Refractory Tourette Syndrome Research Articles

Improvement of Both Dystonia and Tics With 60 Hz Pallidal Deep Brain Stimulation

ABSTRACTDeep brain stimulation has been utilized in both dystonia and in medication refractory Tourette syndrome. We present an interesting case of a patient with a mixture of disabling dystonia and Tourette syndrome whose coexistent dystonia and tics were successfully treated with 60 Hz-stimulation of the globus pallidus region.

Deep Brain Stimulation for Tourette Syndrome: A Prospective Pilot Study in Japan

Refractory Tourette syndrome (TS) disturbs the social life of patients. Deep brain stimulation (DBS) has recently been applied to relieve severe tics. We report a prospective open-labeled case series of DBS for TS as a pilot study.Three patients (19-21 years old, one male) with refractory TS were treated with DBS. They were targeted at the centromedian-parafascicular complex-ventral oral thalamic nuclei of the bilateral thalami.The scores for the Yale Global Tic Severity Scale decreased from 42.7 ± 2.7 (before DBS) to 26.0 ± 1.7 (one year after DBS) (means ± standard error of means). Intelligence levels of the patients showed no change after surgery. There was no morbidity or mortality. All patients presented an increase in satisfaction with activities of daily living.These results support the safety and efficacy of thalamic DBS for TS.

Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome

Deep brain stimulation of the thalamus has been proposed as a therapeutic option in patients with Tourette syndrome who are refractory to pharmacological and psychotherapeutic treatment. Patients with intractable Tourette syndrome were invited to take part in a double-blind randomized cross-over trial assessing the efficacy and safety of stimulation of the centromedian nucleus-substantia periventricularis-nucleus ventro-oralis internus crosspoint in the thalamus. After surgery, the patients were randomly assigned to 3 months stimulation followed by 3 months OFF stimulation (Group A) or vice versa (Group B). The cross-over period was followed by 6 months ON stimulation. Assessments were performed prior to surgery and at 3, 6 months and 1 year after surgery. The primary outcome was a change in tic severity as measured by the Yale Global Tic Severity Scale and the secondary outcome was a change in associated behavioural disorders and mood. Possible cognitive side effects were studied during stimulation ON at 1 year postoperatively. Interim analysis was performed on a sample of six male patients with only one patient randomized to Group B. Tic severity during ON stimulation was significantly lower than during OFF stimulation, with substantial improvement (37%) on the Yale Global Tic Severity Scale (mean 41.1 ± 5.4 versus 25.6 ± 12.8, P = 0.046). The effect of stimulation 1 year after surgery was sustained with significant improvement (49%) on the Yale Global Tic Severity Scale (mean 42.2 ± 3.1 versus 21.5 ± 11.1, P = 0.028) when compared with preoperative assessments. Secondary outcome measures did not show any effect at a group level, either between ON and OFF stimulation or between preoperative assessment and that at 1 year postoperatively. Cognitive re-assessment at 1 year after surgery showed that patients needed more time to complete the Stroop Colour Word Card test. This test measures selective attention and response inhibition. Serious adverse events included one small haemorrhage ventral to the tip of the electrode, one infection of the pulse generator, subjective gaze disturbances and reduction of energy levels in all patients. The present preliminary findings suggest that stimulation of the centromedian nucleus-substantia periventricularis-nucleus ventro-oralis internus crosspoint may reduce tic severity in refractory Tourette syndrome, but there is the risk of adverse effects related to oculomotor function and energy levels. Further randomized controlled trials on other targets are urgently needed since the search for the optimal one is still ongoing.

Neuropsychiatric Outcome of an Adolescent Who Received Deep Brain Stimulation for Tourette's Syndrome

This case study followed one adolescent patient who underwent bilateral deep brain stimulation of the centromedian parafascicular complex (CM-Pf) for debilitating, treatment refractory Tourette's syndrome for a period of 1.5 years. Neurocognitive testing showed no significant changes between baseline and follow-up assessments. Psychiatric assessment revealed positive outcomes in overall adaptive functioning and reduction in psychotropic medication load in this patient. Furthermore, despite significant baseline psychiatric comorbidity, this patient reported no suicidal ideation following electrode implantation. Deep brain stimulation is increasingly being used in children and adolescents. This case reports on the positive neurologic and neuropsychiatric outcome of an adolescent male with bilateral CM-Pf stimulation.

