Descriptive analysis of the French NS-Park registry: Towards a nation-wide Parkinson's disease cohort?

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's. The French clinical research network for PD (NS-Park) has created a national patient registry to i)report medical activity of Parkinson Expert Centers (PECs) to the Ministry of Health, ii)facilitate PD patients pre-screening for clinical trials, iii) provide a source for pharmaco-epidemiology studies. OBJECTIVE: Assess the French Parkinsonian population at a nation-wide level and discover new clinical characteristics. METHODS: In this feasibility study, PECs prospectively collected clinical data in a standardized manner. The population main clinical characteristics are described, focusing on motor and non-motor symptoms and treatments, assessing its representativeness. By using an unbiased clustering with multiple correspondence analysis (MCA), we also investigate potential relationships between multiple variables like symptoms and treatments, as clues for future studies. RESULTS: Between 2012 and 2016, among 11,157 included parkinsonian syndromes, 9454 (85%) had PD. MCA identified various profiles depending on disease duration. Occurrences of motor complications, axial signs, cognitive disorders and Levodopa use increase over time. Neurovegetative symptoms, psychiatric disorders, sleep disturbances and impulse control disorders (ICDs) seem stable over time. As expected, ICDs were associated to dopaminergic agonist use but other associations, such as ICDs and sleep disturbances for instance, or anxiety and depression, were found. CONCLUSIONS: Our results report one of the biggest PD registries ever reported and demonstrate the feasibility of implementing a nation-wide registry of PD patients in France, a potent tool for future longitudinal studies and clinical trials' population selection, and for pharmaco-epidemiology and cost-effectiveness studies.

Early onset Parkinsonism associated with an intronic SOD1 mutation.

We report on a patient belonging to a large family with autosomal-dominant amyotrophic lateral sclerosis, who developed asymmetrical akineto-rigid symptoms at 33 years of age. He had no signs of lower motor neuron disease after four years of follow-up. All seven ALS patients from this family harboured a mutation located in the fourth intron of the SOD1 gene. The proband also harboured the same mutation, associated with a 40% decrease in SOD1 erythrocyte activity. This case report suggests that SOD1 mutations might be associated with marked phenotypic variability (ALS or early onset Parkinsonism in this family).

Gait and balance disorders in Parkinson's disease: impaired active braking of the fall of centre of gravity.

Gait and balance disorders are common in Parkinson's disease (PD), but its pathophysiology is still poorly understood. Step length, antero-posterior, and vertical velocities of the center of gravity (CG) during gait initiation were analyzed in 32 controls and 32 PD patients, with and without levodopa, using a force platform. Brain volumes and mesencephalic surface area were measured in PD patients. During the swing limb period, controls showed a fall in the CG, which was reversed before foot-contact indicating active braking of the CG fall. In PD patients, without levodopa, step length and velocity were significantly reduced and no braking occurred before foot-contact in 22 patients. With levodopa, step length and velocity increased in all patients and 7 patients improved their braking capacity. PD patients with normal braking (n = 17) had significantly lower gait and balance disorder scores and higher normalized-mesencephalic surface areas compared to patients with impaired braking (n = 15). The decreased step length and velocity, characteristic of PD, mainly result from degeneration of central dopaminergic systems. The markedly decreased braking capacity observed in half the PD patients contributes to their gait disorders and postural instability, perhaps as a result of nondopaminergic lesions, possibly at the mesencephalic level.

Use of the Visual Object and Space Perception (VOSP) test battery in two cases of posterior cortical atrophy.

Two patients presenting with predominantly dorsal posterior cortical atrophy were evaluated using the Visual Object and Space Perception (VOSP) test. The objective was to determine whether the VOSP was useful to discriminate damage to the ventral and the dorsal visual pathways. Both patients failed almost all the VOSP subtests, and the battery did not permit confirmation of the integrity of the ventral pathway. In addition, certain subtests evaluating dorsal function were nearly completed, probably due to a compensation strategy. Thus, evaluation using VOSP does not discriminate between predominantly ventral and predominantly dorsal clinical forms of posterior cortical atrophy.

Control of vertical components of gait during initiation of walking in normal adults and patients with progressive supranuclear palsy.

Gait and balance disorders are common in patients with parkinsonian syndromes, but the pathophysiology of these symptoms is still poorly understood. This study examined the initiation of gait in patients with progressive supranuclear palsy (PSP, n=10), characterized by the presence of severe postural instability, and controls (n=43). We used a force plate to measure the step length, and the antero-posterior and vertical velocities of the centre of gravity (CG) during gait initiation, in natural and fast gait conditions. In controls, during the swing limb period, there was a fall in the CG, which was reversed before foot contact. When controls were asked to walk faster, the fall in the CG increased but the ability to brake the fall in CG was unchanged. In PSP patients, length and maximal velocity of the first step were reduced compared to controls and no anticipatory braking in the CG fall occurred prior to the foot-contact, especially in the fast gait condition. The results suggest that normal subjects actively brake the fall in the CG prior to foot-contact. How this phenomenon participates in balance control is unknown. We hypothesize that the absence of active braking of the fall in the CG prior to foot-contact, observed in PSP patients, could contribute to the postural instability, characteristic of this disorder.

Subthalamic stimulation in Parkinson disease: behavior and social adaptation.

