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1.
Neurol India ; 71(Supplement): S31-S38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37026332

RESUMO

Psychiatric disorders are the hidden pandemic of the current century. Despite major advances in medical management, the options for treatment are still limited. Neurosurgical intervention is effective for certain refractory psychiatric illnesses and the options range from stimulation surgeries to precise disconnection procedures influencing the neuronal network. Literature regarding stereotactic radiosurgery (SRS) is now enriched with successful treatment of obsessive compulsive disorder, major depression disorder, and anorexia nervosa. These procedures by reducing compulsions, obsessions, depression, and anxiety, improve substantially the quality of life for patients with a good safety profile. It is a valid treatment alternative for a selected group of patients who otherwise have no therapeutic options for whom the neurosurgical intervention is the only hope. It is also cost effective and highly reproducible among specialists. These procedures are adjuvant to the medical and behavioural treatment of psychiatric disorders. In this study the Contemporary role of Stereotactic radiosurgery is reviewed starting with relevant history of psychosurgery followed by individual psychiatric disorders.


Assuntos
Transtorno Obsessivo-Compulsivo , Psicocirurgia , Radiocirurgia , Humanos , Radiocirurgia/métodos , Qualidade de Vida , Psicocirurgia/história , Psicocirurgia/métodos , Transtorno Obsessivo-Compulsivo/cirurgia , Transtorno Obsessivo-Compulsivo/etiologia , Procedimentos Neurocirúrgicos/métodos
2.
Prog Brain Res ; 270(1): 171-183, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35396026

RESUMO

Psychiatric disorders result in great suffering of affected patients, who often have rather limited treatment options. In cases refractory to standard medical and behavioral therapy, interventional procedures may be the only feasible solution. The authors experience with Gamma Knife bilateral cingulotomy for treatment-resistant major depression disorder (5 cases) and anorexia nervosa (6 cases), and bilateral anterior capsulotomy for severe obsessive-compulsive disorder (10 cases) shows that such radiosurgical techniques may be applied both effectively and safely. During post-treatment follow-up, the vast majority of patients demonstrated gradual reduction of psychiatric symptoms and improvement of the quality of life, which was confirmed by results of regular neuropsychological testing and imaging examinations. No major side effect was observed in any case. More active application of radiosurgery (using standardized technique) for management of mental illnesses in various Gamma Knife centers worldwide should be encouraged.


Assuntos
Transtorno Obsessivo-Compulsivo , Psicocirurgia , Radiocirurgia , Humanos , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/cirurgia , Psicocirurgia/métodos , Qualidade de Vida , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Resultado do Tratamento
3.
Prog Brain Res ; 270(1): 185-195, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35396027

RESUMO

Gamma Knife radiosurgical capsulotomy has been performed for over 40 years as a rarely used surgical intervention for the treatment of obsessive-compulsive disorder. Over time, the procedure has evolved in many ways with most significant modifications being made in target location, number of isocenters and prescribed dose, subsequently producing changes in lesion size and geometry. Long-term clinical response data and adverse outcomes to the earlier empiric treatment parameters have resulted in shifting the target from its initial location within the midpoint of the anterior limb of internal capsule to a currently used point that includes its most ventral portion as well as the ventral striatum. This led to the contemporary Gamma Knife ventral capsulotomy procedure that focuses on ventral capsule/ventral striatum. Many of the early studies, despite demonstrating efficacy in some patients, were complicated by clinically relevant radiation-induced adverse effects. More recent studies have demonstrated strong efficacy with diminished adverse effects with well-placed lesions created at lower radiation doses. Advances in neuroimaging technology such as diffusion tensor imaging (DTI) based fiber tracking may provide further insight into precisely targeting of the ventral capsule/striatum based on patient-specific variations in white matter connectivity.


