Vagus Nerve Stimulation in a Patient with Gilles de la Tourette Syndrome and Major Depression

Gilles de la Tourette Syndrome (GTS) is a chronic disease characterized by motor and vocal tics [4]. Current medical therapy includes dopamine receptor antagonists, mainly atypical antipsychotics [13]. We report a case in which a patient with therapy-resistant major depression and GTS syndrome was successfully treated with vagus nerve stimulation (VNS). He has given informed consent to be decsribed in this communication.

A 63-year-old man, grown up in Germany, had been diagnosed with Gilles de la Tourette syndrome since the age of 16 years with motor tics (head jerks, shoulder jerks, facial tics, tapping) and echolalia. He was treated with olanzapine (dosage 5-20 mg), aripiprazole (7.5-15 mg) and citaloprame (20-60 mg) without success. At the age of 25 years he additionally developed major depression with increasing frequency and intensity during recurrent episodes. He was treated with different classes of antidepressants and electroconvulsive therapy (ECT) in 18 clinical admissions over this long period. The patient failed to respond to any of the aforementioned adequate treatments. On the basis of a therapy-resistant overall course with a transient response to ECT, VNS implantation was chosen and performed in October 2004. Neither motor nor vocal tics decreased during the course of ECT. The intensity of 0.25 mA (pulse frequency 20 Hz, pulse width 500 μs with stimulation ON for 30s every 5 min) was increased gradually (in 0.25 increments) up to 1.25 mA until March 2005 ([Table 1]). Within six months after implantation, the depressive syndrome improved significantly (Hamilton Depression Rating Scale score: 25 and 13, before and after six months of treatment). Furthermore, we assessed the severity of GTS symptoms using the Shapiro Tourette's Syndrome Severity Scale (STSS) and the Yale Global Tic Severity (YGTSS) scale [8] [12]. Before VNS treatment the patient had a score of 5.5 on the STSS and 34 points on the motor and vocal subscale of the YGTTS (17 points motor tics, 17 points vocal tics) consistent with the presence of severe GTS symptoms. Nine months after implantation, the patient reported a marked decrease of his symptoms related to GTS (e.g., head and shoulder jerks, echolalia). This subjective improvement could be confirmed by inspection and neurological examination. When the STSS and YGTTS tests were reassessed, we found a significant decrease in both scores (STSS: 1, YGTTS: 14 [8 motor tics, 6 vocal tics]), indicating mild GTS. This effect remained stable during his visits in the follow-up period up to 15 months after implantation ([Table 1]). Beside a mild voice alteration during stimulation, the patient did not report about other side effects. The reduction of symptoms showed no fluctuation and was stable, independent of stimulation phases and stimulation-free intervals (“on, off” phases). 18 months after implantation the patient did suffer from a return of depression symptoms. However, this was not correlated with an increase of motor and vocal tics.

Table 1 Clinicial course of depression and Gilles de la Tourette syndrome after implantation Months after implantation HAMD=Hamilton Depression Rating Scale; YGTTS=Yale Global Tic Severity; STSS: Shapiro Tourette's Syndrome Severity Scale baseline 3 6 9 12 15 18 stimulation strength 0.25 mA 0.5 0.75 1.0 1.25 1.25 1.25 HAMD 25 23 13 14 14 8 18 YGTTS 34 33 30 14 14 14 14 STSS 5.5 5.5 4.5 1 1 1 1

The biological basis of GTS is unknown as yet, but various findings in GTS patients revealed decreases in metabolism in midbrain, ventral striatum, nucleus caudatus, thalamus [1] [5] and a hypoperfusion in the left dorsolateral prefrontal cortex [9]. Numerous lines of evidence also support the role of catecholamines in the pathophysiology of tics and GTS [10]. Single reports revealed positive effects of atypical antipsychotics (e.g., aripiprazole, olanzapine) and SSRI treatment, mainly with respect to obsessive compulsive disorders [2] [6] [13].

The activating effects of VNS treatment on the locus coeruleus (increase of noradrenergic activity), the amygdale, the thalamus and the prefrontal cortex were recently shown [3] [11]. Therefore, by modulating cerebral structures which are also presumably involved in the pathophysiology of GTS, VNS treatment might have exerted its action in this case. The efficiacy of VNS treatment in GTS might be based on the hypothesis of the activation of the locus coeruleus (increase of noradrenergic activity) and the dorsolateral prefrontal cortex (hyperperfusion). Recently, other successful treatments in GTS were described by the use of electroconvulsive therapy and deep brain stimulation [7] [14]. Our experience suggests that VNS treatment could be an alternative stimulation method in the treatment of GTS. Further studies are warranted to address this interesting question.

References

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1 Both authors contributed equally to this work.

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