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postoperatively [3] .
Similarly, Heubi & Shott reported a similar experience with two
siblings; one with Tourette's syndrome (TS) and one with
obsessive-compulsive disorder (OCD) [4]. The child with OCD
discontinued sertraline 1 year postoperatively and no longer
required follow-up with a psychiatrist. The child with TS was
symptom-free 2 months postoperatively and had his clonidine
dosage reduced.
Murphy, Storch et al. examined a cohort of children with OCD
and found that PANDAS cases had a high association of undergoing
surgery compared to those with OCD without PANDAS [5] . Of note,
they also observed that PANDAS subjects were more likely to have
remission of symptoms when receiving antibiotic therapy. In
another study, Murphy, Lewin et al. examined a group of 43
PANDAS patients, 20 of whom had tonsillectomy and/or adenoi-
dectomy [6] . They found no difference in streptococcal titer levels
or symptom severity between the surgical and nonsurgical groups.
Moreover, a majority of the patients had symptom onset more than
2 years after surgery and so the authors concluded that surgery
does not prevent disease onset. This study corroborates the previ-
ous study that those with PANDAS were more likely to have surgery
compared to non-PANDAS subjects with OCD.
In a prospective study of 120 PANDAS patients, 56 underwent
adenotonsillectomy [7] . There were no differences in symptom
severity or titer elevation (i.e. antistreptolysin O, anti-
deoxyribonuclease B, and antineural antibodies) following surgery
compared to the nonsurgical group. Timing of surgery did not affect
time to first relapse (mean ¼ 45.1 ± 17.8 days). The authors
concluded that PANDAS is not an indication for adenotonsillectomy.
Finally, Demesh et al. recently conducted a retrospective review
of 10 PANDAS patients who received antibiotic therapy followed by
tonsillectomy in 9 patients [8] . The parents of the subjects were also
contacted and administered a questionnaire regarding the severity
of their child's symptoms. Half of the children responded to anti-
biotic treatment per the parents but symptom resolution was not
noted. All nine children who underwent tonsillectomy were noted
to have symptom improvement with 3 experiencing complete
resolution of OCD symptoms. However, the retrospective nature of
the study and post-treatment screening limit the conclusions, as
the interpreted results are susceptible to recall bias.
3.2. Antibiotic therapy
Three articles were selected involving the use of antibiotic
therapy (ABX) [10e12]. In a double-blind randomized control trial
(DB RCT), 37 patients were given oral penicillin V or placebo fol-
lowed by crossover after 4 months [10]. The authors found no dif-
ference in infection rate or symptom severity by treatment phase.
Sixteen of the children were also on neuropsychiatric medications
at various points during the study.
One prospective study evaluated antibiotic therapy for acute
infections and exacerbations in 12 patients over a 3-year period
[11]. Antibiotics (either penicillins or cephalosporins) for treatment
of GABHS infection alleviated neuropsychiatric symptoms,
although half of the patients experienced a recurrence in symp-
toms. Again, when the recurrence was treated with antibiotics
there was improvement in symptoms.
One DB RCT examined the utility of azithromycin or penicillin
prophylaxis in a PANDAS cohort of 23 patients [12] . The patients
served as their own controls and decreased rates of infection and
neuropsychiatric exacerbations were noted in both groups
compared to pretreatment. A limitation of this study was retro-
spective collection of medical history.
Finally, a case report of 2 patients that received benzathine
penicillin showed potential benefit of antibiotics [13]. One 9 year
old patient who had a favorable response received monthly in-
jections. The dosing frequency was tapered over time, and the
patient was symptom-free at 16 years of age. Another showed
improvement but was eventually lost to follow up after 6
months.
3.3. Intravenous immunoglobulin therapy
Two selected articles described the use of IVIG: one RCT and one
retrospective study [14,15]. Perlmutter et al. in a partially DB RCT,
examined the efficacy of IVIG or plasma exchange [14] . In-
vestigators and participants were blinded if IVIG or placebo was
administered, but not plasma exchange. Both treatment groups
showed significant improvement compared to the placebo group at
1 month and 1 year follow up. Adverse events reported included
headache, fever, pallor, dizziness, nausea, and vomiting.
Later, Kovacevic et al. retrospectively presented 12 patients that
received IVIG [15] . Follow up ranged from 4 months to 7 years and
patients reported significant improvement or complete recovery in
all instances. Several patients were also on antibiotic prophylaxis.
Additionally, seven patients were retreated with a second course of
IVIG due to recurrence or no response to initial treatment with a
noted improvement in symptoms.
3.4. Cognitive behavioral therapy
One prospective study examined cognitive-behavioral therapy
(CBT) in seven patients, with 6 concurrently taking selective sero-
tonin reuptake inhibitors (SSRIs) [16]. Subjects underwent 3 weeks
of intensive CBT and were evaluated at 4 weeks prior to treatment,
before the first session, before the final session, and 3 months after
the final session. There was significant and sustained reduction in
symptom severity, however 2 patients experienced complete
relapse and one partial relapse.
4. Discussion
This systematic review examined treatment modalities for a rare
pediatric disease occasionally evaluated by an Otolaryngologist.
The pathophysiology of this disease is still poorly understood,
though it has been likened to Sydenham's chorea given the com-
mon link with GABHS. Autoimmune theories propose molecular
mimicry in which an acute infection triggers the generation of
antineuronal antibodies that cross-react with the basal ganglia [17].
However, such antibodies have not been demonstrated and used to
identify patients with PANDAS [18,19]. Other alterations in the
immune system are also debatable as one study recently demon-
strated distinct differences in cytokine levels among these patients
[20]. Another found no differences in B-Cell expression between
the tonsils of PANDAS and non-PANDAS patients [21] . In light of
these findings, it is still difficult to establish a true immunologic
link.
Most of the included studies graded symptom severity using a
variety of scales, including the Yale Global Tic Severity Scale
(YGTSS) and the Yale-Brown Obsessive Compulsive Scale (YBOCS).
Some studies used questionnaires that were more arbitrary and
asked the parents their overall perception of their child's well-
being. Others simply reported whether the child continued to
experience symptoms. The YGTSS or YBOCS would be the most
appropriate tools to use in symptom evaluation, as they are quite
reliable and valid, although they may not be readily familiar to
Otolaryngologists [22,23].
The benefit of tonsillectomy is uncertain due to conflicting re-
sults. In theory, removing the tonsils would serve to reduce the rate
of infection and therefore exacerbation frequency. Overall,
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