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The emergency department remains the main method of admission for older people to hospital. The management of old elderly in these departments is a complex subject. It's particularities and the specificities of the evaluation of their health contribute to the difficulties of the care teams. For the elderly, a visit to the emergency room is a significant medical event in the care process that can have repercussions on their functional decline. The promotion of a geriatric culture in emergency departments is essential and can be done in different ways, but collaboration between emergency physicians and geriatricians remains essential for successful care adapted to the specific characteristics of elderly patients.

Mild cognitive impairment (MCI) in Parkinson’s disease (PD) includes deficits in theory of mind (ToM). However, associations between ToM and caregiver burden and distress are still unclear. The objective of this pilot study was to preliminarily explore the relation between ToM and caregiver burden and distress in a sample of PD-MCI patients. Twelve PD-MCI patients were evaluated on a ToM task (Faux Pas), whereas their caregivers were assessed on caregiver burden (Zarit Burden Interview-12 items) and distress (Neuropsychiatric Inventory–Distress). Cognitive ToM was significantly associated with caregiver distress, but caregiver burden was associated with the severity of patient psychiatric symptoms.

Background: SMPD1 (acid-sphingomyelinase) variants have been associated with Parkinson's disease in recent studies. The objective of this study was to further investigate the role of SMPD1 mutations in PD. Methods: SMPD1 was sequenced in 3 cohorts (Israel Ashkenazi Jewish cohort, Montreal/Montpellier, and New York), including 1592 PD patients and 975 controls. Additional data were available for 10,709 Ashkenazi Jewish controls. Acid-sphingomyelinase activity was measured by a mass spectrometry-based assay in the New York cohort. α-Synuclein levels were measured in vitro following CRISPR/Cas9-mediated knockout and siRNA knockdown of SMPD1 in HeLa and BE(2)-M17 cells. Lysosomal localization of acid-sphingomyelinase with different mutations was studied, and in silico analysis of their effect on acid-sphingomyelinase structure was performed. Results: SMPD1 mutations were associated with PD in the Ashkenazi Jewish cohort, as 1.4% of PD patients carried the p.L302P or p.fsP330 mutation, compared with 0.37% in 10,709 Ashkenazi Jewish controls (OR, 3.7; 95%CI, 1.6-8.2; P = 0.0025). In the Montreal/Montpellier cohort, the p.A487V variant was nominally associated with PD (1.5% versus 0.14%; P = 0.0065, not significant after correction for multiple comparisons). Among PD patients, reduced acid-sphingomyelinase activity was associated with a 3.5- to 5.8-year earlier onset of PD in the lowest quartile versus the highest quartile of acid-sphingomyelinase activity (P = 0.01-0.001). We further demonstrated that SMPD1 knockout and knockdown resulted in increased α-synuclein levels in HeLa and BE(2)-M17 dopaminergic cells and that the p.L302P and p.fsP330 mutations impair the traffic of acid-sphingomyelinase to the lysosome. Conclusions: Our results support an association between SMPD1 variants, acid-sphingomyelinase activity, and PD. Furthermore, they suggest that reduced acid-sphingomyelinase activity may lead to α-synuclein accumulation. © 2019 International Parkinson and Movement Disorder Society.

Purpose Studies have reported that clear speech has the potential to influence suprasegmental and segmental aspects of speech, in both healthy and dysarthric speakers. While the impact of clear speech has been studied on the articulation of individual segments, few studies have investigated its effects on coarticulation with multisegment sequences such as fricative–vowel. Objectives The goals of this study are to investigate, in healthy and dysarthric speech, the impact of clear speech on (a) the perception of anticipatory vowel coarticulation in fricatives and (b) the acoustic characteristics of this effect. Method Ten speakers with dysarthria secondary to idiopathic Parkinson's disease were recruited as well as 10 age- and sex-matched healthy speakers. A sentence reading task was performed in natural and clear speaking conditions. The sentences contained words with the initial fricatives /s/ and /ʃ/ preceded by /ə/ and followed by the vowels /i/, /y/, /u/, or /a/. For the perceptual measurements, five listeners were recruited and were asked to predict the upcoming word by listening only to the isolated fricative. Acoustic analyses consisted of spectral moment analysis (M1–M4) on averaged time series. Results Perceptual findings report that identification rates were improved with clear speech for the speakers with dysarthria, but only for the fricative–/i/ sequences. Error pattern analysis indicates that this improvement is associated with an increase in the roundness parameter (lip spreading) identification. Acoustic results are unclear for M1 and M3 but suggest that M2 and M4 differentiation between the rounded versus unrounded vowel contexts is increased with clear speech for the speakers with dysarthria. Discussion Taken together, these findings suggest that clear speech may improve lip coordination in dysarthric speakers with Parkinson's disease. However, the impact of clear speech on the acoustic measures of fricative spectral moments is somewhat limited. This suggests that these metrics, when taken individually, do not capture the entire complexity of fricative–vowel coarticulation.

