Elina Tripoliti

MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinsons disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6) mm. There were no haemorrhagic complications. At a median follow-up period of 12 months, there was a mean improvement in the off-medication motor part of the Unified Parkinsons Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinsons disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.

Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation.

Subthalamic nucleus deep brain stimulation (STN‐DBS) is particularly effective in improving limb symptoms in Parkinsons disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN‐DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off‐stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1‐minute monologue. Movement was assessed using the UPDRS‐III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control.

Effects of subthalamic stimulation on speech of consecutive patients with Parkinson disease

Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short- and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change. Methods: Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on- and off-medication with on- and off-stimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year. Results: Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2% ± 20.15% off-medication and 16.9% ± 21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6% ± 5.5% and 4.5% ± 8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year. Conclusion: The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients. Classification of evidence: This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1 month, 6 months, and 1 year compared to baseline and to control subjects treated with best medical therapy.

Patient-Specific Model-Based Investigation of Speech Intelligibility and Movement during Deep Brain Stimulation

Background/Aims: Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson’s disease. The aim of this study was to investigate the anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Methods: Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Results: Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Conclusion: Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus.

Long-term outcome of subthalamic nucleus deep brain stimulation for Parkinson's disease using an MRI-guided and MRI-verified approach

Background Subthalamic nucleus (STN) deep brain stimulation (DBS) represents a well-established treatment for patients with advanced Parkinsons disease (PD) insufficiently controlled with medical therapies. This study presents the long-term outcomes of patients with PD treated with STN-DBS using an MRI-guided/MRI-verified approach without microelectrode recording. Methods A cohort of 41 patients who underwent STN-DBS were followed for a minimum period of 5 years, with a subgroup of 12 patients being followed for 8–11 years. Motor status was evaluated using part III of the Unified Parkinsons Disease Rating Scale (UPDRS-III), in on- and off-medication/on-stimulation conditions. Preoperative and postoperative assessments further included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), neuropsychological and speech assessments, as well as evaluation of quality of life. Active contacts localisation was calculated and compared with clinical outcomes. Results STN-DBS significantly improved the off-medication UPDRS-III scores, compared with baseline. However, UPDRS scores increased over time after DBS. Dyskinesias, motor fluctuations and demands in dopaminergic medication remained significantly reduced in the long term. Conversely, UPDRS-III on-medication scores deteriorated at 5 and 8 years, mostly driven by axial and bradykinesia subscores. Quality of life, as well as depression and anxiety scores, did not significantly change at long-term follow-up compared with baseline. In our series, severe cognitive decline was observed in 17.1% and 16.7% of the patients at 5 and 8 years respectively. Conclusions Our data confirm that STN-DBS, using an MRI-guided/MRI-verified technique, remains an effective treatment for motor ‘off’ symptoms of PD in the long term with low morbidity.

Method for patient-specific finite element modeling and simulation of deep brain stimulation

Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS.

Predictive factors of speech intelligibility following subthalamic nucleus stimulation in consecutive patients with Parkinson's disease

Speech changes after bilateral subthalamic nucleus deep brain stimulation (STN‐DBS) can be variable, with the majority of patients experiencing speech deterioration over time. The aim of this study was to describe the perceptual characteristics of speech following chronic STN‐DBS and to analyze clinical and surgical factors that could predict speech change. Fifty‐four consecutive patients (34 men; mean age ± standard deviation (SD), 58.8 ± 6.3 years; mean ± SD disease duration, 12.5 ± 4.7 years; mean ± SD levodopa equivalent, 1556 ± 671 mg/day; mean ± SD Unified Parkinsons Disease Rating Scale motor part (UPDRS‐III) off‐medication score, 48.1 ± 17.9 [range, 20‐89]; and mean ± SD UPDRS‐III on‐medication score, 12.4 ± 7.8 [range, 2‐31]) participated in this study. They were assessed before and at 1 year after surgery using the Assessment of Intelligibility for the Dysarthric Speech, the perceptual scale from Darley et al., and the UPDRS‐III. Speech intelligibility deteriorated on average by 14.4% (P = 0.0006) after 1 year of STN‐DBS when off‐medication and by 12.3% (P = 0.001) when on‐medication. The effect on speech was not linked to age at surgery, unlike the effect on motor outcome. The most significant predictive factors for deterioration of speech intelligibility when patients were off‐medication/on‐stimulation were lower preoperative speech intelligibility on‐medication, longer disease duration, and medially placed left hemisphere active electrode contact. Speech change after STN‐DBS is variable and multifactorial. Consistent preoperative speech evaluation would help inform patients about the possible effects of surgery. Appropriate consideration of speech deficits might assist surgical targeting, particularly of the left electrode.

