Overview
Definition:
PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) are disorders characterized by abrupt onset of obsessive-compulsive symptoms or severe food restriction, accompanied by a constellation of other neuropsychiatric symptoms
PANDAS is a subset of PANS, specifically linked to group A streptococcal (GAS) infections
PANS is a broader category encompassing similar presentations with identifiable triggers other than GAS or with no identifiable trigger.
Epidemiology:
Estimates vary widely due to diagnostic challenges and evolving criteria
PANDAS is thought to affect approximately 1 in 200 children, with symptoms typically emerging between ages 3 and 12
PANS is considered less common than PANDAS, with a prevalence that is not yet well-established
Female predominance is observed in some studies, particularly for PANS.
Clinical Significance:
PANDAS/PANS presents a diagnostic dilemma for pediatricians, neurologists, and psychiatrists, often mimicking other childhood psychiatric and neurological disorders
Misdiagnosis can lead to delayed or inappropriate treatment, impacting the child's quality of life, academic performance, and family well-being
Understanding these complex conditions is crucial for accurate diagnosis and effective management.
Clinical Presentation
Symptoms:
Abrupt onset of obsessive-compulsive symptoms (OCD)
Severe food restriction or refusal to eat
Sudden emotional lability, including crying spells or irritability
Developmental regression
Sleep disturbances, such as insomnia or hypersomnia
Motor difficulties, including tics or unusual movements
Urinary frequency or urgency
Behavioral symptoms, such as aggression or oppositional behavior
Anxiety or panic attacks
Academic decline.
Signs:
Motor tics (e.g., facial grimacing, shoulder shrugging)
Choreiform movements
Neurological soft signs (e.g., impaired fine motor skills, gait abnormalities)
Signs of an active GAS infection (e.g., pharyngitis, scarlet fever) may be present in PANDAS
Autoinflammatory signs may be observed in some PANS cases.
Diagnostic Criteria:
The original PANDAS criteria required abrupt onset of OCD or tic symptoms, pre-pubertal onset, episodic course of symptoms, association with GAS infection, and acute onset of neurological abnormalities
More recently, the PANS criteria have been proposed, expanding the scope to include acute onset of neuropsychiatric symptoms (including OCD or food restriction) with at least two other symptom categories from a defined list (e.g., anxiety, emotional lability, motor abnormalities)
Diagnosis relies on clinical assessment and ruling out other causes
A definitive diagnostic consensus is still evolving.
Diagnostic Approach
History Taking:
Detailed chronological history of symptom onset and progression
Specific details about the abruptness of symptom onset
History of recent infections, especially GAS (sore throat, rash)
Family history of autoimmune diseases, OCD, tic disorders, or psychiatric conditions
Review of any previous diagnoses and treatments
Inquiry about triggers for symptom exacerbations
Documenting functional impairment (school, social).
Physical Examination:
Comprehensive neurological examination to assess for tics, choreiform movements, or other motor abnormalities
Examination for signs of GAS infection (throat, skin)
General physical examination to identify any underlying systemic illness
Developmental and psychiatric assessment
Screening for signs of anxiety, depression, or mood disorders.
Investigations:
Throat culture or rapid streptococcal antigen detection test for suspected GAS infection
Antistreptolysin O (ASO) titers or anti-DNase B titers to assess for recent GAS infection (elevated titers do not confirm PANDAS, but low or normal titers in the context of clear GAS exposure can be informative)
Complete blood count (CBC) with differential to rule out infection
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess for inflammation
Autoimmune encephalitis antibody panel (e.g., anti-neuronal antibodies like anti-NMDA, anti-CASPR2) may be considered in severe or atypical presentations of PANS
Thyroid function tests
Electroencephalogram (EEG) if seizures are suspected
Neuroimaging (MRI brain) may be used to rule out structural lesions, though typically normal in PANDAS/PANS.
