Longitudinal change of energy expenditure, body composition and dietary habits in Progressive Supranuclear Palsy patients.

INTRODUCTION: Alterations in metabolic status, body composition, and food intake are present in all neurodegenerative diseases. Aim of this study was to detect the progression of these changes in Progressive Supranuclear Palsy (PSP). METHODS: We conducted a longitudinal study of 15 patients with PSP. The assessments were performed at baseline (T0) and after 7(IQR = 5) months of follow-up (T1). We collected anthropometric measures including body weight, height, body mass index and waist circumference, metabolic parameters through indirect calorimeters, body composition using bioimpedance analysis, and dietary habits with a validated questionnaire. PSP-rating scale (PSP-rs) was used to evaluate disease severity and dysphagia. RESULTS: The majority of patients (66.66%) presented PSP-Richardson Syndrome and 33.33% the other variant syndromes of the disease. At T1 there was a decrease in intake of total daily calories (p < 0.001), proteins (p < 0.001), fibers (p = 0.001), calcium (p = 0.008), iron (p < 0.001), zinc (0.034), vitamin E (p = 0.006) and folates (p = 0.038) compared to T0. No other changes were found. As for T1 data, no significant differences were shown according to disease phenotypes or the presence of clinically significant dysphagia for solids. CONCLUSIONS: Within a mid-term follow up, PSP patients presented reduced caloric and proteins intake regardless the presence of dysphagia. The PSP-rs is likely not adequate to assess dysphagia, which should be investigated by specific clinical scales or instrumental examinations. With the goal of maintaining adequate nutritional status, the administration of protein and vitamin supplements should be considered even in the absence of dysphagia evidenced by the rating scales.

Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms. OBJECTIVES: This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP. METHODS: Twenty-five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2-week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance. RESULTS: We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints. CONCLUSIONS: A 2-week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.

Agreement between Optoelectronic System and Wearable Sensors for the Evaluation of Gait Spatiotemporal Parameters in Progressive Supranuclear Palsy.

The use of wearable sensors for calculating gait parameters has become increasingly popular as an alternative to optoelectronic systems, currently recognized as the gold standard. The objective of the study was to evaluate the agreement between the wearable Opal system and the optoelectronic BTS SMART DX system for assessing spatiotemporal gait parameters. Fifteen subjects with progressive supranuclear palsy walked at their self-selected speed on a straight path, and six spatiotemporal parameters were compared between the two measurement systems. The agreement was carried out through paired data test, Passing Bablok regression, and Bland-Altman Analysis. The results showed a perfect agreement for speed, a very close agreement for cadence and cycle duration, while, in the other cases, Opal system either under- or over-estimated the measurement of the BTS system. Some suggestions about these misalignments are proposed in the paper, considering that Opal system is widely used in the clinical context.

Frequency and imaging correlates of neuropsychiatric symptoms in Progressive Supranuclear Palsy.

Neuropsychiatric symptoms are intrinsic to Progressive Supranuclear Palsy (PSP) and a spoonful of studies investigated their imaging correlates. Describe (I) the frequency and severity of neuropsychiatric symptoms in PSP and (II) their structural imaging correlates. Twenty-six PSP patients underwent Neuropsychiatric Inventory (NPI) and brain 3D T1-weighted MRI. Spearman's rho with Bonferroni correction was used to investigate correlations between NPI scores and volumes of gray matter regions. More than 80% of patients presented at least one behavioral symptom of any severity. The most frequent and severe were depression/dysphoria, apathy, and irritability/lability. Significant relationships were found between the severity of irritability and right pars opercularis volume (p < 0.001) as well as between the frequency of agitation/aggression and left lateral occipital volume (p < 0.001). Depression, apathy, and irritability are the most common neuropsychiatric symptoms in PSP. Moreover, we found a relationship between specific positive symptoms as irritability and agitation/aggression and greater volume of the right pars opercularis cortex and lower volume of the left occipital cortex, respectively, which deserve further investigations.

Wearable sensors for assessing disease severity and progression in Progressive Supranuclear Palsy.

