Arnold, Paul D., Richter, Margaret A.
disorder an autoimmune disease?
CMAJ 2001 165: 1353-1358
DISORDER (OCD) IS A COMMON and debilitating neuropsychiatric disorder. Although
it is widely believed to have a genetic basis, no specific genetic factors have
been conclusively identified as yet, leading researchers to look for environmental
risk factors that may interact with an underlying genetic susceptibility in affected
individuals. Recently, there has been increasing interest in a possible link between
streptococcal infections and the development of OCD and tic disorders in children.
It has been suggested that OCD in some susceptible individuals may be caused by
an autoimmune response to streptococcal infections, that is, a similar biological
mechanism to that associated with Sydenham's chorea. The term "pediatric
autoimmune neuropsychiatric disorders associated with streptococcal infections"
(PANDAS) has been used to describe a subset of children with abrupt onset or exacerbations
of OCD or tics, or both, following streptococcal infections. Affected children
have relatively early symptom onset, characteristic comorbid symptoms and subtle
neurological dysfunction. Neuroimaging studies reveal increased basal ganglia
volumes, and the proposed cause involves the cross-reaction of streptococcal antibodies
with basal ganglia tissue. Vulnerability to developing PANDAS probably involves
genetic factors, and elevated levels of D8/17 antibodies may represent a marker
of susceptibility to PANDAS. Prophylactic antibiotic treatments have thus far
not been shown to be helpful in preventing symptom exacerbations. Intravenous
immunoglobulin therapy may be an effective treatment in selected individuals.
Further understanding of the role of streptococcal infections in childhood-onset
OCD will be important in determining alternative and effective strategies for
treatment, early identification and prevention of this common and debilitating
psychiatric disorder." [Full
Hoekstra PJ, Kallenberg CG, Korf J, Minderaa
Is Tourette's syndrome an autoimmune disease?
"We provide a review of recent research
findings which support the involvement of autoimmunity in childhood-onset tic
disorders, in particular the presence of antineuronal autoantibodies, D8/17 B
lymphocyte overexpression, a marker of chorea associated with streptococcal infection,
and possible beneficial effects of immunomodulatory intervention. One of the most
controversial areas in this field is the validity of the proposed PANDAS concept.
Some researchers have delineated a putatively unique subgroup of patients, from
the spectrum of illness encompassing Tourette's syndrome and obsessive-compulsive
disorder (OCD), whose tics and obsessive-compulsive symptoms are shown to arise
in response to beta-hemolytic streptococcal infections. They designated it by
the term pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infections (PANDAS). Herein we additionally present pros and cons concerning the
concept of PANDAS. Finally, recommendations for future research directions are
LA, Swedo SE.
Post-streptococcal autoimmune disorders of the central
Curr Opin Neurol. 2003 Jun;16(3):359-65.
OF REVIEW: Autoimmune disease has long been intertwined with investigations of
infectious causes. Antibodies that are formed against an infectious agent can,
through the process of molecular mimicry, also recognize healthy cells. When this
occurs, the immune system erroneously destroys the healthy cells causing autoimmune
disease in addition to appropriately destroying the offending infectious agent
and attenuating the infectious process. The first infectious agent shown to cause
a post-infectious autoimmune disorder in the central nervous system was Streptococcus
pyogenes in Sydenham's chorea. The present review summarizes the most recent published
findings of central nervous system diseases that have evidence of a post-streptococcal
autoimmune etiology. RECENT FINDINGS: Sydenham's chorea and other central nervous
system illnesses that are hypothesized to have a post-streptococcal autoimmune
etiology appear to arise from targeted dysfunction of the basal ganglia. PANDAS
(pediatric autoimmune disorders associated with streptococcal infections) is the
acronym applied to a subgroup of children with obsessive-compulsive disorder or
tic disorders occurring in association with streptococcal infections. In addition,
there are recent reports of dystonia, chorea encephalopathy, and dystonic choreoathetosis
occurring as sequelae of streptococcal infection. Investigators have begun to
isolate and describe antistreptococcal-antineuronal antibodies as well as possible
genetic markers in patients who are susceptible to these illnesses. SUMMARY: Clinical
and research findings in both immunology and neuropsychiatry have established
the existence of post-streptococcal neuropsychiatric disorders and are beginning
to shed light on possible pathobiologic processes." [Abstract]
TK, Sajid M, Soto O, Shapira N, Edge P, Yang M, Lewis MH, Goodman WK.
pediatric autoimmune neuropsychiatric disorders associated with streptococcus
in children with obsessive-compulsive disorder and tics.
Psychiatry. 2004 Jan 1;55(1):61-8.
"BACKGROUND: A subgroup of children
with obsessive-compulsive and tic disorders are proposed to have an infectious
trigger. The purpose of this study was to investigate the relationship between
group A streptococcal titers and symptom fluctuations in children with a clinical
course resembling that described for pediatric autoimmune neuropsychiatric disorders
associated with streptococcus. METHODS: Twenty-five children with obsessive-compulsive
disorder and/or tic disorder were evaluated for neuropsychiatric severity and
group A streptococcal antibody titers (streptolysin O, deoxyribonuclease B, and
carbohydrate A) at 6-week intervals for > or = six consecutive evaluations
(total visits=277). RESULTS: Children with large symptom fluctuations (n=15) were
compared with children without dramatic fluctuations (n=10). Co-movements of obsessive-compulsive/tic
severity and group A streptococcal antibodies were assessed. In subjects with
large symptom changes, positive correlations were found between streptococcal
titers and obsessive-compulsive severity rating changes (p=.0130). These subjects
were also more likely to have elevated group A streptococcal titers during the
majority of observations (p=.001). Tic symptom exacerbations occurred more often
in the fall/winter months than spring/summer months (p=.03). CONCLUSIONS: Patients
with marked obsessive-compulsive/tic symptom changes may be characterized by streptococcal
titer elevations and exhibit evidence of seasonal tic exacerbations." [Abstract]
TK, Benson N, Zaytoun A, Yang M, Braylan R, Ayoub E, Goodman WK.
toward analysis of D8/17 binding to B cells in children with obsessive compulsive
disorder and/or chronic tic disorder.
J Neuroimmunol. 2001
"BACKGROUND: Previous research has suggested that
a subgroup of children with obsessive compulsive disorder (OCD) have neuropsychiatric
sequelae of streptococcal pharyngitis, similar to that seen in the neurological
manifestation of rheumatic fever (RF). Monoclonal antibody D8/17 demonstrates
increased binding to B cells in patients with RF and in patients with neuropsychiatric
disorders using immunofluorescent microscopy. OBJECTIVE: The aim of this study
was to determine if an earlier immunofluorescent microscopy study of monoclonal
antibody D8/17 in childhood-onset OCD and/or chronic tic disorder (CTD) could
be replicated using the more objective method of flow cytometric analysis. METHOD:
D8/17 binding to B cells was determined in patients with OCD and or CTD (N=32),
and healthy controls (N=12) by flow cytometric analysis. RESULTS: Subjects with
OCD/CTD showed increased mean cell binding (26.0%) of monoclonal antibody compared
with healthy controls (9.1%) (p<0.001). When using the threshold of greater
than 19% binding (95% upper confidence interval) as a measure of positivity, 65.6%
of patients compared with 8.3% of controls showed increased antibody binding to
B cells (p=0.01). CONCLUSIONS: Although this study reports positive results, many
methodological issues will need to be addressed before generalized use of assay
for diagnostic purposes." [Abstract]
TK, Goodman, WK, Fudge, MW, Williams, RC, Jr, Ayoub, EM, Dalal, M, Lewis, MH,
B lymphocyte antigen D8/17: a peripheral marker for
childhood-onset obsessive-compulsive disorder and Tourette's syndrome?
J Psychiatry 1997 154: 402-407
"OBJECTIVE: It has been hypothesized that
Sydenham's chorea, a major manifestation of rheumatic fever, may provide a medical
model for obsessive-compulsive disorder and associated conditions, such as Tourette's
syndrome. Monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded
expression in nearly all patients with rheumatic fever and is thought to be a
trait marker for susceptibility to this complication of group A streptococcal
infection. The authors investigated whether D8/17 expression is greater than normal
in some forms of obsessive-compulsive disorder and Tourette's syndrome. METHOD:
By immunofluorescence techniques, 31 patients with childhood-onset obsessive-compulsive
disorder and/or Tourette's syndrome or chronic tic disorder and 21 healthy comparison
subjects were evaluated for percentage of D8/17-positive B cells. None had rheumatic
fever or Sydenham's chorea. Levels of antineuronal antibodies and streptococcal
antibodies were also determined. RESULTS: The average percentage of B cells expressing
the D8/17 antigen was significantly higher in the patients (mean = 22%, SD = 5%)
than in the comparison subjects (mean = 9%, SD = 2%). When classified categorically,
all patients but only one comparison subject were D8/17 positive. No difference
between groups in the presence of antineuronal antibodies or high streptococcal
titers was found. CONCLUSIONS: Patients with childhood-onset obsessive-compulsive
disorder or Tourette's syndrome had significantly greater B cell D8/17 expression
than comparison subjects despite the absence of documented Sydenham's chorea or
rheumatic fever. These findings suggest that D8/17 may serve as a marker for susceptibility
among some forms of childhood-onset obsessive-compulsive disorder and Tourette's
syndrome, as well as rheumatic fever or Sydenham's chorea." [Abstract]
SE, Leonard, HL, Mittleman, BB, Allen, AJ, Rapoport, JL, Dow, SP, Kanter, ME,
Chapman, F, Zabriskie, J
Identification of children with pediatric
autoimmune neuropsychiatric disorders associated with streptococcal infections
by a marker associated with rheumatic fever
Am J Psychiatry
1997 154: 110-112
"OBJECTIVE: The authors' goal was to determine whether
a trait marker of rheumatic fever susceptibility (labeled D8/17) could identify
children with pediatric autoimmune neuropsychiatric disorders (obsessive-compulsive
disorder and tic disorders) associated with streptococcal infections (PANDAS).
