Indication for molecular testing by multiplex ligation-dependent probe amplification in parkinsonism.

BACKGROUND AND PURPOSE: The monogenic forms of Parkinson's disease represent <10% of familial cases and a still lower frequency of sporadic cases. However, guidelines to orient genetic testing are lacking. The aim was to establish the interest of multiplex ligation-dependent probe amplification (MLPA) as a primary screening test and to propose clinical criteria to guide genetic diagnostic tests for patients with suspected Mendelian Parkinson's disease. METHODS: In all, 567 patients with parkinsonism from 547 unrelated families were recruited and two MLPAs were performed for each. All pathogenic G2019S variants in the LRRK2 gene were confirmed by Sanger sequencing and the PRKN gene was screened for a second mutation in the cases of one heterozygous structural variant in the PRKN gene. RESULTS: The performance of MLPA was 51/567 (9%) for the entire cohort and included 27 (4.8%) LRRK2 G2019S mutations, 19 (3.4%) PRKN mutations and five (0.9%) SNCA locus duplications. The variables significantly associated with a positive test in the total cohort were North African ancestry (p < 0.0001), female sex (p = 0.004) and younger age at onset (p < 0.0008). CONCLUSIONS: Retrospective analysis allowed us to refine our indication criteria: (i) North African ancestry, (ii) an age at onset <40 years or (iii) a familial history of parkinsonism with at least one affected first-degree relative. Our study highlights the interest of MLPA testing for other parkinsonism cases with a family history, especially for patients with dementia with Lewy bodies or a multiple-system-atrophy-like phenotype.

Use of levodopa-carbidopa intestinal gel to treat patients with multiple system atrophy.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment for late-stage Parkinson's disease (PD) but had not been evaluated in levodopa-responsive patients with the parkinsonian variant of multiple system atrophy (MSA-P) and motor fluctuations. We aimed to assess the safety of LCIG in MSA-P patients. METHODS: In a retrospective, single-center study, we analyzed clinical and treatment-related data for all patients with MSA-P or PD treated with LCIG between December 2004 and November 2017. Adverse events (AEs) were classified into three classes: AEs related to gastrointestinal effects or to the PEG-J procedure, AEs related to the device, and AEs related to the pharmacological effect of LCIG. RESULTS: 7 MSA-P and 63 PD patients had been treated with LCIG for a median [interquartile range] period of 31 [16;43] and 19 [8;45] months, respectively. There were no significant intergroup differences in safety. Enteral nutrition was introduced at the same time as LCIG treatment in 4 (57%) MSA-P patients. In the MSA-P and PD groups, LCIG was associated with a better Global Clinical Impression score and discontinuation of oral anti-parkinsonian drugs (in 43% and 27% of cases, respectively). CONCLUSIONS: LCIG treatment is feasible in MSA-P patients with severe motor complications. The safety profile is similar to that seen in PD.

Factors that predict a change in quality of life among Parkinson's disease patients participating in a patient education program.

BACKGROUND: Patient education is essential in Parkinson's disease (PD). However, it is not known which aspects of patient education are associated with an improvement in quality of life (QoL). OBJECTIVE: To identify factors that predicted an improvement in QoL in PD patients that participate in an education program. METHODS: EduPark is a community-hospital patient education program. PD Patients that had participated in the program between September 2013 and March 2017 were retrospectively included. QoL was prospectively evaluated (using the PDQ-8 questionnaire) before and after the patient's participation. We used mixed linear models (adjusted for the initial value of the PDQ-8) to determine socio-demographic and clinical variables that predicted the change in the PDQ-8 score. RESULTS: A total of 181 patients were included (mean±standard deviation age: 62.9±8.2 years; disease duration: 9.1±5.3 years). 76.7% of the 103 patients having undergone a cognitive evaluation did not display cognitive impairment. We did not identify any factors that predicted the program's impact on the patient's QoL. Participation in the program was associated with a significant decrease (improvement) in the PDQ-8 score (39.4±17.81 before and 35.6±15.9 afterwards, P<0.001). CONCLUSION: We did not identify any factors that were predictive of the patient education program's impact on QoL in patients with PD. Participation in the program was associated with a significant improvement in QoL. Our results suggest that Patient Education Programs should be more widely prescribed and developed in the management of PD.

Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study.

