Does botulinum toxin affect psycho-social aspects in dystonia?

Dystonia is a movement disorder in which sustained muscle contractions give rise to abnormal postures or involuntary movements. It is a disabling and disfiguring disorder that affects activities of daily living and gives people a bizarre appearance often associated with psychological morbidity, embarrassment and social avoidance. Intramuscular injection of botulinum toxin (BoNT) is the most effective treatment for motor symptoms in focal dystonia, but little is known about its impact on the psycho-social dimension. The main aim of this study was to evaluate psycho-social changes in patients with focal dystonia after starting BoNT treatment using self-reported scales. The Beck Depression Inventory (BDI-II), the 36-Item Short Form Health Survey (SF-36), the Body Uneasiness Test (BUT), the State-Trait Anxiety Inventory (STAI) and the Visual Analogue Scale (VAS) assessing body self-image, satisfaction with physical aspects, social avoidance, self-reported depression, and self-distress were completed by 11 patients with dystonia and 9 patients with hyperhidrosis as a control group before BoNT (T0). VAS was then performed after four weeks (T1) to assess whether BoNT induced changes in the psychosocial dimension. Our results showed that only depressive symptoms and rumination about body defects improved in patients with dystonia after BoNT treatment, while improvement in self-distress and satisfaction with physical aspects was also found in hyperhidrosis. Individuals with hyperhidrosis experience poorer psychological well-being and suffer from higher levels of distress compared to dystonic patients. This suggests that individuals with this disabling condition are more vulnerable to social impact than dystonic patients.

Association of APOE genotype and cerebrospinal fluid Aß and tau biomarkers with cognitive and motor phenotype in amyotrophic lateral sclerosis.

OBJECTIVE: Little is known about amyotrophic lateral sclerosis (ALS)-nonspecific cognitive deficits - most notably memory disturbance - and their biological underpinnings. We investigated the associations of the Alzheimer's disease (AD) genetic risk factor APOE and cerebrospinal fluid (CSF) biomarkers Aß and tau proteins with cognitive and motor phenotype in ALS. METHODS: APOE haplotype was determined in 281 ALS patients; for 105 of these, CSF levels of Aß42, Aß40, total tau (T-tau), and phosphorylated tau (P-tau181) were quantified by chemiluminescence enzyme immunoassay (CLEIA). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was employed to evaluate the neuropsychological phenotype. RESULTS: APOE-E4 allele was associated with worse ECAS memory score (median, 14.0 in carriers vs. 16.0 in non-carriers) and lower CSF Aß42 (-0.8 vs. 0.1, log-transformed values) and Aß42/40 ratio (-0.1 vs. 0.3). Some 37.1% of ALS patients showed low Aß42 levels, possibly reflecting cerebral Aß deposition. While lower Aß42/40 correlated with lower memory score (ß = 0.20), Aß42 positively correlated with both ALS-specific (ß = 0.24) and ALS-nonspecific (ß = 0.24) scores. Although Aß42/40 negatively correlated with T-tau (ß = -0.29) and P-tau181 (ß = -0.33), we found an unexpected positive association of Aß42 and Aß40 with both tau proteins. Regarding motor phenotype, lower levels of Aß species were associated with lower motor neuron (LMN) signs (Aß40: ß = 0.34; Aß42: ß = 0.22). CONCLUSIONS: APOE haplotype and CSF Aß biomarkers are associated with cognitive deficits in ALS and particularly with memory impairment. This might partly reflect AD-like pathophysiological processes, but additional ALS-specific mechanisms could be involved.

Ecological validity of performance-based cognitive screeners in amyotrophic lateral sclerosis: preliminary evidence.

BACKGROUND: This study aimed at preliminarily assessing, in a cohort of non-demented amyotrophic lateral sclerosis (ALS) patients, the ecological validity, and more specifically the veridicality, of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioral Screen (ALS-CBS™), by relating their scores to caregiver-report ratings of cognitive changes. METHODS: N = 147 patient-caregiver dyads were recruited. Patients were administered the ECAS and ALS-CBS™, whilst caregiver the Caregiver Behavioral Questionnaire (CBQ) and Beaumont Behavioural Inventory (BBI). An Ecological Cognitive Functioning Index (ECFI) was derived from those items of the CBQ and BBI that tap on executive and language changes. Ecological validity was assessed via both correlational and predictive analyses net of caregiver-rated behavioural changes (as assessed by the ECAS-Carer Interview). RESULTS: The ECFI was associated with the total scores on both the ECAS (p = .014) and ALS-CBS™ (p = .017). When looking at ECAS and ALS-CBS™ subscales, those assessing verbal fluency were selectively associated with the ECFI. The ECFI was higher in patients performing defectively on the ECAS (p = .004) and on the ALS-CBS™ (p = .027). DISCUSSION: This study suggests that both the ECAS and the ALS-CBS™ represent a valid estimate of non-demented ALS patients' cognitive status in the real world, also highlighting the clinical relevance of cognitive changes reported by caregivers.

