Background Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in Europe. Besides motor dysfunction, PD is characterized by several non-motor and secondary motor features, such as weight change, sialorrhea, constipation and swallowing problems. Of these, swallowing is one of the most critical, as it is associated with aspiration pneumonia and consequently is the comorbidity with the highest mortality rate. Swallowing problems affect four of every five patients with PD, and even mild swallowing problems have notable psychosocial effects for patients and their caregivers. Consequently, it is essential to find treatment strategies for PD that may alleviate symptoms for patients with swallowing problems and their potential consequences. Deep Brain Stimulation (DBS) is a surgical treatment option for PD, which improves overall motor function and quality of life, but its effect on swallowing function is not clear. The purpose of this thesis was to contribute to the understanding of the effect of deep brain stimulation in the subthalamic nucleus (STN DBS) and the caudal zona incerta (cZI DBS) on pharyngeal swallowing function and on swallow-specific quality of life in patients with PD. The specific aims were to assess longitudinally the effect of STN DBS and cZI DBS on swallowing at 6 and 12 months postoperatively, in order to identify possible effects of the DBS on swallowing function. In addition, the effects of cZI DBS on ratings of swallowing-related non-motor and secondary motor features such as body weight changes, sialorrhea and speech problems were to be assessed. Methods Eleven PD patients with STN DBS (Paper I) and seventeen patients with cZI DBS (Paper II-IV) were included in this thesis. All patients were evaluated preoperatively and 6 and 12 months postoperatively. The effect of STN DBS and cZI DBS on swallowing was assessed with Fibreoptic-Endoscopic Evaluation of Swallowing (FEES) according to a predefined protocol including Penetration-Aspiration scale, Secretion Severity scale, preswallow spillage, pharyngeal residue, and pharyngeal clearance. Self-assessments were addressed using a visual analogue scale. The cZI DBS patients also completed the Swallowing Quality of Life (SWAL-QOL) questionnaire. Weight changes measured by Body Mass Index, and specific items from the Unified Parkinson’s Disease Rating Scale were also examined. Nine controls without PD were included in Paper IV, by answering the SWAL-QOL questionnaire. Results No clear effect of DBS on swallowing function or swallow-specific quality of life could be observed. There was no effect of DBS on the occurrence of aspiration, secretion, pharyngeal residue or clearance in the study groups with STN DBS or cZI DBS. Patients with STN DBS reported a subjective improvement in swallowing function with DBS stimulation turned on at 6 and 12 months after surgery. In patients with cZI DBS, the median body mass index was postoperatively increased with 1.1kg/m2 and the median increase in weight were +3.0 kg after 12 months with cZI DBS. The scores from the SWAL-QOL questionnaire were high overall in the group with cZI DBS, and the scores were unaffected by the cZI DBS surgery and stimulation. The SWAL-QOL total score was not significantly different between the PD patients and the controls, but the scores from the ‘burden’ and the ‘symptom’ subscales were worse in PD patients. Conclusions STN DBS or cZI DBS did not have a negative effect on swallowing function or ratings of swallow-specific ‘quality of life’ aspects in this cohort. Patients with STN DBS reported a self-perceived improvement in swallowing function when DBS was turned on. With regard to swallowing, patients with cZI DBS had an overall good quality of life throughout the conduct of the study and their swallow-specific quality of life was not negatively affected by cZI DBS. There seems to be no increased risk for aspiration or penetration due to surgery or stimulation for either the STN DBS or the cZI DBS groups. cZI DBS caused weight gain postoperatively. Since the sample sizes in these cohorts are small, the findings need to be confirmed in larger studies.

