Energy and protein levels in dairy cow diets to recover milk ethanol stability.

The objective of this study was to evaluate the effect of energy and protein in the diet on the recovery of milk ethanol stability (MES) induced by feed restriction. Twelve Holstein and Holstein x Jersey crossbred cows with an average of 146 ± 50 d in milk, 575.4 ± 70 kg of body weight, and 18.93 ± 5.46 kg/d of milk yield were distributed in a 3x3 Latin square design with 3 treatments and 3 experimental periods. Each experimental period lasted 24 d, comprising 3 phases: a 13-d adaptation phase (100E+100P), a 4-d induction phase for milk ethanol instability (50E+50P), and a 7-d recovery phase for MES (3 treatments). The 3 treatments during the recovery phase consisted of 3 diets aiming to meet the requirements of energy and protein (100E+100P), only energy (100E+50P), or only protein (50E+100P). The diet during the adaptation and induction phases was common for all cows. The energy and protein levels to meet each cow's requirements were based on the group average. Restriction of energy and protein reduced dry matter, crude protein, and total digestive nutrient intake for cows fed 100E+50P and 50E+100P. The lowest body weight was observed for cows fed 50E+100P, with no difference for body condition score. During the induction phase, MES "was" reduced by 9 percentage units. Cows fed 100E+100P recovered MES in the first days of the recovery phase, while 100E+50P slightly improved MES, and 50E+100P had a constant decrease in MES. Cows fed 100E+50P and 50E+100P produced, respectively, 3.6 and 5.9 kg less milk than those fed 100E+100P. The 50E+100P treatment exhibited the highest milk fat content and somatic cell score, along with the lowest milk lactose content. Protein content was higher in the 100E+100P treatment. Cows fed 50E+100P showed higher serum albumin levels compared with those on the 100E+100P treatment, not differing from the 100E+50P treatment. We concluded that the complete recovery of MES in cows with feed restrictions is possible only by supplying both the energy and protein requirements in the cows' diet. However, restricting energy intake poses a greater limitation on MES recovery compared with restricting protein.

Neuronal spiking in the pedunculopontine nucleus in progressive supranuclear palsy and in idiopathic Parkinson's disease.

The pedunculopontine nucleus (PPN) is engaged in posture and gait control, and neuronal degeneration in the PPN has been associated with Parkinsonian disorders. Clinical outcomes of deep brain stimulation of the PPN in idiopathic Parkinson's disease (IPD) and progressive supranuclear palsy (PSP) differ, and we investigated whether the PPN is differentially affected in these conditions. We had the rare opportunity to record continuous electrophysiological data intraoperatively in 30 s blocks from single microelectrode contacts implanted in the PPN in six PSP patients and three IPD patients during rest, passive movement, and active movement. Neuronal spikes were sorted according to shape using a wavelet-based clustering approach to enable comparisons between individual neuronal firing rates in the two disease states. The action potential widths showed a bimodal distribution consistent with previous findings, suggesting spikes from noncholinergic (likely glutamatergic) and cholinergic neurons. A higher PPN spiking rate of narrow action potentials was observed in the PSP than in the IPD patients when pooled across all three conditions (Wilcoxon rank sum test: p = 0.0141). No correlation was found between firing rate and disease severity or duration. The firing rates were higher during passive movement than rest and active movement in both groups, but the differences between conditions were not significant. PSP and IPD are believed to represent distinct disease processes, and our findings that the neuronal firing rates differ according to disease state support the proposal that pathological processes directly involving the PPN may be more pronounced in PSP than IPD.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

Radiofrequency-thermoablation: General principle, historical overview and modern applications for epilepsy.

Stereotactically guided radiofrequency thermoablation (RFTA) for epilepsy has been frequently applied over the last 40 years. Radiofrequency electrodes with temperature control function generate a coagulation lesion with clearly defined borders. In combination with high-resolution MRI imaging, this technique allows minimally-invasive ablation of periventricular nodular heterotopias, small focal type II dysplasias, and hypothalamic hamartomas. This review summarises the literature addressing this topic mainly regarding technical aspects. In essence, RFTA is a safe treatment option for patients suffering from epileptogenic pathologies visible on MRI-images.

