Unawareness of chorea is well-known in Huntington’s disease (HD). This study investigated unawareness for the whole gamut of motor impairments in daily life, which has not been explored previously. Data from 71 consecutive patients with stage I or II HD were assessed retrospectively. The motor section of UHDRS; the total functional capacity; a short battery of cognitive tests; the SANS and SAPS scales for negative and positive psychiatric symptoms; the Hamilton scales for depression (HAM-D) and anxiety (HAM-A); and a semi-structured questionnaire to assign motor anosognosia on a scale from 0 (fully aware) to 3 (severely unaware), were administered. Twenty-seven (38

Background: Progressive Supranuclear Palsy (PSP) is a rare, heterogeneous neurodegenerative disease for which no treatment is currently available. In the context of clinical trials, the representativeness of the included patients is crucial for the generalizability of the results. Herein, we present results from a multicenter perspective study to identify the most restrictive criteria for patient selection and to assess the representativeness of eligible patients. Methods: we enrolled 221 PSP patients diagnosed according to the MDS clinical criteria. All patients were screened with a set of inclusion and exclusion criteria based on previous and ongoing clinical trials in PSP and underwent motor and cognitive evaluation with the Montreal Cognitive Assessment battery and the PSP rating scale, respectively. Then, clinical features of eligible and non-eligible patients were compared at baseline and after 15,93 +/- 8,77 months follow up. Results: Eligible (28 patients, 12,6 %) patients were younger, showed shorter disease duration and lower severity but similar distribution of PSP phenotype and disease progression rates compared to non-eligible patients. The most restrictive non-modifiable criteria were independent gait, disease duration and cognitive status. Willingness to undergo lumbar puncture and treatment stability for previous 60 days represented potentially modifiable criteria. Conclusion: Overall, PSP eligible for clinical trials are representative of the general PSP population. While motor and cognitive impairment represent the most important non-modifiable barriers to enter a clinical trial, other criteria as willingness to undergo lumbar puncture and treatment stability are potentially modifiable. Specific strategies are discussed to increase the number of eligible patients working on potentially modifiable criteria.

BACKGROUND AND OBJECTIVES:Caregivers of progressive supranuclear palsy (PSP) patients frequently show significant distress. The Parkinsonism Carers quality of life (QoL) (PQoL Carer) is a valid tool evaluating the effect of PSP on caregivers' QoL. Main aim of the present study was to develop a short version of the PQoL Carer, named PSP-ShoQoL Carer. METHODS:PQoL Carer was administered within the PSP-NET. Participants underwent clinical, motor, cognitive, and behavioral evaluations. RESULTS:Data from 344 participants were included. The final PSP-ShoQoL Carer included eight items. The internal consistency was high (Cronbach's α = 0.867) and PSP-ShoQoL Carer showed also good acceptability, reliability, and validity. The PSP-ShoQoL Carer showed a significant correlation with caregivers' standard measures of QoL and with patients' motor, cognitive, and behavioral characteristics, such as neuropsychiatric symptoms. Finally, PSP-ShoQoL Carer showed an appropriate sensitivity to change over 6-month follow up. CONCLUSIONS:PSP-ShoQoL Carer is a reliable and valid time-saving tool for the assessment of caregivers' QoL in PSP.

INTRODUCTION:This study aimed to assess the diagnostics and ecological validity of the Parkinson's Disease Cognitive Rating Scale (PD-CRS) within an Italian cohort of non-demented Parkinson's disease (PD) patients. METHODS:N = 128 non-demented PD patients were administered the PD-CRS, Montreal Cognitive Assessment (MoCA), and Parkinson's Disease Cognitive Functioning Rating Scale (PD-CFRS). Receiver-operating characteristic analyses were performed to explore the diagnostics of both raw and adjusted PD-CRS scores, by operationalizing the positive state as a below-cut-off MoCA score. Correlational analyses were run to test the ecological validity of the PD-CRS against the PD-CFRS. RESULTS:Both raw and adjusted PD-CRS scores accurately identified patients with a defective MoCA scores (AUC = 0.84-0.85), yielding optimal diagnostics. A cut-off of <73.93, as identified on demographically adjusted PD-CRS scores, yielded the best diagnostics (sensitivity = 0.70; specificity = 0.89; positive and negative predictive values = 0.83 and 0.79; positive and negative likelihood ratios: 6.23 and 0.37: number needed for screening utility: 0.78). The PD-CRS was related to the PD-CFRS (rs = -0.24; p = 0.018). CONCLUSIONS:The Italian PD-CRS is a diagnostically sound and ecologically valid screener for cognitive impairment in non-demented PD patients.