INTRODUCTION: Progressive supranuclear palsy (PSP) is an atypical parkinsonism characterized by prominent gait and postural impairment. The PSP rating scale (PSPrs) is a clinician-administered tool to evaluate disease severity and progression. More recently, digital technologies have been used to investigate gait parameters. Therefore, object of this study was to implement a protocol using wearable sensors evaluating disease severity and progression in PSP. METHODS: Patients were evaluated with the PSPrs as well as with three wearable sensors located on the feet and lumbar area. Spearman coefficient was used to assess the relationship between PSPrs and quantitative measurements. Furthermore, sensor parameters were included in a multiple linear regression model to assess their ability in predicting the PSPrs total score and sub-scores. Finally, differences between baseline and three-month follow-up were calculated for PSPrs and each quantitative variable. The significance level in all analyses was set at ≤ 0.05. RESULTS: Fifty-eight evaluations from thirty-five patients were analyzed. Quantitative measurements showed multiple significant correlations with the PSPrs scores (r between 0.3 and 0.7; p < 0.05). Linear regression models confirmed the relationships. After three months visit, significant worsening from baseline was observed for cadence, cycle duration and PSPrs item 25, while PSPrs item 10 showed a significant improvement. CONCLUSION: We propose wearable sensors can provide an objective, sensitive quantitative evaluation and immediate notification of gait changes in PSP. Our protocol can be easily introduced in outpatient and research settings as a complementary tool to clinical measures as well as an informative tool on disease severity and progression in PSP.

Temporal muscle thickness and survival in patients with amyotrophic lateral sclerosis.

Temporal muscle thickness (TMT) is a new potential MRI biomarker, which has shown prognostic relevance in neuro-oncology. We aim at investigating the potential prognostic value of TMT in patients with Amyotrophic Lateral Sclerosis (ALS). We retrospectively evaluated 30 ALS patients, whose clinical, Magnetic Resonance Imaging (MRI) and Electrodiagnostic testing (EDX) data were available, in comparison to age-matched 30 healthy subjects. TMT calculated on T1-weighted MR images was significantly lower in ALS patients than in healthy subjects (p < 0.001), correlating with the ALS Functional Rating Scale (FRS) (p:0.018) and compound motor action potential (CMAP) (p:0.012) in the patients group. Multivariate analysis of overall survival (OS) showed that the only parameters that remained significant were TMT (p:0.002, OR 0.45, 95%vCI: 0.28-0.75) and ALS FRS-R (p:0.023, OR: 0.80, 95%CI: 0.67-0.92). TMT seems to be a promising surrogate biomarker of survival and functional status in ALS. Our data deserve further investigations in multicenter and prospective trials.

Retinal thinning in progressive supranuclear palsy: differences with healthy controls and correlation with clinical variables.

BACKGROUND: Available evidence reports conflicting data on retinal thickness in progressive supranuclear palsy (PSP). In studies including healthy controls, PSP showed either the thinning of the retinal nerve fiber layer, macular ganglion cell, inner nuclear, or outer retina layer. OBJECTIVES: The goals of the present study were to describe retinal layer thickness in a large cohort of PSP compared to healthy controls and in PSP phenotypes using spectral-domain optical coherence tomography (SD-OCT). The additional objective was to verify the relationship between retinal layers thickness and clinical variables in PSP. METHODS: Using a cross-sectional design, we examined retinal structure in 27 PSP patients and 27 controls using standard SD-OCT. Motor and cognitive impairment in PSP was rated with the PSP rating scale and the Montreal Cognitive Assessment battery (MoCA), respectively. Eyes with poor image quality or confounding diseases were excluded. SD-OCT measures of PSP and controls were compared with parametric testing, and correlations between retinal layer thicknesses and disease severity were evaluated. RESULTS: PSP showed significant thinning of the inner retinal layer (IRL), ganglion cell layer (GCL), inner plexiform layer (IPL), and the outer plexiform layer (OPL) compared to healthy controls. PSP phenotypes showed similar retinal layer thicknesses. Retinal layer thickness correlated with MoCA visuospatial subscore (p < 0.001). CONCLUSIONS: We demonstrated PSP patients disclosed thinner IRL, GCL, IPL, and OPL compared to healthy controls. Furthermore, we found a significant correlation between visuospatial abilities and retinal layers suggesting the existence of a mutual relationship between posterior cognitive function and retinal structure.

