Disease Course and Response to Immunotherapy in Children With Childhood Disintegrative Disorder: A Retrospective Case Series.

Childhood disintegrative disorder is a poorly understood neurobehavioral disorder of early childhood characterized by acute to subacute profound regression in previously developed language, social behavior, and adaptive functions. The etiology of childhood disintegrative disorder remains unknown and treatment is focused on symptomatic management. Interest in neuroinflammatory mechanisms has grown with the increased recognition of autoimmune brain diseases and similarities between the presenting symptoms of childhood disintegrative disorder and pediatric autoimmune encephalitis. Importantly, a diagnosis of pediatric autoimmune encephalitis requires evidence of inflammation on paraclinical testing, which is absent in childhood disintegrative disorder. Here we report 5 children with childhood disintegrative disorder who were initially diagnosed with possible autoimmune encephalitis and treated with immunotherapy. Two children had provocative improvements, whereas 3 did not change significantly on immunotherapy. Additionally, a sixth patient with childhood disintegrative disorder evaluated in our Autoimmune Brain Disease Clinic showed spontaneous improvement and is included to highlight the variable natural history of childhood disintegrative disorder that may mimic treatment responsiveness.

Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder.

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9-12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, P = 0.001), abnormal MRI (χ2 = 7.78, P = 0.005), and abnormal LP (χ2 = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.

Retrospective Comparison of Patients Evaluated for Pediatric Autoimmune Encephalitis with Typical and Atypical Premorbid Neuropsychiatric Development.

PURPOSE: Patients with neurodevelopmental disorders (NDD) (i.e. autism, developmental delay, early-onset psychiatric or seizure disorders) increasingly seek evaluation of new or exacerbated symptoms concerning for autoimmune encephalitis (AE). Clinical AE evaluation can be challenging in NDD patients with symptom overlap between anti-neuronal autoimmunity and baseline atypical neurodevelopment. This study sought to explore differences in AE features by neurodevelopmental status. METHODS: This retrospective chart review included 67 children with typical development (TD) or NDD evaluated for AE at the authors' institution. AE diagnosis included seronegative AE or seropositive AE with anti-NMDAR or anti-GAD antibodies. Reported AE clinical domains, symptom onset acuity, and treatment response were compared between three groups: (1) TD children with AE (TD-AE, N = 24); (2) NDD children with AE (NDD-AE, N = 21); and (3) NDD children with a non-AE diagnosis following appropriate workup (NDD-nonAE, N = 22). RESULTS: Children with AE had a greater number of reported clinical domains than non-AE children with NDD (p < 0.0001) regardless of baseline developmental status. There were no observed differences in reported domains between TD-AE and NDD-AE groups. Onset acuity differed across the three groups (p = 0.04). No treatment response differences were observed between groups. CONCLUSION: NDD children with AE had a comparable number of reported clinical domains relative to TD children and a similar treatment response. NDD patients with AE had a greater number of reported clinical domains than their NDD peers without an AE diagnosis. These findings suggest that AE is a multi-domain process in both TD and NDD children.

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder.

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean off therapy after 9-12 months of treatment. Baseline, on therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, p = 0.001), abnormal MRI (χ2 = 7.78, p = 0.005), and abnormal LP (χ2 = 5.45, p = 0.02), and a personal history of autoimmunity (OR: 6.11, p < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.

Pediatric rheumatologists' perspectives on diagnosis, treatment, and outcomes of Sjögren disease in children and adolescents.