Introduction:Symptoms of cervical dystonia (CD) can vary in severity and cause significant pain. OnabotulinumtoxinA is an approved treatment for CD. This study assessed health-related quality of life (HRQoL) in patients with CD who received multiple onabotulinumtoxinA treatments.Methods:This prospective, observational standard-of-care study was conducted at multiple neurology centers in Québec, Canada. Patients reported the health impact of CD using the Cervical Dystonia Impact Profile (CDIP)-58, before and after up to eight onabotulinumtoxinA treatments. Other measures included the Cervical Dystonia Severity Rating Scale by physician, employment status using the Work Productivity Questionnaire and pain using the Pain Numeric Rating Scale (PNRS). Adverse events (AEs) were recorded.Results:Sixty-two patients were enrolled (safety population, n = 61; modified efficacy population, n = 58). Participants were mostly females who were employed; most (79.3%) had torticollis. In all, 21/62 patients (33.9%) discontinued the study. At the final visit, there was a statistically significant (p < 0.001) improvement in all eight CDIP-58 subscales, particularly head and neck symptoms (−31.0) and psychosocial functioning (−28.2). Employment increased from baseline (55%) to the end of the study (64%), and there was improvement in work productivity. There was a significant (p < 0.0001) reduction in pain measured by the PNRS, from −0.5 post-treatment 1 to −2.4 at end of study. AEs (neck pain, muscular weakness, dysphagia, nausea) were consistent with onabotulinumtoxinA use.Conclusion:These real-world data indicate that after repeated, long-term use, onabotulinumtoxinA continues to be a safe and effective treatment for CD, improving HRQoL and work productivity.

Introduction As there is currently no pharmacological treatment for Parkinson’s Disease Mild Cognitive Impairment (PD-MCI) with executive dysfunctions, specific cognitive interventions must be investigated. Most previous studies have tested bottom-up cognitive training programs but have not shown very good results. Objectives The aim of this study was to test ease of implementation, differential safety and preliminary efficacy of two top-down (strategy-learning) home-based, individualized, cognitive interventions: Goal Management Training (GMT), adapted for PD-MCI (Adapted-GMT), and a psychoeducation program combined with mindfulness exercises (PSYCH-Mind). Methods This was a single-blind block-randomized between-group comparative study. Twelve PD-MCI with mild executive dysfunctions were divided in four blocks and randomly assigned to any of the two interventions. The participants were included if they had PD-MCI diagnosis (no dementia), with stabilized medication. Both groups (Adapted-GMT and PSYCH-mind) received five intervention sessions each lasting 60–90 minutes for five weeks. Measures were collected at baseline, mid-point, one-week, four-week and 12-week follow-ups. Executive functions were assessed with the Dysexecutive questionnaire (DEX) and the Zoo Map Test (ZMT). Quality of life (QoL) and psychiatric symptoms were also evaluated. Repeated measures ANCOVAs (mixed linear analysis) were applied to all outcomes. Results There was one drop out, and both interventions were feasible and acceptable. Despite the small sample size limiting statistical power, patients of both groups significantly improved executive functions per the DEX-patient (Time: F(4,36) = 2.96, p = 0.033, CI95%: 10.75–15.23) and DEX-caregiver scores (Time: F(4,36) = 6.02, p = 0.017, CI95%: 9.63–17.23). Both groups significantly made fewer errors between measurement times on the ZMT (Time: F(3,36) = 16.66, p = 0.001, CI95%: 1.07–2.93). However, QoL significantly increased only in PSYCH-Mind patients at four-week follow-up (interaction Time*Group: F(4,36) = 5.31, p = 0.002, CI95%: 15.33–25.61). Conclusion Both interventions were easily implemented and proved to be safe. Because both interventions are arguably cost-effective, these pilot findings, although promising, need to be replicated in large samples. ClinicalTrials.gov Identifier NCT04636541.

