Extensive and Temporally Ungraded Retrograde Amnesia in Encephalitis Associated With Antibodies to Voltage-Gated Potassium Channels

Imperial College London, Londinium, England, United Kingdom
JAMA Neurology (Impact Factor: 7.42). 04/2007; 64(3):404-10. DOI: 10.1001/archneur.64.3.404
Source: PubMed


Encephalitis associated with antibodies to voltage-gated potassium channels (VGKC-Ab) is characterized by epilepsy, behavioral changes, and anterograde memory impairment. Magnetic resonance imaging reveals abnormal signal predominantly restricted to the mediotemporal lobes.
To determine the temporal extent and potential reversibility of retrograde amnesia in 3 patients with VGKC-Ab-associated encephalitis.
Case report.
Clinical. Patients Three patients diagnosed as having VGKC-Ab-associated encephalitis underwent cognitive testing before and after immunotherapy.
In addition to standard neuropsychological tests, retrograde memory was assessed using 2 novel tests. Memory for past newsworthy events was assessed using a public events test; test material was divided into epochs of 5 years and spanned approximately 25 years. This was complemented by a famous faces test in which patients were required to identify individuals from the recent and remote past.
All 3 patients were found to have temporally ungraded retrograde amnesia dating back more than 20 years. Magnetic resonance imaging in all patients revealed high-signal abnormalities predominantly affecting the hippocampi. Subsequent testing performed after immunotherapy revealed subjective improvement but no evidence of a temporal gradient in the recovery of past memories.
Encephalitis associated with VGKC-Ab results in extensive and temporally ungraded retrograde amnesia that is partially reversible with immunotherapy. Magnetic resonance imaging high-signal abnormalities were primarily restricted to the hippocampi. These data are supportive of theories postulating a role for the hippocampus in the storage and retrieval of all past memories, irrespective of age, rather than theories of memory consolidation that propose an involvement of the hippocampus only in the temporary storage of memories.

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Available from: Susie M D Henley, Jul 28, 2014
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    • "Three associated proteins have, so far, been recognized: contactin-associated protein-like 2 (CASPR2) (Vincent et al. 2009;Irani et al. 2010a;Vincent and Irani 2010;Lancaster et al. 2011), leucine-rich, glioma-inactivated 1 (LGI1) (Irani et al. 2010a;Lai et al. 2010) and contactin-2 (Irani et al. 2010a). Clinically, these patients present with memory loss, confusion, behavioral changes, and often prominent seizures (Vincent et al. 2004;Chan et al. 2007). Most of these patients do not have an underlying tumor. "
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    ABSTRACT: This review reports the available evidence on the activation of the innate and adaptive branches of the immune system and the related inflammatory processes in epileptic disorders and the putative pathogenic role of inflammatory processes developing in the brain, as indicated by evidence from experimental and clinical research. Indeed, there is increasing knowledge supporting a role of specific inflammatory mediators and immune cells in the generation and recurrence of epileptic seizures, as well as in the associated neuropathology and comorbidities. Major challenges in this field remain: a better understanding of the key inflammatory pathogenic pathways activated in chronic epilepsy and during epileptogenesis, and how to counteract them efficiently without altering the homeostatic tissue repair function of inflammation. The relevance of this information for developing novel therapies will be highlighted.
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    • "This VGKC-complex antibody associated limbic encephalitis is characterized by the acute to subacute onset of amnesia, disorientation and medial temporal lobe seizures. Although substantial recovery is seen after immunotherapy, patients often show residual amnestic deficits (Vincent et al., 2004; Chan et al., 2007). Some patients with VGKC-complex antibody limbic encephalitis also have brief, very frequent seizures, typically involving posturing of the hemiface and ipsilateral arm (Irani et al., 2008). "
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    • "It has subsequently become clear that most of these antibodies are directed not against the voltage-gated potassium channel itself, but instead against specific components of the channels including the LGI1 (leucine-rich, glioma-inactivated 1) molecule, which seems to be important for synaptic communication (Lai et al., 2010; Vincent et al., 2011; Benarroch, 2012). Although previous studies have investigated some cognitive aspects of patients with VGKC-Ab (Maguire et al., 2006; Chan et al., 2007; Hartley et al., 2007), the full spectrum of cognitive impairment—and specifically performance in short-term memory tasks—in this population is still unknown. Many previous studies on MTL involvement in memory over brief delays have studied patients suffering from Korsakoff's syndrome , anoxia or herpes encephalitis, which potentially affect various brain regions outside the MTL. "
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