Assuntos
Transtorno Obsessivo-Compulsivo , Radiocirurgia , Imagem de Tensor de Difusão , Humanos , Cápsula Interna/diagnóstico por imagem , Cápsula Interna/cirurgia , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/cirurgia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Resultado do Tratamento
4.
Am J Psychiatry ; 178(1): 48-64, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32539528

RESUMO

OBJECTIVE: Pediatric obsessive-compulsive disorder (OCD) sometimes appears rapidly, even overnight, often after an infection. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, describes such a situation after infection with Streptococcus pyogenes. PANDAS may result from induced autoimmunity against brain antigens, although this remains unproven. Pilot work suggests that IgG antibodies from children with PANDAS bind to cholinergic interneurons (CINs) in the striatum. CIN deficiency has been independently associated with tics in humans and with repetitive behavioral pathology in mice, making it a plausible locus of pathology. The authors sought to replicate and extend earlier work and to investigate the cellular effects of PANDAS antibodies on cholinergic interneurons. METHODS: Binding of IgG to specific neurons in human and mouse brain slices was evaluated ex vivo after incubation with serum from 27 children with rigorously characterized PANDAS, both at baseline and after intravenous immunoglobulin (IVIG) treatment, and 23 matched control subjects. Binding was correlated with symptom measures. Neural activity after serum incubation was assessed in mouse slices using molecular markers and electrophysiological recording. RESULTS: IgG from children with PANDAS bound to CINs, but not to several other neuron types, more than IgG from control subjects, in three independent cohorts of patients. Post-IVIG serum had reduced IgG binding to CINs, and this reduction correlated with symptom improvement. Baseline PANDAS sera decreased activity of striatal CINs, but not of parvalbumin-expressing GABAergic interneurons, and altered their electrophysiological responses, in acute mouse brain slices. Post-IVIG PANDAS sera and IgG-depleted baseline sera did not alter the activity of striatal CINs. CONCLUSIONS: These findings provide strong evidence for striatal CINs as a critical cellular target that may contribute to pathophysiology in children with rapid-onset OCD symptoms, and perhaps in other conditions.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Neurônios Colinérgicos/imunologia , Corpo Estriado/imunologia , Transtorno Obsessivo-Compulsivo/imunologia , Infecções Estreptocócicas/imunologia , Animais , Doenças Autoimunes/complicações , Estudos de Casos e Controles , Criança , Pré-Escolar , Neurônios Colinérgicos/fisiologia , Corpo Estriado/fisiopatologia , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/etiologia , Infecções Estreptocócicas/complicações
6.
Cogn Behav Neurol ; 32(2): 124-133, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31205124

RESUMO

The two forms of obsessive-compulsive disorder (OCD), idiopathic and acquired, have been linked to abnormalities in the fronto-striato-thalamo-cortical circuitry, involving the orbitofrontal cortex, anterior cingulate cortex, thalamus, and striatum. Accumulating evidence indicates that damage to other brain regions (ie, temporal lobes) is also implicated in the pathogenesis of both types of OCD. In addition, some discrete OCD symptoms have received less attention because of their presumed low occurrence and difficultly of categorization. Among these, one intriguing and potentially severe type of obsessive thinking is the so-called "need to know" (NtK), which is a strong urge to access certain information, particularly proper names. In some patients, this monosymptomatic presentation may constitute the major feature of OCD. Here we report the cases of two patients who developed NtK obsessions with tenacious time-consuming, answer-seeking compulsions as the only or more disabling symptomatology in association with malignant tumors involving the right temporal lobe and connected fronto-subcortical circuits.


Assuntos
Encéfalo/diagnóstico por imagem , Nomes , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/psicologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/psicologia , Adulto , Atenção/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/etiologia , Complicações Pós-Operatórias/etiologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Teste de Sequência Alfanumérica
7.
Rev. Hosp. Ital. B. Aires (2004) ; 39(2): 64-66, jun. 2019.
Artigo em Espanhol | LILACS | ID: biblio-1048015

