Does the guidance method affect the doses of botulinum toxin in writer's cramp?

PURPOSE: Botulinum neurotoxin (BoNT) injections are the main medical treatment of writer's cramp. When the outcome is favourable, patients usually receive injections several times per year in the long-term. However, we know little about the course of BoNT doses and nothing about the impact of the guidance method on the clinical outcome or injection strategy. METHODS: We studied, in the long-term, the doses of BoNT and the target muscles in a group of patients with writer's cramp, according to the guidance method (electrical stimulation or ultrasound). Patients received at least three injection cycles guided by electrical stimulation, followed by at least three injection cycles guided by ultrasound. RESULTS: Twenty-four patients were included. More target muscles were injected after switching to ultrasound guidance, especially the flexor carpi ulnaris and the flexor carpi radialis. The mean dose by muscle was lower when ultrasound guidance was used. When using electrical stimulation guidance, the dose in the flexors of the fingers decreased in the long-term, but increased in the flexors of the wrist. The course of the BoNT doses and of the number of target muscles per cycle were not the same during the first period (electrical stimulation) and the second period (ultrasound). CONCLUSIONS: Switching to ultrasound guidance, the BoNT dose decreased, mainly in the flexors of the wrist. Based on the results of our study, we suggest a starting dose in several muscles (flexor carpi ulnaris, flexor carpi radialis, flexor digitorum profundus and flexor pollicis longus).

Crosschecking the subjective everyday Parkinson's experience among patients and their caregiving spouses: French versions of the Belastungsfragebogen Parkinson Kurzversion (Bela-P-k and Bela-A-k).

BACKGROUND: Parkinson's disease (PD) affects all dimensions of the patient's and the caregiver's daily life. There are two questionnaires in German, Bela-A-k (for caregivers) and Bela-P-k (for PD patients), that can be used to assess the PD-related psychosocial burden in a dyad. The patient's and the caregiver's perspective of living with PD can be crosschecked. Four dimensions are explored: physical performance, emotional load, social relationships, and couple/family life. OBJECTIVES: The purpose of the study was to translate these questionnaires into French and to test them among patients and caregivers. METHODS: The questionnaires were translated from German into French by forward and backward translation, followed by a cultural crosscheck. Participants were invited to test the consensual French version in its online administered version created via Lime Survey® software. Participants filled out the questionnaires twice (five-day interval) according to the test-retest method. Data analysis was performed with SPSS software. RESULTS: Thirty dyads were recruited and eighteen completed the study. Bela-A-K showed strong temporal stability, though it was weak for the social relationships dimension. Bela-P-k showed strong internal consistency, but significant test-retest differences for ten items due to day-by-day changes in patient status. CONCLUSIONS: The questionnaires are useful and reliable for dyad-centered follow-up in case of PD. Some items of the Bela-P-k were simplified to improve its temporal stability, considering the patient's changing status through the day. The items concerning social relationships were adjusted for the Bela-A-k.

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.

Diaphragmatic weakness related to radiotherapy: 2 cases and a review.

Post-radiation diaphragmatic weakness have rarely been described. We report two cases of post-radiation diaphragmatic weakness from our center, and review the other published cases, computing clinical, electromyography and magnetic resonance imaging data. Including our two cases, seven cases of post-radiation diaphragmatic weakness have been described. Most occurred after mantle-field radiotherapy for Hodgkin lymphoma (5/7), often in associations with chemotherapy (4/7). Other radiations-induced complications were found (5/7) such as brachial plexopathy, cardiac involvement or hypothyroidy. When studied, phrenic nerve conduction studies revealed different profiles, from clearly abnormal responses to limit amplitudes. Imaging can be a useful diagnostic tool, displaying abnormalities with sharp limits matching the radiation field. Data is limited about long-term evolution. Presentation of post-radiation diaphragmatic weakness seems relatively homogeneous. We propose a diagnosis work-up for post-radiation diaphragmatic weakness, to exclude potentially treatable differential diagnoses.

Does ultrasound-guidance improve the outcome of botulinum toxin injections in cervical dystonia?

