sadly, affected dogs do not gain a sustained immunity after they recover and can show signs again if they are exposed to an appropriate trigger. 

Please let me know if you have any questions about today's TidBit Tuesday. I hope you have a great week!

Masticatory Muscle Myositis: That's a mouthful!

We are seeing more cases of masticatory muscle myositis lately so I thought we'd look into this interesting diagnosis together. Let's start by defining it.
Masticatory Muscle Myositis (MMM) is an inflammatory, autoimmune myopathy affecting the muscles of mastication (temporalis, masseter, pterygoid and rostral digastricus). All of these muscles are innervated by CN 5, specifically the mandibular branch.

Why only these muscles?
The muscles listed above have a specific myofiber type (type 2M), which is only present in these muscles and some fetal muscles. All other muscles in the body are 1A and 2A fiber types! Therefore, these muscles present a unique antigen for the immune system to target.

What does the clinical picture look like?
There is an acute phase, and a chronic phase. The acute phase occurs first and often includes signs such as jaw pain, swollen muscles, and difficulty chewing. (Note NOT drop jaw or difficulty closing the jaw....that is a different disease.)
If left untreated, patients will then progress into the chronic phase, which includes signs such as muscle atrophy and an inability to open the jaw. Muscle fibers are replaced with scar tissue during the chronic phase making the dog unable to open their mouth more than a few centimeters over time.

Must we take a chunk of muscle to make this diagnosis?
No, you don't! Although you will obtain a diagnosis in both the acute and chronic phase, there is an easier, and less invasive, way. The serum 2M antibody test is both highly sensitive (85-90%) and highly specific (100%) and is the preferred diagnostic test for MMM. Send it to the Comparative Neuromuscular Lab in La Jolla CA (https://vetneuromuscular.ucsd.edu/) if you live in the states. I think there are other choices worldwide but I'm not as aware of those.

Steroids are the best, and most effective treatment.
Immunosuppressive steroids are the most effective treatment for this disease and are strongly recommended in the acute phase. Your goal is to stop that inflammation in its tracks so that the patient doesn't progress to the chronic phase. Once they replace the muscle fibers with connective tissue, the game is over. The dog cannot open its mouth, chew, or be safely intubated or vomit. The chronic stage results in poor quality of life. Steroid protocols vary by neurologist. My protocol starts with 1 mg/kg PO q12h prednisone for 30 days, and then tapers slowly from there. Repeat 2M antibody titers every 1-2 months is recommended. Once the numbers return to normal, it is generally safe to stop the steroid administration.

If any dog has painful muscles of mastication, struggles to open its jaw without pain, and has an elevated CK on lab work a 2M antibody titer is recommended. Don't forget: neospora caninum and toxoplasma gondii can cause myositis and do attack the muscles of mastication. Concurrent testing for these two diseases in all dogs is strongly encouraged before starting immunosuppressive prednisone. I have been taken by surprise how often these tests are positive when I suspect this is "just" MMM.

Hopefully this helps you address muscle pain in your patients. If you have a question about a patient, please contact me via email or schedule a consultation online! Have a great week!

Renal Tubular Acidosis and Zonisamide

Ahh, it is time to examine Zonisamide again. A recent article in Veterinary Medicine and Science described a single dog with lethargy and distal renal tubular acidosis following administration of zonisamide. (https://onlinelibrary.wiley.com/doi/epdf/10.1002/vms3.905)
Distal renal tubular acidosis (RTA) has been defined as a normal anion gap metabolic acidosis with alkaline urine.

What should I look for to diagnose RTA?

The dog in this report had hypochloremia and hyperkalemia on initial blood work. This, coupled with a mild acidosis on blood gas and a urine pH of 7.73, suggested RTA. We're not sure of the consequences of RTA in dogs, yet. In pediatric human epileptic patients, there is some concern for future renal disease with RTA but this hasn't been well established (to my knowledge) for dogs. In this case, the link between the RTA and the dog's clinical lethargy was made, which is what drove the clinicians to pursue treatment.

How is it treated?

The authors described a very slow infusion of bicarbonate (please don't do this unless you have 24 hour monitoring capability!) which reversed the clinical lethargy and normalized the blood gas imbalance for 3 days. They did try to reduce the dose of zonisamide prior to treating the acidosis and achieved mild clinical improvement of sedation when the serum zonisamide concentration went from 38.6 ug/ml to 15.1 ug/ml. No change in biochemical status was noted. If you don't have the option to do a bicarbonate infusion, slowly tapering down or off of zonisamide is recommended to reverse the RTA. It is unknown, in dogs, if sustained RTA has negative health consequences. For many patients, another anticonvulsant drug must be substituted prior to removing zonisamide from the treatment plan.

