Do Acoustic Characteristics of Dysarthria in People With Parkinson's Disease Differ Across Languages?

PURPOSE: Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese. METHOD: This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated off and on optimal medication. Inferential analyses included Disease (controls vs. PwPD) and Language (French vs. Portuguese) as factors, and random decision forest algorithms identified relevant acoustic variables able to distinguish participants: (a) by language (French vs. Portuguese) and (b) by clinical status (PwPD on and off medication vs. controls). RESULTS: French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative. CONCLUSIONS: Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive.

Correction: Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome.

[This corrects the article DOI: 10.5334/tohm.464.].

Hemiplegic Migraine Associated With PRRT2 Variations: A Clinical and Genetic Study.

BACKGROUND AND OBJECTIVE: PRRT2 variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of PRRT2 in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands. METHODS: PRRT2 was analyzed in 860 probands with hemiplegic migraine, and PRRT2 variations were identified in 30 probands. Genotyping of relatives identified a total of 49 persons with variations whose clinical manifestations were detailed. RESULTS: PRRT2 variations were found in 12 of 163 probands who previously tested negative for CACNA1A, ATP1A2, and SCN1A variations and in 18 of 697 consecutive probands screened simultaneously on the 4 genes. In this second group, pathogenic variants were found in 105 individuals, mostly in ATP1A2 (42%), followed by CACNA1A (26%), PRRT2 (17%), and SCN1A (15%). The PRRT2 variations included 7 distinct variants, 5 of which have already been described in persons with paroxysmal kinesigenic dyskinesia and 2 new variants. Eight probands had a deletion of the whole PRRT2 gene. Among the 49 patients with variations in PRRT2, 26 had pure hemiplegic migraine and 16 had hemiplegic migraine associated with another manifestation: epilepsy (8), learning disabilities (5), hypersomnia (4), or abnormal movement (3). Three patients had epilepsy without migraine: 2 had paroxysmal kinesigenic dyskinesia without migraine, and 1 was asymptomatic. DISCUSSION: PRRT2 should be regarded as the fourth autosomal dominant gene for hemiplegic migraine and screened in any affected patient, together with the 3 other main genes. Further studies are needed to understand how the same loss-of-function PRRT2 variations can lead to a wide range of neurologic phenotypes, including paroxysmal movement disorder, epilepsy, learning disabilities, sleep disorder, and hemiplegic migraine.

Altered Inhibitory Mechanisms in Parkinson's Disease: Evidence From Lexical Decision and Simple Reaction Time Tasks.

INTRODUCTION: Although the motor signs of Parkinson's disease (PD) are well defined, nonmotor symptoms, including higher-level language deficits, have also been shown to be frequent in patients with PD. In the present study, we used a lexical decision task (LDT) to find out whether access to the mental lexicon is impaired in patients with PD, and whether task performance is affected by bradykinesia. MATERIALS AND METHODS: Participants were 34 nondemented patients with PD, either without (off) medication (n = 16) or under optimum (on) medication (n = 18). A total of 19 age-matched control volunteers were also recruited. We recorded reaction times (RTs) to the LDT and a simple RT (control) task. In each task, stimuli were either visual or auditory. Statistical analyses consisted of repeated-measures analyses of variance and Tukey's HSD post hoc tests. RESULTS: In the LDT, participants with PD both off and on medication exhibited intact access to the mental lexicon in both modalities. In the visual modality, patients off medication were just as fast as controls when identifying real words, but slower when identifying pseudowords. In the visual modality of the control task, RTs for pseudowords were significantly longer for PD patients off medication than for controls, revealing an unexpected but significant lexicality effect in patients that was not observed in the auditory modality. Performances of patients on medication did not differ from those of age-matched controls. DISCUSSION: Motor execution was not slowed in patients with PD either off or on medication, in comparison with controls. Regarding lexical access, patients off medication seemed to (1) have difficulty inhibiting a cognitive-linguistic process (i.e., reading) when it was not required (simple reaction time task), and (2) exhibit a specific pseudoword processing deficit in the LDT, which may have been related to impaired lateral word inhibition within the mental lexicon. These deficits seemed to be compensated by medication.

