Article

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: 7.01). 04/2007; 64(3):404-10. DOI: 10.1001/archneur.64.3.404
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
79 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Limbic encephalitis (LE) associated with antibodies to the voltage-gated potassium channel complex (VGKC) is a potentially reversible cause of cognitive impairment. Despite the prominence of cognitive dysfunction in this syndrome, little is known about patients' neuropsychological profile at presentation or their long-term cognitive outcome. We used a comprehensive neuropsychological test battery to evaluate cognitive function longitudinally in 19 patients with VGKC-LE. Before immunotherapy, the group had significant impairment of memory, processing speed and executive function, whereas language and perceptual organisation were intact. At follow-up, cognitive impairment was restricted to the memory domain, with processing speed and executive function having returned to the normal range. Residual memory function was predicted by the antibody titre at presentation. The results show that, despite broad cognitive dysfunction in the acute phase, patients with VGKC-LE often make a substantial recovery with immunotherapy but may be left with permanent anterograde amnesia.
    Journal of neurology, neurosurgery, and psychiatry 01/2014; 85(4). DOI:10.1136/jnnp-2013-306724 · 4.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In patients with immune-associated disorders of the gray central nervous system matter (including recurrent seizures), antibodies against intracellular antigens have been discovered since the 1980s/1990s. In recent years, new antibodies against surface antigens have also been discovered. In two respects, these antibodies are even more interesting than the ones to intracellular antigens as, first, they promise a better response to immunotherapy; and, second, these antibodies contribute greatly to the understanding of the disease mechanisms. Whereas in encephalitides with antibodies against intracellular antigens, a cytotoxic T-cell-mediated response seems to be responsible for neuronal cell loss, in encephalitides with autoantibodies against surface antigens these antibodies are probably the relevant pathogenic agents in the associated disease conditions. On the one hand, antibodies to the NR1 subunit of N-methyl-D-aspartate receptors have been suggested to cause internalization and loss of these receptors without any cell destruction. This mechanism can explain the reversible functional effects caused by these antibodies. On the other hand, antibody- and complement-mediated destructive, and the irreversible effects of antibodies against the voltage-gated potassium channel antigens have been noted. These emerging findings make it plausible that immunological therapies, preferably early after characterization of the antibodies, offer opportunities to restore the health of affected patients.
    Journal of the American Society for Experimental NeuroTherapeutics 02/2014; 11(2). DOI:10.1007/s13311-014-0264-3 · 3.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and purposeAutoimmune encephalopathies (AEs) are a heterogeneous group of neurological disorders that affect cognition. Although memory difficulties are commonly endorsed, few reports of AEs inclusively assess all cognitive domains in detail. Our aim was to perform an unbiased cognitive evaluation of AE patients with voltage-gated potassium channel complex antibodies (VGKCC-Abs) in order to delineate cognitive strengths and weaknesses.Methods Serial VGKCC-Ab AE subjects (n = 12) were assessed with a comprehensive evaluation of memory, executive functions, visuospatial skills and language. Clinical magnetic resonance imaging (MRI) (n = 10/12) was evaluated. Five subjects had serial cognitive testing available, permitting descriptive analysis of change.ResultsSubjects demonstrated mild to moderate impairment in memory (mean Z = −1.9) and executive functions (mean Z = −1.5), with variable impairments in language and sparing of visuospatial skills. MRI findings showed T2 hyperintensities in medial temporal lobe (10/10) and basal ganglia (2/10). Serial cognitive examination revealed heterogeneity in cognitive function; whereas most patients improved in one or more domains, residual impairments were observed in some patients.Conclusions This study augments previous neuropsychological analyses in VGKCC-Ab AE by identifying not only memory and executive function deficits but also language impairments, with preservation of visuospatial functioning. The study further highlights the importance of domain-specific testing to parse out the complex cognitive phenotypes of VGKCC-Ab AE.
    European Journal of Neurology 07/2014; 21(10). DOI:10.1111/ene.12482 · 3.85 Impact Factor

Full-text

Download
20 Downloads
Available from
Jul 28, 2014