ABSTRACT
Abstract Introduction It has been hypothesized that pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) etiology results from an abnormal immune response to streptococcal infection. There is evidence that the serotonergic system is involved in both obsessive-compulsive disorder (OCD) physiopathology and immunological processes. In the 5' promoter region of 5-HTT, gene encoding for the serotonin transporter we can find the 5-HTTLPR polymorphism that has been associated with OCD. Being PANDAS a disorder with OCD symptoms and likely immune abnormalities, 5-HTT polymorphisms may be particularly relevant for this disorder. Objective This study aimed to test the association between the 5-HT genotypes and the presence of serum antibodies in patients with PANDAS. Method We compared the genotype frequencies and serum anti-streptococcal, anti-neural, and anti-enolase antibodies titers between 56 patients with PANDAS and 20 healthy controls from Mexico and Cuba. Results Antibody titers were higher (anti-enolase, anti-streptococcal) in PANDAS patients compared to healthy controls. No differences in anti-neural antibody levels between both groups were detected. The anti-enolase and anti-neural antibody titer increased according to the polymorphism of the PANDAS patients as follows: LL >SL >SS. Discussion and conclusion This is the first study evaluating the association between the 5-HTTLPR genotypes and antibody titers in PANDAS patients. Associations between polymorphisms in serotonergic genes and immune response could provide valuable information about the interaction between both systems. Our results suggest an association between the S allele and elevated antibody levels in PANDAS patients.
Resumen Introducción Se ha hipotetizado que el trastorno pediátrico neuropsiquiátrico autoinmune asociado a estreptococo (PANDAS) es resultado de una respuesta inmune anormal a una infección estreptocócica. Existe evidencia de que el sistema serotoninérgico está involucrado tanto en la fisiopatología del trastorno obsesivo compulsivo (TOC) como en procesos inmunológicos. En la región promotora de 5-HTT, gen que codifica el transportador de serotonina, podemos encontrar el polimorfismo 5-HTTLPR que se ha asociado con el TOC. Siendo PANDAS un trastorno con síntomas de TOC y probables anormalidades inmunes, los polimorfismos de 5-HTT pueden ser relevantes en este trastorno. Objetivo Evaluar la asociación entre los genotipos de 5-HT y la presencia de anticuerpos séricos en pacientes con PANDAS. Método Comparamos la frecuencia de genotipos de 5-HT y los títulos de anticuerpos anti-estreptococo, antineurales y antienolasa en suero de 56 pacientes con PANDAS y 20 controles sanos de México y Cuba. Resultados Los títulos de anticuerpos antienolasa y antiestreptococo fueron mayores en pacientes con PANDAS en comparación con los controles. El título de anticuerpos antienolasa y antineural aumentó de acuerdo con el polimorfismo de los pacientes con PANDAS de la siguiente manera: LL >SL >SS. Discusión y conclusión Éste es el primer estudio que evalúa la asociación entre los genotipos de 5-HTTLPR y anticuerpos en pacientes con PANDAS. Las asociaciones entre polimorfismos de genes serotoninérgicos y la respuesta inmune podrían proporcionar información sobre la interacción entre ambos sistemas. Nuestros resultados sugieren una asociación entre el alelo S y niveles altos de anticuerpos en pacientes con PANDAS.
ABSTRACT
Los trastornos neuropsiquiátricos autoinmunes pediátricos asociados a estreptococo (PANDAS) fueron creados para describir un subgrupo teórico de casos de trastornos obsesivo compulsivos (TOC) y / o tics en los que el inicio o la exacerbación de los síntomas es desencadenado por infección del estreptococo hemolítico del grupo A (SBHGA) ; Si bien aún no hay datos de incidencia se estima que el trastorno afecta aproximadamente al 1% de niños menores de 12 años, porque es menos probable que tengan anticuerpos contra el estreptococo y probablemente esté infradiagnosticado. La existencia de este trastorno ha generado considerables avances clínicos y científicos, así como controversia. Fisiopatológicamente, PANDAS se propone ser un trastorno autoinmune postestreptocócico similar a corea de Sydenham, hipotetizandose mas específicamente que los tics y la sintomatología obsesivo compulsiva son el resultado de la activación del sistema inmune adaptativo por el estreptococo del grupo A. Se presenta el caso de un paciente masculino de 6 años, con cuadro de tres semanas de evolución de movimientos involuntarios en cabeza y miembros superiores, así como cambios de conducta, cuyo antecedente de importancia fue una infección respiratoria y en piel varias semanas previo al inicio de los síntomas..(AU)
Subject(s)
Humans , Male , Child , Streptococcal Infections/complications , Neuropsychiatry , Nervous System Diseases , Risk Factors , ChoreaABSTRACT
OBJECTIVES: It has been reported that higher percentage of B cells react with monoclonal D8/17 antibody in patients with rheumatic fever, childhood onset obsessive-compulsive disorder, Tourette's disorder, or prepubertal anorexia nervosa. The purpose of this study is to replicate the previous studies in a Korean young population with tic disorder and to identify any relationship between D8/17 and clinical symptoms. METHODS: The binding of D8/17 to B cells was determined in patients with tic disorder (N=21) and healthy controls (N=9) by Fluorescence-Activated Cell Sorter analysis. RESULTS: In the sample examined by this study, the average percentage of B cells expressing D8/17 in tic disorder was 2.05%; healthy controls was 3.15%. No statistically significant differences were found in the mean percentages of D8/17 between the two groups. CONCLUSION: The expression of D8/17 in B cells was very low in this study. No subjects with tic disorder or healthy controls was above 12% in D8/17 positive proportion. Further studies, including higher number of patients and control group members, should be performed.
