Mild Amnestic Cognitive Impairment and Depressive Symptoms in Autoimmune Encephalitis Associated with Serum Anti-Neurexin-3α Autoantibodies

Abstract

(1) Background: autoimmune encephalitis associated with neurexin-3α antibodies is a seldom reported disease entity often accompanied by a severe clinical neuropsychiatric syndrome. (2) Method: we report on the case of a 58-year-old man diagnosed with neurexin-3α-associated autoimmune encephalitis revealing cognitive decline and depression before the proof of neurexin-3α antibodies. He underwent neuropsychological testing, peripheral blood and cerebrospinal fluid analysis, neuroimaging and electroencephalography. (3) Results: our patient's main clinical feature was amnestic cognitive decline in combination with depressive symptoms. CSF analysis showed elevated phosphorylated tau protein 181 and positive proof of serum neurexin-3α antibodies in a cell-based assay. An 18F-FDG-PET/CT of the brain initially showed bilateral cerebral hypometabolism prefrontal and parietal, which was absent in follow up. The brain MRI was unremarkable. EEG recordings showed frontotemporal slowing in the theta and delta range. (4) Conclusions: taken together, we assumed autoimmune encephalitis associated with serum neurexin-3α antibodies. To the best of our knowledge, we are the first to report on a predominantly mild clinical manifestation entailing amnestic mild cognitive impairment in addition to depression, thus broadening the clinical spectrum associated with neurexin-3α antibodies.

Keywords: autoimmune encephalitis; depression; mild cognitive impairment; neurexin-3α antibody.

Figure 1

Time course of symptoms evolution. Abbreviations: CSF = cerebrospinal fluid, cMRI = cranial magnetic resonance imaging, CT = computed tomography, EEG = electroencephalography, NP = neuropsychological testing, PET CT = positron emission tomography computed tomography, electroencephalography, and PET CT = positron emission tomography computed tomography. The gray syringes indicate the corresponding methylprednisolone cycles.

Figure 2

18F-FDG-PET images of the brain. Three-dimensional surface projections of FDG-uptake in lateral and medial view. (A) initial 18F-FDG-PET scan showed bilateral hypometabolism prefrontal medial and parietal, (B) follow up 18F-FDG-PET showed physiological cerebral FDG uptake. R lat = right lateral view; L lat = left lateral view; R med = right medial view; L med = left medial view.