Flavio Di Stasio

Validation of the Italian version of the Movement Disorder Society--Unified Parkinson's Disease Rating Scale.

The Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an ‘Official MDS translation,’ the Comparative Fit Index (CFI) had to be ≥0.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was ≥0.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages.

Somatosensory temporal discrimination tested in patients receiving botulinum toxin injection for cervical dystonia.

We designed this study to find out more about the relationship between the sensory effects of Botulinum toxin type A (BTX) and the clinical benefits of BTX therapy in patients with cervical dystonia (CD). In 24 patients with CD, we tested sensory temporal discrimination (STD) in the affected and two unaffected body regions (neck, hand, and eye) before and 1 month after BTX injection. In 8 out of the 24 patients with CD, STDT values were tested bilaterally in the three body regions before, 1 and 2 months after BTX injection. As expected, STD testing disclosed altered STD threshold values in all three body regions tested (affected and unaffected by dystonic spasms) in patients with CD. STD threshold values remained unchanged at all time points of the follow‐up in all CD patients. The lack of BTX‐induced effects on STD thresholds suggests that STD recruits neural structures uninvolved in muscle spindle afferent activation.

Neurophysiological correlates of abnormal somatosensory temporal discrimination in dystonia

Somatosensory temporal discrimination threshold is often prolonged in patients with dystonia. Previous evidence suggested that this might be caused by impaired somatosensory processing in the time domain. Here, we tested if other markers of reduced inhibition in the somatosensory system might also contribute to abnormal somatosensory temporal discrimination in dystonia.

Cortical and brainstem plasticity in Tourette syndrome and obsessive-compulsive disorder.

Gilles de la Tourette syndrome is characterized by motor/vocal tics commonly associated with psychiatric disorders, including obsessive‐compulsive disorder. We investigated primary motor cortex and brainstem plasticity in Tourette patients, exposed and unexposed to chronic drug treatment, with and without psychiatric disturbances. We also investigated primary motor cortex and brainstem plasticity in obsessive‐compulsive disorder. We studied 20 Tourette patients with and without psychiatric disturbances, 15 with obsessive‐compulsive disorder, and 20 healthy subjects. All groups included drug‐naïve patients. We conditioned the left primary motor cortex with intermittent/continuous theta‐burst stimulation and recorded motor evoked potentials. We conditioned the supraorbital nerve with facilitatory/inhibitory high‐frequency stimulation and recorded the blink reflex late response area. In healthy subjects, intermittent theta‐burst increased and continuous theta‐burst stimulation decreased motor evoked potentials. Differently, intermittent theta‐burst failed to increase and continuous theta‐burst stimulation failed to decrease motor evoked potentials in Tourette patients, with and without psychiatric disturbances. In obsessive‐compulsive disorder, intermittent/continuous theta‐burst stimulation elicited normal responses. In healthy subjects and in subjects with obsessive‐compulsive disorder, the blink reflex late response area increased after facilitatory high‐frequency and decreased after inhibitory high‐frequency stimulation. Conversely, in Tourette patients, with and without psychiatric disturbances, facilitatory/inhibitory high‐frequency stimulation left the blink reflex late response area unchanged. Theta‐burst and high‐frequency stimulation elicited similar responses in drug‐naïve and chronically treated patients. Tourette patients have reduced plasticity regardless of psychiatric disturbances. These findings suggest that abnormal plasticity contributes to the pathophysiology of Gilles de la Tourette syndrome. However, obsessive‐compulsive disorder patients have normal cortical and brainstem plasticity.

Gray and white matter structural changes in corticobasal syndrome

We investigated gray matter and white matter (WM) changes in corticobasal syndrome (CBS). T1-weighted and diffusion tensor images (3T-magnet) were obtained in 11 patients and 11 healthy subjects (HS). Magnetic resonance imaging data were analyzed using FreeSurfer and Tracts Constrained by Underlying Anatomy to evaluate cortical thickness (CTh), surface area, and subcortical volumes as well as diffusion tensor image parameters along the major WM tracts. Compared with HS, the whole patient group showed decreased CTh in the prefrontal cortex, precentral gyrus, supplementary motor area, insula, and temporal pole bilaterally. When we divided patients into 2 subgroups (left: L-CBS, right: R-CBS) on the basis of the clinically more affected upper limb, the most prominent decrease in CTh occurred in the hemisphere contralateral to the more affected side. The whole patient group also had volume loss in the putamen, hippocampus, and accumbens bilaterally, in the corpus callosum and right amygdala. Finally, we found diffusion changes in several WM tracts with axial diffusivity being altered more than radial diffusivity. The upper limb motor severity negatively correlated with the contralateral CTh in the precentral and/or postcentral gyri and contralateral volumes of putamen and accumbens. The CTh asymmetry in postcentral and/or paracentral gyri also negatively correlated with disease duration. Cortical thinning, volume loss, and fiber tract degeneration in specific brain regions are important pathophysiological abnormalities in CBS.