Subject(s)
Adolescent , Child , Humans , Anorexia Nervosa , B-Lymphocytes , Obsessive-Compulsive Disorder , Rheumatic Fever , Tic Disorders , Tics , Tourette SyndromeABSTRACT
We conducted a case control study to study the association between neuropsychiatric morbidity and group A streptococcal infections in children. Twenty two cases of neuropsychiatric morbidity were compared with 64 controls. Fourteen (63.6%) of the 22 cases were positive for ASO and/or ADNB while 21 of the 64 controls (32.8%) were positive for either or both antibodies (OR = 3.428; CI: 1.15 – 10.18; P=0.026). We conclude that there is a statistically significant association between neuropsychiatric morbidity and streptococcal infection in children.
ABSTRACT
CONTEXTO: A síndrome de Tourette (ST) caracteriza-se pela presença de tiques motores e pelo menos um tique fônico. Algumas semelhanças clínicas com a coréia reumática ou de Sydenham (CS) incentivaram a formulação da hipótese da existência de um grupo de transtornos neuropsiquiátricos associados a processo auto-imune decorrente de infecção estreptocócica (PANDAS). OBJETIVO: Revisar a literatura quanto às evidências em relação à hipótese de que mecanismos auto-imunes pós-estreptocócicos estão envolvidos na etiopatogênese da ST. MÉTODOS: Revisão sistemática na base de dados MedLine com os termos "Tourette", "tic", "PANDAS", "antibodies", "streptococcal" e "rheumatic". RESULTADOS: Retornaram 238 artigos da busca. Selecionaram-se 53 trabalhos, os quais tiveram suas referências bibliográficas também revisadas. São apresentados os resultados de estudos que avaliaram aspectos imunes na ST, incluindo anticorpos antiestreptocócicos e antinúcleos da base, e sua terapêutica imunebaseada, discutindo a validade do conceito de PANDAS. CONCLUSÕES: As evidências ainda não são satisfatórias no que tange a uma base auto-imune pós-estreptocócica para a ST. Um aprimoramento dos métodos investigativos e na seleção das amostras pode trazer maiores contribuições à questão.
BACKGROUND: Tourette's syndrome (TS) is characterized by the presence of motor tics and at least one phonic tic. Some clinical similarities with Sydenham's chorea (SC) lead to the hypothesis of a new group of disorders associated with an autoimmune process due to a streptococcal infection (PANDAS). Objective: To review the literature in search of evidence on the existence of post-streptococcal autoimmune mechanisms involved with the etiopathogenesis of TS. METHODS: A systematic review with the terms "Tourette", "tic", "PANDAS", "antibodies", "streptococcal" and "rheumatic" was carried on using the MedLine. RESULTS: The search found 238 articles. Fifty and three articles were selected which also had their references reviewed. The results of studies that investigated autoimmune aspects of TS, including anti-streptococcal and anti-basal ganglia anti-bodies, and immune-based therapy, were presented and discussed. DISCUSSION: The evidences to date are not satisfactory regarding a post-streptococcal auto-immune process in ST. The improvement on investigative methods and sample selection might contribute to this question.
