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Biomedical subjects

M M Robertson

Publications and source records attributed to M M Robertson.

At least 19 recordsLinked to original sources
PubMed2006

Beck Depression Inventory is a useful screening tool for major depressive disorder in Gilles de la Tourette syndrome.

This study determined the prevalence of and factors associated with comorbid major depressive disorder (MDD) in patients with Gilles de la Tourette syndrome (GTS). How a simple self-report instrument, the Beck Depression Inventory (BDI), correlates with clinical assessment of comorbid MDD in this population was assessed. In a continuous sample of 114 adult patients with GTS, assessed clinically using the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, 26 (23%) patients met criteria for MDD; more severe tics as measured with the Yale Global Tic Severity Scale, conduct disorder in childhood or higher age at the time of assessment were associated with MDD. The BDI score had a high negative predictive value for diagnosis of MDD, but a low positive predictive value. Using the BDI as a screening tool for comorbid MDD in patients with GTS is suggested.

Adult↗
PubMed2005

Soluble adhesion molecules in Gilles de la Tourette's syndrome.

To investigate the immune-mediated response in TS, and its relationship with streptococcal infection, we measured serum levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in patients with TS, compared to healthy and diseased controls. Soluble VCAM-1 and sE-selectin were significantly elevated in children and adults with TS, and sVCAM-1 was higher among anti-basal ganglia antibodies (ABGA)-positive adults with TS. No correlation of adhesion molecule levels to clinical severity or anti-streptococcal antibodies was observed. Children with Sydenham's chorea and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) showed an increased level of sICAM-1, but not sVCAM-1 and sE-selectin. These results provide initial evidence for a role of adhesion molecules and systemic inflammation in TS, and support the hypothesis of an ongoing immune-mediated process in this condition.

Adolescent↗
PubMed2005

Excitability of motor cortex inhibitory circuits in Tourette syndrome before and after single dose nicotine.

The pathophysiology underlying the involuntary tics of Gilles de la Tourette syndrome (GTS) remains unknown. Here we used transcranial magnetic stimulation (TMS) to examine the excitability of two different inhibitory systems in the human motor cortex: short interval intracortical inhibition (SICI) and short interval afferent inhibition (SAI) in 10 healthy non-smoking controls and eight untreated non-smoking patients with GTS. Compared with the healthy control group, both SICI (measured at a range of conditioning intensities) and SAI were reduced in patients. This is consistent with the suggestion that reduced excitability of cortical inhibition is one factor that contributes to the difficulty that patients have in suppressing involuntary tics. In addition, the reduced SAI indicates that impaired intracortical inhibition may not be limited to the motor cortex but also involves circuits linking sensory input and motor output. A single dose of nicotine reduced tic severity as assessed by blind video scoring in the majority of patients. In addition, it abolished the difference between patients and controls in SICI and SAI. There was no effect of nicotine, and no difference between controls and patients in measures of motor or SICI threshold. This indicates that cholinergic input can modulate the efficiency of SICI and SAI differently in GTS and healthy controls.

Adult↗
PubMed2005

Gilles de la Tourette's syndrome and its impact in the UK.

Gilles de la Tourette's syndrome of chronic multiple motor and vocal tics is now acknowledged to be far more common than once thought, affecting up to 1% of schoolchildren with a wide range of severity. At the milder end of the spectrum the associated psychopathologies can in themselves impair social and educational functioning, in particular obsessive compulsive disorder and attention deficit hyperactivity disorder. Many patients with this condition are not being adequately served by health and education services in the UK. The epidemiology, clinical features, aetiological factors, and management of the syndrome are reviewed.

Adolescent↗
PubMed2004

Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome.

OBJECTIVE: A previous study showed no effect of 1Hz repetitive transcranial magnetic stimulation (rTMS) on tics in Gilles de la Tourette Syndrome (GTS). We modified the rTMS protocol in order to investigate some of the possible methodological reasons for the negative outcome in that study. METHODS: In a single blinded placebo-controlled cross-over study in five GTS patients without obsessive compulsive disorder we probed whether longer trains (1800 stimuli) of 1 Hz pre-motor cortex rTMS at 80% of active motor threshold and application to both hemispheres can improve tics in GTS. This was measured with the Yale Global Tic severity rating scale, the MOVES self-rating scale and video analysis. RESULTS: We found no significant effect of either left pre-motor cortex stimulation alone, or left pre-motor followed by right pre-motor cortex stimulation. CONCLUSIONS: These results suggest that the rTMS protocol used in this study is not useful for the treatment of tics in GTS. SIGNIFICANCE: rTMS protocols need to be modified substantially in order to explore their potential for the treatment of tics in GTS.

