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.

A cat with a tilt

Welcome! Today is a going to be a busy day! First on your case list is a sick cat so let's dive in. Here is the story:
The cat was presented for a 2-month history of a left head tilt. She was noted to have effusion from the left ear when signs started and was treated with amoxicillin (dose unknown) for 14 days. Clinical improvement was initially noted, but signs relapsed after medications were discontinued and now the owner's are noting a head tilt to the right, with wide head swinging movements (think Stevie Wonder) bilaterally, especially when she first wakes up. She is an indoor only cat, with a history of indoor-outdoor lifestyle over 5 years ago.

Physical Examination

General: T: 99.4 °F/37.4 C Pulse: 180 bpm Resp: 20 breaths/min
Wt.: 3.4 kg BCS: 4/9 MM
Eyes: Corneas are clear, no ocular discharge, normal conjunctiva.
Ears: Mild waxy debris noted in both external ear canals.
Oral cavity: Patient did not allow evaluation
Teeth: Did not evaluate.
Lymph nodes: Normal, no peripheral lymphadenopathy noted.
Heart: No murmurs or arrhythmias, pulses strong and synchronous.
Respiratory system: No nasal discharge, no tracheal sensitivity. Lungs clear on auscultation.
Abdomen: Normal, soft, non-painful, no masses or organomegaly noted.
Musculoskeletal: Not evaluated
Skin and hydration: dry flaky hair, no ectoparasites noted

NEUROLOGIC EXAMINATION

Palpation: No paraspinal pain elicited on palpation
Postural reactions: normal tactile placing and hopping all limbs.
Reflexes: Normal.
Gait: Ambulatory with mild vestibular ataxia and falling left.
Cranial nerve abnormalities: Wide head swinging with an occasional right AND left head tilt, positional rotary nystagmus, mild miosis OS, remainder normal.
Mentation: BAR, occasionally hissing

What is the neuronatomic lesion localization for THIS cat?
This cat has evidence of vestibular disease based on the presence of a head tilt and nystagmus. Cranial nerves 8 are affected by loss of function of the peripheral nerve, brainstem or cerebellum. To differentiate between these three localizations, it is important to evaluate the remaining neurologic examination for clues. Animals with brainstem disease will exhibit a loss of function of the upper motor neurons and ascending proprioceptive pathways which is demonstrated as evidence of ipsilateral hemiparesis and reduced ipsilateral proprioceptive testing. Furthermore, reduced level of alertness (obtunded, coma, stupor) may be noted. If paresis, proprioceptive deficits or reduced mentation are noted the lesion is most likely in the brainstem. Cerebellovestibular disease will manifest with signs of vestibular disease plus evidence of hypermetria, intention tremors and/or truncal sway, suggestive of cerebellar disease. Absence of these findings suggests a peripheral CN 8 neuroanatomic lesion localization. This cat does not have evidence of brainstem or cerebellar disease therefore the signs were localized to the peripheral component of CN 8.
Reduced sympathetic innervation to the eye may occur through damage to the sympathetic pathway. This pathway starts in the hypothalamus, courses caudally through the brainstem, cervical spinal cord, and exits the T1-T3 spinal cord segment and travels cranially in the jugular groove to the cranial cervical ganglion. From the cranial cervical ganglion this pathway runs through the middle ear and along the trigeminal nerve to end in the periorbital muscles, 3rd eyelid and dilator muscle of the iris. Dysfunction anywhere along this pathway will result in miosis in dim light. The lesion in this case is likely in the region of the middle ear due to a lack of neurologic disease noted in the intracranial structures, spinal cord, or along CN 5.

You may be tempted to call this a central lesion because the head tilts BOTH directions but don't! Without signs of hemiparesis, proprioceptive placing deficits or mentation changes a central lesion is unlikely.

Differential diagnoses: The history suggests that we now have a bilateral otitis media/interna but you couldn't rule out a polyp or neoplastic process with a secondary infection.

