Overview
Definition:
PANDAS is a subtype of Obsessive-Compulsive Disorder (OCD) or tic disorders in children
It is characterized by a sudden onset or exacerbation of neuropsychiatric symptoms, including OCD, tics, and behavioral changes, following a streptococcal infection, typically Group A Streptococcus (GAS)
The proposed mechanism involves an autoimmune response where antibodies, meant to fight the infection, cross-react with basal ganglia structures in the brain.
Epidemiology:
PANDAS is estimated to affect approximately 1 in 200 children with acute-onset OCD or tic disorders
It primarily affects school-aged children, with an onset typically between ages 3 and 12 years
There is no significant gender predilection, though some studies suggest a slight predominance in females
Recurrence is possible, especially with subsequent streptococcal infections.
Clinical Significance:
Understanding PANDAS is crucial for pediatricians and neurologists to differentiate it from other causes of sudden-onset behavioral changes and tics
Timely diagnosis and appropriate management can significantly improve the quality of life for affected children and their families, reducing the burden of debilitating neuropsychiatric symptoms and preventing misdiagnosis or undertreatment.
Clinical Presentation
Symptoms:
Abrupt onset or dramatic worsening of OCD symptoms, including intrusive thoughts, repetitive behaviors, compulsions
Sudden emergence or worsening of motor or vocal tics
Behavioral changes such as anxiety, emotional lability, irritability, mood swings, regression in developmental milestones, sleep disturbances, and school refusal
Symptoms often fluctuate in severity, with exacerbations linked to subsequent infections.
Signs:
Physical examination may reveal signs of a recent or current streptococcal infection, such as pharyngitis, fever, or scarlet fever rash
Neurological examination might show motor or vocal tics
Psychiatric assessment is key to characterizing the nature and severity of OCD and tic symptoms.
Diagnostic Criteria:
The diagnostic criteria for PANDAS, proposed by the PANDAS Steering Committee, include: 1
Presence of childhood-onset OCD and/or tic disorder
2
Symptoms are episodic, with dramatic exacerbations and remissions
3
Association with a preceding GAS infection, confirmed by throat culture or elevated antistreptococcal antibody titers (e.g., ASO, Anti-DNase B)
4
Neurological abnormalities, such as choreiform movements, observed during exacerbations
5
Temporal relationship between GAS infection and symptom onset/exacerbation
Note: The role of specific antibody titers and the need for neurological abnormalities are subjects of ongoing research and clinical debate.
Diagnostic Approach
History Taking:
Detailed history of symptom onset and progression, specifically noting any sudden changes
Inquire about family history of OCD, tic disorders, autoimmune diseases, or rheumatic fever
Obtain history of recent sore throats, fever, or other infectious symptoms
Document any prior diagnosis and treatment for psychiatric or neurological conditions
Assess impact on daily functioning, school attendance, and social interactions
Red flags include a clear temporal link between infection and symptom onset/worsening, and episodic symptom fluctuation.
Physical Examination:
A thorough physical examination is essential, focusing on identifying signs of acute streptococcal infection, such as pharyngitis, tonsillar exudates, scarlet fever rash, and lymphadenopathy
A complete neurological examination is necessary to assess for tics (motor and vocal) and any associated neurological signs like chorea
General pediatric assessment to rule out other systemic causes of behavioral changes.
Investigations:
Strep Testing: Rapid antigen detection test (RADT) for GAS pharyngitis
Throat culture for GAS if RADT is negative or if there is high clinical suspicion
Antistreptococcal Antibody Titers: Anti-streptolysin O (ASO) and Anti-DNase B titers are crucial, especially if the infection was remote
Elevated titers, particularly a rising titer or a high single titer, support a recent GAS infection
A normal titer does not entirely rule out PANDAS, as antibody response can vary
Other investigations: Complete blood count (CBC), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP) to assess for inflammation
Thyroid function tests (TFTs) to rule out thyroid dysfunction
Neuroimaging (MRI brain) is generally not indicated for diagnosis but may be used to rule out structural lesions if other neurological signs are present.
Differential Diagnosis:
Other causes of childhood-onset OCD and tics: Tourette syndrome (typically chronic, not episodic), primary OCD or tic disorder without infectious trigger, PANDAS-like presentations due to other infections (e.g., PANS - Pediatric Acute-onset Neuropsychiatric Syndrome), pediatric autoimmune neuropsychiatric disorders associated with other infections, Sydenham's chorea (more pronounced chorea, less OCD), schizophrenia, ADHD, autism spectrum disorder, behavioral changes due to psychosocial stress, medication side effects, or substance abuse.