METHOD: Blood samples obtained from 27 children with PANDAS, nine children with
Sydenham's chorea, and 24 healthy children were evaluated for D8/17 reactivity.
Individuals were defined as D8/17 positive if they had 12% or more D8/17+ cells.
RESULTS: The frequency of D8/17-positive individuals was significantly higher
in both patient groups than it was among the healthy volunteers: 85% of the children
with PANDAS and 89% of the children with Sydenham's chorea, compared with 17%
of the healthy children, were D8/17 positive. Further, the mean number of D8/17+
cells was similar in the two patient groups and was significantly higher in these
groups than in the group of healthy children. CONCLUSIONS: These results suggest
that there may be a subgroup of D8/17-positive children who present with clinical
symptoms of obsessive-compulsive disorder and Tourette's syndrome, rather than
Sydenham's chorea, but who have similar poststreptococcal autoimmunity."
Susan E., Leonard, Henrietta L., Garvey, Marjorie, Mittleman, Barbara, Allen,
Albert J., Perlmutter, Susan, Dow, Sara, Zamkoff, Jason, Dubbert, Billinda K.,
Pediatric Autoimmune Neuropsychiatric Disorders
Associated With Streptococcal Infections: Clinical Description of the First 50
Am J Psychiatry 1998 155: 264-271
The purpose of this study was to describe the clinical characteristics of a novel
group of patients with obsessive-compulsive disorder (OCD) and tic disorders,
designated as pediatric autoimmune neuropsychiatric disorders associated with
streptococcal (group A beta-hemolytic streptococcal [GABHS]) infections (PANDAS).
METHOD: The authors conducted a systematic clinical evaluation of 50 children
who met all of the following five working diagnostic criteria: presence of OCD
and/or a tic disorder, prepubertal symptom onset, episodic course of symptom severity,
association with GABHS infections, and association with neurological abnormalities.
RESULTS: The children's symptom onset was acute and dramatic, typically triggered
by GABHS infections at a very early age (mean = 6.3 years, SD = 2.7, for tics;
mean = 7.4 years, SD = 2.7, for OCD). The PANDAS clinical course was characterized
by a relapsing-remitting symptom pattern with significant psychiatric comorbidity
accompanying the exacerbations; emotional lability, separation anxiety, nighttime
fears and bedtime rituals, cognitive deficits, oppositional behaviors, and motoric
hyperactivity were particularly common. Symptom onset was triggered by GABHS infection
for 22 (44%) of the children and by pharyngitis (no throat culture obtained) for
14 others (28%). Among the 50 children; there were 144 separate episodes of symptom
exacerbation; 45 (31%) were associated with documented GABHS infection, 60 (42%)
with symptoms of pharyngitis or upper respiratory infection (no throat culture
obtained), and six (4%) with GABHS exposure. CONCLUSIONS: The working diagnostic
criteria appear to accurately characterize a homogeneous patient group in which
symptom exacerbations are triggered by GABHS infections. The identification of
such a subgroup will allow for testing of models of pathogenesis, as well as the
development of novel treatment and prevention strategies." [Abstract]
ML, Pichichero ME.
Prospective identification and treatment of children
with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal
Arch Pediatr Adolesc Med. 2002 Apr;156(4):356-61.
The current diagnostic criteria for pediatric autoimmune neuropsychiatric disorder
associated with group A streptococcal infection (PANDAS) are pediatric onset,
neuropsychiatric disorder (obsessive-compulsive disorder [OCD]) and/or tic disorder;
abrupt onset and/or episodic course of symptoms; association with group A beta-hemolytic
streptococcal (GABHS) infection; and association with neurological abnormalities
(motoric hyperactivity or adventitious movements, including choreiform movements
or tics). OBJECTIVE: To assess new-onset PANDAS cases in relation to acute GABHS
tonsillopharyngitis. DESIGN: Prospective PANDAS case identification and follow-up.
RESULTS: Over a 3-year period (1998-2000), we identified 12 school-aged children
with new-onset PANDAS. Each patient had the abrupt appearance of severe OCD behaviors,
accompanied by mild symptoms and signs of acute GABHS tonsillopharyngitis. Throat
swabs tested positive for GABHS by rapid antigen detection and/or were culture
positive. The GABHS serologic tests, when performed (n = 3), showed very high
antideoxyribonuclease antibody titers. Mean age at presentation was 7 years (age
range, 5-11 years). In children treated with antibiotics effective in eradicating
GABHS infection at the sentinel episode, OCD symptoms promptly disappeared. Follow-up
throat cultures negative for GABHS were obtained prospectively after the first
PANDAS episode. Recurrence of OCD symptoms was seen in 6 patients; each recurrence
was associated with evidence of acute GABHS infection and responded to antibiotic
therapy, supporting the premise that these patients were not GABHS carriers. The
OCD behaviors exhibited included hand washing and preoccupation with germs, but
daytime urinary urgency and frequency without dysuria, fever, or incontinence
were the most notable symptoms in our series (58% of patients). Symptoms disappeared
at night, and urinalysis and urine cultures were negative. CONCLUSION: To our
knowledge, this is the first prospective study to confirm that PANDAS is associated
with acute GABHS tonsillopharyngitis and responds to appropriate antibiotic therapy
at the sentinel episode." [Abstract]
RR, Packard AM.
Immune mechanisms in pediatric neuropsychiatric disorders.
Tourette's syndrome, OCD, and PANDAS.
Child Adolesc Psychiatr
Clin N Am. 1999 Oct;8(4):767-75.
"The authors have reviewed recent data
supporting the presence of immune abnormalities in several neuropsychiatric disorders
(TS, OCD, and PANDAS). Several groups agree that there is a subset of patients
with TS and OCD (perhaps about 10%) for whom there is a clear streptococcal trigger,
validating the PANDAS concept. Also, evidence of biochemical markers for TS and
OCD have begun to emerge, namely D8/17 and antibrain antibodies, which suggest
the presence of similar immune abnormalities, even in idiopathic cases. If this
line of research reveals definable, and relatively specific, immune abnormalities
in at least some cases of TS and OCD, it will likely have important implications
for the diagnosis and treatment of these common neuropsychiatric disorders, particularly
in children who respond poorly to conventional therapies. Child psychiatrists
are encouraged to stay tuned." [Abstract]
F, Hantouche EG, Karila L, Bayart D, Bailly D.
disorder in children induced by streptococcal infection]
Med. 2001 Nov 24;30(35):1747-51.
"FROM OBSESSIVE-COMPULSIVE DISORDER TO
PANDAS: Obsessive-compulsive disorder (OCD) represents a potentially severe and
handicapping disorder that affects several hundreds of thousands of children in
France. OCD has, for many years, been considered as a neurosis resulting from
mental conflicts. It is currently seen as a neurobiological disorder, the etiological
substratum of which is more organic than mental. Recently a sub-type of OCD was
isolated in children following infection by Group A b-hemolytic streptococci.
This sub-type has been described as Paediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (PANDAS). A NEW PHYSIOPATHOLOGICAL APPROACH:
The putative dysimmune relationship between bacterial infection and neurotic disorder
has led to the development of an original etiopathogenic model that may lead to
new therapeutic strategies. The clinical case report of an adolescent presenting
with trichotillomania associated with recurrent pharyngitis is a good illustration
of this. PUBLISHED DATA: Data published in medical literature over the last 10
years indicates a 10% prevalence in the young suffering from OCD, i.e. 0.1 to
0.3% of the young population." [Abstract]
Leonard HL, Swedo SE.
neuropsychiatric disorders associated with streptococcal infection (PANDAS).
J Neuropsychopharmacol. 2001 Jun;4(2):191-8.
"The evidence to date, both
published and unpublished, which addresses the validity of the proposed unique
subgroup of children with early and abrupt onset of obsessive--compulsive disorder
(OCD) and/or tic disorders subsequent to streptococcal infections was reviewed.
The aetiology of OCD and tic disorders is unknown, although it appears that both
disorders may arise from a variety of genetic and environmental factors. Post-streptococcal
autoimmunity has been postulated as one possible mechanism for some. The acronym
PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal
infections) has been given to a subgroup of paediatric patients who meet five
inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom
onset, sudden onset or episodic course of symptoms, temporal association between
streptococcal infections and neuropsychiatric symptom exacerbations, and associated
neurological abnormalities. The proposed model of pathophysiology provides for
several unique treatment strategies, including the use of antibiotic prophylaxis
to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory
interventions (such as intravenous immunoglobulin or therapeutic plasma exchange)
in the treatment severe neuropsychiatric symptoms. For the latter study group,
long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority
of patients, particularly when antibiotic prophylaxis had been effective in preventing
recurrent streptococcal infections. In addition, the episodic nature of the subgroup's
illness provides for opportunities to study brain structure and function during
health and disease, as well as allowing for investigations of the aetiologic role
of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders.
