Specific B- and T-cell populations are associated with cognition in patients with epilepsy and antibody positive and negative suspected limbic encephalitis

Helmstaedter, Christoph; Hansen, Niels; Leelaarporn, Pitshaporn; Schwing, Kerstin; Oender, Demet; Widman, Guido; Rácz, A.; Surges, Rainer; Becker, Albert

doi:10.1007/s00415-020-10158-1

Cited by 23 publications

(16 citation statements)

References 56 publications

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“…Visual memory was assessed by the Diagnosticum für Cerebralschädigung II [diagnostic instrument for cerebral damage] (DCS II; [Weidlich et al, 2011]) frequently used in ALE (see e.g., Bauer et al, 2020; Helmstaedter et al, 2020; Wagner et al, 2015). In this test, pictures of nine abstract figures, each consisting of five straight lines are consecutively presented to the patient one at a time.…”

Section: Methodsmentioning

confidence: 99%

Determinants of cognition in autoimmune limbic encephalitis—A retrospective cohort study

et al. 2021

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Autoimmune limbic encephalitis (ALE) is the most common type of autoimmune encephalitis (AIE). Subacute memory disturbance, temporal lobe seizures, and psychiatric symptoms are clinical hallmarks of the disease. However, little is known on the factors contributing to cognitive functioning in ALE. Hence, we here investigate major determinants of cognitive functioning in ALE. In a retrospective analysis of 102 patients with ALE, we first compared verbal learning capacity, nonverbal learning capacity, and attentional and executive functioning by absence or presence of different types of neural autoantibodies (AABs). Subsequently we established three linear regression models including 63, 38, and 61 patients, respectively to investigate how cognitive functioning in these domains may depend on common markers of ALE such as intrathecal inflammation, blood‐cerebrospinal fluid (CSF)‐barrier function, mesiotemporal epileptiform discharges and slowing, determined by electroencephalography (EEG) and structural mesiotemporal changes, measured with magnetic resonance imaging (MRI). We also accounted for possible effects of cancer‐ and immunotherapy and other centrally effective medication. There was no effect of AAB status on cognitive functioning. Although the regression models could not predict verbal and nonverbal learning capacity, structural mesiotemporal neural network alterations on T2‐/fluid attenuated inversion recovery (FLAIR)‐signal‐weighted MRI and mesiotemporal epileptiform discharges or slowing on EEG exerted a significant impact on memory functions. In contrast, the regression model significantly predicted attentional and executive functioning with CSF white blood cell count and centrally effective medication being significant determinants. In this cohort, cognitive functioning in ALE does not depend on the AAB status. Common markers of ALE cannot predict memory functioning that only partially depends on structural and functional alterations of mesiotemporal neural networks. Common markers of ALE significantly predict attentional and executive functioning that is significantly related to centrally effective medication and CSF white blood cell count, which may point toward inflammation affecting brain regions beyond the limbic system.

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Section: Methodsmentioning

confidence: 99%

Determinants of cognition in autoimmune limbic encephalitis—A retrospective cohort study

et al. 2021

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“…Several autoantibodies ( Table 1 ) are often now reported to be associated with cognitive dysfunction ( Dalmau et al, 1992 ; Pittock et al, 2005 ; Honnorat et al, 2009 ; White and Beringer, 2010 ; Maat et al, 2015 ; Do et al, 2017 ; Ortega Suero et al, 2018 ; Hansen et al, 2020a , b , 2021a ; Maudes et al, 2020 ; Wickel et al, 2020 ; Budhram et al, 2021 ; Helmstaedter et al, 2021 ). Prominent autoantibody candidates strongly associated with cognitive impairment within the spectrum of autoantibodies against intracellular antigens are those directed against GAD65, AK5, GFAP, and Ma2.…”

Section: Autoimmune Dementiamentioning

confidence: 99%

Current Nosology of Neural Autoantibody-Associated Dementia

Hansen

2021

Front. Aging Neurosci.

