Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatonia.

backgroundCatatonia is a psychomotor disorder characterized by diverse clinical features, including mutism, stereotypy, posturing, waxy flexibility, and echophenomena. This condition is often observed in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, in which impaired glutamatergic transmission through antibody-mediated NMDAR internalization is demonstrated. However, cases of anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis presenting as catatonia have rarely been reported, and the mechanisms underlying such presentation remain unclear. CASE PRESENTATION: A 56-year-old Japanese woman presented with headache and fever, followed by rapidly progressive unresponsive state. Upon neurological examination, the patient exhibited resistance to passive eye-opening and avoidance of the face on the arm drop test despite the lack of withdrawal response to noxious stimuli, a finding consistent with a catatonic stupor. Cerebrospinal fluid (CSF) examination revealed pleocytosis and elevated IgG index without CSF-restricted oligoclonal bands. Brain magnetic resonance imaging revealed bilateral medial temporal lesions with two small cerebellar lesions. Electroencephalogram revealed alternating patterns comprising either frontal predominant 1-Hz delta activity or frontocentral predominant 5-Hz theta activity. N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography revealed right-sided predominant frontal hypoperfusion. Antibodies against the GluN1 subunits of NMDAR were not detected in CSF; however, the tissue-based assay revealed intense reactivity with neuronal surface antigens, a staining pattern highly suggesting AMPAR reactivity. AMPAR antibodies were detected in the CSF and serum, confirming the diagnosis of anti-AMPAR encephalitis. No other neuronal surface antibodies were detected. No malignancy was observed. The patient was treated with two cycles of intravenous high-dose methylprednisolone, oral prednisolone, and one cycle of intravenous immunoglobulins, resulting in gradual improvement of symptoms over 2 months.

conclusionsCatatonia is a rare manifestation of anti-AMPAR encephalitis; however, this disorder should be considered in the differential diagnosis of patients presenting with catatonia, particularly when the other core symptoms of anti-NMDAR encephalitis are absent or magnetic resonance imaging findings are not typical of anti-NMDAR encephalitis. The mechanism underlying catatonia in anti-AMPAR encephalitis remains speculative; however, it may be related to impaired glutamatergic transmission in the frontal lobe through antibody-mediated cross-linking and AMPAR internalization.