Diagnostic value of vietnamese smell identification test in Parkinson's disease.

INTRODUCTION: The Vietnamese Smell Identification Test (VSIT) has been validated in determining olfactory dysfunction in the Vietnamese population; however, its value in diagnosing Parkinson's disease (PD) has not been established. METHODS: This case-control study was conducted at University Medical Center HCMC, Ho Chi Minh City, Vietnam. The study sample included non-demented PD patients and healthy controls (HC) who were gender- and age-matched. All participants were evaluated for odor identification ability using the VSIT and the Brief Smell Identification Test (BSIT). RESULTS: A total of 218 HCs and 218 PD patients participated in the study. The median VSIT and BSIT scores were significantly different between PD and HC groups (VSIT, 5 (3) vs. 9 (2), P < 0.0001; BSIT, 6 (3) vs 8 (2), P < 0.0001). Using the cut-off of <8 for correct answers out of 12 odorants, the VSIT had higher sensitivity (84.4%) and specificity (86.2%) than those of the BSIT (sensitivity of 81.7% and specificity of 69.3%) for the diagnosis of PD. The area under the curve (AUC) value was greater for the VSIT than for the BSIT (0.909 vs 0.818). The smell identification scores were not significantly correlated with disease duration, disease severity, or LEDD (all p > 0.05). CONCLUSION: The VSIT can be a valuable ancillary tool for supporting the diagnosis of PD in Vietnam. Olfactory dysfunction in PD was unrelated to the disease duration and severity. The VSIT can be applied to improve the accuracy of clinical PD diagnosis.

Pain is common in early onset Parkinson's disease and pain severity is associated with age and worsening of motor and non-motor symptoms.

The consequences of pain in early onset Parkinson's disease (EOPD) remain under appreciated even though pain may exert an increasingly negative impact on patient quality of life as motor and non-motor symptoms worsen. In this prospective study, we investigate the prevalence and severity of pain in 135 Vietnamese patients with EOPD from three medical centers using the King's PD Pain Scale (KPPS), the Mini Mental Status Exam (MMSE), the Unified Parkinson's Disease Rating Scale (UPDRS) and the Non-Motor Symptoms Scale (NMSS). Pain was reported by 79.3%. The most common subtype of pain was musculoskeletal (70.1%), followed by nocturnal (43.9%), radicular (43.0%), chronic (42.1%), fluctuation-related (34.6%) and orofacial pain (16.8%). Most patients (74.8%) experienced more than one pain subtype. Fluctuation-related pain and orofacial pain were significantly more prevalent among patients with higher Hoehn & Yahr (H&Y) stages (3-5) versus lower H&Y stages (1-2). Pain subtype and severity were not significantly related to gender or age of PD onset. Patients with H&Y stages 3-5 had statistically significantly higher KPPS scores for fluctuation-related pain (p = 0.018) and radicular pain (p = 0.026). Independent associations were found between pain severity and age (p = 0.028), depression severity (p = 0.018), perceptual problems/hallucinations (p = 0.033) and sexual function (p = 0.024). Patients with depression and higher H&Y stages (3-5) had statistically significantly higher mean KPPS scores versus patients without depression and at lower H&Y stages (1-2). Pain may be more common and severe in EOPD patients than previously appreciated. Older age, depression, perceptual problems/hallucinations and sexual dysfunction were independently associated with higher pain severity.

Normative data for the Vietnamese smell identification test.

Introduction: The 12-item Vietnamese smell identification test (VSIT) has been developed to evaluate the olfactory function of the Vietnamese population. This study aimed to investigate the normative value of the VSIT in different age groups and sexes. Methods: This cross-sectional study was conducted at Ho Chi Minh University Medical Center, Vietnam. All participants were evaluated for odor identification ability using the VSIT. We included healthy participants aged 18 years or older with no history of olfactory disturbances. Results: A total of 391 healthy volunteers were recruited with a mean age of 45.80 years (SD: 17.62; range: 18-86; female: 63.4 %). The tenth percentile of scores on the 0-12 VSIT scale was 8.3 in participants aged 18-29 years, 9.0 in 30-39 years, 8.0 in 40-49 years, 7.8 in 50-59 years, 7.9 in 60-69 years and 6.0 in over 70 years. Young adults (18-39 years old) had better olfactory identification ability than older adults (over 50 years), p < 0.001. There was a significant main effect of sex on VSIT score (p = 0.02), suggesting that females outperformed males. Sensitivity to 8 odors were negatively correlated with age: lemon, garlic, banana, coffee, mango, guava, apple and watermelon (p < 0.05 in all cases) whereas four odors were age-independent including orange, fish sauce, soy sauce, and fish. Conclusion: Normative data provide guidance for assessing individual olfactory function. However, there were significant sex and age effects on olfactory identification scores on the VSIT. Therefore, future studies should be conducted to better adjust for those confounders mentioned above.

