[Misdiagnosis of eyelid myoclonia as Tic's disorder: a case report].
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Diagnostic Errors↗
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Psychiatric and neurological predictors of early ADHD medication discontinuation across the lifespan: a multinational study.
BACKGROUND: Early discontinuation of attention-deficit/hyperactivity disorder (ADHD) medication is common and linked to worse outcomes. Identifying clinical predictors could aid personalised treatment yet evidence is inconsistent across ages and countries/regions. OBJECTIVE: Investigate psychiatric and neurological comorbidity as predictors of early ADHD medication discontinuation in new ADHD medication users across age groups, sex and countries/regions. METHODS: Using health records from eight countries/regions, we identified 1 000 411 (44% female) new ADHD medication users (2011-2020). Discontinuation was defined as a ≥180 day gap between dispensations. We examined 23 indicators of psychiatric or neurological comorbidity, severity and psychotropic medication use. Associations were estimated using Cox regression, pooled with random-effects meta-analyses and stratified by age-at-initiation and sex. FINDINGS: Discontinuation rates varied widely (children 19%-61%, adolescents 37%-68%, young adults 52-67%, adults 38%-68%). In pooled analyses, earlier discontinuation in children was predicted by intellectual disability, autism and use of psychotropic medications (HR range 1.32-1.51), while conduct/oppositional defiant disorder (CD/ODD) was protective (HR 0.83, 95% CI 0.73 to 0.94). In adolescents, no indicators remained statistically significant after multiple-testing control. In young adults, CD/ODD (HR 1.42, 95% CI 1.30 to 1.55), and in adults, schizophrenia (HR 1.25, 95% CI 1.09 to 1.44) and tic disorders (HR 1.27, 95% CI 1.11 to 1.46) predicted earlier discontinuation. Statistical heterogeneity was substantial, largely driven by US estimates. In meta-analyses excluding the USA, additional associations emerged. For example, in children, OCD and anxiety disorders predicted earlier discontinuation, while eating disorders and antidepressants/anxiolytics were protective in adults. Associations with schizophrenia, tic disorders and CD/ODD were no longer significant. Country-specific analyses showed similar association patterns, except in the USA, Hong Kong and the UK. Sex differences were limited. CONCLUSIONS: Children with neuropsychiatric comorbidity and related comedication are more likely to discontinue ADHD medication early, whereas few consistent predictors were seen from adolescence onwards. Marked cross-country variation, particularly in the USA, points to system-level influences on treatment patterns. CLINICAL IMPLICATIONS: Improving ADHD medication persistence will require consideration of healthcare context and age-specific strategies, including close monitoring for children with complex neuropsychiatric profiles, and consideration of broader factors in adolescents and adults, where clinical predictors were limited.
Humans↗
Extrapyramidal symptoms with ritonavir/indinavir plus risperidone.
OBJECTIVE: To report a case of suspected extrapyramidal symptoms (EPS) in a patient initiated on ritonavir and indinavir while taking risperidone for a tic disorder. CASE SUMMARY: A 35-year-old white man with AIDS received risperidone 2 mg twice daily for treatment of a Tourette's-like tic disorder. Ritonavir and indinavir were initiated, and 1 week later, he experienced significantly impaired swallowing, speaking, and breathing, and worsening of his existing tremors. Ritonavir and indinavir were discontinued. On the same day, the patient increased the risperidone dosage to 3 mg twice daily. Symptoms continued to worsen over the next 3 days. All investigations and laboratory parameters were unremarkable, and vital signs were stable. Risperidone was discontinued and clonazepam initiated. Three days later, the patient's symptoms were significantly improved. DISCUSSION: The symptoms described herein are consistent with neuroleptic-induced acute dystonia and potentially neuroleptic-induced parkinsonism. We believe this adverse effect occurred as a result of a drug interaction between ritonavir/indinavir and risperidone. Based on the pharmacokinetics of these medications, we hypothesize that inhibition of CYP2D6 and CYP3A4 by ritonavir and indinavir may have resulted in an accumulation of the active moiety of risperidone, which may explain the occurrence of EPS in this patient. CONCLUSIONS: This is the second published case report describing a suspected drug interaction with ritonavir, indinavir, and risperidone. Caution is warranted when risperidone is prescribed with ritonavir/indinavir, and possibly with other antiretrovirals that inhibit the same pathways.
