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PubMed2002

Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS).

BACKGROUND: 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.

Age Factors↗
PubMed2001

Gilles de la Tourette's syndrome with and without obsessive-compulsive disorder compared with obsessive-compulsive disorder without tics: which symptoms discriminate?

Stereotyped repetitive behaviors occur in Gilles de la Tourette's Syndrome (GTS) and obsessive-compulsive disorder (OCD). The present study was undertaken to compare the distribution of obsessive-compulsive and Tourette-related impulsive behaviors in GTS with (+) OCD, GTS without (-) OCD, tic-free OCD, and control subjects. Fourteen GTS + OCD, 18 GTS-OCD, 21 OCD-tic, and 29 control subjects were evaluated using a semistructured interview designed to assess GTS and OCD-related repetitive behaviors. Each reported item was evaluated on the presence of anxiety and goal-directedness. This information was subsequently used to define whether the repetitive behavior was an (anxiety-related) obsession or compulsion, or a (non-anxiety-related) OC-like behavior, impulsion. GTS + OCD subjects reported more overall Tourette-related impulsions than OCD-tic subjects, i.e., more mental play, echophenomena, and touching behaviors but similar frequencies of typical obsessive-compulsive behaviors. Further, GTS + OCD subjects exhibited more overall repetitive behaviors than GTS-OCD subjects, i.e., more Tourette-related impulsions as well as more obsessive-compulsive behaviors. The distribution of symptoms is similar in GTS with and without OCD, and differs from tic-free OCD. These differences suggest that GTS with OCD constitutes a form of GTS, not of OCD, although the possibility that GTS + OCD patients constitute a subgroup distinct from GTS and from OCD can not be excluded by this phenomenological study. Specific non-anxiety-related impulsions seem to discriminate between GTS and OCD-tic individuals. These impulsions possibly reflect differences in underlying mechanisms between GTS and OCD-tics.

Adult↗
PubMed1996

Sensorimotor gating in boys with Tourette's syndrome and ADHD: preliminary results.

Deficits in sensorimotor gating, defined by prepulse inhibition (PPI), have been associated with subcortical dopaminergic overactivity in animal and clinical studies. Utilizing supraorbital nerve electrical stimulation, we produced adequate blink responses and measured decreases in amplitude resulting from electric prestimuli just above sensory threshold. Seven boys comorbid for attention-deficit hyperactivity disorder (ADHD) and a tic disorder had significantly reduced PPI, compared to 14 screened controls and seven boys with ADHD alone. If independently replicated, these results may reflect greater neurologic immaturity in these comorbid subjects. Alternatively, these findings, together with other converging lines of evidence, suggest that deficient pallidal inhibition may be etiologically related to tic and movement disorders.

Adolescent↗
PubMed2001

Childhood-onset obsessive-compulsive disorder: a tic-related subtype of OCD?

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by recurrent obsessions or compulsions that cause significant impairment or distress. Although OCD was once perceived to be relatively rare in childhood, current estimates suggest that as many as half of all adult OCD cases may have their onset in childhood or adolescence. In general, there appears to be a great deal of continuity between the clinical presentation of OCD in children and that in adults. Yet, numerous differences have also been found between child and adult OCD, including differences in sex distribution, patterns of comorbidity, and degree of familial loading. These differences raise the issue of whether obsessive-compulsive symptoms that have their onset in childhood, but perhaps persist into adult life, are meaningfully different from those that emerge de novo in adulthood. In this article, current research on child- and adult-onset OCD is critically reviewed. It is proposed that child-onset OCD represents a phenomenologically and etiologically distinct subtype of OCD, bearing a close genetic relationship to tic-disorders and possibly sharing a common or similar pathogenesis. Clinical implications of the child- versus adult-onset OCD distinction are discussed.

Adolescent↗
PubMed1998

PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is a relatively new diagnostic construct applied to children or adolescents who develop, and have repeated exacerbations of, tic disorders and/or obsessive-compulsive disorder following group A beta-hemolytic streptococcal infections. The proposed pathophysiology is that the group A beta-hemolytic streptococcal bacteria trigger antibodies that cross-react with the basal ganglia of genetically susceptible hosts leading to obsessive-compulsive disorder and/or tics. This is similar to the etiologic mechanisms proposed for Sydenham's chorea, in which group A beta-hemolytic streptococcal antibodies cross-react with the basal ganglia and result in abnormal behavior and involuntary movements. When first proposed, there was much controversy about the idea that streptococcal infections were etiologically related to rheumatic fever. In a like manner, discussion has arisen about the concept of infection-triggered obsessive-compulsive disorder and tic disorders. We review the historical background to these controversies, give an update on the findings provided by research on PANDAS, and address areas of future study.

