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Veerle Visser-Vandewalle, Yasin Temel, Henry Colle and Chris van der Linden

✓ The aim of this study was to investigate the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in patients with a subtype of multiple system atrophy (MSA) in which levodopa-unresponsive MSA parkinsonism (MSA-P) is predominant.

After a local anesthetic was administered, electrodes were stereotactically implanted bilaterally into the STN in four patients with MSA-P and predominantly akinetorigid symptoms. Unified Parkinson's Disease Rating Scale (UPDRS) scores were evaluated preoperatively, at 1 month, and at long-term follow up.

At 1 month the median decrease in the UPDRS III motor score was 22 on the 56-point scale (decreases of 16, 13, 29, and 15 points compared with baseline for Cases 1, 2, 3, and 4, respectively). This was mainly due to an improvement in rigidity and akinesia. The median decrease in the UPDRS II score was 11 on the 52-point scale (respective decreases of 5, 7, 13, and 9 points). At 2 years (mean follow up 27 months) there was a median decrease in the UPDRS III score of 12 (respective decreases of 18, 13, 21, and 9 points), and in the UPDRS II score of 5 (with respective decreases of 2, 2, 17, and 2), both compared with the stimulation off state.

At long-term follow up there was an increase in the individual Schwab and England scores of 10 to 15% in the stimulation on compared with the stimulation off condition.

There was a beneficial effect of STN HFS in these four patients on both a short-term and a long-term basis. A larger prospective study is justified.

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Veerle Visser-Vandewalle, Chris van der Linden, Yasin Temel, Fred Nieman, Halime Celik and Emile Beuls

Object. The aim of this study was to evaluate the long-term effects of unilateral pallidal stimulation on motor function in selected patients with advanced Parkinson disease (PD).

Methods. The authors enrolled 26 patients with idiopathic PD in whom there was an asymmetric distribution of symptoms and, despite optimal pharmocological treatment, severe response fluctuations and/or dyskinesias. After the patient had received a local anesthetic agent, a quadripolar electrode (Medtronic model 3387) was implanted at the side opposite the side affected or, if both sides were affected, the side contralateral to the more affected side. No serious complications occurred. After 3 months, the total Unified PD Rating Scale (UPDRS) Part III score decreased by 50.7% while patients were in the off-medication state (from 26.5 ± 9.2 to 13.1 ± 6.1) and by 55.4% while they were in the on-medication state (from 10.6 ± 6.3 to 4.7 ± 4.4). Only during the on state was the contralateral effect clearly more pronounced. The UPDRS Part IVa score decreased by 75% (from 3.7 ± 2.5 to 0.9 ± 1.1) and the UPDRS Part IVb score by 54.7% (from 3.3 ± 1.3 to 1.5 ± 1.3).

At long-term follow-up review (32.7 ± 10.7 months), there was an 8.3% increase in the UPDRS Part III score while patients were in the off state (from 26.5 ± 9.2 to 28.7 ± 7.6) and a 40.2% increase in this score while patients were in the on state (from 10.6 ± 6.3 to 14.9 ± 5.1). The UPDRS Part IVa score decreased by 28.1% (from 3.7 ± 2.5 to 2.7 ± 2.3) and the UPDRS Part IVb score increased by 3.5% (from 3.3 ± 1.3 to 3.4 ± 1.6).

Conclusions. Based on these unsatisfactory results at long-term review, the authors conclude that unilateral pallidal stimulation is not an effective treatment option for patients with advanced PD.

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Bianca M. L. Stelten, Lieke H. M. Noblesse, Linda Ackermans, Yasin Temel and Veerle Visser-Vandewalle

Addiction or substance dependence is a psychiatric disorder that affects many individuals in the general population. Different theories concerning the neurobiological aspects of addiction have been proposed. Special attention has been paid to models concerning dysregulation of the reward circuit and the inhibitory control system within the cortico-basal ganglia-thalamocortical pathways. In the past, attempts have been made to treat patients suffering from addiction by performing psychosurgery. Lesions were created in specific brain regions that were believed to be dysfunctional in addiction. Procedures such as cingulotomy, hypothalamotomy, and resection of the substantia innominata and the nucleus accumbens have been described as a treatment for severe addictive disorders. Deep brain stimulation, a neurosurgical treatment that has been proven to be a safe alternative for lesions in the treatment of movement disorders, has more recently been proposed as treatments for severe psychiatric conditions such as treatment-refractory obsessive-compulsive disorder and depression. With the expanding knowledge of the neurobiology of addiction, deep brain stimulation could be a future option in the treatment arsenal of addiction.

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Veerle Visser-Vandewalle, Yasin Temel, Peter Boon, Fred Vreeling, Henry Colle, Govert Hoogland, Henk J. Groenewegen and Chris van der Linden

✓✓ Based on the results of thalamotomies described by Hassler in 1970, the authors performed bilateral thalamic highfrequency stimulation (HFS) in three patients with intractable Tourette syndrome (TS). In this report they describe the long-term effects.

Three male patients (42, 28, and 45 years of age) had manifested motor and vocal tics since early childhood. The diagnosis of TS was made according to the criteria of the Tourette Syndrome Classification Study Group. Any drug or alternative treatment had been either ineffective or only temporarily effective in all three patients. There was no serious comorbidity. The target for stimulation was chosen at the level of the centromedian nucleus, substantia periventricularis, and nucleus ventrooralis internus. After 2 weeks of test stimulation, the pulse generators were implanted. After a follow-up period of 5 years in the patient in Case 1, 1 year in the patient in Case 2, and 8 months in the patient in Case 3, all major motor and vocal tics had disappeared and no serious complications had occurred. When stimulation was applied at the voltage necessary to achieve an optimal result on the tics, a slight sedative effect was noted in all three patients. In the patients in Cases 1 and 3 there were stimulation-induced changes in sexual behavior.

Chronic thalamic HFS may be an effective and safe treatment for medically intractable TS in adult patients. Unwanted stimulation-induced side effects may occur.

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Kim Rijkers, Yasin Temel, Veerle Visser-Vandewalle, Linda Vanormelingen, Marjan Vandersteen, Peter Adriaensens, Jan Gelan and Emile A. M. Beuls

✓High-frequency stimulation of the subthalamic nucleus (STN) is a widely performed method to treat advanced Parkinson disease. Due to the limitations of current imaging techniques, the 3D microanatomy of the STN and its surrounding structures in the mesencephalon are not well known. Using images they obtained using a 9.4-tesla magnetic resonance (MR) imaging unit, the authors developed a 3D reconstruction of the STN and its immediate surroundings. During the postmortem investigation of a human brain, a sample of tissue in the area around the STN was isolated. This brain tissue was scanned in the three orthogonal planes at 1-mm slice thickness. The images generated were compared with photographs of conventionally stained brain tissue slices in different neuroanatomical books, and a 3D reconstruction was made. High-field MR imaging is an appropriate method for visualizing the microanatomy of the STN and its surroundings. The images allow an optimal analysis of the microenvironment of the STN in the three orthogonal planes and can be used for 3D reconstructions of this area with possible clinical applications in the future.