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In Parkinson's disease (PD), respiratory insufficiency (including functional and muscle disorders) can impact dysarthria and swallowing. Most studies of this topic have been performed retrospectively in populations of patients with advanced PD. The objective of the present study was to characterize lung function (under off-drug conditions) in early-stage PD patients at baseline and then again two years later. Forty-one early-stage PD patients (mean ± SD age: 61.7 ± 7.7; mean ± SD disease duration: 1.9 ± 1.7 years) were prospectively enrolled and compared with 36 age-matched healthy controls. Neurological evaluations and pulmonary function testing were performed in the off-drug condition at the inclusion visit and then two years later. Pulmonary function testing did not reveal any restrictive or obstructive disorders; at baseline, inspiratory muscle weakness was the only abnormality observed in the PD group (in 53.7% of the patients, vs. 25% in controls; p = 0.0105). The PD patients had a lower mean maximal inspiratory mouth pressure than controls and a lower sniff nasal inspiratory pressure. Two years after the initiation of chronic treatment with antiparkinsonian medications, the maximal inspiratory mouth pressure and the sniff nasal inspiratory pressure tended to be higher. Lastly, overall motor outcomes were not significantly worse in patients with inspiratory muscle weakness than in patients without inspiratory muscle weakness. Inspiratory muscle weakness seems to be common in patients with early-stage PD, and was seen to be stable over a two-year period. Additional long-term follow-up studies are required to specify the impact of this new feature of PD.

IntroductionThe col-cap concept encouraged neurologists to inject a large group of muscles in the treatment of cervical dystonia. This includes deep muscles such as the obliquus capitis inferior or the semispinalis capitis, and muscles close to vascular or neurological structures such as scalene muscles. Our aim was to determine the accuracy of injections in cervical muscles using ultrasonography (US) or palpation of anatomical landmarks.MethodsA mix of paint, gelatin and iodized contrast agent was injected in nine pairs of cervical muscles of human cadavers, according to two injection techniques: US-guided and non-guided. The dye was localized on 1 cm-thick, frozen slices.ResultsA total of 102 muscles was injected in the US-guided group (n = 8). The global accuracy was 88.2%. The lowest accuracy was in the OCI (41.7%); trying to avoid the vertebral artery, injections were too medial. A total of 54 muscles was injected in the non-guided group (n = 3). The global accuracy was 48.0%; moreover, some dye was found in four blood vessels. The embalming process produced texture changes, making difficult the palpation of bony landmarks.ConclusionsOur results indicate that US-guided injections are more accurate than non-guided injections in most cervical muscles.

There is a growing need for surrogate biomarkers for Parkinson’s disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first- and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap.

We tested Parkinson’s disease (PD)-related impairments in the relationship between gaze shifts, body sway and mental workload while performing visual tasks in the standing position. Nineteen on-drug PD patients (Hoehn and Yahr I-II; MDS-UPDRS score part III: 23.37 ± 2.79) and twenty age-matched controls explored large images (visual angle: 100°) and performed a search task (location of targets within images) as well as a free-viewing (control) task. To collect kinematic data, all participants wore body markers (lower back, upper back and head) and an eye tracker. PD patients showed a higher amplitude in gaze shifts and body sway than age-matched controls. The adaptation of gaze shift and body sway velocity from free-viewing to searching was smaller in PD patients. The mental workload (NASA-TLX score) was a significant covariate in all participants. Furthermore, the MDS-UPDRS score was a significant covariate in the shared variance between body (lower back, upper back and head) and eye movement, thus showing a relation between this clinical variable and impairment at the behavioral level. Our results indicate impaired behavioral synergic, i.e. complementary, control between vision, posture and mental workload in PD patients. With a view to restoring synergic functional control, rehabilitation programs should train the three systems together simultaneously.

Parkinson's disease patients with freezing of gait also experience sudden motor blocks (freezing) during other repetitive motor tasks. We assessed the proportion of patients with advanced PD and freezing of gait who also displayed segmental \"freezing\" in tapping tasks. Fifteen Parkinson's disease patients with freezing of gait were assessed. Freezing of gait was evaluated using a standardized gait trajectory with the usual triggers. Patients performed repetitive tapping movements (as described in the MDS-UPDRS task) with the hands or the feet in the presence or absence of a metronome set to 4 Hz. Movements were recorded with a video motion system. The primary endpoint was the occurrence of segmental freezing in these tapping tasks. The secondary endpoints were (i) the relationship between segmental episodic phenomena and FoG severity, and (ii) the reliability of the measurements. For the upper limbs, freezing was observed more frequently with a metronome (21% of trials) than without a metronome (5%). For the lower limbs, the incidence of freezing was higher than for the upper limbs, and was again observed more frequently in the presence of an auditory cue (47%) than in its absence (14%). Although freezing of the lower limbs was easily assessed during an MDS-UPDRS task with a metronome, it was not correlated with the severity of freezing of gait (as evaluated during a standardized gait trajectory). Only this latter was a reliable measurement in patients with advanced Parkinson's disease.

