Descriptive study of general practitioner's practices and knowledge about Parkinson's disease in the north of France.

BACKGROUND: Parkinson's disease (PD), the second most frequent neurodegenerative disease, constitutes a major public health challenge. A guide published by the French National Authority for Health in 2012 and revised in 2016 put forward recommendations for general practitioners (GP) planning care pathways for parkinsonian patients. It is well known that PD can be difficult to diagnose, and that when patients consult their GP, symptoms are often still limited and embedded in clinical uncertainty. This means the pathway to confirmed diagnosis of PD can be lengthy and uncertain. Consequently, it is important to identify the difficulties GPs encounter when caring for PD patients in order to help them better close the gaps in care strategies. METHODS: We conducted a descriptive cross-sectional survey in northern France to evaluate GP practices and knowledge about PD and their accordance with care pathway recommendations. The survey was conducted using a 30-item questionnaire sent to a sample of GPs. RESULTS: There were 164 GPs who responded to the study questionnaire. The responding GPs generally followed current care pathway recommendations. In presence of a parkinsonian syndrome, 93.3% of the GPs reported systematically looking for an iatrogenic cause; 57.4% did not announce the diagnosis without the advice of a neurologist; 97.6% referred patients to a neurologist when they suspected PD; and 80.5% asked the neurologist to modify treatments. Our findings also revealed some difficult aspects of GP practices: only 2.5% had had additional training in neurology; only 53.6% felt comfortable with the diagnosis of PD; 63.6% prescribed additional exams for the diagnosis; most of the GPs were unaware of second-line treatments and their indications, and finally existence of PD expert centers was unknown for 85.2%. CONCLUSIONS: These findings could be useful to guide implementation of new measures supporting more holistic care for PD patients; PD expert centers in France could provide complementary information and training for GPs.

French validation of the Quality of life in Essential Tremor Questionnaire (QUEST) and the Essential Tremor Embarrassment Assessment (ETEA).

Two scales have been developed and validated in English to evaluate the impact of tremor on daily life, namely Quality of life in Essential Tremor Questionnaire (QUEST) and Essential Tremor Embarrassment Assessment (ETEA). The psychometric properties of the French version of these two scales were assessed for 117 patients with head tremor. Both scales showed excellent acceptability, very good internal consistency (Cronbach's alpha coefficient>0.8) and reproducibility (Lin concordance coefficient>0.8), satisfactory external validity and satisfactory sensitivity to change. In conclusion, the French versions of QUEST and ETEA are comprehensive, valid and reliable instruments for assessing patients with head tremor.

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.

[Non-motor symptoms of Parkinson's disease from pathophysiology to early diagnosis]. / Les symptômes non-moteurs de la maladie de Parkinson de la physiopathologie au diagnostic précoce.

Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease. The pathophysiology of Parkinson's disease is complex and imperfectly known. Primum movens is abnormal intra-neuronal accumulation of the protein α-synuclein, leading to metabolic disturbances and neurodegeneration. This abnormal accumulation of α-synuclein is also found in dementia with Lewy bodies and multiple system atrophy, which together with Parkinson's disease form the group of α-synucleinopathies. Well known by its motor signs (bradykinesia, rest tremor, cogwheel rigidity and gait disturbance), Parkinson's disease is above all a systemic disease composed of a myriad of non-motor symptoms (constipation, sense of smell disorders, rapid eye movement sleep behaviour disorders, genitourinary disorders…). These non-motor symptoms caused by accumulation and migration of α-synuclein deposits from the gut and the olfactory bulb to the central nervous system may precede motor signs by ten years and therefore be of interest for early diagnosis. Furthermore, non-motor symptoms have a poorer impact on quality of life than motor signs themselves. Therefore, understanding, recognition and management of non-motor symptoms are crucial in management of parkinsonian patient. In this paper, we offer an update on the main non-motor symptoms of Parkinson's disease, from their pathophysiology to their screening, ending with their management.

Deep brain stimulation programming in Parkinson's disease: Introduction of current issues and perspectives.

Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) leading to a significant reduction in motor and non-motor symptoms. Numerous factors contribute to positive outcomes for DBS including careful patient selection, lead placement and effective programming. Only DBS programming can be modified after patient implantation, therefore DBS programming plays a crucial role in improving clinical outcomes. In this paper, we review the literature to present current issues and perspectives for DBS programming in PD. Only a few algorithms proposed by experts for the initial programming and management of some adverse effects are available. No guidelines are available for programming sessions and medical treatment management during DBS follow-up. Moreover, emergence of increasingly complex lead designs makes programming more and more complex. Fortunately, in the last few years numerous techniques have emerged for optimization of DBS programming in PD.

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.

