The blood-brain-barrier is an important player in epilepsy, even if it is an unsung hero. You may (or perhaps may not) recall from veterinary school that there are 3 parts to the BBB. 1) the tight junction (TJ) proteins between endothelial cells 2) the highly specialized and restrictive transport system in the cellular walls and 3) the capillary wall which utilizes a basement membrane, astrocyte feet (I love that they have feet) and little pericytes. The BBB is one of the best bouncers in the system and it takes extreme caution allowing molecules to pass. Over the years we have learned that the BBB plays an important role in epilepsy. For example, disruption of the TJ proteins, most notably upregulation of MMP9 (if you want to know everyone’s full name, please refer to the article) has contributed to the generation of seizures. Conversely, stabilization of the BBB can prevent seizures in experimental models. Leakage of serum albumin, through a dysfunctional BBB, has been shown to bind to TGF-beta on astrocytes and cause astrogliosis (an increase in astrocytes, or upregulation of their function). The development of astrogliosis, followed by some changes in the extracellular matrix causes a DECREASE in the inhibitory protein GABA and INCREASE in excitatory synapses in the brain. Decreasing the inhibitors and increasing the excitatory proteins. Yikes! Bring on the seizures.
A study was published outlining some novel ways to look at the BBB using MRI (Hanael E, et al from Israel. JVIM 2024). There are parts of that article that I will be skipping for this TidBit Tuesday because they aren't applicable unless an MRI is part of your practice. However, the parts that I think are good for general discussion relate to the location in the brain. Seizures are frequently generated in the piriform lobe, so the researchers looked at that lobe using MRI, histopathology and CSF. They found a significant increase in albumin and MMP9 proteins in the piriform lobe in dogs with idiopathic epilepsy, along with evidence of damage to the BBB on MRI in this region. CSF albumin was increased AND serum MMP9 activity was increased in dogs as well. All of this supports evidence that we are finding damage to the BBB, causing consequences to the brain (specifically the piriform cortex) which is then manifested physically as a recurrent seizure disorder (epilepsy). Perhaps the future will hold some therapies directed at "patching" the BBB as a treatment modality - you'll have to stay tuned!
This week's TidBit Tuesday was a bit heavy on the sciences so I hope you'll forgive me on this first full week of summer. Epilepsy is an ever changing area of study that I find fascinating and hope you don't mind coming along for the ride with me sometimes. Have a terrific week and I hope you can get out and enjoy the sunshine!
Anesthesia for Pets with Seizures
It’s a Tuesday morning, and on your schedule is a 6 year old Maltese dog with a 3 year history of seizures that appear well controlled on phenobarbital monotherapy. She has a history of 1 seizure every 6-8 months and each seizure is less than 3 minutes in length. No interictal signs noted by the owners and she continues to have a normal neurologic exam. Today, they would like to discuss doing a dental for their dear little dog. What should you consider? How does general anesthesia for a patient with neurologic disease differ from those without?
The Risks of Anesthesia
General anesthesia is not necessarily bad. 😊 The biggest two risks of general anesthesia for dogs or cats with seizures are (1) hypotension and (2) negative effect on the seizure threshold. Let’s talk hypotension.
Your goals are to preserve cerebral blood flow, which is largely controlled by the cereal perfusion pressure, which is largely controlled by the mean arterial blood pressure (MABP). MABP is directly related to intracranial pressure (ICP). Thankfully there is a wide range at which MABP will have little negative effect on ICP. MABP between 50-150 mm HG should result in constant ICP, if other parameters are equal. Hypotension can be caused by some of the medications used (I’m looking at you acepromazine) or caused by CO2 levels. If the PaCO2 levels are above 50, a risk of vasodilation occurs which may decrease MABP. Monitoring CO2 can be quite useful to avoid this. If vasodilation occurs, and consequently decreased MABP, perfusion to the brain can be compromised. Hyperventilation will decrease the PaCO2, result in vasoconstriction and maybe lower the ICP. Some references suggest that PaCO2 should be between 30-35 for “appropriate” cerebral perfusion. Big disclaimer today – I am not an anesthesiologist so specific questions about anesthetic protocols should be directed to your local anesthesiologist! Long-standing, serious, hypotension can affect neuronal membranes and in rare situations could cause neuronal cell membrane damage, or a worsening seizure disorder. Thus, try to keep the PaCO2 in a normal range, and monitor blood pressure for pets with seizures undergoing anesthesia.