Adult↗
PubMed2004

Genome scan of Tourette syndrome in a single large pedigree shows some support for linkage to regions of chromosomes 5, 10 and 13.

OBJECTIVES: To localize genes influencing the susceptibility to Gilles de la Tourette syndrome (GTS) and associated chronic multiple tics (CMT). METHOD: A single, large, multiple affected pedigree containing 35 subjects diagnosed with GTS and a further 14 with CMT was genotyped for markers spanning the autosomes. Linkage analysis was carried out using classical lod score analysis and model-free lod score analysis. All markers were subjected to two-point analysis, and markers producing a two-point result significant at P<0.005 were subjected to three-point analysis using adjacent markers. RESULTS: The following markers produced at least one result significant at 0.005 using two-point analysis: D5S1981, D5S2050, D10S591, D10S189, D13S217, and D14S288. Three-point analysis with D5S2050 and D5S400 produced a lod of 2.9 with CMT. Three-point analysis of D10S591 and D10S189 produced lods of 1.9 with GTS and CMT. Three-point analysis of D13S217 and D13S171 produced a lod of 2.7 with GTS. No single haplotype appeared to account for the majority of cases within the pedigree. CONCLUSIONS: It seems likely that more than one susceptibility allele is present in the pedigree. Although none of the three positive regions is conclusively implicated, it seems probable that at least one contains a susceptibility locus. We recommend that association-based studies be carried out in these three regions to produce further evidence for a localization and to carry out fine-mapping.

Chromosome Mapping↗
PubMed2004

Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study.

OBJECTIVE: To investigate dopamine transporter binding in Gilles de la Tourette syndrome (GTS) with SPECT and [123I]FP-CIT. METHOD: Ten neuroleptic naïve/free patients with GTS, and 10 age- and gender-matched normal volunteers were studied. Subjects were clinically evaluated. GTS severity and affective symptoms were measured and the presence of GTS-related behaviours were recorded. RESULTS: The GTS group showed significantly higher binding in both caudate and putamen nuclei than the controls. No associations were found between striatal binding ratios and measures of affect or GTS-related behaviours. CONCLUSION: Patients with GTS show higher striatal binding of FP-CIT to the striatum in comparison with age- and gender-matched control subjects, indicating that dopamine transporter abnormalities are involved in the pathophysiology of GTS. These abnormalities appear to be distributed across both caudate and putamen.

Adolescent↗
PubMed2003

Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis.

BACKGROUND: The classical neurological disorder after group A beta haemolytic streptococcal infection is Sydenham's chorea. Recently a tic disorder occurring after group A streptococcal infection has been described and termed PANDAS (paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). It is proposed that antibodies induced after group A streptococcal infection react with basal ganglia neurones in Sydenham's chorea and PANDAS. Anti-basal ganglia antibodies (ABGA) are present in most cases of acute Sydenham's chorea, but rarely in controls. OBJECTIVE: To investigate the hypothesis that Tourette's syndrome may be associated with group A streptococcal infection and ABGA. METHODS: 100 patients with Tourette's syndrome (DSM-IV-TR) were enrolled in a cross sectional study. Children with neurological disease (n = 50) and recent uncomplicated streptococcal infection (n = 40), adults with neurological disease (n = 50), and healthy adults (n = 50) were studied as controls. Recent group A streptococcal infection was defined using antistreptolysin O titre (ASOT). ABGA were detected using western immunoblotting and indirect immunofluorescence. RESULTS: ASOT was raised in 64% of children with Tourette's syndrome compared with 15% of paediatric neurological disease controls (p < 0.0001), and in 68% of adults with Tourette's syndrome compared with 12% of adult neurological controls and 8% of adult healthy controls (p < 0.05). Western immunoblotting showed positive binding in 20% of children and 27% of adults with Tourette's syndrome, compared with 2-4% of control groups (p < 0.05). The most common basal ganglia binding was to a 60 kDa antigen, similar to the proposed antigen in Sydenham's chorea. Indirect immunofluorescence revealed autoantibody binding to basal ganglia neurones. Serological evidence of recent group A streptococcal infection, assessed by a raised ASOT, was detected in 91% (21/23) of Tourette's syndrome patients with positive ABGA compared with 57% (44/77) with negative ABGA (p < 0.01). CONCLUSIONS: The results support a role of group A streptococcal infection and basal ganglia autoimmunity in a subgroup of patients with Tourette's syndrome and suggest a pathogenic similarity between Sydenham's chorea and some patients with Tourette's syndrome.

Adolescent↗
PubMed2002

Repetitive transcranial magnetic stimulation for Tourette syndrome.

