Figural Memory Impairment in Conjunction With Neuropsychiatric Symptoms in IgLON5 Antibody-Associated Autoimmune Encephalitis

Niels Hansen,Inga Zerr,Claudia Bartels,Anja Manig,Winfried Stöcker,Sina Hirschel,Marielle Ernst,Ruth Vukovich,Hannah Sönne Falk,Jens Wiltfang

doi:10.3389/fpsyt.2020.00576

Abstract

BackgroundIgLON5 disease is an autoimmune disorder that shares neuropathological aspects with a tauopathy. Its clinical spectrum is heterogeneous, and figural memory impairment as an initial phenomenon of IgLON5 syndrome has not yet been described. The rationale of this report is to highlight symptoms related to IgLON5 disease that have not been reported to date. This case report will thereby emphasize how important it is to initiate thorough diagnostic methods including cerebrospinal fluid analysis (CSF) before starting early immunotherapy.MethodsWe examined a 65-year-old Caucasian male via neuropsychological tests, magnetic resonance imaging (MRI), electroencephalography (EEG), neurography and polysomnography. He also underwent two lumbar punctures from which we determined specific autoantibodies in cerebrospinal (CSF) and peripheral blood (PB).ResultsThe patient presented initially complaining of memory loss, gradual dysphagia and sleeping dysfunction. Neuropsychological testing at first presentation and follow-up revealed subtle figural and working memory impairment. At onset and at his 6-month follow-up, we detected IgLON5 antibodies in CSF and PB. Furthermore, we identified in the CSF a blood–brain barrier disturbance at disease onset and follow-up, and markers of neuroaxonal damage such as mildly elevated phosphorylated Tau-181 protein with 86 pg/ml (normal range ≤ 61 pg/ml) at onset. Three months after his initial presentation, he was suffering from axonal neuropathy and transient ataxia in the extremities. Assuming a definitive autoimmune encephalitis-associated with anti-IgLON5 antibodies, we applied high-dose steroids monthly (1g methylprednisolone i.v. for five consecutive days) and his memory complaints, ataxia of extremities and peripheral neuropathy as well as sleeping dysfunction decreased.ConclusionsOur findings broaden IgLON5 disease’s clinical spectrum to include predominant and discrete figural memory impairment together with sleeping dysfunction at disease onset. In addition, our report illustrates how important taking an elaborated diagnostic approach is to assuring an accurate diagnosis and the appropriate therapy if a patient presents with a persisting figural memory impairment and sleeping abnormalities so as to avoid overlooking IgLON5 disease and a potentially poor outcome.

Highlights

IgLON5 antibody-associated encephalitis is a rare autoimmunemediated disorder of the central nervous system often presenting with a tauopathy
We identified in the cerebrospinal fluid (CSF) a blood-brain barrier disturbance and markers of neuroaxonal damage such as mildly elevated phosphorylated Tau-181 protein with 86 pg/ml
Very few patients with IgLON5 antibody-positive encephalitis and cognitive dysfunction have been reported in the literature so far [1, 2, 8,9,10,11]

Summary

Introduction

IgLON5 antibody-associated encephalitis is a rare autoimmunemediated disorder of the central nervous system often presenting with a tauopathy. We here describe for the first time the clinical case of a male patient presenting a subtle figural memory impairment in conjunction with numerous subjective cognitive complaints and additional neuropsychiatric symptoms associated with cerebrospinal fluid (CSF) anti-IgLON5 autoantibodies as an early manifestation of IgLON5 disease. This report’s rationale is to highlight the subtle figural memory impairment together with other neuropsychiatric features as a relevant indicator for taking a sophisticated diagnostic approach encompassing the investigation of IgLON5 autoantibodies in CSF. The rationale of this report is to highlight symptoms related to IgLON5 disease that have not been reported to date This case report will thereby emphasize how important it is to initiate thorough diagnostic methods including cerebrospinal fluid analysis (CSF) before starting early immunotherapy

Results

Discussion

Conclusion