What did we do?
CBC and serum biochemistry were normal. Thoracic radiographs were unremarkable. The brain MRI showed bilateral debris in the bulla with ring enhancement.

Final diagnosis: Bilateral otitis media/interna. A myringotomy was performed, with ear flushing, cultures and cytology. Unfortunately no growth was noted (this is uncommon!) so marbofloxacin was started and clinical signs improved. She had a left head tilt on presentation for 30 day recheck, and this is expected to be permanent. All other signs of vestibular disease had resolved!

Happy first week of Fall everyone! I hope you and your family had a wonderful summer and look forward to working with you as we dig into what I hope will be a lovely Wisconsin fall.

Anisocoria in Dogs and Cats

** 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!

Neutrophil-Lymphocyte Ratio in MUE

Meningoencephalomyelitis of unknown etiology (MUE) is a challenging antemortem diagnosis. MUE is the term used when we diagnosed inflammatory, non-infectious disease in the CNS. In the old days, we would have called this GME, NME or NLE, depending on the breed. However, those three inflammatory conditions cannot be distinguished on clinical picture, diagnostic testing, or treatment response, alone. Histopathology is needed to determine if a patient has GME, NME, and NLE. Without a brain biopsy, or post mortem sample, we cannot call it GME, NME or NLE. Several years ago, the term MUE started getting tossed around as an antemortem term for inflammatory brain disease, without a biopsy.

To diagnose MUE, a patient must have:
1) a neurologic examination with deficits identified (or a history of seizures) and
2) have a MRI with classical changes and
3) and CSF tap with a lymphocytic or monocytic pleocytosis and/or elevated protein level and
4) negative geographically specific infectious disease panel. If the pet meets these criteria, they can be diagnosed with MUE. 

MUE does not show up in routine blood work. Inflammatory leukograms are rare, elevated body temperature is not typically reported and pets are not systemically, clinically ill. However, some immune mediated diseases (such as MS) have garnered attention for a neutrophil to lymphocyte ratio present on routine CBC. 

A recent study out of Korea evaluated the ratio of neutrophils to lymphocytes in a standard CBC to see if we could predict a diagnosis of MUE. As it turns out, you can divide the neutrophil count by the lymphocyte count, and get a significantly higher number in dogs with MUE than healthy dogs. Furthermore, the ratio was significantly higher than dogs with idiopathic epilepsy but NOT different than dogs with brain tumors. The neutrophil-lymphocyte ratio was higher in dogs with MUE than all other forebrain diseases (hydrocephalus, idiopathic epilepsy, and brain tumors) but not always significantly so. 

What does this mean for us?

Unfortunately, nothing...yet. This is an interesting concept and a step towards a much needed tool for diagnosing MUE without invasive diagnostic testing. Performing a CBC, and calculating the ratio, is both simple and readily available in most (all?) veterinary practices today. However, if the ratio is high, it does not mean the pet has MUE. It may support a diagnosis of forebrain disease (which you already know from your neuro exam) and may support structural brain disease (i.e. not idiopathic epilepsy). Very importantly - this study did not find a significant difference between dogs with brain tumors and those with MUE. Sadly, brain tumors and MUE are often our top differentials for pets with forebrain disease so this ratio does not (yet) give us another non-invasive tool to differentiate between these two diseases. 
I enjoyed reading this study and learning about inflammatory markers for humans with MS (the human counterpart to MUE) and how this neutrophil-lymphocyte ratio could be used in the future for pets. If you'd like to read more, please see the link at the bottom of the page. 

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

If you haven't heard yet, please note that I am moving my office. Please try to remit any outstanding invoices by August 30th. If you need my new invoicing address please email me, or watch for a note in the mail. 

