key: cord-1056297-tior7j35
authors: Dubey, Souvik; Ghosh, Ritwik; Dubey, Mahua Jana; Sengupta, Samya; Benito-León, Julián; Ray, Biman Kanti
title: Bilateral thalamic changes in anti-NMDAR encephalitis presenting with hemichorea and dystonia and acute transient psychotic disorder
date: 2020-07-22
journal: J Neuroimmunol
DOI: 10.1016/j.jneuroim.2020.577329
sha: 2620c0b254c78684166a62fcd58ce17da33a0a6f
doc_id: 1056297
cord_uid: tior7j35

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is one of the most common causes of autoimmune encephalitis. Both movement disorders and neuropsychiatric manifestations are considered core features of anti-NMDAR encephalitis. Strong clinical suspicion, along with NMDAR antibody positivity in paired sample of serum and cerebrospinal fluid, with supportive MRI changes clinch diagnosis in majority. We herein report a case of a middle-aged woman with subacute behavioral abnormalities, which were so severe that forced her to attempt suicide. Hemichorea and dystonia, which appeared later in course, are not previously reported movement disorders in combination in anti-NMDAR encephalitis. Further, magnetic resonance imaging showed bilateral thalamic hyperintensities with diffusion restriction, which are in turn not described in this entity. After amalgamation of history, especially the presence of neuropsychiatric symptoms, clinical features, physical examination, and investigations, the diagnosis of anti-NMDAR encephalitis could be established. Our case not only highlights that the combination of hemichorea and dystonia can be features of anti-NMDAR encephalitis, but adds novelty by bilateral symmetric thalamic changes.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common anti-neuronal antibody mediated autoimmune encephalitis. (Gable et al., 2012) The most frequent modes of presentation are behavioral changes, psychiatric problems, seizures, cognitive disabilities, movement disorders and dysautonomia. (Dalmau et al., 2019) This is truly a heterogenous disease in terms of affected age group, being more frequent in young women with ovarian neoplasms. (Dalmau et al., 2011) Both movement disorders and neuropsychiatric manifestations are considered core features of anti-NMDAR encephalitis.(Baizabal-and psychotic symptoms, especially disorganized behavior and visual-auditory hallucinations as well as persecutory delusions. (Sarkis et al., 2019) Amidst the array of prevalent movement disorders in anti-NMDAR encephalitis, dyskinesia (particularly orofacial) is most common (van de Riet et al., 2015) followed by limb and oromandibular dystonia, choreoathetosis, myorhythmia, blepharospasm, opisthotonos and tremor. (Baizabal-Carvallo et al., 2013 , Dalmau et al., 2011 , Mohammad et al., 2014 , van de Riet, et al., 2015 The combination of hemichorea and dystonia associated with anti-NMDAR encephalitis has not been published previously.

Magnetic resonance imaging (MRI) of brain reveals no discernable abnormal signal in the parenchyma in near about 50% cases of anti-NMDAR encephalitis. , Zhang et al., 2018 Even when it reveals abnormal intensities, there is a clinic-radiological paradox and lesion-manifestation discordance (i.e. imaging abnormalities may be unrelated to clinical signs/symptoms). Hippocampi are the most common regions that show altered T2/FLAIR signals, followed by mesial temporal lobes, cerebellum, inferior frontal lobes, insular cortices, basal ganglia, parietal lobes, brainstem, periventricular white matter, internal capsules, and thalami. , Zhang et al., 2018 Isolated thalamus involvement is very rare in anti-NMDAR encephalitis and bilateral symmetric thalamic changes is novel. (Kim et al., 2020 We herein report a case of a middle-aged woman who initially had a psychiatric diagnosis of acute transient psychotic disorder, which was so severe that she tried to commit suicide. Lately she developed a peculiar hyperkinetic J o u r n a l P r e -p r o o f movement disorder with bilateral thalamic hyperintensities with diffusion restriction. She was finally diagnosed with anti-NMDAR encephalitis. The response to combination of intravenous corticosteroids and intravenous immunoglobulin (IVIG) was excellent.