Development and validation of the Vietnamese smell identification test.

BACKGROUND: Correct olfactory identification requires familiarity with the odor stimuli and is culturally dependent. Existing smell identification tests (SIT) are not culturally specific and may not be reliable in detecting hyposmia in all populations. This study aimed to develop a smell identification test suitable for Vietnamese patients (VSIT). METHODS: The study included 4 phases: 1) survey-based evaluation of the familiarity of 68 odors to identify 18 odors for subsequent testing (N = 1050); 2) smell identification test of 18 odors in healthy patients (N = 50) to determine which 12 should be included in the VSIT; 3) comparison of VSIT scores on 12 odors in patients with hyposmia (N = 60; Brief smell identification test (BSIT) score <8 and those with normosmia (N = 120; BSIT score ≥8) to establish the validity of the newly developed test; and 4) retest of the VSIT in 60 normosmic patients from phase 3 (N = 60) to determine test-retest reliability. RESULTS: As expected, the mean (SD) VSIT score was significantly higher in the healthy participants than in the hyposmic patients [10.28 (1.34) vs 4.57 (1.76); P < 0.001]. Using a cut-off score at 8, the sensitivity and specificity of the instrument in detecting hyposmia were 93.3% and 97.5% respectively. The test-retest reliability using the intra-class correlation coefficient was at 0.72 (P < 0.001). CONCLUSION: The Vietnamese Smell Identification Test (VSIT) demonstrated favorable validity and reliability and will allow for assessment of olfactory function in Vietnamese patients.

Bone Health in Young Athletes: a Narrative Review of the Recent Literature.

PURPOSE OF REVIEW: The aim of this review is to discuss the most recent published scientific evidence regarding bone health in the pediatric athlete. RECENT FINDINGS: Pediatric athletes commonly suffer from overuse injuries to the physes and apophyses, as well as bone stress injuries, for which magnetic resonance imaging grading of the severity of injuries may be useful in guiding return to sport. Adolescent athletes, particularly those who train indoors and during the winter season, are at risk for vitamin D deficiency, which has important implications for bone mineral density. However, the relationship between vitamin D status and traumatic fracture risk is still unclear. While the female athlete triad is a well-established condition, the current work has led to the recognition of parallel pathophysiology in male athletes, referred to as the male athlete triad. Recent evidence suggests that transdermal 17ß-estradiol treatment in amenorrhoeic female athletes is an effective adjunctive treatment to improve bone mineral density in treatment of the female athlete triad. Young athletes are at risk for musculoskeletal injuries unique to the growing skeleton. Optimizing nutritional intake, particularly related to adequate vitamin D intake and prevention of the athlete triad, is critical to optimize bone health in the young athlete.

Scales for Antipsychotic-Associated Movement Disorders: Systematic Review, Critique, and Recommendations.