Reference: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16512

Ondansetron for Nausea in Vestibular Disease

Vestibular disease, whether it is central or peripheral in origin, can result in nausea and vomiting. The exact mechanism is unclear, but it is suspected to be via neuronal projections to higher centers (forebrain) and associated with activation of 5-HT3 receptors. Ondansetron is a selective 5-HT3 receptor antagonist (blocker). It has been shown to be effective on subjective observation, in controlling nausea in vestibular patients, but a recent double-blind placebo controlled study took it one step further. In addition to observation of signs of nausea, such as lip licking, facial expression, behavioral clues and hypersalivation, they evaluated blood levels of arginine vasopression (AVP) which has been positively correlated with nausea scores. 

Materials and Methods

Eighteen dogs were enrolled, 14 were included in data analysis. Six dogs received placebo first, followed 2 hours later by ondansetron (0.5 mg/kg IV, diluted 1:1 with 0.9% saline). Eight dogs received ondansetron first, followed 2 hours later by placebo. Dogs were observed at hourly time points for signs of nausea (pre and post treatment) and had serum samples for AVP measurements taken at pre-treatment, 2 and 4 hours post initial treatment. 

Key Results

• Dogs given ondansetron, showed a rapid, significant reduction in nausea compared to dogs given placebo. 

• Only 4 dogs vomited, in addition to signs of nausea. ** Vomiting should not be the only sign you watch for to say a pet needs an anti-nausea medication!

• Serum AVP concentrations decreased significantly after administration of ondansetron, compared to placebo. 

Based on the data presented, it is reasonable to assume any dog with recent onset vestibular signs should be administered ondansetron if signs of nausea and/or vomiting are noted. It would be helpful to educate clients on the signs of nausea (not just refusing food or vomiting!) when performing at-home observation of their pets with vestibular disease.

Interested in learning more about the nausea scores? Please consider this reference:
1. Kenward H. Development of an objective means of assessing nausea in dogs. London:EThOS British Library; 2015. 

I hope you're doing well and look forward to working with you soon! 

 Reference for article discussed above: 0.1111/jvim.16504

Walk This Way: Describing Ataxia and Paresis in the Clinical Patient

Perhaps you’ve wondered what the difference is between ataxia and paresis? Perhaps you already know, in which case you can grab that cup of coffee and move on to your next email!

Still with me? Okay, here we go. Ataxia is the failure of coordination. This suggests a sensory abnormality and when noted, it is a hallmark for neurologic disease. As you’ll see in the next section, paresis can be noted with neurologic, orthopedic, neuromuscular or muscular conditions, making it much less specific. Ataxia, however, is a failure of neurologic sensory information which means it can only be noted with dysfunction of the neurologic system. There are three forms of ataxia: 1) proprioceptive, 2) vestibular and 3) cerebellar.

• Proprioceptive ataxia is an indication of a spinal cord, brainstem or forebrain disease. Ataxia is not noted with neuromuscular disease.  Signs of proprioceptive ataxia include a crossing of the limbs when walking down a straight pathway, or placing the limbs narrow and wide of the midline of the body without regularity.

• Vestibular ataxia indicates dysfunction of the vestibular apparatus.  When observing a patient with vestibular ataxia, the observer can appreciate a falling or drifting towards one side when walking. This can be especially magnified when the patient is turned in a circle. 

• Cerebellar ataxia occurs with disease or injury to the cerebellum. Signs of hypermetria, truncal sway, and a wide based stance with, or without intention tremor are indications of cerebellar ataxia.

Paresis, on the other hand, is a weak movement or incomplete paralysis. This involves most commonly UMN or LMN, but remember the neuromuscular junction, muscle and bones or joints can be a source of paresis also. A patient with mild paresis will exhibit a reduced joint range of motion when walking giving the appearance of shuffling. Severe paresis may be more profound so that an animal is unable to support weight even with purposeful limb movements.
Common terminology when describing paresis:

• Mono: one limb (any)

• Para: pelvic limbs (both)

• Tetra: four limbs

How can you write the gait abnormality in the record?