Oropharyngeal Dysphagia Phenotypes Across Huntington's Disease Stages: Endoscopic Findings and Tongue Pressure Analysis.

Background: Oropharyngeal dysphagia (OD) is a common symptom in Huntington's disease (HD) and is associated with severe health and psychosocial consequences. Different OD phenotypes are defined on the basis of characteristic patterns at fiberoptic endoscopic evaluation of swallowing (FEES), and they may vary during disease progression. Objective: To describe OD phenotypes in different HD stages and to analyze their association with neurological data and tongue pressure measurements. Methods: Twenty-four patients with HD at different stages of disease progression underwent a FEES. Data on penetration/aspiration, pharyngeal residue, and OD phenotypes were gained. Neurological examination was performed with the Unified Huntington's Disease Rating Scale (UHDRS). Patient Maximum tongue pressure (MTP) and tongue endurance were measured. Results: We confirmed that the occurrence of penetration/aspiration increased with disease duration and pharyngeal residue increased from 16.7% to 100% , respectively. The most common OD phenotypes were oropharyngeal dyspraxia (91.7% ), posterior oral incontinence (87.5% ), and delayed pharyngeal phase (87.5% ). These types of dysfunctions are already detectable in >80% of patients in the early disease stages. In more advanced stages, we also observed propulsion deficit (66.7% ), resistive issue (54.2% ), and protective deficit (37.5% ). Propulsion deficit was associated with higher disease stage, greater motor dysfunction (UHDRS-I), and lower MTP and tongue endurance (p <  0.05). Conclusions: OD in HD results from a combination of different swallowing phenotypes. Early assessment of swallowing and periodical follow-ups are necessary to monitor OD severity and phenotypes and to revise diet recommendations.

Behavioral Disorders of Spatial Cognition in Patients with Mild Cognitive Impairment Due to Alzheimer's Disease (The BDSC-MCI Project): Ecological Validity of the Corsi Learning Suvra-Span Test.

BACKGROUND: Spatial navigation deficits are reported as early symptoms of Alzheimer's disease (AD) alongside episodic memory ones. The aim of the present study was to ascertain whether neuropsychological deficits of visuospatial long-term memory can predict behavioral alterations during the navigation of older adults in novel urban environments along the normal aging-dementia continuum of the Alzheimer's type. METHODS: A total of 24 community-dwelling patients with Mild Cognitive Impairment (MCI) due to AD, 27 individuals with subjective cognitive decline (SCD), and 21 healthy controls were assessed in terms of their sequential egocentric and allocentric navigation abilities by using a modified version of the Detour Navigation Test, and neuropsychologically tested by the Corsi learning suvra-span (CLSS) test. Generalized linear models were adopted to verify whether the scores obtained by the three groups in the CLSS test predicted wrong turns and moments of hesitation during the navigation task, with the results presented as topographical disorientation scores. RESULTS: Higher scores in the CLSS test predicted fewer wrong turns (b = -0.05; z = -2.91; p = 0.004; net of between-groups differences) and moments of hesitation for patients with MCI due to AD (b = -0.14; z = -2.43; p = 0.015), and individuals with SCD (b = -0.17; z = -3.85; p < 0.001). CONCLUSIONS: Since the CLSS test has been reported to be a reliable measure of ecological navigational abilities in the progression towards AD dementia, we recommend its use in clinical practice and highlight implications for future research.

Verbal learning in frontal patients: area 9 is critical for employing semantic strategies.

INTRODUCTION: Learning is a long-term memory process heavily influenced by the control processes implemented by working memory, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. AIM: The aim of this study is to investigate the verbal learning strategies of patients affected by a tumor in the left frontal lobe to highlight the role of area 9. METHOD: Ten patients with frontal low-grade gliomas and ten healthy control subjects, matched for age, sex and education, were recruited and then evaluated with a two-part verbal learning test: multi-trial word list learning in free recall, and multi-trial word list learning preceded by an explicit semantic strategy cue. Frontal patients were divided into two groups: those either with frontal lesions involving or sparing area 9. RESULTS: In comparison to healthy control subjects, frontal patients with lesions involving area 9 memorized fewer words and displayed difficulty in using semantic strategies. When the strategy was suggested by the examiner, their performance improved, but to a lesser extent than the healthy control. Conversely, frontal patients with lesions sparing area 9 showed similar results to healthy control subjects. CONCLUSION: The results suggested that, while the identification of the categorical criterion requires the integrity of the entire dorsolateral prefrontal area, only area 9, and not the surrounding areas, could be responsible for the effective use of semantic strategies in learning tasks.

