Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a complex, yet treatable autoimmune disorder characterized by a fairly abrupt onset of a constellation of symptoms attributable to diffuse brain dysfunction (Tarantino et al., 2021). Despite the potential for a severe disease course, most patients have a favorable outcome with substantial recovery (Dalmau et al., 2011; Titulaer et al., 2013). Nevertheless, there is limited literature discussing the long-term outcomes in patients with anti-NMDARE, particularly in pediatric patients. The primary objective of this study is to examine and describe behavioral, emotional, adaptive, and executive functioning outcomes in pediatric and young adult patients with this disease. This study also sought to provide information on the perceived health-related quality of life (HRQoL) of patients and their parents and investigate the impact of anti-NMDARE on parents and family functioning.

All individuals known to have been diagnosed and treated for anti-NMDARE at The Children’s Hospital of Philadelphia (CHOP) between January 1, 2005, and October 1, 2020, were contacted with both patients and their parents/guardians invited to participate. Eighteen pediatric patients between the ages of 6 and 26 and/or their parents/caregivers participated in the study. Of the 18 patients represented in the sample, 50% were white/Caucasian, and 67% were female. The mean duration of time since symptom onset was 7.1 years. Primary outcomes were measured through standardized questionnaires of emotional, behavioral, and adaptive functioning (BASC-3) and executive functioning (BRIEF2 or BRIEF-A). Secondary outcomes related to family functioning and HRQoL were measured through (PedsQL™ and PedsQL™ Family Impact Module.)

All aggregate T-scores for the BASC and BRIEF placed children with anti-NMDARE within an age-appropriate range regarding behavioral, emotional, adaptive, and executive functioning outcomes. Children with anti-NMDARE were not found to have lower HRQoL compared to their healthy same-age peers. Moreover, parents of children with anti-NMDARE did not endorse a prolonged impact of this illness on family functioning and adjustment.

This study aimed to better understand the neurobehavioral profile and the long-term outcomes of children diagnosed with anti-NMDARE, with the ultimate goal of advancing understanding of this encephalitis. Consistent with findings from several reviewed studies on long-term follow-up, the present study suggests that most children with a history of anti-NMDARE show good functional recovery over time. However, data on the neurobehavioral sequelae, quality of life, and adaptive behavior in patients diagnosed with anti-NMDARE are still sparse, especially at pediatric age. In order to understand and learn to manage the needs of patients with anti-NMDARE, particularly regarding the impact this disease can have on daily life and school performance, additional neuropsychological research involving larger samples, longitudinal studies, and increased methodological consistency is required.

Researchers are increasingly finding that the presence of neuronal surface antibodies (NSAb) may account for a larger percentage of outpatient epilepsy cases than previously thought (Elisak et al., 2018; Brenner et al., 2013). However, systematic NSAb screening is not included in standard epilepsy care (Kambadja et al., 2022). The Montreal Cognitive Assessment (MoCA; Nasreddine, 2005) is one of the most commonly used screening tools among physicians (Judge et al., 2019) across various neurological conditions, and has previously been validated in populations with autoimmune encephalitis (Hebert et al., 2018). Because patients with NSAb associated epilepsy often present with cognitive dysfunction (Greco et al., 2006), a MoCA is often administered as part of standard clinical care. The present analysis compared MoCA performance profiles in epilepsy patients with and without the presence of serum NSAbs. We explored what specific cognitive profile, as defined by the MoCA, may predict NSAb positivity.

Forty-eight epilepsy patients were enrolled through an outpatient epilepsy clinic or during non-intensive or elective hospital stays. Participants were eligible if they met one of three diagnostic categories: focal epilepsy of unknown cause (n = 33), lesional focal epilepsy (n = 5), or generalized epilepsy (n = 4). All participants signed consent, underwent a comprehensive interview, which included MoCA testing, and serum NSAb testing paralleling standard clinical practice. Mann-U Whitney tests were run to compare overall MoCA and subgroup domain performance between groups.

Six patients (13%), all with focal epilepsy of unknown cause, had positive NSAb panels (LGI1: n = 3; GAD65: n = 2; CASPR2: n = 1). There was no significant difference in overall MoCA scores between participants with focal epilepsy of unknown cause who were antibody positive versus negative, and antibody positive versus antibody negative lesional or generalized epilepsy. However, when analyzing by MoCA subgroup, we found that antibody positive patients performed significantly worse on delayed recall than antibody negative patients with focal epilepsy of unknown cause (Mdn = 1.5 vs 3), U(Nantibodynegative=27, Nantibodypositive=6) = 69.00, p = .02. There was no significant difference in other MoCA cognitive domain tests, and delayed recall scores did not significantly differ between antibody positive patients and those with lesional focal and generalized epilepsy.