Effect of linguistic context on the perception of consonants in Parkinsonian Read French speech.

We examined the effect of linguistic factors on the perceptual identification of intervocalic consonants produced by speakers with Parkinson's Diseases (PD). To neutralize the effect of preceding and following contexts, all the intervocalic consonants were excised with half the preceding and following vowels.We recorded 10 PD and 10 healthy speakers reading a text. An average of 114 VCV sequences per speaker was obtained. In total, our corpus consisted of 2280 stimuli. For the perception test, 20 adults native speakers of French were instructed that they would be presented utterances produced by different speakers and that they were to identify the sequences and write what they heard. No information was given on the sequence type (VCV).The reported consonant was examined in relation to the intended consonant; the score of distorsion was the number of phonetic features differing from the prototypical consonant. The results were examined as a function of the following/or preceding linguistic factors: consonant nature, oral/nasal vocalic context, class of word (function or content) and prosodic position within sentences.Consonant imprecision was confirmed in the speech of PD speakers. Two groups of patients were observed: the former with a low degree of dysarthria severity and scores of consonant identification close to that of healthy speakers; the latter with a high degree of dysarthria severity and a low identification score.Linguistic factors were shown to affect consonant production and perception. In both normal and PD speech, consonants had more features identified when they belonged to content words, word-initial syllables or final-phrase syllables. This suggests that in Parkinson's disease speech disorders relate to motor control and not to a loss of the linguistic knowledge.

Characterization of Recessive Parkinson Disease in a Large Multicenter Study.

Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene-targeting approaches for Parkinson disease have reached the clinical trial stage. We evaluated the frequencies of PRKN, PINK1, and DJ-1 mutations in a cohort of 1,587 cases. Mutations were found in 14.1% of patients; 27.6% were familial and 8% were isolated. PRKN was the gene most frequently mutated in Caucasians, whereas PINK1 mutations predominated in Arab-Berber individuals. Patients with PRKN mutations had an earlier age at onset, and less asymmetry, levodopa-induced motor complications, dysautonomia, and dementia than those without mutations. ANN NEUROL 2020;88:843-850.

Genetic and Phenotypic Basis of Autosomal Dominant Parkinson's Disease in a Large Multi-Center Cohort.

LRRK2, SNCA, and VPS35 are unequivocally associated with autosomal dominant Parkinson's disease (PD). We evaluated the prevalence of LRRK2, SNCA, and VPS35 mutations and associated clinical features in a large French multi-center cohort of PD patients. Demographic and clinical data were collected for 1,805 index cases (592 with autosomal dominant inheritance and 1,213 isolated cases) since 1990. All probands were screened with TaqMan assays for LRRK2 Gly2019Ser. In the absence of this mutation, the coding sequences of the three genes were analyzed by Sanger sequencing and/or next-generation sequencing. The data for the three genes were analyzed according to age at onset, family history, ethnic origin and clinical features. We identified 160 index cases (8.9%) with known pathogenic variants: 138 with pathogenic LRRK2 variants (7.6%), including 136 with the Gly2019Ser mutation, 19 with SNCA point mutations or genomic rearrangements (1.1%), and three with the VPS35 Asp620Asn mutation (0.16%). Mutation frequencies were higher in familial than isolated cases, consistent with autosomal dominant inheritance (12.0 vs. 7.3%; OR 1.7, 95% CI [1.2-2.4], p = 0.001). PD patients with LRRK2 variants were more likely to have higher rates of late-onset PD (>50 years; OR 1.5, 95% CI [1.0-2.1], p = 0.03), whereas those with SNCA mutations tended to have earlier age at onset disease (≤ 50 years, p = 0.06). The clinical features of LRRK2 carriers and those without any pathogenic variants in known PD-associated genes were similar. The likelihood of detecting disease-causing mutations was higher in cases compatible with autosomal dominant inheritance.