BACKGROUND: Antipsychotic-associated movement disorders remain common and disabling. Their screening and assessment are challenging due to clinical heterogeneity and different use of nomenclature between psychiatrists and neurologists. OBJECTIVE: An International Parkinson and Movement Disorder Society subcommittee aimed to rate psychometric quality of severity and screening instruments for antipsychotic-associated movement disorders. METHODS: Following the methodology adopted by previous International Parkinson and Movement Disorders Society subcommittee papers, instruments for antipsychotic-associated movement disorders were reviewed, applying a classification as "recommended," "recommended with caveats," "suggested," or "listed." RESULTS: Our review identified 23 instruments. The highest grade of recommendation reached is "recommended with caveats," assigned to seven severity rating instruments (Extrapyramidal Symptoms Rating Scale, Barnes Akathisia Rating Scale, Abnormal Involuntary Movements Scale, Drug-Induced Extra-Pyramidal Symptoms Scale, Maryland Psychiatric Research Centre involuntary movements scale, Simpson Angus Scale, and Matson Evaluation of Drug Side effects). Only three of these seven (Drug-Induced Extra-Pyramidal Symptoms Scale, Maryland Psychiatric Research Centre, Matson Evaluation of Drug Side effects) were also screening instruments. Their main caveats are insufficient demonstration of psychometric properties (internal consistency, skewing, responsiveness to change) and long duration of administration. Eight "suggested" instruments did not meet requirements for the "recommended" grade also because of insufficient psychometric validation. Other limitations shared by several instruments are lack of comprehensiveness in assessing the spectrum of antipsychotic-associated movement disorders and ambiguous nomenclature. CONCLUSIONS: The high number of instruments "recommended with caveats" does not support the need for developing new instruments for antipsychotic-associated movement disorders. However, addressing the caveats with new psychometric studies and revising existing instruments to improve the clarity of their nomenclature are recommended next steps. © 2023 International Parkinson and Movement Disorder Society.

Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease : A Randomized Controlled Trial.

BACKGROUND: Parkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD. OBJECTIVE: To evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation. DESIGN: Randomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791). SETTING: Outpatient. PATIENTS: 150 patients with PD and constipation. INTERVENTION: ENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period. MEASUREMENTS: The primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]). RESULTS: The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (P < 0.001). Improvement in secondary end points included SBMs (P = 0.002), stool consistency (P < 0.001), ease of passage (P = 0.006), and laxative use (P = 0.041). In patients with dementia, MMSE scores improved by 3.4 points 6 weeks after treatment in the ENT-01 group (n = 14) versus 2.0 points in the placebo group (n = 14). Among patients with psychosis, SAPS-PD scores improved from 6.5 to 1.7 six weeks after treatment in the ENT-01 group (n = 5) and from 6.3 to 4.4 in the placebo group (n = 6). ENT-01 was well tolerated, with no deaths or drug-related serious adverse events. Adverse events were predominantly gastrointestinal, including nausea (34.4% [ENT-01] vs. 5.3% [placebo]; P < 0.001) and diarrhea (19.4% [ENT-01] vs. 5.3% [placebo]; P = 0.016). LIMITATION: Longer treatment periods need to be investigated in future studies. CONCLUSION: ENT-01 was safe and significantly improved constipation. PRIMARY FUNDING SOURCE: Enterin, Inc.

TNP Analogues Inhibit the Virulence Promoting IP3-4 Kinase Arg1 in the Fungal Pathogen Cryptococcus neoformans.

New antifungals with unique modes of action are urgently needed to treat the increasing global burden of invasive fungal infections. The fungal inositol polyphosphate kinase (IPK) pathway, comprised of IPKs that convert IP3 to IP8, provides a promising new target due to its impact on multiple, critical cellular functions and, unlike in mammalian cells, its lack of redundancy. Nearly all IPKs in the fungal pathway are essential for virulence, with IP3-4 kinase (IP3-4K) the most critical. The dibenzylaminopurine compound, N2-(m-trifluorobenzylamino)-N6-(p-nitrobenzylamino)purine (TNP), is a commercially available inhibitor of mammalian IPKs. The ability of TNP to be adapted as an inhibitor of fungal IP3-4K has not been investigated. We purified IP3-4K from the human pathogens, Cryptococcus neoformans and Candida albicans, and optimised enzyme and surface plasmon resonance (SPR) assays to determine the half inhibitory concentration (IC50) and binding affinity (KD), respectively, of TNP and 38 analogues. A novel chemical route was developed to efficiently prepare TNP analogues. TNP and its analogues demonstrated inhibition of recombinant IP3-4K from C. neoformans (CnArg1) at low µM IC50s, but not IP3-4K from C. albicans (CaIpk2) and many analogues exhibited selectivity for CnArg1 over the human equivalent, HsIPMK. Our results provide a foundation for improving potency and selectivity of the TNP series for fungal IP3-4K.

Patient selection and injection techniques for botulinum neurotoxin in oromandibular dystonia.