BACKGROUND: Treatment with levodopa-carbidopa intestinal gel (LCIG) can effectively relieve motor and non-motor symptoms in advanced Parkinson's disease (PD). However, adverse events (AEs) are frequent. OBJECTIVE: To describe AEs associated with LCIG treatment and the main reasons for treatment discontinuation. We also looked for factors that were potentially predictive of serious AEs and assessed the effectiveness of and satisfaction with LCIG. METHOD: We retrospectively analyzed data on AEs in patients treated with LCIG at a French university medical center. For patients still receiving treatment at last follow-up, effectiveness was assessed according to the Clinical Global Impression (CGI) scale and the Movement Disorders Society - Unified Parkinson's Disease Rating Scale motor score. RESULTS: Of the 63 patients treated with LCIG for a mean (range) of 19 months (8-47), 57 (90%) experienced at least one AE (340 AEs in total). Most of the AEs (in 69.8% of the patients) were related to percutaneous endoscopic gastrostomy with a jejunal tube (PEG-J) or affected the gastrointestinal tract (granuloma, leakage, or a local infection). Device-related AEs (such as PEG-J removal and device occlusion) were frequent (in 63.5% of patients). Forty-three patients (68%) required at least one additional endoscopic procedure. Dopatherapy-related AEs occurred in 30 patients (48%). Most of the AEs occurred long after treatment initiations, and only a small proportion led to discontinuation. On the CGI scale, 53 patients (84.4%) considered that their condition had improved during LCIG treatment. CONCLUSION: Despite the high frequency of AEs, patients with advanced PD gain clinical benefit from treatment with LCIG. This treatment requires a competent, multidisciplinary team on site.

Descriptive study of the parkinsonian population in the north of France: Epidemiological analysis and healthcare consumption.

BACKGROUND: The "neurodegenerative diseases plan" under elaboration for the Hauts-de-France region requires better knowledge of the patient population and care pathways. In France, the prevalence of Parkinson's disease (PD) has been estimated from cohorts to be about 1-3 per 1000 inhabitants, but exhaustive data are scarce for the general population. The purpose of this study was to evaluate the prevalence of PD in the Hauts-de-France region and to assess PD-related healthcare consumption. METHOD: A descriptive study was conducted to identify the parkinsonian population in the Hauts-de-France region (including the administrative districts of Pas-de-Calais and Picardie) for the year 2014. Parkinsonian patients were identified from health insurance fund reimbursement data using the following criteria: (i) reimbursement for a PD-specific medication; (ii) attribution of long-duration disease status coded as PD; (iii) hospital stay with PD diagnosis in the standard discharge report contained in the French medico-economic database on hospital activity (PMSI). RESULTS: The raw prevalence of PD in the region was 5.03 per 1000 inhabitants aged 20 years and older. The standardized prevalence by health territory ranged from 4.0 to 9.0 per 1000 inhabitants aged 20 years and older. During the 1-year study period, 33.5% of patients had a neurology consultation, 57.1% attended a physiotherapy session, and 7.7% received speech therapy. Most of patients (79.6%) were treated with levodopa, sometimes in combination with a catechol-O-methyl transferase inhibitor (14.4%). Dopaminergic agonists were prescribed in 33.5% of cases. A neuroleptic was prescribed for 6.9% of the population (clozapine for 25.9%). CONCLUSION: The prevalence of PD is high in the Hauts-de-France region with a heterogeneous distribution by health territory. Neurology consultations were attended by a minority of patients in 2014. This work provides perspectives for necessary improvement in specialized care for this disease, both in terms of follow-up consultations and home care.

[Impulse control disorders in Parkinson's disease: A cohort of 35 patients]. / Troubles du contrôle des impulsions associés à la maladie de Parkinson : étude d'une cohorte de 35 patients.

INTRODUCTION: Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated with dopamine agonist treatment. Although discontinuation of dopamine agonist is recommended, ICD management has not been precisely stated. The aims of the study were to describe demographic and clinical characteristics in a group of PD patients with ICDs and to evaluate the management of dopamine agonist treatment proposed to the same patients in order to treat the ICDs. METHODS: Thirty-five PD patients with ICD and 607 PD patients without ICD were studied. In the ICD group, demographic and clinical data were collected prospectively (ICD characteristics, motor and cognitive evaluation); demographic and clinical data were obtained retrospectively in the group without ICD. RESULTS: In the ICD group, the sex ratio was 2.9 (versus 1.2 in the absence of ICD; p<0.05), the mean age was 57.5 years (versus 66.9 years; p<0.01) and the mean age at PD onset was 48.3 years (versus 55.5 years; p<0.01). All ICD patients were receiving a dopamine agonist when the ICD started (versus 50.9 % of patients receiving a dopamine agonist in the absence of ICD; p<10(-6)). In mean, ICDs started 2.8 years before they were diagnosed. No particular dopamine agonist was associated with ICDs more frequently than the others. Discontinuation of the dopamine agonist was the treatment the more frequently associated with the recovery of ICDs (93.3 %). Dose lowering and the change of dopamine agonist resulted in complete regression of ICDs respectively in 9.1% and 33.3% of patients. CONCLUSION: Young age, male gender and young age at PD onset are frequent in PD patients developing ICDs, as already described in American or Asian cohorts. We highlighted a long diagnosis delay and confirmed the strong efficacy of dopamine agonist withdrawal.

