Clinical-Serological Characterization and Treatment Outcome of a Large Cohort of Italian Children with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection and Pediatric Acute Neuropsychiatric Syndrome

摘要

Objective: Pediatric autoimmune neuropsychiatric disorder associated with Streptococcus pyogenes infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) are emerging immune-mediated encephalopathies characterized by sudden onset of seemingly inexplicable complex neuropsychiatric symptoms, including obsessions, compulsions, and heterogeneous tics, which occur in children. Main goal of this study was to report our experience in a large cohort of Italian children affected by either PANDAS or PANS and treated long term with an antibiotic regimen similar to that used for acute rheumatic fever. Patients and Methods: The clinical charts of a cohort of 371 consecutive Italian children, 345 with PANDAS (93.0%) and 26 with PANS (7.0%), were retrospectively evaluated. Antistreptococcal, antinuclear antibodies, and serologic evaluation for a group of common autoantibodies and microbial agents were also assessed. A strict differential diagnosis with other autoimmune diseases displaying neuropsychiatric manifestations was performed. Results: Antistreptolysin O and anti-DNase B antibody titers were tested and were positive in all PANDAS subjects, but negative in PANS. Anti-Mycoplasma pneumoniae antibodies and anti-Epstein-Barr virus Nuclear Antigen antibodies were found positive in 11 (42.3%) and 5 (19.2%) patients with PANS, respectively. Among PANDAS cases, a clear streptococcal infection was clinically evident at the onset of neurological symptoms in only 74 patients (21.4%), whereas the relationship with Streptococcus pyogenes was confirmed by serologic tests in the other 271 (78.6%). All patients fulfilling the diagnostic criteria for PANDAS (n = 345) received amoxicillin/clavulanic acid for 10-21 days at diagnosis, while those who were diagnosed with PANS (n = 26) received treatment according to the causative agent. Thereafter, all PANDAS/PANS patients received prophylaxis with benzathine benzylpenicillin for an overall period of at least 5 years to prevent subsequent potential streptococcal infections. To date, 75.0% of PANDAS patients (n = 258) have shown an improvement of neurologic symptoms, mainly observed within 3-5 months of treatment for PANDAS cases, while 88.4% of PANS patients (n = 23) have improved after 6-12 months. Infection-related relapses of neurologic manifestations were observed in both PANDAS and PANS patients (n = 167 out of 371; 45% of the total cohort) in the long term. Conclusions: Our study has confirmed the usefulness of the preliminary diagnostic criteria for PANDAS and PANS, revealing also the importance of early diagnosis to reduce the risk of evolution toward disabling chronic neurologic sequelae. Long-term antibiotic prophylaxis has resulted in a substantial benefit to reduce neurological symptoms for the majority of PANDAS and PANS patients over a 7-year period.