Clinical validity of the Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB) in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. METHODS: One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. RESULTS: Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. CONCLUSIONS: Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

Longitudinal Feasibility of the Montreal Cognitive Assessment (MoCA) in Non-Demented ALS Patients.

INTRODUCTION: The present study aimed at testing the longitudinal feasibility of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented amyotrophic lateral sclerosis (ALS) patients. METHODS: N = 39 non-demented ALS patients were followed-up at a 5-to-10-month interval (M = 6.8; SD = 1.4) with the MoCA and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Practice effects, test-retest reliability, and predictive validity (against follow-up ECAS scores) were assessed. Reliable change indices (RCIs) were derived via a regression-based approach by accounting for retest interval and baseline confounders (i.e., demographics, disease duration, and severity and progression rate). RESULTS: At retest, 100% and 69.2% of patients completed the ECAS and the MoCA, respectively. Patients who could not complete the MoCA showed a slightly more severe and fast-progressing disease. The MoCA was not subject to practice effects (t[32] = -0.80; p = 0.429) and was reliable at retest (intra-class correlation = 0.82). Moreover, baseline MoCA scores predicted the ECAS at retest. RCIs were successfully derived - with baseline MoCA scores being the only significant predictor of retest performances (ps < 0.001). CONCLUSIONS: As long as motor disabilities do not undermine its applicability, the MoCA appears to be longitudinally feasible at a 5-to-10-month interval in non-demented ALS patients. However, ALS-specific screeners - such as the ECAS - should be preferred whenever possible.

Predictors of Psychological Well-Being and Quality of Life in Patients with Hypertension: A Longitudinal Study.

Previous research has highlighted the positive impact of greater health-related quality of life (Hr-QoL) and subjective well-being (SWB) on chronic diseases' severity and progression. There is a paucity of studies investigating the long-term trajectories of these variables among hypertensive patients. The present study aims to investigate the relationships between psychological variables (Type A and D personality, locus of control-LoC, self-esteem, and trait anxiety) with SWB and Hr-QoL in patients with hypertension and comorbid metabolic syndrome. A total of 185 volunteer patients (130 males, 70.3%; mean age 54 ± 10.93) were enrolled. Patients filled out measures of Hr-QoL and SWB, LoC, and self-esteem at three time points-Type A and D behaviors and anxiety measures only at baseline. Analyses were run through two-level hierarchical mixed models with repeated measures (Level 1) nested within participants (Level 2), controlling for sociodemographic and clinical confounders. Neither Hr-QoL nor SWB changed over time. Patients with greater self-esteem and internal LoC (and lower external LoC) increased their SWB and Hr-QoL up to 1-year follow-up. A greater Type A behavior and trait anxiety at baseline predicted a longitudinal increase in most of the dependent variables. Results suggest that it could be useful to tailor interventions targeting specific variables to increase Hr-QoL and SWB among hypertensive patients.

Psychometrics and diagnostics of the Italian version of the Alternate Verbal Fluency Battery (AVFB) in non-demented Parkinson's disease patients.

BACKGROUND: Verbal fluency (VF) tasks are known as suitable for detecting cognitive impairment (CI) in Parkinson's disease (PD). This study thus aimed to evaluate the psychometrics and diagnostics of the Alternate Verbal Fluency Battery (AVFB) by Costa et al. (2014) in an Italian cohort of non-demented PD patients, as well as to derive disease-specific cut-offs for it. METHODS: N = 192 non-demented PD patients were screened with the Montreal Cognitive Assessment (MoCA) and underwent the AVFB-which includes phonemic, semantic and alternate VF tests (PVF; SVF; AVF), as well as a Composite Shifting Index (CSI) reflecting the "cost" of shifting from a single- to a double-cued VF task. Construct validity and diagnostics were assessed for each AVFB measure against the MoCA. Internal reliability and factorial validity were also tested. RESULTS: The MoCA proved to be strongly associated with PVF, SVF and AVF scores, whilst moderately with the CSI. The AVFB was internally consistent and underpinned by a single component; however, an improvement in both internal reliability and fit to its factorial structure was observed when dropping the CSI. Demographically adjusted scores on PVF, SVF and AVF tests were diagnostically sound in detecting MoCA-defined cognitive impairment, whilst this was not true for the CSI. Disease-specific cut-offs for PVF, SVF and AVF tests were derived. DISCUSSION: In conclusion, PVF, SVF and AVF tests are reliable, valid and diagnostically sound instruments to detect cognitive impairment in non-demented PD patients and are therefore recommended for use in clinical practice and research.