• If the pet has only a proprioceptive ataxia: Pet is exhibiting crossing of pelvic limbs, consistent with proprioceptive ataxia.

• If the pet has proprioceptive ataxia AND paresis: Pet shows crossing of pelvic limbs and reduced joint ROM (or weakness /unable to rise/collapsing frequently) consistent with proprioceptive ataxia and paraparesis.

• If the pet is non-ambulatory in the pelvic limbs (cannot walk without support): non-ambulatory paraparesis*

• If the pet does not have any observable motor, even with support, in the pelvic limbs: paraplegia. *

*Comments about ataxia cannot be made once the pet is non-ambulatory or plegic.
 

Hopefully this helps clarify when to use paresis and ataxia when describing the gait. Enjoy your week and stay safe!

Book Announcement!

Small Animal Neuroanatomic Lesion Localization Practice Book

Over the last 18 months I have been collaborating with many amazing neurologists across the globe to write a first ever Neuroanatomic Lesion Localization Practice Book and.... IT'S ALMOST HERE!

I received confirmation recently that they expect to have this baby in the warehouse by November 2022! Self promotion is hard, so hopefully the book will speak for itself.

If you feel the need to brush up on your lesion localization technique, or are entering an internship or residency soon and want to get a jump on the neuroanatomic lesion localization game, or maybe you know a soon-to-be veterinary student that might benefit from this little ditty - you're in luck! Here is the link if you wish to check it out. (http://www.cabidigitallibrary.org/doi/) The book is titled: Small Animal Neuroanatomic Lesion Localization Practice Book. Let me know if you have any questions!

And now...back to the grind. :)

Thanks for reading! I hope you have a good week and stay cool out there in this heat.

Intervertebral Disc Herniation in Cats

Intervertebral disc herniation (IVDH) does occur in cats but is reported at a much lower prevalence than dogs. Is this because the disease is less prevalent or because owners are less likely to pursue advanced diagnostic imaging to obtain a diagnosis? I don't know the answer, however a recently published article reported on 35 cases of feline TL IVDH over 21 years. That sounds like a lot fewer cases than we see for dogs!

Clinical Presentation

Like dogs, the most common presenting complaint is difficulty walking and/or pain. In this study, They found 2 cats had grade I, 20 cats were grade II, 7 cats were grade III, 3 cats were grade IV and 3 cats were grade V on presentation. (Grading scale listed at the bottom). There was no significant difference between outcome at discharge or follow up and initial presenting grade. Does that mean that we shouldn't rush to get cat's seen, imaged, and cut? Probably not. Of the 3 grade V cats (the ones that we would consider a surgical emergency), one improved, one was static and the other was lost to follow-up. What was the timeline for surgery? Unknown. Dogs have a 50% chance of improvement if they are grade V and undergo surgery within 24 hours. This is debated amongst neurosurgeons but as a general rule I subscribe to the plan of cut ASAP whenever possible if deep pain is absent.

Location of the Offending Disc

In the referenced study, thoracolumbar disc herniation was most common at L6-7. This is slightly different from the previous reports in which L7-S1 was reported to be most common, but not far off. I think it is safe to say that cats are more likely to have low lumbar disc herniation than T11-L2 disc herniation, like dogs. Why? Cats are SO MUCH more flexible than most dogs (especially the chondrodystrophic type) that the vertebral dynamics are different as well. Previous reports suggest obesity is more common in cats with IVDH (and in my experience, too) but this cannot be the entire answer. It remains to be seen, why cats are more likely to have a low lumbar disc herniation than TL. When someone knows...I'll tell you!

Key Points:

• Intervertebral disc herniation does occur in cats

• The most common presenting sign is weakness or lumbar pain

• Surgery can be done and SHOULD be done (when appropriate for the patient)

If you have a cat patient with lumbar or lumbosacral pain, reach out. I'd love to see them! Schedule a consult using my online scheduler (for veterinary use only) and let's get your patients feeling better, soon!