Adolescent↗
PubMed1978

Chronic, multiple tics of Gilles de la Tourette's disease. CSF acid monoamine metabolites after probenecid administration.

Central nervous system metabolism in six children and one adult with the syndrome of chronic multiple tics was studied by measuring the accumulation of acid metabolites of dopamine and serotonin (homovanillic acid [HVA] and 5-hydroxyindole-acetic acid [5-HIAA], respectively) in the CSF following probenecid administration. The accumulation of 5-HIAA was reduced in patients with multiple tics in contrast with other pediatric patients (N = 27). The degree of reduction in 5-HIAA relative to HVA appeared to be associated with the severity of the tic disorder. With dextroamphetamine, tic symptoms worsened, CSF HVA level decreased, and CSF 5-HIAA concentration increased. These findings suggest an association in Gilles de la Tourette's disease of reduced functioning of inhibitory serotonergic mechanisms and functional dopaminergic overactivity.

Adolescent↗
PubMedDate not supplied

Four-year follow-up of children with low intelligence and ADHD: a replication.

Twenty children with attention deficit hyperactivity disorder (ADHD) and low IQs, who participated in a drug study, were followed up 4.5 years later, when their ages averaged 12.4 years (range: 8-20 years: SD = 2.78). Participants were assessed by their parents and teachers on the Aberrant Behavior Checklist-Community (ABC; Aman & Singh, 1994), on the Child Symptom Inventory (CSI; Gadow & Sprafkin, 1994), and on a structured interview. A majority of children continued to screen positive for ADHD at follow-up, as well as display high rates of comorbid anxiety disorders, tics, and elimination disorders. Educational placement became slightly more restrictive over the follow-up interval. Multiple medication trials (30 in all, among 14 participants) were attempted between initial contact and follow-up. Ratings on the ABC by parents and teachers showed significantly lower scores at follow-up on the Hyperactivity subscale. Relatively few associations were found between initial ratings and follow-up ratings on standardized scales.

Adolescent↗
PubMed2000

Infection-triggered anorexia nervosa in children: clinical description of four cases.

BACKGROUND: 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.

Adolescent↗
PubMed1996

Case study: acute basal ganglia enlargement and obsessive-compulsive symptoms in an adolescent boy.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAs) may arise when antibodies directed against invading bacteria cross-react with basal ganglia structures, resulting in exacerbations of obsessive-compulsive disorder (OCD) or tic disorders. This is a report of severe worsening of obsessive-compulsive symptoms in an adolescent boy following infection with group A beta-hemolytic streptococci for whom serial magnetic resonance imaging scans of the brain were acquired to assess the relationship between basal ganglia size, symptom severity, and treatment with plasmapheresis. These data provide further support for basal ganglia-mediated dysfunction in OCD and the potential for immunological treatments in PANDAs patients.

Autoantibodies↗
PubMed1994

Autism: fifty years on from Kanner.

It is now 50 years since Leo Kanner first described autism as a distinctive pattern of symptoms in some children with severe developmental problems. Since then the assessment and diagnosis of children with pervasive disorders of development has been refined and much is known about the phenomenology and epidemiology. Autism is a biological disorder of the central nervous system (CNS) of unknown cause. It is associated with a number of organic disorders such as epilepsy and has comorbidity with other psychiatric disorders such as tic disorder. Cognitive abnormalities in social interactions, affect and language are present but there is still debate regarding which of these, if any, is the primary cognitive deficit. Special education and behavioral management has led to modest but important developmental improvement in many children with autism. Autism remains a life-long condition but patterns of symptoms change and skills develop from childhood into adult life.

Autistic Disorder↗
PubMed2001

[Psychiatric disorders in juvenile myoclonic epilepsy].