The Single-Matrix Digit Cancellation Test, a Screener for Selective Attention Deficits: Standardization in an Italian Population Sample and Clinical Usability in Acute Stroke Patients.

INTRODUCTION: This study aimed at validating and providing Italian norms for the Single-Matrix Digit Cancellation Test (SMDCT), a cancellation task to screen for selective attention deficits, as well as providing clinical usability evidence for it in acute stroke patients. METHODS: The SMDCT stimulus is a specular, 4-quadrant, horizontally oriented matrix, across which target distribution is homogeneous. Both accuracy (-A) and time (-T) outcomes were computed. N = 263 healthy participants (HPs) and N = 76 acute stroke patients were recruited. N = 108 HPs also underwent the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Trail-Making Test (TMT), while patients were further assessed by the Mental Performance in Acute Stroke (MEPS). Regression-based norms were derived (equivalent scores). Construct and factorial validity, as well as case-control discrimination, were tested. RESULTS: The matrix was underpinned by a two-component structure reflecting left and right hits. The SMDCT-T and -A were associated with TMT and FAB scores, respectively. Education predicted the SMDCT-A/-T, whereas age predicted the SMDCT-T only. In patients, the SMDCT converged with the MEPS, also accurately discriminating them from HPs. An index of right-left difference differentiated right- from left-damaged patients. CONCLUSIONS: The SMDCT is a valid and normed screener for selective attention deficits, encompassing measures of both accuracy and time, whose adoption is encouraged in acute stroke patients. Relatedly, the horizontal disposition of its matrix does allow for the qualitative report of either leftward of rightward biases due to underlying visual or attentional-representational deficits in this population.

Frontotemporal-spectrum disorders and functional independence in non-demented ALS patients.

BACKGROUND: The present study aimed at determining whether, net of motor confounders, neuropsychological features affect functional independence (FI) in activities of daily living (ADLs) in non-demented amyotrophic lateral sclerosis (ALS) patients. METHODS: N = 88 ALS patients without frontotemporal dementia were assessed for FI-Katz's Basic ADL Scale (BADL) and Lawton-Brody's Instrumental ADL Scale (IADL)-, cognition-Edinburgh Cognitive and Behavioural ALS Screen (ECAS)-and behaviour-Beaumont Behavioural Inventory and Dimensional Apathy Scale. The association between cognitive and behavioural measures and BADL/IADL scores was assessed by covarying for demographics, anxiety and depression levels, disease duration and motor confounders-i.e. ALS Functional Rating Scale-Revised (ALSFRS-R) scores, progression rate and both King's and Milano-Torino stages. RESULTS: Higher scores on the ECAS-Language were associated with higher IADL scores (p = 0.005), whilst higher apathetic features-as measured by the Dimensional Apathy Scale (DAS)-were inversely related to the BADL (p = 0.003). Whilst IADL scores were related to all ECAS-Language tasks, the DAS-Initiation was the only subscale associated with BADL scores. Patients with abnormal ECAS-Language (p = 0.023) and DAS (p = 0.008) scores were more functionally dependent than those without. DISCUSSION: Among non-motor features, language changes and apathetic features detrimentally affect FI in non-demented ALS patients.

Validity, diagnostics and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in Huntington's disease.

BACKGROUND: This study is aimed at assessing the clinimetric properties and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in patients with Huntington's disease (HD). METHODS: N = 39 motor-manifest HD patients, N = 74 Parkinson's disease (PD) patients and N = 92 matched HCs were administered the MoCA. HD patients further underwent the Unified Huntington's Disease Rating Scale (UHDRS), self-report questionnaires for anxiety and depression and a battery of first- and second-level cognitive tests. Construct validity was tested against cognitive and behavioural/psychiatric measures, whereas ecological validity against motor-functional subscales of the UHDRS. Sensitivity to disease severity was tested, via a logistic regression, by exploring whether the MoCA discriminated between patients in Shoulson-Fahn stage ≤ 2 vs. > 2. The same analysis was employed to test its ability to discriminate HD patients from HCs and PD patients. RESULTS: The MoCA converged towards cognitive and behavioural measures but diverged from psychiatric ones, being also associated with motor/functional measures from the UHDRS. In identifying patients with cognitive impairment, adjusted MoCA scores were highly accurate (AUC = .92), yielding optimal diagnostics at the cut-off of < 19.945 (J = .78). The MoCA was able to discriminate patients in the middle-to-advanced from those in the early-to-middle stages of the disease (p = .037), as well as to differentiate HD patients from both HCs (p < .001) and PD patients (p < .001). CONCLUSIONS: The MoCA is a valid, diagnostically sound and feasible cognitive screener in motor-manifest HD patients, whose adoption is thus encouraged in clinical practice and research.

