Chain reaction or time bomb: A neuropsychiatric-developmental/neurodevelopmental formulation of tourettisms, pervasive developmental disorder, and schizophreniform symptomatology associated with PANDAS

Kerbeshian, Jacob; Burd, Larry; Tait, Alison

doi:10.1080/15622970601182652

Cited by 16 publications

(13 citation statements)

References 40 publications

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“…6,7 The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is used to describe a subset of children with OCD or chronic tic disorder after GABHS infection. 8,9 PANDAS diagnostic criteria require presence of a lifetime diagnosis of OCD or a tic disorder; 10 in addition, other clinical features are suggested as part of a broader PANDAS classification, including cognitive, 9 attentional, 11 social, 12 eating 13 and mood disturbances. 3,9 A role for GABHS-induced autoimmunity has also been proposed in AD/HD, 11,14 anorexia nervosa, 15,16 major depression 17 and ASD; 18,19 these conditions are also frequently noted in PANDAS populations as comorbid neuropsychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection

et al. 2009

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Streptococcal infections can induce obsessive-compulsive and tic disorders. In children, this syndrome, frequently associated with disturbances in attention, learning and mood, has been designated pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Autoantibodies recognizing central nervous system (CNS) epitopes are found in sera of most PANDAS subjects, but may not be unique to this neuropsychiatric subset. In support of a humoral immune mechanism, clinical improvement often follows plasmapheresis or intravenous immunoglobulin. We recently described a PANDAS mouse model wherein repetitive behaviors correlate with peripheral anti-CNS antibodies and immune deposits in brain following streptococcal immunization. These antibodies are directed against group A b-hemolytic streptococcus matrix (M) protein and cross-react with molecular targets complement C4 protein and a-2-macroglobulin in brain. Here we show additional deficits in motor coordination, learning/memory and social interaction in PANDAS mice, replicating more complex aspects of human disease. Furthermore, we demonstrate for the first time that humoral immunity is necessary and sufficient to induce the syndrome through experiments wherein naive mice are transfused with immunoglobulin G (IgG) from PANDAS mice. Depletion of IgG from donor sera abrogates behavior changes. These functional disturbances link to the autoimmunity-related IgG1 subclass but are not attributable to differences in cytokine profiles. The mode of disrupting blood-brain barrier integrity differentially affects the ultimate CNS distribution of these antibodies and is shown to be an additional important determinant of neuropsychiatric outcomes. This work provides insights into PANDAS pathogenesis and may lead to new strategies for identification and treatment of children at risk for autoimmune brain disorders.

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Section: Introductionmentioning

confidence: 99%

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection

et al. 2009

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“…2 Swedo et al have identifi ed bacteria-triggered autoimmune response as the cause in some cases of childhood neuropsychiatric illness. 2 Kerbeshian et al 3 proposed the neuropsychiatric-developmental model, which explains that neuropsychiatric developmental disorder (NPDD) is a group of conditions with a childhood onset and a long-term course, with symptom expression varying over the course of maturation. These symptom variations are refl ective of biogenetic elements transacting over time with developmental and epigenetic infl uences.…”

Section: Discussionmentioning

confidence: 99%

“…These symptom variations are refl ective of biogenetic elements transacting over time with developmental and epigenetic infl uences. 3 It is proposed that a vulnerable basal ganglia substrate via autoimmune processes and resulting dopaminergic dysfunction could play a central role in the cooccurrence of Tourette's syndrome and ASD. 4 According to the clinical recommendations offered by American Academy of Child and Adolescent Psychiatry (AACAP), the management recommendations of PANDAS include laboratory testing, use of antibiotics, symptomatic management of neuropsychiatric symptoms, and immunomodulatory therapies.…”

Section: Discussionmentioning

confidence: 99%

A 7-year-Old Boy with ADHD

Chalemian¹,

Amir²,

Jadapalle³

2011

Psychiatric Annals

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A 7-year-old white boy had been diagnosed with attention-deficit/hyperactivity disorder (ADHD), inattentive type, 1 year before. He also had a reading disorder with verbal comprehension impairment. He was brought into the emergency room for agitation and self-injurious behavior while at a day camp. He had barricaded himself with stacked chairs and was banging his head repeatedly into the fi le cabinet after an altercation with his friends.After unsuccessful attempts to calm him, and out of fear for the safety of the other children, the day camp counselor called the mother and police. The patient continued to entrap himself, make animal sounds, sing, and repeat single words while the police brought him into the emergency room for psychiatric evaluation.There was no history of depressive or manic symptoms, no changes in sleep, appetite, or weight, and no history of suicidal or homicidal ideation. The patient had a history of a regulatory sensory processing disorder, which was diagnosed a few months before. He has been enrolled in an individualized education program (IEP) for a few months.The mother reported a sudden dramatic change in her son's behavior 1 month after the IEP was initiated. There was sequential development of symptoms not previously seen in the patient, starting with increased aggression and irritability, and he became physically assaultive toward his brother by trying to choke him. He had showed impulsive behavior and was nearly hit by a dump truck after running into the street when his mother refused to buy him ice cream. A few days after that, he exhibited symptoms of social withdrawal and refused to go to school. When in school, he would hide under desks or in closets.His mother said there were newly developed food preferences, and he began to refuse certain foods based on their texture, such as gravy or mashed potatoes. During a visit with a child neurologist, the patient started rocking back and forth and was banging his head repeatedly against the wall. He displayed rapid, non-rhythmic movements of hands, repeated vocalizations of single words, and choreiform head movements. He had no eye contact. His behavior was temporarily controlled by verbal intervention by the neurologist.A recommendation was made for psychiatric evaluation and an appointment was made. However, his symptoms then escalated to the point that he had to be brought to the ER because of extreme agitation and aggressive behavior during the day camp visit.

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“…Other comorbid diagnoses were oppositional defiant disorder in 40% of cases, major depression in 36%, generalized anxiety disorder in 28%, separation anxiety disorder in 20%, specific phobia in 16%, dysthymia in 12%, enuresis in 12%, encopresis in 10%, and conduct disorder in 4%. Additional reports of other movement disorders other than tics or chorea (dystonia, tremor, stereotypies, opsoclonus, myoclonus, paroxysmal choreoathetosis) [33], catatonia [34], pervasive developmental disorder and schizophreniform symptoms [35], body dysmorphic disorder [36], eating disorder [37][38][39], and even conversion symptoms [40] shortly occurring after a streptococcal throat infection were published in the last years, but at present these should be considered only anecdotal observations.…”

Section: What Is the Full Range Of Symptoms In Patients With Pandas?mentioning

confidence: 99%

The PANDAS subgroup of tic disorders and childhood-onset obsessive–compulsive disorder

Martino¹,

Defazio²,

Giovannoni³

2009

Journal of Psychosomatic Research

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Chain reaction or time bomb: A neuropsychiatric-developmental/neurodevelopmental formulation of tourettisms, pervasive developmental disorder, and schizophreniform symptomatology associated with PANDAS

Cited by 16 publications

References 40 publications

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection

A 7-year-Old Boy with ADHD

The PANDAS subgroup of tic disorders and childhood-onset obsessive–compulsive disorder

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