PANDAS or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection

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Central nervous system (CNS) disorders associated with group-A beta-hemolytic streptococcal (GABHS) infection have been reported occasionally. Disorders include Sydenham's chorea, tics, obsessive compulsive disorder, and extrapyramidal symptoms. Anecdotal evidence indicates a link between Tourette syndrome and infectious agents including GABHS.

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What is PANDAS?

Such GABHS disorders have been labeled as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) and it is being increasingly recognized as a distinct entity.

PANDAS manifests as a conglomeration of neuropsychiatric symptoms, mainly obsessive-compulsive disorder or tic disorders, temporally associated with an immune-mediated response to GABHS. At the same time, most of the issues about PANDAS have been mired in debate causing confusion and frustration among physicians as parents/patients alike.

Diagnostic criteria

OCD and/or tic disorder like Tourette disorder/syndrome, chronic movement or vocal tic
Onset between the age of 2 years and 13 years of age
Acute onset
Remissions and relapses with waxing/waning course of clinical manifestations
Onset as well as relapses are temporally related to GABHS. GABHS can be documented by positive throat or skin culture or rapid antigen detection test. There is an increase in anti-streptococcal and/or anti-DNaseB antibodies 4 weeks later.
Neuropsychiatric manifestations during relapse include hyperactivity, choreiform movements or tics.

What or How PANDAS occur?

Is It Leaky Gut or Leaky Gut Syndrome?

The pathogenesis is controversial to say the least. The GABHS model implicates the infection leading to an abnormal immune response also known as molecular mimicry of the antibodies. There is cross-reactivity between the host’s antibodies to the streptococcal infection and the body and these antibodies target the body’s own tissues including but limited to the brain. This hypothesis is supported by the following evidence:

Presence of antineuronal antibodies
Increased prevalence of a B-cell surface marker also seen in rheumatic fever which is also associated with streptococcal infections
Resolution of manifestations upon treatment with antibiotics and immune-modifying therapies in many cases.
Data contradicting the above hypothesis include:
Lack of correlation between immunologic markers and relapses
Injection of serum from PANDAS into animla brain fails to alter behavioral changes.

Controversies

Is PANDAS a real distinct entity?
Is relationship with GABHS a causal or coincidental?
Could the relapse related to GABHS be related to stress of sickness and not an abbarrent immune response?

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Antibiotic treatment of PANDAS

Antibiotics treatment is required for GABHS whether or not neuro-psychiatric manifestations of PANDAS are present.
Kids with new onset of PANDAS respond to antibiotic treatment
Use of prophylactic long term antibiotic treatment is controversial

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Immune-modifying therapy of PANDAS

Intravenous immunoglobulin and/or plasma exchange has been used. In the only randomized controlled trial reported to date, Perlmutter and colleagues from the Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, found that plasma exchange as well as intravenous immunoglobulin are both beneficial in reducing the severity symptoms in kids with infection-triggered OCD and tic disorders.

Treatment of neurobehavioral manifestations

OCD and tics should be treated as usual whether or not PANDAS has been diagnosed.

Bottom line

The diagnostic as well as treatment considerations for PANDAS are mired in hot debate; In view of lack of consensus, most of the treatments involving use prophylactic long term antibiotics and/or immune-modulatory therapies in patients with PANDAS is being conducted at highly specialized centers.

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