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BackgroundThe detection of neural autoantibodies in patients with cognitive decline is an increasingly frequent phenomenon in memory clinics, and demanding as it does a specific diagnostic approach and therapeutic management, it deserves greater attention. It is this review’s aim to present the latest nosology of neural autoantibody-associated dementia.MethodsA specific literature research via PubMed was conducted to describe the nosology of neural autoantibody-associated dementia.ResultsAn autoimmune dementia comprises with an early onset, atypical clinical presentation and rapid progression in conjunction with neural antibodies, signs of inflammation in the cerebrospinal fluid, and a non-neurodegenerative pattern in neuroimaging. An autoimmune dementia is probably present if the patient responds to immunotherapy. Atypical dementia involving neural autoantibodies with mostly N-methyl-D-aspartate receptor antibodies might not fulfill all the autoimmune-dementia criteria, thus it may constitute an independent disease entity. Finally, a neurodegenerative dementia such as the frontotemporal type also coincides with neural autoantibodies such as the subunit ionotropic glutamate receptors 3 of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibodies, dementia with Lewy bodies with myelin oligodendrocytic protein, myelin basic protein antibodies, or Creutzfeldt-Jakob disease with Zic4 or voltage gated potassium channel antibodies. These dementia entities may well overlap in their clinical features and biomarkers, i.e., their neural autoantibodies or neuroimaging patterns.ConclusionThere are three main forms of neural autoantibody-associated dementia we can distinguish that might also share certain features in their clinical and laboratory presentation. More research is urgently necessary to improve the diagnosis and therapy of these patients, as the progression of their dementia might thus be improved or even reversed.

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“…Potential etiological factors include a possibly reversible inflammation-related hippocampal dysfunction, structural hippocampal damage (i.e., significant cell loss) and any interictal epileptic discharges. In a recent study we demonstrated a link between T- and B-cell activity (as assessed by flow cytometry) and neuropsychological performance in patients with LE [ 5 ]. If the dynamic factors can be controlled at an early stage through successful immunomodulatory and, if necessary, anti-epileptic treatment, a cognitive recovery would be anticipated [ 9 ].…”

Section: Which Neuropsychological Functions Are Affected?mentioning

confidence: 99%

“…Accordingly, cognitive and behavioral alterations can be dynamic and reversible or chronic and irreversible. The type and extent of the impairments depend on several etiological factors including (1) the underlying autoimmune process (type of auto-antibodies [4], B-and T-cell activity [5]) (2) the inflammatory-driven functional and/or structural changes [2,6,7], (3) if applicable, epileptic seizures and interictal epileptic discharges [8], (4) immunomodulatory or anti-epileptic treatment effects [9][10][11]. Finally, (5) pre-existent psychiatric comorbidities or (6) psychiatric symptoms caused by LE may also have a negative impact on cognitive performance.…”

Section: Introductionmentioning

confidence: 99%

Neuropsychological Evaluations in Limbic Encephalitis

Helmstaedter

2021

Brain Sciences

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Limbic encephalitis (LE) can cause dynamic and permanent impairment of cognition and behavior. In clinical practice, the question arises as to which cognitive and behavioral domains are affected by LE and which assessment is suited to monitor the disease progress and the success of treatment. Current findings on cognition and behavior in LE are reviewed and discussed based on current guidelines and consensus papers. In addition, we outline approaches for the neuropsychological monitoring of LE and its treatment. Dependent on disease acuity and severity, LE leads to episodic long-term memory dysfunction in different variants (e.g., anterograde memory impairment, accelerated long-term forgetting, and affection of autobiographical memory) and executive deficits. In addition, affective disorders are very common. More severe psychiatric symptoms may occur as well. In the course of the disease, dynamic phases with functional recovery must be differentiated from residual defect states. Evidence-based neuropsychological diagnostics should be conducted ideally before treatment initiation and reassessments are indicated when any progress is suggested, and when decisive anti-seizure or immunomodulatory treatment changes are made. Cognition and behavior may but must not run in synchrony with seizures, MRI pathology, or immune parameters. Cognitive and behavioral problems are integral aspects of LE and represent important biomarkers of disease acuity, progress, and therapy response beyond and in addition to parameters of immunology, neurological symptoms, and brain imaging. Thus, evidence-based neuropsychological assessments are essential for the diagnostic workup of patients with suspected or diagnosed limbic encephalitis, for treatment decisions, and disease and treatment monitoring.

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Specific B- and T-cell populations are associated with cognition in patients with epilepsy and antibody positive and negative suspected limbic encephalitis

Cited by 23 publications

References 56 publications

Determinants of cognition in autoimmune limbic encephalitis—A retrospective cohort study

Determinants of cognition in autoimmune limbic encephalitis—A retrospective cohort study

Current Nosology of Neural Autoantibody-Associated Dementia

Neuropsychological Evaluations in Limbic Encephalitis

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