Oromandibular dystonia (OMD) is a form of focal dystonia that involves the masticatory, lower facial, labial, and lingual musculature. It is a disabling disorder which had limited treatment options until the recent introduction of botulinum toxin (BoNT) as the recommended first-line therapy by most experts and evidence-based literature. Owing to the complex relationship between the muscles of mastication and surrounding muscles, there is a wide variety of dynamic clinical presentations, making clinical recognition and the corresponding approach to BoNT injection therapy difficult. In this review, the authors provide a framework for practical clinical approaches, beginning with the recognition of clinical subtypes of OMD (jaw-opening, jaw-closing, jaw-deviating, lingual, peri-oral, and/or pharyngeal dystonias), followed by patient selection and clinical evaluation to determine function interferences, with injection techniques illustrated for each subtype. Careful stepwise planning is recommended to identify the muscles that are primarily responsible and employ a conservative approach to dosing titration. Treating physicians should be diligent in checking for adverse events, especially for the first few injection cycles, as muscles involved in OMD are small, delicate, and situated in close proximity. It is recommended that future studies should aim to establish the clinical efficacy of each subtype, incorporating muscle targeting techniques and patient-centred outcome measures that are related to disturbed daily functions.

Efficacy and safety of two incobotulinumtoxinA injection intervals in cervical dystonia patients with inadequate benefit from standard injection intervals of botulinum toxin: Phase 4, open-label, randomized, noninferiority study.

IntroductionSome patients with cervical dystonia (CD) receiving long-term botulinum neurotoxin (BoNT) therapy report early waning of treatment benefit before the typical 12-week reinjection interval. Methods: This phase 4, open-label, randomized, noninferiority study (CD Flex; NCT01486264) compared 2 incobotulinumtoxinA injection schedules (Short Flex: 8 ± 2 weeks; Long Flex: 14 ± 2 weeks) in CD patients. Previous BoNT-responsive subjects who reported acceptable clinical benefit lasting < 10 weeks were recruited. Efficacy and safety were evaluated after 8 injection cycles. The primary endpoint was change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 4 weeks after the eighth injection. Secondary endpoints included TWSTRS total and subscale scores. Immunogenicity was assessed in a subset of patients. Results: Two hundred eighty-two CD patients were randomized and treated (Short Flex, N = 142; Long Flex, N = 140), and 207 completed the study. Significant improvements in TWSTRS severity from study baseline to 4 weeks after cycle 8 were observed in both the Short Flex (4.1 points; P < 0.0001) and Long Flex (2.4 points; P = 0.002) groups; Short Flex was noninferior to Long Flex (LS mean difference = 1.4 points; 95% CI = [-2.9, 0.1] < Δ = 2.0). Key secondary endpoints favored Short Flex intervals. Adverse events (AEs) were comparable between groups. There was no secondary loss of treatment effect. Conclusion: Injection cycles < 10 weeks for incobotulinumtoxinA are effective (and noninferior to longer intervals) for treating CD patients with early waning of clinical benefit. Shorter injection intervals did not increase AEs or lead to loss of treatment effect.

Medications used to treat tremors.

Tremor is one of the most common movement disorders, though it can arise in the context of several unrelated neurological disorders whose pharmacology and anatomical origins differ greatly. Treatment of tremors can take advantage of several medications and neurosurgical treatments. Medications useful for treating tremor are discussed in this review, including those for action tremor as seen in essential tremor, the resting tremor of Parkinson's disease, orthostatic tremor, cerebellar tremor, Holmes tremor, dystonic tremor, and drug-induced tremors. A medication that is useful for most types of tremors is the beta-blocker propranolol, though even in essential tremor it can fail to be effective at tremor control. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.

The etiopathogenetic and pathophysiological spectrum of parkinsonism.

