An 81 year-old man presented to hospital with five days of short-term memory loss and irritability. He was noted to remember 0 out of 3 objects on delayed recall and was only oriented to self, otherwise neurologic and physical exam was unremarkable. Labs were significant for serum sodium of 125 millimoles/liter, urine sodium of 88 millimoles/liter and urine osmolality of 770 milliosmoles/liter. Non-contrast head CT was unremarkable.
Despite improvement in hyponatremia with fluid restriction, patient’s cognitive impairment remained unchanged. Cerebrospinal fluid (CSF) cell count, protein and glucose were within normal limits. A Brain MRI demonstrated T2/FLAIR signal hyperintensities in the left hippocampus, parahippocampal gyrus and left uncus. Serum antibodies were positive for anti-voltage gated potassium channel (VGKC) antibodies. CSF Herpes Simplex polymerase chain reaction testing was negative.
A diagnosis of VGKC antibody-associated limbic encephalitis was made. Patient was started on intravenous methylprednisolone and was transitioned to oral prednisone on discharge from the hospital. CT of the chest, abdominal, and pelvis was performed to rule out paraneoplastic disease and was negative.
A repeat brain MRI 1 month later showed decreased T2 signal and mass effect of the left hippocampus/parahippocampal gyrus, suggesting decreased/resolving limbic encephalitis. Patient’s cognitive impairments improved over 3 months on chronic steroid treatment.
Discussion:
Limbic encephalitis refers to inflammation in limbic system with autoantibodies directed against neurons and manifests as short-term memory deficits, cognitive impairment, and mood changes.1 Limbic encephalitis has been mostly associated with malignancy, but various forms of non-paraneoplastic limbic encephalitis have been recognized in the past decade.1 VGKC antibody encephalitis typically presents in patients without cancer and targets leucine-rich glioma inactivated 1 protein, affecting neuronal activity.2,3 It has also been associated with hyponatremia in some case reports.2,4 Treatment can be attempted with steroids, intravenous immunoglobulin, plasma exchange or other immunosuppressants.5
Conclusions:
There is a growing recognition of non-paraneoplastic limbic encephalitis. In the setting of a compatible clinical syndrome of limbic encephalitis with no evidence of infection or malignancy, testing for autoantibodies should be considered in consultation with a neurologist.
References:
1. Buckley C, Oger J, Clover L, et al. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol. 2001;50(1):73-8. doi:10.1002/ana.1097.
2. Harrower T, Foltynie T, Kartsounis L, et al. A case of voltage-gated potassium channel antibody-related limbic encephalitis. Nat Clin Pract Neurol.2006;2(6):339-43. doi:10.1038/ncpneuro0194.
3. Lai M, Huijbers MG, Lancaster E, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol. 2010;9(8):776-85. doi:10.1016/S1474-4422(10)70137-X.
4. Saleem A, Sophia R. Voltage-gated potassium channel antibody-associated limbic encephalitis. Age Ageing. 2014;43(4):583-5. doi: 10.1093/ageing/afu064.
5. Radja GK, Cavanna AE. Treatment of VGKC complex antibody-associated limbic encephalitis: a systematic review. J Neuropsychiatry Clin Neurosci. 2013;25(4):264-71. doi: 10.1176/appi.neuropsych.13020022.