Differential Diagnosis:
Other forms of Obsessive-Compulsive Disorder (OCD)
Tourette Syndrome
Pervasive Developmental Disorders (PDDs)
Autism Spectrum Disorder (ASD)
Attention-Deficit/Hyperactivity Disorder (ADHD)
Childhood-onset Schizophrenia
Bipolar Disorder
Functional Neurological Disorder
Sydenham's chorea
Other autoimmune encephalitis syndromes
PANDAS/PANS can overlap with or be misdiagnosed as these conditions
Distinguishing features include the abrupt onset and episodic nature of symptoms, and the clear association with a trigger in PANDAS.
Management
Initial Management:
Establishing a diagnosis based on clinical criteria
Addressing immediate safety concerns related to behavior or food refusal
Stabilizing mood and anxiety symptoms
Providing supportive care for the child and family
Multidisciplinary team approach involving pediatricians, neurologists, psychiatrists, and therapists.
Medical Management:
Antibiotic therapy (e.g., penicillin, amoxicillin, azithromycin) if an active GAS infection is present or strongly suspected in PANDAS cases
Prophylactic antibiotics may be considered in recurrent PANDAS
Psychotropic medications for symptom control: Selective Serotonin Reuptake Inhibitors (SSRIs) for OCD and anxiety symptoms
Antipsychotics may be used cautiously for severe behavioral disturbances
Mood stabilizers for emotional lability
Immunomodulatory therapies: Intravenous immunoglobulin (IVIG) or plasma exchange (PLEX) are controversial and typically reserved for severe, refractory cases of PANS, with evidence being variable
Steroids (oral or IV) may also be used in specific refractory cases.
Surgical Management:
Not applicable for PANDAS/PANS itself
However, if there are co-occurring conditions requiring surgical intervention, that would be managed separately.
Supportive Care:
Behavioral therapy, including Cognitive Behavioral Therapy (CBT) and exposure and response prevention (ERP) for OCD symptoms
Nutritional support and counseling for food restriction
Educational support and accommodations at school
Parent education and support groups
Management of sleep disturbances
Occupational and physical therapy for motor difficulties.
Controversies
Diagnostic Validity:
The lack of universally accepted diagnostic criteria for PANS remains a major controversy
The broadness of the PANS definition and the reliance on clinical judgment can lead to overdiagnosis or misdiagnosis
The causality of GAS infection in PANDAS is complex, with questions about the precise autoimmune mechanism and the role of antibodies.
Pathophysiological Mechanisms:
The exact pathophysiology is not fully understood
Theories include molecular mimicry (antibodies against streptococcal antigens cross-reacting with basal ganglia), direct autoimmune attack on neuronal structures, or dysregulation of the immune system
The role of autoantibodies and the specific brain regions targeted are subjects of ongoing research.
Treatment Efficacy:
The efficacy of many proposed treatments, especially immunomodulatory therapies like IVIG and plasma exchange, is debated
Evidence from randomized controlled trials is limited and often conflicting
Determining which patients will respond to specific treatments remains challenging
Over-reliance on antibiotics without clear evidence of active infection in PANDAS is also a concern.
Longitudinal Studies:
There is a need for more robust, long-term prospective studies to define the natural history of PANDAS/PANS, identify predictors of prognosis, and evaluate the long-term outcomes of various treatment strategies
Understanding the relationship between PANDAS/PANS and other neurodevelopmental or psychiatric disorders is also crucial.
Key Points
Exam Focus:
Remember PANDAS is a subset of PANS linked to Group A Strep
Key diagnostic features include abrupt onset of OCD or food restriction plus other neuropsychiatric symptoms
Differentiate from primary OCD, Tourette's, and ASD
Consider autoimmune encephalitis panel in severe/atypical PANS.
Clinical Pearls:
Always elicit a detailed history of symptom onset
abruptness is key
Look for recent strep infections in PANDAS
Multidisciplinary management is essential
Be cautious with empiric antibiotic use without clear indication
Individualize treatment based on symptom severity and response.
Common Mistakes:
Failing to consider PANDAS/PANS in children with sudden onset of neuropsychiatric symptoms
Attributing all sudden behavioral changes to psychosocial factors without investigating underlying medical causes
Over-diagnosing PANDAS based solely on elevated ASO titers without clinical correlation
Inappropriately using antibiotics for presumed PANDAS without evidence of active infection.