A 34-year-old previously healthy woman was referred to emergency with history of attempted hanging and with complaint of new onset involuntary, uncontrollable, dance-like movements involving right half of her body for last four days. Her relatives gave history that she had gradual onset, progressive behavioral abnormality for last three months for which she was getting treatment (quetiapine (100 mg/day), valproate (1200 mg/day), escitalopram (15 mg/day), clonazepam (1 mg/day)) from a psychiatrist without any improvement. Her husband had noticed rather abrupt change in her wife's behavior since she returned from visit to her parents three months ago. Initially, she was more anxious, poorly attentive, indecisive, restless, and was not able to keep conversations for a longer period in a concentrated manner. She complained of hearing singing voices. In addition, she started nurturing a delusional belief that she had been impregnated with a baby from an evil force. She was also bursting into tears every now and then, particularly in front of her husband. With this feeling of extreme guilt, she attempted suicide by hanging herself ten days back. Her relatives were nearby and responded with utmost promptness. She was hospitalized in a nearby rural health facility and discharged after 48 hours of observation as she had no demonstrable neurological deficit other than the pre-existing behavioral abnormality. She was finally referred to tertiary center. On day 5 of hospital stay, intravenous methylprednisolone (1 g/day) was initiated for consecutive 5 days. Her movement disorders were abolished, but cognitive and behavioral problems persisted. Hence, on day 15 of hospital stay she was put on IVIG for 5 days. With this therapy, her behavioral problems abated, and psychotic symptoms disappeared. She was again evaluated by a panel of neurologists and psychiatrists and had no depressive symptoms. There was significant improvement in MMSE with a total score of 27/30 (1 point was deducted from each in registration, recall and the last three-step-command). She was discharged in a stable condition with minor cognitive impairment and oral steroids in tapering doses. Repeat MRI showed decreased hyperintensities as compared to the previous scan in the corresponding areas.

Our patient presented with subacute onset behavioral abnormality, cognitive difficulties, and psychiatric symptoms, followed by hemichorea and dystonia, a constellation of clinical features germane to diagnosis of anti-NMDAR J o u r n a l P r e -p r o o f encephalitis. In about 70% of patients with anti-NMDAR encephalitis, there is a prodromal phase characterized by headache, fever, gastrointestinal symptoms and upper respiratory tract illness, (Dalmau et al., 2011 , Dalmau, et al., 2019 , Sarkis et al., 2019 which was not reported in our patient. Credible explanations are prodromal symptoms were there, but her relatives probably ignored them, as she was not with her at that time and the patient herself could not give proper account of the initial illness. She did not develop severe encephalopathy, seizures and dysautonomia traits requiring intensive care admission fortunately because she was diagnosed relatively earlier. (Dalmau et al., 2011) Suicidality is more common than it was thought of in backdrop of anti-NMDAR encephalitis associated neuropsychiatric issues. Zhang et al. (Zhang et al., 2017) reported that almost 13% of their study population (N=133) had suicidality. Only 6-7% had attempted a suicidal attempt unsuccessfully. (Zhang, et al., 2017) In patients who presented a psychiatric disorder, suicidality was more common, (Zhang, et al., 2017) The neuropsychiatric and cognitive symptoms in our patient could be, at least partially, explained by bilateral thalamic involvement. Emerging data support novel views of thalamic functions that emphasize integrative roles in cognition. (Anticevic et al., 2014; Pinault, 2011; Uhlhaas, et al.,, 2013; Wolff & Vann, 2019) In addition, damage to the thalamus, causing the phenomenon of diaschisis, can be manifested as various neuropsychiatric symptoms. (Anticevic et al., 2014; Pinault, 2011; Uhlhaas et al.,, 2013; Wolff & Vann, 2019) Specifically, damage to the dorsomedial nucleus of thalamus, particularly on the right side, results in disruption of the thalamus from thalamo-cortical-limbic networks. (Julayanont P, et al., 2017) This disrupted network may cause mania, which is secondary to the dysregulation of emotion, motivation, social conducts, reward seeking behaviors, and personality. (Julayanont P, et al., 2017) Similarly, damage to pulvinar nucleus decreases thalamic suppression to the occipital and temporal cortices, known as release phenomenon, which results in visual and auditory hallucinations. (Julayanont P, et al., 2017) Movement disorders, particularly the hyperkinetic ones, usually appear after the onset of prodromal and neuropsychiatric phases in adults. Nevertheless, a specific movement disorder may well be the index symptom of undermined anti-NMDAR encephalitis. (Baizabal-Carvallo, et al., 2013 , Dalmau et al., 2011 , Mohammad et al., 2014 , van de Riet, et al., 2015 . Baizabal-Carvallo et al., (Baizabal-Carvallo et al., 2013) reported that, in adults with anti-NMDAR encephalitis, incidence of movement disorders may be as high as 86%. Clinicians loss of cortico-limbic control over hypothalamus and brainstem as well as loss of fronto-striatal inhibition, resulting in such bizarre movements, (Dalmau et al., 2011 , Jucaite et al., 2010 , Stamelou et al., 2012 In closing, our case not only highlights that the combination of hemichorea with dystonia can be features of anti-NMDAR encephalitis, but adds novelty by bilateral symmetric thalamic changes. 1.Subacute onset behavioral abnormalities along with complex movement disorders warrants investigations to exclude anti-N-methyl-D-aspartate receptor (anti-NMDAR)

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