Mild personality problems have been described in patients with juvenile myoclonic epilepsy (JME), but clinical practice shows that JME can be diagnosed in patients with more or less severe psychiatric disorders (PD). The presence in JME patients of personality disorders has been described repeatedly, but never quantified. We thus decided to evaluate, using the DSM IV, the current prevalence and types of PD in a large series of consecutive, newly referred patients with JME. Among 170 consecutive JME cases referred to two departments of epileptology (Marseilles and Nice) between 1981 and 1998 (66 males, 104 females; aged 11.7-70; mean+/-SD 32.4+/-10.4 follow-up 12.7+/-10 [0.5-52]), we found 45 patients (26.5p.100) with PD. According to the DSM IV, they could be classified as severe mental retardation (main diagnosis) (one case); pervasive developmental disorders (2 cases); tic disorder (1 case); enuresis (1 case); psychotic disorders (5 cases, including schizophrenia paranoid type (1 case), disorganized type (1 case), delusional disorder (1 case), unspecified (2 cases)); depressive disorders (3 cases); generalized anxiety (6 cases); anorexia nervosa (2 cases); personality disorders (24 cases, including borderline personality (11 cases), dependent personality (5 cases), histrionic personality (2 cases), obsessive-compulsive personality (1 case), not specified (5 cases)). Sudden unexplained death occurred in 2 cases (borderline personality and pervasive developmental disorder not otherwise specified, respectively) and death due to pneumonia in 1 cases (anorexia). Although uncommonly severe cases of JME may have been selected in our referral centers, it appears that JME may be associated with PD. Comparatively mild personality disorders are the most common finding, and may be part of the clinical picture to some extent, while severe PD are less common, and probably coincidental. The presence of PD does not exclude the diagnosis of JME, and PD may represent a further challenge in the comprehensive care of these patients.

Adolescent↗
PubMed2000

Comorbidity in juvenile obsessive-compulsive disorder: a report from India.

OBJECTIVE: Using minimal exclusion criteria, to assess systematically the psychiatric comorbidity in children and adolescents with obsessive-compulsive disorder (OCD) and compare the findings with those of previous studies. METHOD: Fifty-four children and adolescents who satisfied DSM-III-R criteria for OCD were assessed using a structured interview schedule, the Children's version of the Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and the questionnaire for tic disorders. All 54 subjects were recruited from the Child and Adolescent Psychiatry (CAP) services of the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, South India. Diagnoses were determined consensually after a review of all the available data. RESULTS: Comorbidity was found in 69% of the sample: 22% were diagnosed with disruptive disorders; 20% met criteria for mood disorders; 19% had anxiety disorders; and 17% had tic disorders. Only 1 subject had bipolar disorder, and none had psychosis. The rates for individual diagnoses--in particular, the rates for disruptive disorders, bipolar disorder, and psychosis--were considerably lower than those reported in previous studies. CONCLUSIONS: Patterns of comorbidity in this study differed from those previously reported. Novel patterns of comorbidity with disruptive disorders, bipolar disorder, and psychosis reported in a few recent studies were not replicated in this study. These differences are probably due to different ascertainment methods. Comorbidity needs to be assessed in large epidemiological samples before definite associations can be made between certain comorbid disorders and juvenile OCD.

Adolescent↗
PubMed1996

Autonomic activity in children and adolescents with obsessive-compulsive disorder.

Electrodermal activity and heart rate were recorded from 55 children and adolescents with obsessive-compulsive disorder (OCD) and 58 normal subjects in a protocol that included rest and mild stress periods, and nonsignal and signal stimuli, to determine if autonomic activity might be involved in the pathogenesis of OCD or might be related to important clinical differences. Few differences were observed between OCD and normal subjects despite adequate power to detect small differences due to the large number of subjects. Thus, autonomic activity appears not to be an important etiological factor in childhood OCD. However, electrodermal activity showed consistent positive correlations with ratings of the severity of OCD symptoms (but not with anxiety or depression ratings), suggesting that severely afflicted cases are autonomically sensitive to OCD-related stimuli or, conversely, that low electrodermal activity may be protective of symptom severity. Patients with a coexisting tic disorder (not Tourette's syndrome) had larger electrodermal responses to a novel stimulus and higher heart rate variability than those without tics but did not differ from normal subjects. These few differences seem insufficient to support the hypothesis of a separate etiology of OCD cases with a coexisting tic disorder.

Adolescent↗
PubMed2003

Autoimmunity and the basal ganglia: new insights into old diseases.

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.

