ISSN 2398-2950      

Feline limbic encephalitis

ffelis
Contributor(s):

Mark Lowrie

Laurent Garosi

Synonym(s): Limbic encephalitis, Feline complex partial cluster seizure with orofacial involvement (FEPSO)


Introduction

  • Cause: suspected immune-mediated condition of geriatric cats.
  • Signs: complex partial cluster seizures (CPS) consisting of facial twitching and staring, facial twitching; post-ictal signs include behavioral changes and aggression.
  • Diagnosis: MRI may reveal hyperintensities within the hippocampus and serology can reveal increased antibody concentrations to voltage-gated potassium channel (VGKC)-complexes. 
  • Treatment: seizures respond poorly to anti-epileptic drugs (AED) but well to immunotherapy. 
  • Prognosis: fair.

Pathogenesis

Etiology

  • Over the last 15 years it has been increasingly recognized that a number of neuronal cell surface proteins can be targets for pathogenic autoantibodies.
  • These autoantibodies bind to their target in vivo  and disrupt normal brain functioning resulting in seizures and limbic encephalitis.

Pathophysiology

  • In people, limbic encephalitis is associated with the production of serum antibodies against voltage-gated potassium channel complexes (VGKC-complexes) resulting in an acute epileptic condition. 
  • Human autoimmune limbic encephalitis is often associated with neoplasm (paraneoplastic) (at least one cat has been identified as having DCC (deleted in colorectal cancer antibodies = netrin-1 receptor antibodies) antibodies that might be the cause of autoimmune LE although no tumor could be identified on imaging). 
  • In people, the antibodies are directed against different proteins in these VGKC-complexes (notably leucine-rich glioma inactivated 1 [LGI1] and contactin-associated protein-like 2 [CASPR2]).
  • Clinical signs include confusion and facial twitching and MRI reveals hyperintensities within the hippocampus.
  • Seizures respond poorly to anti-epileptic drugs (AED) but well to immunotherapy.
  • A similar phenomenon is suspected in cats;
    • Leucine-rich glioma-inactivated 1 (LGI1), a secreted molecule which acts a synaptic bridge and is particularly richly expressed in the hippocampus.
  • Human patients with LGI1-antibodies typically respond very well to immunotherapies, including corticosteroids and plasma exchange.
  • In a study of 14 cats suffering distinctive CPS, consisting of facial twitching and staring, 5/14 cats had VGKC and 4/14 cats had LGI1-antibodies.
  • After AED and corticosteroid treatment, 10/14 experienced full remission and 1 had partial remission. The remaining 3 died, one of which had histopathological examination confirming hippocampal necrosis.

Timecourse

  • Signs usually develop sub-acutely and rapidly progress.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Binks S, Lamquet S, Crawford A H et al (2022) Parallel roles of neuroinflammation in feline and human epilepsies. Vet J PubMed.
  • Hasegawa D, Ohnishi Y et al (2019) Deleted in colorectal cancer (netrin-1 receptor) antibodies and limbic encephalitis in a cat with hippocampal necrosis. JVIM 33 (3), 1440-1445 PubMed.
  • Pakozdy A, Halasz P, Klang A et al (2013) Suspected limbic encephalitis and seizure in cats associated with voltage-gated potassium channel (VGKC) complex antibody. JVIM 27 (1), 212-214 PubMed.

Other sources of information

  • Royal Veterinary College. The International Feline Encephalitis Study Group. Website: https://www.rvc.ac.uk (pdf online).

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