Acquired Immunodeficiency Syndrome↗
Antineural antibody in patients with Tourette's syndrome and their family members.
It has been proposed that antineural antibodies were present in patients with Tourette's syndrome (TS) and other neuropsychiatric disorders. The purpose of our study was to investigate the presence of antineural antibodies in the individuals with Tourette's syndrome and the family members of TS patients. The sera of four TS patients with no current streptococcal infection, their tic-free family members including father, mother and sibling, and a age-matched control group who were tic free were assayed for antineural antibodies directed against rat tissue and neurons in primary cell culture. There were prominent antineural antibodies present in TS patients and their first-degree family members, but not in the control group. Western blotting showed proteins of about 120 kDa in their sera that were not present in the sera of controls. The preliminary results of our study suggest the importance of genetic vulnerability in the immunological pathophysiology of tic disorders. Future studies should investigate the interactions of genetics, environment, infectious agents, and immunity on symptom expression in families with tic disorders.
Adolescent↗
[Aatypical antipsychotics in child and adolescent psychiatry--indications apart from schizophrenia].
OBJECTIVES: Given their special receptor profile, atypical antipsychotics are effective in the treatment of both positive and negative symptoms. Especially the serotonergic affinity suggests their potential utility for the treatment of depressive, anxious, and obsessive-compulsive symptoms as well. Reviewed here are the clinical experience with, studies of, and published reports on the use of atypical antipsychotics in the treatment of different psychiatric disorders other than schizophrenia in children and adolescents. METHODS: The literature from 1998-2004 was reviewed by means of PubMed and CurrentContents. RESULTS: In addition to schizophrenic symptoms, the therapeutic indications for atypical antipsychotics include tic disorders, bipolar affective disorders and mania, impulsiveness and disruptive behaviour, (auto-)aggression, and severe anorexia nervosa. Empirical data such as those from placebo-controlled double-blind or open-label studies in larger child and adolescent populations are rare. Substances are used mostly off-label. CONCLUSIONS: Atypical antipsychotics today comprise part of the standard psychopharmacotherapy in child and adolescent psychiatry. They have proved to be effective in the treatment of schizophrenia, tic disorders, impulsiveness, (auto-)aggression, and eating disorders.
Adolescent↗
Overuse of EEG in the evaluation of common neurologic conditions.
The objective of the present study was to analyze the diagnostic indications that most often prompt the referral of children and adolescents in the outpatient clinical pediatric practice for electroencephalographic evaluation and to check its utility in these clinical conditions. The electroencephalographic records of 547 consecutive children and adolescents (5-16 years of age) referred to a single community laboratory for the evaluation of various neurologic disorders were prospectively read by a single blinded investigator. Common diagnostic indications included the following: clinical seizures (42%), attention-deficit-hyperactivity disorder (23%), headaches (10.4%), syncope (9.9%), and tic disorder (4.9%). Overall, 76% of records were normal. Slowing of electroencephalographic activity was noted in 1% (attention-deficit-hyperactivity disorder) to 26% (probable epilepsy), and epileptiform activity in 53% of the probable and 29% of the clinically possible epileptics. Epileptiform activity was rarely found in the nonepileptic patients. The results of the present study demonstrate that standard interictal electroencephalogram is being overused during evaluation of various neurologic disorders in children and adolescents, suggesting that its use should be reserved for supporting the diagnosis in those cases in which epilepsy is a reasonable clinical possibility.
Adolescent↗
[Tic disease. Current genetic and neurochemical factors].
We review historical, conceptual, clinical and diagnostic criteria as well as present genetic and neurochemical factors of tic disorders. Epidemiologic data suggest that tic is an organic disease with autosomal dominant transmission. We emphasize immunohistochemical studies particularly related to the dopaminergic, noradrenergic and serotonergic systems. These modulate the activity of the cortico-striato-thalamocortical circuits implicated in both Tourette's syndrome and obsessive-compulsive disorder.
Female↗
Blink reflex abnormalities in Tourette syndrome.