Although much research remains to be done, an increasing body of evidence provides
support for the postulate that OCD and tic disorders may arise from post-streptococcal
autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the
presence of volumetric changes in the basal ganglia, and the dramatic response
to immunomodulatory treatments, suggest that symptoms arise from a combination
of local, regional and systemic dysfunction. Ongoing research is directed at understanding
the nature of the abnormal immune response, as well as identifying at-risk children,
in order to provide for novel strategies of prevention and treatment." [Abstract]
Nicolson R, Swedo SE, Lenane M, Bedwell J, Wudarsky
M, Gochman P, Hamburger SD, Rapoport JL.
An open trial of plasma
exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal
J Am Acad Child Adolesc Psychiatry. 2000
"Patients with childhood-onset obsessive-compulsive
disorder (OCD) with symptom exacerbations following streptococcal infections benefit
from treatment with plasma exchange. In this study, 5 patients with treatment-refractory
OCD without a history of streptococcus-related exacerbations underwent an open
2-week course of therapeutic plasma exchange. Behavioral ratings, completed at
baseline and 4 weeks after the initial treatment, included the Clinical Global
Impressions Scale and the Yale-Brown Obsessive Compulsive Scale. All 5 patients
completed the trial with few side effects, but none showed significant improvement.
Plasma exchange does not benefit children and adolescents with OCD who do not
have streptococcus-related exacerbations." [Abstract]
SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, Swedo SE.
plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder
and tic disorders in childhood.
Lancet. 1999 Oct 2;354(9185):1153-8.
In children, exacerbations of tics and obsessive symptoms may occur after infection
with group A beta-haemolytic streptococci. If post-streptococcal autoimmunity
is the cause of the exacerbations, then children might respond to immunomodulatory
treatments such as plasma exchange or intravenous immunoglobulin (IVIG). We studied
whether plasma exchange or IVIG would be better than placebo (sham IVIG) in reducing
severity of neuropsychiatric symptoms. METHODS: Children with severe, infection-triggered
exacerbations of obsessive-compulsive disorder (OCD) or tic disorders, including
Tourette syndrome, were randomly assigned treatment with plasma exchange (five
single-volume exchanges over 2 weeks), IVIG (1 g/kg daily on 2 consecutive days),
or placebo (saline solution given in the same manner as IVIG). Symptom severity
was rated at baseline, and at 1 month and 12 months after treatment by use of
standard assessment scales for OCD, tics, anxiety, depression, and global function.
FINDINGS: 30 children entered the study and 29 completed the trial. Ten received
plasma exchange, nine IVIG, and ten placebo. At 1 month, the IVIG and plasma exchange
groups showed striking improvements in obsessive-compulsive symptoms (mean improvement
on children's Yale-Brown obsessive compulsive scale score of 12 [45%] and 13 [58%],
respectively), anxiety (2.1 [31%] and 3.0 [47%] improvement on National Institute
of Mental Health anxiety scale), and overall functioning (2.9 [33%] and 2.8 [35%]
improvement on National Institute of Mental Health global scale). Tic symptoms
were also significantly improved by plasma exchange (mean change on Tourette syndrome
unified rating scale of 49%). Treatment gains were maintained at 1 year, with
14 (82%) of 17 children "much" or "very much" improved over
baseline (seven of eight for plasma exchange, seven of nine for IVIG). INTERPRETATION:
Plasma exchange and IVIG were both effective in lessening of symptom severity
for children with infection-triggered OCD and tic disorders. Further studies are
needed to determine the active mechanism of these interventions, and to determine
which children with OCD and tic disorders will benefit from immunomodulatory therapies."
AJ, Leonard HL, Swedo SE.
Case study: a new infection-triggered,
autoimmune subtype of pediatric OCD and Tourette's syndrome.
Am Acad Child Adolesc Psychiatry. 1995 Mar;34(3):307-11.
"A review of
clinical observations and literature reports leads to the hypothesis that, via
a process analogous to Sydenham's chorea, infections with group A beta-hemolytic
streptococci, among others, may trigger autoimmune responses that cause or exacerbate
some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders
(including Tourette's syndrome). If this hypothesis is correct, then immunological
treatments should lead to decreased symptoms in some cases. Four cases with abrupt,
severe onset or worsening of OCD or tics are presented from an open treatment
study. All were boys aged 10 to 14 years. One had OCD, one had Tourette's syndrome,
and two had both OCD and Tourette's syndrome. Clinically and on standardized rating
scales, their symptoms were in the moderate to very severe range. Two had evidence
of recent group A beta-hemolytic streptococci infections, and the others had histories
of recent viral illnesses. Two were treated with plasmapheresis, one with intravenous
immunoglobulin, and one with immunosuppressive doses of prednisone. All had a
clinically significant response immediately after treatment. Diagnostic criteria
are provided that describe these cases of pediatric, infection-triggered, autoimmune
neuropsychiatric disorders (PITANDs). Suggestions are made regarding the evaluation
and management of patients who may have this condition." [Abstract]
N, Riedel M, Erfurth A, Moller HJ.
[Immunoglobulin therapy in Gilles
de la Tourette syndrome]
Nervenarzt. 1997 Nov;68(11):914-6.
has known for a long time that Sydenham's chorea and tics, as seen in Gilles de
la Tourette's syndrome (GTS), are phenomenologically very similar. Tics may occur
as symptoms of acute Sydenham's chorea or persist over years as residual symptoms.
Investigating of children suffering from GTS, including obsessive-compulsive symptoms,
have provided signs of a poststreptococcal autoimmune process but also shown that
treatment based on immunological interventions has been effective. We treated
a 14-year-old boy showing all diagnostic criteria of GTS, familial susceptibility,
and an increase in the antibody titer of streptococcal antigens with 75 immunoglobulins
i.v. over 5 days. Response to this therapy was good regarding motor tics, vocal
tics, and behavioral symptoms such as disturbed impulse control which still persisted
after 9 months. These findings and the successful therapy underline reports of
the literature and point to a pathogenetic mechanism of an immunologically triggered
disturbance of the striatal dopaminergic system, at least in a subgroup of GTS."
MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, Witowski ME, Dubbert
B, Swedo SE.
A pilot study of penicillin prophylaxis for neuropsychiatric
exacerbations triggered by streptococcal infections.
Psychiatry. 1999 Jun 15;45(12):1564-71.
"BACKGROUND: Some children with
obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations
triggered by group A beta-hemolytic streptococcal infections in a manner that
is similar to rheumatic fever and its neurologic variant, Sydenham's chorea. Because
penicillin prophylaxis has proven to be effective in preventing recurrences of
rheumatic fever, it was postulated that it might also prevent streptococcal-triggered
neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric
Disorders Associated with Streptococcal infections (PANDAS). These children are
identified by five clinical characteristics: presence of OCD or tic disorder,
prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform
movements) and streptococcal-triggered symptom exacerbations. METHODS: Thirty-seven
children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over
study. Patients were randomized to receive either 4 months of the active compound
(twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo
followed by penicillin V. Tic, OCD, and other psychiatric symptoms were monitored
monthly. Throat cultures and streptococcal antibody titers were also obtained.
RESULTS: There were an equal number of infections in both the active and placebo
phases of the study. There was no significant change seen in either the obsessive-compulsive
or tic symptom severity between the two phases. CONCLUSIONS: Because of the failure
to achieve an acceptable level of streptococcal prophylaxis, no conclusions can
be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing
tic or OCD symptom exacerbations. Future studies should employ a more effective
prophylactic agent, and include a larger sample size." [Abstract]
WM, Harris CL, McGonigal KM, Raynard RC.
Int J Psychiatry Med. 2001;31(3):311-20.
A postinfectious, autoimmune response may be associated with the development of
pediatric obsessive-compulsive disorder (OCD). According to this model, antistreptococcal
antibodies cross-react with basal ganglia neurons following streptococcus infection.
This autoimmune reaction disrupts a basal ganglia-thalamocortical circuit and
generates obsessive-compulsive symptoms. One implication of this model is that
prolonged immunologic stress may be a risk factor for OCD. That is, immunologic
stress may compromise the blood-brain barrier and permit the influx of antistriatal
antibodies into the central nervous system. This article explores one part of
this putative relationship by investigating whether adult OCD patients, compared
to members of other psychiatric groups, demonstrate a higher incidence of recurrent
infections and other conditions suggestive of compromised immune function. METHOD:
To test this hypothesis, we conducted a medical records review of 100 consecutive
patients evaluated at a private psychiatric clinic specializing in the treatment
of anxiety disorders. Sixty-five patients met diagnostic criteria for an Axis-I
syndrome. Primary diagnoses included OCD, posttraumatic stress disorder, social
anxiety disorder, generalized anxiety disorder, panic disorder with agoraphobia,
and dysthymic disorder. Each medical record was reviewed for the presence of target
syndromes or presenting symptoms suggestive of compromised immune function. RESULTS:
Chart review revealed an increased rate of immune-related symptoms and syndromes
among OCD patients in comparison to other anxiety and mood disorder groups. Groups
did not differ significantly in the incidence of non-immune symptoms and syndromes.
CONCLUSION: Adult OCD patients appear to have an increased rate of immune-related
diseases above and beyond that seen in other psychiatric disorders." [Abstract]
JL, Lamke GT, Walikonis JE.
Serologic survey of adult patients with
obsessive-compulsive disorder for neuron-specific and other autoantibodies.