Stereotactic brachytherapy using iodine 125 seeds for the treatment of primary and recurrent anaplastic glioma WHO° III.

The current study analyzed the outcome after stereotactic brachytherapy (SBT) using iodine-125 seeds in anaplastic astrocytoma, oligoastrocytoma or oligodendroglioma not suitable for resection. Out of 223 patients harbouring a malignant glioma treated according to a prospective protocol, 172 patients were selected who received SBT to treat a WHO grade III de-novo/residual tumor (n = 99) or a tumor recurrence after multimodal treatment (n = 73). We assessed progression free survival (PFS), overall survival (OS), radiological and clinical outcome and determined prognostic factors using univariate and multivariate regression analyses. The median follow-up time was 38 months. Median OS and median PFS was 28.9 and 21.4 months in the de-novo group vs. 49.4 and 32.6 months in the recurrence group. Recurrent tumors had more frequently (p = 0.01) an oligodendroglial-component compared to de novo tumors. According to cohort-specific univariate analyses KPS at SBT had a significant (p = 0.008) impact on OS in the de-novo group. In the recurrence group, (Cox regression analysis) OS was significantly associated with histology subtype (oligoastro-/oligodendroglioma vs. astrocytoma, p = 0.043). Transient and permanent morbidity (~1 %) was low. For patients unable to undergo surgery due to eloquent tumour location or reduced general condition SBT is an effective treatment option, which does not foreclose additional therapeutic interventions.

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial.

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.

Direct visualization of anatomic subfields within the superior aspect of the human lateral thalamus by MRI at 7T.

BACKGROUND AND PURPOSE: The morphology of the human thalamus shows high interindividual variability. Therefore, direct visualization of landmarks within the thalamus is essential for an improved definition of electrode positions for deep brain stimulation. The aim of this study was to provide anatomic detail in the thalamus by using inversion recovery TSE imaging at 7T. MATERIALS AND METHODS: The MR imaging protocol was optimized on 1 healthy subject to segment thalamic nuclei from one another. Final images, acquired with 0.5(2)-mm2 in-plane resolution and 3-mm section thickness, were compared with stereotactic brain atlases to assign visualized details to known anatomy. The robustness of the visualization of thalamic nuclei was assessed with 4 healthy subjects at lower image resolution. RESULTS: Thalamic subfields were successfully delineated in the dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had an appearance very similar to that of myelin-stained sections seen in brain atlases. Visualized intrathalamic structures were, among others, the lamella medialis, the external medullary lamina, the reticulatum thalami, the nucleus centre médian, the boundary between the nuclei dorso-oralis internus and externus, and the boundary between the nuclei dorso-oralis internus and zentrolateralis intermedius internus. CONCLUSIONS: Inversion recovery-prepared TSE imaging at 7T has a high potential to reveal fine anatomic detail in the thalamus, which may be helpful in enhancing the planning of stereotactic neurosurgery in the future.

Case report: practicability of functionally based tractography of the optic radiation during presurgical epilepsy work up.

Pre-operative tractography of the optic radiation (OR) has been advised to assess the risk for postoperative visual field deficit (VFD) in certain candidates for resective epilepsy surgery. Diffusion tensor imaging (DTI) tractography relies on a precise anatomical determination of start and target regions of interest (ROIs), such as the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). The post-chiasmal visual pathway and V1 show considerable inter-individual variability, and in epilepsy patients parenchymatous lesions might further complicate this matter. A functionally based tractography (FBT) seems beneficial for precise OR identification. We assessed practicability of FBT for OR identification in a patient with occipital lobe epilepsy due to a temporo-occipital maldevelopmental tumor. The MRI protocol at 3T included a T1-weighted sagittal 3D scan, a T2-weighted axial 2D scan and a DTI scan using an echo planar spin echo sequence. ROIs for fiber tracking of OR (LGN & V1) were determined with T2*-weighted fMRI-based retinotopic assessment. After DTI pre-processing and fiber tracking, paths with similar properties were combined in clusters for visual presentation and OR localization. Retinotopic phase maps allowed for the identification of V1 and LGN for a precise DTI-based reconstruction of OR, which was distant to the patient's tumor. Location and structure of ORs were comparable in each hemisphere. FBT could thus influence the human research of the extrastriate visual pathway and the risk management of post-operative VFD in epilepsy surgery.

Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH).

PURPOSE: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. PATIENTS AND METHODS: Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. RESULTS: During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 ± 5 % after EFRT and 65 ± 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. CONCLUSION: EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative.

LINAC-radiosurgery for nonsecreting pituitary adenomas. Long-term results.

BACKGROUND AND PURPOSE: Stereotactic linear accelerator-based radiosurgery (LINAC-RS) is increasingly used for microsurgically inaccessible or recurrent pituitary adenomas. This single-center study evaluates the long-term follow-up after LINAC-RS of nonsecreting pituitary adenomas (NSA). PATIENTS AND METHODS: Between 1992 and August 2008, 65 patients with NSA were treated. Patient treatment and follow-up were conducted according to a prospective protocol. Indications for LINAC-RS were (1) tumor recurrence or (2) residual tumor. Three patients were treated primarily. For analysis of prognostic factors, patients were grouped according to epidemiological or treatment-associated characteristics. RESULTS: A total of 61 patients with a follow-up ≥ 12 months (median 83 months, range 15-186 months, longest follow-up of published radiosurgery series) were evaluated with regard to their clinical, radiological, and endocrinological course. The median tumor volume was 3.5 ml (± 4.3 ml, range 0.3-17.3 ml) treated with a median surface and maximum dose of 13.0 Gy and 29.7 Gy, respectively. Local tumor control was achieved in 98%. One patient died of unrelated cause after 36 months and 1 patient developed a radiation-induced seizure disorder. Visual complications did not occur. In 37 of 41 patients (90.2%), pituitary function remained stable. Maximum dose to the pituitary ≤ 16 Gy and female gender were positive prognostic factors for the preservation of pituitary function. CONCLUSION: LINAC-RS is a minimally invasive, safe, and effective treatment for recurrent NSA or microsurgically inaccessible residual tumor. LINAC-RS yielded a high rate of local long-term tumor control with a small number of radiation-induced side effects.

[Neurological and technical aspects of deep brain stimulation]. / Neurochirurgische und technische Aspekte der tiefen Hirnstimulation.

Deep brain stimulation (DBS) is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. Despite the functional efficacy of DBS, which in parts is documented on the highest evidence level, the underlying mechanisms are still not completely understood. According to the current state of knowledge electrophysiological and functional data give evidence that high-frequency DBS has an inhibitory effect around the stimulation electrode whilst at the same time axons entering or leaving the stimulated brain area are excited leading to modulation of neuronal networks. The latter effect modifies pathological discharges of neurons in key structures of the basal ganglia network (e.g. irregular bursting activity, oscillations or synchronization) which are found in particular movement disorders such as Parkinson' s disease or dystonia. The introduction of technical standards, such as the integration of high resolution MRI into computer-assisted treatment planning, in combination with special treatment planning software have contributed significantly to the reduction of severe surgical complications (frequency of intracranial hemorrhaging 1-3%) in recent years. Future developments will address the modification of hardware components of the stimulation system, the evaluation of new brain target areas, the simultaneous stimulation of different brain areas and the assessment of different stimulation paradigms (high-frequency vs low-frequency DBS).

[Neurosurgical standards in deep brain stimulation : consensus recommendations of the German Deep Brain Stimulation Association]. / Neurochirurgische Standards bei tiefer Hirnstimulation : Empfehlungen der Deutschen Arbeitsgemeinschaft Tiefe Hirnstimulation.