With respect to the seizure threshold, isoflurane, diazepam, midazolam, and possibly propofol are neuronal protective. If you have the luxury of choice, consider using one (or all!) of these medications in your anesthetic protocol. If you have a patient with poorly controlled seizures, administration of IV phenobarbital 20 minutes before starting anesthetic recovery may be useful to add seizure protection during the recovery process. ALWAYS go slow! Give the phenobarbital over 20-30 minutes as a slow infusion to avoid severe cardiovascular or respiratory suppression. This drug is closely related to pentobarbital, our common euthanasia solution. Most patients can receive benzodiazepine medication if active seizures are noted during the recovery process. Paradoxycal hyperactivity following benzodiazepine adminsitration occurs rarely but would be a reason to avoid using the drug in the future if a patient exibited these signs. Patients with significant hepatic disfunction such as those with portosystemic shunts should either avoid benzodiazepine drugs due to inadequate metabolism, or be adiminsered a 25% dose.
Any anesthetic event, even an uneventful one, can put a patient with a known seizure disorder at risk for seizure breakthrough. This risk persists for at least 24 hours following anesthesia but in rare patients it can be longer. Owners should avoid leaving the pet alone for extended periods of time such as traveling by airplane, boarding the pet or other unobserved time in the first 24 hours after anesthesia. Never withhold chronic anticonvulsant medications prior to anesthesia. Bromide can cause vomiting therefore it should be given with a small meal. Patients receiving bromide (liquid) can receive it rectally if they are anesthetized early in the morning and a small snack with their bromide is not possible. Phenobarbital, levetiracetam and zonisamide can be given on an empty stomach without high risk of GI upset.
This topic was suggested by one of your colleagues - thanks for the suggestion! Do you have a topic you wish I’d cover? Please reach out! Thanks for reading and have a great day!
Status Epilepticus in Cats
Last week we looked at the ACVIM consensus statement for the treatment of status epilepticus and focused on the different stages, and the treatment algorithm outlined by the committee. This week, I thought we should look at this statement through the lens of cat care. Please refer to the article for more details - it's a good one! (DOI 10.111/jvim.16928)
As a reminder, all available literature was reviewed and classified according to it's level of evidence. Studies with a high level of confidence for or against a specific treatment included treatments in which 2 or more clinical studies with a high quality score (more about that in a minute) evaluated this specific intervention. Moderate level of evidence for a treatment needed 2 or more studies with moderate quality score or 1 study with high quality score. A label of low evidence for a specific intervention was used in situations where 2 or more studies with low-quality score were reviewed or 1 with a moderate quality score without any high quality score articles identified. A label of conflicting evidence was used when 2 or more studies, usually with a high quality score, were reviewed and found to have results in conflict. Finally, the label "absence of evidence" is pretty self explanatory. The quality scores were numeric scores assigned each study based on clearly defined criteria such as EEG or clinical confirmation of seizure cessation for each study reviewed.
Definitions
The definitions are the same for cats as they are for dogs. Any seizure longer than 5 minutes is considered status epilepticus (SE). Similarly, cluster seizures are 2 or more seizures within 24 hours in which consciousness is regained between the seizures. Okay, off to a good start.
Antiseizure Therapy for Cats
Figure 3, in the aforementioned article, is a pyramid of hierarchy for therapy recommendations for cats in status epilepticus. Sadly, there are no studies with a high level of confidence for any intervention. This means that no high quality studies, evaluating seizure cessation in cats, were identified. We need to fix this! Intravenous bolus or CRI of midazolam, intravenous bolus of diazepam, intravenous levetiracetam, intravenous phenobarbital and inhalant anesthetics were considered to have moderate level of confidence for cats. This suggests that there is at least clinical evidence (if not EEG evidence) that supports these treatments for SE management in cats. Oral levetiracetam, intravenous bolus or CRI of phenobarbital and propofol had low level of evidence suggesting that giving these drugs, via these routes, to cats with seizures is not supported by the literature. Oral midazolam, intravenous CRI, oral or endotracheal diazepam were not supported by the literature. Not surprisingly, there were many drugs that were withheld from analysis due to a lack of evidence for cats.
As I mentioned last week, the authors made the following statement:
"Although both benzodiazepine drugs are potent and safe for the management of SE in dogs and cats, midazolam may be considered a more potent or safer benzodiazepine drug than diazepam."
