Neuropsychological Testing in Autoimmune Encephalitis

Galioto, Rachel; Grezmak, Tiffany; Swetlik, Carol; Abbatemarco, Justin R.; Titulaer, Maarten J.; Finke, Carsten; Kunchok, Amy

doi:10.1212/nxi.0000000000200179

Cited by 9 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Working Memory and Processing Speed composite scores were selected for this study analysis given the evidence that these are the most frequently studied and testing recommended in adult and paediatric AE and neuroinflammatory disease. 13, 45, 46…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Linking brain networks to cognition with magnetoencephalography in paediatric autoimmune encephalitis

Billaud,

Wood,

Griffiths-King

et al. 2024

Preprint

View full text Add to dashboard Cite

Paediatric autoimmune encephalitis (e.g., acute disseminated encephalomyelitis, N-methyl-D-aspartate receptor antibody encephalitis) is an inflammatory brain disease that causes cognitive deficits, psychiatric symptoms, seizures, MRI, and EEG abnormalities. Patients can continue to experience residual cognitive difficulties months to years after the acute illness. Magnetoencephalography (MEG) can examine neural changes in the absence of frank structural abnormalities and may help identify factors predicting children at risk of long-term cognitive deficits. We predicted that theta and delta brain functional connectivity networks would be associated with processing speed and working memory in children with autoimmune encephalitis. Participants were children diagnosed with autoimmune encephalitis at least 18 months before testing and typically developing children. All completed MEG recording (Elekta Neuromag Triux) at rest, eyes open with a fixation cross during six minutes; T1 MRI scans; and cognitive evaluation using the primary subtests of the Weschler Intelligence Scale for Children, fifth edition. Brain connectivity, specifically in delta and theta brain activity, was estimated with amplitude envelope correlation, and network efficiency was measured using graph measures (global efficiency, local efficiency, modularity). The measures were compared across the two groups with permutation correction for multiple thresholds. Finally, statistical associations with processing speed and working memory scores were tested in the autoimmune encephalitis group. Age and sex-matched cohorts of 12 children with AE (11.2+/-3.5y, IQR 9y; 5M:7F) and 12 typically developing controls (10.6+/-3.2y, IQR 7y; 8M:4F) participated in this study. On average, children with autoimmune encephalitis did not differ from controls in working memory (t(21)= 1.449; p = .162; d = 0.605) but had a significantly lower processing speed (t(21) = 2.463; p = .023; Cohens d = 1.028). The groups did not differ in theta network topology measures but the autoimmune encephalitis group had a significantly lower delta local efficiency across all thresholds tested (d = -1.60 at network threshold 14%). Theta modularity was associated with lower working memory (β = -.781; t(8) = -2.588, p = .032) but this effect did not survive correction for multiple comparisons (p(corr) = .224). No other graph measure was significantly associated with psychometric scores in the autoimmune encephalitis group. MEG was able to capture network alterations in paediatric autoimmune encephalitis patients, specifically in the topological organisation of delta brain activity. This preliminary study demonstrates that MEG is an appropriate tool for assessing children with autoimmune encephalitis; future studies should focus on confirming which functional networks can predict cognitive performance.

show abstract

Section: Methodsmentioning

confidence: 99%

“…A recent review in adults with AE found the most frequent impairments and highest yield neuropsychological measures were found in tests of visual and verbal learning/memory, processing speed, attention, and executive functions. 13…”

Section: Introductionmentioning

confidence: 99%

Linking brain networks to cognition with magnetoencephalography in paediatric autoimmune encephalitis

Billaud,

Wood,

Griffiths-King

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Importantly, clinical studies have identified cognitive deficits as a crucial long-term outcome of LGI1-E, showing that these deficits (i) persist for years after peak illness, 5, 9, 18, 19 (ii) encompass diverse cognitive functions beyond isolated memory impairment, 18–20 and (iii) represent a key predictor of long-term functional disability. 21 However, the structural brain changes that underlie these deficits remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15][16] Similarly, microstructural brain damage as assessed with diffusion-weighted imaging (DWI) has been observed in both limbic and extra-limbic brain structures and correlates with poorer functional outcome. 9,17 Importantly, clinical studies have identified cognitive deficits as a crucial long-term outcome of LGI1-E, showing that these deficits (i) persist for years after peak illness, 5,9,18,19 (ii) encompass diverse cognitive functions beyond isolated memory impairment, [18][19][20] and (iii) represent a key predictor of long-term functional disability. 21 However, the structural brain changes that underlie these deficits remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Persistent cognitive deficits in anti-LGI1 encephalitis are linked to a reorganization of structural brain networks

Krohn,

Müller-Jensen,

Kuchling

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Importance: Despite immunotherapy, most patients with anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E) develop long-term cognitive deficits that persist for years after peak illness. However, the structural brain changes that underlie these deficits remain poorly understood.Objective: To study the relationship between cognitive outcomes and white matter (WM) networks in LGI1-E.Design & Setting: Cross-sectional study. German university center.Participants: 25 patients with LGI1-E (19/25 male [76%], mean age: 63 ± 12 years) and 25 age- and sex-matched healthy controls (HC), recruited between January 2013 and April 2019.Main Outcomes and Measures: Clinical assessments including the modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE); comprehensive cognitive testing; WM tractography using diffusion-weighted MRI.Results: All patients had received first-line immunotherapy, and two-thirds underwent second-line immunotherapy. Patients showed a significant reduction in mRS scores from peak illness to post-acute follow-up (z = -3.8, p < 0.001, n = 20), with 85% presenting "good" functional outcomes (post-acute mRS ≤ 2), paralleled by a significant reduction in CASE scores (z = -3.5, p < 0.001, n = 20). Despite this overall improvement, however, cognitive symptoms were highly prevalent at peak illness (95% of patients affected) and strongly persisted into the post-acute disease stage (85% affected). Neuroimaging at post-acute follow-up (median: 12 months from onset) revealed that LGI1-E is characterized by (i) significantly reduced whole-brain structural connectivity (t = -2.16, p = 0.036, d = -0.61), (ii) a cortico-subcortical hypoconnectivity cluster that strongly affects the hippocampus but also severely impacts extra-limbic brain systems, (iii) systematic limbic and extra-limbic decreases in node degree — a graph-theoretical measure of overall connectedness, and (iv) a "topological reorganization" of structural brain networks, marked by a bidirectional shift in the relative importance of individual brain regions in the network. Importantly, the extent of this network reorganization was significantly related to persistent cognitive deficits in the domains of verbal memory (r = -0.57, p = 0.007, n = 21), attention (r = -0.47, p = 0.030, n = 21), and executive functions (r = -0.60, p = 0.010, n = 17).Conclusion and Relevance: This study characterizes LGI1-E as a network disease that affects both limbic and extra-limbic brain systems and shows that a reorganization of WM networks is linked to multi-domain cognitive deficits in the post-acute disease stage — despite immunotherapy and good overall recovery. These findings highlight the need for extended treatment strategies to improve long-term cognitive outcomes and propose a sensitive new neuroimaging marker to include in prospective clinical trials.

show abstract

“…The use of established generic PROMs (e.g., BDI-II, PSQI) and standardized cognitive batteries will allow for comparability with other disorders. 9 To address the lack of standardization of generic PROMs, the NIH-funded Patient-Reported Outcomes Measurement Information System (PROMIS) was initiated. 10 PROMIS offers fixed-length questionnaires and computerized adaptive tests to reliably measure a wide range of patient-reported outcomes.…”

mentioning

confidence: 99%