Dreaming Characteristics in Non-Rapid Eye Movement Parasomnia and Idiopathic Rapid Eye Movement Sleep Behaviour Disorder: Similarities and Differences.

Background: Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst the notion that dreaming mentations reflect distinct physiologic processes is not new, such studies in patients with sleep disorders remain exceptionally scarce. Here, using SGA and other dream content analyses, we set to investigate structural and thematic differences in morning dream recalls of patients diagnosed with Non-Rapid Eye Movement Parasomnia (NREMP) and Idiopathic REM Sleep Behavior Disorder (iRBD). Methods: A retrospective cross-sectional study of morning dream recalls of iRBD and NREMP patients was undertaken. Traditional dream content analyses, such as Orlinsky and Hall and Van de Castle analyses, were initially conducted. Subsequently, SGA was performed in order to objectively quantify structural speech differences between the dream recalls of the two patient groups. Results: Comparable rate of morning recall of dreams in the sleep laboratory was recorded; 25% of iRBD and 18.35% of NREMP patients. Aggression in dreams was recorded by 28.57% iRBD versus 20.00% in NREMP group. iRBD patients were more likely to recall dreams (iRBD vs NREMP; P = 0.007), but they also had more white dreams, ie having a feeling of having dreamt, but with no memory of it. Visual and quantitative graph speech analyses of iRBD dreams suggested stable sequential structure, reflecting the linearity of the chronological narrative. Conversely, NREMP dream reports displayed more recursive, less stable systems, with significantly higher scores of graph connectivity measures. Conclusion: The findings of our exploratory study suggest that iRBD and NREMP patients may not only differ on what is recalled in their dreams but also, perhaps more strikingly, on how dreams are recalled. It is hoped that future SGA-led dream investigations of larger groups of patients will help discern distinct mechanistic underpinnings and any associated clinical implications.

Deep Learning-based Approach for Brainstem and Ventricular MR Planimetry: Application in Patients with Progressive Supranuclear Palsy.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To develop a fast and fully automated deep learning (DL)-based method for the MRI planimetric segmentation and measurement of the brainstem and ventricular structures most affected in patients with progressive supranuclear palsy (PSP). Materials and Methods In this retrospective study, T1-weighted MR images from healthy controls (n=84) were used to train DL models for segmenting the midbrain, pons, middle cerebellar peduncles (MCP), superior cerebellar peduncle (SCP), third ventricle (3rd V) and frontal horns (FHs). Internal, external and clinical test datasets (n=305) were used to assess segmentation model reliability. DL masks from test datasets were used to automatically extract midbrain and pons areas and the width of MCP, SCP, 3rd V and FHs. Automated measurements were compared with those manually performed by an expert radiologist. Finally, these measures were combined to calculate the midbrain-to-pons area ratio, magnetic resonance parkinsonism index (MRPI) and MRPI 2.0, which were used to differentiate patients with PSP (n=71) from those with Parkinson's disease (PD, n=129). Results Dice coefficients above 0.85 were found for all brain regions when comparing manual and DL-based segmentations. A strong correlation was observed between automated and manual measurements (Spearman's Rho>0.80, p<0.001). DL-based measurements showed excellent performance in differentiating patients with PSP from those with PD, with an area under the receiver operating characteristic curve above 0.92. Conclusion Automated approach successfully segmented and measured the brainstem and ventricular structures. DL-based models may represent a useful approach to support the diagnosis of PSP and potentially other conditions associated with brainstem and ventricular alterations. ©RSNA, 2024.

Sarcopenia in subjects with Alzheimer's disease: prevalence and comparison of agreement between EGWSOP1, EGWSOP2, and FNIH criteria.

