Patient characteristics

The final sample contained 52 patients with possible AE and included 27 females and 25 males. Twenty-six (50%) were seropositive; 11 with anti-N-methyl-d-aspartate receptor (NMDAR) ab-mediated AE, 10 with anti-leucine-rich glioma-inactivated-1 (LGI-1) ab-mediated AE, 2 with contactin-associated protein-like 2 (CASPR-2) ab-mediated AE, and 1 with voltage-gated potassium channel complex (Unspecified; VGKC) ab-mediated AE antibodies, and 2 with another antibody. Twenty-six (50%) were seronegative. In the total cohort, 16 individuals (30.76%) underwent assessment between 6 to 12 months from their initial hospital admission. Thirteen individuals (25.00%) were assessed between 1 and 3 years after their admission, while 22 individuals (42.31%) underwent assessment between 3 and 10 years after admission. One individual (1.92%) was assessed 10 years post-admission. Demographic data is available in Table 1.

Table 1 Cohort demographicsMemory test characteristics

The characteristics of each memory test are summarised in Table 2. A visualisation of the distribution of scores across the total cohort, seropositive, and seronegative cohorts is provided in Fig. 1.

Table 2 Subtests characteristics for the total cohortFig. 1

Box plot scores on memory tests for the cohort of AE patients. Normative data mean is denoted by a black line. Scores below the dotted lines are 1.5 standard deviations below the normative mean and are considered mildly impaired. Scores below the dashed line are -2.0 standard deviations below the normative mean and are considered severely impaired. LM logical memory; VR visual reproduction; VPA verbal paired associates; CVLT California verbal learning test; E easy pair; H hard pair; T total; F free recall; C cued recall; TP true positive; FP false positive; LD long delay

Subtest characteristics for the seropositive and seronegative cohort are available in the supplementary material (Table S1).

Frequency of impairment on memory tests

When impairment was defined at 1.5 standard deviations below the normative mean, the frequency of impairments on memory tests is available in the supplementary material (Table S2). Figures 2 and 3 visualise the percentage of impairments for the total cohort and then for the seronegative and seropositive cohorts, respectively.

Fig. 2

Frequency of deficits when defined at 1.5 SD below the normative mean. The pale yellow represents the upper 95% confidence interval, the dark red represents the lower 95% CI, and the orange with a dark line represents the frequency for the total cohort. LM logical memory; VR visual reproduction; VPA verbal paired associates; CVLT California verbal learning test; F free recall; C cued recall; TP true positive; FP false positive; SD short delay; LD long delay

Fig. 3

Frequency of deficits by seropositive and seronegative when at 1.5 SD below the normative mean. The blue line represents the seropositive cohort, whilst the red line represents the seronegative cohort. LM logical memory; VR visual reproduction; VPA verbal paired associates; CVLT California verbal learning test; F free recall; C cued recall; TP true positive; FP false positive; SD short delay; LD long delay

Chi-squared goodness of fit tests

For the total cohort, Chi-squared goodness of fit tests were conducted to compare the actual number of impaired patients to the expected number of impaired patients under a normal distribution, where impaired is defined at 1.5 standard deviations below the normative mean. This revealed significant differences for LM1 (χ2(1, N = 49) = 5.68, p = 0.017), LM2 (χ2(1, N = 49) = 8.87, p = 0.003), VR2 (χ2(1, N = 47) = 22.78, p < 0.00001), CVLT T1 (χ2(1, N = 48) = 35.61, p < 0.00001), CVLT T5 (χ2(1, N = 48) = 17.45, p = 0.00003), CVLT SD (F) (χ2(1, N = 48) = 17.42, p = 0.00003), CVLT SD (C) (χ2(1, N = 48) = 28.8, p < 0.00001), CVLT LD (F) (χ2(1, N = 48) = 28.8, p < 0.00001), CVLT LD (C) (χ2(1, N = 48) = 22.76, p < 0.00001), CVLT TP (χ2(1, N = 48) = 22.76, p < 0.00001) and CVLT FP (χ2(1, N = 48) = 12.8, p = 0.0035). There were no significant differences for LM Recog, VR1, VR Recog, VPA (E), VPA (H), and CVLT (T).