Uncovering clinical and radiological asymmetry in progressive supranuclear palsy-Richardson's syndrome.

BACKGROUND: Richardson's syndrome (RS) is considered the most symmetric phenotype of progressive supranuclear palsy (PSP) as opposed to PSP with predominant corticobasal syndrome (PSP-CBS) or parkinsonism (PSP-P). OBJECTIVES: Evaluate asymmetrical motor and higher cortical features in probable PSP-RS and compare the degree of asymmetry of cortical lobes and hemispheres between PSP-RS, PSP-CBS, PSP-P, and age-matched healthy controls (HC). METHODS: Asymmetry of motor and higher cortical features evaluated with an extensive videotaped neurologic examination was investigated in 28 PSP-RS, 8 PSP-CBS, and 14 PSP-P. Brain MRI to compute the laterality index (LI) was performed in 36 patients as well as in 56 HC. RESULTS: In PSP-RS, parkinsonism was the most common asymmetric motor feature (53.6%), followed by dystonia and myoclonus (21.4% and 17.9%, respectively). Among higher cortical features, limb apraxia was found asymmetric in about one-third of patients. PSP-RS disclosed higher LI for hemispheres compared to HC, indicating a greater degree of asymmetry (p = 0.003). The degree of asymmetry of clinical features was not different between PSP-RS and those qualifying for PSP-CBS or PSP-P. As for imaging, LI was not different between PSP-RS, PSP-CBS, and PSP-P in any cortical region. CONCLUSIONS: Motor and higher cortical features are asymmetric in up to 50% of PSP-RS who also present a greater degree of asymmetry in hemispheres compared to age-matched HC. Lateralization of clinical features should be annotated in PSP.

Energy expenditure, body composition and dietary habits in progressive supranuclear palsy.

INTRODUCTION: Little is known about metabolic changes in progressive supranuclear palsy. Goals of the present study are to: (1) investigate whether early progressive supranuclear palsy is associated with changes in energy expenditure, body composition and dietary intake compared with Parkinson's disease and healthy controls; (2) assess the accuracy of the Harris-Benedict equation to predict measured rest energy expenditure in progressive supranuclear palsy; (3) verify differences according to sex, phenotypes, disease severity and presence of dysphagia in progressive supranuclear palsy. METHODS: Twenty-one progressive supranuclear palsy, 41 Parkinson's disease and nine healthy controls were included. Rest energy expenditure was assessed with indirect calorimeter, body composition with bio-impedance analysis and physical activity and dietary intake were estimated with a validated frequency questionnaire. Parametric testing was used to analyze differences between groups. RESULTS: Progressive supranuclear palsy showed reduced total daily energy expenditure and physical activity compared to both other cohorts (p < 0.001) and a tendency toward lower fat-free mass compared to Parkinson's disease (p > 0.05). Limited accuracy was shown for the Harris-Benedict equation (accurate prediction frequency < 60%). Greater disease severity was associated with lower rest energy expenditure (p = 0.030), fat-free mass (p = 0.026) and muscle mass (p = 0.029). CONCLUSION: Greater disease severity is associated with reduction in rest energy expenditure likely due to the reduction in lean mass and muscle mass. Such data may pave the way to clinical trials evaluating the efficacy of muscle-targeted nutritional support and physical therapy in preserving muscle mass and improving motor performances in progressive supranuclear palsy at early stages.

Psychometric properties of the Beck Depression Inventory-II in progressive supranuclear palsy.