Another short, but sweet TidBit Tuesday. Please let me know if you have any questions!
I hope those of you here in Wisconsin enjoyed the wonderful weather we had this past weekend and have found your winter hats and gloves in preparation for this coming weekend. Bring it on, am I right??

Consensus Statement for Intervertebral Disc Herniation in Dogs, 2022

October, 2022... We have long known that intervertebral disc herniation type I (IVDH) affects chondrodystrophic dogs, at a young age, disproportionately compared to non-chondrodystrophic dogs. We also know that many dogs benefit from surgical and medical intervention. We also know that the neurologic examination is a major predictive factor on recovery (medical and surgical intervention). What we don't know, is how to put what we know into a digestible nugget for clients to hear and understand when in our exam rooms with a dog with suspected IVDH.

First things first... We diagnose IVDH with MRI, CT, CT-myelogram or just myelogram. We don't diagnose IVDH on plain radiographs, or on neurologic exam. (Sorry, soapbox here.) When I say a dog "with IVDH" I mean that they have undergone some sort of diagnostic imaging (MRI, CT, CT-myelography or myelogram) and have been found to have compression to the spinal cord from suspected or confirmed herniated disc material. Presumably, of type I nature for this TidBit. If we don't have diagnostic imaging, but have a chondrodystrophic dog (beagles are included in this group) with appropriate neurologic signs we can call it "presumptive or suspect IVDH". We should, honestly, discuss other differential diagnoses with clients to ensure they understand that there are other possible causes so their decisions are informed. Common diseases that can mimic IVDH could include (but are not limited to) meningomyelitis, neoplasia, Syringohydromyelia, discospondylitis, and spinal trauma/fracture.

Medical intervention... The cornerstone of medical intervention is bedrest for 3+ weeks, anti-inflammatory (typically NSAIDS, but some neurologists prefer steroids), and muscle relaxants or pain management, if the pet is painful. See below for the consensus statement recommendations for medical intervention.

Surgical intervention.... I think this one is self explanatory (mostly). One small point I'll make is that fenestration is not always included when discussing surgical intervention. I consider fenestration an important part of surgical treatment but it does NOT decompress the spinal cord and is therefore excluded in lots of literature. Fenestration means to make a "window" in the affected disc UNDER the spinal canal and remove disc through a lateral or ventral incision (TL vs C-spine). This is also performed in adjacent discs in most cases.

July 2022...ACVIM consensus statement on diagnosis and management of acute canine thoracolumbar intervertebral disc exclusion (doi/epdf/10.1111/jvim.16480). A few key points are listed below and I will have more to share with you in future weeks.

Outcome of dogs managed medically or surgically, based on severity of presenting signs

• Pain only. 80% of dogs had positive outcomes with medical management. 98.5% of dogs had positive outcome with surgical management.

• Non-ambulatory paraparesis. 81% had positive outcomes with medical management however the level of recovery was less complete with medical management. 93% had positive outcomes with surgical management.

• Paraplegia, deep pain intact. 60% of dogs had positive outcomes with medical management however this was prolonged and less complete compared to surgical management. 93% of dogs had positive outcomes with surgical management.

• Paraplegia, deep pain absent. 21% of dogs had a positive outcome. 61% of dogs had a positive outcome.

• The loss of deep pain causes the biggest shift in predictive statistics for surgical intervention. If you have any question about checking deep pain, please ask!

Medical management key points

• Strict rest of 4 weeks is recommended based on low-level evidence to allow for healing of the annulus fibrosus. Strict rest is recommended by all, the 4 weeks part has low-level evidential support in the literature.

• Corticosteroids are NOT recommended in acute intervertebral disc herniation and their use did not demonstrate superior outcomes in many studies. The exception is management of chronic signs in which corticosteroid use may show some benefit. (Not addressed in this article.)

• NSAID use is recommended for at least 5-7 days, assuming no specific contraindication exists.

• There is low-level evidential support for acupuncture or rehabilitation for dogs.

Surgical management key points

• Much of the information provided is useful if you perform the surgery. If you do, please seek out the article as I won't be presenting those points here.

• The timing of surgical decompression is hotly contested amongst neurologists (and surgeons performing neurosurgery). Conventional wisdom suggests early decompression leads to better long-term outcomes, and faster. This has not been consistently shown in the literature therefore the consensus statement elected to skirt the issue and not provide a "optimal window of time" recommendation. My thoughts (I was not on the consensus team, please note) is that if your client is able to seek surgical management please do so as quickly as possible.