Table 3 presents the chi-squared goodness of fit tests for the seropositive and seronegative groups.

Table 3 Chi-squared goodness of fit tests for seropositive and seronegative groupsPattern analysis

Pattern analysis encompassed both the learning/immediate tests and the tests for free delayed recall of the material. Forty-two patients were eligible for inclusion in the analysis as they had successfully completed all the tests incorporated in the pattern analysis. Seventeen distinct patterns were identified and are presented in Table 4. Table S7 presents the patterns for the seropositive and seronegative groups. The prevailing pattern observed was intact memory outcomes, with 52.76% of patients exhibiting this particular pattern. Notably, 47.24% of patients experienced impairment in at least one test.

Table 4 Patterns of memory outcomesIndependent T-testsSeropositive vs seronegative

There was no evidence of differences across all memory tests between patients classified as seropositive and those classified as seronegative (supplementary data Table S3) using independent samples t-tests.

Seropositive patients (M = 49.62, SD = 32.37) had a significantly longer time between symptom onset and assessment compared to seronegative patients (M = 30.36, SD = 29.94) (U [Nseropositive = 26, Nseronegative = 25] = 188.50, p = 0.010). Seropositive patients (M = 46.11, SD = 30.73) had longer between main hospital admission and assessment than seronegative patients (M = 28.68, SD = 9.47) (U [Nseropositive = 26, Nseronegative = 25] = 202.00, p = 0.021). Seropositive patients (M = 3.58, SD = 4.88) had a longer time between symptom onset and admission than seronegative patients (M = 1.61, SD = 5.85) (U [Nseropositive = 26, Nseronegative = 25] = 224.00, p = 0.024). Seronegative patients were more likely to have had second-line therapies than seropositive patients (χ2 (1,51) = 4.46, p = 0.035).

Anti-NMDAR ab-mediated AE vs anti-LGI1 ab-mediated AE

Results from an independent samples t-test indicated that patients diagnosed with anti-NMDAR ab-mediated AE patients (M = 0.25, SD = 0.87, N = 11) scored higher on LM2 than patients diagnosed with anti-LGI1 ab-mediated AE (M = −0.76, SD = 1.31, N = 9), t (18) = 2.30, p = 0.03). There were no significant differences for the remaining memory tests (supplementary data table S4). There was no evidence of differences in demographic or clinical data between these two groups.

Anti-NMDAR ab-mediated AE versus all other seropositive AE cases

Results from an independent sample t-test indicated that patients diagnosed with anti-NMDAR ab-mediated AE patients (M = 0.25, SD = 0.87, N = 11) scored higher on LM2 than all other patients who were seropositive (M = −0.83, SD = 1.08, N = 14), t(23) = −2.71, p = 0.03). There was no evidence of differences between the rest of the memory tests (supplementary data table S4). There was no evidence of differences in demographic or clinical data between these two groups.

Anti-LGI-1 ab-mediated AE versus all other seropositive AE cases

There was no evidence of differences across all memory tests between patients diagnosed with anti-LGI1 ab-mediated AE and all other seropositive patients (supplementary data Table S6). There was no evidence of differences in demographic or clinical data between these two groups.

Correlations between demographic and clinical variables and memory tests

There was a significant correlation between time between symptom onset and admission and VR Recog (r(45) = 0.32, p = 0.03), VPA (H) (r(44) = 0.38, p = 0.01) and CVLT T1 (r(45) = 0.33, p = 0.03). There were significant correlations between mRS at discharge and a number of variables from the CVLT: CVLT T5 (r(45) = −0.33, p = 0.03), CVLT T (r(45) = −032, p = 0.05), CVLT SD (F) (r(45) = −0.43, p = 0.004), CVLT SD (C) (r(45) = −0.31, p = 0.04), CVLT LD (F) (r(45) = −0.38, p = 0.01), CVLT LD (C) (r(45) = −0.39, p = 0.009), and CVLT Recog (FP) (r(45) = −0.34, p = 0.03).