To describe a case of adenylate kinase-5 (AK5) antibody encephalitis presenting with rapidly progressive amnesia and response to aggressive immunotherapy.

The incidence of anti-AK5-associated limbic encephalitis is exceedingly rare, with sparse documented cases in the literature. It is a non-paraneoplastic autoimmune limbic encephalitis lacking early epileptic features with poor response to immunotherapy. 

A 66-year-old African American man presented with a one-month history of progressive working memory deficits. Brain magnetic resonance imaging revealed symmetric bilateral medial temporal and hippocampal FLAIR hyperintense signals suggestive of autoimmune encephalitis. CSF testing was notable only for lymphocytic pleocytosis (19 WBCs). Comprehensive infectious evaluation and CSF paraneoplastic panel were negative. EEG was normal. He received intravenous methylprednisolone for five days and 2 mg/kg of intravenous immunoglobulin for four days with no clinical improvement. At two-month outpatient follow-up, his symptoms persisted, and scored 18/30 on a Montreal Cognitive Assessment (MOCA). A repeat MRI confirmed persistent FLAIR hyperintensities in the medial temporal lobes and hippocampi. The CSF continued to show lymphocytic pleocytosis (7 WBCs) with 17 unmatched oligoclonal bands, and an elevated IgG index of 1.74 g/L. Serum and CSF autoimmune encephalopathy panels were negative. A 48-hour EEG was normal. Treatment with intravenous methylprednisolone and plasma exchange resulted in mild clinical improvement.

Research testing at a reference laboratory identified a staining pattern consistent with anti-AK5 antibodies in the CSF, which was confirmed on immunofixation. After 6 cycles of 1000 mg IV cyclophosphamide monthly, his family reported significant improvements in working memory and activities of daily living. He scored 21/30 on repeat MOCA.

Anti-AK5 antibodies are implicated in a distinct form of rapidly progressive, non-paraneoplastic autoimmune limbic encephalitis that typically lacks early epileptic features. In this patient, early and aggressive treatment was crucial in stabilizing memory deficits and achieving subtle clinical improvements.