David Lichter

Sensory tics in Tourette's syndrome

Sensory tics are localized uncomfortable sensations for which patients attempt to obtain relief by producing movements or vocalizations. We report 3 patients with Tourettes syndrome (TS) and sensory tics to illustrate this poorly recognized symptom. A survey of 34 randomly selected TS patients indicates that sensory tics are common and should be considered part of a clinical spectrum of tics and associated sensory phenomena.

Efficacy and Safety of Galantamine in Patients with Dementia with Lewy Bodies: A 12-Week Interim Analysis

Observations on the neurochemistry of dementia with Lewy bodies (DLB) have suggested that cholinesterase inhibitors (ChEIs) might be beneficial in treating some clinical symptoms of DLB. A 24-week, multicenter open-label study was designed to assess the safety and efficacy of the ChEI galantamine in patients with DLB, and an interim analysis of results was performed at 12 weeks. Efficacy analyses were performed on data from 25 patients. Scores on the Neuropsychiatric Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks (marginally significant, p = 0.061). NPI-12 scores decreased by half in 12 of the 25 patients. Highly significant improvement was observed in scores on the NPI-4 subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores on the Clinician’s Global Impression of Change (CGIC) improved by 0.95 points (significant, p = 0.02). Improvements also were found in secondary efficacy variables, including cognitive, functional, activities of daily living, sleep and confusion assessments. Motor scores, as measured by the UPDRS motor subscale, showed mild improvement, which demonstrates that galantamine has no adverse effect on parkinsonian symptoms. Adverse events generally were transient and of mild-to-moderate intensity. Two of the 25 patients discontinued galantamine because of nausea and anorexia. One serious adverse event was recorded, but it was judged to be unrelated to the study medication.

Slowed reaction time during a continuous performance test in children with Tourette's syndrome.

The phenomonology of Tourettes syndrome (TS) not only includes tics but also apparent deficits in attention. These attentional deficits in TS likely involve anomalies in frontal-striatal circuits. In this study, performance of 22 boys with TS and 22 age-matched boys without TS was compared on a continuous performance test (CPT) of attention. TS children demonstrated a normal capacity for discriminating targets from nontargets during the task, but showed significantly slower reaction times than controls. Severity of complex vocal tics was predictive of reaction time performance. Possible explanations for these findings are discussed and include the presence of attentional difficulties in TS, interference associated with tic suppression, a conservative strategy taken by TS children, and a general impairment of motor performance.

Clinical evidence of genomic imprinting in Tourette's syndrome

Article abstract—Recent genetic studies of Tourettes syndrome (TS) have suggested a sex-specific expression of TS behaviors but not a sex-associated difference in their transmission. In a retrospective study designed to assess the influence of gender of the affected parent on childhood TS phenotype, we compared unrnedicated TS subjects with pat-rilineal (n = 25) or matrilineal (n = 25) inheritance of TS, as determined by family history methodology, with respect to demographic variables, temporal profile of tic evolution, and clinical ratings of tics and associated behaviors, particularly obsessive-compulsive symptoms and attention deficit hyperactivity disorder (ADHD). Maternal transmission of TS was characterized by trends toward greater motor tic complexity and more frequent noninterfering rituals (p <0.05); paternal transmission was associated with increased vocal tic frequency (p = 0.01), an earlier onset of vocal tics relative to motor tics (p < 0.01), and more prominent ADHD behaviors, including motor restlessness (p < 0.01). These findings are consistent with genomic imprinting in TS. Confirmation of this phenomenon promises not only to advance understanding concerning the genetic link between TS and ADHD but may also help to explain the apparent fit of competing models of genetic transmission in TS.

Efficacy and safety of Galantamine in patients with Dementia with Lewy bodies: A 24-week open-label study

Background: Dementia with Lewy bodies (DLB) is a common dementia of the elderly. A significant cholinergic deficit has been demonstrated that may be responsive to treatment by cholinesterase inhibitors (ChEIs). Methods: A 24-week, open-label study was designed to assess the efficacy and safety of a ChEI, galantamine, in 50 patients with DLB. Results: This study showed beneficial effects with galantamine in 2 of the 3 primary efficacy parameters. The scores on the Neuropsychiatric Inventory (NPI-12) improved by 8.24 points from baseline (p = 0.01) especially in visual hallucinations and nighttime behaviors (p = 0.004). The scores on the Clinician’s Global Impression of Change improved by 0.5 points from baseline (p = 0.01). The third primary efficacy parameter, the Cognitive Drug Research Computerized Cognitive Assessment System, was unchanged from baseline. Adverse events were generally mild and transient. Conclusion: Galantamine appears to be an effective and safe therapy for patients with DLB.

Pilot study of effect of emotional stimuli on tic severity in children with Tourette's syndrome

To assess objectively the effects of emotional stimuli on the severity of tics and to determine if such effects were mediated by the autonomic nervous system, we carried out videotape ratings of tics and electrophysiological monitoring of heart beat and respiration on 4 children with Tourettes syndrome while they were watching a movie known to elicit emotional responses relevant to normal childhood events. Measured tic severity was highest during periods associated with anticipation, resolution of emotional changes, and lower concentration, lowest during periods of anger and happiness, and intermediate during periods of sadness and fear. Tic severity did not correlate with heart or respiratory rate. Thus, tics seem influenced differentially by various emotional states, but this effect does not seem to be autonomically mediated.