Res. 1998 Dec 14;81(3):371-80.
"A subset of patients with pediatric onset
obsessive-compulsive disorder (OCD) and tic syndromes (e.g. Tourette's syndrome)
have symptom onset or exacerbation associated with infection. Some of these patients
have been demonstrated to have antineuronal antibodies reactive with nuclei of
the basal ganglion. It has been hypothesized that these patients have an immune
process initiated by infection that affects the basal ganglion and causes obsessive-compulsive
symptoms. The term pediatric autoimmune neuropsychiatric disorders associated
with streptococcal infections (PANDAS) has been coined to describe those patients
with evidence of recent group A beta hemolytic streptococcal infection. We tested
the serum from 13 adult patients with obsessive-compulsive disorder for panels
of autoantibodies that serve as markers of autoimmunity in the practice of neurology
and internal medicine. We investigated the frequency of neuron-specific autoantibodies
[N-type and P/Q-type voltage-gated calcium channel antibodies, type 1 Purkinje
cell antibodies, types 1 and 2 antineuronal nuclear antibodies, amphiphysin antibodies,
and glutamic acid decarboxylase (65 kDa) antibodies], other organ-specific autoantibodies
(muscle acetylcholine receptor-binding antibodies, striated muscle antibodies,
thyroid microsomal and thyroglobulin antibodies), and non-organ-specific autoantibodies
(antinuclear antibodies, antimitochondrial antibodies, and smooth muscle antibodies)
to determine if any of these antibodies might serve as a serological marker for
adult OCD or yield evidence of an autoimmune diathesis. Although most of our subjects
had onset of OCD before 19 years of age (N=8) or before puberty (N=4), the study
revealed no humoral evidence of autoimmunity involving the neuron-, organ-, and
non-organ-specific antibodies that we assayed." [Abstract]
Autoimmunity and the basal ganglia: new insights into old diseases
2003 96: 183-191
"Sydenham's chorea (SC) occurs weeks or months after
Group A streptococcal infection, and is characterized by involuntary, purposeless
movements of the limbs, in addition to behavioural alteration. There is a body
of evidence which suggests that SC is an immune-mediated brain disorder with regional
localization to the basal ganglia. Recent reports have suggested that the spectrum
of post-streptococcal CNS disease is broader than chorea alone, and includes other
hyperkinetic movement disorders (tics, dystonia and myoclonus). In addition, there
are high rates of behavioural sequelae, particularly emotional disorders such
as obsessive-compulsive disorder, anxiety and depression. These findings have
lead to the hypothesis that similar immune-mediated basal ganglia processes may
be operating in common neuropsychiatric disease such as tic disorders, Tourette
syndrome and obsessive-compulsive disorder. This review analyses the historical
aspects of post-streptococcal CNS disease, and the recent immunological studies
which have addressed the hypothesis that common neuropsychiatric disorders may
be secondary to basal ganglia autoimmunity." [Abstract]
TK, Goodman WK, Ayoub EM, Voeller KK.
On defining Sydenham's chorea:
where do we draw the line?
Biol Psychiatry. 2000 May 15;47(10):851-7.
chorea (SC) is a major manifestation of rheumatic fever characterized by an array
of neuropsychiatric symptoms that vary in severity, timing, and character. Some
of the same symptoms are seen in Tourette's syndrome and childhood-onset obsessive-compulsive
disorder. Genetic vulnerability appears to play a role in all three conditions.
The term PANDAS (pediatric autoimmune neuropsychiatric disorder associated with
streptococcus) has been introduced to describe a putative subset of obsessive-compulsive
disorder and Tourette's syndrome that bears some resemblance to Sydenham's chorea.
This article discusses whether PANDAS should be subsumed under Sydenham's chorea,
thus expanding the diagnostic boundaries of Sydenham's chorea to include primarily
neuropsychiatric presentations now classified as cases of obsessive-compulsive
disorder or Tourette's syndrome. We conclude that PANDAS is a useful construct,
but that it would be premature to view it as a subset of Sydenham's chorea-whether
defined narrowly or broadly." [Abstract]
FR, Ramos RT, Negrao AB, Gentil V.
Case series: increased vulnerability
to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea.
Am Acad Child Adolesc Psychiatry. 1999 Dec;38(12):1522-5.
between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports
the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated
with group A beta-hemolytic streptococcal infection underlying both conditions.
Four children with 2 distinct SC episodes were evaluated to assess the course
of OCS. All patients developed OCS during their second episodes (3 met criteria
for obsessive-compulsive disorder [OCD]), but not in their first episodes (2 developed
OCS and met criteria for OCD). These data suggest that the recurrence of SC episodes
may result in a cumulative effect, thus increasing the risk of appearance and
intensification of OCS." [Abstract]
A, Topcuoglu V, Yazgan MY.
[Acute Rheumatic Fever, Sydenham's Chorea
Turk Psikiyatri Derg. 2002 Summer;13(2):137-41.
rheumatic fever (ARF) is an autoimmune disorder that is triggered by group A beta-hemolytic
streptococcal infections. ARF consists of several combinations of carditis, polyarthritis
and Sydenham's chorea, and rarely seen erythema marginatum and subcutaneous nodules.
Sydenham's chorea is seen in about 20% of patients with ARF. As a late symptom
of ARF, Sydenham's chorea usually occurs 3 months or longer after the streptococcal
infection. Sydenham's chorea is a neuropsychiatric disorder that may present with
emotional lability, anxiety, obsessive compulsive symptoms, attention deficit
and hyperactivity symptoms or tics. Obsessive-compulsive symptoms occur in 70%
of patients with Sydenham's chorea. The role of the autoimmune mechanisms and
the dysfunction of the basal ganglia have been demonstrated in Sydenham's chroea.
Antibodies against group A beta-hemolytic streptococs cross-react with basal ganglia.
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal
Infections (PANDAS) shares the same mechanism with Sydenham's chorea, but PANDAS
has not been shown to require penicillin prophylaxis. Thus it is important to
distinguish between them. Sydenham's chorea is associated with adulthood OCD,
Tourette syndrome and schizophrenia. These features make Sydenham's chorea an
explanatory model for obsessive-compulsive disorder (OCD) and related disorders.
This poststreptococcal disorder provides a treatment opportunity with new therapies
like antibiotic therapy, plasma exchange and intravenous immunoglobulin therapy
for psychiatric disorders. In this paper we summarize the phenomenological and
treatment studies of OCD, attention deficit and hyperactivity disorder (ADHD),
and tic disorders in subjects with ARF, with or without Sydenham's chorea."
Kiessling LS, Marcotte AC, Culpepper L.
antibodies in movement disorders.
Pediatrics. 1993 Jul;92(1):39-43.
To determine whether children with recent onset of movement disorders (Tourette
syndrome, motor and/or vocal tics, chorea, choreiform movements) show evidence
of serological antibodies directed against the human central nervous system as
previously documented in research on Sydenham's chorea. METHODS. Serum antibodies
against previously frozen human caudate nucleus sections were analyzed using a
blinded design and immunofluorescent staining methods. The sera of one group of
50 children referred for evaluation of attention deficit hyperactivity disorder,
behavior disorders, and learning disabilities (24 with an associated movement
disorder) seen between June 1989 and June 1990 were analyzed. The study was replicated
in 33 children (21 with an associated movement disorder) seen between June 1990
and November 1990. RESULTS. In the original sample of 50 children, those with
movement disorders were significantly more likely to have evidence of antineuronal
antibodies than were those without movement disorders (odds ratio [OR] 4.80, 95%
confidence interval [CI] 2.58 to 8.93). Results of the replication were similar
(OR 6.00, 95% CI 2.56 to 14.03). For the total group, the OR was 5.50, (95% CI
3.54 to 8.99), which is highly significant. The percentage of children with a
movement disorder whose sera were strongly positive for antineuronal antibodies
(44%) was very similar to that previously found in children with Sydenham's chorea
(46%). Children with movement disorders were also more likely than children without
movement disorders to have at least one antistreptococcal titer elevated. CONCLUSIONS.
The data strongly suggest an association between antecedent group A beta-hemolytic
streptococcal infection as inferred from elevated antistreptococcal titers and
the presence of serum antineuronal antibodies, which may, in turn, be linked to
childhood movement disorders." [Abstract]
Snider LA, Swedo SE.
obsessive-compulsive disorder and tic disorders: case report and literature review.
Child Adolesc Psychopharmacol. 2003;13 Suppl 1:S81-8.
"A subgroup of childhood-onset
obsessive-compulsive disorder (OCD) and tic disorders has been found to have a
postinfectious autoimmune-mediated etiology. Clinical observations and systematic
investigations have shown that a subgroup of children with OCD and/or tic disorders
have the onset and subsequent exacerbations of their symptoms following infections
with group A beta-hemolytic streptococci (GABHS). This subgroup has been designated
by the acronym PANDAS: pediatric autoimmune neuropsychiatric disorders associated
with streptococcal infections. Five clinical characteristics define the PANDAS
subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden
onset or abrupt exacerbations, association with neurological abnormalities during
exacerbations (adventitious movements or motoric hyperactivity), and the temporal
association between symptom exacerbations and GABHS infections. The proposed poststreptococcal
inflammatory etiology provides a unique opportunity for treatment and prevention,
including immunomodulatory therapies such as plasma exchange and intravenous immunoglobulin.
