What school psychologists should know about streptococcal infections

The author examines the tie between streptococcal infections and neuropsychiatric symptoms in school children

By Ashley S. Fournier

The fall and winter months have been characterized as the most common time to experience a streptococcal infection among the pediatric population (Murphy et al., 2007; Murphy et al., 2004). Prevalence rates of streptococcal infections such as pharyngitis, commonly referred to as strep throat, and scarlet fever indicate that most children experience a streptococcal infection at some point in their lives (Murphy et al., 2004). The school setting is a common place for these infections to spread among children given the contagious nature of the streptococcal bacteria and the close proximity of children. It has been well-documented that infection with streptococcus results in neuropsychological sequelae among children that impact functioning in the school setting (Gabbay & Coffey, 2003; Mink & Kurlan, 2011; Walker, Lawrenson, & Wilmshurst, 2005); thus, a clear understanding of the educational implications of streptococcal infection among schoolpsychologists is warranted.

While there are numerous types of streptococci, group-A beta-hemolytic streptococcus pyogenes (GABHS) has received much attention in the literature (Gabbay et al., 2008; Moretti, Pasquini, Mandarelli, Tarsitani, & Biondi, 2008; Murphy, Kurlan, & Leckman, 2010). GABHS infections most commonly manifest among children as rheumatic fever, scarlet fever and pharyngitis (Bisno & Stevens, 2009; Murphy et al., 2010; Swedo & Grant, 2004; Swedo et al., 1998). Rheumatic fever is an inflammatory disease characterized by stomach pain, fever and autoimmune responses that commonly impact the heart, joints, skin or brain (Bisno & Stevens, 2009). It typically occurs following infection with GABHS manifesting as scarlet fever or pharyngitis. The hallmark of scarlet fever is the presence of a large, red rash associated with fever, chills, abdominal pain and sore throat. Pharyngitis typically results in fever, chills, headache and nausea distinctive for the presence of a sore, red throat often with white patches. Most importantly, each of these bacterial infections has been associated with the presence of postinfectious neuropsychiatric symptoms (Swedo & Grant, 2005; Swedo et al., 1998).

Specific neuropsychiatric sequelae

Recently, GABHS infections have been investigated with regard to the presence of an autoimmune response resulting in motor and vocal tics and symptoms consistent with obsessive-compulsive disorder (OCD) among the pediatric population (Moretti et al., 2008; Murphy et al., 2010; Swedo & Grant, 2005; Swedo et al., 1998). The presence of tics, OCD symptoms and other neuropsychiatric sequelae following pharyngitis, scarlet fever, and other GABHS infections, with the exception of rheumatic fever, has been referred to as pediatric autoimmune neuropsychiatric disorders associated with streptococcus or PANDAS.

Documentation of the association between movement disorders and infectious diseases has occurred for several decades (Murphy et al., 2010). In the late 1920s, a temporal association between sinusitis and the onset of tics was noted; however, psychoanalytic theories of movement disorders were predominant resulting in neglect of the medicalization of postinfectious tic disorders, with the exception of Sydenham’s chorea, until the early 1990s. At this time, researchers described several patients who exhibited novel tic disorders and OCD symptoms, or worsening of previous symptoms following GABHS or viral infection (Moretti et al., 2008). The characteristics noted among these patients were conceptualized as representing a distinct subgroup of patients with OCD and tic disorders initially referred to as pediatric infection-triggered autoimmune neuropsychiatric disorders or PITANDs. Additional research indicated that pediatric patients exhibiting postinfectious OCD and tic disorders could be reliably distinguished based on the presence of GABHS rather than viral infections; thus, the PANDAS acronym was developed (Swedo et al., 1998). In addition, tentative diagnostic criteria were established including the presence of OCD and/or a tic disorder as described by the "Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision" (DSM-IV-TR; American Psychiatric Association [APA], 2000), onset between the age of three and the beginning of puberty, and an episodic course of symptom presentation. More specifically, the onset of novel symptoms consistent with tic disorders and OCD should be abrupt, or previous symptoms should be significantly exacerbated in an abrupt manner. The tentative diagnostic criteria also suggested that there should be a clear temporal association between GABHS infection and symptom onset. This temporal association could be established through the presence of positive throat cultures and/or elevated anti-GABHS antibody titers such as antistreptolysin-O (ASO), antideoxyribonuclease B (ADNB) and anticarbohydrate A (ACHO; Murphy et al., 2004; Swedo et al., 1998).

