Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatonia
Abstract Background Catatonia 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 impair...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | BMC Psychiatry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12888-025-07185-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849343571335839744 |
|---|---|
| author | Yuki Nakagawa Atsuhiko Sugiyama Manato Yasuda Hideo Handa Yume Koizumi Yoshihisa Kitayama Marina Nakatani Takahiro Iizuka Satoshi Kuwabara |
| author_facet | Yuki Nakagawa Atsuhiko Sugiyama Manato Yasuda Hideo Handa Yume Koizumi Yoshihisa Kitayama Marina Nakatani Takahiro Iizuka Satoshi Kuwabara |
| author_sort | Yuki Nakagawa |
| collection | DOAJ |
| description | Abstract Background Catatonia 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. Conclusions Catatonia 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. |
| format | Article |
| id | doaj-art-2a4051330f2e4adcb3cc50211e577832 |
| institution | Kabale University |
| issn | 1471-244X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Psychiatry |
| spelling | doaj-art-2a4051330f2e4adcb3cc50211e5778322025-08-20T03:42:56ZengBMCBMC Psychiatry1471-244X2025-07-012511810.1186/s12888-025-07185-5Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatoniaYuki Nakagawa0Atsuhiko Sugiyama1Manato Yasuda2Hideo Handa3Yume Koizumi4Yoshihisa Kitayama5Marina Nakatani6Takahiro Iizuka7Satoshi Kuwabara8Department of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Kitasato University School of MedicineDepartment of Neurology, Graduate School of Medicine, Chiba UniversityAbstract Background Catatonia 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. Conclusions Catatonia 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.https://doi.org/10.1186/s12888-025-07185-5CatatoniaAutoimmune encephalitisAnti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitisAnti-N-methyl-D-aspartate receptor encephalitisCase report |
| spellingShingle | Yuki Nakagawa Atsuhiko Sugiyama Manato Yasuda Hideo Handa Yume Koizumi Yoshihisa Kitayama Marina Nakatani Takahiro Iizuka Satoshi Kuwabara Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatonia BMC Psychiatry Catatonia Autoimmune encephalitis Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis Anti-N-methyl-D-aspartate receptor encephalitis Case report |
| title | Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatonia |
| title_full | Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatonia |
| title_fullStr | Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatonia |
| title_full_unstemmed | Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatonia |
| title_short | Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis presenting as catatonia |
| title_sort | anti alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid receptor encephalitis presenting as catatonia |
| topic | Catatonia Autoimmune encephalitis Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis Anti-N-methyl-D-aspartate receptor encephalitis Case report |
| url | https://doi.org/10.1186/s12888-025-07185-5 |
| work_keys_str_mv | AT yukinakagawa antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia AT atsuhikosugiyama antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia AT manatoyasuda antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia AT hideohanda antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia AT yumekoizumi antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia AT yoshihisakitayama antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia AT marinanakatani antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia AT takahiroiizuka antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia AT satoshikuwabara antialphaamino3hydroxy5methyl4isoxazolepropionicacidreceptorencephalitispresentingascatatonia |