A placebo-controlled trial revealed that both intravenous immunoglobulin and plasma
exchange were effective in reducing neuropsychiatric symptom severity (40 and
55% reductions, respectively) for a group of severely ill children in the PANDAS
subgroup. Further research is required to determine why the treatments are helpful
and to ascertain whether or not antibiotic prophylaxis can help prevent poststreptococcal
symptom exacerbations." [Abstract]
L, Gammon P, Sullivan K, Franklin M, Foa E, Maid R, March JS.
parental report of upper respiratory infection at the onset of obsessive-compulsive
disorder suggestive of pediatric autoimmune neuropsychiatric disorder associated
with streptococcal infection?
J Child Adolesc Psychopharmacol.
"The diagnosis of pediatric autoimmune neuropsychiatric
disorder associated with streptococcal infection (PANDAS) requires a prospectively
determined association between group A beta-hemolytic streptococcal (GABHS) infection
and obsessive-compulsive disorder (OCD) or tic disorder. Screening for GABHS infection
imposes a significant burden on both patient and clinician. To heighten the index
of suspicion for PANDAS, it would be useful to know if parent-reported upper respiratory
infection (URI) is associated with PANDAS symptoms or associated characteristics.
Eighty-three consecutive, clinically referred patients aged 6 to 17 years with
a primary diagnosis of OCD and their primary caregivers were asked about URI signs
and symptoms at the time of OCD onset, PANDAS symptoms, OCD and tic symptoms,
comorbidity, and putative PANDAS risk factors. Specific inquiry regarding URI
symptoms proved more informative than general inquiry. In the URI present versus
URI absent group, more patients experienced a sudden rather than insidious onset
of symptoms. Additionally, more patients with a URI plus sudden onset exhibited
a comorbid tic disorder. Until validated biomarkers permit retrospective diagnosis,
a history that OCD began around the time of a URI should clue the clinician to
look prospectively for PANDAS. Additional research is required to define the boundaries
of PANDAS and to develop psychometrically reliable and valid diagnostic strategies."
Orvidas LJ, Slattery MJ.
neuropsychiatric disorders and streptococcal infections: role of otolaryngologist.
"OBJECTIVE: To increase awareness and understanding
of the putative role of streptococcal infection in the development of neuropsychiatric
disorders in children and to discuss therapeutic options in this group of patients.
METHODS: Case illustration and literature review. RESULTS: Two siblings, one with
obsessive-compulsive disorder (OCD) and one with a tic disorder, had tonsillectomy
for recurrent streptococcal pharyngitis. At the latest follow-up visit (11 mo
postoperatively), both patients exhibited significant improvement in their psychiatric
illnesses. We discuss these cases as well as the diagnosis, pathophysiology, and
treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infections (PANDAS). CONCLUSION: PANDAS is an active area of research investigating
the relationship between streptococcal infections and the development of obsessive-compulsive
disorder or tic disorders (or both) in children. The etiopathogenesis of PANDAS
is thought to reflect autoimmune mechanisms and involvement of the basal ganglia
of susceptible hosts. Because otolaryngologists evaluate a large portion of pediatric
patients with recurrent streptococcal pharyngitis, it is important to be aware
of this association and to manage these patients appropriately." [Abstract]
Heubi C, Shott SR.
PANDAS: pediatric autoimmune
neuropsychiatric disorders associated with streptococcal infections--an uncommon,
but important indication for tonsillectomy.
Int J Pediatr
Otorhinolaryngol. 2003 Aug;67(8):837-40.
"Pediatric autoimmune neuropsychiatric
disorders associated with streptococcal infections, also know as "PANDAS,"
is well described in the neurologic and psychiatric literature. PANDAS is associated
with obsessive compulsive disorders (OCD) and tic disorders. The streptococcal
infections may trigger an autoimmune reaction that exacerbates these conditions.
Recurrent streptococcal tonsillitis is one of the recurrent infections associated
with PANDAS. This paper reviews the case reports of two brothers, one with OCD
and the other with a tic disorder, both of whom improved significantly after undergoing
adenotonsillectomy for treatment of their recurrent tonsillitis. A review of the
pathophysiology and current understanding of PANDAS is presented." [Abstract]
L, Perlmutter SJ, Nicolson R, Garvey MA, Swedo SE.
in first-degree relatives of children with pediatric autoimmune neuropsychiatric
disorders associated with streptococcal infections (PANDAS).
Am Acad Child Adolesc Psychiatry. 2000 Sep;39(9):1120-6.
determine the rates of psychiatric disorders in the first-degree relatives of
children with infection-triggered obsessive-compulsive disorder (OCD) and/or tics
(pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infections; PANDAS). METHOD: The probands of this study were 54 children with
PANDAS (n = 24 with a primary diagnosis of OCD; n = 30 with a primary diagnosis
of a tic disorder). One hundred fifty-seven first-degree relatives (100 parents
[93%] and 57 siblings [100%]) were evaluated for the presence of a tic disorder.
One hundred thirty-nine first-degree relatives (100 parents [93%] and 39 of 41
siblings over the age of 6 [95%]) were evaluated with clinical and structured
psychiatric interviews to determine the presence of subclinical OCD, OCD, and
other DSM-IV Axis I disorders. RESULTS: Twenty-one probands (39%) had at least
one first-degree relative with a history of a motor or vocal tic; 6 mothers (11%),
9 fathers (19%), and 8 siblings (16%) received this diagnosis. Fourteen probands
(26%) had at least one first-degree relative with OCD; 10 mothers (19%), 5 fathers
(11%), and 2 siblings (5%), received this diagnosis. An additional 8 parents (8%)
and 3 siblings (8%) met criteria for subclinical OCD. Eleven parents (11%) had
obsessive-compulsive personality disorder. CONCLUSIONS: The rates of tic disorders
and OCD in first-degree relatives of pediatric probands with PANDAS are higher
than those reported in the general population and are similar to those reported
previously for tic disorders and OCD. Further study is warranted to determine
the nature of the relationship between genetic and environmental factors in PANDAS."
Giedd, Jay N., Rapoport, Judith L., Garvey, Marjorie A.,
Perlmutter, Susan, Swedo, Susan E.
MRI Assessment of Children With
Obsessive-Compulsive Disorder or Tics Associated With Streptococcal Infection
J Psychiatry 2000 157: 281-283
"OBJECTIVE: The authors assessed selective
basal ganglia involvement in a subgroup of children with obsessive-compulsive
disorder (OCD) and/or tics believed to be associated with streptococcal infection.
METHOD: Using computer-assisted morphometric techniques, they analyzed the cerebral
magnetic resonance images of 34 children with presumed streptococcus-associated
OCD and/or tics and 82 healthy comparison children who were matched for age and
sex. RESULTS: The average sizes of the caudate, putamen, and globus pallidus,
but not of the thalamus or total cerebrum, were significantly greater in the group
of children with streptococcus-associated OCD and/or tics than in the healthy
children. The differences were similar to those found previously for subjects
with Sydenhams chorea compared with normal subjects. CONCLUSIONS: These
results support the hypothesis that there is a distinct subgroup of subjects with
OCD and/or tics who have enlarged basal ganglia. These findings are consistent
with the hypothesis of an autoimmune response to streptococcal infection."
A J, Dale, R C, Lees, A J, Giovannoni, G, Robertson, M M
syndrome: a cross sectional study to examine the PANDAS hypothesis
Neurol Neurosurg Psychiatry 2003 74: 602-607
"BACKGROUND: The classical
neurological disorder after group A beta haemolytic streptococcal infection is
Sydenham's chorea. Recently a tic disorder occurring after group A streptococcal
infection has been described and termed PANDAS (paediatric autoimmune neuropsychiatric
disorders associated with streptococcal infection). It is proposed that antibodies
induced after group A streptococcal infection react with basal ganglia neurones
in Sydenham's chorea and PANDAS. Anti-basal ganglia antibodies (ABGA) are present
in most cases of acute Sydenham's chorea, but rarely in controls. OBJECTIVE: To
investigate the hypothesis that Tourette's syndrome may be associated with group
A streptococcal infection and ABGA. METHODS: 100 patients with Tourette's syndrome
(DSM-IV-TR) were enrolled in a cross sectional study. Children with neurological
disease (n = 50) and recent uncomplicated streptococcal infection (n = 40), adults
with neurological disease (n = 50), and healthy adults (n = 50) were studied as
controls. Recent group A streptococcal infection was defined using antistreptolysin
O titre (ASOT). ABGA were detected using western immunoblotting and indirect immunofluorescence.
RESULTS: ASOT was raised in 64% of children with Tourette's syndrome compared
with 15% of paediatric neurological disease controls (p < 0.0001), and in 68%
of adults with Tourette's syndrome compared with 12% of adult neurological controls
and 8% of adult healthy controls (p < 0.05). Western immunoblotting showed
positive binding in 20% of children and 27% of adults with Tourette's syndrome,
compared with 2-4% of control groups (p < 0.05). The most common basal ganglia
binding was to a 60 kDa antigen, similar to the proposed antigen in Sydenham's
chorea. Indirect immunofluorescence revealed autoantibody binding to basal ganglia
neurones. Serological evidence of recent group A streptococcal infection, assessed
by a raised ASOT, was detected in 91% (21/23) of Tourette's syndrome patients
with positive ABGA compared with 57% (44/77) with negative ABGA (p < 0.01).