In a single-blinded, placebo-controlled, crossover repetitive transcranial magnetic stimulation (rTMS) trial, 16 patients with Gilles de la Tourette syndrome (GTS) received in random sequence 1 Hz motor, premotor, and sham rTMS, which each consisted of two 20-minute rTMS sessions applied on 2 consecutive days. In the 12 patients who completed the trial, there was no significant improvement of symptoms after any of the rTMS conditions as assessed with the Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey.

Anxiety↗
PubMed2002

Uncomplicated Gilles de la Tourette syndrome and probable Ganser syndrome. A case report and review of the literature.

Gilles de la Tourette syndrome (GTS) is a genetic neuropsychiatric disorder, which is more common than previously thought. Ganser syndrome is an uncommon disorder, particularly in children. We present the first report of a young girl aged 7 who was diagnosed independently as having both GTS and Ganser syndrome and who was otherwise well and remained well and improved at follow-up 8 years later. This highlights how the clinicians must always be vigilant when atypical behaviours begin, especially when one diagnosis has already been given. There may well be treatment implications.

Adolescent↗
PubMed2001

Quality of Life (QOL) of patients with Gilles de la Tourette's syndrome.

OBJECTIVE: This is the first study to investigate the Quality of Life (QOL) of patients with Gilles de la Tourette's Syndrome (GTS). METHOD: One hundred and three out-patients with GTS completed a semi-structured interview and 90 of these completed questionnaires screening for depression, anxiety and obsessive-compulsive behaviour. QOL was measured with the SF-36 and the Quality of Life Assessment Schedule (QOLAS). RESULTS: Patients with GTS showed significantly worse QOL than a general population sample. They had better QOL than patients with intractable epilepsy as measured by the QOLAS, although the SF-36 showed significant differences on the subscales Role Limitation due to physical problems and Social Functioning only. Factors influencing QOL domains were employment status, tic severity, obsessive-compulsive behaviour, anxiety and depression. CONCLUSION: QOL is impaired in patients with GTS. Measurement of QOL could be used alongside conventional measurements to assess benefit of treatment. We recommend the QOLAS and SF-36 be used.

Adolescent↗
PubMed2001

Prevalence of tics and Tourette syndrome in an inpatient adult psychiatry setting.

OBJECTIVE: Given the widely recognized genetic basis for Gilles de la Tourette syndrome (TS) and the suggestion that the putative TS gene(s) may be expressed as or associated with a variety of psychiatric illnesses, this study was undertaken to assess the prevalence of tics and TS in a psychiatric inpatient population. DESIGN: Cross-sectional study. SETTING AND PATIENTS: 200 consecutive adult patients who were admitted to the psychiatric wards of University College London Teaching Hospitals. OUTCOME MEASURES: TS and related behaviours, as assessed by the comprehensive semi-structured National Hospital Interview Schedule. RESULTS: None of the 200 patients had definite TS, but 2 were observed to have motor tics; 10 had a history of tics (present for less than a year), and 7 reported a family history of tics. Thus, 19 (9.5%) inpatients qualified for inclusion in a broadly defined TS diathesis. These rates are significantly lower than those reported in a similar community based epidemiological study of adolescents (p = 0.018). CONCLUSIONS: Our findings do not support the theory that TS and related behaviours are over-represented among adult inpatients with psychiatric illnesses.

Adolescent↗
PubMed2000

A functional neuroanatomy of tics in Tourette syndrome.

BACKGROUND: Tics are involuntary, brief, stereotyped motor and vocal behaviors often associated with irresistible urges. They are a defining symptom of the classic neuropsychiatric disorder, Tourette syndrome (TS), and constitute an example of disordered human volition. The neural correlates of tics are not well understood and have not been imaged selectively. METHODS: Event-related [(15)O]H(2)O positron emission tomography techniques combined with time-synchronized audio and videotaping were used to determine the duration of, frequency of, and radiotracer input during tics in each of 72 scans from 6 patients with TS. This permitted a voxel-by-voxel correlational analysis within Statistical Parametric Mapping of patterns of neural activity associated with the tics. RESULTS: Brain regions in which activity was significantly correlated with tic occurrence in the group included medial and lateral premotor cortices, anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior parietal cortex, putamen, and caudate, as well as primary motor cortex, the Broca's area, superior temporal gyrus, insula, and claustrum. In an individual patient with prominent coprolalia, such vocal tics were associated with activity in prerolandic and postrolandic language regions, insula, caudate, thalamus, and cerebellum, while activity in sensorimotor cortex was noted with motor tics. CONCLUSIONS: Aberrant activity in the interrelated sensorimotor, language, executive, and paralimbic circuits identified in this study may account for the initiation and execution of diverse motor and vocal behaviors that characterize tics in TS, as well as for the urges that often accompany them. Arch Gen Psychiatry. 2000;57:741-748

Adult↗
PubMed2000

Gilles de la Tourette syndrome: symptomatic treatment based on evidence.