OBJECTIVES: Depression is one of the most common neuropsychiatric symptoms in progressive supranuclear palsy (PSP). Yet, few studies have examined the ability of available instruments to detect depressive symptoms in PSP. Aims of the present study were to (I) report psychometric properties of the Beck Depression Inventory Second Edition (BDI-II) in PSP, (II) establish the BDI-II cut-off indicating the presence of depression in PSP and (III) describe clinical correlates as well as correlation with quality of life of depressive symptoms in PSP. DESIGN, SETTING AND PARTICIPANTS: At the Center for Neurodegenerative Diseases of the University of Salerno, Italy, the BDI-II was validated in 62 PSP patients diagnosed according to the Movement Disorder Society criteria. Patients underwent a clinical interview, a motor evaluation, extensive cognitive and behavioral testing. RESULTS: The mean BDI-II total score was 15.92 ± 10.31. The internal consistency was high (Cronbach's alpha = 0.868); corrected item-total correlation was >0.40 for the majority of items. The significant and moderate correlation of the BDI-II with other tools evaluating depressive symptoms indicated adequate convergent validity of the scale. The satisfactory cut-off to identify patients with clinically significant depression was >14.5. We also showed a correlation between higher scores on BDI-II and lower quality of life, irrespective of motor and cognitive burden. CONCLUSION: In conclusion, the BDI-II is a reliable and valid tool for the assessment of depression symptoms in PSP. Such data are useful to standardize studies of depression in PSP and to quantify the effectiveness of any interventions on this disabling symptom.

Gait Analysis in Progressive Supranuclear Palsy Phenotypes.

The objective of the present study was to describe gait parameters of progressive supranuclear palsy (PSP) phenotypes at early stage verifying the ability of gait analysis in discriminating between disease phenotypes and between the other variant syndromes of PSP (vPSP) and Parkinson's disease (PD). Nineteen PSP (10 PSP-Richardson's syndrome, five PSP-parkinsonism, and four PSP-progressive gait freezing) and nine PD patients performed gait analysis in single and dual tasks. Although phenotypes showed similar demographic and clinical variables, Richardson's syndrome presented worse cognitive functions. Gait analysis demonstrated worse parameters in Richardson's syndrome compared with the vPSP. The overall diagnostic accuracy of the statistical model during dual task was almost 90%. The correlation analysis showed a significant relationship between gait parameters and visuo-spatial, praxic, and attention abilities in PSP-Richardson's syndrome only. vPSP presented worse gait parameters than PD. Richardson's syndrome presents greater gait dynamic instability since the earliest stages than other phenotypes. Computerized gait analysis can differentiate between PSP phenotypes and between vPSP and PD.

Gait analysis may distinguish progressive supranuclear palsy and Parkinson disease since the earliest stages.

Progressive supranuclear palsy (PSP) is a rare and rapidly progressing atypical parkinsonism. Albeit existing clinical criteria for PSP have good specificity and sensitivity, there is a need for biomarkers able to capture early objective disease-specific abnormalities. This study aimed to identify gait patterns specifically associated with early PSP. The study population comprised 104 consecutively enrolled participants (83 PD and 21 PSP patients). Gait was investigated using a gait analysis system during normal gait and a cognitive dual task. Univariate statistical analysis and binary logistic regression were used to compare all PD patients and all PSP patients, as well as newly diagnosed PD and early PSP patients. Gait pattern was poorer in PSP patients than in PD patients, even from early stages. PSP patients exhibited reduced velocity and increased measures of dynamic instability when compared to PD patients. Application of predictive models to gait data revealed that PD gait pattern was typified by increased cadence and longer cycle length, whereas a longer stance phase characterized PSP patients in both mid and early disease stages. The present study demonstrates that quantitative gait evaluation clearly distinguishes PSP patients from PD patients since the earliest stages of disease. First, this might candidate gait analysis as a reliable biomarker in both clinical and research setting. Furthermore, our results may offer speculative clues for conceiving early disease-specific rehabilitation strategies.

Association of MRI Measures With Disease Severity and Progression in Progressive Supranuclear Palsy.