BACKGROUND: Sjögren disease in children and adolescents (pedSD) presents differently than adult disease. Diagnosis and classification are controversial, optimal treatment is unknown and outcomes are poorly understood. Here, we describe the current perspectives of pediatric rheumatologists on diagnosis, treatment, and outcomes of pedSD. METHODS: A voluntary, 17-question survey was distributed to providers in the Childhood Arthritis and Rheumatology Research Alliance and/or the American College of Rheumatology Childhood Sjögren's Study Group at the 2020 Convergence Virtual Conference. Findings are reported using descriptive statistics and chi-square testing. RESULTS: Of 465 eligible providers, 157 (34%) responded with 135 (29%) completing the survey. The majority (85%) saw five or fewer patients with pedSD in the past year. Parotitis, dry eye and/or dry mouth, and constitutional symptoms were among the most specific and common clinical features. Most providers (77%) used clinical judgment guided by adult criteria for diagnosis. The vast majority (86-99%) of survey participants indicated routine use of serologic testing, while salivary gland ultrasound, minor salivary gland biopsy and other diagnostic tests were less often used. The most commonly prescribed systemic immunomodulators were hydroxychloroquine, corticosteroids, methotrexate, rituximab, and mycophenolate. Seven providers reported malignancy in a patient with pedSD, including one death. CONCLUSIONS: Pediatric rheumatologists diagnose and treat pedSD; however, most only see a few patients per year and rely on clinical judgment and laboratory testing for diagnosis. Treatment frequently includes systemic immunomodulators and malignancies are reported. More studies are needed to better understand natural history, risk factors, and the impact of interventions on outcomes.

Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus.

Objective: To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome. Background: There are no consensus criteria for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area. Methods: The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome. Results: During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on "other" studies) as were diagnostic criteria (96% agreement). Conclusions: The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.

Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder.

BACKGROUND: Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention. METHODS: A retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms. RESULTS: Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04-1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64-37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88-9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective. CONCLUSIONS: This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists. METHODS: Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comparison, and Outcomes (PICO) question format. Systematic literature reviews were conducted for each PICO question. We used the Grading of Recommendations, Assessment, Development and Evaluation method to assess the quality of evidence and formulate recommendations. Each recommendation required consensus from at least 70% of the Voting Panel. RESULTS: We present 1 good practice statement, 11 recommendations, and 1 ungraded position statement to guide the management of KD and clinical scenarios of suspected KD. These recommendations for KD are focused on situations in which input from rheumatologists may be requested by other managing specialists, such as in cases of treatment-refractory, severe, or complicated KD. The good practice statement affirms that all patients with KD should receive initial treatment with intravenous immunoglobulin (IVIG). In addition, we developed 7 strong and 4 conditional recommendations for the management of KD or suspected KD. Strong recommendations include prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in the setting of unexplained macrophage activation syndrome or shock. Conditional recommendations include use of IVIG with other adjuvant agents for patients with KD and high-risk features of IVIG resistance and/or coronary artery aneurysms. These recommendations endorse minimizing risk to the patient by using established therapy promptly at disease onset and identifying situations in which adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and use of echocardiography in patients with suspected or confirmed KD.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists. METHODS: Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comparison, and Outcomes (PICO) question format. Systematic literature reviews were conducted for each PICO question. We used the Grading of Recommendations, Assessment, Development and Evaluation method to assess the quality of evidence and formulate recommendations. Each recommendation required consensus from at least 70% of the Voting Panel. RESULTS: We present 1 good practice statement, 11 recommendations, and 1 ungraded position statement to guide the management of KD and clinical scenarios of suspected KD. These recommendations for KD are focused on situations in which input from rheumatologists may be requested by other managing specialists, such as in cases of treatment-refractory, severe, or complicated KD. The good practice statement affirms that all patients with KD should receive initial treatment with intravenous immunoglobulin (IVIG). In addition, we developed 7 strong and 4 conditional recommendations for the management of KD or suspected KD. Strong recommendations include prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in the setting of unexplained macrophage activation syndrome or shock. Conditional recommendations include use of IVIG with other adjuvant agents for patients with KD and high-risk features of IVIG resistance and/or coronary artery aneurysms. These recommendations endorse minimizing risk to the patient by using established therapy promptly at disease onset and identifying situations in which adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and use of echocardiography in patients with suspected or confirmed KD.

Pediatric GAD-65 Autoimmune Encephalitis: Assessing Clinical Characteristics and Response to Therapy With a Novel Assessment Scale.

