PANDAS was first described in 1998 by Swedo and colleagues, who proposed diagnostic criteria centered on the presence of obsessive-compulsive disorder or a tic disorder, symptom onset between three years of age and puberty, a dramatic onset or exacerbation of symptoms, a temporal relationship with group A streptococcal infection confirmed by culture or serological evidence, and neurological abnormalities similar to those seen in Sydenham chorea. The condition is thought to be triggered by Streptococcus pyogenes, typically in the form of acute pharyngitis. A broader construct, pediatric acute-onset neuropsychiatric syndrome (PANS), was later introduced to capture similar acute presentations triggered by non-streptococcal infections or noninfectious factors, and it is not restricted by age or etiology. PANDAS is therefore best conceptualized as a streptococcus-associated subgroup within the wider PANS spectrum.

Whether PANDAS can first present after puberty has remained uncertain. Because the PANS diagnosis is not limited by age or by streptococcal infection, post-pubertal patients with evidence of a streptococcal-triggered autoimmune neuropsychiatric syndrome are often classified as having PANS rather than PANDAS. Although this distinction rarely alters immediate management, the authors argue it has important implications for understanding disease pathogenesis, epidemiology, biomarker development, and genetic susceptibility. Their series describes three individuals who developed neuropsychiatric symptoms following pharyngeal illness, thereby testing the current age-based diagnostic framework.

The first case involved an 18-year-old female with no prior psychiatric or medical history. At age 16, while living abroad, she developed an upper respiratory tract infection characterized by pharyngitis and low-grade fever requiring one day of hospitalization. No throat culture was obtained. Approximately one month later, she experienced an abrupt onset of disabling motor and vocal tics, obsessive-compulsive behaviors, and urinary incontinence. Motor tics included repetitive abdominal contractions, sniffing, and facial grimacing that persisted during sleep. Her academic performance declined markedly, eventually preventing school attendance. Psychiatric evaluation abroad fulfilled DSM-5 criteria for obsessive-compulsive disorder, with compulsions including repetitive switching of lights, repeated hand movements, and stepping rituals at doorways.

Her extensive workup abroad for infectious, metabolic, and autoimmune etiologies was unremarkable. Autoimmune encephalitis antibodies in both serum and cerebrospinal fluid were negative, including anti-NMDAR, anti-GAD, anti-AMPAR 1/2, anti-GABABR, anti-CASPR2, anti-LGI1, and anti-gangliosides GM1-4. Paraneoplastic panels were negative, and imaging showed no evidence of malignancy. Multiple antibiotic courses and psychiatric medications, including clonazepam and sertraline, were ineffective. At the reporting institution, serial antistreptolysin O (ASO) titers during symptom exacerbation increased from 102 IU/mL to 443 IU/mL, with the normal reference below 200 IU/mL. The anti-DNase B titer was elevated at 502 IU/mL, erythrocyte sedimentation rate was markedly elevated at 102 mm/h, and brain MRI demonstrated preserved basal ganglia structures with a small nonspecific right frontal white matter FLAIR hyperintensity. Neurological examination revealed symmetric cogwheel rigidity and bradykinesia, and her Yale-Brown Obsessive Compulsive Scale score of 25 was consistent with severe obsessive-compulsive symptomatology. At follow-up visits she became largely mute with features suggestive of catatonia.

Her treatment course proved difficult. Sequential empiric antimicrobial therapy with amoxicillin, doxycycline, and azithromycin, along with corticosteroids and multiple psychotropic medications, produced no meaningful improvement. Escalation to intravenous immunoglobulin (IVIG), initially every four weeks and ultimately weekly across 12 sessions, produced consistent but short-lived improvement lasting approximately five to seven days per session. Plasmapheresis followed: six sessions resulted in marked temporary improvement, including restored mobility, social engagement, and normalized urinary continence lasting one month, while a second six-session course produced only minimal and transient benefit. Her 21-year-old brother, the second case, developed urinary incontinence, vocal tics, severe restrictive eating driven by a fixed belief that his food was poisoned, persecutory delusions, and approximately 10 kg of weight loss one month after a self-limited febrile throat infection at age 20. His ASO titer was 190 IU/mL, within the stated reference range, possibly due to late presentation, and his brain MRI was normal. Four sessions of IVIG resulted in marked improvement across all symptom domains, sustained for approximately six months, although he experienced an acute relapse before enrolling in university and declined further immunotherapy.

The third case involved a previously healthy 16-year-old male who developed a sudden onset of repetitive, rapid, involuntary head movements three days after acute sore throat and fever. Within days of being prescribed quetiapine and escitalopram at an outside institution, he developed auditory hallucinations, persecutory delusions, and abnormal behavior, deteriorating over three months into mutism and near-complete dependence for daily care. Clinically diagnosed with PANDAS at the reporting hospital, he did not fulfill current PANS criteria because neither abrupt-onset obsessive-compulsive disorder nor avoidant/restrictive food intake disorder was documented. Quetiapine and escitalopram were discontinued, and amoxicillin 500 mg orally every eight hours was started. Within seven days, he showed dramatic clinical improvement, becoming alert and communicative with marked reduction of his abnormal movements. A 14-day amoxicillin course was followed by prophylactic benzathine penicillin G every three weeks, and his head movements resolved completely after two years, with sustained remission and only minimal residual motor signs at three-year follow-up.