An exploratory study on counterfactual thinking in amyotrophic lateral sclerosis.

Objectives: This study aimed at exploring (1) the motor and non-motor correlates of counterfactual thinking (CFT) abilities in non-demented amyotrophic lateral sclerosis (ALS) patients and (2) the ability of CFT measures to discriminate these patients from healthy controls (HCs) and patients with and without cognitive impairment. Methods: N = 110 ALS patients and N = 51 HCs were administered two CFT tasks, whose sum, resulting in a CFT Index (CFTI), was addressed as the outcome. Patients further underwent an in-depth cognitive, behavioral, and motor-functional evaluation. Correlational analyses were run to explore the correlates of the CFTI in patients. Logistic regressions were performed to test whether the CFTI could discriminate patients from HCs. Results: The CFTI was selectively associated (p ≤ 0.005) with fluency and memory subscales of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), but not with other variables. CFTI scores discriminated patients from HCs (p < 0.001) with high accuracy (82%), but not patients with a normal vs. defective performance on the ECAS-Total. Conclusion: CFT measures in non-demented ALS patients were associated with verbal fluency and memory functions, and they were also able to discriminate them from HCs.

Early Detection of Depression in Parkinson's Disease: Psychometrics and Diagnostics of the Spanish Version of the Beck Depression Inventory.

OBJECTIVE: Depression is one of the most disabling non-motor symptoms in Parkinson's disease (PD) and requires proper diagnosis as it negatively impacts patients' and their relatives quality of life. The present study aimed to examine the psychometric and diagnostic properties of the Beck Depression Inventory-I (BDI-I) in a Spanish PD cohort. METHOD: Consecutive PD outpatients completed the Spanish version of the BDI-I and other questionnaires assessing anxiety and apathy. Patients' caregivers completed the depression/dysphoria domain of the Neuropsychiatric Inventory (NPI-D). The internal consistency, convergent and divergent validity and the factorial structure of BDI-I were evaluated, and an optimal cut-off was defined by means of the Youden index. RESULTS: The BDI-I proved to have a good internal consistency and was underpinned by a mono-component structure. Regarding construct validity, the BDI-I was substantially related to anxiety and apathy measures in PD. Furthermore, the BDI-I overall showed good accuracy with adequate sensitivity and specificity. The optimal cut-off point was defined at 10. CONCLUSIONS: We provided evidence of the psychometric and diagnostic properties of the Spanish version of the BDI-I as a screening tool for depression in Spanish speaking PD patients, suggesting its usefulness in clinical research and practice.

Verbal Learning Impairment in Parkinson's Disease: Role of the Frontostriatal System in Working and Strategic Memory.

INTRODUCTION: Learning is a long-term memory process, influenced by working memory control processes, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. The aim of the study was to investigate the verbal learning strategies of individuals with Parkinson's disease (PD). METHODS: Thirty individuals with idiopathic PD and healthy control (HC) subjects were tested with a multi-trial word list learning, under two conditions: without cue and then with an explicit cue suggesting the categories in the list, respectively. RESULTS: In comparison to HC subjects, individuals with PD recalled fewer words and achieved a reduced number of categorical clusters; the strategical cue did not improve their performance. CONCLUSION: This suggests, besides a difficulty in identifying the correct learning strategy, a deficit in working memory, which undermines the strategy implementation.

Coexistence of Amyotrophic Lateral Sclerosis and Alzheimer's Disease: Case Report and Review of the Literature.

We describe a case of amyotrophic lateral sclerosis (ALS) associated with Alzheimer's disease (AD) and review the literature about the coexistence of the two entities, highlighting the following: mean age at onset is 63.8 years, with slight female predominance; ALS tends to manifest after cognitive impairment and often begins in the bulbar region; average disease duration is 3 years; cognitive phenotype is mostly amnestic; the pattern of brain involvement is, in most cases, consistent with AD. Our case and the reviewed ones suggest that patients with ALS and dementia lacking unequivocal features of FTD should undergo additional examinations in order to recognize AD.