Surgery combining stereotactically guided implantation of brain electrodes in subcortical key structures of the brain with the connection of these brain electrodes to subcutaneously implanted impulse generators is one precondition for the therapeutic application of deep brain stimulation (DBS). During the last 10-15 years minimal requirements concerning this surgery have been formulated, addressing in particular technical equipment and operational procedures and being also in parts supported quantitatively by systematic investigations. Only appropriate patient management, high technical standards and an adequate surgical technique can minimize the frequency of those complications, which are supposed to be directly caused by surgery. High-resolution imaging is the basis for target definition, determination of the surgical approach, documentation of final electrode position and postoperative exclusion of iatrogenic intracerebral haemorrhage. In addition, the quality of treatment planning depends largely on the image processing and viewing possibilities provided by specific planning software. Further issues, for which standards are defined, address electrophysiological and clinical examinations to be performed intraoperatively and general surgical measures, which should be considered during implantation of DBS systems. This review summarizes and evaluates requirements imposed on the aforementioned system components and working steps, taking into consideration data from the literature.

Frontal FDG-PET activity correlates with cognitive outcome after STN-DBS in Parkinson disease.

BACKGROUND: Inconsistent changes of cognitive functioning have been reported in patients with Parkinson disease (PD) with deep brain stimulation (DBS) of the subthalamic nucleus (STN). To investigate the underlying pathomechanisms, we correlated alterations of cognitive test performance and changes of neuronal energy metabolism in frontal basal ganglia projection areas under bilateral STN stimulation. METHODS: We conducted verbal fluency, learning, and memory tests and 18-fluorodeoxyglucose (FDG) PET in nine patients with PD with STN-DBS before and 6 months after surgery. Using coregistered MRI, postoperative changes of the normalized cerebral metabolic rates of glucose (nCMRGlc) in the dorsolateral prefrontal cortex (DLPFC), lateral orbitofrontal cortex (LOFC), ventral and dorsal cingulum (v/dACC), and in Broca area were determined and correlated with alterations of neuropsychological test results. RESULTS: After surgery, highly variable changes of both cognitive test performance and frontal nCMRGlc values were found with significant correlations between verbal fluency and FDG uptake in the left DLPFC (Brodmann area [BA] 9, 46), left Broca area (BA 44/45), and the right dACC (BA 32). A decrease of nCMRGlc in the left OFC (BA 11/47) and dACC (BA 32) correlated with a decline of verbal learning. All patients showed reduced metabolic activity in the right anterior cingulate cortex after DBS. Baseline cognitive abilities did not predict verbal learning or fluency changes after surgery. CONCLUSIONS: These data show a significant linear relationship between changes in frontal 18-fluorodeoxyglucose PET activity and changes in cognitive outcome after deep brain stimulation of the subthalamic nucleus (STN) in advanced Parkinson disease. The best correlations were found in the left frontal lobe (dorsolateral prefrontal cortex and Broca area). Baseline performance on cognitive tests did not predict cognitive or metabolic changes after STN electrode implantation.

Long-term efficacy and safety of chronic globus pallidus internus stimulation in different types of primary dystonia.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) offers a very promising therapy for medically intractable dystonia. However, little is known about the long-term benefit and safety of this procedure. We therefore performed a retrospective long-term analysis of 18 patients (age 12-78 years) suffering from primary generalized (9), segmental (6) or focal (3) dystonia (minimum follow-up: 36 months). METHODS: Outcome was assessed using the Burke-Fahn-Marsden (BFM) scores (generalized dystonia) and the Tsui score (focal/segmental dystonia). Follow-up ranged between 37 and 90 months (mean 60 months). RESULTS: Patients with generalized dystonia showed a mean improvement in the BFM movement score of 39.4% (range 0-68.8%), 42.5% (range -16.0 to 81.3%) and 46.8% (range -2.7 to 83.1%) at the 3- and 12-month, and long-term follow-up, respectively. In focal/segmental dystonia, the mean reduction in the Tsui score was 36.8% (range 0-100%), 65.1% (range 16.7-100%) and 59.8% (range 16.7-100%) at the 3- and 12-month, and long-term follow-up, respectively. Local infections were noted in 2 patients and hardware problems (electrode dislocation and breakage of the extension cable) in 1 patient. CONCLUSION: Our data showed Gpi-DBS to offer a very effective and safe therapy for different kinds of primary dystonia, with a significant long-term benefit in the majority of cases.