BACKGROUND: Sarcopenia is an age-related clinical syndrome characterized by the progressive loss of muscle mass and muscle strength. It appears to be closely linked to dementia, particularly Alzheimer's disease (AD); however, its prevalence among AD patients remains unclear. In this study, we assessed differences in sarcopenia prevalence between non-demented individuals and AD patients. Moreover, we assessed sex-specific differences in sarcopenia prevalence and explored the diagnostic value of the Muscle Quality Index (MQI) for diagnosing sarcopenia among AD patients. METHOD: Cross-sectional study including 145 patients with probable AD and 51 older adults with normal cognition. Sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP1 and EWGSOP2) and of the Foundation for the National Institutes of Health (FNIH). The MQI was computed as the ratio of handgrip strength to skeletal muscle mass. RESULTS: No significant difference in sarcopenia prevalence was observed between AD patients and controls. Prevalence ranged from 3.4 to 23.4% in AD patients and from 2 to 11.8% in controls, depending on diagnostic criteria. Prevalence was higher using EWGSOP1 and decreased using EWGSOP2 and FNIH. Prevalence was higher in males than in females with AD. The MQI was lower in AD patients than in controls (95%CI: - 0.23, - 0.05, p < 0.001), but displayed poor diagnostic accuracy in identifying sarcopenia cases. CONCLUSIONS: AD patients and controls show comparable sarcopenia prevalence. Sarcopenia prevalence is higher in males than females among AD patients and higher when using EWGSOP1 compared to FNIH and EWGSOP2 criteria.

Nucleus Basalis of Meynert Degeneration Predicts Cognitive Decline in Corticobasal Syndrome.

BACKGROUND: Cognitive changes are common in corticobasal syndrome (CBS) and significantly impact quality of life and caregiver burden. However, relatively few studies have investigated the neural substrates of cognitive changes in CBS, and reliable predictors of cognitive impairment are currently lacking. The nucleus basalis of Meynert (NbM), which serves as the primary source of cortical cholinergic innervation, has been functionally associated with cognition. This study aimed to explore whether patients with CBS exhibit reduced NbM volumes compared with healthy control participants and whether NbM degeneration can serve as a predictor of cognitive impairment in patients with CBS. METHODS: In this study, we investigated in vivo volumetric changes of the NbM in 38 patients with CBS and 84 healthy control participants. Next, we assessed whether gray matter degeneration of the NbM evaluated at baseline could predict cognitive impairment during a 12-month follow-up period in patients with CBS. All volumetric analyses were performed using 3T T1-weighted images obtained from the 4-Repeat Tauopathy Neuroimaging Initiative. RESULTS: Patients with CBS displayed significantly lower NbM volumes than control participants (p < .001). Structural damage of the NbM also predicted the development of cognitive impairment in patients with CBS as assessed by longitudinal measurements of the Clinical Dementia Rating Sum of Boxes (p < .001) and Mini-Mental State Examination (p = .035). CONCLUSIONS: Our findings suggest that NbM atrophy may represent a promising noninvasive in vivo marker of cognitive decline in CBS and provide new insights into the neural mechanisms that underlie cognitive impairment in CBS.

Narcissistic Personality Disorder as Prodromal Feature of Early-Onset, GRN-Positive bvFTD: A Case Report.

Background: Behavioral variant frontotemporal dementia (bvFTD) typically involves subtle changes in personality that can delay a timely diagnosis. Objective: Here, we report the case of a patient diagnosed of GRN-positive bvFTD at the age of 52 presenting with a 7-year history of narcissistic personality disorder, accordingly to DSM-5 criteria. Methods: The patient was referred to neurological and neuropsychological examination. She underwent 3 Tesla magnetic resonance imaging (MRI) and genetic studies. Results: The neuropsychological examination revealed profound deficits in all cognitive domains and 3T brain MRI showed marked fronto-temporal atrophy. A mutation in the GRN gene further confirmed the diagnosis. Conclusions: The present case documents an unusual onset of bvFTD and highlights the problematic nature of the differential diagnosis between prodromal psychiatric features of the disease and primary psychiatric disorders. Early recognition and diagnosis of bvFTD can lead to appropriate management and support for patients and their families. This case highlights the importance of considering neurodegenerative diseases, such as bvFTD, in the differential diagnosis of psychiatric disorders, especially when exacerbations of behavioral traits manifest in adults.

Sleep and circadian rhythm disruptions in behavioral variant frontotemporal dementia.