Based on this, and my own clinical impression, if you aren't carrying injectable midazolam yet, now is a good time to consider adding this to your cabinet!
The authors also specifically addressed CRI reduction and recommended reducing by 25-50% every 4-6 hours after a cat (or dog) has been seizure free for at least 12 hours, preferred 24 hours. It is always preferred to taper the medication, not stop abruptly, whenever feasible.
I think that is enough for today. I hope you had a good holiday, didn't go too crazy on Black Friday, and I look forward to working with you soon!
As always, the holidays bring many challenges. If you cannot find a suitable time for a consult using my online scheduler please reach out to me via email. I will always try to accommodate your request if I can.
Status Epilepticus Consensus Statement 2023
Status Epilepticus and Acute Seizure Management Consensus Statement 2023
The ACVIM Consensus statement about status epilepticus (SE) was published this past summer (2023) and I felt it was applicable to all of us faced with acute seizure management. They dove right in and addressed the need for a definition of a prolonged seizure as one occurring for longer than 5 minutes. The human equivalent of our International Veterinary Epilepsy Task Force (IVETF) is the International League Against Epilepsy (ILAE). The ILAE has recently also revised their definition of SE to any seizure longer than 5 minutes as well. Previously, SE was defined as anything between 5-30 minutes. Thirty minutes was the cut off because at that point, brain damage is common. The reason for adopting the 5 minute rule was to 1) minimize the risk of systemic and brain complications associated with continuous seizure activity reaching up to 30 minutes; 2) prevent worsening of the prognosis and drug resistance associated with increasing duration of uncontrolled seizure activity and 3) limit any potentially unfavorable outcomes and adverse effects associated with the prolonged administration of multiple therapeutic interventions.
Status Epilepticus is divided into 4 stages:
1) Impending (occurs at 5-10 minutes of seizures) - there is neurotransmitter imbalance and ion channel opening/closing. Animals are likely to be responsive to first line anticonvulsant drugs (ACD) during stage 1.
2) Established (occurs at 10-30 minutes)- Inhibitory neurotransmitters are reduced, the receptors for the inhibitory neurotransmitters are internalized and there is upregulation of NMDR and AMPAR. Some animals may still be responsive to first line ACD, but most will be responsive to second line ACD.
3) Refractory - (occurs > 30 minutes) - There is a sustained imbalance between inhibitory and excitatory neuropeptides with BBB drug transporter upregulation. Most pets will not be responsive to first or second line ACD, but should be responsive to third line ACD.
4) (Super)refractory - (occurs > 24 hours) - There are gene expression alterations and animals are expected to be refractory to all ACDs.
What were considered first line ACDs? IV benzodiazepine drugs were considered the most effective and safest for in-hospital use and intranasal benzodiazepines are the preferred treatment for out-of-hospital treatment. "Although both midazolam and diazepam are potent and safe for the management of SE in dogs and cats, midazolam may be considered a more potent or safer benzodiazepine drug than diazepam." There we go!
They provided a list of the steps to follow, based on the evidence reviewed, when treating SE. I have repeated it here, but encourage you to read the entire article if you treat SE regularly as there are loads of pearls of wisdom peppered throughout the paper.
Steps to follow for SE:
Give midazolam or diazepam IV. A benzodiazepine bolus is effective if the seizure stops < 5 minutes after administration and no relapse occurs <10 minutes
If seizure activity is controlled with a benzodiazepine drug but recurs 10-60 minutes later is considered recurrent SE
Recurrent SE, or those that don't respond to the first bolus of benzodiazepine, should get a second IV dose of benzodiazepine drug
If seizures persist after two bolus, administer a 3rd dose immediately followed by a CRI. Dogs = midazolam or diazepam CRI is acceptable; Cats = diazepam should be avoided.
If seizures still persist, administer a 4th dose of benzodiazepine and administer a second line ACD
Second line ACD include levetiracetam IV, followed by phenobarbital IV and lastly fosphenytoin IV. Only administer the subsequent drug if the prior failed to stop the seizures.
Note: Levetiracetam or phenobarbital IV can be started after step 2 above if long-term maintenance is desired for either medication. They do not need to be reserved for second line use only.
I think that is enough for today. I'll go through some more data from the study in another TidBit Tuesday. I hope you enjoy the rest of this week, have a safe, relaxing holiday and look forward to working with you soon!