Subject(s)
Autoimmune Diseases , Rheumatic Fever/immunology , Streptococcal Infections , Neurobiology , Tourette Syndrome/immunology , Tics/immunologyABSTRACT
Nesta revisão narrativa, o nosso objetivo foi descrever as síndromes neuropsiquiátricas pós estreptocócicas e discuti-las à luz das evidências científicas atuais sobre os possíveis mecanismos patogenéticos envolvidos. Nos últimos anos, uma série de distúrbios do movimento, como tiques, distonia, parkinsonismo, e transtornos psiquiátricos, como o transtorno obsessivo-compulsivo (TOC) e o transtorno da hiperatividade com déficit de atenção (THDA), vem sendo considerada parte do espectro das manifestações pós-estreptocócicas. O termo PANDAS (acrônimo do inglês: pediatric autoimmune neuropsychiatric disorder associated with streptococcus) foi inclusive cunhado para descrever um subgrupo de pacientes com TOC e tiques que inibe flutuação clínica dos sintomas associada a infecção estreptocócica. Entretanto a análise crítica das evidências clinicolaboratoriais não apóia esse espectro ampliado das manifestações pós-estreptocócicas. Apenas na coréia de Sydenham há evidências consistentes de patogênese mediada por processo auto-imune pós-estreptocócico.
In this narrative review, our objective was to describe the post-streptococcal neuropsychiatric syndromes and to discuss the possible pathogenetic mechanisms involved in their clinical expression. Recently, several movement disorders, such as tics, dystonia, and parkinsonism, and psychiatric disorders like obsessive-compulsive disorders (OCD) and attention deficit hyperativity disorder (ADHD), are being considered part of a putative spectrum of post-streptococcal infection disorder. The term PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcus) has been introduced to describe a subset of patients with these diagnoses in which onset of symptoms or symptom exacerbations are related to streptococcal infection. However the critical analysis of clinical and laboratory data does not support the hypothesis of an extended spectrum of post-streptococcal neuropsychiatric disorders. Only for Sydenham chorea there is consistent evidence for a post-streptococcal autoimmune mediated pathogenesis.
Subject(s)
Humans , Child , Cerebrum/immunology , Chorea/etiology , Central Nervous System Diseases/etiology , Streptococcal Infections/complications , Risk Factors , Streptococcus pyogenes , Tourette Syndrome/etiology , Obsessive-Compulsive Disorder/etiology , Motor Disorders/etiology , Tic Disorders/etiologyABSTRACT
En 1998, el Instituto Nacional de Salud Mental de los Estados Unidos definió los criterios de diagnóstico para los trastornos neuropsiquiá-tricos asociados a infección por estreptococo beta hemolítico del grupo A (PANDAS). Desde entonces se ha investigado la génesis de la autoinmunidad mediada por este microorganismo y sus impli-caciones clínicas, ya que se ha asociado con el trastorno obsesivo compulsivo, trastorno de la Tourette, corea de Sydenham y con menor evidencia con el trastorno de hiperactividad con déficit de atención, trastorno autista y anorexia nerviosa. La presente es una revisión sobre los aspectos más importantes que se han definido hasta el momento con respecto a la fisiopatología, presentación clínica y manejo de los pacientes del espectro PANDAS, pues son un grupo en el que se podrá cambiar el paradigma de tratamiento en psiquiatría de sintomático a etiológico. [Cadena LP, Toloza CR, Rueda GE. PANDAS: un modelo autoinmune de trastorno cerebral. MedUNAB 2004; 7:106-14]
PANDAS: an autoimmune model of mental disorder. In 1998, the National Institute of Mental Health defined the criteria of diagnosis for the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Since then there has been investigating the genesis of the autoimmunity caused by this micro-organism and its clinical implications, since it has been associated with the obsessive-compulsive disorder, Tourette's disorder and Sydenham's chorea and with minor evidence it has been related to of hyperactivity disorder with lack of attention, autistic disorder and anorexia nervosa. The present article is a review on the most important aspects that have been defined up to now in regards to the physiopatlogy, clinical presentation and management of the patients with PANDAS spectrum, since they are a group of diseases in which it will be possible to change the paradigm of treatment in Psychiatry, from being a symptomatic disease to an etiological one
Subject(s)
Humans , Streptococcus , Tourette Syndrome , Obsessive-Compulsive DisorderABSTRACT
The authors report a case of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and emotional lability. This is a 12-year-old girl who developed normally until the age of 11, when she had a high fever with headache followed by abnormal tic movement, emotional lability, ands high antistreptolysin-O (ASO) titer. The case illustrates difficulties in diagnosing and treating the PANDAS.