The value of novel MRI techniques in Parkinson-plus syndromes: diffusion tensor imaging and anatomical connectivity studies.

Conventional MRI is a well-described, highly useful tool for the differential diagnosis of degenerative parkinsonian syndromes. Nevertheless, the observed abnormalities may only appear in late-stage disease. Diffusion tensor imaging (DTI) can identify microstructural changes in brain tissue integrity and connectivity. The technique has proven value in the differential diagnosis of multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and Parkinson's disease (PD). Here, we performed a systematic review of the literature on the main corticosubcortical DTI abnormalities identified to date in the context of the diagnosis of MSA and PSP with diffusion-weighted imaging, diffusion tensor imaging and anatomical connectivity studies. In good agreement with the histological data, increased diffusivity in the putamen (in MSA and PSP), in the middle cerebellar peduncles (in MSA) and in the upper cerebellar peduncles (in PSP) has been reported. Motor pathway involvement is characterized by low fraction anisotropy (FA) in the primary motor cortex in MSA-P and PSP, a high apparent diffusion coefficient (ADC) and low FA in the supplementary motor area in PSP. We then outline the value of these techniques in differential diagnosis (especially with respect to PD). Anatomical connectivity studies have revealed a lower number of fibers in the corticospinal tract in MSA and PSP (relative to PD and controls) and fewer tracked cortical projection fibers in patients with PSP or late-stage MSA (relative to patients with early MSA or PD and controls). Lastly, we report the main literature data concerning the value of DTI parameters in monitoring disease progression. The observed correlations between DTI parameters on one hand and clinical scores and/or disease duration on the other constitute strong evidence of the value of DTI in monitoring disease progression. In MSA, the ataxia score was correlated with ADC values in the pons and the upper cerebellar peduncles, whereas both the motor score and the disease duration were correlated with putaminal ADC values. In conclusion, DTI and connectivity studies constitute promising tools for differentiating between "Parkinson-plus" syndromes.

Targeting the red nucleus for cerebellar tremor.

Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.

[Parkinsonian disorders: from clinical manifestations to diagnostic classification]. / Les syndromes parkinsoniens : de l'analyse sémiologique au diagnostic nosologique.

Parkinsonism may include atypical clinical manifestations, which are warning signs for the clinicians and motivate further investigations to identify an etiology other than idiopathic Parkinson's disease. The dismemberment of pathological entities, the advances of morphological and functional imaging of the brain, and new insights into molecular biology have successively led to more precise clinical phenotype and mechanisms. Except for etiologies with specific treatment, such as Wilson's disease or Parkinsonism secondary to a lesion of basal ganglia, or the discontinuation of a culprit drug, the treatment of Parkinsonian syndrome is mainly based on a multidisciplinary approach, involving occupational therapist, physiotherapist, speech therapist, psychologist and social worker. L-Dopa may be tried but it is less effective in atypical Parkinsonian syndrome than in Parkinson's disease. Formal diagnosis, only achievable post-mortem, is not available during the lifetime of the patient. Although some additional tests provide undeniable assistance, the clinical approach remains an essential and critical step to avoid costly and unnecessary investigations.

Reduced levodopa-induced complications after 5 years of subthalamic stimulation in Parkinson's disease: a second honeymoon.

The purpose of this paper is to describe the effect of 5 years of subthalamic nucleus deep brain stimulation (STN DBS) on levodopa-induced complications, both in everyday life and during an acute challenge with levodopa. Thirty three patients were evaluated during an acute levodopa challenge before surgery and then 1 and 5 years afterwards (both off stim and on stim), using the UPDRS III scale and the CAPSIT-PD scales for dystonia and peak-dose dyskinesia. The UPDRS IV scale was used to assess motor complications in everyday life. The levodopa daily dose and DBS parameters were also recorded. Levodopa-induced complications in everyday life (UPDRS IV) and during an acute levodopa challenge had improved markedly after 1 year (both on and off stim) and still further at 5 years. Peak-dose dyskinesia decreased between the 1- and 5-year measurements. STN DBS decreases levodopa-induced motor complications over the long term. This phenomenon may be explained by (a) overall stabilization of the basal ganglia network and (b) striatal synaptic changes. Our results suggest that DBS leads to both qualitative and quantitative modulations in the corticostriatal loops.

ERG and anatomical abnormalities suggesting retinopathy in dementia with Lewy bodies.

The authors used flash electroretinography to demonstrate dysfunction of the photopic and scotopic retina in patients with dementia with Lewy bodies and visual hallucinations (VHs) compared with patients with Parkinson disease, patients without VHs, and controls. The retinal dysfunction may be related to slight alteration of the photoreceptors and numerous pale inclusions in the outer plexiform layer found at the post mortem examination, suggesting a specific retinopathy.