Zonisamide Use in Dogs

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

Results

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

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

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

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.

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!

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!

Abrupt Benzodiazepine Withdrawal in Dogs

Abrupt withdrawal of benzodiazepine drugs can result in withdrawal seizures. A recent report describes withdrawal seizures in 3 young dogs and I thought we could take this opportunity to review this concept.

What is a benzodiazepine drug?

Benzodiazepine class drugs commonly include diazepam, midazolam and lorazepam. These drugs are GABA agonists in the CNS which results in suppression of activity. GABA activation causes inhibition in the forebrain, cerebellum, and in other parts. So, if you activate an inhibitor, you will suppress activity. Got it?

How long is too long?

Abrupt withdrawal resulting in seizures and other signs of CNS overstimulation can occur after constant rate infusion (CRI) use, or chronic oral use. Use of a benzodiazepine drug as a CRI for more than 12 hours usually warrants tapering. The three dogs in the recent report received one of these drugs for 39, 64, and 48 hours, respectively. After abrupt withdrawal of the drugs they experienced ataxia and seizures within 4- 48 hours. A return of the benzodiazepine CRI at a low dose, followed by a 12-24 hour taper, resulted in a successful wean from the medication and no additional neurologic events. All three of these dogs were also undergoing mechanical ventilation, and received other medications, so there is always the questions about a direct link between the benzodiazepine withdrawal and the seizures, however the authors suggest this link follows an expected pattern with abrupt withdrawal in humans and in animals. I agree.

As a general rule of thumb (based on human literature), if I prescribe a benzodiazepine drug for oral use longer than 7 days I taper the medication. Abrupt withdrawal is sometimes called "Jim jams" which, honestly, is a pretty fantastic term but probably not a fantastic feeling. Withdrawal ataxia, cerebellar signs and seizures can be seen from abrupt discontinuation of a benzodiazepine drug.

How do I taper to avoid withdrawal seizures?

CRI:

• Typical dosing range is 0.1-0.5 mg/kg/hr. I reduce the dose by 50% every 12 hours until the pet would be receiving less than 0.1 mg/kg/hr. For example, if we are at 0.25 mg/kg/hr and wish to taper I would start with a reduction to 0.12 mg/kg/hr x 12 hours, then stop, because the dose would then be less than 0.1 mg/kg/hr.

Oral dosing

• Typical dosing is 0.25-0.5 mg/kg PO q8-12hours. If the dog receives the drug for more than 7 days, I would recommend a 50% taper for 3-5 days, followed by another 50% reduction for another 3-5 days and the stop. Cats are at risk of acute hepatic necrosis with oral diazepam administration so I rarely use this medication. However, if you find yourself treating a cat on chronic benzodiazepine drugs, a similar taper can be employed.

Thanks for reading and enjoy your summer! 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.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/vec.13221

Seizures in the Post Operative Period

Seizures in the immediate post operative period can indicate a poor prognosis for humans undergoing brain surgery. The same is suspected for dogs, but isn't known. A recent article (see below) recently discussed this question and I thought you might be interested in reading some key points from the article.

Key points:

• 88 dogs underwent 125 procedures. Most had either a brain biopsy or a brain surgery, but some had both.

• All included surgeries were rostro tentorial because caudal tentorial surgery and tumors have a very low incidence of seizures.

• Most dogs (72%) had seizures before brain surgery was performed, therefore diagnosed with structural epilepsy.

• All types of seizures were noted (35% generalized only, 29% focal and generalized and 17% focal only)

• Forty-one of 88 dogs (46%) had a normal interictal neurologic examination. This is MUCH higher than some other studies have shown and is worth noting in general practice. The neurologic examination can help guide you towards advanced diagnostic testing, or not. According to this study, almost 1/2 of the dogs had a normal exam and had a brain tumor!

• About 42% of dogs had an abnormal neurologic examination consistent with a focal lesion and 11% had examination findings consistent with multifocal disease.

What I learned from this article

This article was full of data, so if you're a practicing brain surgeon, it is worth a full read. That said, there were a few points that may benefit the non-neurosurgeons amongst us. I've summarized them below and included a link to the open access article at the bottom if you'd like to read more yourself.

• Early post-operative seizures in humans, are diagnosed in the first month after brain surgery. One of the hypotheses was that dogs receiving anticonvulsant drugs (ACD) would have a lower incidence of post-operative seizures. Interestingly, this article did not detect a difference in post operative seizures between dogs with or without ACD pre-operatively!

• Tumor location nor brain herniation were associated with the development of post operative seizures.

• Curative intent surgery carried a higher risk of post operative seizures when compared to biopsy procedures.

• Dogs with glioma had a higher incidence of seizures compared to other tumor types, except meningioma.

• Dogs with early post operative seizures were less likely to survive to discharge.

• Early post operative seizures occurred in the first 24 hours for all dogs, and were associated with longer hospitalization.

Take Away Message

What does this mean? It means that seizures are a small, but mighty way for the brain to express it's displeasure with human touch. Even the most careful surgeon risks causing seizures that could be life threatening for their patients. I still give ACD pre-operatively but am compelled, by this data, to consider stopping that practice. Why administer an ACD if it isn't associated with a lesser chance of seizures? For most of you, brain surgery is not a part of your daily practice, so I would suggest that the most important take away from this article might be that almost half of dogs had a normal neurologic exam and yet were diagnosed with a brain tumor. Also, if a client asks you about post operative seizures, you can refer to this article! Thank you, Science.

Thanks for reading all the way through! I hope you have a great week and look forward to working with you, and your patients, soon.

