The Road to Recovery: A Pilot Study of Driving Behaviors Following Antibody-Mediated Encephalitis

Day, Gregory S.; Babulal, Ganesh M.; Rajasekar, Ganesh; Stout, Sarah H.; Roe, Catherine M.

doi:10.3389/fneur.2020.00678

Cited by 5 publications

(6 citation statements)

References 40 publications

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“…Future studies should leverage comprehensive measures of disease severity in AME together with CSF biomarker measures to determine the influence of patient- and disease-specific factors on established and innovative measures of function in patients recovering from AME. 47,48…”

Section: Limitationsmentioning

confidence: 99%

“…The Clinical Assessment Scale for Autoimmune Encephalitis was recently proposed and validated as a means to prospectively quantify disease severity and grade clinical status in patients with autoimmune encephalitis46 ; this measure was not applied to enrolled patients. Future studies should leverage comprehensive measures of disease severity in AME together with CSF biomarker measures to determine the influence of patient-and disease-specific factors on established and innovative measures of function in patients recovering from AME 47,48. CSF biomarkers of neuronal injury suggest that neuronal integrity is acutely maintained in NMDAR and LGI1/CASPR2 antibody encephalitis, despite increases in NfL, a marker of neuroaxonal injury.…”

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confidence: 99%

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Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis

et al. 2021

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Objectives:To determine whether neuronal and neuroaxonal injury, neuroinflammation and synaptic dysfunction associate with clinical course and outcomes in antibody-mediated encephalitis (AME), we measured biomarkers of these processes in CSF from patients presenting with AME and cognitively normal individuals.Methods:Biomarkers of neuronal (total-tau, VILIP-1) and neuroaxonal damage (neurofilament light chain [NfL]), inflammation (YKL-40) and synaptic function (neurogranin, SNAP-25) were measured in CSF obtained from 45 patients at the time of diagnosis of NMDA receptor (n=34) or LGI1/CASPR-2 (n=11) AME, and 39 age- and sex-similar cognitively normal individuals. The association between biomarkers and modified Rankin Scores were evaluated in a subset (n=20) of longitudinally followed patients.Results:Biomarkers of neuroaxonal injury (NfL) and neuroinflammation (YKL-40) were elevated in AME cases at presentation, while markers of neuronal injury and synaptic function were stable (total-tau) or decreased (VILIP-1, SNAP-25, neurogranin). The log-transformed ratio of YKL-40/SNAP-25 optimally discriminated cases from cognitively normal individuals (AUC=0.99; 95%CI: 0.97, >0.99). Younger age (ρ=-0.56; p=0.01), lower VILIP-1 (ρ=-0.60; p<0.01) and SNAP-25 (ρ=-0.54; p=0.01), and higher log10(YKL-40/SNAP-25) [(ρ=0.48; p=0.04] associated with greater disease severity (higher modified Rankin Score) in prospectively followed patients. Higher YKL-40 (ρ=0.60; p=0.02) and neurogranin (ρ=0.55; p=0.03) at presentation were associated with higher modified Rankin Scores 12-months following hospital discharge.Conclusions:CSF biomarkers suggest that neuronal integrity is acutely maintained in AME patients, despite neuroaxonal compromise. Low-levels of biomarkers of synaptic function may reflect antibody-mediated internalization of cell-surface receptors, and may represent an acute correlate of antibody-mediated synaptic dysfunction, with the potential to inform disease severity and outcomes.

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Section: Limitationsmentioning

confidence: 99%

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confidence: 99%

Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis

et al. 2021

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“…Only a minority of patients scored below the respective cut-off score, consistent with an earlier study on 15 patients with LGI1 AABs ( Hanert et al, 2019 ). Others found reduced processing speed in comparison to a healthy control group ( Butler et al, 2014 ; Day, Babulal, Rajasekar, Stout, & Roe, 2020 ; Sola-Valls et al, 2020 ). However, it is debatable, how valid processing speed assessed by the Trail Making Test (TMT-A, see e.g., Reitan et al, 1956) is a measure of attention.…”

Section: Discussionmentioning

confidence: 93%

Neuropsychological Performance in Autoimmune Limbic Encephalitis: Evidence from an Immunotherapy-Naïve Cohort

Mueller

Langenbruch

Rau

et al. 2022

Archives of Clinical Neuropsychology

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Objective Autoimmune limbic encephalitis (ALE) is characterized by memory impairment, psychiatric symptoms, and epileptic seizures. Though, the neuropsychological profile of ALE is not yet well defined. However, there is some evidence that neuropsychological impairments might exceed those related to the limbic system and that different autoantibodies (AABs) are associated with distinguishable pattern of neuropsychological impairments. We provide a comprehensive presentation of neuropsychological performance of ALE in an immune therapy-naïve sample. Methods We retrospectively analyzed 69 immunotherapy-naïve ALE-patients (26 seropositive—[8 LGI1-, 4 CASPR2-, 2 GABAB-R-, 3 Hu-, 4 GAD65-, 2 Ma2-, 2 unknown antigen, and 1 Yo-AABs] and 43 seronegative patients, mean age 56.0 years [21.9–78.2], mean disease duration 88 weeks [0–572]). Neuropsychological evaluations comprised of the domains memory, attention, praxis, executive functions, language, social cognition, and psychological symptoms. We compared these functions between seronegative −, seropositive patients with AABs against intracellular neural antigens and seropositive patients with AABs against surface membrane neural antigens. Results No effect of AAB group on neuropsychological performance could be detected. Overall, ALE predominantly presents with deficits in long-term memory and memory recognition, autobiographical-episodic memory loss, impairment of emotion recognition, and depressed mood. Furthermore, deficits in praxis of pantomimes and imitations, visuo-construction, and flexibility may occur. Conclusion ALE shows a wide spectrum of neuropsychological impairments, which might exceed the limbic system, with no evidence of differences between AAB groups. Neuropsychological assessment for diagnosing ALE should include long-term memory, memory recognition, autobiographical-episodic memory, emotion recognition, and a detailed investigation of depression.

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“…Cognitive screening. MMSE-scores were in pathological range in 4 studies [38,40,42,54] in a total of 13 patients and within normal range in 2 studies [48,55] in a total of 11 patients. A MoCA score indicating a moderate cognitive impairment was reported in 4 studies in a total of 21 patients (see [42,54,56,57], with Hébert et al presenting 2 follow-up measurements after immunotherapy).…”

Section: Anti-lgi1 Ale After Initiation Of Immunotherapymentioning

confidence: 88%