Novel CCM2 missense variants abrogating the CCM1-CCM2 interaction cause cerebral cavernous malformations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Most deleterious variants are loss of function mutations in one of the three CCM genes. These genes code for proteins that form a ternary cytosolic complex with CCM2 as a hub. Very few CCM2 missense variants have been shown to be deleterious by modifying the ternary CCM complex stability. OBJECTIVES: To investigate the causality of novel missense CCM2 variants detected in patients with CCM. METHODS: The three CCM genes were screened in 984 patients referred for CCM molecular screening. Interaction between CCM1 and CCM2 proteins was tested using co-immunoprecipitation experiments for the CCM2 missense variants located in the phosphotyrosine binding (PTB) domain. RESULTS: 11 distinct CCM2 rare missense variants were found. Six variants predicted to be damaging were located in the PTB domain, four of them were novel. When co-transfected with CCM1 in HEK293T cells, a loss of interaction between CCM1 and CCM2 was observed for all six variants. CONCLUSION: We showed, using co-immunoprecipitation experiments, that CCM2 missense variants located in the PTB domain were actually damaging by preventing the normal interaction between CCM1 and CCM2. These data are important for diagnosis and genetic counselling, which are challenging in patients harbouring such variants.

Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome.

Background: Genes involved in Tourette syndrome (TS) remain largely unknown. We aimed to identify genetic factors contributing to TS in a French cohort of 120 individuals using a combination of hypothesis-driven and exome-sequencing approaches. Methods: We first sequenced exons of SLITRK1-6 and HDC in the TS cohort and subsequently sequenced the exome of 12 individuals harboring rare variants in these genes to find additional rare variants contributing to the disorder under the hypothesis of oligogenic inheritance. We further screened three candidate genes (OPRK1, PCDH10, and NTSR2) preferentially expressed in the basal ganglia, and three additional genes involved in neurotensin and opioid signaling (OPRM1, NTS, and NTSR1), and compared variant frequencies in TS patients and 788 matched control individuals. We also investigated the impact of altering the expression of Oprk1 in zebrafish. Results: Thirteen ultrarare missense variants of SLITRK1-6 and HDC were identified in 12 patients. Exome sequencing in these patients revealed rare possibly deleterious variants in 3,041 genes, 54 of which were preferentially expressed in the basal ganglia. Comparison of variant frequencies altering selected candidate genes in TS and control individuals revealed an excess of potentially disrupting variants in OPRK1, encoding the opioid kappa receptor, in TS patients. Accordingly, we show that downregulation of the Oprk1 orthologue in zebrafish induces a hyperkinetic phenotype in early development. Discussion: These results support a heterogeneous and complex genetic etiology of TS, possibly involving rare variants altering the opioid pathway in some individuals, which could represent a novel therapeutic target in this disorder.

Effects of cognitive impairment on prosodic parameters of speech production planning in multiple sclerosis.

Cognitive impairment (CI) affects 40-65% of patients with multiple sclerosis (MS). CI can have a negative impact on a patient's everyday activities, such as engaging in conversations. Speech production planning ability is crucial for successful verbal interactions and thus for preserving social and occupational skills. This study investigates the effect of cognitive-linguistic demand and CI on speech production planning in MS, as reflected in speech prosody. A secondary aim is to explore the clinical potential of prosodic features for the prediction of an individual's cognitive status in MS. A total of 45 subjects, that is 22 healthy controls (HC) and 23 patients in early stages of relapsing-remitting MS, underwent neuropsychological tests probing specific cognitive processes involved in speech production planning. All subjects also performed a read speech task, in which they had to read isolated sentences manipulated as for phonological length. Results show that the speech of MS patients with CI is mainly affected at the temporal level (articulation and speech rate, pause duration). Regression analyses further indicate that rate measures are correlated with working memory scores. In addition, linear discriminant analysis shows the ROC AUC of identifying MS patients with CI is 0.70 (95% confidence interval: 0.68-0.73). Our findings indicate that prosodic planning is deficient in patients with MS-CI and that the scope of planning depends on patients' cognitive abilities. We discuss how speech-based approaches could be used as an ecological method for the assessment and monitoring of CI in MS.

Long-term GPi-DBS improves motor features in myoclonus-dystonia and enhances social adjustment.

