The clinical course of PANDAS is characterized by an episodic pattern of symptoms with acute onset of OCD symptoms and significant comorbidity associated with the exacerbations. Emotional lability, school issues, anxiety, nighttime fears and bedtime rituals, urinary symptoms, cognitive deficits, depression, behavioral regression, deterioration in math skills and handwriting and motoric hyperactivity are frequently observed [7] [8] [9] [10].

The five working criteria for the diagnosis of PANDAS are as follows [1]:

• Presence of OCD or tic disorder
• Prepubertal onset
• Episodic course and acute onset of symptoms and/or exacerbation
• Temporal association with group A streptococcal infection
• Association with neurologic abnormalities such as motoric hyperactivity or choreiform movements

Distinguishing PANDAS from tic disorder, OCD, or Sydenham chorea may be challenging, but recent studies suggest clinical and laboratory factors which aid in establishing the diagnosis [10] [11].

Antimicrobial therapy indicated for the treatment of group A streptococcal infections irrespective of the presence of neuropsychiatric symptoms [3]. The treatment of the neuropsychiatric manifestation consists of standard management of children with OCD. Patients may benefit from intravenous immunoglobulin or plasma exchange, but data about immune modulating therapy is limited [12] [13].

The prognosis of PANDAS is unknown.

Streptococci are gram-positive, nonmotile, non-spore-forming cocci. Group A Streptococci cause acute inflammatory infections (eg. pharyngitis, impetigo, necrotizing fasciitis, etc.), as well as postinfectious, immune-mediated conditions in humans [4]. Cases of PANDAS are associated with group A streptococcal infections, at least temporally. The disorder seems to develop due to cross-reactive antibodies produced in response to molecular mimicry, causing basal ganglia dysfunction. Due to the high incidence of group A streptococcal infections in the pediatric population and GAS carriage, the exact relationship between PANDAS and group A streptococcal infection is difficult to establish [5].

The incidence and prevalence of PANDAS are not established, but it seems to be a rare disorder. Males are more commonly affected, but the reason is unknown.

The proposed pathophysiology of PANDAS includes group A streptococcal infections, abnormal immune responsivity and genetic susceptibility leading to central nervous system manifestations [6]. However, this hypothesis has yet to be proven.

Since the exact pathogenesis of PANDAS is unknown, the potential benefit of prophylactic antimicrobial therapy remains unclear.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a rare pediatric disorder associated with obsessive-compulsive disorder and tic disorder. The first 50 cases were described by Dr. Susan Swedo in 1998 [1]. The five diagnostic criteria for the disorder are as follows [1]:

• Presence of obsessive-compulsive disorder (OCD) or tic disorder
• Prepubertal onset
• Episodic course and acute onset of symptoms and/or exacerbation
• Temporal association with group A streptococcal (GAS) infection
• Association with neurologic abnormalities such as motoric hyperactivity or choreiform movements

The proposed pathophysiology of PANDAS includes various factors - a group A streptococcal infection, an abnormal immune response and genetic susceptibility leading to central nervous system manifestations. This model was based upon the similarity to Sydenham chorea [2]. PANDAS is a clinical diagnosis and treatment frequently consists of standard management of group A streptococcal infection and OCD/or tic disorder [3].

PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) is a rare condition occurring in children. It may be diagnosed when an obsessive compulsive disorder (OCD) and/or a tic disorder suddenly develops or worsens following a streptococcal infection. PANDAS usually first appears in childhood from age 3 to puberty. The exact cause and disease mechanism of PANDAS are not known, but the streptococcal infection is thought to trigger a misdirected immune response causing a reaction in the brain.

The presentation is usually dramatic and acute. Symptoms may include tics, obsessions, compulsions, anxiety, emotional lability, night-time fears, mood changes, hyperactivity, sleep disturbance, deterioration in math skills and handwriting and cognitive deficits. The diagnosis of PANDAS is made clinically with the aid of the following diagnostic criteria:

• Presence of OCD or tic disorder
• Prepubertal onset
• Episodic course and acute onset of symptoms and/or exacerbation
• Temporal association with group A streptococcal infection
• Association with neurologic abnormalities such as physical hyperactivity or jerky, unusual (choreiform) movements

Treatment consists of standard management of Group A streptococcal infection and OCD/or tic disorder including antibiotics, behavioral therapy or selective serotonin reuptake inhibitors (SSRIs). Plasma exchange or intravenous immunoglobulin may be beneficial in acute and severe cases.

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2. Swedo SE. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Mol Psychiatry. 2002;7 Suppl 2:S24-5.
3. Swedo SE, Leonard HL, Rapoport JL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics. 2004 Apr;113(4):907-11.
4. Walker MJ, Barnett TC, McArthur JD, Cole JN, Gillen CM, Henningham A, Sriprakash KS, Sanderson-Smith ML, Nizet V. Disease manifestations and pathogenic mechanisms of Group A Streptococcus. Clin Microbiol Rev. 2014 Apr;27(2):264-301. doi: 10.1128/CMR.00101-13.
5. Tan J, Smith CH, Goldman RD. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Canadian Family Physician. 2012;58(9):957-959.
6. Dale RC, Heyman I. Post-streptococcal autoimmune psychiatric and movement disorders in children. Br J Psychiatry. 2002 Sep;181:188-90.
7. Orefici G, Cardona F, Cox CJ, Cunningham MW. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Streptococcus pyogenes: Basic Biology to Clinical Manifestations]. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2016-2016 Feb 10.
8. Kovacevic M, Grant P, Swedo SE. Use of Intravenous Immunoglobulin in the Treatment of Twelve Youths with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. Journal of Child and Adolescent Psychopharmacology. 2015;25(1):65-69. doi:10.1089/cap.2014.0067.
9. Swedo SE, Seidlitz J, Kovacevic M, et al. Clinical Presentation of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections in Research and Community Settings. Journal of Child and Adolescent Psychopharmacology. 2015;25(1):26-30. doi:10.1089/cap.2014.0073.
10. Murphy ML, Pichichero ME. Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS) Arch Pediatr Adolesc Med. 2002;156(4):356–61.
11. Murphy TK, Storch EA, Lewin AB, Edge PJ, Goodman WK. Clinical Factors Associated with PANDAS. The Journal of Pediatrics. 2012;160(2):314-319. doi:10.1016/j.jpeds.2011.07.012.
12. Kovacevic M, Grant P, Swedo SE. Use of Intravenous Immunoglobulin in the Treatment of Twelve Youths with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. Journal of Child and Adolescent Psychopharmacology. 2015;25(1):65-69. doi:10.1089/cap.2014.0067.
13. Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, Swedo SE. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet 354:1153–1158, 1999