To Seize is to Grab, to Seizure is to Convulse
Seizures and Deficits...What to Do?
Today, we have, back by popular request, another lesion localization practice case! Enjoy!!
Signalment: 7 year old MC Pitbull-X (maybe Boxer dog?)
History: The dog presented with a history of 2 seizures, 1 day apart. Since the seizures, the dog has been walking compulsively to the left, and appears to bump into objects. Although a decreased appetite has been appreciated, the dog is still eating when hand fed.
Physical Examination: unremarkable
Neurologic Examination:
Mentation: Obtunded
Cranial nerves: Absent menace OD, intact PLR OU, mild head turn left, remainder normal.
Gait: Ambulatory with intermittent compulsive circling to the left. He is able to walk to the right when asked but will not continue the circles without inspiration.
Postural reactions: normal all limbs.
Reflexes: Normal all limbs.
Palpation: no spinal pain and normal cervical ROM and tail jack.
Neuroanatomic lesion localization (NALL) Practice
Let's look at the examination is sequence as it is listed above. If you wish to use the table format that I prefer, please look at the tables provided in the Small Animal Neuroanatomic Lesion Localization Practice Book (publisher CABI, date 2022 by yours truly). We'll discuss it in conversation format for this TidBit Tuesday.
Seizures: Seizures ALWAYS localize to the forebrain and are not readily lateralized (left or right side).
Obtunded: reduced mentation is noted with lesions in the forebrain and brainstem. This is NOT a clinical sign of cerebellar, spinal cord or neuromuscular disease, nor a non-neurologic finding. This narrows our lesion localization to forebrain or brainstem.
Cranial nerves: The menace pathway, in it's most basic sense, involves CN 2, the forebrain and CN 7. PLR involves CN 2, midbrain and CN 3. The blink reflex is not states as being abnormal above (blink reflex: CN 5 and CN 7) therefore by process of elimination, the menace deficit OD is most likely due to a forebrain lesion. The second part of the story is lateralization. Only the right eye is affected. This is a crossing tract (mostly) which means that the lesion should be on the left side of the forebrain.
Gait: The compulsive circling to the left is localized to the forebrain and, rarely, vestibular system. Localization to the vestibular system is most likely when a head tilt is present. Without a head tilt, I would consider a forebrain lesion most likely and they circle TOWARDS their lesion. This would further support a left forebrain lesion.
NALL: Left forebrain
How'd you do? Did anything surprise you with the NALL? If you enjoyed this case, thank your colleagues for suggesting a seizure NALL case for practice. :)
As a reminder, I will be out of the country starting next week through November 14th. I will be available by email ONLY (no cell phone service) and will be doing my best to keep up on emails. Please expect minor delays in my response because I will be lecturing and we'll be on different time zones but I will do my best to be as responsive as possible. Have a great week!
The Gut and The Brain
The gastrointestinal microbiota (GIM) is the new hot topic in neurology. This contractile organ, far distant from the brain is now considered a a possible source for drug resistant epilepsy in canine epilepsy research as well as a potential cause for behavioral disease in epileptic and non-epileptic dogs alike. A recent article by Watanangura et al highlighted the importance of the GIM in epilepsy.
The aim of their study was to investigate the effect of phenobarbital (monotherapy) on the composition of the GIM and to determine if it resulted in a change to behavior in a select group of dogs. To be included in this study, all dogs had to meet Tier II level of confidence for epilepsy (normal brain MRI, spinal tap, normal blood work and neurologic examination) and be naive on any anticonvulsant treatment. They had 12 dogs who meet these inclusion criteria. On day 1, they started phenobarbital at 2.5 mg/kg PO q12h and took fecal samples. The drug was continued without dose adjustment for 90 days at which time another fecal sample was taken. Behavioral questionnaires were submitted on day 1 and day 90 as well.
The results:
Serum phenobarbital concentrations ranged from 19.8-18.1 mg/L (day 30 and day 90)
Seven of 12 dogs were seizure free throughout the study and called responders.
Five of 12 dogs were not seizure free and were called non-responders.
Short chain fatty acids (SCFA) did increase significantly in the study, specifically propionate and butyrate.
Butyrate was significantly higher in the responder group compared to the non-responder group. Butyrate is an anti-inflammatory fatty acid which may benefit epileptic dogs, yielding better response to treatment. Perhaps this is due to the neuroprotective effects, or by providing an alternative energy source for the brain.