CONCLUSIONS: The results support a role of group A streptococcal infection and
basal ganglia autoimmunity in a subgroup of patients with Tourette's syndrome
and suggest a pathogenic similarity between Sydenham's chorea and some patients
with Tourette's syndrome." [Abstract]
N, Riedel M, Straube A, Gunther W, Wilske B.
antibodies in patients with Tourette's syndrome.
Res. 2000 Apr 24;94(1):43-9.
"Infection or postinfectious phenomena have
been postulated to play a role in the pathogenesis of children afflicted with
the typical symptoms of Tourette's syndrome (TS). We investigated whether an increase
of titers of antistreptococcal antibodies can be reproduced in our children with
TS, and whether this increase is restricted to children. We examined the titers
of two different antistreptococcal antibodies, antistreptolysin (ASL) and anitDNase
B, both in children and adults. Titer s of ASO and antiDNase B were measured (1)
in 13 children/adolescents suffering from TS and in an aged-matched comparison
group;(2) in 23 adult patients, a comparison group of 23 aged-matched controls,
and in another group of 17 aged-matched, non-medicated acute schizophrenics. ASO
and antiDNase B titers were determined by laser nephelometry using a commercially
available kit. Two antistreptococcal cut-off levels were compared (> 250 U/ml
and 400 U/ml). As expected, increases ASO titers (>400 IU/ml) were found in
a higher portion of children/adolescents with TS compared to controls. Regarding
adults, titers >250 U/ml for both antistreptococcal antigens were found in
significantly more TS patients than in schizophrenic patients or healthy control
subjects. The mean values of ASO and antiDNase titers were significantly higher
in both groups of TS patients compared to control children/adolescents, to the
comparison groups of healthy adults and to schizophrenics. No difference in antistreptococcal
titers was found between schizophrenics and the group of healthy adults. TS patients
exhibited higher antistreptococcal titers than age-matched comparison groups of
both children/adolescents and adults using different types of calculation. Our
findings support the theory that a postinfectious immune mechanism may play a
role in the pathogenesis of TS. The mechanism still needs to be elucidated."
Morshed SA, Parveen S, Leckman JF, Mercadante
MT, Bittencourt Kiss MH, Miguel EC, Arman A, Yazgan Y, Fujii T, Paul S, Peterson
BS, Zhang H, King RA, Scahill L, Lombroso PJ.
neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults
with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders.
Psychiatry. 2001 Oct 15;50(8):566-77.
"BACKGROUND: Some cases of Tourette's
syndrome (TS) are hypothesized to be caused by autoantibodies that develop in
response to a preceding group A beta hemolytic streptococcal infection. METHODS:
To test this hypothesis, we looked for the presence ot total and IgG antibodies
against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect
immunofluorescent assays and Western blot techniques in three patient groups:
TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in
normal controls (n = 67). Subjects were ranked after titrations of autoantibodies
from 0 to 227 according to their level of immunoreactivity. RESULTS: TS patients
had a significantly higher mean rank for total antineural and antinuclear antibodies,
as well as antistreptolysin O titers. However, among children and adolescents,
only the total antinuclear antibodies were increased in TS patients compared to
age matched controls. Compared to SC patients, TS patients had a significantly
lower mean rank for total and IgG class antineural antibodies, significantly lower
IgG class anticytoskeletal antibodies, and a significantly higher rank for total
antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the
TS patients had a significantly lower mean rank for total and IgG class antineural
antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal
antibodies, and a significantly higher rank for antistreptococcal antibodies.
CONCLUSIONS: TS patients had significantly higher levels of total antineural and
antinuclear antibodies than did controls. Their relation to IgG class antineural
and antinuclear antibodies, markers for prior streptococcal infection, and other
clinical characteristics, especially chronological age, was equivocal." [Abstract]
N, Kroll B, Schwarz MJ, Riedel M, Straube A, Lutticken R, Reinert RR, Reineke
T, Kuhnemund O.
Increased titers of antibodies against streptococcal
M12 and M19 proteins in patients with Tourette's syndrome.
Res. 2001 Mar 25;101(2):187-93.
"It has been suggested that a post-streptococcal
autoimmune process may be involved in the pathogenesis of a subgroup of children
with tics and obsessive-compulsive symptoms (PANDAS). Elevated antibody titers
against streptococcal antigens have also been described in adult patients suffering
from Tourette's syndrome (TS). In order to characterise further streptococcal
antigens, we focussed on M proteins. M proteins are a major virulence factor of
group A streptococci and known to evoke an immunologic cross-reaction with diverse
epitopes of human tissue including brain tissue. Therefore, antibodies against
M proteins may play a role in the pathophysiology of at least a subgroup of TS
patients. Antibodies against M proteins were studied in 25 adult patients suffering
from TS and 25 healthy controls after careful medical examination. The antibody
titers against the peptides M1, M4, M6, M12 and M19 were estimated by ELISA. Our
results show increased titers of antibodies against the streptococcal M12 and
M19 proteins in TS patients as compared with controls, while antibody titers against
M1, M4 and M6 did not differ between the TS and control groups. Elevated serum
titers of antibodies against M12 and M19 proteins support the view that a streptococcus-induced
autoimmune process may be involved in TS. The finding of a possible autoimmune
origin of TS has implications for both pathophysiology and future therapeutic
Singer HS, Loiselle CR, Lee O, Minzer K, Swedo S, Grus FH.
Anti-basal ganglia antibodies in PANDAS.
Mov Disord. 2004 Apr;19(4):406-15.
An autoimmune-mediated mechanism involving molecular mimicry has been proposed for a variety of pediatric movement disorders that occur after a streptococcal infection. In this study, anti-basal ganglia antibodies (ABGA) were measured in 15 children with the diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and compared with those in 15 controls. ELISA and Western immunoblotting (WB) methods were used to detect ABGA against supernatant (S1), pellet (P2), and synaptosomal preparations from adult postmortem caudate, putamen, and globus pallidus. ELISA optical density values did not differ between PANDAS patients and controls across all preparations. Immunoblotting identified multiple bands in all subjects with no differences in the number of bands or their total density. Discriminant analysis, used to assess mean binding patterns, showed that PANDAS patients differed from controls only for the caudate S1 fraction (Wilks' lambda = 0.0236, P < 0.0002), with PANDAS-primarily tic subjects providing the greatest discrimination. Among the epitopes contributing to differences between PANDAS and control in the caudate S1 fraction, mean binding to the epitope at 183 kDa was the most different between groups. In conclusion, ELISA measurements do not differentiate between PANDAS and controls, suggesting a lack of major antibody changes in this disorder. Further immunoblot analyses using a caudate supernatant fraction are required to completely exclude the possibility of minor antibody repertoire differences in PANDAS subjects, especially in those who primarily have tics. [Abstract]
HS, Giuliano JD, Hansen BH, Hallett JJ, Laurino JP, Benson M, Kiessling LS.
against human putamen in children with Tourette syndrome.
"BACKGROUND: Similar to the model for Sydenham's
chorea, antineuronal antibodies, which develop in response to a preceding streptococcal
infection, have been speculated to have a role in the development of Tourette
syndrome (TS). METHODS: Serum antibodies against human caudate, putamen, and globus
pallidus (interna and externa) were assayed by enzyme-linked immunosorbent assay
(ELISA) and Western blot techniques and results were correlated with clinical
characteristics and markers of streptococcal infection. SUBJECTS: A total of 41
children with TS (mean age, 11.3 years) and 39 controls (mean age, 12.1 years)
were included. RESULTS: Compared with controls, TS subjects had a significant
increase in the mean (p=0.006) and median (p=0.002) ELISA optical density (OD)
levels of serum antibodies against putamen, but not caudate or globus pallidus.
Western blots on 20 control and 20 TS serum samples showed that specific antibodies
to caudate/putamen occurred more frequently in TS subjects at 83, 67, and 60 kDa;
antigens were present in a synaptosomal fraction. TS subjects with a positive
family history of tics had higher OD values (p < or = 0.04), but no association
was shown with age of tic onset, tic severity, sudden onset of tics, or presence
of attention-deficit hyperactivity disorder or obsessive-compulsive disorder.
Risk ratio calculations in TS and control groups and in study subjects dichotomized
for high and low putamen OD values were similar for titers of antistreptolysin
O > or = 166 or antideoxyribonuclease B > or = 170. A subgroup analysis
limited to subjects with elevated streptococcal titers, however, showed a significantly
(p < or = 0.004) larger number of TS subjects with elevated OD levels. CONCLUSION:
Children and adolescents with TS had significantly higher serum levels of antineuronal
antibodies against putamen than did controls, but their relation to clinical characteristics
and markers for streptococcal infection remains equivocal." [Abstract]
Singer HS, Giuliano JD, Hansen BH, Hallett JJ, Laurino
JP, Benson M, Kiessling LS.
Antibodies against a neuron-like (HTB-10
neuroblastoma) cell in children with Tourette syndrome.
Psychiatry. 1999 Sep 15;46(6):775-80.
