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Deep brain stimulation (DBS) is a neurosurgical treatment, in which electrodes are implanted in deep regions of the brain. This procedure can be used to treat patients with movement disorders, such as Parkinson’s disease (PD) and dystonia. The implanted electrodes deliver electrical pulses, that help to control the main disease symptoms. Until recently, stimulation could only be continuously applied, without taking into account daily symptom fluctuations.Adaptive DBS (aDBS) is an upgrade of this treatment. With aDBS, the stimulation delivered is regulated (in real time), based on the severity of symptoms. To indicate when and how stimulation should be delivered, brain oscillations are used as feedback signal. These oscillations are able to reflect the clinical state of the patients. By dynamically adjusting the stimulation according to the needs of each patient, aDBS might be able to provide a better symptom control. In addition to this, aDBS could prevent the occurrence of side effects caused by excessive stimulation. This thesis investigates the intraoperative efficacy of aDBS in patients with PD and dystonia at the University Medical Center Groningen, The Netherlands. The first part of this thesis describes the characteristics of the signals that can be used to estimate the severity of symptoms in these patients. The second and third parts of the thesis evaluate the immediate effects of aDBS in patients with PD and dystonia, respectively. The main conclusions are that aDBS is effective for PD, and feasible for dystonia. This opens the possibility to further investigate aDBS outside the hospital.

Since stroke is a major cause of death worldwide, understanding its underlying pathology and determining prognostic factors is essential. The circle of Willis (CoW) is a critical arterial relay system located at the base of the brain. Therefore, hemodynamics within the CoW plays an important role in the pathology of stroke. In this thesis, CoW anatomy and internal carotid artery (ICA) stenosis are pointed out to influence cerebrovascular territory perfusion. This is clinically relevant if the ICA-stenosis grade is more than 70%. With a numerical model, hemodynamics in the CoW can be simulated. This thesis introduces a simplified numerical model for personalized CoW hemodynamics. The CoW-model is explained and validated, against the background of a systematic review of the literature. Since there is an extensive heterogeneity between proposed numerical models, in current studies hemodynamic parameters based on CoW-configuration still cannot be associated with the development of anatomical causes for stroke, such as intracranial aneurysm. Additional simulation accuracy is warranted before the numerical model can be applied in clinical practice. Finally, in this thesis, myosteatosis was found to be associated with the clinical severity of a subtype of stroke, the subarachnoid haemorrhage. However, muscle atrophy and myosteatosis were not associated with neurological outcome nor long term survival. In conclusion, this thesis is a next step in the association between hemodynamics in the CoW and several stroke types, and thus in personalizing and optimizing stroke management.

Spontaneous subarachnoid hemorrhage (SAH) is a devastating type of stroke, with the most frequent cause being a ruptured intracranial aneurysm. One of the most important things after the occurrence of a SAH, is the prevention of a rebleeding of the aneurysm. Therefore, the aneurysm needs to be occluded by either endovascular coiling or neurosurgical clipping, traditionally performed in the first 72 hours after the ictus. In this thesis, risk factors for early rebleeding after SAH are identified. Based on this, a new treatment paradigm for the acute phase of aSAH is proposed, recommending treatment of patients at high risk for rebleeding on an emergency base. Furthermore, this thesis highlights the importance of accurate identification of patients in a poor clinical condition for decisions regarding timing and type of treatment. The developed SAFIRE-grading scale is proposed as a new tool to assess the patients’ outcome soon after the ictus. Last, it revealed the impact of treatment delay and rebleeding on the outcomes of the International Subarachnoid Aneurysm Trial (ISAT), a large trial comparing both treatments, and found that after correcting for this, coiling and clipping could be considered comparable in long term based. All together, these new insights can lead to improved treatment of patients with aneurysmal SAH and a further decline in mortality and morbidity rates.

Tinnitus is the perception of sound or noise in the absence of a physical sound source. For some patients, tinnitus has a significant impact on their quality of life and conventional treatment options can be insufficient. In this thesis, we evaluated and investigated several neurosurgical treatment options for patients with severe, intractable tinnitus. Tinnitus can be the result of compression of the cochlear nerve with a blood vessel (neurovascular conflict). In this thesis, we showed that a decompression surgery for this conflict has a low success percentage and a relatively high surgical complication rate. However, when patients experience both tinnitus and vertigo, the success percentage is considerably higher. A neurovascular conflict may be diagnosed with MR-imaging, however they do not always relate to ipsilateral symptoms. Our research showed that the type of compression, e.g. causing a dimple in the nerve, is not a good indicator for a symptomatic neurovascular conflict.In order to reduce tinnitus, neurostimulation can be performed. The effect of direct stimulation of the cochlear nerve with a ring electrode was evaluated, but appeared to be not a viable treatment option as damage of the nerve lead to increase in hearing loss in the majority of patients. Another novel option is neurostimulation of the cochlear nucleus in the brainstem with an auditory brainstem implant (ABI). We described a pilot study studying the effect of the ABI on tinnitus. Preliminary results (one year follow-up) in two patients show a stable tinnitus reduction. Also, hearing ability was undamaged after implantation.