Case Study by Christopher Paul Manbeck , MD ; 1 Kapil Arya , MD , MBBS 2
PANDAS and PANS : A Short Review
1
Department of Pediatrics , Section of Child Neurology , UAMS
2
Department of Pediatrics , Section of Child Neurology , UAMS
Abstract
A
diagnosis of PANDAS ( Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections ), is often considered for children with tics and obsessive-compulsive behavior . The term PANS ( Pediatric Acute-onset Neuropsychiatric Syndrome ) or PITAND ( Pediatric Infection Triggered Autoimmune Neuropsychiatric Disorder ) is often used interchangeably for this condition . Each patient needs careful individual consideration to prevent overdiagnosis and to ensure appropriate management .
Introduction
The treatment of childhood obsessive compulsive disorder ( OCD ), as well as tics , is challenging and not uniformly successful . The etiology of these disorders is also not clearly elucidated . Although most patients suffering from OCD or tics have an insidious onset and a chronic course , anecdotally others seem to have a rather acute onset or periodic worsening , at times temporally related to a concurrent infection . If an objective infectious or inflammatory cause for these disorders could be established , this might lead to treatment and resolution of these disorders with the use of antibiotics or anti-inflammatory medication .
Dr . Susan Swedo , while working at the Child Psychiatry Branch at the National Institute of Mental Health , attempted to establish such a causal link between Group A beta-hemolytic streptococci infection ( GABHS ) and described a “ new subtype of pediatric OCD .” 1 In her 1998 research paper , she named this condition “ PANDAS ”: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections . She established diagnostic criteria as summarized in Table 1 . 2 Dr . Swedo stressed that the episodic course of this syndrome was characterized by an abrupt onset or by dramatic symptom exacerbations , with the symptoms diminishing significantly or resolving completely within 6-8 weeks of onset or exacerbation . 3
Pathophysiology
There are numerous proposed mechanisms of pathophysiology of PANDAS . Perhaps the most convincing theory is that of molecular mimicry . Antibodies intended to target GABHS instead target brain proteins , and numerous studies have demonstrated that antibodies directed at the basal ganglia create inflammation in these regions . Regulatory T-cells ( RegT ) suppress T-cell response against self-antigens at the site of injury ; thus , to prevent neuronal injury caused by autoimmunity , it is desirable to enhance the RegT activity . Dopamine has been found to reduce the suppressive activity of RegT . It has been hypothesized that GABHS infection causes greater permeability of the bloodbrain barrier , which leads to increased dopamine release . In turn , this leads to local suppression of RegT and ultimately causes acute and chronic inflammation within the basal ganglia , which is the suspected cause of the clinical syndrome . Kawikova et al have studied this association . Thirty-seven children diagnosed with either OCD or tics were compared to a control group of ‘‘ healthy ’’ children . Children with more severe tics ( Yale Global Tic Severity Scale of 20 or greater ) were found to have lower RegT . However , when the group
Table 1 DIAGNOSTIC CRITERIA FOR PANDAS ( per Dr . Swedo ) a ) Presence of OCD and / or tic disorder b ) Prepubertal symptom onset c ) Episodic course of symptom severity of children diagnosed with PANDAS was compared to children without that diagnosis , there was no significant difference in the number of RegT . 4 Therefore , even though the above-described etiological hypothesis is attractive , it is not yet firmly established .
Dr . Swedo reviewed the first ‘‘ 50 cases ’’ of acute childhood onset neuropsychiatric symptoms and found that 36 of the 50 children studied had symptom onset triggered by GABHS infection . 2 A patient was deemed to have GABHS infection on the basis of either a positive throat culture or elevated anti-GABHS antibody titers . However , numerous studies have reported up to 20 % of children aged 3 to 15 are pharyngeal carriers of GABHS ; 5 therefore , prior to assigning a diagnosis of PANDAS , it is imperative to establish whether the child has an acute GABHS infection or is simply a carrier . Kurlan et al have attempted to address this issue . They prospectively evaluated 40 pediatric patients previously diagnosed with PANDAS with intensive lab testing over the course of two years . As a control , they also prospectively evaluated a group of pediatric patients who were diagnosed with OCD or chronic tic disorder , without an association with GABHS . A throat culture was performed every four weeks , ASO and anti-DNAse B titers drawn every 12 weeks , and clinical exam performed every 12 weeks . They concluded that the PANDAS group had a higher risk
d ) Associated with group A beta hemolytic streptococci ( GAS ) infections e ) Association with neurological abnormalities ( i . e . tics )
206 • The Journal of the Arkansas Medical Society www . ArkMed . org