INTRODUCTION: Sleep and rest-activity rhythm alterations are common in neurodegenerative diseases. However, their characterization in patients with behavioral variant frontotemporal dementia (bvFTD) has proven elusive. We investigated rest-activity rhythm alterations, sleep disturbances, and their neural correlates in bvFTD. METHODS: Twenty-seven bvFTD patients and 25 healthy controls completed sleep questionnaires and underwent 7 days of actigraphy while concurrently maintaining a sleep diary. Cortical complexity and thickness were calculated from T1-weighted magnetic resonance (MR) images. RESULTS: Compared to controls, bvFTD patients showed longer time in bed (95% confidence interval [CI]: 79.31, 321.83) and total sleep time (95% CI: 24.38, 321.88), lower sleep efficiency (95% CI: -12.58, -95.54), and rest-activity rhythm alterations in the morning and early afternoon. Increased sleep duration was associated with reduced cortical thickness in frontal regions. DISCUSSION: Patients with bvFTD showed longer sleep duration, lower sleep quality, and rest-activity rhythm alterations. Actigraphy could serve as a cost-effective and accessible tool for ecologically monitoring changes in sleep duration in bvFTD patients. HIGHLIGHTS: We assessed sleep and circadian rhythms in behavioral variant frontotemporal dementia (bvFTD) using actigraphy. Patients with bvFTD show increased sleep duration and reduced sleep quality. Patients with bvFTD show rest-activity alterations in the morning and early afternoon. Sleep duration is associated with reduced cortical thickness in frontal regions. These alterations may represent an early sign of neurodegeneration.

Survival in Incident Cases with Frontotemporal Lobar Degeneration: A Registry-Based Study.

Population-based registries represent a unique sample to estimate survival. The aim of the present study was to assess survival rates and predictors of outcome in incidental frontotemporal lobar degeneration (FTLD). Incident cases with FTLD, included between January 1, 2017 to December 31, 2017, have been followed for five years. Median survival was 8.16 years from disease onset and 5.38 years from diagnosis. Survival rates did not differ between phenotypes. Shorter disease duration from onset to diagnosis was associated with poorer outcome (p = 0.01). FTLD is a relatively homogeneous disease in terms of survival. Future multinational population-based studies are needed to confirm these findings.

Grey-matter correlates of empathy in 4-Repeat Tauopathies.

Loss of empathy is an early and central symptom of frontotemporal lobar degeneration spectrum diseases. We aimed to investigate the topographical distribution of morphometric brain changes associated with empathy in Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS) patients. Twenty-seven participants with CBS and 31 with PSP were evaluated using Interpersonal Reactivity Index scales in correlation with gray matter atrophy using a voxel-based morphometry approach. Lower levels of empathy were associated with an increased atrophy in fronto-temporal cortical structures. At subcortical level, empathy scores were positively correlated with gray matter volume in the amygdala, hippocampus and the cerebellum. These findings allow to extend the traditional cortico-centric view of cognitive empathy to the cerebellar regions in patients with neurodegenerative disorders and suggest that the cerebellum may play a more prominent role in social cognition than previously appreciated.

Hypothalamus and amyotrophic lateral sclerosis: potential implications in sleep disorders.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects both motor and non-motor functions, including sleep regulation. Emerging evidence suggests that the hypothalamus, a brain region that plays a critical role in sleep-wake regulation, may be involved in the pathogenesis of ALS-related sleep disturbances. In this review, we have summarized results of studies on sleep disorders in ALS published between 2000 and 2023. Thereafter, we examined possible mechanisms by which hypothalamic dysfunctions may contribute to ALS-related sleep disturbances. Achieving a deeper understanding of the relationship between hypothalamic dysfunction and sleep disturbances in ALS can help improve the overall management of ALS and reduce the burden on patients and their families.

Cortical signature of depressive symptoms in frontotemporal dementia: A surface-based analysis.

