Autoimmune encephalitis is a unique pathology, identified in perhaps up to 50% of humans with encephalitis, and recently identified in a large cohort of cats. In a study published in Vet Journal (2023), Glantschnigg-Eisl et al described the clinical, laboratory, radiological and pathological findings in 32 cats diagnosed with this specific form of epilepsy. Human autoimmune epilepsy is caused by immune attack of the voltage-gated potassium channel (VGKC), generating specific antibodies to this protein complex and the secreted protein LGI1 as well. It is now proposed that the presence of these antibodies reflect a specific form of limbic epilepsy in cats, similar to the autoimmune epilepsy noted in humans. Most importantly to us (veterinarians), cats with this form of epilepsy have a normal MRI and CSF analysis! Therefore, calling it encephalitis based on our standard testing is challenging. Is it a form of idiopathic epilepsy, or an encephalitis? Time shall tell. The authors describe this as an encephalitis, similarly to the human counterpoint. Below is a small summary of their findings. For the full study, please refer to the article link at the bottom.

Clinical Picture

All cats in the study had seizures as their presenting complaint. All cats had positive antibodies to VGKC, with 26 cats having LGI1 antibodies as well. No clinical findings distinguished cats with LGI1 antibodies from those without. Focal and generalized seizures were almost evenly divided as a presenting seizure type with cluster seiuzres in 27/32 cats. Similar to humans with limbic epilepsy, many of the cats (22/32) had interictal behavior changes with a history of unprovoked aggression in 12/32 cats. This was identified as a common finding but not yet pathognomonic for this form of epilepsy. Median age at onset was 3.42 years.

Laboratory Findings

.No significant laboratory abnormalities were identified. As noted above, CSF analysis was normal for all but 1 cat and that cat had only a mildly elevated protein.

Long-term Outcome

Phenobarbital was started in 26/28 cats that underwent treatment with about 1/2 of the cats having a second AED added throughout treatment. Prednisone was administered in 10/32 cats (most of which were the LGI1 positive cats).The cats that received steroids, often received prednisone. This medication was administered to the cats with the most severe neurologic signs, including seizure frequency or severity, and was linked to poorer survival. As the authors noted, it is unclear if the prednisone is linked with poorer outcome or if the survival is linked to more severe condition and therefore prognosis. This was interesting because the human seizure disorder associated with LGI1 antibodies is typically rapidly and markedly responsive to steroids.

Two factors were associated with prognosis in this study. The first was number of seizures at presentation. Cats with a higher seizure frequency were more likely to be euthanized. The second was the association with hippocampal pathology. Higher MRI scores suggested a lower prognosis and higher likelihood of euthanasia. The overall survival rate was 70-80%, which was similar to survival rates for idiopathic epilepsy in cats. At 1 year, most cats had a marked decrease in seizure activity from a mean of 3.6 seizures daily to 1-2 per year. This suggests that if they survive the short term, their long-term prognosis is good. QoL scores were good to acceptable in the long-term follow-up group.

What are my take away points from this study for practice?
1. Be aware that this disease exists. If you see cats with seizures, especially severe onset seizures, VGKC autoantibodies could be an underlying cause.
2. Treat with phenobarbital - it works terrifically for most cats, regardless of the underlying cause.
3. Steroids may not be the answer. Then again, maybe they are if we catch the disease earlier?? I don't think we can make this a take away just yet; more information is needed.

I hope you have a wonderful week and thanks for reading!

A gentle reminder: I've had an uptick in cancelations over the past few days. I know my schedule is getting booked out further than is typical, and I apologize for the resulting delay. Please cancel your appointments with as much notice as possible, whenever possible. I have a waitlist and would LOVE to move folks forward if I have an opening. I am hopeful that the waitlist will diminish soon now that I able to open up a few more days for consults. Thank you!

Lastly, gut yantif to those of you celebrating! I hope you had a safe fast yesterday.

Reference: https://www.sciencedirect.com/science/article/pii/S1090023323000254

Etiology

Rabies is neurotropic rhabdovirus that causes fatal infection in dogs, cats and humans. Usually infection is transmitted by inoculation with saliva by means of a bite. The virus then spreads into the CNS via peripheral nerves. Once the brain is infected, the virus spreads out through peripheral nerves to the salivary glands among other targets – 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. 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 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 real 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! Furthermore, a rabies positive bat was identified on a sidewalk in Dane county just this week. Although fewer Rabies positive bats have apparently been identified this year (so far) the virus is still around and therefore still something we should be talking about!

Thanks for reading! Rabies virus infection is something I think about daily, given the cases that I see, and is one of the more daunting diseases we are faced with. Please reach out if you have any questions!

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

Autoimmune Feline Encephalitis

Rabies Awareness