BACKGROUND: Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with ε-sarcoglycan (DYT11)-positive myoclonus-dystonia. METHODS: Consecutive myoclonus-dystonia patients with ε-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. RESULTS: Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. CONCLUSIONS: GPi-DBS seems to be a safe and efficacious treatment for medically refractory ɛ-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.

Deep brain stimulation does not enhance neuroinflammation in multiple system atrophy.

Slowly progressive, levodopa-responsive multiple system atrophy (MSA) may be misdiagnosed as Parkinson's disease (PD). Deep brain stimulation (DBS) is mostly ineffective in these patients and may even worsen the clinical course. Here we assessed whether neuropathological differences between patients with MSA who were treated with DBS of the subthalamic nucleus because of a misleading clinical presentation and typical disease cases may explain the more benign disease course of the former, and also the rapid clinical decline after surgery. The post-mortem assessment included the subthalamic nucleus, the globus pallidus, the thalamus and the putamen in five patients with MSA who received DBS and nine typical disease cases. There was no evidence for distinct neuroinflammatory profiles between both groups that could be related to the surgical procedure or that could explain the rapid clinical progression during DBS. Patients who received deep brain stimulation displayed a higher proportion of α-synuclein bearing neuronal cytoplasmic inclusions in the putamen compared with typical cases, while the number of surviving neurons was not different between groups. Our findings suggest that DBS does not induce neuroinflammatory changes in patients with MSA, at least several years after the surgery. We further hypothesize that the peculiar pattern of α-synuclein pathology may contribute to differences in the clinical phenotype, with a greater proportion of neuronal inclusions in the putamen being associated to a milder, "PD-like" phenotype with sustained levodopa response and slower disease progression.

Dysarthria in individuals with Parkinson's disease: a protocol for a binational, cross-sectional, case-controlled study in French and European Portuguese (FraLusoPark).

INTRODUCTION: Individuals with Parkinson's disease (PD) have to deal with several aspects of voice and speech decline and thus alteration of communication ability during the course of the disease. Among these communication impairments, 3 major challenges include: (1) dysarthria, consisting of orofacial motor dysfunction and dysprosody, which is linked to the neurodegenerative processes; (2) effects of the pharmacological treatment, which vary according to the disease stage; and (3) particular speech modifications that may be language-specific, that is, dependent on the language spoken by the patients. The main objective of the FraLusoPark project is to provide a thorough evaluation of changes in PD speech as a result of pharmacological treatment and disease duration in 2 different languages (French vs European Portuguese). METHODS AND ANALYSIS: Individuals with PD are enrolled in the study in France (N=60) and Portugal (N=60). Their global motor disability and orofacial motor functions is assessed with specific clinical rating scales, without (OFF) and with (ON) pharmacological treatment. 2 groups of 60 healthy age-matched volunteers provide the reference for between-group comparisons. Along with the clinical examinations, several speech tasks are recorded to obtain acoustic and perceptual measures. Patient-reported outcome measures are used to assess the psychosocial impact of dysarthria on quality of life. ETHICS AND DISSEMINATION: The study has been approved by the local responsible committees on human experimentation and is conducted in accordance with the ethical standards. A valuable large-scale database of speech recordings and metadata from patients with PD in France and Portugal will be constructed. Results will be disseminated in several articles in peer-reviewed journals and in conference presentations. Recommendations on how to assess speech and voice disorders in individuals with PD to monitor the progression and management of symptoms will be provided. TRIAL REGISTRATION NUMBER: NCT02753192, Pre-results.

Quality of life in Parkinson's disease improved by apomorphine pump: the OPTIPUMP cohort study.