Approximately 30% of patients with Parkinson's disease experience mild cognitive impairment (PD-MCI), often affecting executive functions. Our objective was to assess tolerability, safety and preliminarily efficacy of Goal Management Training® (GMT) for PD-MCI. GMT was administered at home, for five weeks. Dysexecutive Questionnaire (DEX), Parkinson Disease Questionnaire (PDQ-39), Zoo Map Test and Dementia Rating Scale-II were administered before, one and four weeks after Adapted-GMT. Reliable Change Index (RCI) was calculated. One participant completed GMT with caregiver. Executive complaints decreased (DEX RCIs between -2.10 and -1.68), PDQ-39 was maintained (RCI = -0.18). Adapted-GMT seems safe for PD-MCI, but efficacy remains doubtful.

Background Clinical and anecdotal observations propose that patients with Parkinson's disease (PD) may show drug-induced dyskinesia (DID) concomitantly with cardinal motor features. However, the extent of the concomitant presence of DID and cardinal features remains to be determined. Objectives This cross-sectional study measured peak-dose choreic-type DID in a quantitative manner in patients diagnosed with PD, and determined whether symptoms such as tremor, bradykinesia, rigidity, postural instability or freezing of gait (FoG) were still detectable in these patients. Methods 89 patients diagnosed with PD were recruited and assessed using a combination of quantitative measures using inertial measurement units to capture DID, tremor, bradykinesia, and FoG. Clinical evaluations were also used to assess rigidity and postural instability. Motor symptoms of PD were assessed 3 times during the testing period, and a series of activities of daily living were repeated twice, in between clinical tests, during which the level of DID was quantified. Peak-dose was identified as the period during which patients had the highest levels of DID. Levels of tremor, rigidity, bradykinesia, postural instability, and FoG were used to determine the percentage of patients showing these motor symptoms simultaneously with DID. Results 72.4% of patients tested presented with measurable DID during the experiment. Rest, postural and kinetic tremor (12.7% , 38.1% , and 15.9% respectively), bradykinesia (28.6% ), rigidity (55.6% ), postural instability (71.4% ) and FoG (9.5% ) were detected simultaneously with DID. Conclusions PD symptomatology remains present in patients showing peak-dose choreic-type DID, illustrating the challenge facing physicians when trying to avoid dyskinesia while attempting to alleviate motor symptoms.

ObjectivesObjectives Hypertension, dyslipidemia, diabetes, and obesity are well-established risk factors for cognitive impairment and dementia in older adults. In contrast, previous studies that have assessed the impact of vascular risk factors (VRFs) on cognition in Parkinson's disease (PD) have had methodological limitations and reported conflicting findings. We address this question in a large well-characterized cohort of de novo PD patients. Methods A total of 367 untreated and non-demented patients aged 50 years and older with early PD (H&Y = 1.0–2.0) underwent a comprehensive clinical and neuropsychological assessment at baseline and 24 months later. A series of linear mixed models were used to determine the effects of VRFs on cognition while controlling for patient and disease characteristics. The outcomes included norm-referenced Z-scores of global cognition, visuospatial skills, verbal episodic memory, semantic verbal fluency, attention, and working memory tests. Results A longer history of hypertension and a higher pulse pressure were significant predictors of lower Z-scores on immediate and delayed free recall, recognition, and verbal fluency tests. On average, every 10 mmHg increase in pulse pressure was associated with a 0.08 reduction on the cognitive Z-scores. The effects were independent of age, education, disease duration, motor impairment, medication, and depressive symptoms. Other VRFs were not associated with cognitive outcomes. Conclusions Our results are consistent with previous studies suggesting that hypertension exerts a detrimental effect on memory and verbal fluency in early PD. Management of blood pressure and cardiovascular health may be important to reduce risk of cognitive decline in PD. Copyright © 2017 John Wiley & Sons, Ltd.