The treatment of the Gilles de la Tourette syndrome has evolved from case reports, clinical experience and more recently blinded trials usually in small numbers of patients. We have reviewed the evidence available to clinicians. The oldest and still most widely prescribed drug, haloperidol, should now not be considered the first-line agent in children as other agents have superior adverse effects profiles. Symptomatic treatment should be targeted to the specific additional psychopathologies seen in the syndrome. For the treatment of tics, sulpiride, tiapride, possibly pimozide and in some cases clonidine may be considered first-line agents. Although a body of data supports pimozide, caution has to be exercised in relation to possible cardiac effects. Antidepressants and stimulants have an important place in the management of depression, obsessionality and attention deficit hyperactivity disorder. The latter also responds to clonidine making it a rational first choice where ADHD coexists with GTS. There are a multitude of other drugs advocated in the literature in addition to reports of neurosurgery and the novel use of immune modulation. Therapeutic trials for GTS are challenging. However, further data from blinded trials are required before many of these treatments can be considered to be mainstream treatment options.

Adolescent↗
PubMed2000

An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries.

We have established a multisite, international database of 3,500 individuals diagnosed with Tourette syndrome (TS). The male:female ratio is 4.3:1 for the total sample, with wide variation among sites; the male excess occurs at every site. Anger control problems, sleep difficulties, coprolalia, and self-injurious behavior only reach impressive levels in individuals with comorbidity. Anger control problems are strongly correlated with comorbidity, regardless of site, region, or whether assessed by neurologists or psychiatrists. The mean age at onset of tics is 6.4 years. At all ages, about 12% of individuals with TS have no reported comorbidity. The most common reported comorbidity is attention-deficit-hyperactivity disorder. Males are more likely to have comorbid disorders than females. The earlier the age at onset, the greater the likelihood of a positive family history of tics. An understanding of the factors producing these and other variations might assist in better subtyping of TS. Because behavioral problems are associated with comorbidity, their presence should dictate a high index of suspicion of the latter, whose treatment may be at least as important as tic reduction. The established database can be used as the entry point for further research when large samples are studied and generalizability of results is important.

Adolescent↗
PubMed2000

Tourette syndrome, associated conditions and the complexities of treatment.

Tourette syndrome (TS) is characterized by multiple motor tics plus one or more vocal (phonic) tics, which characteristically wax and wane. It can no longer be considered the rare and bizarre syndrome that it was once thought to be. The concepts surrounding TS, and our understanding of it, are also becoming increasingly complex and, in some individuals, TS is now recognized to be associated with a wide variety of associated behaviours and psychopathologies. It is suggested that TS is heterogeneous from a variety of standpoints including clinical presentation and psychopathology, and thus neuropharmacological responses and possibly even aetiological and genetic mechanisms. In this paper, mention is made of recent findings in epidemiology and genetics, highlighting the complexities of the disorder; these have been chosen because findings in both areas have clinical and management implications. The literature on the clinical manifestations, associated behaviours, psychopathology (and/or comorbid conditions) and management, in particular, is reviewed in detail.

Antidepressive Agents↗
PubMed1999

The Tourette syndrome diagnostic confidence index: development and clinical associations.

BACKGROUND: The clinical characteristics of Tourette syndrome (TS) present challenges for the systematic determination of whether individuals are affected and severity. Vocal and motor tics wax and wane, decrease over time, and may be voluntarily suppressible, and therefore may be absent at interview. Current instruments measure symptoms at interview or rate symptom severity only. METHOD: To minimize error in case ascertainment and produce an instrument measuring lifetime likelihood of having had TS, clinical members of the American Tourette Syndrome Association International Genetic Collaboration developed the Diagnostic Confidence Index (DCI). The expert group worked collaboratively with progressive revision in consensus workshops using existing diagnostic criteria as guidelines. The DCI produces a score from 0 to 100 that is a measure of the likelihood of having or ever having had TS. RESULTS: The DCI was administered to 280 consecutive patients with TS attending a TS clinic; 264 (94%) completed it, indicating high feasibility and acceptability. Its correlation with other instruments and associations with psychopathology provide support for its being a lifetime measure of TS. CONCLUSIONS: The DCI is a useful, practicable instrument in the clinic or research practice allowing an assessment of lifetime likelihood of TS. Further work is needed to test the DCI's psychometric properties, such as its validity and reliability in populations of interest.

Adolescent↗