Management
Initial Management:
The primary goal is to treat the underlying streptococcal infection and manage acute neuropsychiatric symptoms
For confirmed GAS infection, appropriate antibiotic therapy is initiated
For children presenting with PANDAS symptoms without current infection but with a history of recent GAS infection and elevated antistreptococcal titers, a course of antibiotics may be considered, although the evidence for its efficacy in resolving psychiatric symptoms is debated
Supportive care is paramount.
Medical Management:
Pharmacological management targets the neuropsychiatric symptoms: Selective Serotonin Reuptake Inhibitors (SSRIs): First-line treatment for OCD and anxiety symptoms
Examples include fluoxetine, sertraline, fluvoxamine, citalopram, escitalopram
Dosing should be started low and titrated slowly, as children can be sensitive
Antipsychotics: For severe tics or agitation
Low-dose atypical antipsychotics like risperidone or aripiprazole may be used cautiously
Stimulants are generally avoided as they can exacerbate tics
Mood stabilizers or antidepressants may be considered for associated mood lability
Antibiotics: If a current GAS infection is present, antibiotic treatment (e.g., penicillin or cephalexin) is essential
Prophylactic antibiotics may be considered for recurrent infections, but evidence is limited for PANDAS symptom control.
Surgical Management:
Surgical management is not a standard treatment for PANDAS
However, in severe, refractory cases of OCD not responding to medical management, some investigational surgical approaches like deep brain stimulation (DBS) or lesioning procedures are being explored for severe pediatric OCD, but these are highly experimental and not specific to PANDAS.
Supportive Care:
Cognitive Behavioral Therapy (CBT): Particularly Exposure and Response Prevention (ERP) for OCD, is a cornerstone of management
CBT for tics can also be beneficial
Parent psychoeducation and support are vital
School accommodations and support services can help children cope with academic and social challenges
Regular monitoring of symptoms, treatment response, and potential side effects of medications is crucial.
Complications
Early Complications:
Severe functional impairment due to uncontrolled OCD and tics
Significant distress and anxiety for the child and family
School refusal and academic decline
Social isolation
Aggravation of symptoms following subsequent infections if not recognized.
Late Complications:
Chronic OCD or tic disorder
Persistence of neuropsychiatric symptoms into adulthood
Social, emotional, and academic long-term deficits
Potential for rheumatic fever if streptococcal infection is not adequately treated (though PANDAS itself is not rheumatic fever).
Prevention Strategies:
Prompt and adequate treatment of all streptococcal infections in children
Early recognition and diagnosis of PANDAS to initiate appropriate management and supportive care
Careful monitoring for recurrence of symptoms after subsequent infections
Educating parents and caregivers about PANDAS and its management
Research into immunomodulatory therapies (e.g., IVIG, plasmapheresis) for severe, refractory cases is ongoing but not yet standard of care.
Prognosis
Factors Affecting Prognosis:
Severity of initial symptoms
Timeliness and appropriateness of diagnosis and treatment
Frequency and severity of subsequent infections
Response to SSRIs and CBT
Presence of co-occurring conditions
Family support and engagement.
Outcomes:
Many children with PANDAS experience significant improvement in symptoms with appropriate treatment, including antibiotics, SSRIs, and CBT
Symptom remission is possible, especially if treatment is initiated early
However, some children may have a chronic or relapsing course, requiring long-term management
The episodic nature means symptoms can wax and wane, making long-term prognosis variable.
Follow Up:
Regular follow-up with pediatricians, child psychiatrists, and neurologists is essential
Monitoring for symptom recurrence, treatment efficacy, and medication side effects
Long-term management may involve continued use of SSRIs and/or ERP, especially during periods of increased infection risk or documented relapses
Educational support and therapy should continue as needed.
Key Points
Exam Focus:
Remember the diagnostic criteria for PANDAS, particularly the episodic nature and link to GAS infection
Differentiate PANDAS from primary OCD/tics
Key investigations include ASO/Anti-DNase B titers and throat cultures
Management involves antibiotics, SSRIs, and CBT (ERP).
Clinical Pearls:
Always consider PANDAS in children with sudden, dramatic onset of OCD or tics, especially if recurrent
A thorough history of infections is critical
Fluctuating symptom severity is a hallmark
Start SSRIs at low doses and titrate slowly
Do not underestimate the power of ERP for OCD symptoms in PANDAS
Educate families thoroughly about the condition and its management plan.
Common Mistakes:
Attributing all sudden behavioral changes to PANDAS without a thorough workup
Failing to adequately test for GAS infection or interpret antistreptococcal titers correctly
Over-reliance on antibiotics alone without addressing neuropsychiatric symptoms
Inappropriately using stimulants which can worsen tics
Not considering PANS as a differential diagnosis in cases without a clear GAS link.