RESUMO

El trastorno obsesivo-compulsivo (TOC) afecta al 2% de la población general, llegando en ocasiones a causar un deterioro funcional severo y de la calidad de vida de las personas afectadas. Entre el 10 y el 30% de los pacientes con este trastorno no responde a los tratamientos recomendados: farmacológicos y terapia cognitivo-conductual. La Food and Drug Administration de los Estados Unidos (FDA) aprobó en el año 2008 la Estimulación cerebral profunda (ECP) para pacientes con TOC resistente a tratamiento. La ECP, utilizada frecuentemente para el tratamiento de la enfermedad de Parkinson refractaria, es una opción viable para los pacientes con TOC resistente, con efectos adversos poco frecuentes y transitorios. (AU)


Obsessive-compulsive disorder (OCD) affects 2% of the general population, sometimes resulting in severe impairment of functional capacity and quality of life of affected people. Between 10 and 30% of these patients do not respond to recommended treatments: pharmacological and cognitive behavioral therapy. In 2008, the FDA approved Deep Brain Stimulation (DBS) for patients with OCD resistant to treatment. DBS, frequently used for the treatment of refractory Parkinson's disease, is a viable option for the treatment of patients with resistant OCD, with infrequent and transient adverse effects. (AU)


Assuntos
Humanos , Estimulação Encefálica Profunda/métodos , Transtorno Obsessivo-Compulsivo/terapia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Qualidade de Vida , Sinais e Sintomas , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/tendências , Transtornos Mentais/cirurgia , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/tratamento farmacológico
8.
BMC Neurol ; 18(1): 60, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29720109

RESUMO

BACKGROUND: Pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS) is a specific autoimmune response to group-A streptococcal infections in children and adolescents with a sudden onset of obsessive-compulsive disorders or tic-like symptoms. Cerebral metabolic changes of patients have not yet been observed. CASE PRESENTATION: We present a case of an 18-year old male with a PANDAS-like condition after developing tic-like symptoms and involuntary movements three weeks after cardiac surgery. The patient had suffered from pharyngotonsillitis before the symptoms started. The anti-streptolysin O (ASO) titer was elevated (805 kU/l). Antibiotic therapy did not improve his condition. Intravenous immunoglobulins and high-dose cortisone therapy had minor beneficial effects on his involuntary movements. 18F-Fluorodeoxyglucose positron emission tomography/ computer tomography (18F-FDG PET/CT) demonstrated pronounced hypermetabolism of the basal ganglia and cortical hypometabolism. The patient was treated with five cycles of plasmapheresis. A marked clinical improvement was observed after four months. Cerebral metabolic alterations had completely normalized. CONCLUSIONS: This is the first report of cerebral metabolic changes observed on FDG-PET/CT in a patient with a PANDAS-like condition with a normalization following immunomodulatory treatment. Cerebral FDG-PET/CT might be a promising tool in the diagnosis of PANDAS.


Assuntos
Doenças Autoimunes/terapia , Encéfalo/fisiopatologia , Glucose/metabolismo , Plasmaferese/métodos , Infecções Estreptocócicas/complicações , Adolescente , Antibacterianos/uso terapêutico , Doenças Autoimunes/etiologia , Doenças Autoimunes/fisiopatologia , Autoimunidade , Encéfalo/metabolismo , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Infecções Respiratórias/complicações , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/psicologia
9.
Braz J Psychiatry ; 40(4): 349-353, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29451585

RESUMO

OBJECTIVE: To evaluate the association between abuse of and dependence on different psychoactive substances and the presence of anxiety disorders in a sample of young adults from a city in southern Brazil. METHODS: Between 2007 and 2009, we carried out a cross-sectional, population-based study of individuals aged 18-24 years who lived in Pelotas, a city in southern Brazil. We evaluated anxiety disorders using the Mini International Neuropsychiatric Interview 5.0 (MINI), and use of psychoactive substances with the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST 2.0/0MS). We used Fisher's exact test for univariate analysis, and Poisson regression models with robust variance for multivariable analysis. RESULTS: The sample consisted of 1,560 young adults. The overall prevalence of abuse/dependence was 26.9% for alcohol, 24.9% for tobacco, and 7.3% for illicit substances. Individuals with agoraphobia had a 32% higher prevalence of tobacco abuse/dependence (prevalence ratio [PR] = 1.32 [95%CI 1.01-1.74]). Individuals with posttraumatic stress disorder (PTSD) or generalized anxiety disorder (GAD) had a 2.41-fold (95%CI 1.22-4.77) and 1.76-fold (95%CI 1.00-3.11) higher prevalence of illicit substance abuse/dependence, respectively. CONCLUSION: In this population-based sample, we found associations between GAD, PTSD, and increased prevalence of illicit substance abuse/dependence. In addition, individuals with agoraphobia seem to have increased tobacco abuse/dependence.