BACKGROUND: Bilateral subthalamic high-frequency stimulation significantly improves motor functions in patients with advanced forms of Parkinson disease (PD). This favorable effect contrasts with a growing number of reports that the treatment may result in psychiatric complications. OBJECTIVE: To analyze the presence of behavioral disorders and social maladjustment in PD patients successfully treated with continuous bilateral subthalamic stimulation. DESIGN: Prospective study. SETTING: University hospital. METHODS: Twenty PD patients underwent prospective evaluation for behavioral and personality changes, quality of life, and social functioning, 6 and 24 months after surgery to implant bilateral stimulating electrodes within the subthalamic nucleus. RESULTS: At 6 and 24 months after surgery, parkinsonian motor disability (on-stimulation/off-medication) was improved by 81% and 67%, respectively, and the severity of levodopa-related motor complications was improved by 84% and 70%, respectively. Levodopa-equivalent dosage was decreased by 79% and 66%, respectively; severity of depression was improved by 21% and 33%, respectively; and severity of anxiety was improved by 43% and 64%, respectively. The patients' personality traits were unmodified. Twenty-four months after surgery, the global score for quality of life was improved by 28%, whereas scores for social adjustment remained stable. CONCLUSIONS: Provided that patients with PD are rigorously selected for neurosurgery, subthalamic stimulation (1) improves mood, anxiety, and quality of life; (2) does not result in severe permanent psychiatric disorders or modify patients' personality; and (3) does not ameliorate social adaptation.

Spirometer-dependence of vital capacity in ALS: validation of a portable device in 52 patients.

Since the evaluation of vital capacity (VC) needs to be carried out every three months in patients with amyotrophic lateral sclerosis (ALS), a portable spirometer would be of value in clinical practice. Over the follow-up of 52 ALS patients, we compared the values of slow vital capacity measured by two spirometers: a reference flow-metered spirometer based on a Hans-Rudolph pneumotachograph and a portable Venturi spirometer. The objectives were to analyse the overall concordance of the measurements from the two devices and determine a discordance cut-off. The correlation between measurements was high (r = 0.936) and significant (p<10(-20)). Bland and Altman analysis showed that the measurements were concordant at a statistical risk of 5%; nevertheless, on examination of the raw differences between the measurements, two sub-populations could be identified on either side of the 56% cut-off where the means of the differences were significantly different (p<0.0001). The 56% cut-off was also statistically significant in plotting differences against the coefficient of variations of the data pairs expressed as (100 x s/mean). The differences observed between the two spirometers could be explained by technical differences between the devices as well as by an increase in variability with progression of the disease. In conclusion, this study demonstrates that a portable spirometer can be used reliably at the bedside. For values of vital capacity below the discordance cut-off of 56%, vital capacity should be determined by operators trained in pulmonary function examinations.

Hypermetabolism in ALS: correlations with clinical and paraclinical parameters.

Despite a reduction in fat-free mass (FFM), a hypermetabolism has been reported with an average of 10% in amyotrophic lateral sclerosis (ALS) patients as compared with a healthy population. The objectives of this study were to confirm the level of hypermetabolism determined by using indirect calorimetry in 168 patients with a probable or a definite ALS and to study correlations with survival. Consecutive evaluations of resting energy expenditure (REE) were performed from diagnosis to the proximity of death in 44 ALS patients. Differences with the calculated value determined a DeltaREE. FFM was given by bioimpedance. At T(1), REE was significantly increased by an average of 14% as compared with the calculated value. 62.3% of ALS patients were considered as hypermetabolic. REE was correlated in univariate analysis with age, sex, clinical form at onset, presence of a denutrition, weight, FFM, phase angle and ALS Functional Rating Scale (ALSFRS). In multivariate analysis, REE was linked to age and FFM. DeltaREE was correlated in univariate analysis with sex, phase angle and manual muscle testing (MMT). In multivariate analysis, age and sex remained significantly correlated. During progression of ALS, REE levels remained higher than calculated values with a trend to decrease at proximity of death, whereas FFM remained stable. From T(1), survival was linked to MMT, ALSFRS, vital capacity, REE and phase angle. We confirmed the existence of a stable hypermetabolic state in ALS which depends mainly on age, sex and FFM. REE is a prognostic factor for survival in univariate analysis.

Diagnostic value of nerve biopsy for atypical chronic inflammatory demyelinating polyneuropathy: evaluation of eight cases.

The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) relies primarily on clinical and electrophysiologic examination, but the nerve biopsy findings may be supportive, especially in atypical cases. In order to define the usefulness of nerve biopsy in this disease, we retrospectively studied 44 consecutive patients whom we classified as having CIDP on pathological grounds. We found that 8 of these 44 patients had pathological findings indicative of CIDP but did not meet any of the usually accepted electrophysiological criteria for its diagnosis. Among these eight patients, five responded favorably to conventional therapy. All of these eight patients had an electrophysiological pattern of generalized axonopathy with additional subtle findings suggestive of demyelination that prompted us to perform a nerve biopsy. Our data suggest that a significant number of patients with unrecognized CIDP are erroneously classified as having chronic idiopathic axonal polyneuropathy. CIDP should be suspected if the electrophysiological examination displays subtle abnormalities suggestive of demyelination, even in the presence of a prominent axonal pattern. Nerve biopsy in these patients may reveal abnormalities suggestive of CIDP and guide therapeutic options.