Background The ability to simulate alternatives to factual events is called counterfactual thinking (CFT) and it is involved both in emotional and behavioral regulation. CFT deficits have been reported in psychiatric and neurological conditions, possibly contributing to patients' difficulties in modulating behaviors and affections. Thus, acknowledging the presence and possible consequences of CFT impairments might be essential for optimal clinical management. Objectives This scoping review aims to summarize the previous evidence about CFT in psychiatric and neurological diseases to determine the extent of the previous research and what has been discovered so far, the variety of clinical conditions considered, the methodologies adopted, and the relevant issues to be addressed by future investigations. Methods PsycInfo, PubMed, Scopus, and Web of Science were searched to identify articles published up to January 2020, written in English and focused on CFT in adults affected by psychiatric or neurological conditions. Results Twenty-nine studies have been included; most of them focused on psychiatric conditions, a minority considered neurological diseases. The generation of counterfactual thoughts related to a negative real-life or a fictional event and the counterfactual inference test were the most popular tasks adopted. CFT impairments were reported in both psychiatric and neurological conditions, likely associated with a fronto-executive dysfunction. Conclusions Future research might further explore CFT in those psychiatric and neurological conditions in which CFT difficulties have been preliminary reported. Furthermore, it would be recommendable to extend this investigation to all the clinical conditions possibly at risk of fronto-executive dysfunction. In the end, we speculate that since CFT plays a role in driving everyday behaviors, it might be crucial also when medical decisions are involved; thus, future research might extend the investigation of CFT especially to those populations that implicate complex clinical management.

BACKGROUND:Family history of Parkinson's disease (PD) is a common finding in PD patients. However, a few studies have systematically examined this aspect. OBJECTIVES:We investigated the family history of PD patients, comparing demographic and clinical features between familial PD (fPD) and sporadic PD (sPD). METHODS:A cross-sectional study enrolling 2035 PD patients was conducted in 28 Italian centers. Clinical data and family history up to the third degree of kinship were collected. RESULTS:Family history of PD was determined in 21.9% of patients. fPD patients had earlier age at onset than sporadic patients. No relevant differences in the prevalence of motor and nonmotor symptoms were detected. Family history of mood disorders resulted more prevalently in the fPD group. CONCLUSIONS:fPD was found to recur more frequently than previously reported. Family history collection beyond the core family is essential to discover disease clusters and identify novel risk factors for PD.

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.

Mutations in the PRKN gene encoding the protein parkin cause autosomal recessive juvenile parkinsonism (ARJP). Harnessing this mutation to create an early-onset Parkinson's disease mouse model would provide a unique opportunity to clarify the mechanisms involved in the neurodegenerative process and lay the groundwork for the development of neuroprotective strategies. To this end, we created a knock-in mouse carrying the homozygous PrknR275W mutation, which is the missense mutation with the highest allelic frequency in PRKN patients. We evaluated the anatomical and functional integrity of the nigrostriatal dopamine (DA) pathway, as well as motor behaviour in PrknR275W mice of both sexes.We report here that PrknR275W mice show early DA neuron dysfunction, age-dependent loss of DA neurons in the substantia nigra, decreased DA content and stimulus-evoked DA release in the striatum, and progressive motor impairment. Together, these data show that the PrknR275W mouse recapitulates key features of ARJP. Thus, these studies fill a critical need in the field by introducing a promising new Parkinson's disease model in which to study causative mechanisms of the disease and test therapeutic strategies. Mutations in the PRKN gene are the most common cause of autosomal recessive juvenile parkinsonism (ARJP). Regoni et al. create a new mouse model of ARJP that recapitulates key features of the human disease, providing a means of studying casual mechanisms and testing therapeutic strategies.

