Alberto Marzegan

A role for locus coeruleus in Parkinson tremor

We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease (PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [123I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor.

Gait initiation in children with Rett syndrome.

Rett syndrome is an X-linked neurodevelopmental condition mainly characterized by loss of spoken language and a regression of purposeful hand use, with the development of distinctive hand stereotypies, and gait abnormalities. Gait initiation is the transition from quiet stance to steady-state condition of walking. The associated motor program seems to be centrally mediated and includes preparatory adjustments prior to any apparent voluntary movement of the lower limbs. Anticipatory postural adjustments contribute to postural stability and to create the propulsive forces necessary to reach steady-state gait at a predefined velocity and may be indicative of the effectiveness of the feedforward control of gait. In this study, we examined anticipatory postural adjustments associated with gait initiation in eleven girls with Rett syndrome and ten healthy subjects. Muscle activity (tibialis anterior and soleus muscles), ground reaction forces and body kinematic were recorded. Children with Rett syndrome showed a distinctive impairment in temporal organization of all phases of the anticipatory postural adjustments. The lack of appropriate temporal scaling resulted in a diminished impulse to move forward, documented by an impairment in several parameters describing the efficiency of gait start: length and velocity of the first step, magnitude and orientation of centre of pressure-centre of mass vector at the instant of (swing-)toe off. These findings were related to an abnormal muscular activation pattern mainly characterized by a disruption of the synergistic activity of antagonistic pairs of postural muscles. This study showed that girls with Rett syndrome lack accurate tuning of feedforward control of gait.

Novel DYT11 gene mutation in patients without dopaminergic deficit (SWEDD) screened for dystonia

Objective: To test the hypothesis that adult-onset primary dystonia may be the underlying etiology of tremulous patients with clinical diagnosis of Parkinson disease (PD) but without evidence of dopaminergic deficit at nigrostriatal SPECT imaging. Methods: We retrospectively reviewed clinical and imaging data of patients with clinical diagnosis of PD assessed at our tertiary movement disorder clinic, who underwent dopamine transporter SPECT imaging consecutively between 2002 and 2011. Molecular screening for DYT1, DYT5, DYT6, DYT11, and DYT16 dystonia genes was performed in all cases who met the following criteria at the time of SPECT scan: (1) clinical diagnosis of PD; (2) normal dopamine transporter SPECT; (3) asymmetric rest tremor, with or without postural/kinetic component; (4) ≥12-month follow-up; and (5) normal brain MRI. We excluded subjects with (6) overt dystonic features, and (7) head or voice tremor. Results: Twenty-three subjects were eligible for molecular analysis. Positive family history for tremor or PD was present in 45% of probands. We found one patient with a novel heterozygous frameshift mutation in the DYT11 gene (c.1058-1062 delCACCA/p.Gln352fsX376). Electrophysiologic study of tremor revealed that the main contributor was 5- to 6-Hz pseudo-rhythmic myoclonus, primarily involving extensor muscles. In 2 brothers, we found a missense variant in the DYT5 gene (c.334A>G; p.Thr112Ala) of uncertain pathogenicity in humans. Conclusion: Our findings provide further support to the hypothesis that adult-onset monogenic dystonia may underlie a “PD look-alike” clinical phenotype. In addition to dystonic tremor, pseudo-rhythmic myoclonus may be mischaracterized as “rest tremor.”

Tridimensional kinematic analysis on a kayaking simulator: key factors to successful performance

BackgroundThe aim of this study was to identify the kinematic variables contributing to successful performance in kayaking using a kayak simulator and three-dimensional kinematic analysis. In addition, the presence of side-to-side asymmetries in selected linear and angular variables was investigated.MethodsFive élite, four intermediate and six novice paddlers participated in this study. The subjects performed on a paddling simulator near their race pace. Three-dimensional coordinates of 17 anatomical landmarks were acquired at 100 Hz on an automatic motion analyser equipped with seven video cameras.ResultsÉlite paddlers showed a significantly higher (absolute and relative to arm length) paddling amplitude than the other two groups, with no significant difference in anthropometric dimensions. In addition, they demonstrated a significantly lower level of asymmetry in some joint angles with respect to novice and intermediate paddlers. In contrast, less-experienced paddlers (novice and intermediate) showed more accentuated saddle and pelvis movements in the frontal plane.ConclusionSimilar to previously findings in other symmetrical cyclic sporting activities (cross-country skiing, running), élite paddlers showed higher movement amplitude than intermediate and novice kayakers. Muscle strength and technical skills developed during training may explain the differences found.

The Influence of Dopaminergic Striatal Innervation on Upper Limb Locomotor Synergies

To determine the role of striatal dopaminergic innervation on upper limb synergies during walking, we measured arm kinematics in 13 subjects with Parkinson disease. Patients were recruited according to several inclusion criteria to represent the best possible in vivo model of dopaminergic denervation. Of relevance, we included only subjects with normal spatio-temporal parameters of the stride and gait speed to avoid an impairment of upper limbs locomotor synergies as a consequence of gait impairment per se. Dopaminergic innervation of the striatum was measured by FP-CIT and SPECT. All patients showed a reduction of gait-associated arms movement. No linear correlation was found between arm ROM reduction and contralateral dopaminergic putaminal innervation loss. Still, a partition analysis revealed a 80% chance of reduced arm ROM when putaminal dopamine content loss was >47%. A significant correlation was described between the asymmetry indices of the swinging of the two arms and dopaminergic striatal innervation. When arm ROM was reduced, we found a positive correlation between upper-lower limb phase shift modulation (at different gait velocities) and striatal dopaminergic innervation. These findings are preliminary evidence that dopaminergic striatal tone plays a modulatory role in upper-limb locomotor synergies and upper-lower limb coupling while walking at different velocities.

Walking efficiency assessment through the analysis of mechanical energy and energy recovery index

The mechanical energy exchanges of normal subjects during walking have been investigated. Two groups of subjects including healthy children and healthy adults participated in this study. Kinematic data have been captured by a motion analysis system composed of 8 TV-cameras with an acquisition frequency of 50 Hz and retro-reflective markers positioned on main reference points of the body. Based on the estimation of mass and centre of mass of the main anatomical segments the kinetic and potential energy were computed. The total mechanical energy along a stride was compared to the kinetic and potential energy excursions as to obtain an index of energy recovery. Preliminary results show that significant differences exist between children and adults and walking efficiency is higher in adults.