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  • Updated 12.22.2022
  • Released 11.15.1999
  • Expires For CME 12.22.2025




Pediatric autoimmune neuropsychiatric disease associated with streptococcal infections (PANDAS) is a syndrome characterized by acute onset and relapsing-remitting course of obsessive-compulsive symptoms, tics, and other behavioral symptoms in children with streptococcal infections. Pediatric acute-onset neuropsychiatric syndrome (PANS), pediatric infection triggered autoimmune neuropsychiatric disorders (PITANDs) and pediatric acute-onset neuropsychiatric syndrome (PANS) have also been described as PANDAS-related disorders. The etiology is thought to involve immune-mediated auto aggressive attack on basal ganglia antigens following recent streptococcal infection, as supported by clinical studies and animal model developments. Diagnosis is based on clinical criteria and exclusion of known infectious, metabolic, or structural causes. Immunomodulatory therapy, including plasmapheresis and IVIGIVIg, remains highly investigational.

Key points

• The clinical definition of PANDAS is currently under revision.

• PANDAS temporal relationship to group A beta hemolytic streptococcal infection (GABHS) is still the object of debate.

• Novel animal models suggest a possible involvement of antibody-mediated pathomechanisms.

• There are no specific laboratory or imaging tests with which to diagnose the disorder.

Historical note and terminology

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) refers to a subgroup of pediatric patients with tic or obsessive-compulsive disorders temporally associated with streptococcal infections (130). It was first described in a group of 50 patients with an acute, sudden onset of obsessive compulsive disorder (OCD) and/or tics, and behavioral changes in the context of a previous streptococcal infection. However, the concept of PANDAS originally stemmed from 19th century published observations of acute onset neuropsychiatric symptoms, which included emotionality, irritability, deterioration in handwriting and attention, and bizarre behaviors (79). Osler reported obsessive-compulsive behaviors in patients with Sydenham chorea. In his accounts, parents reported an abrupt change in character of their children, and some cases suggested even the possibility of acute-onset psychosis (89). Half a century later, these findings were confirmed by larger case series (17; 26). In 1989, Kiessling described 8 patients with tic disorder who had evidence of recent infection with group A beta-hemolytic Streptococcus (GABHS) at the time of their initial presentation or symptom exacerbation (43). That same year, researchers at the National Institute of Mental Health reported on patients with Sydenham chorea who often exhibited obsessive-compulsive symptoms (119) with a fluctuating clinical course (120). These observations have led to the speculation that at least some cases of tic and obsessive-compulsive disorders may have an etiological relationship to GABHS infection. PANDAS may share similar pathogenesis with Sydenham chorea, the scientifically established prototype of GABHS-mediated autoimmune neuropsychiatric disease and a complication of rheumatic fever.

Longitudinal observations identified cases in which initial onset or exacerbation of tic or obsessive-compulsive symptoms showed temporal correlation with GABHS infections. The first series of such cases appeared in 1995 (01). Initially referred to as Pediatric, Infection-Trigerred, Autoimmune Neuropsychiatric Disorders (PITANDs), this entity was eventually renamed PANDAS by Swedo and colleagues in 1998 and has since gained wide recognition under this acronym. Several reviews of the subject are available (113; 110; 124; 33; 46; 80; 93; 99; 79).

Previous cases that resembled PANDAS were reported sporadically in the literature. Historically, anecdotal reports have linked an acute onset of tics to chronic sinusitis with bouts of acute sinusitis, including streptococcal etiology (98). A case report from Japan described an 11-year-old boy who was noted to have developed Tourette syndrome approximately ten days after a febrile illness associated with elevated antistreptolysin O antibody titers (48). In an Italian case series of pediatric patients, exposure to streptococcal antigens was associated with an increased incidence of tics (12). Community outbreaks of GABHS infections have been reportedly associated with a 10-fold increase in the number of pediatric patients presenting with tics (44).