Motor programme for gait initiation can vary as a function of attentional resources. The objective of the present study was to determine whether alertness, orientation and executive control can modulate cortical activation during step initiation. The attention network test (ANT) was used to control the influence of different attentional components on kinetic characteristics of step initiation and the associated cortical activity. Thirty healthy adults performed ANT combined with step initiation. The step execution time (SET) and anticipatory postural adjustments (APAs) were recorded. Movement-related cortical potentials (MRCPs) and event-related spectral perturbations (ERSPs) after response emission were analysed according to the presence or absence of cueing or conflict resolution. Step reaction time and thus SET were significantly shorter with cueing, whereas APA duration and SET were longer during conflict resolution. Moreover, alertness was related to a higher rate of anticipated responses, and conflicting situations were associated with a greater amount of multiple APAs. Attentional load did not affect MRCPs but ERSPs: trials with a cue showed earlier posterior alpha and beta desynchronisations before APA onset. Furthermore, we found earlier, more pronounced and longer alpha- and beta-band desynchronisations over the sensorimotor cortex for trials with incongruent flankers. Our results showed that attention has an impact on step initiation. A specific pattern of response-locked ERSPs seems to mirror behavioural effects of attentional load on step initiation. This new paradigm combining ANT and step initiation is, therefore, promising to investigate the interaction between attention and gait initiation in pathological populations.

For couples facing Parkinson's disease, marital relationships are significantly impacted, even at the early stages of the disease. However, very few studies have explicitly explored the functioning of the couple and how both partners deal with Parkinson's disease. The aim of this study was to explore the experiences and strategies of couples facing Parkinson's disease in the early stage using dyadic interpretative phenomenological analysis. Fifteen couples agreed to participate in the study. Semistructured interviews were conducted with each partner separately regarding his or her individual experience with Parkinson's disease, the couple's history, the impact of the diagnosis on the functioning of the couple, and his or her projections for the future. Three higher-order themes emerged from the analyses. The first theme, \"Being tested by the diagnosis\", highlights 4 dyadic configurations according to the individual's and the couple's capacity for adjustment following the diagnosis: \"noncongruent\", \"collapsed\", \"relieved\" and \"avoidant\". The second theme, \"Talking about everything except the disease\", underlines that communication about the disease is often avoided both within the couple and with relatives to protect the persons with Parkinson's disease or respect their wishes. The third theme, \"Supporting each other\", describes the different levels of harmony between the two partners in the management of daily life and symptoms and their relational impacts. These results allow us to better understand the experiences of both partners and to highlight the importance of promoting better acceptance of the diagnosis by persons with Parkinson's disease to allow better communication between partners and with relatives. Such support prevents disease-specific distress and facilitates better adjustment in the later stages of the disease.

Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson's disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD. Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients. The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages. Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease.

Psychiatric symptoms are common in neurodevelopmental movement disorders, including some types of dystonia. However, research has mainly focused on motor manifestations and underlying circuits. Myoclonus-dystonia is a rare and homogeneous neurodevelopmental condition serving as an illustrative paradigm of childhood-onset dystonias, associated with psychiatric symptoms. Here, we assessed the prevalence of psychiatric disorders and the severity of depressive symptoms in patients with myoclonus-dystonia and healthy volunteers (HV). Using resting-state functional neuroimaging, we compared the effective connectivity within and among non-motor and motor brain networks between patients and HV. We further explored the hierarchical organization of these networks and examined the relationship between their connectivity and the depressive symptoms. Comparing 19 patients to 25 HV, we found a higher prevalence of anxiety disorders and more depressive symptoms in the patient group. Patients exhibited abnormal modulation of the cerebellum on the cerebral cortex in the sensorimotor, dorsal attention, salience, and default mode networks. Moreover, the salience network activity was directed by the cerebellum in patients and was related to depressive symptoms. Altogether, our findings highlight the role of the cerebellar drive on both motor and non-motor cortical areas in this disorder, suggesting cerebellar involvement in the complex phenotype of such neurodevelopmental movement disorders.

With disease progression, patients with Parkinson’s disease (PD) may have chronic visual hallucinations (VH). The mechanisms behind this invalidating non-motor symptom remain largely unknown, namely because it is extremely difficult to capture hallucination events. This study aimed to describe the patterns of brain functional changes when VH occur in PD patients. Nine PD patients were enrolled because of their frequent and chronic VH (> 10/day). Patients with severe cognitive decline (MMSE<18) were excluded. Patients were scanned during ON/OFF hallucinatory states and resting-state functional imaging (rs-fMRI) was performed. Data were analyzed in reference to the two-step method, which consists in: (i) a data-driven analysis of per-hallucinatory fMRI data, and (ii) selection of the components of interest based on a post-fMRI interview. The phenomenology of VH ranged from visual spots to distorting faces. First, at the individual level, several VH-related components of interest were identified and integrated in a second-level analysis. Using a random-effects self-organizing-group ICA, we evidenced increased connectivity in visual networks concomitant to VH, encompassing V2, V3 and the fusiform gyri bilaterally. Interestingly, the stability of the default-mode network (DMN) was found positively correlated with VH severity (Spearman’s rho = 0.77, p = 0.05). By using a method that does not need online self-report, we showed that VH in PD patients were associated with functional changes in associative visual cortices, possibly linked with strengthened stability of resting-state networks.