Article links: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16391

Canine Distemper Causing Lameness?

An interesting case report came across my desk awhile ago so I thought I might share some key points with you this week. (Green L, Cook L, et al. Distemper encephalomyelitis Presenting with Lower Motor Neuron Signs in a Young Dog. JAAH 2020)

Signalment: 4 month old spayed female dog

History: The puppy was presented to the neurology service with a several day history of right thoracic limb monoparesis. Key findings in the neurologic examination included axial pain on palpation, thoracic limb lameness, weak withdrawal of the affected limb and a paw replacement deficit in that limb. Absent cutaneous trunci reflex was also noted on the right side. Other than the neurologic findings, the only other interesting finding on physical examination was a mildly febrile state of 102.7F) and crusting of the foot pads.

She was initially managed conservatively however signs progressed to inappropriate mentation which was suspected to be due to the fentanyl patch. This was removed and signs improved however the clients elected to proceed with additional testing at that time.

Neuroanatomic lesion localization? You tell me!! (see below when ready)

Differential diagnoses listed at this time included non-infectious inflammatory conditions (MUE), infectious meningomyelitis, and hemorrhage or trauma.

Diagnostic testing

• Spinal MRI: Abnormalities in the central spinal cord

• Brain MRI: Unremarkable

• CSF: Mild pleocytosis cell count 10/ul: reference < 5/ul) with normal protein and RBC.

• Infectious disease testing: Neospora IFA was negative however the Toxoplasma IgG was markedly elevated with a borderline IgM. Parvovirus testing and cryptococcus antigen testing was negative. PCR on CSF for distemper (CDV) was positive. A whole lot of other infectious diseases were tested for, and negative.
  

Treatment with clindamycin, sucralfate, gabapentin, tramadol, famotidine, metronidazole and a single dose of dexamethasone was started.

Progression: She was discharged 4 days later, but returned due to progressive mentation changes and worsening ambulation. During evaluation she had a focal seizure. (Now we have multifocal neuroanatomic lesion localization!). She was humanely euthanized and submitted for necropsy.

Necropsy: Findings consistent with CDV were found and in addition, immunohistochemistry of the C5 and lumbar spinal cord and strong nuclear and cytoplasmic brown staining for CDV and no staining for Toxoplasma.

What is so noteworthy about this case?

• She was partially vaccinated. Did you know that 40% of dogs with confirmed distemper infection, in one study, were vaccinated? (Tipold A: 1995).

• She had hyperesthesia associated with her neurologic signs. Pain is a very unusual finding for a distemper case and the authors suggest this is the first case report of confirmed CDV in a dog with limb pain.

• The progression from limb to brain is unusual but not unreported.

Take Home Message
A young dog, with multifocal neurologic findings, or findings of spinal pain in conjunction with neurologic findings, may have CDV. I suggest adding this disease to your ever-growing-list of infectious diseases that can cause spinal pain in dogs.

Neuroanatomic lesion localization answer: C6-T2 radiculopathy or neuropathy. There is no evidence of spinal cord involvement initially so a myelopathy is less likely.

As always, thanks for reading! I hope you have a NON-PAINFUL week, that isn't LAME! (Sorry...I just couldn't help myself.)

Orthostatic Tremor in Dogs

How often do you hear "my dog's legs shake when s/he stands?" (Okay, perhaps not as often as I do...but I'm going to assume you hear it at least a LITTLE bit of the time!)

Etiology
Orthostatic tremors can be primary, meaning the tremor is the disease itself. This is suspected to originate from the cerebellum or brainstem but is still, as of now, unknown. The disease is progressive therefore neurodegenerative causes have been considered.
Tremors that are associated with another neurologic disease are termed OT-Plus and include an assortment of spinal cord compressive diseases such as Wobbler's or LS disc herniation. The tremors with OT-PLUS are therefore suspected to be associated with weakness driven from the primary myelopathy, not a disease process in its own right.

Description
When rising to stand, during standing, or occasionally when rising to sit, dogs will exhibit a fine, involuntary tremor in pelvic limbs (most commonly), all four limbs (second most commonly) or thoracic limbs only (rarely). These abate when recumbent, or in active motion (walking, running). Specific awake electrodiagnostic testing confirms the disease but the clinical suspicion is high with the history alone. Orthostatic tremor (OT) has been described in large or giant breed dogs only. Signs begin between 9 months and 2 years of age for OT, and a bit older for OT-plus. In fact, Retrievers and older age were associated factors with OT-plus in a recent retrospective study reporting on orthostatic tremors. (10.1111/jvim.16328.)

Treatment
Okay this is super interesting to me (and hopefully you)! This data is for primary OT, not OT-plus.

• Phenobarbital/primidone - 15/15obtained remission (2 lost to follow up)

• Gabapentin/pregabalin - 25/29obtained remission (3 lost to follow up)

• Clonazepam - 5/6 obtained remission (1 lost to follow up)

Improvement was more likely to be partial than complete resolution (7:3) but some improvement was noted. Interestingly, clonazepam is reported to be the drug of choice for human OT and yet the response to treatment is minimal compared to what we see with our canine patients.

Why do these treatments help? Unknown. It isn't a convulsive disorder therefore these medications are helping from a different angle. I'll keep you posted as we hear more!

Take away from this:
Young, large or giant breed dogs with tremors may have OT
Look for an underlying cause if signs onset at an older age, especially in a retriever breed
Try one of the treatments listed, let me know what you think!

As always, thanks for reading. Please let me know if you have any questions about OT, or any other case you are evaluating.

I appreciate your business and look forward to continuing to work with you and your team!