Background In advanced Parkinson’s disease (PD) the motor symptoms can be treated with deep brain stimulation (DBS). Subthalamic nucleus (STN) has been the most common target and caudal zona incerta (cZi) is a more recent target for stimulation. Stimulation in both of these targets has proved to be positive for the motor symptoms but there is no consensus about how DBS affects the speech and the articulation. Aim The aim of this study was to investigate how fricatives are realized within patients suffering from PD treated with DBS in STN or cZi. Method 9 patients stimulated in STN and 10 patients stimulated in cZi were recorded reading a shorter text.  The recordings were made preoperatively (Pre) and 12 months after surgery with the stimulation switched off (sOff) and on (sOn). From the recordings the fricatives were extracted and assessed in a blinded and randomized procedure. Results For the patients stimulated in cZi the target fricative /s/ had significant lower correct realizations in the sOn condition compared to the other two conditions. The other target fricatives in cZi showed the same pattern as well. For the STN group no unequivocal pattern could be seen. Conclusions The results suggest that stimulation in cZi may affect the patients’ articulation of fricatives and thereby their extended articulatory movements more negative than stimulation in STN.

Background: Essential tremor (ET) is the most common movement disorder. In cases resistant to pharmacological treatment, functional stereotactic neurosurgery can be an alternative. Lesional surgery has largely been replaced by deep brain stimulation (DBS). The current target of choice is the ventrolateral thalamus (Vim). Vim DBS has generally shown good results, but in some cases it is associated with a suboptimal effect as well as side effects. DBS in the posterior subthalamic area/caudal zona incerta (PSA/cZi) has recently shown promising effects. Recently the role of lesional therapy in selected cases has been discussed. Aim: The aim is to evaluate stereotactic functional procedures in the treatment of ET, with special emphasis on PSA DBS. Further the effects of DBS in the PSA are evaluated. The optimal target is also assessed by evaluating the effect of Vim and PSA DBS in relation to the position of the electrode. An attempt to identify patient-specific factors of prognostic importance for the outcome after DBS will be made. The quality of life (QoL) of patients treated with PSA DBS for ET will be assessed. Finally, the aim is also to analyze retrospectively the long-term outcome of lesional procedures (thalamotomies). Method: The thesis consists of five studies. The optimal electrode location is evaluated in a study analyzing the location of the electrode contact yielding the best effect in Vim DBS and PSA DBS groups. The efficacy of PSA DBS in 21 patients is evaluated in a prospective study. The correlation between outcome, age, tremor grade and gender is established in a prospective study consisting of 68 patients. Finally, the degree of improvement in QoL is determined in 16 patients operated on in the PSA. The very long-term effect of lesional surgery has been investigated in a retrospective study of nine patients who have undergone thalamotomy. Results: In the study of PSA DBS the total score on the Essential Tremor Rating Scale (ETRS) was reduced by 60% compared to the baseline value. Tremor of the arm was improved by 95%. The study evaluating the optimal contact location showed that the best effect was in the PSA in 54% and in the Vim in 12%. The efficacy of DBS was not related to age, gender, or the severity of tremor with regard to the percentage reduction of tremor on stimulation. In patients with a more severe tremor at baseline, a higher degree of residual tremor on stimulation was seen. With regard to QoL, the activities of daily living (ADL) according to the ETRS score were significantly improved, as well as according to the ADL and psychosocial subscores on the Questionnaire for Essential Tremor (QUEST) scale. No significant changes were found on the generic Short Form (SF-36) QoL scale. Thalamotomy had some positive effects, but also a significant amount of side effects that might be attributed to the surgery. Conclusions: The effect of PSA DBS was very satisfying and compares well with the results from Vim DBS. When both Vim and PSA DBS are considered, the optimal target seems to be located in the PSA. PSA DBS shows good results in improving ADL, but the results have been difficult to demonstrate on QoL scales. The efficacy of DBS could not be shown to be associated with gender or age. Nor was it associated with the severity of tremor regarding the percentage of tremor reduction on stimulation. The preoperative severity of tremor was the most important factor regarding outcome following DBS. With regard to thalamotomies, some possible remaining benefit of the surgery could be seen along with some severe side effects.