Pain-motor integration in the primary motor cortex in Parkinson's disease

In Parkinson's disease (PD), the influence of chronic pain on motor features has never been investigated. We have recently designed a technique that combines nociceptive system activation by laser stimuli and primary motor cortex (M1) activation through transcranial magnetic stimulation (TMS), in a laser-paired associative stimulation design (Laser-PAS). In controls, Laser-PAS induces long-term changes in motor evoked potentials reflecting M1 long-term potentiation-like plasticity, arising from pain-motor integration

Corticobasal syndrome: neuroimaging and neurophysiological advances

Corticobasal degeneration (CBD) is a neurodegenerative condition characterized by 4R-tau protein deposition in several brain regions that clinically manifests itself as a heterogeneous atypical parkinsonism typically expressing in the adulthood. The prototypical clinical phenotype of CBD is corticobasal syndrome (CBS). Important insights into the pathophysiological mechanisms underlying motor and higher cortical symptoms in CBS have been gained by using advanced neuroimaging and neurophysiological techniques. Structural and functional neuroimaging studies often showed asymmetric cortical and subcortical abnormalities, mainly involving perirolandic and parietal regions and basal ganglia structures. Neurophysiological investigations including electroencephalography and somatosensory evoked potentials provided useful information on the origin of myoclonus and on cortical sensory loss. Transcranial magnetic stimulation demonstrated heterogeneous and asymmetric changes in the excitability and plasticity of primary motor cortex and abnormal hemispheric connectivity. Neuroimaging and neurophysiological abnormalities in multiple brain areas reflect the asymmetric neurodegeneration, leading to the asymmetric motor and higher cortical symptoms in CBS. This article is protected by copyright. All rights reserved

Red blood cells membrane micropolarity as a novel diagnostic indicator of type 1 and type 2 diabetes

Classification of the category of diabetes is extremely important for clinicians to diagnose and select the correct treatment plan. Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins, as well as impairment in cholesterol homeostasis, can alter lipid density, packing, and interactions of Red blood cells (RBC) plasma membranes in type 1 and type 2 diabetes, thus varying their membrane micropolarity. This can be estimated, at a submicrometric scale, by determining the membrane relative permittivity, which is the factor by which the electric field between the charges is decreased relative to vacuum. Here, we employed a membrane micropolarity sensitive probe to monitor variations in red blood cells of healthy subjects (n=16) and patients affected by type 1 (T1DM, n=10) and type 2 diabetes mellitus (T2DM, n=24) to provide a cost-effective and supplementary indicator for diabetes classification. We find a less polar membrane microenvironment in T2DM patients, and a more polar membrane microenvironment in T1DM patients compared to control healthy patients. The differences in micropolarity are statistically significant among the three groups (p<0.01). The role of serum cholesterol pool in determining these differences was investigated, and other factors potentially altering the response of the probe were considered in view of developing a clinical assay based on RBC membrane micropolarity. These preliminary data pave the way for the development of an innovative assay which could become a tool for diagnosis and progression monitoring of type 1 and type 2 diabetes. Keywords: Diabetes mellitus, Membrane micropolarity, Red blood cells, Fluorescence lifetime microscopy, Metabolic imaging, Personalized medicin

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. © Springer-Verlag 2010

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. (C) 2010 Movement Disorder Societ

Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease

Background Animal models of Parkinson's Disease (PD) demonstrated increased facilitatory cortico-striatal activity, reflecting overactive glutamatergic neurotransmission and contributing to the pathophysiology of l-dopa induced dyskinesias (LIDs). Objective To assess different facilitatory intracortical circuits in the primary motor cortex (M1) in patients with PD and LIDs by means of a combination of transcranial magnetic stimulation (TMS) protocols. Methods We tested the Input/Output (I/O) curve, intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) at baseline (T0), ‘OFF’ and ‘ON’ state, in 20 PD patients with LIDs. The same parameters were examined after 2 weeks of chronic intake of 50 mg (T1) and 100 mg/day (T2) of safinamide. Finally, we tested SICF in a further group of patients without LIDs. Results At T0, patients with LIDs showed increased I/O curve steepness, which was partly ameliorated by l-dopa. These patients also had normal ICF, and abnormally increased SICF, which did not change with l-dopa. Safinamide improved the I/O curve both at T1 and T2, it reduced SICF at T1 and normalized this measure at T2. In patients with PD and LIDs, SICF correlated with the severity of dyskinesia. In patients without LIDs, SICF was less prominently abnormal and responsive to l-dopa. Conclusions Patients with PD and LIDs have abnormal cortical facilitation, possibly suggesting overactive glutamatergic neurotransmission in specific circuits within M1. Although not responsive to l-dopa, this dysfunction is restored by the anti-glutamatergic properties of safinamide 100 mg. The results suggest that the abnormal cortical facilitation in M1 contributes to the pathophysiology of LIDs

Motor training reduces surround inhibition in the motor cortex

OBJECTIVE: Surround inhibition (SI) is thought to facilitate focal contraction of a hand muscle by keeping nearby muscles silent. Unexpectedly, SI is reduced in skilled pianists. We tested whether repeated practice of focal contraction in non-pianists could reduce SI. METHODS: Motor-evoked potentials were elicited by transcranial magnetic stimulation in the relaxed abductor digiti minimi randomly at the onset and 5s after offset of a 2s focal contraction (10% maximum) of the first dorsal interosseous (FDI). Over 5 blocks of 40 trials participants obtained points for increasing contraction speed and stability in FDI. In a final block, the interval between contractions was varied randomly to increase attention to the task. RESULTS: Over the first 5 blocks, SI declined as performance (points scored) improved. In the final "attention" block SI increased towards baseline without affecting performance. CONCLUSIONS: Although SI may be useful during the early stages of learning, skilled focal finger movement does not require SI to prevent activity in non-involved muscles. This could be due to better targeting of the excitatory command to move. Results from the final block suggest that increased attention can re-engage SI when task parameters change. SIGNIFICANCE: SI is not necessary for successful focal contraction, but may contribute during learning and during attention to task