. The present study aimed at deriving regression-based reliable change indices (RCIs) for the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented Parkinson’s disease (PD) patients. N = 33 consecutive, non-demented PD patients were followed-up at a 5-to-8-month interval (M = 6.6; SD = 0.6) with the MoCA. Practice effects and test-retest reliability were assessed via dependent-sample t-tests and intra-class correlation (ICC) coefficients, respectively. RCIs were derived separately for raw and demographically adjusted MoCA scores according to a standardized regression-based approach by accounting for both baseline confounders (i.e., demographics, disease duration and Unified Parkinson’s Disease Rating Scale scores) and retest interval. No practice effects were found (t(32) = 0.29; p = .778), with acceptable test-retest reliability being detected (ICC = 0.67). MoCA scores at T0 proved to be the only significant predictor of T1 MoCA performances within both the model addressing raw scores and that addressing adjusted scores (ps < 0.001). The present study provides Italian practitioners and researchers with regression-based RCIs for the MoCA in non-demented PD patients, which can be reliably adopted for retest interval ≥ 5 and ≤ 8 months without encountering any practice effect.

Dataset associated with the paper: "Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson’s disease patients"

Background: The ecological validity of performance-based cognitive screeners needs to be tested in order for them to be fully recommended for use within clinical practice and research. Objectives: The objective of this study was to examine, within an Italian cohort of non-demented Parkinson’s disease (PD) patients, the ecological validity of the Montreal Cognitive Assessment (MoCA) by assessing its association with (1) functional independence (FI), (2) quality of life (QoL), and (3) behavioural-psychological (BP) outcomes. Methods: Seventy-four non-demented PD patients were administered the MoCA and underwent motor functional – i.e., Unified Parkinson’s Disease Rating Scale (UPDRS), Modified Hoehn-Yahr Scale (HY), and Schwab and England Scale (SES) –, behavioural and psychological – i.e., State- and Trait-Anxiety Inventory-Form Y (STAI-Y1/-Y2), Beck Depression Inventory (BDI), and Dimensional Apathy Scale (DAS) – and QoL evaluations – i.e., MOS 36-Item Short Form Health Survey (SF-36). Associations of interest against FI, QoL, and BP outcomes were tested via Bonferroni-corrected Pearson’s/Spearman’s correlations while covarying for demographics, disease duration as well as UPDRS-III, UPDRS-IV, and HY scores. Intake of psychotropic drugs was also covaried when assessing the association between the MoCA and BP/QoL measures. Results: MoCA scores were significantly associated with the SES (rs(73) = 0.34; p = 0.005) and the DAS-Executive (r(67) = −0.47; p < 0.001), while not to other FI/BP outcomes and QoL measures. Conclusions: The MoCA is a valid estimate of daily life functional autonomy in non-demented PD patients, also reflecting apathetic features of a dysexecutive nature.

Datasets associated with the paper: 'Validity, diagnostics and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in Huntington’s disease'

This is the dataset for the article "Progressive motor neuron syndromes with single CNS lesions and CSF oligoclonal bands: never forget solitary sclerosis!"

This study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson’s disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties. A retrospective cohort of N = 237 non-demented PD patients having been administered the MoCA was addressed, of whom N = 169 further underwent the Mini-Mental State Examination (MMSE) and N = 68 the Parkinson’s Disease Cognitive Rating Scale (PD-CRS). A subsample (N = 60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score. The MoCA was associated with both PD-CRS scores (p < .001) and the vast majority of second-level cognitive measures (ps < .003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and < 19.015 is herewith suggested as indexing cognitive impairment in this population (AUC = .92; sensitivity = .92; specificity = .80). The Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.