Enhanced glutamatergic phenotype of mesencephalic dopamine neurons after neonatal 6-hydroxydopamine lesion.

There is increasing evidence that a subset of midbrain dopamine (DA) neurons uses glutamate as a co-transmitter and expresses vesicular glutamate transporter (VGLUT) 2, one of the three vesicular glutamate transporters. In the present study, double in situ hybridization was used to examine tyrosine hydroxylase (TH) and VGLUT2 mRNA expression during the embryonic development of these neurons, and postnatally, in normal rats and rats injected with 6-hydroxydopamine (6-OHDA) at P4 to destroy partially DA neurons. At embryonic days 15 and 16, there was a regional overlap in the labeling of TH and VGLUT2 mRNA in the ventral mesencephalon, which was no longer found at late embryonic stages (E18-E21) and postnatally. In normal pups from P5 to P15, only 1-2% of neurons containing TH mRNA in the ventral tegmental area (VTA) and substantia nigra, pars compacta, also displayed VGLUT2 mRNA. In contrast, after the cerebroventricular administration of 6-OHDA at P4, 26% of surviving DA neurons in the VTA of P15 rats expressed VGLUT2. To search for a colocalization of TH and VGLUT2 protein in axon terminals of these neurons, the nucleus accumbens of normal and 6-OHDA-lesioned P15 rats was examined by electron microscopy after dual immunocytochemical labeling. In normal rats, VGLUT2 protein was found in 28% of TH positive axon terminals in the core of nucleus accumbens. In 6-OHDA-lesioned rats, the total number of TH positive terminals was considerably reduced, and yet the proportion also displaying VGLUT2 immunoreactivity was modestly but significantly increased (37%). These results lead to the suggestion that the glutamatergic phenotype of a VTA DA neurons is highly plastic, repressed toward the end of normal embryonic development, and derepressed postnatally following injury. They also support the hypothesis of co-release of glutamate and DA by mesencephalic neurons in vivo, at least in the developing brain.

Spontaneous internal carotid artery dissection with lower cranial nerve palsy.

BACKGROUND: Typical presentation of spontaneous internal carotid artery (ICA) dissection is an ipsilateral pain in neck and face with Horner's syndrome and contralateral deficits. Although rare, lower cranial nerve palsy have been reported in association with an ipsilateral spontaneous ICA dissection. CASE STUDIES: We report three new cases of ICA dissection with lower cranial nerve palsies. RESULTS: The first symtom to appear was headache in all three patients. Examination disclosed a Horner's syndrome in two cases (1 and 2), an isolated XIIth nerve palsy in two patients (case 1 and 3) and IX, X, and XIIth nerve palsies (case 2) revealing an ipsilateral carotid dissection, confirmed by MRI and angiography. In all cases, prognosis was good after a few weeks. CONCLUSIONS: These cases, analysed with those in the literature, led us to discuss two possible mechanisms: direct compression of cranial nerves by a subadventitial haematoma in the parapharyngeal space or ischemic palsy by compression of the ascending pharyngeal artery.

Engaging distortions: are we idealizing marriage?

The present study was an investigation of the premarital status of engagement in terms of relationship satisfaction and marital expectations using the Evaluation and Nurturing Relationship Issues, Communication and Happiness (ENRICH) Marital Satisfaction Scale (EMS) and its two subscales of Idealistic Distortion (ID) and Marital Satisfaction (MS) (D. G. Fournier, D. H. Olson, & J. M. Druckman, 1983). There were 104 students (23 men and 81 women), of which 15 were married, 19 were engaged, and 70 had extended dating relationships. On average, participants had been in the relationship for 3.8 years, and the mean age was 22 years. Results demonstrated that individuals engaged to be married had significantly higher idealistic distortion scores (M = 86.89) than did either married individuals (M = 56.67) or those in extended dating relationships (M = 61.19). Finally, a negative relation was found between length of relationships and marital satisfaction subscores. Results are discussed in light of factors contributing to such idealized thinking.

[Pseudomigraine with transient neurological signs and lymphocytic pleiocytosis]. / Pseudomigraine avec signes neurologiques transitoires et pléiocytose lymphocytaire.

We report the case of a 32-year-old man without previous medical history of migraine, who presented with severe headache and temporary focal neurological deficits. Lumbar puncture revealed aseptic lymphocytic pleiocytosis. The patient completly recovered within 2 months. This condition was suggestive of a transient syndrome of headache with neurologic deficits and CSF pleiocytosis. The main characteristics and the physiopathology of this uncommon disorder are discussed.