Non-Convulsive Seizures in Dogs

Non-Convulsive Seizures in Dogs and Cats With Cluster Seizures

This week we're going to dig into non-convulsive seizures in dogs a bit before we jump off of the seizure bandwagon and back into other topics in neurology next week. (Sorry to the surgeons that read these!) A recent study out of Germany by Tastensen et al (DOI: 10.1111/jvim.16953) evaluated nonconvulsive seizures in dogs and cats with cluster seizures. A few definitions, first....

Cluster seizures: 2 or more seizures within 24 hours in which pets regain consciousness between seizures. 
Status Epilepticus (SE): Seizures lasting for longer than 5 minutes or 2 or more seizures in which consciousness is not regained. 
Nonconvulsive seizures (NCS): no visible somatic or autonomic manifestation of seizures with evidence on EEG. 
Nonconvulsive status epilepticus (NCSE): no visible somatic or autonomic manifestation of seizures, with evidence on EEG and the seizures are lasting longer than 5 minutes. (yikes!)

This study evaluated 26 dogs and 12 cats with EEG monitoring following cluster seizures and found 11 of the animals (9 dogs, 2 cats) had NCS. Of these 11 dogs and cats, 4 dogs and 2 cats (16%) had NCSE. They found repeated doses of benzodiazepine drugs and levetiracetam did not break the seizures. Only inhalant anesthesia with propofol induction resulted in a return to baseline EEG. 

Six of 11 animals had a decreased level of awareness and a few of them had mild twitching of an ear which could have represented the somatic movement of the seizure. Sadly, this group had a much higher mortality rate (73% NCS; 67% NCSE) than the general population of dogs without NCS or NCSE (27%). Overall, cluster seizures have a higher mortality rate than for dogs or cats without cluster seizures (~40%) as well. None of these patients died as a result of NCSE or NCS however several were euthanized. 

The seizure etiology was more often structural epilepsy (neoplasia, encephalitis, malformation, vascular cause or trauma) and accounted for 22/38 (58%) of the animals in the study. About 18% (7/38) had idiopathic epilepsy, 11% (4/38) had unknown epilepsy and about 18% (7/38) had reactive seizures. Does this mean that dogs and cats with structural epilepsy are more likely to have cluster seizures, or does it mean that the prognosis is inherently poorer for animals with structural epilepsy? If the prognosis is poorer, do clients elect humane euthanasia when in a situation of NCSE more readily, driving up the mortality rate, or does the disease make it harder to treat? Non-convulsive epilepsy is more common in humans with cluster seizures as well, and has a higher mortality rate than people without NCE or NCSE. I don't have the answers to these questions but pose them as a way of critically reviewing the data provided.

Take home message:
If you have a dog or cat with a history of cluster seizures and they are persistently, mentally inappropriate (obtunded, stupor or coma) after stopping the physical appearance of the seizure consider nonconvulsive seizures. Inhalant anesthesia would be recommended however without additional diagnostic testing (such as MRI or spinal tap) it would be unknown if there is high intracranial pressure from the underlying disease which could increase the risk of complication with anesthesia. So what do you do in general practice? If the owner wants a referral for 24 care - start there. If not, consider a bolus of diazepam or midazolam. OR you could monitor for 1-2 hours to determine if the change in behavior is secondary to postictal changes. 

Not sure how to manage a seizure case? Feel free to email or call me or schedule a neurology consult! Please always text or call if it is an emergency; I don't check my email very often during the day.  Have a great rest of your 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!

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.