Briefly, streptococcal antibody titers indicate the presence of a previous infection with streptococcus (Moretti et al., 2008; Murphy et al., 2010). Because the immune system produces antibodies specific to impending infections as a method of fighting these infections, elevated titers would suggest that a child had been recently infected with GABHS. However, this criterion has been criticized given many children exhibit elevated levels of streptococcal antibody titers due to frequent exposure to the bacteria or simply individual differences; therefore, it has been recommended that both a positive throat culture and elevated streptococcal antibody titers be obtained as a more definitive method of establishing temporal association between GABHS infection and tic/OCD symptom onset (Swedo & Grant, 2005). The final tentative diagnostic criterion suggested that neurological abnormalities must be present (Swedo et al., 1998). This includes excessive motor activity, choreiform movements, and vocal or motor tics. A distinction has been made between the presence of overt or frank chorea and choreiform movements (Murphy et al., 2007). Chorea refers to “arrhythmic, rapid, often jerky movement that might be simple or complex” (p. 279). This type of movement is most commonly observed in Huntington’s or Sydenham’s chorea. In contrast, choreiform movements are twitching or writhing movements “elicited by a clinician exclusively upon neurological examination” (p. 279).

The proposed mechanism of pathology in PANDAS is molecular mimicry (Moretti et al., 2008; Murphy et al., 2010; Swedo & Grant, 2005; Swedo et al., 1998). This is the process by which the GABHS bacterium imitates proteins associated with parts of the brain. The specific neuroanatomical location imitated includes the basal ganglia, made up of the globus pallidus, putamen, caudate, subthalamic nuclei and substantia nigra, which are important for controlling motor functioning (Carter, 2009). These are the same structures implicated in a number of other disorders characterized by motor sequelae including Tourette’s disorder, Sydenham’s and Huntington’s chorea, and Parkinson’s disease. In PANDAS, the immune system presumably produces antibodies intended to attack GABHS; however, because of molecular mimicry, antibodies that attack proteins associated with the basal ganglia are produced as well resulting in vocal and motor tics (Moretti et al., 2008; Murphy et al., 2010; Swedo & Grant, 2005; Swedo et al., 1998). The molecular mimicry resulting in Sydenham’s chorea noted to occur in rheumatic fever has been used a framework for the description and explanation of PANDAS.

Research has also indicated that the molecular mimicry engaged in by GABHS bacteria may impact dopamine receptors in the brain resulting in the release of excitatory neurotransmitters in PANDAS (Murphy et al., 2010). Within the basal ganglia, this can result in tics and symptoms of OCD. The role of epigenetic influences in the manifestation of PANDAS has also been suggested (Lewin, Storch, & Murphy, 2011). Research has indicated that the clinical presentation of PANDAS can differ significantly among identical twins. This is suggestive of the impact of pre- and postnatal events that may result in changes to deoxyribonucleic acid (DNA) at the epigenetic level. In general, mechanism of pathology has been explored; however, it has not been clearly and definitively outlined. The prevalence of PANDAS is not known although research has indicated that 11 percent of children presenting with tic disorders exhibited abrupt onset or exacerbation of symptoms within six weeks of GABHS infection (Murphy et al., 2004). An initial clinical description of 50 children who met diagnostic criteria for PANDAS applied retrospectively indicated that the ratio of boys to girls was 2.6 to 1; however, in those under the age of 8, the ratio was 4.7 to 1 (Swedo et al., 1998).

Differential diagnosis

The accurate diagnosis of PANDAS versus other disorders characterized by motor sequelae requires careful clinical consideration. Because neuropsychiatric and neurobehavioral disorders are often first noticed at school given the amount of time children spend there, differential diagnosis is particularly relevant to school psychologists. There is significant symptom overlap in children presenting with Sydenham’s chorea and those presenting with PANDAS (Moretti et al., 2008; Murphy et al., 2010; Swedo & Grant, 2005). Sydenham’s chorea is the neurological manifestation of rheumatic fever, which is also the result of infection with GABHS. The molecular mimicry associated with rheumatic fever can impact proteins in the heart, joints, skin, and brain. When this mimicry results in the production of antibodies directed at the basal ganglia, Sydenham’s chorea or overt chorea, results. Based on the tentative diagnostic criteria associated with PANDAS, children experiencing this disorder should exhibit only choreiform movements (Moretti et al., 2008). In addition, children experiencing PANDAS are noted to exhibit more significant neurobehavioral sequelae than those with Sydenham’s chorea (Murphy et al., 2010). These include personality changes, aggressive and/or oppositional behaviors, symptoms consistent with attentiondeficit/ hyperactivity disorder (AD/HD), and anxiety; however, these neurobehavioral sequelae are not required diagnostically. Deficits in academic functioning specifically within the areas of writing and mathematics have also been commonly associated with PANDAS diagnoses.

Those meeting diagnostic criteria for tic disorders such as Tourette’s disorder must exhibit both vocal and motor tics nearly every day for more than one year with no ticfree period longer than three months (APA, 2000; Phelps & Smerbeck, 2011). Diagnosis of other tic disorders such as chronic motor or vocal tic disorder adheres to these same criteria with regard to time frame of symptom presentation. Diagnostically, tic disorders such as transient tic disorder and tic disorder not otherwise specified (NOS) require that tics are exhibited for a time frame between four weeks and 12 months. Those with PANDAS must exhibit an episodic course of symptom severity wherein symptoms decrease significantly between episodes (Swedo et al., 1998). Presumably, this time period may be longer than 3 months as the seasonality of symptoms has been noted. Although these symptoms have been noted to quickly cease following treatment for GABHS, this would not clearly distinguish PANDAS from transient tic disorder or tic disorder NOS; however, the establishment of temporal association between symptom onset, which must be abrupt or dramatic in nature, and GABHS infection can assist with differential diagnosis. As demonstrated here, there is some symptom overlap between PANDAS and tic disorders.