BACKGROUND: Glutamic acid decarboxylase (GAD) encephalitis is a neuroinflammatory disease characterized by a broad range of symptoms including cognitive deficits, behavioral changes, and seizures. Children with this disorder have heterogeneous presentations, and little is known about symptom progression over time and response to immunotherapy. METHODS: This study reports 10 pediatric GAD encephalitis cases and symptoms found at presentation and follow-up. In addition, symptom severity was reported utilizing a novel scale evaluating functional outcomes across the domains affected by autoimmune encephalitis including cognition, language, seizures, psychiatric symptoms, sleep, and movement. Retrospective chart review was conducted for 10 patients aged <18 years, diagnosed with GAD encephalitis, and followed for one year or more. Chart review included clinical, imaging, and laboratory findings at time of diagnosis and at six- and 12-month follow-ups. RESULTS: At presentation, cognitive deficits were found in all patients, seizures in six of 10, and language decline in seven of 10. Psychiatric symptoms were prominent for all but one patient with three of nine patients presenting with psychosis. Fatigue, sleep disruption, and movement disorders were less prominent symptoms, occurring in approximately half of the cohort. Cognition and fatigue improved significantly over time when compared with symptom severity, whereas seizures, psychiatric symptoms, and sleep did not. Language and sleep showed improvement only in early stages. Analysis of seizure frequency and type noted variability mirroring trends noted in adult studies of GAD encephalitis. CONCLUSIONS: This study demonstrated the variability of symptom profiles of pediatric GAD encephalitis and benefits of symptom severity scales. Symptom profiles and progression vary in this population.

The Role of Pediatric Rheumatologists in Autoimmune Brain Disease.

The spectrum of autoimmune and inflammatory brain diseases continues to evolve with medical advances facilitating both the detection of inflammation of the central nervous system and the discovery of novel disease mechanisms. The clinical overlap of these disorders with primary rheumatic diseases and the efficacy of immunotherapy have led to strong partnerships between pediatric rheumatologists, neurologists, psychiatrists, and other providers in the care of children with these conditions. Early diagnosis and initiation of targeted therapy improve clinical outcomes, highlighting the importance of interdisciplinary collaborative care.

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis.

Importance: Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear. Objective: To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. Data Sources: Systematic search in PubMed from inception to January 1, 2019. Study Selection: Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data. Data Extraction and Synthesis: Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models. Main Outcomes and Measures: The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset). Results: Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05). Conclusions and Relevance: Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

OBJECTIVE: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE). METHODS: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement). RESULTS: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided. CONCLUSION: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients.

Psychiatric Phenotypes of Pediatric Patients With Seropositive Autoimmune Encephalitis.

OBJECTIVES: Patients with autoimmune encephalitis (AE) often present with symptoms that are broadly characterized as psychiatric or behavioral, yet little attention is given to the precise symptomatology observed. We sought to more fully define the psychiatric symptoms observed in patients with anti-N-methyl-D-aspartate receptor (NMDAR), anti-glutamic-acid-decarboxylase 65 (GAD65), and anti-voltage-gated-potassium-channel complex (VGKC) antibody-mediated AE using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition nomenclature. METHODS: We present a case series (n = 25) using a retrospective chart review of 225 patients evaluated for AE in a tertiary care academic medical center between 2014 and 2018. The included patients were ≤18 years old with anti-NMDAR AE (n = 13), anti-GAD65 AE (n = 7), or anti-VGKC AE (n = 5). The frequency of neuropsychiatric symptoms present at the onset of illness and time to diagnosis were compared across groups. RESULTS: Psychiatric symptoms were seen in 92% of patients in our cohort. Depressive features (72%), personality change (64%), psychosis (48%), and catatonia (32%) were the most common psychiatric symptoms exhibited. On average, patients experienced impairment in ≥4 of 7 symptom domains. No patients had isolated psychiatric symptoms. The average times to diagnosis were 1.7, 15.5, and 12.4 months for anti-NMDAR AE, anti-GAD65 AE, and anti-VGKC AE, respectively (P < .001). CONCLUSIONS: The psychiatric phenotype of AE in children is highly heterogenous. Involving psychiatry consultation services can be helpful in differentiating features of psychosis and catatonia, which may otherwise be misidentified. Patients presenting with psychiatric symptoms along with impairments in other domains should prompt a workup for AE, including testing for all known antineuronal antibodies.

Case Report: Improvement Following Immunotherapy in an Individual With Seronegative Down Syndrome Disintegrative Disorder.