Assuntos
Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtornos de Ansiedade/epidemiologia , Psicotrópicos/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Tabagismo/epidemiologia , Adolescente , Agorafobia/complicações , Agorafobia/epidemiologia , Agorafobia/etiologia , Transtornos Relacionados ao Uso de Álcool/complicações , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/etiologia , Brasil/epidemiologia , Análise por Conglomerados , Estudos Transversais , Feminino , Humanos , Entrevista Psicológica , Masculino , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/etiologia , Prevalência , Transtornos de Estresse Pós-Traumáticos/complicações , Inquéritos e Questionários , Tabagismo/complicações , Adulto Jovem
10.
J Neurogenet ; 31(3): 153-160, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28608743

RESUMO

Obsessive-compulsive disorder (OCD) is characterized by recurrent obtrusive and repetitive acts typically occurred following anxiety. In the last two decades, studies done on the gene sequences, large-scale and point mutations and gene-gene, gene-environment and gene-drug interactions have led to the discovery of hundreds of genes associated with OCD. Although each gene in turn is a part of the etiology of this disorder; however, OCD, like other mental disorders is complex and a comprehensive and integrated view is necessary to understand its genetic basis. In this study, through an extensive review of existing published studies, all genes associated with OCD were found. Then, in order to integrate the results, all the interactions between these genes were explored and the achievement was represented as an interactive genetic network. Furthermore, the reconstructed network was analyzed. It was found that GRIN2A, GRIN2B and GRIA2 are the most central nodes in the network. Functional and pathway enrichment analysis showed that glutamate-related pathways are the main deficient systems in patients with OCD. By studying genes shared between OCD and other diseases, it was cleared that OCD, epilepsy and some types of cancer have the most number of shared genes. The results of this study, in addition to reviewing the available results as a comprehensive and integrated manner, provide new hypotheses for future studies.


Assuntos
Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/genética , Receptores de N-Metil-D-Aspartato/genética , Feminino , Redes Reguladoras de Genes/genética , Predisposição Genética para Doença/genética , Testes Genéticos , Humanos , Masculino , Receptores de AMPA/genética
11.
Int J Pediatr Otorhinolaryngol ; 92: 38-44, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28012531

RESUMO

INTRODUCTION: Accumulating evidence supports a role for inflammation in psychiatric illness, and the onset or exacerbation of psychiatric symptoms may follow non-CNS infections. Here, we provide the first detailed description of obsessive-compulsive and related psychiatric symptoms arising concurrently with sinusitis. METHODS: We reviewed the charts of 150 consecutive patients evaluated in our Pediatric Acute-onset Neuropsychiatric Syndromes clinic for documented sinusitis as defined by the American Academy of Pediatrics guidelines. Sinusitis treatments, sinonasal imaging, and neuropsychiatric symptoms before, during, and after sinusitis onset were noted. Patients were included in the final review if they had a clear diagnosis of isolated sinusitis (without concurrent illness and/or immunodeficiency), and were evaluated during an episode of sinusitis. RESULTS: 10/150 (6.6%) patients had isolated sinusitis at the time of their neuropsychiatric deterioration. Eight patients received antibiotics to treat sinusitis, three of whom also received sinus surgery. Neuropsychiatric symptoms improved in all eight patients concurrent with resolution of sinusitis per parent report and clinician assessment. One patient did not follow through with recommended sinus surgery or antibiotics and her psychiatric symptoms persisted. One patient was lost to follow-up. CONCLUSIONS: Improvement of psychiatric symptoms correlated with resolution of sinus disease in this retrospective study. Identification, treatment, and resolution of underlying infections, including sinusitis, may have the potential to change the trajectory of some neuropsychiatric illnesses. Randomized clinical trials are needed.