Similarities in the clinical presentation between PANDAS and OCD have also been noted (Leckman et al., 2011; Moretti et al., 2008; Murphy et al., 2010). Most typically, those with OCD experience symptom onset in adolescence or early adulthood (APA, 2000). In contrast, those with PANDAS must experience symptom onset between the age of 3 and the beginning of puberty (Swedo et al., 1998). Most individuals with OCD exhibit a course of illness characterized by waxing and waning of symptoms mediated by the experience of stress (APA, 2000). In addition, a minority of individuals diagnosed with OCD exhibit an episodic course of illness with minimal or no symptoms present between episodes. Although this seems consistent with the described course of illness associated with PANDAS, those exhibiting this disorder must have a documented temporal association with GABHS and symptom onset which should be abrupt or dramatic in nature (Swedo et al., 1998). In addition, the episodic nature of symptom presentation and exacerbation is often associated with the fall and winter seasons, which has not been consistently noted with OCD; however, the overlap in symptomatology between PANDAS and OCD cannot be ignored.

The subgroup of children who have been described as meeting the working diagnostic criteria for PANDAS differs in many ways, as noted above, from children exhibiting Syndenham’s chorea or those diagnosed with tic disorders and OCD. However, the existence of PANDAS as a distinct subgroup has been criticized (Leckman et al., 2011; Moretti et al., 2008; Murphy et al., 2004). The overlap in symptom presentation and lack of specificity of the tentative diagnostic criteria associated with PANDAS has led some authors to suggest that PANDAS may simply represent a less severe form of Sydenham’s chorea or a subset of those with Tourette’s disorder or OCD (Moretti et al., 2008). This suggestion is particularly relevant when considering that 59 percent of those with Tourette’s disorder have a comorbid diagnosis of OCD (Phelps & Smerbeck, 2011). Based on these concerns, researchers have suggested that the tentative diagnostic criteria be strengthened by requiring that both sudden onset of a tic disorder and OCD be present when diagnosing PANDAS (Leckman et al., 2011). In addition, symptom onset or exacerbation must increase to maximum severity between 24 and 48 hours. Research has also suggested that requiring the presence of three associated neurobehavioral symptoms may improve the specificity of the tentative diagnostic criteria currently associated with PANDAS.

The existence of PANDAS has also been criticized given the large number of children who experience streptococcal infections coupled with only a minimal number of children who exhibit seemingly subsequent tic disorders and OCD symptoms (Murphy et al., 2004). It may be likely that “streptococcal infections are endemic enough that reported associations are occurring by chance only” (p. 61). Although the prevalence rates of PANDAS are not currently known, it is likely that true PANDAS cases are rare (Leckman et al., 2011). The incidence of Sydenham’s chorea in the United States is estimated to be between .6 to .7 out of every 1,000 (Walker et al., 2005). This may suggest that a similar disorder such as PANDAS would be similarly rare; however, it is important to note that streptococcal infections such as rheumatic fever are much less likely to occur in the United States in comparison with streptococcal infections such as pharyngitis.

Implications for the School Setting Children who meet diagnostic criteria for PANDAS exhibit symptoms that may impact academic and social functioning (Gabbay & Coffey, 2003; Mink & Kurlan, 2011; Murphy et al., 2010); essentially, their overall educational functioning may be impacted. The abrupt onset or dramatic exacerbation of symptoms associated with PANDAS can impact neuropsychological functioning across a number of domains (Murphy et al., 2010; Swedo & Grant, 2005; Swedo et al., 1998). Because these neuropsychological domains are supportive of academic skills (Miller, 2007), it is likely that children suspected of having PANDAS will evince a need for academic or positive behavioral supports in the school setting. Despite the diagnostic issues associated with this illness, children exhibiting this symptomatology still require a free and appropriate public education (FAPE), which can be obtained through use of response to intervention (RTI), special education or Section 504 services. However, it is incumbent upon the school psychologist to not only assist in the implementation of a FAPE, but also to make appropriate and useful recommendations to primary caregivers and school personnel associated with a child with PANDAS as a method of best serving that child. Knowledge of PANDAS and the associated diagnostic issues informs these recommendations and directs primary caregivers to additional resources that may be implemented outside the school setting.


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About the author

Ashley S. Fournier is a doctoral student in the school psychology program at Texas Woman's University (TWU) in Denton, Texas. This program places an emphasis on neuropsychological assessment and intervention with children and adolescents. Ashley obtained a master of arts in school psychology from Sam Houston State University (SHSU) and is credentialed as a Nationally Certified School Psychologist (NCSP). She worked as a licensed specialist in school psychology (LSSP) in Katy Independent School District (ISD) before returning to graduate school to complete her doctorate.