"BACKGROUND: Similar to the model
for Sydenham's chorea, antineuronal antibodies (ANAb), which develop in response
to a preceding streptococcal infection, have been speculated to have a role in
the development of Tourette syndrome (TS). METHODS: Serum antibodies against the
neuron-like HTB-10 neuroblastoma cell were assayed by ELISA methods and Western
blot analysis on 41 children with TS (mean age 11.3 years) and 39 control subjects
(mean age 12.1 years). RESULTS: Group comparisons of ELISA assay optical density
(OD) showed that mean OD values for serum antibodies were not different [control
(mean +/- SEM), .506 +/- .076; and TS, .584 +/- .053 (p = .38)]. In contrast,
median values [.353 in control subjects and .477 in TS subjects (p = .012)] were
significantly different. Western blots identified numerous bands in all TS and
control sera with no difference in identified HTB-10 antigens. There was no relationship
between the presence of ANAb and age of tic onset, family history, tic severity,
attention deficit hyperactivity disorder, or obsessive compulsive disorder. No
relationship existed between positive strep titers (ASO > or = 166 and/or antiDNAaseB
> or = 170) and ANAb determinations or the severity of tics. CONCLUSIONS: Children
with TS have higher median, but not mean, levels of ANAb, as measured by the HTB-10
neuroblastoma cell membrane assay. This assay system identified antibodies in
both control and clinical groups and failed to identify a relationship between
antibodies and clinical phenotype or one-time markers for streptococcal infection.
Further studies are required to define a possible immune-mediated hypothesis for
HS, Giuliano JD, Zimmerman AM, Walkup JT.
Infection: a stimulus for
Pediatr Neurol. 2000 May;22(5):380-3.
object of this study was to investigate the potential association of infections,
especially group A hemolytic streptococcal infection, with the abrupt onset/exacerbation
of tics or obsessive-compulsive behaviors. A structured clinical interview was
used to evaluate 80 consecutive children, 5-17 years of age, with a diagnosis
of tic disorder. Forty-two patients (53%) described a sudden, explosive onset
or worsening of tic symptoms; 15 of these 42 had their exacerbation historically
associated with an infection, nine of the 15 specifically with a streptococcal
infection. Comparisons between those nine individuals and the remainder of the
study population are presented. The results of this study reveal that descriptions
of an abrupt tic onset or exacerbation are not uncommon in children with tic disorders;
approximately 11% of children with tic disorders described abrupt changes of tic
behavior within a 6-week period after a streptococcal infection." [Abstract]
Loiselle CR, Wendlandt JT, Rohde CA, Singer HS.
neuronal, and nuclear antibodies in Tourette syndrome.
Neurol. 2003 Feb;28(2):119-25.
"Previous studies have suggested associations
between Tourette syndrome and attention-deficit-hyperactivity disorder and antistreptococcal
antibodies and between Tourette syndrome and antinuclear antibodies. In this study,
antistreptolysin O, antideoxyribonuclease B, antinuclear, and antineuronal antibodies
were measured in 41 children with Tourette syndrome and 38 controls, selected
without regard to history of streptococcal infection. Results revealed that mean
antistreptococcal titers did not differ between diagnostic groups. In addition,
multiple regression analysis was unable to predict antistreptococcal antibody
titers according to age and diagnosis. The frequency of elevated antistreptolysin
O titers, based on a cutoff of 1:240, was significantly higher (P = 0.04) in patients
with attention-deficit-hyperactivity disorder (64%) than in the group without
attention-deficit-hyperactivity disorder (34%) but not when dichotomized according
to age-matched normal values. No analysis of antideoxyribonuclease B titers identified
any differences between groups. Antinuclear antibody titers were at least 1:160
in three of 33 Tourette syndrome patients; only one subject manifested a homogeneous
staining pattern. Multiple regression analyses were unable to predict antinuclear,
antineuronal, or anti-HTB-10 antibody titers according to the combination of age,
diagnosis, and antistreptococcal titer. We suggest that longitudinal rather than
single-point-in-time laboratory measurements be evaluated before definitive conclusions
are drawn on associations between the diagnosis of Tourette syndrome, attention-deficit-hyperactivity
disorder, or obsessive-compulsive disorders and antistreptococcal or antinuclear
antibody titers." [Abstract]
BS, Leckman JF, Tucker D, Scahill L, Staib L, Zhang H, King R, Cohen DJ, Gore
JC, Lombroso P.
Preliminary findings of antistreptococcal antibody
titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity
Arch Gen Psychiatry. 2000 Apr;57(4):364-72.
Previous studies have provided preliminary serological evidence supporting the
theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may
be sequelae of prior streptococcal infection. It is unclear, however, whether
previously reported associations with streptococcal infection were obscured by
the presence of diagnostic comorbidities. It is also unknown whether streptococcal
infection is associated in vivo with anatomical alterations of the brain structures
that have been implicated in the pathophysiology of these disorders. METHODS:
Antistreptococcal antibody titers were measured in 105 people diagnosed as having
CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community
controls without a disorder. Subjects were unselected with regard to their history
of streptococcal exposure. Basal ganglia volumes were measured in 113 of these
subjects (79 patients and 34 controls). RESULTS: A DSM-IV diagnosis of ADHD was
associated significantly with titers of 2 distinct antistreptococcal antibodies,
antistreptolysin O and anti-deoxyribonuclease B. These associations remained significant
after controlling for the effects of CTD and OCD comorbidity. No significant association
was seen between antibody titers and a diagnosis of either CTD or OCD. When basal
ganglia volumes were included in these analyses, the relationships between antibody
titers and basal ganglia volumes were significantly different in OCD and ADHD
subjects compared with other diagnostic groups. Higher antibody titers in these
subjects were associated with larger volumes of the putamen and globus pallidus
nuclei. CONCLUSIONS: These findings suggest that the prior reports of an association
between antistreptococcal antibodies and either CTD or OCD may have been confounded
by the presence of ADHD. They also support the hypothesis that in susceptible
persons who have ADHD or OCD, chronic or recurrent streptococcal infections are
associated with structural alterations in basal ganglia nuclei." [Abstract]
Mae S., Ward, Pamela E., Tamiya, Hiroko, Kondo, Douglas G., Houston, Douglas,
Zabriskie, John B.
D8/17 Expression on B Lymphocytes in Anorexia
Am J Psychiatry 2002 159: 1430-1432
The authors' goal was to determine whether D8/17, a rheumatic fever susceptibility
trait marker, identifies a possible type of anorexia nervosa: pediatric autoimmune
neuropsychiatric disorders associated with streptococcus (PANDAS) anorexia nervosa.
METHOD: Using immunofluorescence, the authors measured the percentage of D8/17-positive
B lymphocytes in the peripheral blood of 16 subjects 7-21 years old who had not
had rheumatic fever but who had possible PANDAS anorexia nervosa. The comparison
subjects were 17 psychiatric patients with no eating disorder and no PANDAS characteristics.
Subjects were considered D8/17 positive if they had 12% or more D8/17+ cells.
RESULTS: There were more D8/17-positive individuals among those with PANDAS anorexia
nervosa (81%) than among the comparison subjects (12%). The subjects with PANDAS
anorexia nervosa had a higher percentage of D8/17+ cells (mean=27.1%, SD=17%)
than the comparison subjects (mean=5.3%, SD=7.4%). CONCLUSIONS: A larger study
is needed to determine whether D8/17 serves as a marker for susceptibility to
a type of anorexia nervosa." [Abstract]
Infection-triggered anorexia nervosa in children: clinical description
of four cases.
J Child Adolesc Psychopharmacol. 2000 Summer;10(2):133-45.
Anorexia nervosa (AN) is a serious illness with no definitive treatment. Clinical
and research evidence led to the hypothesis that some children with AN may have
a pediatric autoimmune neuropsychiatric disorder associated with streptococcus
(PANDAS), similar in pathogenesis to other hypothesized PANDAS disorders. METHODS:
Four youngsters (ages, 11-15 years) with PANDAS AN were treated with an open trial
of antibiotics, in addition to conventional treatment. They were evaluated for
eating disorder and obsessive-compulsive symptoms, and for weight gain. Evidence
of streptococcal infection came from clinical evaluation, throat cultures, and
two serological tests: anti-deoxyribonuclease B (anti-DNase B) and anti-streptolysin
O (ASO) titers. The "rheumatic" marker D8/17 was also measured. This
B-cell alloantigen is associated, in several publications, with poststreptococcal
autoimmunity: Rheumatic fever (RF), Sydenham's chorea (SC), and possibly PANDAS
obsessive compulsive disorder (OCD) and tic disorders. RESULTS: There was clinical
evidence of possible antecedent streptococcal infection in all four patients,
two of whom had comorbid OCD, with possible infection-triggered AN. All four had
the rheumatic marker: A percentage of D8/17-positive B cells of 28-38%, with a
mean of 33% (12% or more is considered positive for the marker). The patients
responded to conventional treatment plus antibiotics with weight restoration and
decreased eating disorder and obsessive-compulsive symptoms. Three needed to gain
weight and did so. CONCLUSIONS: There may be a link between infectious disease
and some cases of AN, which raises the possibility of new treatment." [Abstract]
MS, Gray NS.
Case study: an infection-triggered, autoimmune subtype
of anorexia nervosa.
J Am Acad Child Adolesc Psychiatry.
"OBJECTIVE: Certain cases of anorexia nervosa
(AN) may be similar to the recently described subtype of childhood-onset obsessive-compulsive
disorder hypothesized to be one of the pediatric infection-triggered autoimmune
neuropsychiatric disorders (PITANDs). METHOD: Three clinical cases are reported.