Assuntos
Transtornos Mentais/etiologia , Sinusite/psicologia , Adolescente , Antibacterianos/uso terapêutico , Criança , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/etiologia , Estudos Retrospectivos , Sinusite/tratamento farmacológico , Sinusite/cirurgia
12.
JAMA Psychiatry ; 73(11): 1135-1144, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27706475

RESUMO

IMPORTANCE: Perinatal complications may increase the risk of obsessive-compulsive disorder (OCD). Previous reports were based on small, retrospective, specialist clinic-based studies that were unable to rigorously control for unmeasured environmental and genetic confounding. OBJECTIVE: To prospectively investigate a wide range of potential perinatal risk factors for OCD, controlling for unmeasured factors shared between siblings in the analyses. DESIGN, SETTING, AND PARTICIPANTS: This population-based birth cohort study included all 2 421 284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1 403 651 families in the cohort, differentially exposed siblings from the 743 885 families with siblings were evaluated; of these, 11 592 families included clusters of full siblings that were discordant for OCD. Analysis of the data was conducted from January, 26, 2015, to September, 5, 2016. EXPOSURES: Perinatal data were collected from the Swedish Medical Birth Register and included maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age (for preterm birth), birth weight, birth weight in relation to gestational age, 5-minute Apgar score, and head circumference. MAIN OUTCOMES AND MEASURES: Previously validated OCD codes (International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish National Patient Register. RESULTS: Of 2 421 284 individuals included in the cohort, 17 305 persons were diagnosed with OCD. Of these, 7111 were men (41.1%). The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years. An increased risk for OCD remained after controlling for shared familial confounders and measured covariates (including sex, year of birth, maternal and paternal age at birth, and parity), for smoking 10 or more cigarettes per day during pregnancy (hazard ratio [HR], 1.27; 95% CI, 1.02-1.58), breech presentation (HR, 1.35; 95% CI, 1.06-1.71), delivery by cesarean section (HR, 1.17; 95% CI, 1.01-1.34), preterm birth (HR, 1.24; 95% CI, 1.07-1.43), birth weight 1501 to 2500 g (HR, 1.30; 95% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08; 95% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95% CI, 1.05-1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95% CI, 1.07-2.09). Gestational age and birth weight followed inverse dose-response associations, whereby an increasingly higher risk for OCD was noted in children with a shorter gestational age and lower birth weight. We also observed a dose-response association between the number of perinatal events and increased OCD risk, with HRs ranging from 1.11 (95% CI, 1.07-1.15) for 1 event to 1.51 (95% CI, 1.18-1.94) for 5 or more events. CONCLUSIONS AND RELEVANCE: A range of perinatal risk factors is associated with a higher risk for OCD independent of shared familial confounders, suggesting that perinatal risk factors may be in the causal pathway to OCD.


Assuntos
Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/etiologia , Assistência Perinatal , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Adulto , Índice de Apgar , Peso ao Nascer , Apresentação Pélvica , Estudos de Casos e Controles , Cesárea , Estudos de Coortes , Epigênese Genética , Feminino , Interação Gene-Ambiente , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/genética , Masculino , Transtorno Obsessivo-Compulsivo/genética , Gravidez , Estudos Retrospectivos , Fatores de Risco , Irmãos , Suécia , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto Jovem
13.
J Am Acad Child Adolesc Psychiatry ; 55(9): 784-91, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27566119

RESUMO

OBJECTIVE: We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD). METHOD: In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions. RESULTS: In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio = 1.66, 95% CI = 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than 2-fold increased risk for TS/CT with any non-ADHD psychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships. CONCLUSION: Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT.