A review of brain circuitries involved in stuttering

Stuttering has been the subject of much research, nevertheless its etiology remains incompletely understood. This article presents a critical review of the literature on stuttering, with particular reference to the role of the basal ganglia (BG). Neuroimaging and lesion studies of developmental and acquired stuttering, as well as pharmacological and genetic studies are discussed. Evidence of structural and functional changes in the BG in those who stutter indicates that this motor speech disorder is due, at least in part, to abnormal BG cues for the initiation and termination of articulatory movements. Studies discussed provide evidence of a dysfunctional hyperdopaminergic state of the thalamocortical pathways underlying speech motor control in stuttering. Evidence that stuttering can improve, worsen or recur following deep brain stimulation for other indications is presented in order to emphasize the role of BG in stuttering. Further research is needed to fully elucidate the pathophysiology of this speech disorder, which is associated with significant social isolation.

Adaptive deep brain stimulation for Parkinson's disease demonstrates reduced speech side effects compared to conventional stimulation in the acute setting

Deep brain stimulation (DBS) for Parkinsons disease (PD) is currently limited by costs, partial efficacy and surgical and stimulation-related side effects. This has motivated the development of adaptive DBS (aDBS) whereby stimulation is automatically adjusted according to a neurophysiological biomarker of clinical state, such as β oscillatory activity (12–30 Hz). aDBS has been studied in parkinsonian primates and patients and has been reported to be more energy efficient and effective in alleviating motor symptoms than conventional DBS (cDBS) at matched amplitudes.1 ,2 However, these studies have not considered whether side effects can also be avoided with clinically effective stimulation. In PD, it is well recognised that a significant proportion of patients develop speech deterioration following DBS of the subthalamic nucleus (STN), which may be reversible.3 Here we test bilateral stimulation, optimising parameters for aDBS, and evaluate speech intelligibility. We hypothesised that acute aDBS would be more effective and more efficient than cDBS at matched stimulation parameters while causing less speech impairment. We recruited 10 patients with advanced idiopathic PD following implantation of DBS electrodes into the STN.2 Recordings took place 3–6 days following electrode placement during a temporary period of externalisation. All participants gave informed written consent, and were tested following overnight withdrawal of dopaminergic medication (see online supplementary material). Two patients were excluded due to external stimulator failure leading to no voltage delivery under aDBS and cDBS conditions. ### supplementary data [jnnp-2016-313518supp.pdf] aDBS stimulation was delivered bilaterally, only when β amplitude exceeded a threshold as previously described.2 aDBS contacts, voltages and trigger thresholds were independently set for the two sides according to motor benefit versus induced paraesthesiae, with the same contacts/voltages used for cDBS. Stimulation in each block continued for 15 min prior to evaluation. Participants were assessed …

Treatment of dysarthria following subthalamic nucleus deep brain stimulation for Parkinson's disease

Deep brain stimulation of the subthalamic nucleus (STN‐DBS) is an established treatment for patients with Parkinsons disease (PD). Speech impairment is a frequent side effect of the surgery. This study examined the efficacy of an intensive speech treatment, the Lee Silverman Voice Treatment (LSVT) on dysarthria after STN‐DBS.