PURPOSE: Ultrasound-guided injections of botulinum neurotoxin in cervical dystonia have a number of theoretical advantages. However, their action has never been compared to that of non-guided injections. The objectives of the study were to compare the outcome of botulinum neurotoxin type A treatment in patients with idiopathic, focal cervical dystonia, according to two methods: inspection and palpation of anatomical landmarks (non-guided group) or ultrasound guidance (ultrasound-guided group). METHODS: We included consecutive patients in this single-center, prospective, real-life, non-randomized study. The outcomes were evaluated one month after the injections: Cervical Dystonia Impact Profile 58 (main outcome), Toronto Western Spasmodic Torticollis Rating Scale-2 (pain and disability subscores), Toronto Western Spasmodic Torticollis Rating Scale-PSYCH, patient-rated Clinical Global Impression - Improvement and adverse events. We used propensity score methods for statistical analysis; ten predefined confounding factors were used to build the propensity score. RESULTS: Sixty-three patients were included in the non-guided group, and 60 other patients in the ultrasound-guided group. We found no difference in main and secondary outcomes between the two study groups. CONCLUSION: This is the first direct comparison between ultrasound-guided and non-guided botulinum neurotoxin type A injections in patients with cervical dystonia. We hypothesize that ultrasound guidance made it possible to obtain the same results in the most severe (or the most demanding) patients as in the best responders. Further studies are still needed to assess the impact of botulinum neurotoxin injections into deep cervical muscles.

Validation of a non-motor fluctuations questionnaire in Parkinson's disease.

INTRODUCTION: Non-motor fluctuations (NMF) in Parkinson's disease (PD) remain poorly recognized but have a high impact on patients' quality of life. The lack of assessment tools limits our understanding of NMF, compromising appropriate management. Our objective was to validate a hetero-questionnaire for NMF in PD patients at different stages of the disease: without treatment, without motor fluctuations, with motor fluctuations. METHODS: We included patients in 15 centers in France. Our questionnaire, NMF-Park, resulted from previous studies, allowing us to identify the more pertinent NMF for evaluation. Patients reported the presence (yes or no) of 22 selected NMF, and their link with dopaminergic medications. The assessment was repeated at one and two years to study the progression of NMF. We performed a metrological validation of our questionnaire. RESULTS: We included 255 patients (42 without treatment, 88 without motor fluctuations and 125 with motor fluctuations). After metrological validation, three dimensions of NMF were found: dysautonomic; cognitive; psychiatric. The sensory/pain dimension described in the literature was not statistically confirmed by our study. DISCUSSION: Our questionnaire was validated according to clinimetric standards, for different stages of PD. It was clinically coherent with three homogeneous dimensions. It highlighted a link between fatigue, visual accommodation disorder, and cognitive fluctuations; and the integration of sensory/pain fluctuations as part of dysautonomic fluctuations. It focused exclusively on NMF, which is interesting considering the described differences between non-motor and motor fluctuations. CONCLUSION: Our study validated a hetero-questionnaire of diagnosis for NMF for different stages of PD.

Electro-clinical presentation of hereditary transthyretin related amyloidosis when presenting as a polyneuropathy of unknown origin in northern France.

INTRODUCTION: Hereditary transthyretin related amyloidosis (h-ATTR) classically presents as a small fiber neuropathy with positive family history, but can also be revealed by various other types of peripheral neuropathy. OBJECTIVE: To describe the initial electro-clinical presentation of patients from in a single region (northern France) of h-ATTR when it presents as a polyneuropathy of unknown origin. METHOD: We reviewed the records of patients referred to two neuromuscular centers from northern France with a peripheral neuropathy of unknown origin who were subsequently diagnosed with h-ATTR. RESULTS: Among 26 h-ATTR patients (10 Val30Met, 16 Ser77Tyr), only 14 patients had a suspicious family history (53.8%). The electro-clinical presentation was mostly a large-fiber sensory motor polyneuropathy (92.3%), which could be symmetric or not, length-dependent or not, or associated with nerve entrapment or not. Demyelinating signs were observed in 17 patients (70.8%), among whom nine fulfilled the criteria for a definite diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (37.5%). CONCLUSION: h-ATTR may have a wide spectrum of clinical profiles, and should be considered in the screening of polyneuropathies of unknown origin.