OBJECTIVE: Tourette syndrome (TS) is a not uncommon disorder which represents the most complex manifestation of the spectrum of tic disorders, with onset during childhood or early adolescence. There are no definitive tests for diagnosis of TS. The objective of this study has been to demonstrate whether neurophysiological abnormalities of the blink reflex can be observed in patients affected with TS and correlate with the severity of TS. METHODS: We enrolled 17 patients with Tourette syndrome, diagnosed according to DSM IV Diagnostic Criteria, and 10 healthy volunteers. Tic severity was assessed using a self rating scale (Tourette Syndrome Symptom List, TSSL) and examiner ratings (Yale Global Tic Severity Scale (YGTSS), and Tourette-Syndrome Global Scale (TSGS)). The blink reflex was elicited by stimulating the supraorbital nerve in order to measure the early response (R1), homolateral and contralateral R2 (late) responses, amplitude of R1 and duration of R2. RESULTS: We observed a mean duration of R2 significantly longer in the patient group than in the control group (P<0.01, Student t test), without any statistically significant differences of R1 and R2 latencies and of R1 amplitude between the patient group and the control group. Correlations between changes in clinical rating scores and R2 duration were tested by simple linear regression analysis, which has not demonstrated a significant correlation between TSSL scores, clinical rating scores (measured by TSGS and YGTSS) and duration of R2. CONCLUSIONS: A pattern as to excitability of the blink reflex can be a frequent abnormality in TS patients, not correlated with its severity.
Adult↗
Tourette's syndrome: are stimulants safe?
Clinicians commonly encounter children with comorbid attention deficit hyperactivity disorder (ADHD) and the tic disorder Tourette's syndrome. The pharmacologic treatment of children with this particular combination of conditions has been problematic because of long-standing warnings against using psychostimulants due to concerns about worsening tics. The basis for these warnings was anecdotal clinical observations. A recent group of placebo-controlled, double-blinded clinical trials have consistently shown that certain stimulants, particularly methylphenidate and dextroamphetamine, are effective, well tolerated, and safe when administered to treat ADHD in children with tics. Methylphenidate appears to be the best-tolerated stimulant compound, with tics often lessening during treatment.
Animals↗
Ziprasidone treatment of children and adolescents with Tourette's syndrome: a pilot study.
OBJECTIVE: To evaluate the efficacy and tolerability of ziprasidone in children and adolescents with Tourette's syndrome and chronic tic disorders. METHOD: Twenty-eight patients aged 7 to 17 years were randomly assigned to ziprasidone or placebo for 56 days. Ziprasidone was initiated at a dose of 5 mg/day and flexibly titrated to a maximum of 40 mg/day. RESULTS: Ziprasidone was significantly more effective than placebo in reducing the Global Severity (p = .016) and Total Tic (p = .008) scores on the Yale Global Tic Severity Scale. Compared with placebo, ziprasidone significantly reduced tic frequencies as determined by blind videotape tic counts (p = .039). The mean (+/- SD) daily dose of ziprasidone during the last 4 weeks of the trial was 28.2 +/- 9.6 mg. Mild transient somnolence was the most common adverse event. No clinically significant effects were observed on specific ratings of extrapyramidal symptoms, akathisia, or tardive dyskinesia. CONCLUSIONS: In this limited sample, ziprasidone (5-40 mg/day) appears to be effective and well tolerated in the treatment of Tourette's syndrome. Ziprasidone may be associated with a lower risk of extrapyramidal side effects in children. However, additional studies are necessary to evaluate more fully its safety and efficacy in children with tic disorders.
Adolescent↗
Tourette's syndrome. Tics, jerks, and quirks.
Over the past 20 years, public and physician awareness of tic disorders, including Tourette's syndrome, has increased remarkably. In fact, Tourette's syndrome is now "diagnosed" by many families before they consult a physician. Patients seek help not only for the involuntary movements and noises that characterize the illness but also for the accompanying learning, behavioral, and social problems. The authors of this article define the various tic disorders and discuss diagnosis and treatment of the most severe type, Tourette's syndrome.
Adolescent↗
Bilineal transmission and phenotypic variation of Tourette's disorder in a large pedigree.
