Hippocampal sclerosis in feline epilepsy

Abstract

Hippocampal sclerosis (HS) refers to loss of hippocampal neurons and astrogliosis. In temporal lobe epilepsy (TLE), HS is a key factor for pharmacoresistance, even though the mechanisms are not quite understood. While experimental TLE models are available, there is lack of models reflecting the natural HS development. Among domestic animals, cats may present with TLE-like seizures in natural and experimental settings. With this study on the prevalence, segmental pattern and clinicopathological correlates of feline HS, we evaluated the translational value for human research. Evaluation schemes for human brains were applied to epileptic cats. The loss of neurons was morphometrically assessed and the degree of gliosis was recorded. Hippocampal changes resembling human HS were seen in about one third of epileptic cats. Most of these were associated with infiltrative diseases such as limbic encephalitis. Irrespective of the etiology and semiology of seizures, total hippocampal sclerosis was the most prevalent form seen in epileptic animals. Other HS types also occur at varying frequencies. Segmental differences to human HS can be explained by species-specific synaptic connectivities and a different spectrum of etiologies. All these variables require consideration when translating results from feline studies regarding seizure-associated changes of the temporal lobe and especially HS.

Keywords: MTLS; TLE; feline; hippocampus temporal lobe epilepsy; mesial temporal lobe sclerosis; seizure.

Figure 1

Segment‐specific  INND  values of the control group and the seizure group. The red lines indicate the cut‐off for mild (SD × 2), moderate (SD × 4) and severe (SD × 6) INND increase. Values lying within the defined boundaries are expressed as percentages for both groups, respectively.

Figure 2

Combined pathologies in epileptic cats.

Figure 3

A positive correlation between age and  INND  is seen in control cats, while the interdependence is lost in hippocampi of epileptic cats.

Figure 4

The left pictures show the physiological ( A ) and pathological ( B ) subgross appearance of the temporal hippocampus. B features the most common polysegmental HS with losses throughout all CA segments (black arrows) and a few residual pyramidal clusters (white arrows) in CA1. On the right, GFAP‐positive astrocytes are shown in the unaffected hilus (C) and this of a cat with severe HS (D).

Figure 5

(A) Pyramidal cell degeneration in limbic encephalitis compared to a normal CA segment. (B) Neuronal loss shows morphologic features of excitotoxicity in terms of eosinophilic necrosis (red arrow). The black arrow indicates scanty perivascular inflammation. (C) Note the perineuronal infiltrates (blue frames).

Figure 6

Segmental  HS  pattern seen in the hippocampi of epileptic cats from both sides. The picture in the left corner visualizes the borders of each CA segment.

Figure 7

INND  values sorted for the individual seizure type. The red rhombi represent the values that were accompanied by reactive astrogliosis and therefore are consistent with HS. Note that clinical seizure types did not predict reduction of neuronal cell density in certain CA segments in cats with or without HS. Gen = generalized seizures; SSE = secondary status epilepticus; Foc = focal seizures; PSE = primary status epilepticus.

Figure 8

INND  values sorted for the etiological category. There is no significant interdependence between seizure nosology and the segmental pattern of HS. Red rombi resemble HS‐affected hippocampi. Comb = combined pathologies; IC mass = intracranial mass effects; Inflam = inflammatory; Met = metabolic/degenerative changes; Vasc = vascular/vasogenic changes.