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Recent phase II pilot clinical trials suggested that tauro-urso-deoxycholic acid (TUDCA) might slow functional decline and increase survival in patients with amyotrophic lateral sclerosis (ALS). We performed a multivariate analysis of the original TUDCA cohort to better define the treatment effect and allow comparability with other trials. Linear regression slope analysis showed statistical differences in the decline rate, favoring the active treatment arm (p-value < 0.01; −0.262 for the TUDCA group and −0.388 for the placebo group). Mean survival time, estimated by the Kaplan–Meier analysis, showed a 1-month difference, favoring active treatment (log-rank test p-value = 0.092). Cox regression analysis demonstrated that placebo treatment was associated with a higher risk of death (p-value = 0.055). These data further support the disease-modifying effect of TUDCA monotherapy and raise the question of what could be the additional effect of combining TUDCA with sodium phenylbutyrate.

Additional file 3. Patient survey.

Additional file 4. Plain language summary.

Additional file 2. Verbatim quotes from the expert focus group.

Additional file 1.. Full version of the CD patient journey map.

We aimed to study the attitude of Italian neurologists in the use of conventional MRI in patients with idiopathic adult-onset focal dystonia. Patients were included in the Italian Dystonia Registry by experts working in different Italian centers. MRI was available for 1045 of the 1471 (71%) patients included in the analysis. Using logistic regression analysis, we found that MRI was more likely to be performed in patients with cervical dystonia, spasmodic dysphonia, or non-task-specific upper limb dystonia, whereas it was less likely to be performed in patients with blepharospasm or task-specific upper limb dystonia. We did not find differences in the number of MRIs performed between neurological centers in Northern, Central, and Southern Italy. We conclude that although the diagnosis of idiopathic adult-onset dystonia is mainly based on clinical grounds, many movement disorder experts rely on MRI to confirm a diagnosis of idiopathic dystonia. We suggest that neuroimaging should be used in patients with adult-onset focal dystonia to rule out secondary forms.

Knowledge on dystonia has greatly improved recently, because of a renewed effort in understanding its cause, pathophysiology, and clinical characterization. Different drug classes traditionally have been used for the symptomatic treatment of dystonia, more recently surpassed by the introduction of botulinum neurotoxins and deep brain stimulation. No curative or disease-modifying treatments are available. Recent knowledge regarding the pathophysiology of inherited dystonias is highlighting new potential treatment strategies. We review therapeutic advances in dystonia that have been published over the last 3 years, particularly regarding oral medications, local injections of botulinum neurotoxins, deep brain stimulation, and transcranial or epidural brain stimulations. We discuss evidence of efficacy, highlight recent advances, and focus on key areas under development.

We aimed to develop and validate a novel rating scale for multiple system atrophy (Unified Multiple System Atrophy Rating Scale - UMSARS). The scale comprises the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale. For validation purposes, 40 MSA patients were assessed in four centers by 4 raters per center (2 senior and 2 junior raters). The raters applied the UMSARS, as well as a range of other scales, including the Unified Parkinson's Disease Rating Scale (UPDRS) and the International Cooperative Ataxia Rating Scale (ICARS). Internal consistency was high for both UMSARS-1 (Crohnbach's alpha = 0.84) and UMSARS-II (Crohnbach's alpha = 0.90) sections. The interrater reliability of most of the UMSARS-I and -II items as well as of total UMSARS-I and -II subscores was substantial (k (w) = 0.6-0.8) to excellent (k (w) > 0.8). UMSARS-II correlated well with UPDRS-III and ICARS (rs > 0.8). Depending on the degree of the patient's disability, completion of the entire UMSARS took 30 to 45 minutes. Based on our findings, the UMSARS appears to be a multidimensional, reliable, and valid scale for semiquantitative clinical assessments of MSA patients.

Motor complications in Parkinson's disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Assessing the frequency of Wearing-Off (WO) in Parkinson's disease (PD) patients, and its impact on Quality of Life (QoL). METHODS: Consecutive ambulatory patients, who were on dopaminergic treatment for ≥ 1 year, were included in this multicentre, observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as using the validated Italian version of a patient self-rated 19-question Wearing-Off Questionnaire (WOQ-19); WO was defined for scores ≥ 2. QoL was evaluated by the 8-item Parkinson's Disease Questionnaire (PDQ-8). RESULTS: 617 subjects were included, with a mean anti-Parkinson treatment duration of 6.6 ± 4.6 years, 87.2% were on levodopa treatment. Neurologists identified presence of WO in 351 subjects (56.9%), whereas 415 subjects (67.3%) were identified by the self-administered WOQ-19. In patients with a

Subthalamic nucleus deep brain stimulation (STN DBS) and continuous dopaminergic infusions (jejunal levodopa or subcutaneous apomorphine) are indicated in complicated Parkinson's disease (PD), although it remains unsettled how they compare to each other.We investigated the daytime motor condition in patients with advanced PD under monotherapy with jejunal levodopa, subcutaneous apomorphine, or STN DBS and also measured the motor changes produced by an additional standard morning dose of levodopa. Motor performance was assessed with the UPDRS-III, hand taps, the AIMS dyskinesia score and patients' diaries. Outcome measures were time to best motor 'on' after start of morning treatment, daytime variability of motor condition, motor scores.The time to 'on' was longest in the jejunal levodopa group. DBS and jejunal levodopa treatments produced stable motor conditions without appreciable 'off' episodes. Continuous apomorphine infusion was associated with the worst motor scores (UPDRS-III and taps) and the most frequent off-states. Jejunal levodopa infusion was associated with the highest AIMS scores. Addition of a levodopa dose produced shortening of time to 'on' and a transient motor improvement in the jejunal levodopa group without increase in dyskinesias; in the DBS and apomorphine groups, there was an increase in dyskinesias without changes in UPDRS-III or taps.STN DBS provided adequate trade-off between motor improvement and dyskinesia control, although dyskinesias could be elicited by adding oral levodopa. Jejunal levodopa infusion produced adequate motor improvement with slow time to 'on' and moderate dyskinesias. Apomorphine infusion produced insufficient motor control and negligible dyskinesias.