The behavior survey showed a significant decrease in stranger-directed fear, and non-social fear with an increase in trainability! Phenobarbital has been used as an anxiolytic for humans and veterinary patients, supporting this finding. An idiosyncratic hyperexcitability and aggression has been reported with phenobarbital however it is rare. (More commonly seen with levetiracetam.)
There was no difference in the bacterial taxa in this study except for a significant decrease in Clostridiales on day 90. The significance of this remains to be seen, however it may affect the distribution of MCFA and other products.
The Take Home Message
What do we do with this information? Well…we tuck it away in our heads and know that phenobarbital, or seizures themselves, might affect the GI microbiome and SCFA in the GI. Does this mean we should supplement? Not yet. I am not sure we know who, how and when to supplement based on this study. This was a critical step forward in our path towards understanding the GIM and I am excited to share additional information that comes forth in this area!
Have a wonderful week and enjoy what August has to offer us! I look forward to working with you soon.
Seizures, Quality of Life and Side Effects, oh my!
A study published in JAVMA (Gristina BR et al. JAVMA 2023) just recently caught my eye and I thought, perhaps it might interest you as well. The study evaluated 100 dogs with , with Tier I or Tier II level confidence of idiopathic epilepsy and assessed owner satisfaction, seizure control and adverse effects (the fancy name for side effects) of various drugs.
*Tier I = normal CBC, serum biochemistry, neurologic examination and bile acid test
* Tier II = all of tier I plus normal brain MRI and CSF analysis
How was the Seizure Control?
Improvement in seizure control was reported in 86% of dogs with phenobarbital, 76% in the levetiracetam and 65% in the zonisamide group. Treatment failure, due to inadequate seizure control, was 48% for phenobarbital, 32% for levetiracetam and 35% for zonisamide. Importantly, they didn't corelate seizure control with serum drug concentrations because we don't have target serum concentrations for levetiracetam and zonisamide. HTerefore, some dogs could have been under medicated, and thus poorly controlled. Interestingly, 88% of dogs were still on their original antiepileptic drug (AED) at the time this study was performed. Mean daily doses for phenobarbital, levetiracetam and zonisamide were 4.9 mg/kg, 53.8 mg/kg and 12.4 mg/kg, respectively.
What side effects made a splash?
Phenobarbital had the highest reported adverse effects at 77%, followed by levetiracetam at 59% and zonisamide at 39% of dogs. The most common adverse effects are listed below for each drug:
Phenobarbital: polyphagia, polydipsia, ataxia, sedation and polyuria
Zonisamide: sedation, ataxia, hyporexia
Levetiracetam: Sedation, ataxia, hyporexia, diarrhea, behavioral changes.
What was the perceived Quality if Life?
Owners perceived a significant improvement in quality of life, regardless of the anticonvulsant used, between pre and post treatment assessment. This is important for us to realize: clients can tolerate adverse effects if they perceive improved seizure control and quality of life! Although this retrospective, owner-perception study has limitations (all studies do), I felt it was worth repeating a bit of the information for you to add to your knowledge when addressing seizure management with your clients.
Have a wonderful week! Remember, early bird registration ends May 31st for the July CE event so register soon if you are planning to do so! Details are available on my website.
Reference: doi.org/10.2460/javma.22.10.0469
How to Question an Owner
Careful questioning of the owner is required to determine if the episodes described ARE seizures. Syncope, vestibular signs, neck pain, and movement disorders (think Scottie cramp) have episodic presentations with similarities to seizures. Nothing is fool proof, even an EEG, but here are some tips to get you going in the right direction.
Describe the event, please!
Discrete episodes, with a finite start and stop, combined with autonomic signs often indicate a seizure. Level of mentation can be confusing and difficult to determine (especially for those pesky night time seizures) so don't spend too much time grilling an owner on this one. Videos can be priceless. I have evaluated many dogs and cats for seizures that actually have something else after reviewing the video. Neck pain, movement disorders, and syncope are the most common pretenders that I've seen. Finally, ask how long the events are lasting. This question is subject to tremendous bias, but if the owner says "all day" I start wondering about other non-seizure events.
How often have the events occurred?