Grading scale:
Grade I: normal gait with hyperpathia
Grade II: ambulatory paraparesis
Grade III: non-ambulatory paraparesis
Grade IV: paraplegia with intact nociception
Grade V: paraplegia with absent nociception

Reference: https://journals.sagepub.com/doi/pdf/10.1177/1098612X211028031

Midazolam vs. Diazepam for At-home Care

History of Cluster Buster Protocols

In 1995 Dr. Michael Podell championed the idea of at-home, rectal diazepam use for canine cluster seizures. In that study, dogs that received rectal diazepam had fewer cluster seizures compared to those that didn't receive the drug. Since then, at home cluster care has become standard practice for many veterinarians.
According to human literature, benzodiazepine drugs (midazolam, diazepam and lorazepam) are the "best" first line anticonvulsant drugs to stop status epilepticus. As is typical, we simply adopted this idea in veterinary medicine without data to support it's use. But...the benzodiazepine drugs do show improved seizure cessation so...they probably help our canine patients in some manner.

Which Benzodiazepine is Better?

Here is where the science gets a bit muddy. We've compared rectal diazepam to intranasal midazolam and intranasal midazolam was superior. We've compared intranasal midazolam to intravenous midazolam and intranasal midazolam stopped seizures faster. However, all of these studies involved few animals and ethically we cannot have a group of untreated animals to determine true efficacy. So, which is better? They all work, but intranasal is perhaps faster and easier than other non-intravenous routes when IV access is restricted.

What are the current recommendations?

At this time, intranasal midazolam at a dose of 0.2 mg/kg up to 3 times in 24 hours is my recommendation for dogs with a cluster or status epilepticus history. Do your best to use a nasal atomizer because this has been shown to be the superior technique compared to nasal-drop application. (I have found them at Midwest Vet:https://www.midwestvetsupply.com/products and also carry them in my car. Ask, when I'm at your clinic, if you need one!).

Nasal drop vs. Atomizer?

The nasal drop technique requires the client to drip the midazolam intranasal slowly during the active seizure while also avoiding getting bitten. The atomizer looks like a conical shaped marshmallow that is attached to the end of the syringe and the client is then able to press the atomizer against the nare and dispense the dose in one "push". Not clear on this technique? Please ask me, I am happy to clarify! I do not have a financial incentive or disclosure for this product, or Midwest Vet Supply. :)

I hope you're enjoying summer and all it has to offer! I am at the Dane County 4-H Fair cheering on my kids so my hours are a bit limited. Please reach out if you need me and cannot find a suitable consult time online. Have a great week!

Zonisamide Induced Blood Dyscrasia in Dogs

Really, zonisamide? You couldn't just let this one slide? Phenobarbital already has dibs on blood dyscrasias and I'm struggling to like you as it is. Why did you go and have to do THIS to dogs, too??

If you've been a TidBit Tuesday reader for awhile you'll know I struggle to love zonisamide. Yes, it has it's place in movement disorder management. Yes, it can be a wonderful anticonvulsant. in some dogs. But in my hands, in my experience, it either hasn't worked well or I've seen undesirable side effects that I've attributed to zonisamide. And it is a Sulfa antibiotic. So, there's that worry, too.

New this week, we can read about 4 dogs with blood dyscrasias likely secondary to zonisamide administration.

Dog 1: 7 year old Shih Tzu. Presented for vomiting, lethargy and fever. He had received Zonisamide (ZNS) for 400 days at a dose of 5 mg/kg q12h. Severe leukopenia with neutropenia, monocytopenia and lymphopenia were noted along with an elevated ALP, ALT, hypocalcemia, hypochloremia, hyponatremia, and hyperbilirubinemia. ZNS was discontinued and antimicrobials were started. 19 days later, the leukopenia was resolved.