Assuntos
Transtorno Obsessivo-Compulsivo/etiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Fumar/efeitos adversos , Transtornos de Tique/etiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Lactente , Masculino , Transtorno Obsessivo-Compulsivo/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/epidemiologia , Transtornos de Tique/epidemiologia , Síndrome de Tourette/epidemiologia , Síndrome de Tourette/etiologia
15.
Int J Pediatr Otorhinolaryngol ; 80: 49-52, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26746612

RESUMO

OBJECTIVE: To determine if Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) patients demonstrate a significantly different number of B-Cells or markers of activity when compared to recurrent Group A Streptococcus or Obstructive Sleep Apnea patients. STUDY DESIGN: Prospective Cohort Study. STUDY SETTING: Academic University Hospital. METHODS: Tonsil tissue was collected from twenty-two patients in the operating room and organized into three groups. Ten clinically diagnosed PANDAS, six Group A Streptococcus and six Obstructive Sleep Apnea patients were included in this study. Each tissue sample was extracted with MSD Tris Lysis Buffer and protein lysates were analyzed for CD 19, B-Cell Activating Factor and B-Cell Activating Receptor by western blot methods. RESULTS: Based on ANOVA analysis, there was no significant difference in the expression of B-Cell Activating Factor, B-Cell Activating Receptor or CD 19 when comparing the three study groups by western blot analysis methods. CONCLUSIONS: In this prospective cohort study, it appears that PANDAS patients do not demonstrate increased number of B-Cells, expression of B-Cell Activating Factor or B-Cell Activating Receptor when compared to Group A Streptococcus or Obstructive Sleep Apnea cohorts. As a result, further evaluation of the cell-mediated immune system is warranted to provide further insight into the pathophysiology of PANDAS. In addition, we must investigate if PANDAS patients only demonstrate increased B-Cell number or activity when undergoing an acute Tic/OCD exacerbation.


Assuntos
Doenças Autoimunes/imunologia , Linfócitos B/química , Tonsila Palatina/química , Infecções Estreptocócicas/imunologia , Streptococcus pyogenes , Antígenos CD19/análise , Doenças Autoimunes/microbiologia , Doenças Autoimunes/psicologia , Fator Ativador de Células B/análise , Receptor do Fator Ativador de Células B/análise , Linfócitos B/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/etiologia , Tonsila Palatina/patologia , Estudos Prospectivos , Apneia Obstrutiva do Sono/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/psicologia
16.
J Child Adolesc Psychopharmacol ; 25(1): 76-85, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25658702

RESUMO

BACKGROUND AND OBJECTIVE: Antineuronal antibodies have been implicated in tic and obsessive compulsive disorders (OCD) associated with group A streptococcal infections. We investigated antineuronal autoantibody levels as well as antibody-mediated neuronal cell signaling activity, as previously reported for Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS), to determine immunological profiles for a large cohort of children with tics and/or OCD. METHODS: Study participants (n=311; ages 4-27 years, 66% male) were selected from a larger group of individuals with self-reported neuropsychiatric symptoms (n=742) and included only those with accurate knowledge of group A streptococcal infection status, except for four individuals in whom streptococcal infection status was unknown. Healthy control samples (n=16; ages 5-14 years, 81% male), came from the National Institute of Mental Health and Yale University. In addition to serum donations, participants and/or legal guardians provided neuropsychiatric and related medical histories of symptoms that had lasted >1 year. Antineuronal immunoglobulin G (IgG) titers were measured by standard enzyme-linked immunosorbent assay (ELISA) and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was tested in serum. RESULTS: Of 311 individuals, 222 (71%) had evidence of group A streptococcal infection, which was associated with tics and/or OCD status (p=0.0087). Sera from individuals with tics and/or OCD (n=261) had evidence of elevated serum IgG antibodies against human D1R (p<0.0001) and lysoganglioside (p=0.0001), and higher serum activation of CaMKII activity (p<0.0001) in a human neuronal cell line compared with healthy controls (n=16). Furthermore, patients with tics and OCD had significantly increased activation of CaMKII activity compared with patients with only tics or only OCD (p<0.033 for each). CONCLUSION: Our study suggested a significant correlation of streptococcal-associated tics and OCD with elevated anti-D1R and antilysoganglioside antineuronal antibodies in serum concomitant with higher activation of CaMKII in human neuronal cells. Youth and young adults with chronic tics and OCD may have underlying infectious/immunologic etiology.


