Seronegative limbic encephalitis manifesting as subacute amnestic syndrome: a case report and review of the literature

Abstract

Background: Limbic encephalitis (LE), a variant of autoimmune encephalitis, is inflammation of the limbic system of the brain. The disorder presents with subacute impairment of short-term memory, psychiatric manifestations, confusion and seizures. "Seronegative LE" is a challenging diagnosis in the absence of well-characterized autoantibodies.

Case presentation: A 33-year-old Kuwaiti woman with no relevant past history presented with subacute progressive amnesia of 6-month duration. Magnetic resonance imaging (MRI) showed bilateral hyperintensity of the limbic structures. An extensive workup of the blood and cerebrospinal fluid (CSF) failed to identify paraneoplastic or autoimmune antibodies. The diagnosis of seronegative LE was made, and immunotherapy was initiated, with improvement in cognitive function.

Conclusion: Seronegative LE is a challenging diagnosis. Inability to detect autoantibodies, especially early in the disease course, should not rule out the diagnosis of autoimmune encephalitis. Early diagnosis and treatment with immunotherapy may prevent irreversible brain damage.

Keywords: Amnesia; Autoimmune; Limbic encephalitis; Memory; Seronegative.

Fig. 1

Magnetic resonance imaging findings. a Axial fluid-attenuated inversion recovery (FLAIR), b axial T2-weighted images, showing bilateral hyperintense signals and hypertrophy of medial temporal lobes and hippocampi, c, d sagittal T2-weighted images showing hypertrophy of hippocampi (left: head thickness 11 mm, body thickness 9.8 mm, right: head thickness 15 mm, body thickness 10 mm) and amygdala bilaterally (arrows), e diffusion-weighted imaging showing no restriction, f coronal T2-weighted images showing bilateral hippocampal hypertrophy (arrows), g magnetic resonance perfusion images showing a focal increase in regional cerebral blood flow on the left side (arrow), and h magnetic resonance spectroscopy showing increased Cho/NAA ratio on the left side

Fig. 2

Follow-up magnetic resonance imaging after 2 months of immunotherapy. a Axial fluid-attenuated inversion recovery (FLAIR), b axial T2-weighted images, c coronal T2-weighted images, e, f sagittal T2-weighted images, showing decrease in the T2/FLAIR high signal intensity of the hippocampi bilaterally, and regression of the hypertrophy of hippocampi (left: head thickness 7 mm, body thickness 8.5 mm, right: head thickness 10 mm, body thickness 8 mm) and amygdala bilaterally (arrows), d diffusion-weighted imaging showing no diffusion restriction.

Fig. 3

Timeline of the clinical course