STN-DBS activates the target area in Parkinson disease: an FDG-PET study.

OBJECTIVE: The immediate effects of deep brain stimulation (DBS) on subcortical neurons of its target region are controversial. METHODS: We measured the regional normalized resting cerebral metabolic rate of glucose (nCMRGlc) with 18-fluorodeoxyglucose (FDG) and PET in 12 patients with Parkinson disease (PD) and bilateral DBS of the subthalamic nucleus (STN) compared to 10 age-matched controls. PET was performed before surgery and 6 months after electrode implantation in DBS off- and on-conditions. Stereotactic coordinates of active STN electrode poles were determined with intraoperative skull x-ray and transferred to preoperative MR images. Subsequently, volumes of interest (VOIs) were placed around active electrode contacts, in the STN and in the globus pallidus. DBS induced changes of nCMRGlc values were determined in each VOI after PET and MRI coregistration. RESULTS: Electrode placement without stimulation led to significant FDG uptake reduction in the electrode region and in the STN (microlesional effect). Under active DBS, the local nCMRGlc significantly increased in all VOIs under investigation. CONCLUSIONS: The data demonstrate that deep brain stimulation (DBS) induced metabolic activation of the subthalamic region and the directly connected globus pallidus which is in line with local and remote excitation of neurons by high frequency stimulation. These PET findings most likely reflect tonic driving of the DBS target area and its projection sites via ortho- and antidromic fiber conduction. We conclude that subthalamic nucleus DBS has predominant excitatory properties and does, therefore, fundamentally differ from lesional neurosurgery.

Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism.

OBJECTIVES: To study the frequency of different gene mutations in patients with early-onset parkinsonism and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and the short- and long-term surgical outcome in mutation-positive (MUT+) and -negative (MUT-) patients. METHODS: Eighty patients with disease onset at age

Deep brain stimulation for Parkinson's disease.

Indications for the treatment of Parkinson's disease (PD) with deep brain stimulation (DBS) are severe, therapy refractory tremor and complications of long-term levodopa uptake. Since its first application DBS has become a standard therapy for these patients. Theoretically, the ventrolateral part of the internal pallidum (GPI) or the subthalamic nucleus (STN) are suitable targets in order to treat all cardinal symptoms of patients in an advanced stage of PD stereotactically. Although clinical efficacy of both GPI or STN stimulation is obviously comparable, it has become widely accepted to prefer STN over GPI DBS. If PD-associated, medically intractable tremor is the most disabling symptom, stimulation of the ventrolateral motor thalamus can be an alternative. Anatomical targets for DBS are small and located in critical brain areas. Furthermore, this type of surgery is highly elective. As a consequence, high resolution multiplanar imaging and adequate treatment planning software are indispensable prerequisites for DBS surgery. Currently, commercially available impulse generators deliver a permanent high frequency periodic pulse train stimulation that interacts rather unspecifically with the firing pattern of both normal and pathological neurons. Prospectively, the development of more specific stimulation paradigms may help to improve the efficacy of this treatment modality.

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery--experiences from a single centre.

OBJECTIVE: To determine the surgery-related and hardware-related complications of deep-brain stimulation (DBS) at a single centre. METHODS: 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long-term complications (352 electrodes, mean follow-up 36.3 (SD 20.8) months). RESULTS: The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long-term observation period, hardware-related problems were registered in 25 of 180 (13.9%) patients. CONCLUSIONS: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients' prolonged hospital stay and repeated surgery were wound infections and hardware-related complications.

Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation.

OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. METHODS: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. RESULTS: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.