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.

Anatomy-guided injections of botulinum neurotoxin in neck muscles: how accurate is needle placement?

BACKGROUND AND PURPOSE: In cervical dystonia, the accuracy of botulinum neurotoxin (BoNT) injections may influence the response to the treatment. METHODS: We used ultrasound to evaluate the accuracy of anatomy-guided injections of BoNT in the neck muscles. RESULTS: A total of 56 consecutive patients and 332 injections were evaluated. The overall accuracy was 76.6%. The lowest accuracy (67.9%) was observed for the splenius capitis muscle. CONCLUSIONS: Anatomic guidance of BoNT injections in the neck muscles is often inaccurate. Imaging guidance may improve the accuracy of BoNT injections in cervical dystonia.

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.

MRI of the cervical spinal cord predicts respiratory dysfunction in ALS.

For patients with amyotrophic lateral sclerosis (ALS), the primary therapeutic goal is to minimize morbidity. Non-invasive ventilation improves survival. We aim to assess whether Magnetic Resonance Imaging (MRI) of the cervical spinal cord predicts the progression of respiratory disorders in ALS. Brain and spinal MRI was repeatedly performed in the SOD1G86R mouse model, in 40 patients and in healthy controls. Atrophy, iron overload, white matter diffusivity and neuronal loss were assessed. In Superoxide Dismutase-1 (SOD1) mice, iron accumulation appeared in the cervical spinal cord at symptom onset but disappeared with disease progression (after the onset of atrophy). In ALS patients, the volumes of the motor cortex and the medulla oblongata were already abnormally low at the time of diagnosis. Baseline diffusivity in the internal capsule was predictive of functional handicap. The decrease in cervical spinal cord volume from diagnosis to 3 months was predictive of the change in slow vital capacity at 12 months. MRI revealed marked abnormalities at the time of ALS diagnosis. Early atrophy of the cervical spinal cord may predict the progression of respiratory disorders, and so may be of value in patient care and as a primary endpoint in pilot neuroprotection studies.

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.

Ethical considerations and palliative care in patients with amyotrophic lateral sclerosis: A review.

Amyotrophic lateral sclerosis (ALS) is not a curable disease, but it is treatable. By definition, much of the care provided to ALS patients is palliative, even though active life-sustaining strategies are available to prolong survival. Healthcare professionals must develop communication skills that help patients cope with the inexorable progression of the disease and the inevitability of death. Symptomatic treatments as well as respiratory insufficiency and nutritional life-sustaining therapies must be regularly evaluated as the disease progresses, without losing sight of the burden placed on the patient's non-professional caregivers. The decision-making process regarding tracheostomy with invasive ventilation (TIV) is of greater complexity. Providing full information is crucial. Several long interviews are necessary to explain, discuss and allow assimilation of the information. Also, physicians should be careful not to focus exclusively on the biomedical aspects of disease, as ALS patients generally welcome the opportunity to discuss end-of-life issues with their physicians. Psychological factors, education level and cognitive status (especially the level of executive dysfunction) have a major influence on their decisions. However, as many patients do not complete advance directives with regard to TIV, advance care planning may instead be suggested in anticipation of emergency interventions. This should be discussed by healthcare professionals and the patient, and based on the wishes of the patient and caregiver(s), and communicated to all healthcare professionals. Many healthcare professionals are involved in the management of an ALS patient: they include not only those at ALS centers who provide diagnosis, follow-up and treatment initiation (particularly for respiratory and nutritional care), but also the medical and social care networks involved in disability support and home care. Specialist palliative care teams can work in partnership with ALS centers early in the course of the disease, with the center coordinating information-sharing and collaborative discussions.

Clinical features of amyotrophic lateral sclerosis and their prognostic value.

In classic amyotrophic lateral sclerosis (ALS), the relative degree of impairment of cortical vs spinal motor neurons serving the different body regions is highly variable. This means that an accurate, systematic assessment of the patient's clinical presentation is essential for both the diagnosis and prognosis. The patient's phenotype, rate of disease progression, time of onset (if early) of respiratory failure and nutritional status all have prognostic value, and should be specified in the nosological classification of the disease.