Unfortunately, a reliable diagnostic test for PANDAS has never been established. This diagnosis has always relied on longitudinal observation of clinical course supplemented by laboratory tests documenting streptococcal infection. The diagnostic criteria for PANDAS proposed by Swedo and colleagues are shown in Table 1 (116):

Table 1. Proposed Diagnostic Criteria for PANDAS

(1) Presence of a tic disorder and/or obsessive-compulsive disorder

(2) Prepubertal age (between 3 and the beginning of puberty) at onset

(3) Abrupt symptom onset or episodic course of symptom severity with dramatic symptom exacerbations. Exacerbations may also occur months to years after the onset. Remissions may not be complete.

(4) Temporal association between symptom exacerbations and streptococcal infections

(5) Presence of neurologic abnormalities (eg, choreiform movements, tics, or motor hyperactivity) during periods of symptom exacerbation

The first case series of 50 patients identified using these diagnostic criteria was published in 1998 (116). In this report, neuropsychiatric symptoms started about 7 to 14 days after the putatively inciting infection. Several other characteristic features beyond core criteria were described in PANDAS patients. The average age of onset of tics (6.3 years) and obsessive-compulsive symptoms (7.4 years) appeared to be younger than in non-PANDAS childhood-onset tic disorder and obsessive-compulsive disorder. Patients exhibited comorbid symptoms such as emotional lability (66%), personality changes (54%), bedtime fears or rituals (50%), and separation anxiety (46%). These symptoms also appeared to be episodic and temporally related to GABHS infections. Seventy-seven percent of patients had some evidence of exacerbation associated with positive throat culture or scarlet fever and history of upper respiratory infection symptoms, associated with previous GABHS exposure. In a larger, longitudinal series that correlated behavior and movement abnormalities with GABHS infections in 693 elementary school-age children (ages 3 to 12 years), it was observed that, over 8 months, GABHS infection between 0 and 3 months prior is correlated with the onset of behavioral changes including ADHD symptoms (RR 1.71; p< 0.0001), particularly in the fall season (83). In 64 children with repeat GABHS infections, there was an observed increase in the incidence of behavioral abnormalities and choreiform movements (p=0.005), providing further evidence for a link between PANDAS and GABHS infection. Data from a small case series have also suggested that the severity and persistence of PANDAS symptoms may relate to the number of prior GABHS infections (77). Other abnormal behaviors have been anecdotally reported, occurring shortly after a GABHS infection (ie, dystonia, stereotypies, opsoclonus, myoclonus, paroxysmal choreoathetosis, catatonia, body dysmorphic disorder), but their relationship to PANDAS is unclear (79). A metaanalysis did not demonstrate any significant evidence for higher rates of temporally associated GABHS infection and neuropsychiatric symptom exacerbation for children with PANDAS (87).

Family history for obsessive-compulsive symptoms has been reported in youth fulfilling PANDAS criteria (81), suggesting a genetic predisposition to these symptoms similar to that observed in young patients with non-PANDAS obsessive-compulsive disorder. At the same time, 25% of mothers of youth with PANDAS had autoimmune disease, compared to 13.4% of mothers of children with non-PANDAS obsessive-compulsive disorder/tics (81b). Anecdotal evidence of a strong family history of tics and accompanying neuropsychiatric features characteristic of PANDAS, occurring in temporal association with GABHS infections, has also been reported (126). On the other hand, clinical presentation among identical siblings may vary from a typical PANDAS to being completely asymptomatic (59).

Cognitive abnormalities in youth diagnosed with PANDAS have been explored (60). In this study, marked impairment in visuospatial recall memory (as assessed using the Rey-Osterrieth Complex Figure Test) was observed in spite of average to above-average performance on academic and other neurocognitive measures. Group A beta-hemolytic Streptococcus titer elevations were associated with worse performance on tasks of neurocognitive and executive ability (Stroop Color-Word Interference Test), visuospatial memory, and fine motor speed (finger tapping) as well as elevated obsessive-compulsive symptom severity. Another study also found difficulties in visual-motor skills, short memory tasks (Symbol Search subtest of Wechsler Intelligence Scale for Children or Digit Span subtest of Wechsler Intelligence Scale for Children), attention (symbol search subtest of Wechsler Intelligence Scale for Children), and elaboration speed (elaboration of speed index) in patients with PANS, but no statistically significant differences were identified between PANDAS and Sydenham chorea patients (28).