This single-case research-designed study explored whether intermittent theta-burst stimulation (iTBS) of the right dorsolateral prefrontal cortex (DLPFC) could improve metaphor comprehension in people with Parkinson disease (PD) and language impairments. A right-handed participant with PD diagnosed 9 years ago, receiving long-term treatment with levodopa, and with metaphor comprehension impairment was recruited to undergo 10 sessions of sham stimulation (in 2wk), a washout period (6wk), and then 10 sessions of iTBS (in 2wk). Clinical scores of metaphor comprehension and motor evaluation (Unified Parkinson Disease Rating Scale part III) and transcranial magnetic stimulation to test the excitability of the primary motor cortex (M1) were used at baseline, postsham, post-iTBS, and at 3 follow-ups (8, 14, and 20wk post-iTBS). Metaphor comprehension was improved after iTBS, and the highest scores were obtained 8 weeks later (P=.01). This improvement was correlated with the increase of the right M1 excitability (r=-.86, P=.03) and with the decrease of transcallosal inhibition latency from the left to the right hemisphere (r=-.88, P=.02). Sham yielded no effect (P>.05). Administration of iTBS over the right DLPFC improved metaphor comprehension likely by a long-term influence on brain synaptic plasticity, including improvement of interhemispheric dialogue. More studies are warranted to confirm these findings in larger samples of participants with PD.

Treatment-resistant seizures affect about a third of patients suffering from epilepsy. To fulfill the need for new medications targeting treatment-resistant seizures, a number of rodent models offer the opportunity to assess a variety of potential treatment approaches. The use of such models, however, has proven to be time-consuming and labor-intensive. In this study, we performed pharmacological characterization of the allylglycine (AG) seizure model, a simple in vivo model for which we demonstrated a high level of treatment resistance. ( d , l )-Allylglycine inhibits glutamic acid decarboxylase (GAD) – the key enzyme in γ-aminobutyric acid (GABA) biosynthesis – leading to GABA depletion, seizures, and neuronal damage. We performed a side-by-side comparison of mouse and zebrafish acute AG treatments including biochemical, electrographic, and behavioral assessments. Interestingly, seizure progression rate and GABA depletion kinetics were comparable in both species. Five mechanistically diverse antiepileptic drugs (AEDs) were used. Three out of the five AEDs (levetiracetam, phenytoin, and topiramate) showed only a limited protective effect (mainly mortality delay) at doses close to the TD50 (dose inducing motor impairment in 50% of animals) in mice. The two remaining AEDs (diazepam and sodium valproate) displayed protective activity against AG-induced seizures. Experiments performed in zebrafish larvae revealed behavioral AED activity profiles highly analogous to those obtained in mice. Having demonstrated cross-species similarities and limited efficacy of tested AEDs, we propose the use of AG in zebrafish as a convenient and high-throughput model of treatment-resistant seizures.

The purpose of this study was to investigate the impact of the Lee Silverman Voice Treatment (LSVT®) on vowel articulation and consonant-vowel (C-V) coarticulation in dysarthric speakers with Parkinson's disease (PD). Nine Quebec French speakers diagnosed with idiopathic PD underwent the LSVT®. Speech characteristics were compared before and after treatment. Vowel articulation was measured using acoustic vowel space and calculated with the first (F1) and second formant (F2) of the vowels /i/, /u/ and /a/. C-V coarticulation was measured using locus equations, an acoustic metric based on the F2 transitions within vowels in relation to the preceding consonant. The relationship between these variables, speech loudness and vowel duration was also analysed. Results showed that vowel contrast increased in F1/F2 acoustic space after administration of the LSVT®. This improvement was associated with the gain in speech loudness and longer vowel duration. C-V coarticulation patterns between consonant contexts showed greater distinctiveness after the treatment. This improvement was associated with the gain in speech loudness only. These results support the conclusions of previous studies investigating the relationship between the LSVT®, speech loudness and articulation in PD. These results expand clinical understanding of the treatment and indicate that loud speech changes C-V coarticulation patterns. Clinical applications and theoretical considerations are discussed.