Assuntos
Autoanticorpos/sangue , Neurônios , Transtorno Obsessivo-Compulsivo/sangue , Infecções Estreptocócicas/sangue , Tiques/sangue , Adolescente , Adulto , Linhagem Celular Tumoral , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/etiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/diagnóstico , Tiques/diagnóstico , Tiques/etiologia , Adulto Jovem
17.
JAMA Otolaryngol Head Neck Surg ; 141(3): 272-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25569020

RESUMO

IMPORTANCE: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) in children describes neuropsychiatric symptom exacerbations that relate temporally to streptococcal infections. Recent case reports suggest tonsillectomy may effectively reduce these symptoms; however, no consensus treatment guidelines exist. This study examines whether tonsillectomy improves neuropsychiatric symptoms in children with PANDAS who have incomplete response to antibiotic therapy. OBSERVATIONS: Ten patients met strict diagnostic criteria for PANDAS. Comparisons were made between parental reports of symptom severity at diagnosis, after antibiotic treatment (in 10 patients), and after tonsillectomy (in 9). From a baseline severity score of 10, antibiotics alone improved symptoms to a median (interquartile range [IQR]) score of 8 (6.5-10.0) (P = .03). Nine children who subsequently underwent tonsillectomy reported symptom improvement in comparison with treatment with antibiotics alone, including those with no response to antibiotics. Symptom severity improved at all periods after tonsillectomy compared with antibiotics alone. The median score [IQR] 3 months postoperatively was 3 (0.0-6.5) (P = .01); 6 months postoperatively, 3 (0.0-5.0) (P = .02); 1 year postoperatively, 3 (0.0-5.0) (P = .02); and 3 years postoperatively, 0.5 (0.0-2.3) (P = .03). Four of the 9 had complete resolution after tonsillectomy. CONCLUSIONS AND RELEVANCE: This PANDAS cohort whose neuropsychiatric symptoms did not respond sufficiently to antibiotics may have gained benefit from tonsillectomy.


Assuntos
Ansiedade/terapia , Doenças Autoimunes/complicações , Transtorno Obsessivo-Compulsivo/terapia , Infecções Estreptocócicas/complicações , Transtornos de Tique/terapia , Tonsilectomia , Antibacterianos/uso terapêutico , Ansiedade/etiologia , Criança , Feminino , Seguimentos , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Transtornos de Tique/etiologia
18.
J Clin Neurosci ; 22(2): 398-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25124646

RESUMO

Structural lesions of the basal ganglia may lead to obsessive compulsive disorder (OCD). We report a 31-year-old woman who developed OCD after a previously asymptomatic left caudate intracerebral cavernous malformation (ICM) hemorrhaged. Her neurologic examination was normal. Her OCD required hospitalization and improved with medication and therapy. The pathophysiology of this psychiatric disorder probably reflects a frontal cortex deafferentation mechanism. In patients with known ICM, any abrupt change in neurologic or psychiatric symptoms should prompt repeat imaging to assess for hemorrhage.


Assuntos
Núcleo Caudado , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemorragias Intracranianas/complicações , Transtorno Obsessivo-Compulsivo/etiologia , Adulto , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/psicologia , Hospitalização , Humanos , Hemorragias Intracranianas/psicologia , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/terapia , Córtex Pré-Frontal/patologia , Resultado do Tratamento
19.
Int J Immunopathol Pharmacol ; 27(3): 371-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25280028

RESUMO

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.


Assuntos
Doenças Autoimunes/etiologia , Transtorno Obsessivo-Compulsivo/etiologia , Infecções Estreptocócicas/complicações , Streptococcus pyogenes , Tiques/etiologia , Tonsilectomia , Adenoidectomia , Criança , Feminino , Humanos , Masculino
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