Acute psychotic onset in LGI1-related limbic encephalitis

Abstract

Leucine-rich glioma-inactivated 1 (LGI1)–related limbic encephalitis is a rare autoimmune disorder associated with antibodies to voltage-gated potassium channel complex that is infrequently accompanied by tumors and with a good response to therapy [1]. The onset and core symptoms are seizures and cognitive disorders. Seizures include generalized tonic-clonic seizures, partial seizures, and dystonia-like episodes involving face and limbs on the same side (FBDS). Among cognitive disorders, short-term memory impairment is the most common. We here describe a patient with LGI1related encephalitis presenting with isolated acute psychosis. Additionally, we performed a PubMed search to identify papers reporting patients with LGI1-related encephalitis and psychiatric manifestations from January 2010 (the year of description of LGI1-related encephalitis) to May 2020 by using the following terms: LGI1 antibody, limbic encephalitis LGI1, combined with acute psychosis, psychiatric symptoms, and acute behavior disturbances. The search was restricted to full-text papers in English. A 71-year-old female was admitted because she was found wandering aimlessly and confused around the town. The relatives reported that since the day before the patient had a state of agitation, irascibility, and anxiety, with impulsive and bizarre behavior. The patient did not have history of psychiatric disorders, traumatic brain injury, and alcohol consumption, and was not taking medications. She did not have fever in the previous days, nor a history of thyroid dysfunction and hepatic and kidney diseases. In the emergency department, the patient had normal vital parameters but was agitated, aggressive with the medical staff, and repeatedly tried to leave. Moreover, the patient was disoriented and unable to fall asleep. Two days after hospitalization, the patient reported paranoid ideation about the neighbors, and her speech begun to disorganize with perseveration of words and phrases. The consultant psychiatrist diagnosed a paranoid disorder. Although it was difficult to administer neuropsychological tests, because of the patient’s suspicious attitude, the Mini Mental State Examination (MMSE) score was 30, and the Montreal cognitive assessment (MOCA) score was 26. There was no significant memory deterioration. Neurological examination showed plastic rigidity and bradykinesia without any other focal signs. The patient in the following days became progressively verbally unresponsive; she would occasionally make eye contact but more often stared blankly. Liver and renal function, serum electrolytes, lactate dehydrogenase, erythrocyte protein rate, PCR, procalcitonin, and leukocytes were all in the normal range. Antibodies against toxoplasma, rubella, cytomegalovirus, herpes virus, tuberculosis, Borrelia, and HIV screening were negative. Antinuclear, anti-DNA, anticardiolipin, thyroperoxidase, and thyroglobulin antibodies were negative. CPK were increased up to 1000 U/L (normal: 60–190 U/L). Cerebrospinal fluid examination did not reveal inflammatory or neoplastic cells; protein content was normal and 14-3-3 protein was absent. Electroencephalography showed nonspecific features, with diffuse slowing in theta band on the anterior regions, without clear lateralization. Magnetic resonance imaging showed, only in FLAIR sequences, a mild increased signal intensity and swelling of the hippocampus bilaterally with no contrast enhancement. Diffusion-weighted imaging was normal. Chest and abdomen CT were normal. The clinical and neuroimaging findings prompted us to hypothesize a limbic encephalitis, and 4 days after hospitalization, intravenous immunoglobulin (0.4 g/kg) was given for 5 days. One week after the admission, the patient began to show involuntary jerky movements of the upper limb and face mixed with dystonia-like movement suggesting FBDS. Haloperidol 0.5 mg three times a day and levetiracetam 500 mg twice a day were also introduced. The patient continued to be unresponsive; therefore, methylprednisolone 500 mg i.v. was administered for 5 days [2]. In the meanwhile, by two independent methods, line blot (EUROLINE) and * Francesca Notturno [email protected]