Case reports have linked the onset of PANDAS symptoms not only to streptococcal pharyngitis, but also to dermatological streptococcal infections, including streptococcal perianal dermatitis (14; 123).

Investigators from the United States have independently suggested a nosographic reappraisal of this entity. Their approach has been similar, aiming at a definition of the broader spectrum of acute neuropsychiatric syndromes with onset in young patients. The first of these newly proposed concepts is childhood acute neuropsychiatric syndromes (CANS), presented by Singer and colleagues (104). CANS are not defined by a specific set of criteria but encompass all acute fulminant neuropsychiatric symptoms with onset in childhood, which obviously require a complex active search for underlying causes. According to these authors, a certain proportion of these cases will not be associated with a clear etiology, and the group of patients formerly labeled as PANDAS would fall into this category of “idiopathic” CANS. The definition of idiopathic CANS comprises acute onset before 18 years of age of behavioral and motor signs encompassing obsessive-compulsive disorder (primary criterion), anxiety, psychosis, developmental regression, sensitivity to sensory stimuli, emotional lability, tics (listed a secondary criterion), dysgraphia, clumsiness, hyperactivity, and an either mono- or polyphasic course. At the conclusion of their article, Singer and colleagues strongly recommend “that a national centralized registry be established for the collection of standardized and longitudinal information on this cohort” of idiopathic CANS” (104).

In a second article, 6 expert clinicians discussed data extracted from their evaluations of more than 400 children and adolescents who had been diagnosed with PANDAS (115). Clinicians had to identify the symptoms that best characterized the collective group of patients, and the acknowledged key clinical feature was “acute and dramatic symptom onset,” in some particular cases “severe enough that parents took the child to the ER.” On this basis, these authors consensually identified new operational diagnostic criteria for the whole spectrum of pediatric acute-onset neuropsychiatric syndrome (PANS), which is summarized in Table 2. It was characterized by an abrupt onset of obsessive compulsive disorder along with at least 2 other cognitive, motor, sensory, or behavioral symptoms (115). In this set of criteria, the presentation of tics without obsessive-compulsive disorder is not accepted as part of the syndrome.

Table 2. Proposed Diagnostic Criteria for PANS

(1) Abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted food intake (< 48 h)

(2) Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and acute onset, from at least 2 of the following 7 categories:

(a) Anxiety
(b) Emotional lability and/or depression
(c) Irritability, aggression and/or severely oppositional behaviors
(d) Behavioral (developmental) regression
(e) Deterioration in school performance
(f) Sensory or motor abnormalities including increased sensitivity to sensory stimuli, hallucinations, dysgraphia, complex motor, and/or vocal tics
(g) Somatic signs and symptoms, including sleep disturbances, enuresis or urinary frequency

(3) Symptoms are not better explained by a known neurologic or medical disorder, such as Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others

Sensory abnormalities reported in PANS also have an abrupt onset and include sensitivity to light, sensitivity to environmental auditory stimuli (misphonia), refusal to wear clothes or shoes as a result of hypersensitivity to tactile stimuli, generalized pain, and also a new-onset tendency to food refusal as a result of being bothered by taste and texture of foods commonly used, as well as worries about choking. This latter symptom is the usual reason for the restricted food intake in these children. However, typical anorexia nervosa has been anecdotally reported by others in connection with PANDAS (11; 25).

A streptococcal infection and a temporal relationship of it to the onset of neurologic symptoms is required to make a diagnosis of PANDAS, but not PANS. PANS symptoms overlap with many psychiatric disorders including obsessive compulsive disorder, attention deficit hyperactivity disorder, and mood disorders.

Additional considerations on the clinical concepts of CANS and PANS and their possible development can be found in the Resolution section.

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