These preliminary findings suggest that episodic memory impairment, as measured by delayed recall on the MoCA, may predict NSAb antibody positivity among patients with focal epilepsy of unknown cause. This may relate to specific predilection of the hippocampal regions in antibody-mediated epileptogenesis and pathology.

Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a rare and progressive neurological autoimmune disease that disproportionally affects pediatric patients (Yeshokumar et al., 2022). Patients diagnosed with ANMDARE experience a host of neurocognitive and psychiatric sequelae, but data on the rate of recovery are generally mixed (Wilkinson-Smith et al., 2022). Misdiagnosis of ANMDARE is common and may complicate recovery given the progressive nature of the syndrome (Shimoyama et al., 2016); thus, knowledge of the etiology may result in enhanced resolution of symptoms. The current study assessed the rate of functional recovery for pediatric patients diagnosed with ANMDARE and admitted to an inpatient rehabilitation program. Specifically, we hypothesized that patients with idiopathic autoimmune encephalitis (IAE) would have a protracted rate of acute recovery compared to patients diagnosed with ANMDARE.

The current study included archival data of pediatric patients (N=10) aged 3-16 years (M=12.39, SD=4.97) admitted to an inpatient rehabilitation program at a metropolitan academic medical center between 2017-2022; of these patients, 7 were characterized as having IAE, 5 were female-at-birth, and 7 were of Hispanic/Latine origin. The Functional Independence Measure for Children (WeeFIM; Msall et al., 1994) domain scores (i.e., cognition, self-care, mobility, motor) were utilized to assess acute recovery. Welch’s t-tests were analyzed separately at admission and discharge between etiological conditions (i.e., idiopathic vs. known) for each WeeFIM domain. Subsequently, change scores were calculated across the length of inpatient stay for each WeeFIM domain, and Welch’s t-tests determined statistical differences in change scores between etiological conditions.

Contrary to predictions, WeeFIM self-care domain scores were significantly higher at inpatient admission for patients with IAE (M=27.57) as compared to patients with ANMDARE (M=13.00), t(7) = 1.95, p < .05; trending differences were also found in admission scores on the WeeFIM motor domain between IAE (M=43.86) and ANMDARE (M=24.00) diagnostic groups, t(6) = 1.71, p = .07. Consistent with predictions, patients with ANMDARE generally had an appreciable acute recovery as compared to patients with IAE. Specifically, trending differences were found in change scores on the WeeFIM self-care domain between IAE (M=10.29) and ANMDARE (M=30.33) diagnostic groups, t(6) = -1.64, p = .05. Likewise, trending differences were found in change scores on the WeeFIM motor domain between IAE (M=21.43) and ANMDARE (M=47.67) diagnostic groups, t(5) = -1.82, p = .06. No significant or trending differences were observed at discharge.

Results have implications for optimizing the assessment and treatment of pediatric patients diagnosed with autoimmune encephalitis. Specifically, patients with ANMDARE may have a more severe initial presentation yet improved recovery course compared to patients characterized as idiopathic during their inpatient stay, particularly in motor and self-care functional domains; data highlights the importance of inpatient rehabilitation for patients diagnosed with ANMDARE. Current limitations include small sample sizes across diagnostic groups, likely due to the rarity of the disease. It is recommended that future research investigate the prognosis of pediatric patients diagnosed with autoimmune encephalitis longitudinally, at follow-up and across the lifespan.

Postural tachycardia syndrome is more frequently being recognised in adolescents and adults. However, its pathophysiology remains undefined. We evaluated our database for patterns in family history of clinical symptoms and associated disorders in these patients.

Patients with postural tachycardia syndrome diagnosed in our clinic between 2014 and 2018 and who were less than 19 years at diagnosis were included. The history was reviewed for family members with postural tachycardia syndrome, dizziness and/or syncope, joint hypermobility with or without hypermobile Ehlers–Danlos syndrome, and autoimmune disorders. Statistical analysis assessed the entire cohort plus differences in gender, presence or absence of joint hypermobility, and presence or absence of familial autoimmune disease.

A total of 579 patients met inclusion criteria. We found that 14.2% of patients had a family member with postural tachycardia syndrome, with male patients more likely to have an affected family member (20% versus 12.7%, p = 0.04). If the patient also had joint hypermobility, male patients were more likely to have a family member with postural tachycardia syndrome (25% versus 12.6%, p = 0.017), more than one affected family member (7.1% versus 0.74%, p = 0.001), and a family member with joint hypermobility (37.5% versus 23.7%, p = 0.032). Autoimmune disease was seen in 45.1% of family members, but more likely in female patients with concurrent hypermobility (21.1% versus 8.9%, p = 0.035).

This in-depth analysis of associated familial disorders in patients with postural tachycardia syndrome offers further insight into the pathophysiology of the disorder, and informs further screening of family members in these patients.