Dog 2: 1 year old Siberian Husky. Presented for a history of groaning, and appearing tense. He had received ZNS for 29 days at a dose of 17 mg/kg q12h. On presentation the dog was also febrile, had a leukopenia with neutropenia, and increased ALP and hypoalbuminemia. Zonisamide was discontinued and the leukopenia persisted through 40 days. On day 180 from discontinuation, the WBC was within the reference range.

Dog 3: 9 yr old Miniature Poodle. She presented for lethargy, anorexia, labored breathing and reluctance to walk. She had received zonisamide for 20 days at a dose of 8.5 mg/kg q12h. No fever was noted on presentation however overnight a fever developed. Severe leukopenia with neutropenia was documented after the zonisamide was discontinued (within 24 hours, I think) along with increased ALP activity and hyponatremia. Leukopenia and neutropenia resolved by day 6.

Dog 4: 5 year old Miniature Poodle. He presented for vomiting, lethargy and anorexia as well as fever. ZNS was started 1,196 days prior to presentation at a dose of 8.4 mg/kg q12h. Again, CBC showed a leukocytosis with neutropenia and mild thrombocytopenia. Serum biochemistry showed increased ALP, hyponatremia, hypokalemia, hypochloremia and hypercholesterolemia. Zonisamide was discontinued and leukopenia improved within 2 days, and normal by day 3.

The authors attributed the blood dyscrasia to an idiosyncratic drug reaction. Idiosyncratic, of course, means that it is unpredictable in scope and severity and not reliably related to dose. Other idiosyncratic reactions to ZNS include hepatopathies, skin eruptions and rental tubular acidosis. Perhaps all of these reactions are because this is a sulfonamide derived anticonvulsant? Discontinuing the drug is the best way to try to reverse the blood dyscrasia. I found it interesting that in one of the cases they continued phenobarbital (a drug also known to have a risk of idiosyncratic blood dyscrasia) and the bone marrow was still able to regenerate.

Key point: If you find an abnormal CBC for a pet receiving ZNS, please consider an idiosyncratic blood dyscrasia and discontinue the drug (safely).

Reference: https://doi.org/10.1111/vec.13222

Have a great week and thanks for reading!

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

Syncope Vs Seizures

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 cool, 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. 

Early detection of Pug Encephalitis

Pug encephalitis, termed necrotizing meningoencephalitis (NME), is a common cause of CNS inflammation in Pug, Maltese, Chihuahua, Shih Tzu and other small breed dogs. The typical presentation is a dog less than 4 years old with acute, progressive, multifocal CNS signs. (However, meningoencephalitis is the great pretender so it may present in ANY age, breed, sex, and with neurologic examination findings!) Many Pugs are reported to be resistant to immune suppression, however this is not a global truth. On histopathology, areas of necrosis are identified, along with infiltration of inflammatory cells which leads to the term necrotizing meningoencephalitis. Antemortem, a diagnosis cannot be rendered. MRI and CSF changes would lead a practitioner to a diagnosis of meningoencephalitis but without histopathology (biopsy or necropsy) the dog would be diagnosed with meningoencephalitis of unknown etiology (MUE). MUE includes the necrotizing meningoencephalitis and granulomatous meningoencpehalitis thus it is not a histopathologic diagnosis but a clinical one.

What if we could detect NME earlier?

Researchers recently published a study with this question in mind. They evaluated 36 pug dogs that were deemed clinical normally by their owners. Genetic studies were performed; 5 homozygous/high risk, 19 heterozygous/medium risk and 12 low genetic risk (previously published data about genetic link) dogs were included. They then performed 2, sequential neurologic examinations on these dogs at least 4-6 weeks apart. Dogs that were considered repeatably abnormal subsequently underwent MRI (spine, brain, or both) and had a CSF analysis performed.

Results of the study

Dogs considered low risk had 0 repeatable abnormalities on neurologic examination. Eight of the 36 "at risk" pugs had repeatable abnormalities. Abnormalities included back pain, menace deficits, ataxia and paw replacement deficits (1 or more). The only statistically significant finding was multifocal spinal pain. The 8 dogs underwent imaging and mild brain abnormalities were noted in all dogs with variable severity. CSF changes were noted in 3 of the 8 dogs.