Okay sorry, I need to harp on this one. My pet peeve is hearing "about once a month" as an answer! This is an easy one and something we should encourage ALL clients with seizure pets to do. Keep a calendar! Tell owners to write it down, put it in a spreadsheet, mark it on their phone, keep a list - the choices are as varied as the seizures they record! You will NEED this to be in place to help you direct treatment. The single biggest reason to change treatment is that the seizures do not meet the seizure goals for epileptic pets. What are the seizure goals? Animals should have 1 seizure or less every 3 months.
Your second goal here is to learn about cluster seizures. If the animal has 2 or more seizures in 24 hours that is defined as cluster seizures. Cluster seizures need at home cluster seizure management (another topic for another day). Furthermore, some drugs work better for dogs with cluster seizures than those with single seizures. I personally believe that bromide is a terrific option for cluster seizures and will readily use it for patients with this type of pattern.
How long is each seizure?
This question is utilized to learn about status epilepticus. Any seizure longer than 3-5 minutes (people argue about what is the correct time) is considered status. Status warrants emergency management with injectable solutions (intranasal, intravenous, other). Untreated status can set an animal up for systemic side effects as well as increase the risk of permanent brain damage.
What does the animal do after the event is finished?
Your goal here is to evaluate the post ictal phase so that you can decide if a change in treatment is needed. Based on the rules outlined by the International Veterinary Epilepsy Task Force, severe post ictal changes (such as aggression) warrant treatment even if the other parameters for treatment haven't been met. I also use this question to determine how the owner is feeling about the event. Answers such as "he was fine" or "he paced and paced and seemed really upset" give me a window into how they feel about as much as how the dog did. Helping owners cope with seizures is also part of our job!
Do you have a seizure case that isn't meeting your seizure goals? Let me know! My favorite part of neurology is long-term seizure management so I'd love to help you, help your patients!
I'm headed to Chicago Vet Conference on Friday for a few talks on seizures, the neuro exam and lesion localization. I'd love to see you if you're at the conference so stop by and say "hi" if you have time!
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
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!
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!
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!
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
Client Communication Surrounding Seizure Management
Client Communication Surrounding Seizure Management
Client communication is critical during the initial seizure consultation. Many clients arrive in my exam rooms with one or more of the following expectations:
Their pet will not have any more seizures (this is a common one)
Medications should not have side effects (yes, this is often requested)
Inexpensive medication
Easy to administer, once to maybe twice daily medication (this is key for cat owners)
These goals do not align with our expectations, do they? Here are my goals:
Seizures will likely continue, if they've had 2 or more already.
Realistically, everybody gets 1 free seizure in their life. If you've had 2, or more, we probably should see your dog or cat and have a chat. If we place the pet on anticonvulsant drugs (ACD), our goal is to have 1 seizure or less every 3 months. That is a reasonable goal. The other option is to have a 50% reduction in seizure activity. This means that we need to know the interval of the seizures before treatment, and then calculate what a 50% reduction looks like for that individual. I am a goal oriented person and most clients also respond favorable to setting appropriate goals. This allow us to feel a sense of success when we achieve them, and a reason to continue to modify treatment if we don't.
Side effects WILL happen.
Any ACD has side effects, our goal is to have tolerable side effects for that family and pet. Tolerable may mean that they are okay with PU/PD, or it may mean that a level of sedation is acceptable. Each family is unique so this approach is tailored directly to the family I am working with. I am diligent outlining known side effects of the drugs at the time they are prescribed. Be sure to tell the client that many side effects improve or resolve by the time the pet reaches steady-state. This means we can set goals for resolution of signs, too. If the time to steady-state is 14 days (phenobarbital) then give clients that information so that when they see side effects (they will) they know to hang in there for 14 days and it is likely to get better. If it isn't, we can adjust after evaluating the serum drug concentration at steady-state (when applicable for the drug prescribed).
Cost
The cost of ACD varies over time. Phenobarbital when through a period where it was difficult to obtain and was, therefore, very expensive compared to previous and subsequent years. The fluctuation in cost is really due to production, availability and (as with all things right now), shipping costs. It can be helpful to outline the cost of the drug up front, but ensure that the client knows this can change over time depending on the aforementioned causes.
Administration is key!
