PANDAS THE OCD/STREP CONNECTION

By Marc W. Reitman, MD

Over the last ten years, there has appeared a mounting body of evidence that suggests there is a small subgroup of individuals whose childhood onset Obsessive-Compulsive Disorders may have been triggered by streptococcal throat infections. This association of an infectious cause with a neurobiological disorder may also be true for tic disorders, such as Tourette's Disorder, Trichotillomania (compulsive hair pulling), and possibly Attention Deficit Hyperactivity Disorder.

These conclusions were drawn from research conducted by Drs. Susan Swedo, Judith Rappaport, and their associates at The National Institute of Mental Health. During the late 1980's, they observed that children with Sydenham's Chorea, the neurobiological manifestation that follows bouts of Rheumatic Fever, had an unusually high percentage of OCD symptoms, including both obsessions and compulsions. Rheumatic Fever is caused by Group A Beta hemolytic streptococcal bacteria, commonly known as strep throat. In a vulnerable subgroup of children, the immune response to the bacteria goes awry, causing the antibodies to mistakenly identify the basal ganglia (an area deep within the brain) as foreign bodies. The basal ganglia then become inflamed as a result of this "mistaken identification." This chain reaction is what is known as an autoimmune response, when the immune system misidentifies an individual's own cells as foreign.

Noting that 70% of Sydenham's Chorea patients have OCD symptoms, Drs. Swedo and Rappaport conducted research of children with sudden onset of OCD, looking for a casual relationship between a strep infection and OCD symptoms. To identify this group of children, the acronym PANDAS was proposed representing Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. The proposed working criteria that has been developed to make a diagnosis of PANDAS include:

• The presence of OCD and/or a tic disorder
• Childhood onset (between the age of 3 and puberty)
• Episodic course (sudden burst of symptoms followed by a gradual decline, then absence of symptoms until the next sudden burst of symptoms)
• The presence of a group A Beta hemolytic streptococcal infection (established by a positive throat culture and/or elevated titer of anti-streptococcal antibodies)
• The presence of abnormal neurological signs

The National Institute of Mental Health group has recently published their findings of 50 children, following them over a 2-year course. The results indicate that these children have typical OCD symptoms but atypical associated features, which would include:

• The onset of symptoms is sudden and dramatic such that parents can frequently recall the date of onset. The usual onset of OCD is more gradual.
• This group of children has an earlier age of onset of symptoms than compared to the usual onset.
• PANDAS children are seen to have complete remissions of symptoms between episodes of symptoms. The non-PANDAS OCD symptoms usually follow a waxing and waning course.
• The presence of accompanying neurological signs such as tics, hyperactivity, or choreiform movements (irregular spasmodic involuntary movements of the limbs or facial muscles) further distinguishes this subgroup of children with OCD.
• Other symptoms can include emotional lability (over reactions to minor events), separation anxiety, nighttime fears and oppositional behaviors.
• Symptoms worsen following a strep infection.

The identification of this subgroup of OCD has advanced our understanding of this disorder by providing evidence through neuroimaging studies of a specific location in the brain and possible causes. Genetic vulnerability in those who develop these symptoms is also being explored. There is a biological marker in certain blood cells that appears to have a higher frequency of expression among children with PANDAS. However, this test is only available in research laboratories and is not commonly used as a diagnostic tool.

Treatments for this type of OCD have included plasma exchange (a filtering of the plasma eliminating antigen/antibody complexes), intravenous immunoglobulin (IVIG), steroids or antibiotics. There is an ongoing study exploring the chronic use of antibiotics to prevent re-infection by strep, which could theoretically avoid further episodes of OCD. The results of this study could help guide clinicians in the treatment of this subgroup of OCD. However, these are no current recommendations that antibiotics should routinely be administered as a formal treatment.

Until more is learned about the outcome of these experimental treatments, it is wise to follow these suggestions for children who may be vulnerable to have PANDAS:

• Treat all strep infection aggressively with antibiotics.
• Be sure to complete the course of antibiotic treatment to avoid development of resistant strains of bacteria.
• Make use of proven therapies such as cognitive/behavioral therapy and serotonin medication (SSRI's) as are utilized to treat the more usual forms of OCD.
• The "quick" strep throat culture is not accurate enough for demonstrating the presence of streptococcal infection. The older method of incubation of a throat swab on agar for 48 hours is far more accurate.
• In addition to throat cultures, there are blood tests that the pediatrician can request to help identify the association of strep infection and exacerbation of symptoms. These include anti-streptolysin O titer and anti-streptococcal DNase B titer.

The current interest about the role of the immune system in neuropsychiatric disorders will increase our understanding of brain functioning and potential treatments for these disorders in children and adults.