BackgroundNeuroimaging studies help us better understand the pathophysiology and symptoms of Parkinson's disease (PD). In several of these studies, diffusion tensor imaging (DTI) was used to investigate structural changes in cerebral tissue. Although data have been provided as regards to specific brain areas, a whole brain meta-analysis is still missing.MethodsWe compiled 39 studies in this meta-analysis: 14 used fractional anisotropy (FA), 1 used mean diffusivity (MD), and 24 used both indicators. These studies comprised 1855 individuals, 1087 with PD and 768 healthy controls. Regions of interest were classified anatomically (subcortical structures; white matter; cortical areas; cerebellum). Our statistical analysis considered the disease effect size (DES) as the main variable; the heterogeneity index (I2) and Pearson's correlations between the DES and co-variables (demographic, clinical and MRI parameters) were also calculated.ResultsOur results showed that FA-DES and MD-DES were able to distinguish between patients and healthy controls. Significant differences, indicating degenerations, were observed within the substantia nigra, the corpus callosum, and the cingulate and temporal cortices. Moreover, some findings (particularly in the corticospinal tract) suggested opposite brain changes associated with PD. In addition, our results demonstrated that MD-DES was particularly sensitive to clinical and MRI parameters, such as the number of DTI directions and the echo time within white matter.ConclusionsDespite some limitations, DTI appears as a sensitive method to study PD pathophysiology and severity. The association of DTI with other MRI methods should also be considered and could benefit the study of brain degenerations in PD.

Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short-and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change.Methods: Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on-and off-medication with on-and offstimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year. Results:Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2% Ϯ 20.15% off-medication and 16.9% Ϯ 21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6% Ϯ 5.5% and 4.5% Ϯ 8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year. Conclusion:The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients. Classification of evidence:This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1 month, 6 months, and 1 year compared to baseline and to control subjects treated with best medical therapy. Neurology

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We investigated safety issues and potential experimental confounds when performing functional magnetic resonance imaging (fMRI) investigations in human subjects with fully implanted, active, deep brain stimulation (DBS) systems. Measurements of temperature and induced voltage were performed in an in vitro arrangement simulating bilateral DBS during magnetic resonance imaging (MRI) using head transmit coils in both 1.5 and 3.0T MRI systems. For MRI sequences typical of an fMRI study with coil-averaged specific absorption rates (SARs) less than 0.4 W/Kg, no MRI-induced temperature change greater than the measurement sensitivity (0.1ºC) was detected at 1.5T, and at 3T temperature elevations were less than 0.5ºC, i.e. within safe limits. For the purposes of demonstration, MRI pulse sequences with SARs of 1.45 W/Kg and 2.34 W/kg (at 1.5T and 3T respectively) were prescribed and elicited temperature increases (>1ºC) greater than those considered safe for human subjects. Temperature increases were independent of the presence or absence of active stimulator pulsing. At both field strengths during echo planar MRI the perturbations of DBS equipment performance were sufficiently slight, and temperature increases sufficiently low to suggest that thermal or electromagnetically mediated experimental confounds to fMRI with DBS are unlikely. We conclude that fMRI studies performed in subjects with subcutaneously implanted DBS units can be both safe and free from DBS-specific experimental confounds. Furthermore, fMRI in subjects with fully-implanted rather than externalised DBS stimulator units may offer a significant safety advantage. Further studies are required to determine the safety of MRI with DBS for other MRI systems, transmit-coil configurations and DBS arrangements.3

In Parkinson's disease, functional imaging studies during limb motor tasks reveal cerebral activation abnormalities that can be reversed by subthalamic nucleus (STN) stimulation. The effect of STN stimulation on parkinsonian dysarthria has not, however, been investigated using PET. The aim of the present study was to evaluate the effect of STN stimulation on regional cerebral blood flow (rCBF) during speech production and silent articulation in patients with Parkinson's disease. Ten Parkinson's disease patients surgically implanted bilaterally in the STN and with significant improvement of their dysarthria induced by STN stimulation were included. Ten healthy control subjects also participated in this study. Control subjects performed six sessions of [15O]H2O-PET scanning corresponding to three duplicated conditions externally cued by an auditory signal. The conditions were: (i) rest; (ii) production of a short, simple sentence; and (iii) silent articulation of the same sentence. Parkinson's disease patients carried out the six PET sessions twice, i.e., in the ON and OFF STN stimulation states. PET data analysis was performed using statistical parametric mapping (SPM99). In control subjects, speech production (SP) compared with rest was associated with increased rCBF bilaterally in the primary motor cortex (M1) corresponding to the orofacial somatotopy, the supplementary motor area (SMA), the associative auditory cortex and the cerebellar hemispheres. Silent articulation (SA) compared with rest induced a bilateral rCBF increase restricted to the orofacial M1 and cerebellar hemispheres. In Parkinson's disease patients in the OFF stimulation condition, during both SP and SA there was a lack of activation in the right orofacial M1 and in the cerebellum, abnormal increased rCBF in the right superior premotor cortex, and overactivation of the SMA. There was also an abnormal, increased rCBF in the dorsolateral prefrontal cortex (DLPFC) only during SP and increased rCBF in the left insula only during SA. In Parkinson's disease patients ON stimulation, for both SP and SA the activation pattern appeared similar to that in control subjects. In conclusion, our results suggest that parkinsonian dysarthria is associated with altered recruitment of the main motor cerebral regions (orofacial M1, cerebellum), and increased involvement of the premotor and prefrontal cortices (DLPFC, SMA, superior premotor cortex). These abnormal activations are different from those reported during hand motor tasks. They could be a compensatory mechanism, but might also arise directly as part of the pathophysiology of Parkinson's disease. STN stimulation tends to reverse these abnormal activations, which is consistent with the observed improvement of Parkinson's disease dysarthria.

Micrographia, an abnormal reduction in writing size, is a specific behavioral deficit associated with Parkinson's disease (PD). In recent years, the availability of graphic tablets has made it possible to study micrographia in unprecedented detail. Consequently, a growing number of studies show that PD patients also exhibit impaired handwriting kinematics. Is micrographia still the most characteristic feature of PD-related handwriting deficits? To answer this question, we identified studies that investigated handwriting in PD, either with conventional pencil-and-paper measures or with graphic tablets, and we reported their findings on key spatiotemporal and kinematic variables. We found that kinematic variables (velocity, fluency) differentiate better between control participants and PD patients, and between off- and on-treatment PD patients, than the traditional measure of static writing size. Although reduced writing size is an important feature of PD handwriting, the deficit is not restricted to micrographia stricto sensu. Therefore, we propose the term PD dysgraphia, which encompasses all deficits characteristic of Parkinsonian handwriting. We conclude that the computerized analysis of handwriting movements is a simple and useful tool that can contribute to both diagnosis and follow-up of PD.

Chronic treatment with low-frequency STN DBS may have a beneficial impact on dysarthropneumophonia, even in advanced PD patients.