If an owner cannot administer the medication, it doesn't matter how effective it SHOULD be because the pet isn't taking it. This concept is especially near and dear to cat owner's. In human medicine, when a prescription was recommended 1x daily, the compliance was over 80% (the drug was given as prescribed over 80% of the time). However, when the prescription was recommended at a 3-4x daily dosing, the compliance dropped as low as 10-15% in some studies. This becomes especially true in the pediatric world, in which an individual is having something given TO them. I think it is reasonable to translate this to our veterinary world and realize that three times a day levetiracetam, even if the perfect drug for other reasons, may not be a good option for some clients simply because compliance will be low. It has been well established in neurology that the variation between peak and trough can be just as important as one serum concentration at one time point. If there is a wide swing between peak and trough, there may be a greater chance of breakthrough seizures or poor control. Missed doses can result in wide swings of the peak and trough serum concentrations and therefore should be avoided.
So there you have it! I hope this pep talk has been helpful for you as you help clients navigate the (at times) choppy water of seizure management. If you need help with a seizure case, or feel the client would benefit from a second opinion, please reach out. Seizure management is one of my favorite aspects of neurology!
Have a great week and keep those consults coming!
Status Epilepticus
Status epilepticus (SE) is defined as continuous seizure activity for more than 5 minutes or two seizures in which consciousness isn't resumed in between. SE has a potentially fatal outcome in dogs and humans and is devastating to watch, try to fix, and explain to clients. I wish it wasn't so.
A recent study out of the UK (see below) outlined risk factors for short term mortality (death during hospitalization for SE) and long-term recurrence of SE in dogs. Here are some key points but, as always, if you want more depth please read this open access article.
Short-term mortality:
124 cases included, 87 survived to discharge (70%)
Increasing age, shorter duration of hospitalization, onset of SE before hospitalization and SE being caused by a potentially fatal etiology were related to mortality.
Of the survivors - 42 had idiopathic epilepsy ( this was the first seizure in 6 dogs), 21 had structural epilepsy (first seizure in 12 of the dogs) and 8 had reactive seizures (first seizure in 10 of the dogs).
Recurrence of SE
74 of 87 dogs had follow-up information after discharge. Recurrence happened in 20 of 74 dogs.
Pharmacoresistant epilepsy and having focal seizures were the only significant risk factor identified. .
50% of recurrence was within 2 months from discharge
What do we make of this?
Status epilepticus is a serious form of a seizure. We cannot fully prevent it, but we can counsel clients on the possibility if their animal has one of the predisposing factors identified above (advancing age, fatal etiology or focal seizures). Do not delay on treatment of seizures. Waiting and seeing can result in SE and avoidance is definitely the best policy for management of SE.
JVIM (2022): 36: 353-662.
Thanks for reading! Happy Easter and Passover to those of you that celebrate. Safe fast to those of you in the midst of Ramadan. I look forward to continuing to work with you and your staff to help pets with neurologic disease.
Acute and Chronic Adverse Effects of Zonisamide in Dogs
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
How to Use Phenobarbital Serum Concentrations
The 5 year old Golden Retriever
The set up...
Decker presented to me with a history of 3 seizures in the preceding 2 weeks. The seizures were consistent with generalized, tonic-clonic seizures of a duration about 30 seconds to 2 minutes (depending on the parent reporting the seizure). Decker was a very big boy. Not fat...just one of those super large Goldens that we occasionally see. He had a pretty healthy history prior to the seizures other than occasional ear and skin issues that the primary veterinarian had addressed. He wasn't taking any current treatment, was up to date on vaccines, hadn't traveled out of Wisconsin in the last 6 months, did not have a history of head trauma and wasn't a working dog. Yes, I do ask all of those questions during a seizure consult, every time. Unless I forget. But I try not to forget.
The Exam...
Decker's exam was normal. Normal physical (other than his giant, wonderful self) and a normal neurologic examination. So his lesion localization was... (you fill in this blank. Look at the bottom to check your answer).
The Plan...
Decker needed anticonvulsants. More than 1 seizure every 3 months is a good reason to start anticonvulsant therapy according to the IVETF. So, we did! We started phenobarbital at about 4 mg/kg PO q12h and requested a serum phenobarbital concentration in 14 days.
The Serum Concentration...
14 days after starting phenobarbital the serum phenobarbital concentration was 22 ug/ml (reference range: 15-40 ug/ml)
What do you do with this information?
Well, to answer that question you must first ask yourself why you took the serum phenobarbital concentration in the first place? Was it...