This study aimed at assessing the clinimetrics of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of patients with adult-onset idiopathic focal dystonia (AOIFD). N = 86 AOIFD patients and N = 92 healthy controls (HCs) were administered the MoCA. Patients further underwent the Trail-Making Test (TMT) and Babcock Memory Test (BMT), being also screened via the Beck Depression Inventory-II (BDI-II) and the Dimensional Apathy Scale (DAS). Factorial structure and internal consistency were assessed. Construct validity was tested against TMT, BMT, BDI-II and DAS scores, whilst diagnostics against the co-occurrence of a defective performance on at least one TMT measure and on the BMT. Case–control discrimination was examined. The association between MoCA scores and motor-functional measures was explored. The MoCA was underpinned by a mono-component structure and acceptably reliable at an internal level. It converged towards TMT and BMT scores, as well as with the DAS, whilst diverging from the BDI-II. Its adjusted scores accurately detected cognitive impairment (AUC = .86) at a cut-off of < 17.212. The MoCA discriminated patients from HCs (p < .001). Finally, it was unrelated to disease duration and severity, as well as to motor phenotypes. The Italian MoCA is a valid, diagnostically sound and feasible cognitive screener in AOIFD patients.

Background Oropharyngeal dysphagia (OD) is common in Huntington’s disease (HD) and aspiration pneumonia is the leading cause of death in this population. Nevertheless, OD pathophysiology in HD is not well understood. Aims To investigate OD pathophysiology in patients with HD and its association with neurological data in different stages of the disease. Methods Twenty-four patients with HD (6 in stage I, 6 in stage II, 6 in stage III and 6 in stage IV) were recruited. Neurological examination was performed with the Unified Huntington’s Disease Rating Scale (UHDRS). Patient underwent a Fiberoptic Endoscopic Evaluation of Swallowing (FEES) and data on penetration/aspiration, residue and OD pathophysiology were gained. Maximum tongue pressure (MTP) and tongue endurance were measured. Results Regardless of HD stage, the most common pathophysiological mechanisms of OD were oropharyngeal dyspraxia (91.7%), posterior oral incontinence (87.5%), and delayed pharyngeal phase (87.5%). As the disease stage progresses, protective and propulsion deficits became more prevalent (Figure 1). Propulsion deficit was associated with disease stage and total motor function (UHDRS I) (p<0.05). Propulsion (p=0.010) and protective deficits (p<0.001) were significantly associated with penetration and aspiration. Propulsion deficit, resistive issue, posterior oral incontinence, and delayed pharyngeal phase were significantly associated with pharyngeal residues (p<0.05). MTP and tongue endurance significantly reduces in the more advanced stages of the disease (p<0.05) and were lower in patients with propulsion deficit (p<0.05). Conclusions OD in HD results from a combination of different pathophysiological mechanisms whose prevalence changes over the course of the disease.

Telemonitoring, a branch of telemedicine, involves the use of technological tools to remotely detect clinical data and evaluate patients. Telemonitoring of patients with Parkinson's disease (PD) should be performed using reliable and discriminant motor measures. Furthermore, the method of data collection and transmission, and the type of subjects suitable for telemonitoring must be well defined.

BackgroundThe semiology and determinants of apathy are largely unknown across amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Huntington’s disease (HD), due to both motor and non-motor confounders. This study thus aimed at (1) profiling apathy in ALS, PD, and HD and (2) exploring its clinical determinants.MaterialsConsecutive ALS (N = 99), PD (N = 73), and HD (N = 25) patients underwent a motor-free assessment of apathy (Dimensional Apathy Scale, DAS), global cognition, anxiety and depression. Function was assessed through disease-specific scales. The DAS was also completed by N = 101 healthy controls (HCs). Between-group comparisons on DAS scores were implemented by covarying for all applicable confounders. Predictive models on DAS scores were built through multiple, stepwise regressions.ResultsParkinson’s disease and HD, but not ALS, patients were more apathetic than HCs—with HD patients also selectively showing lower initiation and poorer goal-directed planning than HCs. Higher apathetic features were detected in PD and HD as compared to ALS. Education was a protective factor against apathy in ALS. Anxiety was a risk factor for global apathy in ALS, HD, and to a lesser extent, in PD, whereas, protective only toward affective disintegration in PD and ALS. Cognitive inefficiency was a risk factor toward apathy in both PD and ALS. Depression was a risk factor for executive-related apathy in PD.DiscussionThis study provides unprecedented insights into the heterogeneous semiology and determinants of apathy across ALS, PD, and HD via the DAS, in turn informing clinical practice and research.