OBJECTIVE: Variability in the clinical phenotype of Tourette's disorder (TD) was assessed in a single large family, with a focus on the influence of bilineal transmission. METHOD: Tics, obsessive-compulsive symptoms, and attention-deficit symptoms were evaluated through interview and standardized checklists for 175 descendants and 16 spouses who married into a single four-generation pedigree. RESULTS: Some form of tic disorder was diagnosed in 67% of descendants and 44% of married-in spouses. TD was found in 36% of descendants and in 31% of married-in spouses. Impairment was minimal in most cases, but age at onset and location and number of tics were typical of TD described in clinic samples. Obsessive-compulsive symptoms were found in 38% of descendants and 62% of those with current TD, but obsessive-compulsive disorder was found in only four individuals. Attention-deficit hyperactivity disorder occurred in 25% of children. Multivariate analysis indicated that offspring of two parents with tic disorders manifested significantly more lifetime tics, more severe categories of tic disorders, and an earlier age at onset for TD compared with offspring of one or no affected parents. CONCLUSIONS: TD in this family is most often a mild disorder but otherwise similar to published clinical cases. Increased morbidity is significantly associated with bilineality. The frequency and impact of bilineality raise questions about possible assortative mating, the prevalence of TD, and assumed mechanisms of transmission and etiology.
Adolescent↗
Psychiatric outcomes in low-birth-weight children at age 6 years: relation to neonatal cranial ultrasound abnormalities.
BACKGROUND: This study examined the relation of neonatal cranial ultrasound abnormalities to psychiatric disorder at age 6 years in a regional birth cohort of low-birth-weight children. METHODS: Neonatal cranial ultrasound abnormalities were classified as (1) isolated germinal matrix and/or intraventricular hemorrhage (suggestive of injury to glial precursors) or (2) parenchymal lesions and/or ventricular enlargement (suggestive of white matter injury) with or without germinal matrix-intraventricular hemorrhage. Psychiatric disorders by DSM-III-R at age 6 years were assessed by means of a structured parent interview. Children with severe mental retardation were excluded. Analyses were conducted first in the entire sample and then in children with normal intelligence. RESULTS: Twenty-two percent of the cohort had at least 1 psychiatric disorder, the most common being attention deficit hyperactivity disorder (15.6%). In the entire sample, parenchymal lesions and/or ventricular enlargement increased risk relative to no abnormality, independently of other biological and social predictors, for any disorder (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.8-10.3; P < .001), attention deficit hyperactivity disorder (OR, 3.4; CI, 1.3-8.7; P = .02), and tic disorders (OR, 8.7; CI, 1.3-57.7; P = .02). In children of normal intelligence, parenchymal lesions/ventricular enlargement independently increased risk for any disorder (OR, 4.8; CI, 1.6-12.0; P < .01), attention deficit hyperactivity disorder (OR, 4.5; CI, 1.3-16.0; P = .02), and separation anxiety (OR, 5.3; CI, 1.1-24.8; P = .03). These effects were not ameliorated by female sex or social advantage. Isolated germinal matrix/intraventricular hemorrhage was not related to psychiatric disorder at age 6 years. CONCLUSION: Neonatal cranial ultrasound abnormalities suggestive of white matter injury significantly increased risk for some psychiatric disorders at age 6 years in low-birth-weight children.
Age Factors↗
Cerebral morphometric abnormalities in Tourette's syndrome: a quantitative MRI study of monozygotic twins.
Although the pathologic substrate of Tourette's syndrome (TS) is unknown, studies have implicated subtle changes in the basal ganglia. To further investigate structural basal ganglia pathology in TS, we performed morphometric analyses of MRIs of 10 monozygotic twin pairs discordant for severity of TS but concordant for the presence of tic disorders (mean age, 16.3 years; range, 9 to 31 years). Right caudate volume was slightly but significantly reduced in the relatively more severely affected twins as a group compared with the less affected twins (mean difference = 6%, p < 0.01). Most of this difference was attributable to volume reduction in the anterior right caudate (p < 0.02), which was smaller in the more severely affected twin in nine of 10 twin sets. The mean volume of the left lateral ventricle was 16% smaller in the more severely affected twins than in the less severely affected twins (p < 0.01). The normal asymmetry of the lateral ventricles (left greater than right) was not present in the more severely affected twins, who had a trend toward a larger right lateral ventricle. Moreover, the difference within a pair in the degree of loss of the normal ventricular asymmetry correlated with the difference within a pair in the severity of the tic disorder (r = 0.75, p < 0.02). There were no other basal ganglia, ventricular volumetric, or asymmetry abnormalities. These findings partially replicate other MRI studies and suggest that subtle structural abnormalities in the CNS, particularly in the caudate, may play a role in the pathophysiology of TS.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Discharge rate of substantia nigra pars reticulata neurons is reduced in non-parkinsonian monkeys with apomorphine-induced orofacial dyskinesia.