What is the actionable result of this study?

The take away here is that the MRI was more sensitive to detecting "pre clinical" NME than CSF analysis. Is this actually "pre clinical" if the dogs had repeatable neurologic examination abnormalities? I argue perhaps not, perhaps they were "undetected" by clients rather than preclinical. That said, we don't subject dogs to annual neurologic exams without reason so perhaps this is a reasonable way to conduct the study. (Maybe we should??) I always ask myself: what I would do with the information gained when I suggest a test or procedure? In this case, would I treat this dog with "pre clinical" MRI changes or would we wait to see if this develops into progressive disease? I don't know the answer to this question and they didn't pursue treatment in this study so I don't have an objective answer for you. For me, these types of studies will help us help dogs considered genetic "at risk" for NME. Perhaps we identify treatment earlier? Perhaps we find out that there is a specific environmental trigger? Perhaps you learned that there is a genetic "risk" for pugs. Have a pug patient or pet that you think should be genetic tested? Here is the link: http://www.vgl.ucdavis.edu/services/dog.php

The big question is - at risk does NOT equate to disease - so what do we do with the information??

Thanks for reading today. I really enjoyed reading this study and hope you enjoyed my summary.

Have a great week and keep those consults rolling. My kids will be in and out of different camps this summer so my schedule will be changing week-by-week. As always, please reach out if you cannot find a suitable time for your patient using the online scheduler and I will do my best to find timely spot!

How to handle a jerk

Have you evaluated an elderly patient with a history of sudden, unprovoked jerk movements lasting several seconds and not been sure what to make of it? It's easy to disregard this information because it doesn't fit into one category but perhaps, we shouldn't.

Myoclonic "jerks" can occur as a part of an epileptic syndrome (myoclonic epilepsy) or as a separate movement disorder. As a movement disorder, they may arise from neuromuscular, spinal, cortical or subcortical origin and therefore may have many different etiology. A report in Cavalier King Charles Spaniels came out recently (https://doi.org/10.1111/jvim.16404) which detailed myoclonic jerks in older CKCS. This study was not conclusive about the origin of the jerk, but suggested a cortical or subcortical origin. Several of the dogs in this group had idiopathic epilepsy, diagnosed with MRI/CSF/blood work prior to the onset of the myoclonic jerk so it is possible this is simply a manifestation of their epileptic syndrome. However, several of the dogs were on treatment with primary anticonvulsant drugs (imepitoin and phenobarbital) and the seizures improved but the myoclonic jerk worsened! This suggests a more likely non-epileptic origin. This study was SMALL so it is much too early to draw conclusions about the cause but it does provoke thought.

Here is what I took away:

1. Older adult or geriatric onset myoclonic jerks may be seizure, or non-seizure in origin
2. Phenobarbital (and imepitoin) didn't help
3. Levetiracetam helped in 3 or 6 cases. This could mean it is epileptic or non-epileptic in origin, remember!
4. If non-epileptic in origin, myoclonic jerks do not warrant treatment as they are unlikely to result in progressive neurologic disease (but knowing if they are non-epileptic is difficult)
5. Myoclonic jerks are seen as rapid movements of the face, head or thoracic limbs that are several seconds in duration and do not have a pre or post ictal period associated with the signs. Not sure what I'm talking about? Follow the link to the article and scroll to the supplementary material. There are two videos attached to help you visualize what is being noted.

So what do I do?
1. If the neurologic examination is ABnormal - suggest diagnostic imaging of the brain or spinal cord to determine if pathology is present to account for the jerk motion.
2. If the neurologic examination is normal, consider non-epileptic jerks and either start levetiracetam or monitor if infrequent.

Thanks for reading and have a great week! Stay cool out there and watch out for jerks!