Intracerebral haematomas after deep brain stimulation surgery in a patient with Tourette syndrome and low factor XIIIA activity

A 24-year-old male patient with refractory Tourette syndrome was treated with deep brain stimulation (DBS) and developed subsequent bilateral subcortical haematomas. Additional blood tests revealed abnormalities of plasma factor XIIIA and tryptophan levels, which may be associated with Tourette syndrome. Neurosurgeons who perform DBS surgery on patients with Tourette syndrome must be aware of possible disastrous complications resulting from factor XIIIA disorders of blood haemostasis. Routine screening for this condition is not typically performed prior to surgery in these patients.

Oral Δ9-Tetrahydrocannabinol Improved Refractory Gilles de la Tourette Syndrome in an Adolescent by Increasing Intracortical Inhibition

To describe the clinical course of the Delta 9-tetrahydrocannabinol (Delta 9-THC) treatment of a boy with Gilles de la Tourette Syndrome (TS) and comorbid attention-deficit/hyperactivity disorder (ADHD) in relation to Delta 9-THC plasma levels and intracortical inhibition measured by transcranial magnetic stimulation. The clinical course and pharmacological and neurophysiological measures are reported in a 15-year-old boy with treatment refractory TS plus ADHD leading to severe physical and psychosocial impairment. Administration of Delta 9-THC improved tics considerably without adverse effects, allowing parallel stimulant treatment of comorbid ADHD. Along with the Delta 9-THC treatment, intracortical inhibition was increased, reflected in the enhanced short-interval intracortical inhibition and the prolongation of the cortical silent period. Our observation suggests that Delta 9-THC might be a successful alternative in patients with severe TS refractory to classic treatment. Particularly in the case of stimulant-induced exacerbation of tics, Delta 9-THC might enable successful treatment of comorbid ADHD. The enhancement of intracortical inhibition might be mediated by modulating release of several neurotransmitters including dopamine and gamma-aminobutyric acid. Further studies are needed to substantiate our findings.

Thalamic deep brain stimulation for treatment-refractory Tourette syndrome

Eighteen patients with severe and refractory Tourette syndrome (TS) underwent bilateral thalamic deep brain stimulation (DBS). To assess the long-term outcome on tics, behavioral symptoms, and cognitive functions in the largest case series of thalamic DBS for TS to date. In this prospective cohort study, 15 of the original 18 patients were evaluated before and after surgery according to a standardized protocol that included both neuropsychiatric and neuropsychological assessments. In addition to marked reduction in tic severity (p = 0.001), 24-month follow-up ratings showed improvement in obsessive-compulsive symptoms (p = 0.009), anxiety symptoms (p = 0.001), depressive symptoms (p = 0.001), and subjective perception of social functioning/quality of life (p = 0.002) in 15 of 18 patients. There were no substantial differences on measures of cognitive functions before and after DBS. At 24-month follow-up, tic severity was improved in patients with intractable Tourette syndrome (TS) who underwent bilateral thalamic deep brain stimulation. Available data from 15 of 18 patients also showed that neuropsychiatric symptoms were improved and cognitive performances were not disadvantaged. Controlled studies on larger cohorts with blinded protocols are needed to verify that this procedure is effective and safe for selected patients with TS. This study provides class IV evidence that bilateral thalamic deep brain stimulation reduces global tic severity measured 24 months after implantation in patients with severe intractable Tourette syndrome.

IMPROVEMENT OF TICS AFTER SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION

Deep brain stimulation (DBS) of the medial thalamic nuclei and globus pallidus internus (GPi)1,2 has been tried in the treatment of medically refractory Tourette syndrome (TS). Subthalamic nucleus (STN) is the target most commonly used for DBS in Parkinson disease (PD). A double-blind randomized study has shown the efficacy of STN-DBS in obsessive compulsive disorder (OCD),3 which is considered within the spectrum of TS. We report a patient with PD who also had a history of TS in whom bilateral STN-DBS improved both PD and tics. ### Case report. A 38-year-old man with an 8-year history of PD was referred for DBS consideration. He had a history of tics that began at the age of 7 and improved by the age of 12. Tics increased in adulthood prior to the diagnosis of PD. No changes of tics were noticed following the onset of PD or dopaminergic medication. No treatment for tics was ever prescribed. Prior to surgery he had motor and phonic tics and compulsion of checking that doors were locked. A single exon 5 deletion in the parkin gene was detected. Quadripolar 3389 DBS electrodes (Medtronic, Minneapolis, MN) were implanted bilaterally in the STN …