Involuntary movements (dyskinesia) are a common symptom of dopamine-replacement therapy in parkinsonian patients, neuroleptic drug treatment of mental patients, and tic disorders. Levodopa-induced dyskinesia has been shown to be associated with substantial reduction of firing rate in the internal part of the globus pallidus. This study characterizes the changes that occur in the activity of the substantia nigra pars reticulata (SNr) of non-parkinsonian (normal) monkeys with apomorphine (APO)-induced orofacial dyskinesia. We conducted extracellular recordings of SNr neurons of two monkeys before and after induction of orofacial dyskinesia by systemic administration of APO. Involuntary orofacial movements appeared a few minutes after the injections and lasted 20-40 min. Almost all recorded neurons changed their firing rate after APO injection (96%), and most declined (70%). The mean amplitude of decreases was also larger than that of increases (40 vs. 21% of the control rate). Changes in firing pattern were not significant on average. Pairs of SNr neurons were uncorrelated before APO injection, similar to the normal pallidum. However, unlike the increased correlations in the pallidum that accompany parkinsonism, orofacilal dyskinesia in non-parkinsonian monkeys was not associated with changes in correlation between SNr neurons. We conclude that normal monkeys treated with APO can model orofacial dyskinesia and tic disorders that are a consequence of dopaminergic over-activity. These symptoms appear to be more related to reduced firing rate of SNr neurons and thus to disinhibition of their targets, than to changes in pattern and synchronization.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study.
BACKGROUND: Our objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder (ADHD) through young adulthood using contemporaneous diagnostic and analytic techniques. METHOD: We conducted a case-control, 10-year prospective study of ADHD youth. At baseline, we assessed consecutively referred male, Caucasian children with (n=140) and without (n=120) DSM-III-R ADHD, aged 6-18 years, ascertained from psychiatric and pediatric sources to allow for generalizability of results. At the 10-year follow-up, 112 (80%) and 105 (88%) of the ADHD and control children, respectively, were reassessed (mean age 22 years). We created the following categories of psychiatric disorders: Major Psychopathology (mood disorders and psychosis), Anxiety Disorders, Antisocial Disorders (conduct, oppositional-defiant, and antisocial personality disorder), Developmental Disorders (elimination, language, and tics disorder), and Substance Dependence Disorders (alcohol, drug, and nicotine dependence), as measured by blinded structured diagnostic interview. RESULTS: The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls, with hazard ratios and 95% confidence intervals of 6.1 (3.5-10.7), 2.2 (1.5-3.2), 5.9 (3.9-8.8), 2.5 (1.7-3.6), and 2.0 (1.3-3.0), respectively, for the categories described above. CONCLUSIONS: By their young adult years, ADHD youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial, addictive, mood and anxiety disorders. These prospective findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies.
Adolescent↗
A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder.
OBJECTIVE: Meta-analysis was used to review the literature on the clinical use of clonidine to treat symptoms of attention-deficit hyperactivity disorder (ADHD). METHOD: A review of the literature from 1980 to 1999 revealed 39 studies that reported clonidine's efficacy and side effects for symptoms of ADHD and comorbid conditions. Of these, 11 reports provided sufficient information to be included in a meta-analysis. RESULTS: Meta-analysis using weighted variables revealed clonidine demonstrates a moderate effect size of 0.58 +/- 0.16 (95% confidence interval = 0.27-0.89) on symptoms of ADHD in children and adolescents with ADHD and ADHD comorbid with conduct disorder, developmental delay, and tic disorders. CONCLUSIONS: Clonidine may be an effective second-tier treatment for symptoms of ADHD, but it has an effect size less than that of stimulants. Clinical use of clonidine is associated with many side effects.
Adolescent↗
The contribution of drug effects to the understanding of child psychiatric disorders.
The paper is part of a special section on 'psychopharmacotherapy in children'. Drugs not only help to treat symptoms successfully but may also help researchers and clinicians to gain a better understanding of the pathophysiology underlying these disturbances. This is exemplified in three child psychiatric disorders that exhibit disturbances in motor activity as a prominent symptom. These are general motor restlessness (ADHD), tic-disorder (sudden circumscribed motor actions) and stuttering (non-fluent speech). There is evidence that clinically useful drugs increase the cortical-subcortical interaction and tuning mechanisms providing the patients with a better self-regulation related to the motor performance.
Adolescent↗