Dopamine neurotransmission plays a key role in several brain activities, including motor, cognitive, and behavioral functions. Parkinson's disease (PD) typically begins with asymmetrical motor features related to asymmetrical dopamine denervation. This study was designed to examine whether distinct cognitive, behavioral, and personality features are related to this asymmetry.Fifty-six patients with mild PD and lateralized motor features were grouped according to dominant side of motor features and evaluated using a neuropsychological assessment focused on attention and executive functions, impulse control disorders, and personality inventory.There were no differences in neuropsychological functions between patients with right and left lateralized PD, but differences occurred in personality features. Patients with motor impairment predominant on the left-hand side had prevalence of hypomania and conversion profile.This study suggests that side dominance of dopaminergic denervation may be related to personality features in patients with PD that could influence behavioral aspects.

Three patients who presented with parkinsonian signs resulting from a focal midbrain lesion are reported. In all patients parkinsonian features occurred acutely and improved following acute challenge with apomorphine but not with levodopa. Remission of parkinsonian signs occurred spontaneously to a different degree. Inconsistent clinical response following administration of levodopa has been well documented in patients with focal midbrain lesions associated with parkinsonian signs; however, the efficacy of apomorphine has not been tested before. Anatomic or etiologic features do not allow us to predict in which cases parkinsonian signs secondary to a midbrain lesion would respond to levodopa or to dopamine agonists. A trial with apomorphine is warranted in all such cases.

The therapeutic role of botulinum neurotoxin (BoNT) in spasticity is controversial. We examined the efficacy and tolerability of BoNT in the management of upper limb post-stroke spasticity in adults. We identified 11 eligible double-blind randomized placebo-controlled trials of variable methodological quality. Primary outcomes were mean changes in Ashworth scores (Ashworth scores) in each limb joint, and the number of participants with least a one-point score reduction. Ten studies compared BoNT-A with placebo. The overall effect on upper limb spasticity was significantly in favor of BoNT-A. Improvement on standardized weighted differences occurred for elbow, wrist and finger flexor spasticity, 3–6 weeks and 9–12 weeks after treatment. No improvement in weighted mean difference was observed in the trial of BoNT-B. Meta-analysis of the number of patients with reduction in Ashworth scores favored BoNT-A compared to placebo; similar data were not available for BoNT-B. BoNT was generally well tolerated. The results of this study indicate that BoNT-A is safe and effective in reducing muscle hypertonia due to spasticity in upper limb joints. Insufficient data were available to assess the efficacy and tolerability of BoNT- B in spasticity.

Item does not contain fulltext OBJECTIVE: Differentiating Parkinson's disease (PD) from atypical parkinsonian disorders (APD) such as Multiple System Atrophy, parkinsonian type (MSA-p) or Progressive Supranuclear Palsy (PSP-RS) can be challenging. Early signs of postural Instability and gait disability (PIGD) are considered clues that may signal presence of APD. However, it remains unknown which PIGD test - or combination of tests - can best distinguish PD from APD. We evaluated the discriminative value of several widely-used PIGD tests, and aimed to develop a short PIGD evaluation that can discriminate parkinsonian disorders. METHODS: In this multicentre cohort study patients were recruited by 11 European MSA Study sites. Patients were diagnosed using standardized criteria. Postural instability and gait disability was evaluated using interviews and several clinical tests. RESULTS: Nineteen PD, 21 MSA-p and 25PSP-RS patients were recruited. PIGD was more common in APD compared to PD. There was no significant difference in axial symptoms between PSP-RS and MSA-p, except for self-reported falls (more frequent in PSP-RS patients). The test with the greatest discriminative power to distinguish APD from PD was the ability to perform tandem gait (AUC 0.83; 95% CI 71-94; p

Pathological gambling (PG) is an impulse control disorder that manifests in 2.2–7% of patients with Parkinson's disease (PD). Although the underlying neural mechanisms remain controversial, parkinsonian patients with PG show enhanced risk propensity, especially when assuming dopamine agonist drugs. The dopaminergic reward circuit, a neural network that participates in developing and monitoring motivated behaviours,1 includes the subthalamic nucleus (STN). Local field potentials (LFPs) recorded from macroelectrodes implanted in the STN for deep brain stimulation (DBS) show specific low-frequency oscillations in patients with PD with impulsive control disorders at rest and in patients with PG during the preparation of conflictual economics decisions.2 ,3 No study has yet investigated STN involvement in monetary reward processing, namely the phase that follows economics decisions, when participants face the outcome of their choice in patients with PD. Besides helping to understand the mechanisms underlying PG, this knowledge could promote the optimisation of therapies for impulse control disorders. We investigated the STN's role in risk-related monetary reward in parkinsonian patients. To do so, we studied the reward-related STN LFPs changes in patients with PD with and without PG engaged in an economics decision task. We enrolled 12 patients with PD 4 days after STN DBS macroelectrode positioning surgery as described elsewhere3 (for clinical details, see table 1 from Ref. 3, patients number 1–4, 8–12, 14, 15, 17). Of the 12 patients, 6 met the criteria for PG according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR). All patients gave informed consent. The study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board. Patients were tested with the economics decision task (figure 1A,C) during bilateral STN LFP recording from DBS macroelectrode contact pair 0–2. Figure 1 (A) The economics decision task. Each trial comprised …