De novo and rescue DBS leads for refractory Tourette syndrome patients with severe comorbid OCD: a multiple case report

Invasive treatment for Gilles de la Tourette syndrome has shown interesting results in a number of published reports; it seems to be evolving into a promising therapeutic procedure for those patients demonstrating disabling clinical pictures who are refractory to conservative treatments. There are important issues concerning the stimulated brain target, with different nuclei currently under investigation. Our group asked in this pilot study whether Tourette syndrome could be treated by tailoring specific brain targets for specific symptoms. Deep brain stimulation for Tourette syndrome may thus in the future be tailored and patient specific, utilizing specific target regions for individual clinical manifestations. In our early experience we did not adequately address non-motor clinical symptoms as we only used a thalamic target. More recently in an obsessive compulsive disease cohort we have had success in using the anterior limb of the internal capsule and nucleus accumbens region as targets for stimulation. We therefore explored the option of a "rescue" procedure for our Tourette patients with persistent obsessive-compulsive disorder following ventralis oralis/centromedianus-parafascicularis (Vo/CM-Pf) deep brain stimulation. Following two cases where rescue anterior limb of internal capsule/nucleus accumbens leads were employed, we performed two additional procedures (anterior limb of the internal capsule plus ventralis oralis/centromedianus-parafascicularis and anterior limb of the internal capsule alone) with some mild improvement of comorbid obsessive-compulsive disorder, although the number of observations in this case series was low. Overall, the effects observed with using the anterior limb of the internal capsule either alone or as a rescue were less than expected. In this report we detail our experience with this approach.

198. Deep brain stimulation of different anatomic structures in therapeutically refractory Tourette syndrome

198. Deep brain stimulation of different anatomic structures in therapeutically refractory Tourette syndrome

Nifedipine augments haloperidol in the treatment of Tourette syndrome

In anecdotal case reports, verapamil and nifedipine, calcium channel blockers, have provided rapid and dramatic relief in refractory Tourette syndrome [ 1,2]. The following report illustrates the use of nifedipine to augment haloperidol in the treatment of a child who did not respond when either drug was used alone. This 9-year-old boy was referred for intractable Tourette syndrome over a 3 year period with associated attention deficit hyperactivity disorder. His tics had worsened over the previous 5 months, making fine motor control impossible. He had received a variety of medications, including clonidine, haloperidol, pimozide, and fluphenazine, all of which proved ineffective. Neurologic examination, includingcranial computedtomography,electroencephalography, and magnetic resonance imaging, was normal. The patient received a therapeutic trial of nifedipine; tics and vital signs were monitored. After i week of therapy there was neither relief of symptoms, nor presence of side effects. Blood pressure and pulse remained stable. With the addition of haloperidol (2 mg/day orally in 2 divided doses), there was a significant reduction in tics and a marked improvement in attention and school performance. Nifedipine was discontinued to determine whether the observed improvement was due to haloperidol. Within 2 days the tics worsened and his attention deficit returned to pretreatment levels. To determine whether the deterioration in function was due to a placebo effect, a placebo was administered (3 tablets per day at equal intervals): the patient and patient's family were told that it was a medication similar to The patient continued to receive the placebo for 10 days, during which time his tics and attentional difficulties continued. After 10 days, nifedipine therapy was reinstated. Within 2 weeks the patient's tics were markedly improved. His school performance also improved because of an increase in attention, a decrease in impulsivity, a decrease in the frequency and severity of tics, and an improvement in fine motor control. This is the first report to systematically demonstrate the use of nifedipine to augment haloperidol treatment of Tourette syndrome. These results suggest that an alternative in the treatment of Tourette syndrome in treatmentresistant cases is the combination of haloperidol and nifedipine. In addition to the marked reduction in tics, characteristics of attention deficit disorder were affected: attention improved and impulsivity decreased. The precise basis of the psychopharmacologic impact remains unclear: however, neither nifedipine nor haloperidol alone altered his course. We postulate that the effect observed in this patient represents functional reduction in dopamine receptors with the chronic administration of nifedipine, with a resulting increased efficacy of haloperidol [3]. Further studies are indicated to substantiate this effect, and if present, to determine its mechanism of action.