Teaching Case

A 53-year-old male developed memory disturbance in the form of misplacing things, way finding difficulty, repeatedly asking the same questions, not being able to identify relatives, behavioural disturbance such as wandering behaviour, irrelevant talk, and recurrent episodes of focal seizures involving the face for 6 months duration. Initially, he was treated as dementia with behavioural disturbance.

MR imaging of the brain was performed in 3T MRI (SKYRA, SIEMENS HEALTHINEERS, ERLANGEN, GERMANY) which showed symmetrical decreased signal intensities in the bilateral medial temporal lobe on sagittal T1 weighted sequences [Fig Ia, Ib] and symmetrical increased signal intensities in the bilateral medial temporal lobe on axial T2 weighted sequences [Fig IIa, IIb] and FLAIR  coronal sequences [Fig IIIa, IIIb]. Arterial spin labelling shows decreased cerebral blood flow in the bilateral temporal lobe [Fig IV]. Basal ganglia and remaining brain parenchyma appear normal. MRI imaging suggested the diagnosis of Limbic encephalitis and which was further confirmed by autoimmune encephalitic profile as Anti-leucine-rich glioma inactivated 1(LGI1 ) antibody positive.

Background

Autoimmune Limbic Encephalitis with antibodies targeted to neuronal cell membrane antigens is a group of neuropsychiatric disorders that manifests as altered mental behavior, memory loss, and recurrent seizures. Anti-leucine rich–glioma inactivated protein-1(LGI1) Limbic Encephalitis is a subset of Autoimmune Voltage-Gated Potassium Channel complex (VGKC) Encephalitis.

Clinical perspective

Limbic Encephalitis(LE) is a rare neurological disorder predominantly affecting the Medial Temporal lobe. [1] It can either be Infectious (most commonly  Herpes Simplex Virus) or Autoimmune. LE has been commonly associated with a lot of neuronal antibodies. [2] These Neuronal antibodies can either be targeted against intracellular antigens in the case of Classic Paraneoplastic LE(anti-HU,anti-YO,anti-CV2/CRMP5,anti-Ri,anti-Ma2, and anti-amphiphysin) or it can be targeted against neuronal cell membrane antigens, ion channels like Voltage-Gated Potassium Channels(VGKC) and ligand-gated ion channels like NMDA, AMPA, GABA-B receptor channels. These antibodies are not commonly associated with tumours [3] and respond well to high-dose steroids and immunomodulatory therapy, whereas Classic Paraneoplastic LE does not respond to such treatment. [2]

VGKC is a multi-protein complex channel that has several antigens against which different autoantibodies are formed and accordingly different clinical syndromes appear. Leucine-rich glioma-inactivated protein 1(LGI1) and contactin-associated protein-like 2 (Caspr2) are the main antigens of the VGKC. LGI1 autoantibodies are more commonly associated with limbic encephalitis. Caspr2 autoantibodies are associated with peripheral nerve hyperexcitability known as neuromyotonia or Isaacs syndrome and a combination of peripheral nerve hyperexcitability and encephalitis known as Morvan Syndrome. [4]

Anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis predominantly occurs in the median age of 60 years who develop memory loss, confusion, and temporal lobe seizures. Classically presents with sudden brief asymmetrical tonic or dystonic contraction in the orofacial region and upper limbs. [4]

Imaging perspective

MR imaging of the brain shows increased signal intensity on T2 and FLAIR sequences in the medial temporal lobes in approximately 74%–84% of patients. [6] Initial MR imaging findings include unilateral or bilateral amygdala and/or hippocampal enlargement and T2 hyperintensity in 78.6% of patients at some time point during the disease course. Nearly half of the patients demonstrate restricted diffusion and a quarter will show associated mild ill-defined contrast enhancement and a minority will demonstrate extra-temporal findings. These findings are nonspecific and are similar to those associated with infectious limbic encephalitis and diverse paraneoplastic limbic encephalitis. [7] Autoimmune VGKC encephalitis with restricted diffusion should be targeted for aggressive immunotherapy to prevent progression to Mesial Temporal Sclerosis. [7]

Outcome

Neurobehavioral symptoms improved well with steroids and immunomodulators.