Recent studies further indicate that allosteric modulation of NMDAR may be a promising complementary treatment approach, particularly in refractory cases (23). Second, an emerging association between the COVID-19 disease and NMDAR AE, if further substantiated in the future, should prompt differential diagnostic concern in cases of acutely emerging psychiatric symptoms following after a recent SARS-CoV-2 infection as present in this case. cell-based assay. Reflex at 1:2 on tissue-based assay non-reactive. NMDAR Ab positive, N-methyl-D-Aspartate Receptor Antibody. 2.1. Clinical findings During our initial evaluation, the patient displayed intense and labile impact and periods of confusion, loss of orientation to time, location, and situation, with aggressive behavior. He voiced subjective complaints about problems with his nerves and memory. He appeared Ethoxzolamide internally preoccupied and reported both visual and auditory hallucinations. Additionally, he exhibited significant paranoia, believing that individuals were pursuing him with an attempt to actually and sexually assault him. These manifestations lasted for hours at a time and were interleaved with periods of linear thought process and appropriate thought content. The presentation appeared most consistent with delirium with psychotic features, even though etiology was unknown at the time. A primary psychotic disorder was considered as a differential diagnosis and had in the beginning been suspected by the referring hospital. However, this seemed less likely on our assessment given the absence of any psychiatric history and the strong fluctuance of symptoms. The initial neurological examination performed while the individual was fully oriented and with organized thought process revealed deficits in attention and delayed recall, but no focal neurological deficits were recognized. In the later hospital course, 2C3?weeks after admission (Physique 1), the patient further developed hypersomnolence and fluctuating catatonic features, including verbigeration, stupor, minimal verbal responsiveness, staring, posturing, negativisms, waxy flexibility, Mitgehen, and mild Ethoxzolamide autonomic instability [Bush-Francis score (21) up to 23]. In addition, he started to show neurological symptoms, specifically dysarthria and gait ataxia. Open in a separate window Physique 1 Timeline of relevant events. IVIG, intravenous immunoglobulins. During the physical exam, a maculopapular rash was observed on the patients chest and back (as shown in Physique 2A). This rash experienced started to develop approximately 2C3? weeks prior to the initial presentation. Magnetic resonance imaging with gadolinium contrast (Figures 2B,?,C)C) did not show any structural abnormalities or abnormal intracranial enhancement. An electroencephalogram with video observation was discontinued by the patient after 6?h and showed very mild diffuse polymorphic slowing with no evidence for focal cerebral dysfunction or epileptiform activity. Cerebrospinal fluid (CSF) revealed normal cell counts, protein, and glucose levels (Table 1), but later tested positive for autoantibodies against NMDA receptors. Further infectious, metabolic, and autoimmune serum and CSF studies provided no significant findings (Table 1). CT studies of the chest and stomach, along with a testicular ultrasound, did not indicate any underlying malignancy. Open in a separate window Physique 2 (A) Maculopapular rash (chest). (B) Ax FLAIR (T2) pre contrast, no abnormal transmission enhancement. (C) Post contrast AxT1 FLAIR, no abnormal contrast enhancement. 2.2. Treatment and outcomes Initial treatment attempts with Risperidone, started in the outside hospital and later switched to Chlorpromazine upon admission to our unit, resulted in modest improvements of agitation without major changes in psychotic symptoms (Table 2). Due to the reported occurrence of a generalized seizure prior to hospitalization, valproic acid was added to the treatment regimen in the first week of admission and continued throughout the hospitalization. The patient remained seizure-free for the remainder of the follow-up period. Lorazepam was added after the development of catatonic symptoms 3?weeks into the hospitalization, resulting in improvements in catatonia (Table 2). However, residual verbigeration, posturing, rigidity, negativisms, and verbal paucity persisted. These symptoms continued to fluctuate and were not usually present at the same time. The patient did not tolerate increases in Ethoxzolamide the dose of Lorazepam above 1.5?mg three times daily due to excessive sedation. CSF studies were considered early in the hospital course, but the results were delayed for a number of logistical reasons. The presence of autoantibodies against NMDAR in the CSF was confirmed 3?weeks into the hospital course, and the treatment with methylprednisolone, IVIG, and rituximab was initiated and tolerated without major side effects. This led to significant improvements in neurological symptoms, behavioral control, and business of his thought process, which enabled us to discharge the patient 5?weeks later with near-total recovery from his baseline mental functioning. Table 2 Treatment attempts and responses.
Risperidone0.5?mg twice dailyDays 1C2 of admissionSymptoms unchangedChlorpromazine50?mg twice dailyWeek 1C2Modest improvements in agitation.Sodium valproate500?mg every 12?hWeek 1C8No overt Rabbit polyclonal to IL9 seizures throughout admission.Lorazepam1C1.5?mg 2C3 occasions dailyWeek 3C8Improvements in Bush-Francis score (23 to 12) but residual catatonic symptoms (see text).Methylprednisolone1?g i.v. dailyWeek 4 for 5?daysNo further progression of neurological symptoms and reduction in agitation. Restoration of thought processIntravenous (i.v.) immunoglobulins100?g i.v. dailyWeek 4 for 2?daysRituximab1?g.