To report on OPTIPUMP, a cohort study, investigating the impact in real-life clinical settings of continuous subcutaneous apomorphine infusion (CSAI) on the quality of life (HRQoL) of patients with Parkinson's disease. OPTIPUMP was a prospective, open-label, observational cohort study involving 30 investigational sites in France. CSAI was proposed as part of routine clinical care to patients aged ≥18 years, in absence of dementia, with a PD diagnosis and based on the presence of motor fluctuations not controlled by oral treatments. The impact of APO-pump on quality of life was evaluated as the difference in PDQ-39 scores between the initiation treatment and the follow-up visit after 6 months' treatment. All adverse events were recorded. Hyper- and hypodopaminergic behavioral tolerance was assessed on the Ardouin Scale of Behavior in Parkinson's Disease. Between September 2011 and January 2013, we enrolled 142 patients: 42 patients were withdrawn due to pump removal (33), death (4), lost of follow-up (4), no available data (1). 100 completed the study. At 6 months, their HRQoL had significantly improved (p = 0.011), as had their total UPDRS score (p < 0.001). Regarding the safety profile, Ardouin scale scores indicated that their hyperdopaminergic behaviors had not increased. CSAI had a favorable impact on HRQoL, with benefits outweighing risks. The analysis of the withdrawn patients highlights the heterogeneity of the use of the pump having an impact on its efficacy and tolerability.

Outcome of deep brain stimulation in slowly progressive multiple system atrophy: A clinico-pathological series and review of the literature.

OBJECTIVES: To highlight the risk of clinical worsening after deep brain stimulation in histologically proven multiple system atrophy (MSA) patients presenting slow and relatively benign disease progression mimicking Parkinson's disease (PD). In such cases but also in more typical MSA patients, the results of deep brain stimulation have been mostly reported as case reports and small patient series. METHODS: The present study describes the outcome of the largest series of histologically proven MSA patients who underwent deep brain stimulation (DBS) of the subthalamic nucleus because they were considered as having PD at the time of surgery. RESULTS: Three patients showed significant improvement of motor signs after surgery while two did not. Clinical improvement was short-lasting and rapidly followed by the occurrence of disabling manifestations of MSA that counteracted DBS benefits. CONCLUSIONS: Together with previous reports, our study demonstrates that DBS should not be recommended for MSA patients. It also underlines that detecting subtle red flags is crucial to avoid DBS surgery in this population.

Theory of mind in Alzheimer disease: Evidence of authentic impairment during social interaction.

OBJECTIVE: The present study aimed to investigate theory of mind (the ability to infer others' mental states) deficit in 20 patients with mild Alzheimer's disease and 20 healthy controls, with 2 theory of mind tasks, 1 of them being a real interactive task. Previous results concerning preserved or altered theory of mind abilities in Alzheimer's disease have been inconsistent and relationships with other cognitive dysfunctions (notably episodic memory and executive functions) are still unclear. METHOD: The first task we used was a false belief paradigm as frequently used in literature whereas the second task, a referential communication task, assessed theory of mind in a real situation of interaction. Participants also underwent neuropsychological evaluation to investigate potential relationships between theory of mind and memory deficits. RESULTS: The results showed that Alzheimer patients presented a genuine and significant theory of mind deficit compared to control participants characterized notably by difficulties to attribute knowledge to an interlocutor in a real social interaction. CONCLUSION: These results further confirm that theory of mind is altered in early stages of Alzheimer dementia which is consistent with previous works. More specifically, this study is the first to objectivize this impairment in social interaction.

Different Patterns of Theory of Mind Impairment in Mild Cognitive Impairment.

Theory of Mind refers to the ability to infer other's mental states, their beliefs, intentions, or knowledge. To date, only two studies have reported the presence of Theory of Mind impairment in mild cognitive impairment (MCI). In the present study,we evaluated 20 MCI patients and compared them with 25 healthy control participants using two Theory of Mind tasks. The first task was a false belief paradigm as frequently used in the literature, and the second one was a referential communication task,assessing Theory of Mind in a real situation of interaction and which had never been used before in this population. The results showed that MCI patients presented difficulties inferring another person's beliefs about reality and attributing knowledge to them in a situation of real-life interaction. Two different patterns of Theory of Mind emerged among the patients. In comparison with the control group, some MCI patients demonstrated impairment only in the interaction task and presented isolated episodicmemory impairment, while others were impaired in both Theory of Mind tasks and presented cognitive impairment impacting both episodic memory and executive functioning. Theory of Mind is thus altered in the very early stages of cognitive impairment even in real social interaction, which could impact precociously relationships in daily life.

