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: 7.42). 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.

Download full-text

Full-text

Available from: Susie M D Henley, Jul 28, 2014
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Dec 2015 · Cold Spring Harbor Perspectives in Medicine
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Voltage-gated potassium channel complex antibodies, particularly those directed against leucine-rich glioma inactivated 1, are associated with a common form of limbic encephalitis that presents with cognitive impairment and seizures. Faciobrachial dystonic seizures have recently been reported as immunotherapy-responsive, brief, frequent events that often predate the cognitive impairment associated with this limbic encephalitis. However, these observations were made from a retrospective study without serial cognitive assessments. Here, we undertook the first prospective study of faciobrachial dystonic seizures with serial assessments of seizure frequencies, cognition and antibodies in 10 cases identified over 20 months. We hypothesized that (i) faciobrachial dystonic seizures would show a differential response to anti-epileptic drugs and immunotherapy; and that (ii) effective treatment of faciobrachial dystonic seizures would accelerate recovery and prevent the development of cognitive impairment. The 10 cases expand both the known age at onset (28 to 92 years, median 68) and clinical features, with events of longer duration, simultaneously bilateral events, prominent automatisms, sensory aura, and post-ictal fear and speech arrest. Ictal epileptiform electroencephalographic changes were present in three cases. All 10 cases were positive for voltage-gated potassium channel-complex antibodies (346-4515 pM): nine showed specificity for leucine-rich glioma inactivated 1. Seven cases had normal clinical magnetic resonance imaging, and the cerebrospinal fluid examination was unremarkable in all seven tested. Faciobrachial dystonic seizures were controlled more effectively with immunotherapy than anti-epileptic drugs (P = 0.006). Strikingly, in the nine cases who remained anti-epileptic drug refractory for a median of 30 days (range 11-200), the addition of corticosteroids was associated with cessation of faciobrachial dystonic seizures within 1 week in three and within 2 months in six cases. Voltage-gated potassium channel-complex antibodies persisted in the four cases with relapses of faciobrachial dystonic seizures during corticosteroid withdrawal. Time to recovery of baseline function was positively correlated with time to immunotherapy (r = 0.74; P = 0.03) but not time to anti-epileptic drug administration (r = 0.55; P = 0.10). Of 10 cases, the eight cases who received anti-epileptic drugs (n = 3) or no treatment (n = 5) all developed cognitive impairment. By contrast, the two who did not develop cognitive impairment received immunotherapy to treat their faciobrachial dystonic seizures (P = 0.02). In eight cases without clinical magnetic resonance imaging evidence of hippocampal signal change, cross-sectional volumetric magnetic resonance imaging post-recovery, after accounting for age and head size, revealed cases (n = 8) had smaller brain volumes than healthy controls (n = 13) (P < 0.001). In conclusion, faciobrachial dystonic seizures can be prospectively identified as a form of epilepsy with an expanding phenotype. Immunotherapy is associated with excellent control of the frequently anti-epileptic drug refractory seizures, hastens time to recovery, and may prevent the subsequent development of cognitive impairment observed in this study.
    Full-text · Article · Sep 2013 · Brain
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Some prominent studies have claimed that the medial temporal lobe is not involved in retention of information over brief intervals of just a few seconds. However, in the last decade several investigations have reported that patients with medial temporal lobe damage exhibit an abnormally large number of errors when required to remember visual information over brief intervals. But the nature of the deficit and the type of error associated with medial temporal lobe lesions remains to be fully established. Voltage-gated potassium channel complex antibody-associated limbic encephalitis has recently been recognized as a form of treatable autoimmune encephalitis, frequently associated with imaging changes in the medial temporal lobe. Here, we tested a group of these patients using two newly developed visual short-term memory tasks with a sensitive, continuous measure of report. These tests enabled us to study the nature of reporting errors, rather than only their frequency. On both paradigms, voltage-gated potassium channel complex antibody patients exhibited larger errors specifically when several items had to be remembered, but not for a single item. Crucially, their errors were strongly associated with an increased tendency to report the property of the wrong item stored in memory, rather than simple degradation of memory precision. Thus, memory for isolated aspects of items was normal, but patients were impaired at binding together the different properties belonging to an item, e.g. spatial location and object identity, or colour and orientation. This occurred regardless of whether objects were shown simultaneously or sequentially. Binding errors support the view that the medial temporal lobe is involved in linking together different types of information, potentially represented in different parts of the brain, regardless of memory duration. Our novel behavioural measures also have the potential to assist in monitoring response to treatment in patients with memory disorders, such as those with voltage-gated potassium channel complex antibody limbic encephalitis.
    Full-text · Article · Jun 2013 · Brain
Show more