Parkinsonian presentation in a child with Anti‐<scp>NMDAR</scp> Encephalitis

A 14-year-old developmentally normal boy who was otherwise healthy presented with progressive stiffness involving the face, trunk, and all four limbs. His illness started 25 days back when he developed fever, projectile vomiting, and headache, which were relieved with symptomatic management. Two weeks later, the child started with emotional lability and restricted movements of limbs and trunk, progressing to generalized movement restriction in the next 5 days. There was no history of recent travel, vaccination, drug intake, or any high-risk behavior. The differential diagnosis of post-viral encephalitis sequelae, autoimmune encephalitis, acute decompensation of metabolic disorders like Hyperhomocysteinemia, and posterior fossa space-occupying lesion were considered. On examination, the child had mask facies, rigidity, waxy flexibility, and catalepsy, with resting and postural tremors in all four limbs, causing significant impairment in daily living (Video 1). He had an unstable stance and Parkinsonian gait with bradykinesia, rigid posture, short stride length, and bilateral hand tremors (left > right) (Video 2). The child also fulfilled the ICD-11 diagnostic criteria for catatonia (mutism, rigidity, catalepsy, symptoms causing significant impairment in daily functioning and not explained by another movement disorder). Given the involvement of the Substantia nigra and the characteristic features of Parkinsonism (rigidity, resting tremor, postural instability), along with the overlap of catatonic symptoms in Parkinson's disease, we chose to use the term “Parkinsonism” to describe the clinical presentation more accurately. He was unable to open his mouth. He also had an accompanying pendular nystagmus in primary gaze without any restriction of extraocular movements. There was no bladder-bowel involvement, seizures, cranial nerve involvement, or neuropathic or cerebellar signs. His initial Motor Disability Score—Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score was 141. Since there was a period of symptomatic improvement preceding the subsequent clinical deterioration, the possibility of autoimmune encephalitis was strongly considered. A lumbar puncture was done, which showed a normal CSF picture (sugar—84 mg/dL, protein—59 mg/dL; 5 WBC/hpf). His ANA, HIV serology, serum myelin oligodendrocyte glycoprotein, and CSF Japanese encephalitis virus PCR were negative. However, CSF anti-N-Methyl D-Aspartate receptor (NMDAR) IgG antibodies were positive at a titer of 1:10 by indirect immunofluorescence. The electroencephalogram showed a paucity of posterior dominant rhythm with a lack of reactivity in the awake state. MRI brain at admission showed the involvement of bilateral substantia nigra (Fig. 1). The child was started on methylprednisolone pulse therapy for 5 days, leading to the resolution of ocular nystagmus by the next day and significant improvement in tremors and rigidity by the third day. By the fifth day, he could walk with minimal support and started vocalizing with improved catalepsy and waxy flexibility. Other supportive measures such as trihexyphenidyl, levodopa-carbidopa, and selegiline were started near discharge to enhance the symptomatic improvement. He was discharged on oral steroids, which were tapered and stopped over 1 month. There was a significant improvement in the modified Rankin scale (mRS) and pediatric cerebral performance category (PCPC) scale scores from four each at admission to two each at discharge. At the 2-week follow-up, there was a significant symptomatic improvement (mRS – 0; PCPC – 1), and selegiline was stopped (Video 3). However, there were residual symptoms (UPDRS – 14). Hence, the child was planned for further immunomodulation on follow-up. Subsequently, he received two doses of rituximab at 1 and 2-month follow-ups. At 9-month follow-up, levodopa was also stopped. At 14 months follow-up, the child remained asymptomatic (off medications) with a UPDRS score of 0 (Video 4). Also, the follow-up MRI showed near resolution of T2-hyperintensity, with residual gliosis (Fig. 1). Our patient presented with isolated parkinsonism, emotional lability, and ocular nystagmus. Typical clinical presentation of anti-NMDAR encephalitis in children includes a combination of seizures, behavioral abnormalities, and movement disorder.1 The basis of Parkinsonian presentation in anti-NMDAR encephalitis still remains unknown, but a complex interplay of dopamine and NMDAR in the basal ganglia is speculated to be the cause.2 Presentations can vary as these patients may be falsely labeled as having somatoform disorder.3 While the index case was ultimately diagnosed as autoimmune encephalitis, in the absence of this diagnosis, the preferred approach would have been to use NMDA antagonists in conjunction with levodopa rather than immunomodulation.2, 4 A distinctive feature of this case is the resolution of catatonia with immunotherapy, without the need for benzodiazepines (traditional treatment of choice for catatonia).5 (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. S.A.: 1A, 1C, 3A, 3B. K.K.: 1A, 1B, 3B. A.K.: 1C, 3B. S.T.: 1C, 3B. L.S.: 1A, 1C, 3B. Ethical Compliance Statement: The study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences, Jodhpur. A written informed patient consent was obtained. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosure for the Preceding 12 Months: The authors declare that there are no additional disclosures to report. The data that support the findings of this study are available on request from the corresponding author. The data is not publicly available due to privacy or ethical restrictions.