Metaphoric language is used every day. The manner in which a metaphor is understood may depend on different factors such as polysemy (the property of a word to have multiple related meanings). Polysemy may have an impact on metaphor comprehension particularly in individuals with executive impairments such as patients with Parkinson's disease (PD). The goal of this study was to investigate the influence of polysemy on metaphor comprehension processing in PD and healthy matched controls. Twenty individuals with PD and twenty controls completed a metaphor comprehension task including metaphors build with a polysemous (MP) and non-polysemous word (MNP). Both groups made significantly more comprehension errors and took significantly longer to understand MNP than MP, suggesting that polysemy has the same effect on metaphor comprehension regardless of the group. Interestingly, a comprehension impairment was observed in the PD group for both types of metaphors, indicating that polysemy does not seem to influence the metaphor comprehension deficit in PD. Further investigations are needed to better understand this finding.

Theory of mind (TOM), i.e. the capacity to attribute mental states to oneself and others, would be impaired in Parkinson's disease (PD). Nonliteral language (NLL) comprehension would also be impaired in this disease. The goal of this study was to verify the presence of an association between the TOM and NLL comprehension deficits. We assessed 15 individuals in the early stages of PD and 17 healthy controls (HC), comparable on gender, age and education. Each subject completed a TOM evaluation task and a NLL task (i.e. metaphor comprehension). They also completed executive functioning (mental flexibility, inhibition and working memory) evaluation tasks. Our results showed that patients with PD had significant difficulties in the TOM and NLL comprehension tasks compared to HC participants. A significant relationship was found between TOM and NLL comprehension results. Moreover, NLL scores were associated with a task evaluating mental flexibility. Thus, PD might cause both TOM and NLL comprehension deficit even in the early stages of the disease. Our results showed that there would be a close relationship between TOM and NLL in people with PD.

Hypertension, dyslipidemia, diabetes, and obesity are well-established risk factors for cognitive impairment and dementia in older adults. In contrast, previous studies that have assessed the impact of vascular risk factors (VRFs) on cognition in Parkinson's disease (PD) have had methodological limitations and reported conflicting findings. We address this question in a large well-characterized cohort of de novo PD patients.A total of 367 untreated and non-demented patients aged 50 years and older with early PD (HY = 1.0-2.0) underwent a comprehensive clinical and neuropsychological assessment at baseline and 24 months later. A series of linear mixed models were used to determine the effects of VRFs on cognition while controlling for patient and disease characteristics. The outcomes included norm-referenced Z-scores of global cognition, visuospatial skills, verbal episodic memory, semantic verbal fluency, attention, and working memory tests.A longer history of hypertension and a higher pulse pressure were significant predictors of lower Z-scores on immediate and delayed free recall, recognition, and verbal fluency tests. On average, every 10 mmHg increase in pulse pressure was associated with a 0.08 reduction on the cognitive Z-scores. The effects were independent of age, education, disease duration, motor impairment, medication, and depressive symptoms. Other VRFs were not associated with cognitive outcomes.Our results are consistent with previous studies suggesting that hypertension exerts a detrimental effect on memory and verbal fluency in early PD. Management of blood pressure and cardiovascular health may be important to reduce risk of cognitive decline in PD. Copyright © 2017 John WileySons, Ltd.

The utility of the Mattis Dementia Rating Scale 2 (MDRS-2) in screening for dementia in Parkinson disease (PD) is well documented. However, little is known about its sensitivity to mild cognitive impairment in PD (PD-MCI). This study sought to document the validity of the MDRS-2 for diagnoses of PD-MCI and dementia in PD (PDD). Twenty-two healthy controls (HCs), 22 PD-MCI, and 16 PDD were compared on each MDRS-2 subscales and MDRS-2 total standard scores. Patients with PDD performed significantly worse than the other groups (all Ps < .05) on the MDRS-2 total and on all subscales, except attention. PD-MCI had significant lower scores than HCs on the MDRS-2 total and on initiation/perseveration and memory subscales. The optimal cutoff score for PD-MCI diagnosis was ≤ 140/144 and ≤ 132/144 for PDD. These findings suggest that MDRS-2 is a useful tool to identify dementia but that there might be a ceiling effect in the MDRS-2 cutoff score to diagnose MCI in PD.