The underlying pathophysiology of PANDAS is hypothesized to involve a type II hypersensitivity reaction triggered by molecular mimicry between streptococcal antigens and host neuronal tissue, particularly within the basal ganglia. Antineuronal antibodies elicited by group A streptococcal infection may cross-react with host structures, resulting in neuroinflammation and neuropsychiatric manifestations through a mechanism analogous to acute rheumatic fever. However, this hypothesis remains controversial, as attempts to consistently identify specific pathogenic antibodies in patients with PANDAS have produced inconclusive and nonspecific findings. Accurate diagnosis requires careful exclusion of overlapping conditions, including Sydenham chorea, Tourette syndrome, primary obsessive-compulsive disorder, autoimmune encephalitis, and neuropsychiatric lupus. PANDAS is not recognized as a distinct entity in the WHO’s International Classification of Diseases, 11th Revision, though it may conceptually fall within autoimmune disorders affecting the central nervous system.

The true prevalence of PANDAS remains uncertain. Early estimates suggested that up to 10 percent of children diagnosed with obsessive-compulsive disorder or tic disorders might meet criteria, while more recent data from the PANS Research Consortium estimate a prevalence of approximately 1 to 2 percent in the pediatric population. Data from the Middle East are particularly sparse. The strength of evidence for a streptococcal trigger differed among the cases: the first patient had rising ASO and elevated anti-DNase B titers during symptom exacerbation, the second had a history of febrile throat illness but negative cultures and a reference-range ASO titer, and the third had a close temporal association with sore throat and fever but no serological testing. Published post-pubertal cases remain limited and have typically involved individuals with pre-existing psychiatric disorders, whereas the patients in this series had no prior psychiatric history, strengthening the clinical suspicion for a post-streptococcal autoimmune neuropsychiatric process.

The authors acknowledge that all three patients could also be classified within the broader PANS spectrum, and that current therapeutic recommendations for PANS and PANDAS are largely similar. Nevertheless, they argue that distinguishing a probable streptococcal-triggered subgroup remains clinically and scientifically relevant, potentially facilitating future studies of pathogen-specific immune mechanisms, genetic susceptibility, biomarkers, prognosis, and preventive strategies including antimicrobial prophylaxis. Familial clustering further raises the possibility of underlying genetic or immunologic susceptibility: the two siblings developed the disorder at different ages, one in early adolescence and the other at 20 years, a familial pattern not previously reported. This observation parallels the well-established genetic predisposition in acute rheumatic fever, in which monozygotic twins have a six-fold increased risk when a co-twin is affected, with heritability estimates approaching 60 percent. Previous studies have also demonstrated increased rates of autoimmune diseases, tic disorders, and obsessive-compulsive symptoms among first-degree relatives of affected individuals.

Treatment responses in the series were variable and often transient, suggesting that persistent immune activation, incomplete pathogen clearance, or host-specific immunologic factors may influence outcomes. The efficacy of immunomodulatory therapies remains controversial: Perlmutter and colleagues reported significant improvement with IVIG and plasmapheresis compared with placebo in children with PANDAS, whereas Nicolson and colleagues found no benefit of plasmapheresis in refractory obsessive-compulsive disorder or Tourette syndrome without evidence of streptococcal infection. More recently, Melamed and colleagues demonstrated sustained symptom improvement with repeated IVIG infusions in patients with PANS, while Williams and colleagues found no significant benefit of IVIG over placebo in a randomized controlled trial, although participants who later received open-label IVIG demonstrated a mean 49 percent reduction in obsessive-compulsive symptoms. Current consensus recommendations from the PANS Research Consortium emphasize coordinated medical, psychiatric, behavioral, and psychosocial management addressing both the underlying inflammatory process and the associated neuropsychiatric manifestations.

Several limitations temper the findings. Retrospective symptom reporting introduces potential recall bias, none of the patients had microbiological confirmation of group A streptococcal infection at symptom onset, antibody testing was incomplete in one case, and concurrent use of antibiotics, immunomodulatory therapies, and psychotropic medications complicates interpretation of treatment response. These constraints highlight the need for prospective studies incorporating standardized biomarkers and longitudinal assessment. Still, the clinical pattern observed aligns with a post-infectious neuropsychiatric syndrome temporally related to pharyngeal illness. The authors conclude that clinicians should consider post-infectious autoimmune neuropsychiatric syndromes, including PANDAS-like presentations, in older adolescents and young adults who develop abrupt-onset obsessive-compulsive disorder, tics, or acute behavioral changes following pharyngeal illness. Although many such patients may currently be classified as having PANS, recognition of a possible streptococcal-triggered subgroup remains important for advancing understanding of disease mechanisms, refining future diagnostic criteria, and identifying pathogen-specific biomarkers.

Subject of Research: Post-pubertal PANDAS-like neuropsychiatric presentations in three patients including two siblings

Article Title: Possible Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS) Presenting in Late Adolescence and Early Adulthood: A Case Series

Article References: Madani, T. A., Alsallum, F. S., Abudaowd, O. H., & Madani, S. T. (2026). Possible Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections ( PANDAS ) Presenting in Late Adolescence and Early Adulthood: A Case Series. Clinical Case Reports, 14(11), Article e73768. https://doi.org/10.1002/ccr3.73768

Image Credits: AI Generated

DOI: 10.1002/ccr3.73768

Keywords: PANDAS, PANS, streptococcal infection, autoimmune neuropsychiatry, obsessive-compulsive disorder, tics, case series, adolescent health, Possible, Pediatric, Autoimmune, Neuropsychiatric