LAUSR

Dear Editor, Autoimmune limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to focal hippocampal atrophy and persistent episodic memory impairment (Butler et al., 2014; Loane et al., 2019). In an interesting study of 7 VGKCC-Ab-LE patients with hippocampal damage, Lad, Mullally, Houston, Kelly, and Griffiths (2019) reported (a) impaired recall, in the face of preserved recognition memory, as disclosed by the Doors and People Test (DPT; Baddeley, Emslie, & Nimmo-Smith, 1994). This was interpreted as consistent with frameworks attributing recollection processes to hippocampal function (Yonelinas, 2002); (b) impairment of autobiographical (“episodic”) memory in the face of preserved personal semantic memory, without temporal gradient (Autobiographical Memory Interview—AMI; Kopelman, Wilson, & Baddeley, 1989). This was interpreted as inconsistent with systems consolidation accounts (Squire, Genzel, Wixted, & Morris, 2015) and dovetails with reports on temporally ungraded retrograde amnesia post-VGKCC-Ab-LE (Chan, Henley, Rossor, & Warrington, 2007). Given the rarity of VGKCC-Ab-LE, it is important to examine the replicability of such dissociations employing the same tests and patient selection criteria. In a recent paper, we reported on the brain abnormalities underlying anterograde amnesia in a large cohort of VGKCC-Ab-LE patients (n = 24) (Loane et al., 2019). Our patients scored lower than healthy controls (CTRs) in verbal/visual recall and verbal recognition. However, the selection criteria employed by Lad et al. (2019) were different, highlighting the possibility that an appropriate subset of our cohort would replicate their findings. Among those criteria were: (a) structural MRI conducted >1 year post-acutely; (b) atrophic hippocampi and spared parahippocampal gyri in the stable chronic phase. However, the definition of atrophy was based on visual inspection. In contrast, the data we reported in Loane et al. (2019) allow us to apply this criterion in a more precise fashion, since we had conducted gold-standard manual volumetry of medial temporal lobe structures; (c) VGKCC-Ab level > 1,000 pmol/L at diagnosis. This value is very high relative to commonly used cut-offs [100 pmol/L (Celicanin et al., 2017; Zuliani et al., 2007); 150 pmol/L (Barajas, Eric Collins, Cha, & Geschwind, 2010); 400 pmol/L (Irani et al., 2010; Vincent et al., 2004)]; (d) a clinical phenotype consistent with LGI1-LE. While the paper relied on neurological assessment to determine the presence of an “LGI1-type,” our data allow us to select cases that tested positive exclusively for LGI1-Ab. We first identified four patients with LGI1-Ab-LE, focal hippocampal atrophy [right and/or left hippocampus: z < −1.96 relative to a group of 48 age-matched CTRs (Argyropoulos et al., 2019), reflecting significant volume reduction (p < .05); right/left entorhinal/perirhinal/ parahippocampal cortex volumes: z > −1.29], assessed > 1 year postsymptom onset (“HPC patients”). Consistent with the post-acute profile of our cohort as a whole (Loane et al., 2019), these patients showed preserved semanticmemory and language, visuospatial, motor, and executive function. Since Lad et al. (2019) had employed ageand sex-matched CTRs on an individual basis, we compared our 4 male HPC patients with the 26male CTRs of our study (patients' age at assessment: mean = 63.43; SD = 8.99 years; male CTRs' age: mean = 60.20; SD = 10.06 years; patients vs. male CTRs: t =−0.60, p = 0.551).We also conducted comparisons against population means, wherever available, in order to enhance the generalizability of our findings. Unlike Lad et al. (2019), HPC patients showed clearly impaired verbal recognition, along with impaired delayed verbal recall (Table 1). Regarding retrograde amnesia, they showed impairment in both autobiographical and personal semantic memory. However, their impaired personal semantic memory was driven by their low scores in the recent epoch: they showed no evidence of personal semantic memory impairment for childhood or early adulthood, but impairment for recent events. On the contrary, patients showed impaired autobiographical memory for events in all three periods assessed (childhood, early adulthood, recent events). Given that our different findings could potentially be attributed to the lower sample size, we then (a) included another 3 LGI1-Ab-LE cases that satisfied all criteria above except for the fact that: 1 patient had been assessed 1 year [instead of >1 year as in Lad et al. (2019)] post-symptom onset, and another 2 had presented with acute VGKCC-Ab levels < 1,000 pmol/L (but still >400 pmol/L; “HPC2 patients”); consistent with (Loane et al., 2019), no negative correlation was observed, even at trending levels, between the acute VGKCC-Ab levels and DPT/AMI scores or right/left hippocampal volumes across those 7 HPC2 patients (all rhos/ps, −0.234 ≤ rho ≤ 0.580; p ≥ .228); (b) identified another 5 (1 female) LGI1-Ab-LE patients with no atrophy in the hippocampus or the parahippocampal gyrus Received: 19 October 2019 Revised: 26 March 2020 Accepted: 31 March 2020