Influence of family history on clinical expression of Tourette’s syndrome

Objective: To determine the influence of family history on clinical expression of Tourette’s syndrome (TS). Background: Recent studies have suggested that clinical expression of TS is similar among sporadic (SP) and familial patients but may be influenced by bilineal (BIL) transmission of tics or obsessive-compulsive behavior (OCB) in high-density pedigrees. Methods: The authors used family history methodology, supported by direct examination of affected relatives in 73% of familial patients, to determine the frequency of SP TS, and of unilineal (UNL) and BIL transmission of tics or OCB in 111 consecutively ascertained juvenile TS patients. For individuals in each group, severity of tics, attention deficit hyperactivity disorder (ADHD), and OCB were assessed at presentation and after a mean follow-up interval of 2.6 years, using the Tourette’s Syndrome Global Scale and the Clinical Global Impression scales. The phenomenology of OCB was evaluated using the symptom checklist of the Children’s Yale-Brown Obsessive Compulsive Scale. Results: The authors documented BIL transmission of tics in seven patients (6%). Patient age and sex were similar for the SP (n = 21; 19%), UNL (n = 66; 59%), and BIL (n = 24; 22%) groups, as was ADHD and tic severity at presentation and follow-up. Severity of OCB differed significantly between groups, with moderate to severe OCB affecting 5% of SP, 12% of UNL, and 37% of BIL patients at presentation (p = 0.007), and 5% of SP, 17% of UNL, and 54% of BIL patients at follow-up (p = 0.0001). Relative to UNL or SP patients, BIL patients were more likely to exhibit self-injurious behaviors (p = 0.0005). Conclusions: OCB is less prominent in SP than in familial TS, perhaps reflecting a more restricted pathophysiology in this subgroup. Although BIL transmission of tics is relatively infrequent in consecutive TS pedigrees, cotransmission of OCB from an otherwise unaffected parent is common and significantly influences development of OCB and self-injurious behaviors, but not tics, in offspring. Genetic heterogeneity, epigenetic factors, and gene–environment interactions may play a more important role than genetic dosage effects in determining tic severity in TS.

Predictors of Clonidine Response in Tourette Syndrome: Implications and Inferences

Clonidine is an α-adrenergic agonist which may alleviate emerging symptoms in Tourette syndrome, an observation that has fueled speculation regarding involvement of stress-sensitive central noradrenergic systems in this disorder. We conducted a retrospective study of 53 juvenile patients with Tourette syndrome to assess predictors of short-term behavioral and tic response to oral clonidine and to examine the relationship, if any, among pretreatment blood pressure, tic severity, and clonidine response. When adverse effects were considered, older subjects experienced a better therapeutic response to clonidine, independent of dose. Improvement in symptoms of attention-deficit hyperactivity disorder was associated with a longer duration of vocal tics before treatment. Baseline sitting diastolic blood pressure was directly correlated with measures of tic severity but not with tic response to clonidine. The findings (1) provide indirect support for involvement of central noradrenergic systems in tic expression; (2) suggest that emergence of a tic-related neurophysiologic dysfunction may be necessary for optimal behavioral response to clonidine in Tourette syndrome; and (3) provide broad guidelines for the clinician considering clonidine therapy for pediatric patients with Tourette syndrome, particularly those with comorbid attention-deficit hyperactivity disorder. (J Child Neurol 1996; 11:93-97).

Carbamazepine-induced tics

Although a variety of dyskinesias are known to develop during anticonvulsant therapy, carbamazepine-induced tics are rarely recognized. We report three patients with an underlying movement disorder (Huntingtons disease, tardive dyskinesia, and Tourettes syndrome) who experienced the onset or exacerbation of tics after the introduction of carbamazepine. These cases confirm the phenomenon of carbamazepine-induced tics and suggest that basal ganglia neuropathology may be an important predisposing factor. The dopaminergic effects of carbamazepine may be responsible for the induction of tics.

Parkinsonism Associated with Fluoxetine and Cimetidine: A Case Report:

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) are effective for the treatment of depression in the elderly and offer a safer side-effect profile as compared to tricyclics and monoamine oxidase inhibitors. We report a case in which a patient treated with fluoxetine developed parkinsonism following the introduction of cimetidine. Inhibition of hepatic P450 cytochrome enzymes by cimetidine with an increase in serum levels of norfluoxetine may have precipitated this extrapyramidal syndrome, which has been related to agonism of the serotonergic input to nigrostriatal tracts and basal ganglia. Parkinsonism as a side effect of SSRIs occurs infrequently, suggesting an idiosyncratic response resulting from a functional imbalance of serotonergic and dopaminergic activity in susceptible individuals. Careful monitoring of geriatric patients treated with fluoxetine is indicated, particularly for those on high doses, those with impaired hepatic functioning, or those treated with concurrent medications that slow the metabolism of fluoxetine.