Pregunta 25. Cuando pensar en organicidad en pacientes psiquiátricos

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A 39-year-old man who has a history of personality changes and severe depression is anxious, confused, and extremely agitated on presentation. He also demonstrates auditory and visual hallucinations. According to family members, his personality has changed substantially in less than a year. The patient previously had enlarged cervical lymph nodes for which imaging studies were ordered. His chest CT scan shows a left-sided lung mass and cervical lymphadenopathy, highly suggestive of lymphoma. Antibodies to which of the following receptors may be the reason for the patient’s psychiatric symptoms?

A. NMDA receptor subunit 1 (NR1) **
B. Metabotropic glutamate receptor subunit 5 (mGluR5)
C. Antineuronal nuclear antibody type 3 (ANNA-3)
D. Leucine-rich glioma-inactivated protein 1 (LGI1)
E. Contactin-associated protein-like 2 (Caspr2)
** = Your answer
The patient most likely has an autoimmune encephalopathy due to an underlying malignancy or tumor, most likely lymphoma. Autoimmune encephalopathy is increasingly recognized by its early psychiatric symptoms in which prompt recognition can lead to effective treatment; therefore, a high degree of suspicion for autoimmunity must be maintained, especially in patients who present with unusual neuropsychiatric syndromes. Two categories of encephalopathy are recognized as the direct result of autoimmunity: rheumatic conditions with neuropsychiatric symptoms and antibody-associated autoimmune encephalitis (AAE). AAEs describe conditions of brain inflammation associated with IgG autoantibodies targeting either neuronal surface epitopes or intracellular antigens. Antineuronal surface epitope antibodies are infrequently paraneoplastic, whereas anti-intracellular antigen antibodies often are known as onconeural antibodies due to their close association with malignancy. Glutamate modulates a variety of synaptic responses by activating metabotropic glutamate receptors. mGluR5, expressed primarily in the hippocampus and amygdala, is known to play a role in behavioral learning and memory. Antibody against mGluR5 frequently reposted in patients with Hodgkin lymphoma, is also called “Ophelia syndrome”. The antibody against NMDA receptor subunit 1 (NR1) can cause limbic encephalitis and can be associated with a viral prodromal. The associated tumor is rare in men and children, but a high association to teratoma can be seen in women. The antineuronal nuclear antibody type 3 (ANNA-3) usually presents with encephalomyelitis rather than a psychiatric presentation and is associated with pulmonary or extra-pulmonary small cell tumors. The antibody to leucine-rich glioma-inactivated protein 1 (LGI1) is rarely associated with tumors. Although limbic encephalitis is common, seizure usually is one of the presenting symptoms. The antibody to contactin-associated protein-like 2 (Caspr2) can be associated with thymoma and endometrial carcinoma. Neuromyotonia usually is the most common predominant feature.
* Oldham M. Autoimmune encephalopathy for psychiatrists: when to suspect autoimmunity and what to do next. Psychosomatics. 2017 May-Jun;58(3):228-244.
* Kalman B. Autoimmune encephalitides: a broadening field of treatable conditions. Neurologist. 2017 Jan;22(1):1-13.
* 3. Lu YM, Jia Z, Janus C, et al. Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J Neurosci 1997;17:‪5196–5205‬
* Mat A, Adler H, Merwick A, et al. Ophelia syndrome with metabotropic glutamate receptor 5 antibodies in CSF. Neurology. 2013 Apr 2;80(14):1349-1350.

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