Identifying patients at higher risk of developing dementia is important. The usefulness of the Mattis Dementia Rating scale-Second Edition (MDRS-2) to detect and differentiate between patients with amnestic mild cognitive impairment (A-MCI), Parkinson’s disease and MCI (PD-MCI), PD with dementia (PDD), and Alzheimer’s disease (AD) was investigated. In all, 22 healthy controls (HC), 22 A-MCI, 22 PD-MCI, 16 PDD, and 22 AD patients were evaluated using an extensive neuropsychological battery, including the MDRS-2. The MDRS-2 total standardized score detected all groups of patients. The dementia groups performed worse than HC on the 5 MDRS-2 subscales. Alzheimer’s disease patients scored higher than PDD on MDRS-2 conceptualization and lower on memory. Healthy controls were better than PD-MCI on MDRS-2 initiation/perseveration and memory and better than A-MCI on memory. No difference was found between the MCI groups. The MDRS-2 is a suitable short scale for MCI and dementia screening but is not specific enough to differentiate between A-MCI and PD-MCI.

International audience; Neurostimulation represents an interesting alternative therapy for patients resistant to drug treatment or who cannot benefit from resective surgery. Theoretically, neurostimulation allows the control of seizures to be tailored to the individual patient and specific form of epilepsy. Here, we review both experimental and clinical studies that have reported the possible control of epileptic seizures by means of different approaches using electrical stimulation (vagus nerve stimulation, deep brain stimulation and repetitive transcranial magnetic stimulation). The rationale for targeting specific areas that have thus far been considered (i.e., vagus nerve, cerebellum, anterior or centromedial thalamus, basal ganglia, cortex and temporal lobe) is addressed in the light of experimental data and clinical effectiveness in different models and forms of epilepsy. The type of seizures that can be considered for neurostimulation, as well as the optimal parameters such as stimulation frequency and modes of stimulation (chronic, continuous or adaptative), are discussed to determine the best candidates for such a therapeutic strategy. This review points out the need for improved knowledge of neural circuits that generate seizures and/or allow their propagation, as well as a better understanding of the mechanisms of action of neurostimulation.

Patients with Parkinson's disease (PD) are more likely to suffer from cognitive impairment and dementia than healthy older adults. The aim of this study was to investigate smoking history as a risk factor for cognitive decline in PD.One hundred thirty-nine PD patients aged 50 years and older (Hoehn and Yahr = 1-3) were recruited from a clinical database. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE) and smoking history was investigated as part of a standard clinical interview. A multiple linear regression analysis was used to develop a model for predicting participants' MMSE scores from age, education, Hoehn and Yahr stage, disease duration, the number of vascular risk factors and the number of smoking pack-years.The regression model significantly accounted for 22.9% of the variance in MMSE scores. Significant predictors were education (β = .312, p.001), age (β = -.215, p = .013) and total smoking pack-years (β = -.180, p = .029). In former smokers, the number of years since quitting had no effect on global cognition and there were no significant difference between patients who had quit smoking more than 10 years ago and those who had quit less than 10 years ago, F(1, 63) = 1.72, p = .195.Smoking history was associated to global cognitive impairment in PD even in patients who had quit smoking. These results are in line with findings in healthy older adults that have linked smoking to cognitive impairment, global brain atrophy and functional changes. Future studies should consider a broader assessment of cognitive functions.

