Nonlinear interactions in the thalamocortical loop in essential tremor: A model-based frequency domain analysis.

There is increasing evidence to suggest that essential tremor has a central origin. Different structures appear to be part of the central tremorogenic network, including the motor cortex, the thalamus and the cerebellum. Some studies using electroencephalogram (EEG) and magnetoencephalography (MEG) show linear association in the tremor frequency between the motor cortex and the contralateral tremor electromyography (EMG). Additionally, high thalamomuscular coherence is found with the use of thalamic local field potential (LFP) recordings and tremulous EMG in patients undergoing surgery for deep brain stimulation (DBS). Despite a well-established reciprocal anatomical connection between the thalamus and cortex, the functional association between the two structures during "tremor-on" periods remains elusive. Thalamic (Vim) LFPs, ipsilateral scalp EEG from the sensorimotor cortex and contralateral tremor arm EMG recordings were obtained from two patients with essential tremor who had undergone successful surgery for DBS. Coherence analysis shows a strong linear association between thalamic LFPs and contralateral tremor EMG, but the relationship between the EEG and the thalamus is much less clear. These measurements were then analyzed by constructing a novel parametric nonlinear autoregressive with exogenous input (NARX) model. This new approach uncovered two distinct and not overlapping frequency "channels" of communication between Vim thalamus and the ipsilateral motor cortex, defining robustly "tremor-on" versus "tremor-off" states. The associated estimated nonlinear time lags also showed non-overlapping values between the two states, with longer corticothalamic lags (exceeding 50ms) in the tremor active state, suggesting involvement of an indirect multisynaptic loop. The results reveal the importance of the nonlinear interactions between cortical and subcortical areas in the central motor network of essential tremor. This work is important because it demonstrates for the first time that in essential tremor the functional interrelationships between the cortex and thalamus should not be sought exclusively within individual frequencies but more importantly between cross-frequency nonlinear interactions. Should our results be successfully reproduced on a bigger cohort of patients with essential tremor, our approach could be used to create an on-demand closed-loop DBS device, able to automatically activate when the tremor is on.

The Anatomy of the Medial Lemniscus within the Brainstem Demonstrated at 3 Tesla with High Resolution Fat Suppressed T1-Weighted Images and Diffusion Tensor Imaging.

The medial lemniscus is part of the main somatosensory pathways ascending within the brainstem. It is formed by the heavily myelinated axons of the second order neurones of the dorsal column nuclei. This pathway ascends through the rostral medulla, pons and mesencephalon to finally terminate by synapsing with third order neurones in the ventral posterior nucleus of the thalamus. The medial lemniscus conveys proprioception and fine tactile discrimination as part of the somatosensory system. Conventional MRI studies of the brainstem have been relatively poor in demonstrating these fibre pathways. Diffusion tensor imaging and tractography may demostrated fibre pathways in the brainstem. These techniques do however suffer from relatively poor spatial resolution and some degree of image distortion - especially if based on echo planar imaging techniques. Knowledge of the anatomical relationships of the medial lemniscus is important for the understanding of clinical manifestations of disease processes affecting the somatosensory pathways and also to demonstrate important adjacent structures. Specifically, the pedunculopontine nucleus (PPN) lies in close anatomical relationship to the medial lemniscus and the decussation of the superior cerebellar peduncle. This nucleus is a promising target for deep brain stimulator placement for alleviation of non-dopamine responsive dystonias. Six healthy male volunteers (mean age 33 years) were imaged at 3 Tesla. Imaging protocols consisted of thin section, high resolution, fat suppressed T1-weighted sequences as well as thin section, high isotropic resolution diffusion tensor imaging (DTI), which was analysed to generate colour fractional anisotropy (FA) maps. These were correlated with the fat suppressed T1 weighted images. In all volunteers the medial lemniscus was seen as a pair of bands of low signal on axial, high resolution, fat suppressed T1-weighted images. They were indentified through the upper medulla, pons and mesencephalon. They correlated well with the head to foot orientated fibres on the colour FA maps generated from the DTI data. This study of normal volunteers has illustrated the value of high resolution, fat suppressed T1-weighted images in demonstrating the anatomy of the heavily myelinated medial lemniscus within the brainstem. These high resolution images with good spatial accuracy can potentially be used to aid the localisation of other nuclei, such as the PPN.

Externalising deep brain electrodes: an increased risk of infection?

It is the practice in many centres to externalise deep brain electrodes in functional neurosurgery to confirm efficacy of therapy prior to full implantation of the pacemaker. It has been a concern that such practice might lead to an increased rate of infection. We report a retrospective study of the rates of infection in two major centres where all electrodes are externalised in one centre and directly implanted in the other. We have not found an increased rate of infection as a result of externalisation and feel, particularly in pain patients, that doing so can lead to significant cost savings by avoiding ineffective implantations.

Increased risk of lead fracture and migration in dystonia compared with other movement disorders following deep brain stimulation.

Deep brain stimulation (DBS) therapy is a continually expanding field in the functional neurosurgical treatment of movement disorders. However, the occurrence of adverse events related to implanted hardware cannot be overlooked. We report on a specific feature noted in our experience of DBS-related complications. From 1998 until present we have found an overall rate of 5.3% of DBS electrode lead dysfunction (out of 133 patients) in our series (slipped leads 2.3%, lead fracture 3.8%). Interestingly, all of these failures occurred in dystonia patients (18.4% of all dystonia patients and 9.2% of all electrodes). We postulate on mechanisms that may explain why these complications predominate in this group of patients.

Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation.

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.

Making PVC more biocompatible.

Poly(vinyl chloride) (PVC) is used extensively for disposable medical devices. However, it produces adverse reactions when in contact with body tissues and fluids, and can lead to thrombus formation. This article proposes coating material surfaces with synthetic phosphorylcholine-containing polymers to mimic the outer surface of the natural cell membrane. Experimental evidence is provided to support the use of this approach to enhancing the biocompatibility of PVC and other materials.