Parkinsonism is a syndrome characterized by bradykinesia, rigidity, and tremor. Parkinsonism is a common manifestation of Parkinson's disease and other neurodegenerative diseases referred to as atypical parkinsonism. However, a growing body of clinical and scientific evidence indicates that parkinsonism may be part of the phenomenological spectrum of various neurological conditions to a greater degree than expected by chance. These include neurodegenerative conditions not traditionally classified as movement disorders, e.g., dementia and motor neuron diseases. In addition, parkinsonism may characterize a wide range of central nervous system diseases, e.g., autoimmune diseases, infectious diseases, cerebrospinal fluid disorders (e.g., normal pressure hydrocephalus), cerebrovascular diseases, and other conditions. Several pathophysiological mechanisms have been identified in Parkinson's disease and atypical parkinsonism. Conversely, it is not entirely clear to what extent the same mechanisms and key brain areas are also involved in parkinsonism due to a broader etiopathogenetic spectrum. We aimed to provide a comprehensive and up-to-date overview of the various etiopathogenetic and pathophysiological mechanisms of parkinsonism in a wide spectrum of neurological conditions, with a particular focus on the role of the basal ganglia involvement. The paper also highlights potential implications in the diagnostic approach and therapeutic management of patients. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.

Parkinsonism in viral, paraneoplastic, and autoimmune diseases.

Secondary parkinsonism, namely parkinsonism due to causes other than idiopathic neurodegeneration, may have multiple etiologies. Common secondary etiologies of parkinsonism such as drug-induced or vascular etiologies are well documented. Other secondary causes of parkinsonism such as infectious (mainly viral and prion-like diseases), autoimmune (systemic/drug-induced) and paraneoplastic etiologies are rare but are a topic of increasing interest. Older examples from the existing literature demonstrate the intricacies of viral infection from the last pandemic of the 20th century on the development of hypokinetic symptoms experienced in post-encephalitic patients. Viral and prion-like infections are only part of a complex interplay between the body's immune response and aberrant cell cycle perturbations leading to malignancy. In addition to the classic systemic autoimmune diseases (mainly systemic lupus erythematosus - SLE, and Sjögren syndrome), there have been new developments in the context of the current COVID-19 pandemic as well as more prominent use of immunotherapies such as immune checkpoint inhibitors in the treatment of solid tumors. Both of these developments have deepened our understanding of the underlying pathophysiologic process. Increased awareness and understanding of these rarer etiologies of parkinsonism is crucial to the modern diagnostic evaluation of a patient with parkinsonian symptoms as the potential treatment options may differ from the conventional levodopa-based therapeutic regimen of idiopathic Parkinson's disease. This review article aims to give an up-to-date review of the current literature on parkinsonian symptoms, their pathogenesis, diagnostic methods, and available treatment options. Many potential future directions in the field of parkinsonian conditions remain to be explored. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.

AbobotulinumtoxinA provides flexibility for the treatment of cervical dystonia with 500 U/1 mL and 500 U/2 mL dilutions.

INTRODUCTION: Cervical dystonia (CD) is a neurologic movement disorder with potentially disabling effects and significant impact on quality of life of those affected. AbobotulinumtoxinA (aboBoNT-A) was initially approved for a dilution of 500 U/1 mL and subsequently for a dilution of 500 U/2 mL, providing flexibility for clinicians to treat CD. Here, we explore the safety and efficacy of the 500 U/2 mL dilution versus 500 U/1 mL dilution of aboBoNT-A in a retrospective analysis based on published clinical trial data. METHODS: The safety and efficacy of aboBoNT-A in patients with CD was evaluated in three multicenter, double-blind, randomized, placebo-controlled trials and open-label extensions. Trials 1 (NCT00257660) and 2 (NCT00288509) evaluated the 500 U/1 mL dilution in 80 and 116 patients, respectively; Trial 3 (NCT01753310) evaluated the 500 U/2 mL dilution in 125 patients. RESULTS: Comparison of the adjusted mean difference in TWSTRS total scores at Week 4 from baseline for aboBoNT-A in Trial 1 (-6.0; 95% CI, -10.8, -1.3), Trial 2 (-8.8; 95% CI, -12.9, -4.7), and Trial 3 (-8.7; 95% CI, -13.2, -4.2) showed similar, significant improvements. Dysphagia and muscle weakness patterns were comparable across the three trials, indicating that an increased dilution of aboBoNT-A does not result in an increased risk of diffusion-related adverse events. CONCLUSION: The results of these trials show that aboBoNT-A is similarly efficacious using either dilution, with similar safety and tolerability across trials. Having the 500 U/1 mL and 500 U/2 mL dilution volumes available provides further flexibility in administration, benefiting patient care.

The effect of Non-Motor symptoms on Health-Related quality of life in patients with young onset Parkinson's Disease: A single center Vietnamese Cross-Sectional study.

BACKGROUND: Young onset Parkinson's disease (YOPD) is a distinct entity from typical late onset Parkinson's disease (LOPD). The influene of non-motor features on the health - related quality of life (HRQoL) in LOPD has been previously reported, but little is known about the impact of non-motor features in YOPD. OBJECTIVE: The aim of this study was to explore the relationship between non-motor burden and HRQoL in patients with YOPD. METHODS: This was an observational, cross-sectional study in patients with a PD, whose age at disease onset ranged from 21 to 40 years (YOPD). Participants were assessed with the MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39; range 0-100). Spearman's rank test was used to identify correlations between NMSS domains and several dimension of HRQoL. Stepwise multiple linear regression analysis was performed to identify the independent predictors of HRQoL as measured by PDQ-39 summary index. RESULTS: 89 patients with YOPD mean (SD) age = 42.15 (5.84) participated. Patients reported 10.17 (4.74) non-motor symptoms, the most common (75%) and severe (median = 3) of which was was fatigue (IQR = 7). The most frequently reported and severely affected NMSS domain was sleep/fatigue (89.9%, median = 8; IQR = 13) followed by mood/cognition (83.1%, median = 6; IQR = 18) and attention/memory (82%, median = 5; IQR = 8). The mean (SD) summary index of PDQ-39 was 32.89 (16.8). The means (SD) of each PDQ-39 dimensions were: mobility 37.33 (21.96), ADL 42.93 (25.33), emotional well-being 39.77 (25.47), stigma 38.19 (28.44), social support 19.03 (22.89), cognition 29.59 (20.63), communication 26.96 (23.57), and bodily discomfort 29.96 (23.19). With the exception of gastrointestinal tract and sexual function, all other NMSS domain scores were correlated with the PDQ-39 summary index. The multivariate model revealed that three NMSS domains including sleep/fatigue, mood/cognition and attention/memory accompanied with UPDRS part III were independent predictors of HRQoL as measured by PDQ-39SI. CONCLUSIONS: Non-motor symptoms pertaining to sleep disturbances/fatigue, mood/cognition and attention/memory negatively impact HRQoL in patients with YOPD.

Fist-Edge-Palm (FEP) test has a high sensitivity in differentiating dementia from normal cognition in Parkinson's disease.

BACKGROUND: The Fist-Edge-Palm (FEP) test takes 0.5-3 min to complete and is highly sensitive in differentiating Alzheimer's disease and frontotemporal dementia from normal cognition, but it has not yet been studied in Parkinson's disease (PD). OBJECTIVE: To determine the sensitivity and specificity of the FEP test in screening patients with PD for cognitive impairment and dementia. METHODS: PD patients were recruited and divided into three groups based on cognitive status: normal cognition, mild cognitive impairment (MCI) and dementia according to 2015 MDS clinical diagnostic criteria for PD and clinical dementia rating scale (CDR) assessment for cognitive status. MMSE, FEP and clock drawing test (CDT) were tested in all recruited PD patients. Chi-square test was used to compare the sensitivity of FEP and CDT in detecting PDD and PD-MCI. RESULTS: A total of 108 PD patients were included: 52 normal cognition, 28 MCI, and 28 dementia. The sensitivity of FEP in differentiating PDD from PD-NC was 96.4% and the sensitivity for PD-MCI from PD-NC was 71.4%. The sensitivity of CDT in differentiating PDD from PD-NC was 71.4% and PD-MCI from PD-NC was 53.6%. The sensitivities of FEP and CDT were 83.9% and 62.5%, respectively, in identifying cognitive impairment (CDR ≥ 0.5) in PD patients. CONCLUSION: FEP is a sensitive screening tool in differentiating PDD or PD-MCI from PD-NC, and it is much faster than MMSE and more sensitive than CDT. FEP may be a practical screening tool for daily clinical practice.

Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion.

BACKGROUND AND PURPOSE: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread. METHODS: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping. RESULTS: Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread. CONCLUSIONS: This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.