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Cognitive neurology

RESEARCH PAPER

Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex Christopher R Butler,1 Thomas D Miller,1 Manveer S Kaur,2 Ian W Baker,2 Georgie D Boothroyd,2 Nathan A Illman,3 Clive R Rosenthal,1 Angela Vincent,1 Camilla J Buckley1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jnnp-2013-306724). 1

Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK 2 Russell-Cairns Unit, John Radcliffe Hospital, Oxford, UK 3 Institute of Psychiatry, Kings College London, London, UK Correspondence to Dr Christopher R Butler, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Level 6, West Wing, Headley Way, Oxford OX3 9DU, UK; [email protected] Received 6 September 2013 Revised 9 December 2013 Accepted 10 December 2013 Published Online First 8 January 2014

ABSTRACT Objective 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. Methods We used a comprehensive neuropsychological test battery to evaluate cognitive function longitudinally in 19 patients with VGKC-LE. Results 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. Conclusions 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.

and the degree to which VGKC-LE responds to treatment remain largely unknown. Here, we present data from a comprehensive battery of clinical neuropsychological tests administered to 19 patients before and after immunotherapy for VGKC-LE.

METHODS Patient identification We identified 19 patients who had been diagnosed with LE (ie, had the clinical features of ‘subacute onset…of seizures, short-term memory loss, confusion, and psychiatric symptoms’13) by an experienced neurologist (CJB), had tested positive for serum VGKC-complex antibodies (AV) and had undergone neuropsychological assessment (IWB, Assessment 1) during the acute phase of the illness at the Russell Cairns Unit, Oxford, between November 1998 and May 2009. Details of the clinical presentation, investigations and response to treatment were obtained from the medical notes. All of the patients were fluent in English and had no history of previous psychiatric or neurological disorder that may result in cognitive impairment. Ethical approval for the study was granted by North Staffordshire Research Ethics Committee. All participants gave written, informed consent.

INTRODUCTION

To cite: Butler CR, Miller TD, Kaur MS, et al. J Neurol Neurosurg Psychiatry 2014;85: 387–391.

Limbic encephalitis (LE) is a neurological syndrome characterised by acute or subacute amnesia and seizures and is frequently associated with autoantibodies against components of the voltage-gated potassium channel complex (VGKC):1 leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2).2 3 Patients with VGKC-LE typically show clinical improvement following a course of immunosuppression.1 2 MRI may reveal focal abnormalities, especially T2 hyperintensity and subsequent atrophy, within the medial temporal lobes (MTL),1 4– 7 a region critical for learning and memory.8 9 To date, cognitive outcome has been assessed in single cases and small case series, some of which have reported residual memory deficits1 10 11 and others apparent recovery.5 12 The conflicting nature of these reports is likely attributable to the small number of patients studied (nine5 and one12 in reports of normal cognitive function and seven,1 one10 and three11 in reports of persistent memory deficits) and the limited range of neuropsychological tests often used. Therefore, the extent of cognitive impairment

Butler CR, et al. J Neurol Neurosurg Psychiatry 2014;85:387–391. doi:10.1136/jnnp-2013-306724

Neuropsychometry Assessment 1 was conducted before or shortly after commencement of immunotherapy. When the assessment occurred after treatment initiation (eight patients), the delay was in the order of a few days and unlikely to have allowed significant clinical improvement. Assessment 2 was conducted 3–44 months after Assessment 1 and involved the same test battery. In order to minimise practice effects, alternative forms of tests, where available, were used in Assessments 1 and 2. Patients’ scores were standardised according to published normative data. The neuropsychological battery assessed the following domains: ▸ Premorbid intelligence: National Adult Reading Test14 or Wechsler Adult Reading Test.15 ▸ Memory: immediate and delayed recall of the Logical Memory Story (from Wechsler Memory Scale-III);16 immediate and delayed recall of a 15-item word list from the Adult Memory and Information Processing Battery (AMIPB);17 immediate and delayed recall of a complex 387

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Cognitive neurology

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figure from the AMIPB or the Rey–Osterreith Complex Figure.18 Executive function: letter and category verbal fluency;19 Trail making test part B;20 digit span from the Wechsler Adult Intelligence Scale Third Edition (WAIS-III).21 Processing speed: digit-symbol coding from the WAIS-III.21 Language: vocabulary and similarities subtests from the WAIS-III.21 Perceptual organisation: block design and matrix reasoning subtests from the WAIS-III;21 copy of the AMIPB17 or Rey–Osterreith Complex Figure.18

Statistical analyses To compare performance across patients, assessment sessions and cognitive domains, raw scores from individual tests were converted to z-scores ( population mean=0, SD=1). An index score for each cognitive domain was calculated for each patient by averaging their z-scores across the tests within that domain. Only the delayed recall scores were used for the memory indices as these were highly correlated with immediate-recall scores (story recall: r=0.76, p

Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex.

Limbic encephalitis (LE) associated with antibodies to the voltage-gated potassium channel complex (VGKC) is a potentially reversible cause of cogniti...
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