BACKGROUND AND OBJECTIVES: Depressive symptoms are frequently reported in patients affected by frontotemporal dementia (FTD). At structural MRI, cortical features of depressed FTD patients have been poorly described. Our objective was to investigate correlations between cortical measures and depression severity in FTD patients. METHODS: Data were obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) database. We included 98 controls and 92 FTD patients, n = 38 behavioral variant FTD (bvFTD), n = 26 non-fluent variant Primary Progressive Aphasia (nfvPPA), and n = 28 semantic variant Primary Progressive Aphasia (svPPA). Patients underwent clinical and cognitive evaluations, as well as a 3D T1-weighted MRI on a 3 Tesla scanner (Siemens, Trio Tim system). Depression was evaluated by means of Geriatric Depression Scale (GDS). Surface-based analysis was performed on T1-weighted images to evaluate cortical thickness, a measure of gray matter integrity, and local gyrification index (lGI), a quantitative metric of cortical folding. RESULTS: Patients affected by svPPA were more depressed than controls at NPI and depression severity at GDS was higher in svPPA and bvFTD. Severity of depression correlated with a decrease in lGI in left precentral and superior frontal gyrus, supramarginal and postcentral gyrus and right precentral, supramarginal, superior parietal and superior frontal gyri. Furthermore, depression severity correlated positively with cortical thickness in the left medial orbitofrontal cortex. DISCUSSION: We found that lGI was associated with depressive symptoms over brain regions involved in the pathophysiology of major depressive disorder. This finding provides novel insights into the mechanisms underlying psychiatric symptoms in FTD.

A Clinical Scale for Rating the Severity of Bulbar Lower Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of upper (UMN) and lower motor neurons (LMN) in four different body regions (bulbar, cervical, thoracic, and lumbosacral). Over the past decades, several clinical scoring systems have been developed to assess the UMN and LMN burden in ALS. However, concerning the bulbar LMN burden, the available scoring systems solely assess the presence/absence of bulbar LMN signs without providing a degree of impairment. Therefore, in this study, we proposed a novel scale to stratify subjects with ALS according to the bulbar LMN involvement and assessed its prognostic value. METHODS: We developed a four-item scale based on the LMN signs according to the El Escorial criteria. Ten raters, specializing in ALS or neurocognitive disorders, retrospectively applied the scale to the first evaluation of 195 patients with ALS. Cohen's kappa (Cohen's k) and an intra-class correlation coefficient (ICC) were used to assess the inter-rater reliability. The Kaplan-Mayer estimator was used to estimate survival distribution according to the bulbar scale scores. RESULTS: The raters showed a substantial to excellent agreement with Cohen's k, ranging from 0.834 to 0.975, with an overall ICC of 0.922 (95% CI = 0.906-0.936). The survival distribution was statistically different across the three bulbar scale scores (χ2(2) = 9.50, p < 0.01). CONCLUSIONS: Our bulbar LMN scale represents a reliable measure of the bulbar LMN signs in ALS. This easy-to-administer clinical scale could provide unique information in phenotyping and predicting survival in ALS.

Neurofilament light predicts worse nonmotor symptoms and depression in Parkinson's disease.