That's it for this week. This is supposed to be a "TidBit" so I don't want to overwhelm you and discourage you from reading. If you perform these surgeries, or refer frequently, please consider reading the consensus statement. If you have any questions about what I've covered so far, or IVDH in general, please reach out! I will cover more from this statement paper in future TidBit Tuesdays!

Have a great week, stay warm, and enjoy these glorious sunny days of fall!

Predictive Signs for MUO

Meningoencephalitis of unknown origin (MUO) is a non-infectious, inflammatory brain disease common in dogs. The vast majority of dogs diagnosed with meningoencephalitis have MUE, not infectious meningitis. MUO includes granulomatous meningoencephalitis (GME) and the necrotizing encephalitides (NME,NLE) and is the term used to describe antemortem non-infectious, inflammatory CNS diseases in dogs and cats. Providing owners with a prognosis when diagnosed with MUO is extremely challenging. A recent study evaluated several prognostic factors on the early survival in dogs with MUO. (https://www.sciencedirect.com/science/article/abs/pii/S1090023322000995)

Key Points:

• 98 dogs with MUO were included. 30/98 died within 30 days of the diagnosis.

• Adding cytosar to a glucocorticoid protocol did NOT alter the prognosis.

• Obtundation at presentation was the ONLY factor statistically associated with poor prognosis. Dogs had a 6.6x higher odds of death in the first 7 days, 2.1x increased risk in the first 30 days when presenting with obtunded mentation.

What does this mean for your patients?
It means that we still have a long way to go when sorting out what MUO means, and how it affects dogs. It means that a dog with a severely elevated WBC on CSF, or with other abnormalities on neurologic examination do not necessarily have a poorer prognosis. If you are seeing a patient with multifocal CNS neuroanatomic lesion localization, be sure to evaluate the pet's level of mentation. Survival may be reduced if obtundation is present. Refer as soon as possible for a neurology consultation and/or work up, depending on client preferences.

References: Lawn RW, Harcourt-Brown TR. Risk factors for early death or euthanasia within 100 days of diagnosis in dogs with meningoencephalitis of unkonwn origin. Vet J 2022. vol. 287.

Short and sweet this week. This article was too good to pass up, so please excuse the short TidBit Tuesday this week.

Safe fast to those of you observing Yom Kippur, Happy Feast of St. Francis of Assisi day and Happy Cinnamon Roll day to the rest of you! (Yes, that is actually a THING on October 4th.

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, alas it isn't perfect.

Misconception vs. 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.

Happy Rosh Hashana to those celebrating and happy first day of Fall (a few days late)!

Keep those consults coming; I look forward to seeing you soon.

*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.

Trazodone and the Neurologic Exam

Finally!! Trazodone and gabapentin are frquently recommended medications used for anxiolysis in the veterinary clinic but it has long been suspected that they have an impactful effect on the neurologic examination. We now have data! In this month's JVIM (https://doi.org/10.1111/jvim.16536), Drs. Lueck, Cameron and Zidan (from the University of Wisconsin-Madison!) evaluated 32 apparently healthy dogs pre and post trazodone administration and documented their findings.
Here are the key points:

1. The dose of trazodone in this study was 6.25-8.60 mg/kg PO single dose.
2. Neurologic examinations were performed before and 2.5 hours after trazodone administration
3. Decreased mentation changes were noted in about 25% of dogs (BAR going to QAR). Oddly enough, 7 dogs were noted to be QAR on initial exam and 3 were graded as BAR on post dosing exam. Not sure what to do with that except to say that we're obviously quite subjective on this assessment and BOTH are considered normal so should it matter?
4. Paw replacement deficits changed with identification of new, or worsened deficits in 22% of dogs. This finding isn't surprising but it bothers me. The neurologic examination is perhaps the most important tool to localize as well as determine differential diagnoses. We could misguide a client if we acted on the deficits identified while under the influence of trazodone!
5. Not a single dog had a worsening evaluation of their cranial nerves or reflexes in this study. Even 1 dog with reduced reflexes on the pre-trazodone assessment had similarly graded reflexes following trazodone administration.

What should we do with this information?

First, don't extrapolate to cats. Second, I strongly urge you not to have a client give trazodone to a pet prior to a neurologic examination based on this data. This recommendation has been previously based on my clinical suspicion so I'm thankful the authors went through the effort to perform and publish this data for the rest of us! Lastly, if you happen to do a neurologic examination on a pet ON trazodone and find deficits, consider repeating the examination without administration of trazodone to document consistence in the findings prior to recommending extensive work up. If that isn't possible, acknowledgement to the client of the possibility of a confounding factor, is recommended.

I look forward to hearing from you and working with you again soon! Have a great week and stay safe.