Human T-cell leukemia virus type I (HTLV-I) transcription generally depends on the ability of the viral Tax protein to bind the CREB transcription factor and form an active complex by recruiting CBP/p300 coactivators to the long terminal repeat (LTR). Studies have demonstrated that T-cell activating agents that stimulate CREB are potent inducers of HTLV-I transcription. Herein, we demonstrate that bpV[pic], a protein tyrosine phosphatase (PTP) inhibitor activates the HTLV-I LTR in the presence and absence of Tax expression. Optimal activation occurred at 8 h and was synergistic with forskolin or PGE(2). Infected cell lines and cells transfected with HTLV-I proviral DNA were equally responsive to the synergistic effect of bpV and forskolin on HTLV-I gene expression. Activation of the LTR by bpV[pic] was T-cell receptor-independent, but required ZAP70, calcineurin activity and functional calcium entry. Inhibition of the SHP-1 PTP was suggested to be important. Transfection experiments with a CREB dominant-negative mutant and with isolated TRE1- or CREB-responsive reporter constructs and treatment with the MDL-12,330A adenylate cyclase inhibitor all supported the involvement of a CREB/ATF family member in this bpV-dependent activation of the HTLV-I LTR, although CREB itself did not seem to be involved. Analysis of HTLV-I reporter constructs containing mutated CREB-binding sites also implied the involvement of another element in this activation. These results demonstrate for the first time a powerful effect of PTP inhibitors on HTLV-I LTR activity and suggest participation of both CREB-dependent and -independent pathways in this activation.

Dystonia is a syndrome of sustained muscular contractions with numerous underlying etiologies. This review examines the varied phenomenology of dystonias, its evolving classification including recent genetic data as well as its clinical investigation and treatment. Although age of onset, anatomical distribution and family history are key elements of the investigation of dystonia, classification increasingly relies on etiologic and genetic criteria. Physiological abnormalities in striatocortical circuits are common in dystonia but the pathophysiology is still unclear. In recent years, a great deal has been learned on the more common primary dystonias such as primary torsion dystonia and on dystonia-plus syndromes such as dopamine responsive dystonia. Treatment of dystonia has also evolved and there are now a number of therapeutic agents with clear beneficial effects including anticholinergics, benzodiazepines, and botulinum toxin and there is growing interest in neurofunctional surgery including deep brain stimulation.

The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD) on different language abilities are still controversial and its impact on high-level language abilities such as metaphor comprehension has been overlooked. The aim of this study was to determine the effects of STN electrical stimulation on metaphor comprehension and language abilities such as lexical and semantic capacities. Eight PD individuals with bilateral STN-DBS were first evaluated OFF-DBS and, at least seven weeks later, ON-DBS. Performance on metaphor comprehension, lexical decision, word association and verbal fluency tasks were compared ON and OFF-DBS in addition to motor symptoms evaluation. STN stimulation had a significant beneficial effect on motor symptoms in PD. However, this stimulation did not have any effect on metaphor comprehension or any other cognitive ability evaluated in this study. These outcomes suggest that STN stimulation may have dissociable effects on motor and language functions.

Wernicke’s Encephalopathy (WE) is a preventable neurologic condition characterized by altered mental status, ophthalmoplegia, and ataxia. Although historically associated with alcoholism, a few authors have described WE in patients with non-alcohol related psychiatric disorders. We report herein the case of a 36-year-old young man with paranoid schizophrenia who was brought to hospital for confusion and difficulties with his vision. His roommate said he had gone about thirty days without eating ‘…because he was on a slimming cure’. History and physical examination suggested WE as a result of isolation and poor diet leading to nutritional deficiency. This was confirmed by brain magnetic resonance imaging showing classic thalamic, mammillary bodies and brainstem lesions. Of note, his cognitive profile was far more heterogeneous than what had classically been described in the literature and involved both cortical and subcortical pathology, generating memory but also significant executive deficits. Intravenous treatment with thiamine was given and our patient showed mild improvements in visual acuity and nystagmus. However, persistent cognitive and physical disabilities consistent with Korsakoff syndrome remained, and he now lives in a supervised home. This case illustrates the tragic consequences of nutritional deficiencies in a patient with paranoid schizophrenia. The threshold to suspect WE in schizophrenic patients should be lowered and in doubt prophylactic parenteral thiamine should be administered.

In the paper titled “Changes in Vowel Articulation with Subthalamic Nucleus Deep Brain Stimulation in Dysarthric Speakers with Parkinson's Disease,” in Section 2.3.1, the authors cited incorrectly a study by Sapir and colleagues [10]. The correct reference should have been “S. Sapir, L. O. Ramig, J. L. Spielman, and C. Fox, ‘Formant centralization ratio: a proposal for a new acoustic measure of dysarthric speech,' Journal of Speech, Language and Hearing Research, vol. 53, no. 1, pp. 114–125, 2010. doi: 10.1044/1092-4388 (2009/08-0184).”