From micrographia to Parkinson's disease dysgraphia.

Micrographia, an abnormal reduction in writing size, is a specific behavioral deficit associated with Parkinson's disease (PD). In recent years, the availability of graphic tablets has made it possible to study micrographia in unprecedented detail. Consequently, a growing number of studies show that PD patients also exhibit impaired handwriting kinematics. Is micrographia still the most characteristic feature of PD-related handwriting deficits? To answer this question, we identified studies that investigated handwriting in PD, either with conventional pencil-and-paper measures or with graphic tablets, and we reported their findings on key spatiotemporal and kinematic variables. We found that kinematic variables (velocity, fluency) differentiate better between control participants and PD patients, and between off- and on-treatment PD patients, than the traditional measure of static writing size. Although reduced writing size is an important feature of PD handwriting, the deficit is not restricted to micrographia stricto sensu. Therefore, we propose the term PD dysgraphia, which encompasses all deficits characteristic of Parkinsonian handwriting. We conclude that the computerized analysis of handwriting movements is a simple and useful tool that can contribute to both diagnosis and follow-up of PD.

Withdrawing amantadine in dyskinetic patients with Parkinson disease: the AMANDYSK trial.

OBJECTIVE: The AMANDYSK trial was designed to assess long-term efficacy of chronic treatment with amantadine in patients with Parkinson disease (PD) and levodopa-induced dyskinesia (LID). METHODS: This was a 3-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group, wash-out study conducted in 57 amantadine-treated (≥200 mg/d for ≥6 months) dyskinetic patients with PD. The primary outcome measure was the change from baseline in a Unified Parkinson's Disease Rating Scale (UPDRS) dyskinesia subscore (items 32 [duration] + 33 [severity]). Secondary outcomes included other LID measurements ("responders" analysis, premature dropout for LID, Abnormal Involuntary Movement Scale). Exploratory outcomes included time with troublesome dyskinesia as measured by diaries, UPDRS Motor Examination (part III) for motor symptoms of PD, and fatigue and apathy scores for nonmotor symptoms. RESULTS: UPDRS items 32 + 33 deteriorated more in patients switched to placebo ("discontinuing" group) (+1.7 ± 2.0 units; 95% confidence interval 0.9, 2.4) as compared with those maintained on amantadine ("continuing" group) (+0.2 ± 1.5 units; 95% confidence interval -0.4, 0.8; p = 0.003). Secondary outcomes confirmed this difference because there were significantly more responders, more dropouts for LID, greater increase in "ON" time with troublesome dyskinesia, and greater worsening of Abnormal Involuntary Movement Scale score in the discontinuing group. There were no between-group differences in the UPDRS Motor Examination, whereas apathy (as measured by caregivers) and fatigue scores tended to worsen more in patients randomized to placebo. CONCLUSION: Wash-out of amantadine in dyskinetic patients with PD significantly worsened LID. No significant effect was observed on motor parkinsonian symptoms, while exploratory outcomes suggested that amantadine might improve apathy and fatigue in such patients. CLASSIFICATION OF EVIDENCE: This article provides Class II evidence that in patients with PD, withdrawing amantadine significantly aggravates LID in a median time of 7 days.

Using memories to understand others: the role of episodic memory in theory of mind impairment in Alzheimer disease.

Theory of mind (TOM) refers to the ability to infer one's own and other's mental states. Growing evidence highlighted the presence of impairment on the most complex TOM tasks in Alzheimer disease (AD). However, how TOM deficit is related to other cognitive dysfunctions and more specifically to episodic memory impairment - the prominent feature of this disease - is still under debate. Recent neuroanatomical findings have shown that remembering past events and inferring others' states of mind share the same cerebral network suggesting the two abilities share a common process .This paper proposes to review emergent evidence of TOM impairment in AD patients and to discuss the evidence of a relationship between TOM and episodic memory. We will discuss about AD patients' deficit in TOM being possibly related to their difficulties in recollecting memories of past social interactions.