BACKGROUND: The identification of biomarkers that reflect worse progression of nonmotor symptoms (NMS) in Parkinson's disease (PD) is currently an unmet need. The main aim of this study was to investigate whether cerebrospinal fluid (CSF) and serum neurofilament light (NfL), measured at baseline or longitudinally, can be used to predict the progression of NMS in patients with PD. METHODS: Baseline and longitudinal NfL levels were measured in the CSF and serum in 392 PD patients and 184 healthy controls from the Parkinson's Progression Marker Initiative. NMS were assessed using several scales, including, but not restricted to, the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, the Geriatric Depression Scale (GDS) and the State-Trait Anxiety Inventory (STAI). The relationship between baseline and longitudinal NfL levels with changes in NMS was assessed using linear mixed effects models (LME) in PD patients. In addition, we compared CSF and serum NfL levels between groups and assessed the relationship between NfL biomarkers with baseline NMS. Finally, to assess the specificity of our findings we ran the previous LME models using other biomarkers such as CSF amyloid-ß1-42, total tau, phosphorylated tau181 and total α-synuclein and we also ran the models in healthy controls. RESULTS: Baseline levels and longitudinal changes in serum and CSF NfL predicted worse longitudinal MDS-UPDRS-I and depression scores over time in PD (p < 0.01). This relationship remained significant only for CSF NfL when controlling for motor and cognitive status. Furthermore, longitudinal changes in serum and CSF NfL were associated with worse anxiety over time in PD patients (p < 0.05). In contrast to CSF NfL, serum NfL levels were slightly higher at baseline (p = 0.043) and showed significant longitudinal increases (p < 0.001) in PD patients compared to controls. There were no significant correlations between NfL levels (CSF or serum) with other NMS scales, baseline NMS variables, other biomarkers or in healthy controls. CONCLUSIONS: Our findings indicate that both serum and CSF NfL are associated with worse longitudinal NMS burden, particularly in relation to the progression of depression and anxiety. Serum NfL showed stronger associations with NMS suggesting it could potentially be used as a non-invasive marker of NMS progression for PD.

Increased basal forebrain volumes could prevent cognitive decline in LRRK2 Parkinson's disease.

BACKGROUND AND OBJECTIVES: It has been recently suggested that LRRK2 mutations are associated with a more benign clinical phenotype and a potentially more preserved cholinergic function in Parkinson's disease (PD). However, to our knowledge, no studies have tested whether the better clinical progression observed in LRRK2-PD patients is associated with more preserved volumes of a cholinergic brain area, the basal forebrain (BF). To address this hypothesis, here we compared BF volumes in LRRK2 carriers with and without PD with respect to idiopathic PD (iPD) patients and controls, and assessed whether they are associated with better clinical progression observed in LRRK2-PD compared to iPD. METHODS: Thirty-one symptomatic LRRK2-PD patients and 13 asymptomatic LRRK2 individuals were included from the Parkinson's Progression Markers Initiative. In addition, 31 patients with iPD and 13 healthy controls matched to the previous groups were also included. BF volumes were automatically extracted from baseline T1-weighted MRI scans using a stereotactic atlas of cholinergic nuclei. These volumes were then compared between groups and their relationship with longitudinal cognitive changes was evaluated using linear mixed effects models. Mediation analyses assessed whether BF volumes mediated differences in cognitive trajectories between groups. RESULTS: LRRK2-PD patients showed significantly higher BF volumes compared to iPD (P = 0.019) as did asymptomatic LRRK2 subjects compared to controls (P = 0.008). There were no other significant differences in cortical regions or subcortical volumes between these groups. BF volumes predicted longitudinal decline in several cognitive functions in iPD patients but not in LRRK2-PD, who did not show cognitive changes over a 4-year follow-up period. BF volumes were a significant mediator of the different cognitive trajectories between iPD and LRRK2-PD patients (95% CI 0.056-2.955). DISCUSSION: Our findings suggest that mutations in LRRK2 are associated with increased BF volumes, potentially reflecting a compensatory hypercholinergic state that could prevent cognitive decline in LRRK2-PD patients.

The impact of upper and lower motor neuron burden on diagnostic certainty, and clinical course of spinal-onset amyotrophic lateral sclerosis: a cluster-based approach.

