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Retrograde Amnesia in LGI1 and CASPR2 Limbic Encephalitis: Two Case Reports and a Systematic Literature Review
Malvaso Antonio1,2, Denise Cerne3, Bernini Sara4
1Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
European Journal of Neurology
|March 21, 2025
Summary
Isolated retrograde amnesia is rare in limbic autoimmune encephalitis (LAE) associated with voltage-gated potassium channel (VGKC) complex antibodies, particularly CASPR2-LAE. This rare presentation is linked to poor cognitive recovery and warrants further investigation.
Area of Science:
- Neuroimmunology
- Cognitive Neuroscience
Background:
- Limbic autoimmune encephalitis (LAE) often presents with both anterograde and retrograde amnesia.
- Antibodies targeting the voltage-gated potassium channel (VGKC) complex, specifically CASPR2 and LGI1, are common causes of LAE.
- Isolated retrograde amnesia, without other cognitive deficits, is exceptionally rare in LAE.
Purpose of the Study:
- To describe two novel cases of CASPR2-LAE presenting with isolated retrograde amnesia.
- To systematically review the literature for cases of LAE with retrograde amnesia, focusing on VGKC-complex antibodies.
- To investigate the prevalence and clinical characteristics of isolated retrograde amnesia in LAE.
Main Methods:
- Case report of two patients with CASPR2-LAE and isolated retrograde amnesia.
- Systematic literature review following PRISMA guidelines.
- Analysis of studies involving LAE, VGKC-complex antibodies (LGI1, CASPR2), and memory impairment.
Main Results:
- Out of 467 patients with VGKC-complex antibodies and LAE, 14 (2.9%) had retrograde amnesia, usually with anterograde amnesia.
- The two reported cases of CASPR2-LAE were the only instances of isolated retrograde amnesia (0.4%).
- Retrograde amnesia, especially when isolated, was associated with limited cognitive improvement in most patients.
Conclusions:
- Retrograde amnesia is an under-recognized symptom in VGKC-complex antibody-associated LAE.
- Isolated retrograde amnesia expands the clinical spectrum of CASPR2-LAE.
- The findings highlight the importance of investigating retrograde amnesia in autoimmune encephalitis and suggest potential insights into its pathophysiology.
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