29-year-old single woman, living with her parents, with no history of organic or psychiatric pathology or drug abuse, admitted to neurology for behavioural alterations, disorientation and lack of connection with the environment. The family reported that it was the first episode of these characteristics, that for the last 2 weeks they had seen the patient discouraged, not very communicative (they did not identify any trigger or decompensating factor, the relationship with the patient was good, she had a good social support network, good job performance, etc.), she sometimes looked lost, even spoke incoherently ("the veins in her head were dry"), there was no alteration in her biological rhythms. All this was a cause for great family anxiety, so the family doctor was consulted, and she was treated as depressed and prescribed sertraline 50 mg/day (1 week before admission). The evolution was torpid, with episodes of psychomotor agitation and disorientation, which is why the family decided to take the patient to the emergency department. There was no family history of significant psychiatric or organic disease. On examination, apart from the spatio-temporal disorientation and agitation, nothing remarkable was found, and there was no neurological focality.
Laboratory tests (haemogram, coagulation, liver function tests, renal, thyroid, urine, folic acid and vitamin B12) and brain tomography were normal. Urine toxins were negative. Lumbar puncture (LP) showed 26 leukocytes/mm3. In the ED she presented with a generalised tonic-clonic seizure and was admitted with a presumptive diagnosis of viral encephalitis, and treatment was started with acyclovir and valproic acid.
During her admission she was assessed by psychiatry. The family again reported that the patient had been listless for 2 weeks, repeating that she had "dry veins in her head". She was classified as psychotic depression and venlafaxine 75 mg/day was prescribed. Serology for HIV, Brucella, Cytomegalovirus, Herpes Simplex, Syphilis, Toxoplasmosis and Epstein Barr were negative.
During the first week of hospitalisation the patient was confused, presented with soliloquies and unmotivated laughter. LP was repeated (34 leucocytes/mm3, lymphocytes 100%, serology and cerebrospinal fluid (CSF) culture for Brucella, Lúes and Borrellia were negative). Brain magnetic resonance imaging (MRI) was normal. The antidepressant was discontinued and tiapride was prescribed.
During the second week, electroencephalogram (EEG) showed signs of moderate diffuse slow encephalopathy. The patient was unresponsive to simple commands, mutative, stuporous, so tiapride was discontinued, leaving her on intramuscular haloperidol in case of agitation. Due to the torpid evolution, she was admitted to the ICU, discontinuing valproic acid and starting levetirazepam. The patient started to present involuntary movements and dystonia. Transthoracic echocardiography was normal. Megadoses of corticosteroids and haemin were added (suspected acute intermittent porphyria). Due to the most frequent complex tonic seizures, sedation and endotracheal intubation were decided. No uroporphyrins were detected, coproporphyrins and zinc were within normal limits (so haemin was discontinued). LP was repeated, with polymerase chain reaction for mycoplasma and mycobacteria being normal.
During the fourth week, sedation was withdrawn: he responded to simple commands, had facial myoclonus and buccolingual movements, and extubation was performed. EEG continued to show signs of diffuse encephalopathy. Prion disease was ruled out (negative for CSF protein). The gynaecological ultrasound showed a slightly enlarged ovary.
During the sixth week, ceruloplasmin, serum copper and abdominal ultrasound were normal. The patient was more conscious and reactive. The possibility of encephalitis was raised in relation to a teratoma that was not found. LP was repeated looking for the presence of paraneoplastic antibodies (anti-Hu, anti-Yo, anti-Ri, anti-CV2, anti-fysin, anti-Tr and anti-calcium channel), which were negative, except for anti-NMDA antibodies. Psychiatry was called again due to psychomotor agitation and self-referential delusions, and ziprasidone 40 mg/day was started, reaching up to 160 mg/day with progressive improvement. The final diagnosis was encephalitis against N-methyl-D-aspartate receptors (ECR-NMDA) and psychotic disorder secondary to organic pathology (ECR-NMDA).