Down syndrome disintegrative disorder (DSDD) is a condition of unknown etiology characterized by acute cognitive decline, catatonia, insomnia, and autistic features in individuals with Down syndrome. A prior report of four patients with DSDD suggested a potential autoimmune etiology based on the presence of autoantibodies and on successful treatment with immunotherapy that included intravenous immunoglobulin (IVIG). Herein, we present the case of an 8-year old girl who developed acute cognitive decline to a dementia-like state, insomnia, catatonia, and autistic features. In contrast to the four patients with DSDD above, she had no evidence of autoimmunity and presented at a younger age. Given the gravity of her acute deterioration and the exclusion of other etiologies, she was treated with immunotherapy presumptively. She responded with near complete resolution of symptoms, but demonstrated a pattern of mild decline as she approached each monthly dosing of IVIG and steroids, reversed by treatment. Mycophenolate mofetil (MMF) was therefore added, with stability throughout the month and the ability to taper off IVIG. After stopping IVIG, she had a mild recurrence of symptoms that again resolved with repeat IVIG followed by tapering off. Outcome was assessed at 2.5 years after presentation, at which time she was back to her premorbid condition, except for persistent tics off immunotherapy. This case supports the contention that patients with a rapid onset of severe symptoms consistent with DSDD, who have a thorough evaluation with the exclusion of other etiologies, may warrant a trial of immunotherapy with steroids, IVIG and/or other agents like MMF even in the absence of evidence of autoimmunity on standard evaluation.

Idiopathic Pulmonary Hemosiderosis as a Mimic of Pulmonary Vasculitis: A Case Report and Review of the Literature.

PURPOSE OF REVIEW: Idiopathic pulmonary hemosiderosis (IPH) is one of the rarest and least understood causes of pulmonary hemorrhage in children. Illustrated by a complex case presentation, we discuss the clinical manifestations, diagnosis, pathology, proposed etiologies, and treatment of this rare disease. We also compare IPH with anti-glomerular basement membrane antibody syndrome (anti-GBM disease), another rare causes of pediatric pulmonary hemorrhage. RECENT FINDINGS: Recent retrospective studies regarding IPH along with advanced immunotherapy have led to an improved understanding of how to best treat this condition, potential associations, and improved prognosis. Pathogenesis remains unknown, but several reports have suggested involvement of the alveolar capillary basement membrane. IPH is a poorly understood disease of unknown etiology that is a diagnosis of exclusion. Our patient was diagnosed with IPH after an exhaustive workup, including lung biopsy, into other immune-mediated causes of disease. While the pathogenesis of this rare disease remains elusive, our patient's immunofluorescent staining along the alveolar basement membrane without evidence of circulating antibody to type IV collagen raises the question of an immune-mediated pathogenesis of the disease with involvement of the alveolar basement membrane.

Evaluation of Diagnostic Criteria for Hashimoto Encephalopathy Among Children and Adolescents.

BACKGROUND: The recently proposed adult diagnostic criteria for the Hashimoto encephalopathy (HE) include a requirement of subclinical or mild thyroid disease. However, most reports indicate that most children treated for HE do not have evidence of thyroid disease. We aim to evaluate the impact of applying the current adult diagnostic criteria to pediatric patients. METHODS: Pediatric patients with HE were evaluated at time of symptom onset and follow-up at least 1 year after initiation of immunomodulatory treatment for degree of impairment within the neuropsychiatric domains of cognition, language, psychiatric disturbance, seizure, movement disorder, sleep disruption, and overall functionality. We compared the response to treatment among patients stratified by the presence or absence of subclinical or mild thyroid disease using the Modified Rankin Scale, the Liverpool Outcome Score, and a novel multidomain scale designed for the population with pediatric autoimmune brain disorders. RESULTS: Of 17 pediatric patients treated for HE, 6 met full adult diagnostic criteria, whereas 11 patients did not meet criteria solely owing to the absence of thyroid disease. Using our novel scale, the 6 patients meeting full criteria had statistically significant improvement from time of onset of disease to follow-up in the domain of cognition. The 11 patients who did not meet full criteria based on their absence of thyroid disease exhibited statistically significant improvement from time of onset of disease to follow-up in the domains of cognition, language, psychiatric disturbance, movement, and sleep. CONCLUSIONS: Rigidly applying the current diagnostic criteria to pediatric patients with suspected HE may result in the failure to treat potential responders. We propose a set of diagnostic criteria for HE in children, which does not require thyroid disease but include abrupt onset cognitive regression with deficits in one or more other neuropsychiatric domains in the setting of antithyroid antibodies.