The first patient is a 12-year-old boy whose AN worsened acutely after a group
A beta-hemolytic streptococcal (GABHS) infection. His symptoms were alleviated
after antibiotic treatment. Two other patients with possible PITANDs-related AN
are described. RESULTS: An infection-triggered process may contribute to the pathogenesis
of a subtype of AN. CONCLUSIONS: Future research is needed to explore the nature
of PITANDs and their relationship with AN." [Abstract]
E, DelGiudice-Asch G, Simon L, Schmeidler J, Cartwright C, DeCaria CM, Kwon J,
Cunningham-Rundles C, Chapman F, Zabriskie JB.
B lymphocyte antigen
D8/17 and repetitive behaviors in autism.
Am J Psychiatry.
"OBJECTIVE: Monoclonal antibody D8/17 identifies
a B lymphocyte antigen with expanded expression in rheumatic fever, Sydenham's
chorea, and subgroups of obsessive-compulsive disorder and Tourette's syndrome
with repetitive behaviors. The authors examined the rate of D8/17 expression in
children with autism and its correlation with severity of repetitive behaviors.
METHOD: Blood samples from 18 patients with autism and 14 comparable medically
ill children were evaluated for percentage of D8/17-positive B cells by immunofluorescence
and for streptococcal antibodies. Severity of repetitive behaviors was also determined.
RESULTS: The frequency of individuals with > or =11% D8/17-positive cells was
significantly higher in the autistic patients (78%) than the comparison subjects
(21%), severity of repetitive behaviors significantly correlated with D8/17 expression,
and D8/17-positive patients had significantly higher compulsion scores than D8/17-negative
patients. CONCLUSIONS: D8/17 expression is high in patients with autism and may
serve as a marker for compulsion severity within autism." [Abstract]
SM, Morshed SA, Peterson BS.
The question of PANDAS in adults.
Psychiatry. 2001 May 1;49(9):807-10.
"BACKGROUND: Pediatric autoimmune
neuropsychiatric disorders associated with streptococcal infections (PANDAS) are
a well-defined cause of obsessive-compulsive disorder in children. However, they
have not been described or fully investigated in adults newly diagnosed with obsessive-compulsive
disorder. METHODS: We describe an adult with onset of obsessive-compulsive disorder
at 25 years of age after a severe antibiotic-responsive pharyngitis. He was evaluated
with multiple psychiatric rating scales for obsessive-compulsive disorder and
Tourette's syndrome, as well as with serologic assays and radiologic studies.
RESULTS: In all respects except age our patient fulfilled established criteria
for PANDAS. Assays for antibodies to group A beta-hematolytic streptococci, serum
D8,17 lymphocytes, antistriatal (neuronal) antibodies, and anticytoskeletal antibodies
all supported the hypothesis that a poststreptococcal process was active. Magnetic
resonance imaging was abnormal and is described. CONCLUSIONS: The findings suggest
that this patient's illness is similar to PANDAS in presentation and that poststreptococcal
disease may result in adult-onset obsessive-compulsive disorder." [Abstract]
Tourette's syndrome and 'PANDAS': will the relation bear out?
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal
Neurology. 1998 Jun;50(6):1530-4. [Abstract]
Tourette syndrome, associated conditions and the complexities
Brain 123: 425-462. [Full
Garvey MA, Giedd J, Swedo SE.
the search for environmental triggers of pediatric neuropsychiatric disorders.
Lessons from rheumatic fever.
J Child Neurol. 1998 Sep;13(9):413-23.
PH, Leckman J.
[Obsessive-compulsive disorders in children. Subtypes
of OCD and their relation to infection with group A streptococci]
Laeger. 2002 Aug 5;164(32):3763-7.
"The present review describes the theory
of a spectrum of obsessive-compulsive disorders (OCD). This spectrum includes
such disorders as trichotillomania, eating disorders, body dysmorphic disorder,
and possibly pervasive developmental disorders. OCD with an onset in childhood
is presented as a specific subtype, with more boys affected and frequently co-morbid
with tics and Tourette's syndrome. Furthermore, it seems to be more genetically
determined and have more significant deviations, as measured by neuro-imaging
studies, than has OCD with an adult onset. The PANDAS theory (paediatric autoimmune
neuropsychiatric disorder associated with streptococcal infections) is described.
This subtype of OCD is, still on a speculative basis, connected to infections
with beta-haemolytic streptococci. The obsessive-compulsive symptoms are characterised
by a sudden onset, "sawtoothed" course with relapses and remissions,
and are associated with neurological abnormalities. There are still no clinical
consequences in terms of penicillin treatment of this PANDAS subtype of OCD."
[Streptococcus pyogenes and the brain: living with the enemy]
Neurol. 2003 Jul 1-15;37(1):92-7.
"Streptococcus pyogenes (or group A
beta hemolytic streptococcus) is a pathogenic bacterium that can give rise to
a range of invasive and autoimmune diseases, although it is more widely known
as the cause of tonsillitis. It is particularly interesting to note that this
germ only causes disease in humans. For many years it has been acknowledged that
it can cause an autoimmune brain disease (Sydenham s chorea). Yet, the spectrum
of post streptococcal brain disorders has recently been extended to include other
movement disorders such as tics or dystonia. A number of systematic psychiatric
studies have shown that certain emotional disorders generally accompany the movement
disorder (particularly, obsessive compulsive disorder). The proposed pathogenetic
mechanism is that of a neuronal dysfunction in which antibodies play a mediating
role. The antibodies that are produced after the streptococcal infection cross
react with neuronal proteins, and more especially so in individuals with a propensity.
This represents a possible model of immunological mimicry and its potential importance
with respect to certain idiopathic disorders such as Tourette syndrome and obsessive
compulsive disorder." [Abstract]
Murphy TK, Petitto JM, Voeller KK, Goodman WK.
compulsive disorder: is there an association with childhood streptococcal infections
and altered immune function?
Semin Clin Neuropsychiatry.
"During the last few years, an increased interest
in the possibility of immune mediated pathophysiology of obsessive compulsive
disorder (OCD) and related disorders has been seen. In the late 1980s, the National
Institute of Mental Health reported an increase of obsessive compulsive symptoms
in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal
infection in children with sudden onset of OCD symptoms but no chorea led to the
coining of PANDAS (pediatric autoimmune neuropsychiatric disorders associated
with streptococcus).This association has furthered interest in studying immune
parameters in non-PANDAS OCD as well. This article will review the neuropsychiatric
findings in OCD and Tourette syndrome (TS) with emphasis placed on PANDAS, and
its association with SC, and a review of the existing studies that have assessed
immunologic measures in patients with OCD and TS." [Abstract]
Singer HS, Loiselle C.
PANDAS. A commentary.
J Psychosom Res. 2003 Jul;55(1):31-9.
an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with
Streptococcal infection. As defined, the criteria include prepubertal children
with either a tic or obsessive-compulsive disorder in whom a Group A beta-hemolytic
streptococcal infection (GABHS) triggers the abrupt onset or exacerbation of tics/obsessive-compulsive
behaviors. Pathophysiologically, it is proposed that antibodies produced against
GABHS cross-react with neuronal cells, in a process involving molecular mimicry.
Although PANDAS has received widespread notoriety, the existence of this condition
has been questioned. This commentary reviews clinical and laboratory issues pertinent
to the diagnosis of this entity. We conclude that PANDAS is an intriguing hypothesis
that requires further confirmation." [Abstract]
Betancourt YM, Jimenez-Leon JC, Jimenez-Betancourt
CS, Castillo VE.
[Autoimmune neuropsychiatric disorders associated
to infection by streptococcus in the paediatric age: PANDAS]
Neurol. 2003 Feb;36 Suppl 1:S95-107.
"INTRODUCTION: The acronym PANDAS
(Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus)
describes the neuropsychiatric disorders resulting from an autoimmune response
to an infection by streptococcus in children. AIMS: The aim of this study was
to clinically analyse 38 patients under the age of 16 with tics, Tourette syndrome
(TS) or obsessive compulsive disorder (OCD) and their possible association to
an infection caused by group A beta-haemolytic streptococcus (GABHS). METHOD:
We reviewed the medical records at the Instituto Neurologico in Valencia (Venezuela)
over a 12 year period (1988-2000). All the patients met the inclusion criteria
set out by the National Institute of Mental Health in Bethesda (1997) and the
DSM-IV. RESULTS: Onset of the symptoms was higher in the group of schoolchildren
(n=24), followed by the group of preschool children (n=8) and adolescents (n=6).
Males were predominant (n=33) (86.8%). 17 patients presented chronic tics (44.7%),
13 had transitory tics (34.2%) and there were eight cases of TS (21.1%). The most
frequently related comorbid disorders were: difficulties in learning (n=30) (78.9%),
ADHD (n=27) (71.1%), OCD 14 (36.8%), sleep disorders (n=14) (36.8%), behavioural
disorders (n=12) (31.6%), language disorders (n=11) (28.9%), psychomotor disorders
(n=10) (26.3%) and nocturnal enuresis (n=7) (18.4%). Electroencephalogram patterns
were abnormal in 72.4% (n=12), and the disorganised pattern was the most frequently
observed (n=12) (41.4%), followed by a slow diffuse pattern (n= 7) (24.1%) and
the left centro-parieto-temporal focal paroxysmal specific pattern (n=7) (24.1%).
Less frequently we found unspecific generalised paroxysmal patterns, in four cases
(13.8%), and asymmetrical patterns (n=1) (3.4%). The association with an infection
by streptococcus was shown in two cases, which amounted to 5.2% of the sample.
CONCLUSIONS: The obtained are similar to those reported in the literature. Only
5.2% of the cases were linked to a prior streptococcus infection." [Abstract]