BACKGROUND: Upper motor neuron (UMN) and lower motor neuron (LMN) involvement represent the core clinical features of amyotrophic lateral sclerosis (ALS). Several studies divided patients into prevalent UMN and LMN impairment phenotypes to investigate the association between motor systems impairments and ALS clinical course. However, this distinction was somehow heterogeneous and significantly affected the comparability across studies. AIMS: This study aimed to investigate whether patients spontaneously segregate based on the extent of UMN and LMN involvement without a-priori categorization and to identify potential clinical and prognostic features of different clusters. METHODS: Eighty-eight consecutive spinal-onset ALS patients were referred to an ALS tertiary center between 2015 and 2022. UMN and LMN burden was assessed with the Penn Upper Motor Neuron scale (PUMNS) and the Devine score, respectively. PUMNS and LMN scores were normalized into 0-1 and analyzed using a two-step cluster analysis and the Euclidean distance measure. The Bayesian Information Criterion was used to determine the cluster number. Demographic and clinical variables were tested for differences among the clusters. RESULTS: Three distinct clusters emerged at cluster analysis. Patients in "cluster-1" showed moderate UMN and severe LMN involvement, corresponding to the typical ALS phenotype. Patients in "cluster-2" showed mild LMN and severe UMN damage, corresponding to a predominant UMN phenotype, while "cluster-3" patients showed mild UMN and moderate LMN damage, corresponding to a predominant LMN phenotype. Patients in "cluster-1" and "cluster-2" showed a higher prevalence of definite ALS than those in "cluster-3" (61% and 46 vs 9%, p < 0.001). "Cluster-1" patients had a lower median ALSFRS-r score compared to both "cluster-2" and 3 patients (27 vs 40 and 35, < 0.001). "Cluster-1" (HR: 8.5; 95% CI 2.1-35.1 and p = 0.003) and 3 (HR: 3.2; 95% CI 1.1-9.1; p = 0.03) were associated with shorter survival than those in "cluster-2". CONCLUSIONS: Spinal-onset ALS can be categorized into three groups according to LMN and UMN burden. The UMN burden is related to higher diagnostic certainty and broader disease spread, while LMN involvement is associated with higher disease severity and shorter survival.

Asymmetry of radiomics features in the white matter of patients with primary progressive aphasia.

Introduction: Primary Progressive Aphasia (PPA) is a neurological disease characterized by linguistic deficits. Semantic (svPPA) and non-fluent/agrammatic (nfvPPA) variants are the two main clinical subtypes. We applied a novel analytical framework, based on radiomic analysis, to investigate White Matter (WM) asymmetry and to examine whether asymmetry is associated with verbal fluency performance. Methods: Analyses were performed on T1-weighted images including 56 patients with PPA (31 svPPA and 25 nfvPPA) and 53 age- and sex-matched controls. Asymmetry Index (AI) was computed for 86 radiomics features in 34 white matter regions. The relationships between AI, verbal fluency performance (semantic and phonemic) and Boston Naming Test score (BNT) were explored through Spearman correlation analysis. Results: Relative to controls, WM asymmetry in svPPA patients involved regions adjacent to middle temporal cortex as part of the inferior longitudinal (ILF), fronto-occipital (IFOF) and superior longitudinal fasciculi. Conversely, nfvPPA patients showed an asymmetry of WM in lateral occipital regions (ILF/IFOF). A higher lateralization involving IFOF, cingulum and forceps minor was found in nfvPPA compared to svPPA patients. In nfvPPA patients, semantic fluency was positively correlated to asymmetry in ILF/IFOF tracts. Performances at BNT were associated with AI values of the middle temporal (ILF/SLF) and parahippocampal (ILF/IFOF) gyri in svPPA patients. Discussion: Radiomics features depicted distinct pathways of asymmetry in svPPA and nfvPPA involving damage of principal fiber tracts associated with speech and language. Assessing asymmetry of radiomics in PPA allows achieving a deeper insight into the neuroanatomical damage and may represent a candidate severity marker for language impairments in PPA patients.

Different patterns of spreading direction and motor neurons involvement in a cohort of limb-onset amyotrophic lateral sclerosis patients from Southern Italy: Potential implication on disease course or progression?