Autoimmune Diseases of the Nervous System↗
PubMed2003

Clinical characteristics of adult patients with tics and/or Tourette's syndrome.

OBJECTIVE: This study was conducted to describe the natural course of tic disorders over a long period of time in Japanese adults patients with Tourette's syndrome (TS) in terms of symptomatology. METHODS: An extensive literature on TS cases was reviewed selectively and 31 TS patients (mean age: 31.4 years; sex: 28 males and 3 females) at our outpatient clinic were examined. The mean follow-up period of the patients was 7.6 years (SD: 8.1; 0 to 26). All the data available for this study, including medical charts, were examined systematically by two experienced child psychiatrists. RESULTS: The adult patients with tic disorders could be classified into the four groups: group A - tics only, group B - tics + comorbidities, group C - comorbidities only and group D - sub-clinical (remission) cases. Our 31 subjects consisted of 10 patients (32.3%) for group A, 14 (45.2%) for group B, 7 (22.6%) for group C, and 0 for group D. CONCLUSIONS: Further investigation into the natural course and clinical characteristics of adult TS needs to be done in order to acquire a better understanding of the broad spectrum of TS and to make improvements to the treatment for this illness.

Adult↗
PubMed1997

[A case of congenital hypomyelination neuropathy with type I Chiari malformation and mental retardation].

A four-year old boy with congenital hypomyelination neuropathy (CHMN) had mental retardation and a tic disorder, the latter commencing at 2 years of age. The diagnosis of CHMN was confirmed by electron microscopy of his biopsied sural nerve which showed loss of large myelinated fibers, decreased density of myelinated fibers, many naked axons and atypical onion bulb formation. MR imaging showed type I Chiari malformation in the absence of clinical signs attributable to it. Auditory brainstem response (ABR) showed delayed wave I peak latency, prolonged I--III interpeak latency, broad wave II duration and normal III--V interpeak latency, suggesting abnormal peripheral and normal central myelination. The association of CHMN with mental retardation. Chiari malformation and tic disorder has never been reported, the significance of which remained unclear.

Arnold-Chiari Malformation↗
PubMed1993

[Unusual symptoms in brain tumors in childhood].

Headache, nausea, ataxia and diplopia are leading symptoms of brain tumors in children. We report of 3 children with unusual symptoms and findings. Patient 1 complained of occasional headaches. Clinical examination showed neurological deficits and uveitis. Lumbar puncture revealed a pleocytosis and the oligoclonal banding study was positive. Cranial MRI demonstrated an enlarged pons. Under treatment with cortisone a clinical improvement was seen, but no change of the abnormalities in MRI. Several weeks later a biopsy was performed, which verified an astrozytoma. The second child developed a torticollis, following an accident, and later a refractory constipation was noted. A clinical evaluation was within normal limits. Several weeks later the patient complained of bladder disturbances. Patient 3 had a lateralized tic disorder without any neurologic deficits. CT showed an infratentorial tumor above the 4th ventricle. The tic disorder vanished only after the tumor was completely resected in the second operation. The reported cases demonstrate the fact that in an individual patient a brain tumor can cause unusual symptoms and findings which do not make the diagnosis obvious.

Astrocytoma↗
PubMed2001

The PANDAS subgroup: recognition and treatment.

A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD) has been identified who share a common clinical course characterized by dramatic symptom exacerbations following Group A beta-hemolytic streptococcal (GABHS) infections. The term PANDAS has been applied to the subgroup, to indicate the postulated etiology of their symptoms: 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 (sawtooth course), association with neurological abnormalities (presence of adventitious movements or motoric hyperactivity during exacerbations), and temporal association between symptom exacerbations and GABHS infections. Post-streptococcal symptom exacerbations are typically quite dramatic, with patients reporting that their symptoms "...came on overnight" or "...appeared all of a sudden a few days after I had a sore throat." The post-streptococcal inflammatory nature of the neuropsychiatric symptoms provides novel opportunities for treatment and prevention, including immunomodulatory therapies such as therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG). A recently completed placebo-controlled trial revealed that both IVIG and TPE were effective in reducing neuropsychiatric symptom severity (40% to 55% reductions, respectively) for a group of severely ill children with OCD and/or tic disorders. Further research is required to determine why the treatments are helpful, as well as to ascertain whether or not antibiotic prophylaxis can help prevent post-streptococcal symptom exacerbations.

Journal Article↗