Objective: To verify the association of midbrain-based MRI measures as well as cortical volumes with disease core features and progression in patients with Progressive Supranuclear Palsy (PSP). Methods: Sixty-seven patients (52.2% with Richardson's syndrome) were included in the present analysis. Available midbrain-based MRI morphometric assessments as well as cortical lobar volumes were computed. Ocular, gait and postural involvement at the time of MRI was evaluated with the PSP rating scale. Specific milestones or death were used to estimate disease progression up to 72 months follow up. Hierarchical regression models and survival analysis were used for analyzing cross-sectional and longitudinal data, respectively. Results: Multivariate models showed vertical supranuclear gaze palsy was associated with smaller midbrain area (OR: 0.02, 95% CI 0.00-0.175, p = 0.006). Cox regression adjusted for age, disease duration, and phenotype demonstrated that lower midbrain area (HR: 0.122, 95% CI 0.030-0.493, p = 0.003) and diameter (HR: 0.313, 95% CI 0.112-0.878, p = 0.027), higher MR Parkinsonism Index (HR: 6.162, 95% CI 1.790-21.209, p = 0.004) and larger third ventricle width (HR: 2.755, 95% CI 1.068-7.108, p = 0.036) were associated with higher risk of dependency on wheelchair. Conclusions: Irrespective of disease features and other MRI parameters, reduced midbrain size is significantly associated with greater ocular motor dysfunction at the time of MRI and more rapid disease progression over follow up. This is the first comprehensive study to systematically assess the association of available midbrain-based MRI measures and cortical volumes with disease severity and progression in a large cohort of patients with PSP in a real-world setting.

Effects of gender on cognitive and behavioral manifestations in multiple system atrophy.

Gender differences have been described in several neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The effects of gender on cognitive and behavioral manifestations in multiple system atrophy and the changes of cognitive functions over time according to gender have not been investigated so far. Fifty-five patients with a diagnosis of multiple system atrophy underwent a comprehensive neuropsychological and neuropsychiatric battery at baseline and 26 of them could be re-evaluated at 1-year follow-up. At baseline women with multiple system atrophy had poorer global cognitive state and visuo-spatial abilities, and a higher prevalence of depression and apathy than males. At follow-up, female patients deteriorated more than males on attention abilities and motor functions, and had a higher prevalence of depression than men. Executive functions and visuo-spatial abilities significantly worsened over time in both groups. Mild Cognitive Impairment single domain was significantly more frequent in females than males. Cognitive and behavioral differences between genders in multiple system atrophy involve global cognition, planning, attention, visual-perceptive skills, and depression, with female patients more compromised than males. Female patients deteriorated more than men over time as for motor functions and attention. Further longitudinal studies are deserved to confirm gender differences in progression of cognitive and behavioral features of multiple system atrophy.

Midbrain MRI assessments in progressive supranuclear palsy subtypes.

OBJECTIVES: To explore the role of the available midbrain-based MRI morphometric assessments in (1) differentiating among progressive supranuclear palsy (PSP) subtypes (PSP Richardson's syndrome (PSP-RS), PSP with predominant parkinsonism (PSP-P) and the other variant syndromes of PSP (vPSP)), and (2) supporting the diagnosis of PSP subtypes compared with Parkinson's disease (PD) and healthy controls (HC). METHODS: Seventy-eight patients with PSP (38 PSP-RS, 21 PSP-P and 19 vPSP), 35 PD and 38 HC were included in the present analysis. Available midbrain-based MRI morphometric assessments were calculated for all participants. RESULTS: Current MRI midbrain-based assessments do not display an adequate sensitivity and specificity profile in differentiating PSP subtypes. On the other hand, we confirmed MR Parkinsonism Index (MRPI) and pons area to midbrain area ratio (P/M) have adequate diagnostic value to support PSP-RS clinical diagnosis compared with both PD and HC, but low sensitivity and specificity profile in differentiating PSP-P from PD as well as from HC. The same measures show acceptable sensitivity and specificity profile in supporting clinical diagnosis of vPSP versus HC but not versus PD. Similar findings were detected for the newer MRPI and P/M versions. CONCLUSIONS: Further studies are warranted to identify neuroimaging biomarkers supporting the clinical phenotypic categorisation of patients with PSP. MRPI and P/M have diagnostic value in supporting the clinical diagnosis of PSP-RS. CLASSIFICATION OF EVIDENCE: This study provides class III evidence that available MRI midbrain-based assessments do not have diagnostic value in differentiating the Movement Disorder Society PSP subtypes.