Psychosis as an initial symptom of autoimmune encephalitis with negative antibodies

Dear Editor,

Autoimmune encephalitides form part of the inflammatory neurological syndromes of the central nervous system. They are measured by a inflammatory cross-over reaction to intracellular antigens (Hu, Yo, Ri, Ma2, CV2/CRMP5, amphiphysin) or the neuronal surface (NMDA, AMPA, GABAb, glycin, VGKC complex) and are associated in some cases with oncological diseases.^1,2 They usually present in the form of cognitive disorders, epileptic seizures, mood disorders and/or psychotic disorders. Symptoms vary depending on the antibodies involved³ and non presentation of all the symptoms is common.⁴ Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is another neurological disorder where an encephalopathy and an autoimmune thyroiditis present together. SREAT may present with or without involvement of thyroid hormones and is associated with epileptic seizures, disorientation, myoclonus, ataxia, cognitive impairment and psychosis.⁵ It is an interesting fact that in 10% of cases, symptomatology is reduced exclusively to affective disorders⁶ or psychotic disorders.^7,8 Autoimmune encephalitis and encephalopathies such as SREAT are neurological pathologies, which may imitate psychiatric syndromes, but unlike these, they present with changes in cerebral nuclear magnetic resonance (NMR), in cerebrospinal fluid and/or in the electroencephalogram.

We present the case of a 29-year-old patient diagnosed with autoimmune encephalitis with negative antibodies. He did not consume toxic substances nor was there any history of other psychiatric disorders in the family. The start of the disease began when he was 20 years of age with a psychotic episode characterised by paranoid delusional ideation, auditory and visual hallucinatory symptoms and conciliation and maintenance-sleep insomnia. The patient was admitted to the acute psychiatric unit, where in the analysis on entry positive anti-thyroid antibodies were observed (MAK-TPO > 1.300 UI/ml, TAK > 175 UI/ml) with no alteration to thyroid hormones. After starting antipsychotic treatment with olanzapine at 20 mg/day, the patient was referred to the neuro-rehabilitation unit. A brain NMR scan was performed there which was normal. Lumbar puncture showed intrathecal IgG synthesis rate of 11%. Antineuronal antibodies and neuronal surface antibodies tested negative in serum and in cerebrospinal fluid. In the electroencephaologram a general slowing down of moderate severity was observed without potential epileptiforms. On suspicion of a SREAT, treatment was initiated with 100 mg/day prednisone, but the psychotic symptoms severely worsened and treatment had to be suspended 4 days later. After 72 h symptoms remitted and the patient was discharged with a diagnosis of unspecified psychotic disorder and Hashimoto thyroidism in treatment with 20 mg/day olanzapine. Two years later, the patient ceased antipsychotic medication and was asymptomatic up to 27 years of age, when he was admitted to the acute neurological unit with consistent symptoms of intense headache, delusional ideation of prejudice against his mother, psychomotor restlessness and conciliation and sleep-maintenance insomnia. Cerebral NMR was normal. Lumbar puncture again showed intrathecal IgG synthesis of 10.7% and negative antineuronal cell antibodies and neuronal cell surface antibodies.

The electroencephalogram showed a general moderate/serious slowing down without potential epileptiforms. In the Dem-Tect (cognitive Test) the patient obtained 5/18 points (indicator of a severe cognitive impairment). On suspicion of autoimmune encephalitis, treatment was initiative with immunoglobulins (3 × 10 g) for 5 days together with antipsychotic treatment with 20 mg/day olanzapine. As no improvement was observed, treatment with plasmapherisis was initiated (5 cycles) combined with 150 mg/day azathioprine which was effective and it was possible to reduce the olanzapine dose to 5 mg/day. Following absolute resolution of symptoms and with an ad integrum (Dem-Tect 18/18) cognitive recovery, the patient was discharged and sent home. At present, the patient is symptom-free and has been 24 months without any pharmacological treatment.

Al-Diwani et al.⁹ (2019), in their systematic review with 1,100 patients on psychiatric symptoms in the population with encephalitis NMDA-R, observed that the most common psychiatric symptoms were affective and psychotic disorders. The clinical case we present shows the importance of carrying out an appropriate neurological screening in psychiatric patients, and the diagnostic difficulty between the SREAT and autoimmune encephalitis in a patient with Hashimoto thyroiditis. In our case, good response to plasmapheresis with azathioprine and the worsening of symptoms observed with corticoids suggested that this was an autoimmune encephalitis. Early treatment in autoimmune encephalitis with immunosuppressants, immunoglobulin or plasmapheresis is effective,¹⁰ although specific relapses may appear in the future.⁴