1. To document that it was therapeutic for Decker?
2. To ensure it wasn't toxic?
3. To show if the client wasn't giving it right?
4. To document if the serum concentration was too low?
How do you know if the dose was appropriate for Decker? You look at the seizure calendar, which we cannot do until Decker has been on phenobarbital for at least 3 "seizure cycles". What is a seizure cycle? It is the interval between seizures. In his case, it is less than 2 weeks (3 seizures within 2 weeks). So, we must evaluate efficacy by looking at about a 6 week interval of time.
Toxicity is seen by clinical adverse effects in the pet, which we cannot truly evaluate until the drug reaches steady-state. Steady-state is about 14 days in dogs, therefore signs of toxicity (or that the dose is too HIGH) should be assessed at the 14 day visit, or shortly thereafter. If adverse clinical effects are problematic after 14 days, the dose may be too high.
If the client isn't giving the drug, the serum concentration will be lower, but how much lower really depends on how often they miss a dose. This is not an appropriate way to ensure the client is giving the drug, in my opinion.
So, why take a serum concentration at all?? I do it to determine if the dose is too LOW. Serum concentrations below 15 ug/ml are outside of the accepted canine therapeutic range and therefore the dose should be increased. I would argue that serum concentrations below 25 ug/ml are clinically less desirable and typically advocate a dose increase for many pets (depending on clinical adverse effects).
What is the take away message?
Take the serum concentration to ensure it is not too low, use the dog to determine if the side effects are too high, and use the seizure calendar to determine if the dose is effective.
Thanks for reading! If reading this makes you groan, please reach out! I'm happy to help you manage your patients and love doing seizure consults. (Yes, for real!)
I am on vacation until Friday February 18th and ask for your patience if you reach out this week. I will reply but it probably won't be as quickly as you are used to!
Neospora Meningoencephalitis vs Immune Mediated Meningoencephalitis
Immune mediated meningoencephalitis (aka meningitis of unknown origin: MUO) is very common and is a cause of intracranial disease for many pets. Infectious meningoencephalitis accounts for only about 2% of the cases seen through a referral center and is, therefore, in the minority. Infectious meningitis may be secondary to fungal infection, protozoal (Toxoplasma or Neospora), viral, bacterial or in southern states, some tick borne diseases. Neospora infection is one of the more common causes of infectious meningoencephalitis we see in Wisconsin (probably second only to fungal) and therefore one of the main differential diagnoses for a pet with meningoencephalitis. The current way to diagnose Neospora is via serum titer elevation, evidence of encysted protozoa on biopsy or necropsy, or PCR on serum or CSF. All of these tests take a variable amount of time, depending on the laboratory, so some researchers in the UK came up with another idea. (https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16334)
Scientific Question: Can we differentiate between Protozoal meningoencephalitis and MUO using CK and AST values?
Rational: Protozoa (Toxoplasma and Neospora) are often found in muscle which would result in membrane disruption, thus elevating CK (and subsequently AST). Seizures, a common sign of MUO and protozoal meningoencephalitis, can also elevate CK so the researchers also aimed to evaluate the temporal relationship between seizures and CK elevation.
Methods: This was a retrospective study of 59 dogs diagnosed with MUO and 21 dogs diagnosed with Neospora (no dogs were diagnosed with Toxoplasma in this study).
Results: A significantly higher CK and AST value were identified in dogs with Neospora compared to those with MUO. Using a cutoff value of 458 U/L, there was a sensitivity of 95.24% and specificity of 96.61% for active Neospora meningoencephalitis and using a prevalence of 2.25% for active infection in the UK, there was a negative predictive value of 99%. This suggests that dogs with a CK less than 485 U/L are unlikely to have a diagnosis of Neospora infection associated with their intracranial signs. Twenty of 21 dogs with Neospora had CK higher than 485 U/L, and 2 dogs with MUO had CK > than 485 U/L in this study.
Things to remember: CK has a short half-life (22 hours) so if you test, do so within the acute phase of disease. CK and AST are not muscle specific and can be found in myocardium, intestine and AST in the liver also.
What do you do with this information? If you have a dog with suspected meningoencephalitis, consider running a CK and AST on initial blood work. If it is greater than 485 U/L, a Neospora titer should be performed.
Have a great week and thanks for reading!
Note about the holidays: I will be available for emergency cases on December 24, and 25th.
New Years Eve and Day, I will be spending time with my family building a colossal gingerbread house and stables. If I'm not baking, cutting and cooling gingerbread I will be making sticky frosting glue and won't be available for phone calls, texts or email. Thank you for your understanding!