Aggravated stuttering following subthalamic deep brain stimulation in Parkinson's disease - two cases

Stuttering is a speech disorder with disruption of verbal fluency characterized by involuntary repetitions or prolongations of sounds or syllables. The pathogenesis of stuttering is not well understood. The most common form of stuttering is developmental stuttering, which evolves in childhood. Neurogenic or acquired stuttering occurs after a definable brain damage, e.g. stroke, intracerebral hemorrhage, or head trauma [1]. Acquired stuttering has been observed after lesions in a variety of brain areas, including lesions in the striatum or thalamus. The occurrence of basal ganglia disorders, such as Parkinson's disease (PD), occasionally leads to a re-emergence of recovered developmental stuttering [2].

PD is a movement disorder defined by the presence of the cardinal motor features bradykinesia, rigidity and tremor. Long-term medical management of PD is frequently complicated by treatment-associated motor complications in the form of fluctuating motor function and dyskinesias. High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in advanced PD, improving all cardinal motor symptoms and treatment-related motor complications [3].

DBS of different parts of the basal ganglia and thalamus have become widely applied surgical procedures. Observations on surgical and target related side effects have provided novel insights into the function of these parts of the brain. STN-DBS is currently the most common surgical procedure for patients with PD suffering from intolerable motor complications despite optimal medical treatment. Here we report the re-occurrence and aggravation of stuttering following STN-DBS in two male patients treated for advanced PD. This supports previous studies indicating a role for the STN in the development of stuttering.

We describe two cases of aggravated stuttering after STN-DBS in our series of 144 PD patients operated between January 2001 and December 2007. One of the patients had a history of developmental stuttering, whereas the other patient first developed stuttering years after receiving a diagnosis of PD. The main problem for both patients was difficulty in speech initiation, with blocks and repetitions at word onset. Stuttering improved somewhat in the first postoperative months, but remained a problem in daily life for patient 1. The effect of neurostimulation on stuttering was clearly associated with its effects on motor functions in these two patients, and both patients had marked improvements of motor fluctuations and dyskinesias. In addition, in both patients the speech fluency improved considerably when the neurostimulator was turned off. This indicates that the electrodes were correctly placed, and that stuttering aggravation was related to neurostimulation of the STN itself, its afferent or efferent projections, and/or to structures localized in the immediate proximity.

Stuttering is a speech dysfluency. Verbal fluency tests are often used to assess executive cognitive function, and a decline in verbal fluency is consistently reported following DBS for PD. Virtually all surveys assessing phonological and/or semantic controlled word association tasks after STN-DBS report a significant and long-standing worsening of performance with respect to the pre-operative level [4]. Similar findings have also been obtained after pallidal and thalamic surgery [5]. Impaired verbal fluency after DBS has been interpreted as impairment executive functioning [6]. However, the identified aggravation of stuttering indicates that the decline in verbal fluency measured after subthalamic stimulation is, at least partly, not related to executive dysfunction, but a motor dysfunction of speech.

The STN is one of the main regulators of motor function related to the basal ganglia, through its fundamental role within the basal ganglia-thalamocortical motor circuit [7]. This motor circuit is postulated to play a key role in the etiology of stuttering. The main dysfunction is thought to be impairment in the ability of the basal ganglia to produce timing cues for the initiation of the next motor segment of speech [8]. The aggravated stuttering in the two presented patients support that alterations of the mentioned circuit at the level of the STN can influence stuttering, and indicates that the basal ganglia play a central role in speech production. The striking finding that STN-stimulation is able to modulate stuttering severity reversibly underlines the importance of the STN and the basal ganglia network in general for motor activity regulation during normal and abnormal speech.

Our findings are supported by two previous reports of worsening of developmental and acquired stuttering following bilateral STN-DBS. Moretti et al reported speech initiation problems in a PD patient without speech problems prior to DBS surgery [9]. In a report by Burghaus and colleagues a marked worsening of stuttering was found after STN-DBS [10]. In their patient developmental stuttering had re-occurred after the development of PD. As in our patients, the stimulation-induced speech dysfluency slowly improved in the first months after surgery. Notably, unilateral stimulation of the STN in the language-dominant hemisphere has been reported to improve acquired stuttering [11]. It is unknown whether this discrepancy could be explained by different placements of the electrodes in the subthalamic region, differences between unilateral and bilateral stimulation, or different causes of stuttering in the reported patients. The result of unilateral stimulation was unfortunately not tested in our patients. Interestingly, it has recently been reported that DBS of another part of the basal ganglia, the internal globus pallidus, in two patients treated for dystonia also induced stuttering [12]. The sensorimotor GPi is connected to the same parts of the motor circuit as the STN, and in patients with PD stimulation of the GPi has similar effects on motor complications as stimulation in the STN [13]. Thus, alterations of the same network on different places may induce or worsen stuttering.

It seems clear that lesions of the basal ganglia-thalamocortical motor circuit are a frequent cause of neurogenic stuttering [8]. Verbal fluency improves following the administration of haloperidol and other dopamine antagonists, a neurotransmitter in the motor circuit [14]. Dopamine antagonists generally markedly increase bradykinesia and rigidity of the limbs in parkinsonian patients. This indicates that speech and body motor systems might be neuroanatomically distinct. The findings in our two patients support the hypothesis of a STN contribution to speech processes both in developmental and neurogenic stuttering. Interestingly, a striking area of overactivity was recently seen in the midbrain in people with developmental stuttering relative to controls [15].

STN-DBS is generally an effective and safe treatment [3]. However, prior to performing STN-DBS, patients with PD and stuttering should be informed about the risk of aggravated symptoms. Although stimulation-induced worsening of stuttering seemed to improve over time, it could still be a significant problem for the individual patient.

Written informed consent was obtained from the patients for publication of these case reports.