We describe 3 cases of solitary sclerosis (SS), a rare condition characterized by a single inflammatory demyelinating lesion in the white matter of the brain or spinal cord. All patients had progressive limb motor impairment (patient 1, 66-year-old female: left spastic hemiparesis; patient 2, 39-year-old male: right spastic hemiparesis; patient 3, 42-year-old female: proximally predominant left upper limb weakness with amyotrophy and fasciculations). In all patients, MRI disclosed a single small T2-hyperintense demyelinating lesion: in the right anterior paramedian upper medulla, in the median-left paramedian anterior lower medulla, and in the left paramedian anterior cervical spinal cord at C4 level, respectively. In patients 1 and 2, transcranial magnetic stimulation (TMS) demonstrated altered motor evoked potentials (MEPs) and increased central motor conduction time (CMCT) in the affected limbs; in patient 3, needle EMG revealed chronic neurogenic changes in C5–C7 muscles of left upper limb. Patients 1 and 2 had normal brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). CSF analysis demonstrated IgG oligoclonal bands in all patients. In patients 2 and 3, levels of neurofilament light chain (NFL) in CSF and serum, respectively, were within normal limits. The three cases were consistent with the diagnosis of SS. Notably, while the first two cases mimicked Mills’ syndrome (the hemiparetic variant of primary lateral sclerosis, PLS), the third one was rather reminiscent of amyotrophic lateral sclerosis (ALS). This suggests including SS in the differential diagnosis not only of PLS, but also of ALS. We also report the first quantification of NFL levels in SS.

BackgroundThis study aimed at assessing the diagnostic properties of the Frontal Assessment Battery (FAB) as to its capability to (1) discriminate healthy controls (HCs) from patients with Huntington’s disease (HD) and (2) identify cognitive impairment in this population.MaterialsThirty-eight consecutive HD patients were compared to 73 HCs on the FAB. Patients further underwent the Montreal Cognitive Assessment (MoCA) and the Unified Huntington’s Disease Rating Scale (UHDRS). Receiver-operating characteristics (ROC) analyses were run to assess both intrinsic—i.e., sensitivity (Se) and specificity (Sp), and post-test diagnostics, positive and negative predictive values (PPV; NPV) and likelihood ratios (LR+; LR–), of the FAB both in a case–control setting and to identify, within the patient cohort, cognitive impairment (operationalized as a below-cut-off MoCA score). In patients, its diagnostic accuracy was also compared to that of the cognitive section of the UHDRS (UHDRS-II).ResultsThe FAB and UHDRS-II were completed by 100 and 89.5% of patients, respectively. The FAB showed optimal case–control discrimination accuracy (AUC = 0.86–0.88) and diagnostic properties (Se = 0.68–0.74; Sp = 0.88–0.9; PPV = 0.74–0.8; NPV = 0.84–0.87; LR+ = 5.6–7.68; LR– = 0.36–0.29), performing even better (AUC = 0.9–0.91) at identifying cognitive impairment among patients (Se = 0.73–1; Sp = 0.86–0.71; PPV = 0.79–0.71; NPV = 0.82–1; LR+ =5.13–3.5; LR– = 0.31–0) and comparably to the UHDRS-II (89% vs. 85% of accuracy, respectively; p = 0.46).DiscussionIn HD patients, the FAB is highly feasible for cognitive screening aims, being also featured by optimal intrinsic/post-test diagnostics within both case-control and case-finding settings.