MRI gray and white matter measures in progressive supranuclear palsy and corticobasal syndrome

We evaluated MRI measures of gray and white matter damages in 19 patients with progressive supranuclear palsy (PSP), 11 with corticobasal syndrome (CBS), and 14 healthy subjects (HS) to differentiate patients with PSP from those with CBS. We calculated surface-based maps of the cortical volume, cortical thickness, surface area, and voxel level maps of sub-cortical volume, and diffusion tensor imaging parameters using automated scripts implemented in FreeSurfer and FSL toolboxes. No significant differences in cortical volume loss were observed between PSP and CBS. When cortical volume was divided into cortical thickness and surface area, cortical thickness in peri-rolandic brain regions was significantly smaller in CBS than in PSP patients, whereas surface area was significantly smaller in PSP than HS. We also found widespread volume loss in sub-cortical structures in patients with PSP and CBS in comparison to HS. Both patient groups displayed diffusion tensor imaging abnormalities: compared to HS, widespread fractional anisotropy and radial diffusivity changes were observed in PSP, whereas axial and radial diffusivity changes were prominent in CBS. Mini-mental state examination positively correlated with diffusion changes in patients with PSP. In conclusion, cortical thickness, surface area, and diffusion tensor imaging parameters may be sensitive enough to help differentiate patients with PSP from those with CBS.

Effect of camptocormia on lung volumes in Parkinson's disease

Camptocormia is defined as an abnormal flexion of the thoracolumbar spine of 45°, or more, that typically increases during walking or standing and completely disappears in the supine position. Camptocormia may occur in patients with Parkinsons disease; when it does, it is usually associated with greater disease severity. Respiratory complications, which may be secondary to abnormal chest function, are one of the most frequent causes of death in patients with Parkinsons disease. No data on lung volumes are available for Parkinsons disease patients with camptocormia. The aim of this study was to evaluate the effect of camptocormia on lung function. Eleven patients with Parkinsons disease and camptocormia and ten age-matched healthy subjects underwent lung spirometry (in the standing position, inclining the trunk forward at approx. 45° and supine) measurement of arterial oxygen-hemoglobin saturation and heart rate. We found that Parkinsons disease with camptocormia is not associated with major clinical changes in lung volumes.

Functional disconnection of thalamic and cerebellar dentate nucleus networks in progressive supranuclear palsy and corticobasal syndrome

AIM To assess functional rearrangement following neurodegeneration in the thalamus and dentate nucleus in patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). METHODS We recruited 19 patients with PSP, 11 with CBS and 14 healthy subjects. All the subjects underwent resting-state (rs) fMRI using a 3T system. Whole brain functional connectivity of the thalamus and dentate nucleus were calculated by means of a seed-based approach with FEAT script in FSL toolbox. Thalamic volume was calculated by means of FIRST, and the dentate area by means of Jim software. RESULTS Both thalamic volume and dentate area were significantly smaller in PSP and CBS patients than in healthy subjects. No significant difference emerged in thalamic volume between PSP and CBS patients, whereas dentate area was significantly smaller in PSP than in CBS. Thalamic functional connectivity was significantly reduced in both patient groups in various cortical, subcortical and cerebellar areas. By contrast, changes in dentate nucleus functional connectivity differed in PSP and CBS: it decreased in subcortical and prefrontal cortical areas in PSP, but increased asymmetrically in the frontal cortex in CBS. CONCLUSIONS Evaluating the dentate nucleus size and its functional connectivity may help to differentiate patients with PSP from those with CBS.

Soluble and controlled-release preparations of levodopa: do we really need them?

The controlled-release preparations of levodopa or newer soluble preparations of levodopa may improve levodopa bioavailability and tolerability and help managing (or even preventing) motor complications. Whether the controlled-release preparations or soluble preparations can really take the place of standard levodopa remains highly controversial, especially in patients receiving chronic levodopa therapy. Controlled-release formulations have a longer half-life and provide more stable plasma levels than standard levodopa. In de novo parkinsonian patients, controlled-release levodopa and standard levodopa are equally efficacious, and carry similar motor complication rates. In patients with advanced disease, whether motor fluctuations respond better to controlled release than to standard oral levodopa remains unclear. In selected parkinsonian patients, single bedtime doses of controlled-release levodopa may improve sleep and nocturnal disability. The poor solubility of levodopa may be overcome by soluble formulations that achieve maximal absorption. A levodopa formulation that guarantees faster and more reliable absorption would be especially useful in the clinical treatment of Parkinson’s disease patients experiencing “no-on” or “delayed-on” phenomena. However, further studies with these new formulations are needed to understand if they offer better benefit to parkinsonian patients. New dual formulations incorporating both a faster absorption and an increased half-life than standard levodopa are currently under study.

Neurophysiological studies on atypical parkinsonian syndromes

There have been a relatively large number of experimental investigations using neurophysiological techniques in patients with atypical parkinsonian syndromes (APs), including progressive supranuclear palsy, cortico-basal syndrome and multiple system atrophy. Earlier studies focused on the startle, blink and trigemino-cervical reflexes and showed several brainstem abnormalities. Studies using transcranial magnetic stimulation have revealed a number of abnormalities in primary motor cortex and inter-hemispheric connectivity. More recent studies have highlighted the role of cerebellar dysfunction and have reported altered movement kinematics. Neurophysiological abnormalities in APs reflect degeneration or functional changes at multiple brain levels. In the majority of cases, APs share common abnormalities even though some neurophysiological changes differ among the various APs. Evidence of a correlation between neurophysiological abnormalities and clinical signs and symptoms in APs is limited. This paper provides an update on the results of experimental investigations using neurophysiological techniques in APs and also reviews similarities and differences between APs and Parkinsons disease. The potential role of neurophysiological abnormalities in the clinical context of APs is also discussed.