Management of hardware infections following deep brain stimulation

Summary Objective. To report our experience on hardware-related infections following deep brain stimulation (DBS).Methods. The present article presents the retrospective clinical notes review of gained in a two-centre, single-surgeon study experience of 108 consecutive DBS cases between 1996 and 2002. In all patients the minimum follow-up was six months. One hundred and eight patients received an intracerebral electrode implantation and 106 underwent internalization.Results. In total 178 electrodes were implanted with a mean follow-up of 42.6 months and a cumulative follow-up of 367.7 patient-years. Four patients (3.8%) developed an infection related to the DBS-hardware and all were initially treated with antibiotics. Two patients eventually required additional surgical treatment.Conclusion. Infections due to DBS-hardware can result in considerable levels of morbidity. In certain cases antibiotic therapy may be adequate. In others, surgical intervention to externalise the electrodes may be necessary. In our experience, there was never a need to remove the electrodes.     

Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus

Bilateral, high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the surgical therapy of choice for movement disability in advanced Parkinson's disease (PD), but this procedure evokes debilitating psychiatric effects, including depressed mood, of unknown neural origin. Here, we report the unexpected finding that HFS of the STN inhibits midbrain 5-hydroxytryptamine (5-HT) neurons to evoke depression-related behavioral changes. We found that bilateral HFS of the STN consistently inhibited (40-50%) the firing rate of 5-HT neurons in the dorsal raphe nucleus of the rat, but not neighboring non-5-HT neurons. This effect was apparent at clinically relevant stimulation parameters (> or =100 Hz, > or =30 microA), was not elicited by HFS of either neighboring or remote structures to the STN, and was still present in rat models of PD. We also found that bilateral HFS of the STN evoked clear-cut, depressive-like behavior in a widely used experimental paradigm of depression (forced swim test), and this effect was also observed in a PD model. Importantly, the depressive-like behavior elicited by HFS of the STN was reversed by a selective 5-HT-enhancing antidepressant, thereby linking the behavioral change to decreased 5-HT neuronal activity. Overall, these findings link reduced 5-HT function to the psychiatric effects of HFS of the STN observed in PD patients and provide a rational basis for their clinical management. More generally, the powerful interaction between the STN and 5-HT system uncovered here offers insights into the high level of comorbidity of basal ganglia disease and mood disorder.     

Deep brain stimulation of the nucleus accumbens core and shell: opposite effects on impulsive action

The nucleus accumbens is gaining interest as a target for deep brain stimulation in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. Here, we tested the hypothesis that stimulation of the nucleus accumbens core and shell would have different effects on impulsivity. Rats received bilateral stimulation at the level of the nucleus accumbens core or shell during a reaction time task. Stimulation of the nucleus accumbens core significantly decreased impulsivity, while stimulation of the shell increased it. Our results support the hypothesis that the nucleus accumbens is a potential target to treat neuropsychiatric disorders related to impulsivity by deep brain stimulation. However, different behavioral effects resulting from stimulation of the subterritories should be taken into account.     

Targets for deep brain stimulation in Parkinson's disease

The use of stimulation electrodes implanted in the brain to control severely disabling neurological and psychiatric conditions is an exciting and fast emerging area of neuroscience. An excellent example is Parkinson's disease (PD), in which tens of thousands of patients have now been implanted with stimulation electrodes. Patients with PD underwent deep brain stimulation (DBS) at the level of the thalamus, globus pallidus internus, subthalamic nucleus, pedunculopontine nucleus and prelemniscal radiation. The results of these interventions revealed that each target has its own specific stimulation-related positive and negative effects. Clinicians can choose their DBS target based on the situation of their individual PD patients. In the authors' opinion, patient-specific targeting should be preferred over disease-specific targeting. In this review, the authors give an overview of the targets that have been used for DBS in PD and discuss patient-specific targeting.     

High frequency stimulation of the subthalamic nucleus increases c-fos immunoreactivity in the dorsal raphe nucleus and afferent brain regions

High frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced Parkinson’s disease, but this treatment can elicit disabling mood changes. Our recent experiments show that in rats, HFS of the STN both inhibits the firing of 5-HT (5-hydroxytryptamine; serotonin) neurons in the dorsal raphe nucleus (DRN) and elicits 5-HT-dependent behavioral effects. The neural circuitry underpinning these effects is unknown. Here we investigated in the dopamine-denervated rat the effect of bilateral HFS of the STN on markers of neuronal activity in the DRN as well as DRN input regions. Controls were sham-stimulated rats. HFS of the STN elicited changes in two 5-HT-sensitive behavioral tests. Specifically, HFS increased immobility in the forced swim test and increased interaction in a social interaction task. HFS of the STN at the same stimulation parameters, increased c-fos immunoreactivity in the DRN, and decreased cytochrome C oxidase activity in this region. The increase in c-fos immunoreactivity occurred in DRN neurons immunopositive for the GABA marker parvalbumin. HFS of the STN also increased the number of c-fos immunoreactive cells in the lateral habenula nucleus, medial prefrontal cortex but not significantly in the substantia nigra. Collectively, these findings support a role for circuitry involving DRN GABA neurons, as well as DRN afferents from the lateral habenula nucleus and medial prefrontal cortex, in the mood effects of HFS of the STN.     

Magnetic resonance imaging techniques for visualization of the subthalamic nucleus

The authors reviewed 70 publications on MR imaging-based targeting techniques for identifying the subthalamic nucleus (STN) for deep brain stimulation in patients with Parkinson disease. Of these 70 publications, 33 presented quantitatively validated results. There is still no consensus on which targeting technique to use for surgery planning; methods vary greatly between centers. Some groups apply indirect methods involving anatomical landmarks, or atlases incorporating anatomical or functional data. Others perform direct visualization on MR imaging, using T2-weighted spin echo or inversion recovery protocols. The combined studies do not offer a straightforward conclusion on the best targeting protocol. Indirect methods are not patient specific, leading to varying results between cases. On the other hand, direct targeting on MR imaging suffers from lack of contrast within the subthalamic region, resulting in a poor delineation of the STN. These deficiencies result in a need for intraoperative adaptation of the original target based on test stimulation with or without microelectrode recording. It is expected that future advances in MR imaging technology will lead to improvements in direct targeting. The use of new MR imaging modalities such as diffusion MR imaging might even lead to the specific identification of the different functional parts of the STN, such as the dorsolateral sensorimotor part, the target for deep brain stimulation.     

German registry of paediatric deep brain stimulation in patients with childhood-onset dystonia (GEPESTIM)

Background

Data on paediatric deep brain stimulation (DBS) is limited, especially for long-term outcomes, because of small numbers in single center series and lack of systematic multi-center trials.

Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts

Background

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS.