Autobiographical age awareness disturbance syndrome in autoimmune limbic encephalitis: two case reports

A 42-year-old Japanese woman, with a junior college education level, initially had a headache and slight fever (day 0). On day 2, after breakfast, she had a generalized, tonic-clonic seizure, beginning with her left jaw. On day 9, her linguistic ability spontaneously changed to that of an approximate 5-year-old, and she behaved in a childish manner, demanding that her mother serve her ‘gyoza’ (a favourite dish among Japanese children). She sometimes made pronunciation errors typical of a child, such as using the word ‘dechu’ to represent the Japanese copula ‘desu’. She was hospitalized on day 12. On admission, she showed signs of spatial and temporal disorientation. Retrograde and anterograde amnesia were also present. She did not remember a large earthquake that occurred 2 years ago in Tohoku, Japan. She also forgot the doctor she met and the examination that he performed in the morning. A standard bedside neurological evaluation revealed normal functioning of her cranial nerves, motor and sensory functions, and coordination. Bradycardia was present during sleep, possibly due to autonomic nerve dysfunction. She had no special medical and family history or relevant past interventions.

During hospitalization, the patient told us on one instance that she was 17 years old, and currently in her high school classroom. When she perceived herself as a 17-year-old, she spoke and laughed in the manner of a Japanese teenager. During this time, she was able to recognize her parents, but she had no apparent memories of her husband or children. She could not remember where and when she met her husband, or when she got married. On the other hand, she remembered the elementary school and junior high school from which she graduated. However, the woman was informed of her correct age, she reacted with surprise, and replied that it was strange that she was still in high school. Eventually the woman recalled that she was 42 years old, and was able to remember her marriage and three children.

Her mini-mental state examination (MMSE) score was 15 (out of 30). There was also a reduction in verbal and general memory quotient (MQ) scores and delayed recognition, as assessed by the Wechsler memory scale-revised (WMS-R). A decrease in general, verbal and performance intelligence quotient (IQ) scores was also observed, as assessed by the Wechsler adult intelligence scale (WAIS)-III. A cerebral spinal fluid (CSF) analysis revealed a cell density of 20 per mm³ (consisting of predominantly lymphocytes) with normal protein levels. There was no elevation in antibody titres of herpes simplex virus (HSV), varicella zoster virus (VZV) and Epstein-Barr virus (EBV). Similar results were found for HSV deoxyribonucleic acid using polymerase chain reaction (PCR). A blood examination revealed normal findings, aside from slightly elevated C-reactive protein. Anti-NMDA receptor titres were elevated in both serum and CSF. Fluid-attenuated inversion recovery (FLAIR) brain magnetic resonance imaging (MRI) showed bilateral, high-intensity signals in the medial temporal lobe (Fig. 1a). Single-photon emission computed tomography (SPECT) using ¹²³I-IMP brain perfusion showed that blood flow was bilaterally increased in the medial temporal lobe and decreased in the right orbitofrontal cortex (Fig. 1b and c). No ovarian teratoma was detected via enhanced pelvic MRI. A sporadic, right-temporal-lobe-dominant spike discharge and diffuse slow waves were visible by electroencephalography (EEG). After evaluation, the patient was diagnosed with anti-NMDA receptor encephalitis and was treated with intravenous high-dose corticosteroids (methylprednisolone, 1 g/day for 3 days), immunoglobulin therapy (0.4 g/kg/day for 5 days), and oral anti-epileptic drugs (levetiracetam, 3 g/day). The treatments improved all AAAD-related symptoms, such as disorientation and amnesia, and the patient was discharged from the hospital on day 81. The performance in WMS-R and WAIS-III administered 2 months after discharge significantly improved up to the normal range. There was no abnormal hyperperfusion in the medial temporal lobe or hypoperfusion in the right orbitofrontal cortex in ¹²³I-IMP brain perfusion SPECT performed 9 months later.

A 55-year-old Japanese woman who was employed as a part-time childcare assistant initially experienced a slight sore throat (day 0). She reported being under stress caused by the daily problems of looking after her elderly parents. On day 8, she became emotionally unstable and required supervision by her daughter all day. She lost all awareness of time and frequently checked the television display and clock. She mistook night for day and was unable to tell the date. In the evening, she was unable to carry out simple cooking tasks, and asked her daughter for help. On day 9, she was conscious but unable to walk as a result of involuntary limb movement; she also repeatedly recalled old memories and expressed concern about her parents. On day 11, she was admitted to a psychiatric hospital, but was transferred to our facility due to suspected encephalitis. At the time of admission, she showed signs of instability in cognition and attention to her surroundings. Although she retained verbal ability, she was disoriented with respect to time and place. Retrograde and anterograde amnesia were also present; she could not recall the work she was engaged in or when and how she was admitted to our hospital. Spontaneous tonic spasms appeared in her limbs bilaterally. A standard bedside neurological examination revealed otherwise normal findings for her cranial nerves, motor and sensory functions, and coordination. She had no special medical and family history or relevant past interventions.

During her hospitalization, the patient informed us that she believed she was 27 years old. She informed us that she was currently living in Aomori Prefecture and working as a receptionist, which accurately reflected events she experienced at age 27. She could recall memories of her marriage at age 25, but not her daughter, whom she gave birth to at 27. On a separate occasion, the patient adopted a birthing posture, as if she was re-experiencing the delivery that she had gone through when she was 27. However after informing her of her true age (55 years old), she recognized this fact, and her memory was transiently corrected accordingly.

Her MMSE score was 26. She showed decreased measures of attention and concentration, along with delayed recognition, as assessed by the WMS-R; however, her WAIS-III evaluation was normal. A CSF analysis revealed normal cell density, protein, and glucose levels. Antibody titres to HSV, VZV, and EBV were also normal, and HSV was undetected by PCR. Subsequently, elevated serum anti-NMDA receptor antibody titres were detected in both serum and CSF.

There were no abnormal findings revealed by brain MRI (Fig. 1d). However, ¹²³I-IMP brain perfusion SPECT showed increased blood flow bilaterally in the medial temporal lobes and orbitofrontal cortex (Fig. 1e and f). Epileptic discharges and abnormal slow waves were not detected by EEG. Following evaluation, she received a diagnosis of anti-NMDA receptor encephalitis. Oral anti-epileptic drugs (carbamazepine, 200 mg/day; levetiracetam, 2 g/day) and intravenous high-dose corticosteroid therapy (methylprednisolone, 1 g/day for 3 days) improved her symptoms, confirming the diagnosis of AAAD. The patient was discharged on day 51. At the time of discharge, there was no disorientation or amnesia, her MMSE score improved to 28/30. Subsequently, she stopped coming to our hospital and we were unable to perform follow-ups.

Clinical findings for both cases are summarized in Table 1.