BACKGROUND: Currently, there is a lack of knowledge concerning where the pathological process starts and how the neurodegeneration spreads during the course of amyotrophic lateral sclerosis (ALS). AIMS: This study aims to evaluate the spreading direction of the disease and the corresponding clinical characteristics in a cohort of patients with limb-onset ALS. PATIENTS AND METHODS: Consecutive incident ALS patients referring to an ALS tertiary center from Southern Italy, between 2015 and 2021, were recruited in the study. According to the initial directions of spread, patients were dichotomized into horizontal spreading pattern (HSP) or vertical spreading pattern (VSP) groups. RESULTS: Among 137 newly diagnosed ALS, 87 presented a spinal onset. Ten patients with pure LMN were not included in the study. All cases reported a clear spread direction. The frequency of HSP and VSP spreading was similar overall (47 vs. 30). The prevalence of HSP was higher (74% vs. 50%) in patients with upper limb-onset (UL-ALS), compared to patients with lower limb-onset (LL-ALS; p < .05). Conversely, the occurrence of VSP spread was threefold higher in patients with LL-ALS, compared to UL-ALS (p < .05). Patients with VSP showed a wider upper motor neuron impairment, whereas the involvement of LMN resulted greater in patients with HSP. Patients with HSP exhibited a greater drop of ALSFRS-r sub-score in the region of onset, while VSP showed a slighter but more diffuse reduction of ASLFRS-r subscore in more body districts beyond the site of onset. Patients with VSP were also characterized by a higher median progression rate and an earlier median bulbar involvement, compared to HSP. CONCLUSIONS: Our findings suggested investigating the spreading direction of ALS among patients with spinal onset, to better delineate the clinical profiles of patients with ALS, and predict an earlier impairment of bulbar muscle and a more rapid progression of the disease.

Split-elbow sign in the PRO-ACT and Southern Italy ALS cohorts: a potential marker of disease severity and lower motor neuron involvement?

INTRODUCTION: Split phenomena in ALS refers to the preferential dysfunction of some groups of muscles over others. The split-elbow sign (SE) is characterized by the predominant weakness of the biceps compared to the triceps, but available results are conflicting. OBJECTIVES: To evaluate the prevalence of the SE in two independent cohorts: the randomized controlled trial-based PRO-ACT cohort (n = 500) and a monocentric cohort of patients with ALS from Southern Italy (n = 144); to investigate the demographic and clinical variables associated with the SE sign. METHODS: Wilcoxon signed-rank test was used to compare biceps with triceps power in the same limb measured by hand-held dynamometry in the PRO-ACT cohort and Medical Research Council (MRC) in our cohort. Each limb was considered independently and not paired within the same individual. The arm where the triceps was stronger than the biceps was defined SE + , whereas the arm where the biceps was stronger than the triceps was considered SE-. A backward stepwise multivariate logistic regression was used to analyze the relationship between clinical and demographic variables and SE. PENN Upper Motor Neuron and Devine scales were used to evaluate the different upper (UMN) and lower (LMN) motor neuron impairments between the SE + and SE- arms. RESULTS: In both cohorts, the biceps were on average stronger than the triceps, and the SE sign was present in 41% of the PRO-ACT cohort and just 30% of the Southern Italy cohort. The multivariate logistic regression revealed that older age (OR: 1.45; p = 0.01), male gender (OR: 1.55; p = 0.002), spinal onset (OR: 1.59; p = 0.007), and higher disease severity (OR: 1.70; p = 0.001) were significant predictors of the SE sign in the PRO-ACT cohort. Conversely, in Southern Italy patients, only a lower ALSFRS-R score was a significant determinant of the SE (OR: 8.47; p = 0.008). Finally, SE + arms exhibited a significantly higher median Devine sub-score compared to SE- [1 vs 0, p = < 0.05], while arms SE- showed a significantly higher median PUMNS sub-score [2 vs 0; p = < 0.05)]. CONCLUSION: In our study, most patients with ALS do not show SE. Patients with SE are more likely older, males, with spinal onset, a higher degree of disease severity, and predominant and wider LMN impairment.

Amyotrophic Lateral Sclerosis-The Complex Phenotype-From an Epidemiological Perspective: A Focus on Extrapyramidal and Non-Motor Features.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease (MND) and has emerged, among the disorders, with the largest increase in incidence in Western countries. Although the typical clinical phenotype of ALS involves simultaneous upper and lower motor neurons, there is growing evidence that the neurodegeneration during the course of the disease can also involve other motor and non-motor regions. In this review, we analyzed and discussed available data from epidemiological population-based studies on extrapyramidal and non-motor features during the course of ALS.