Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation.

We present an in-depth clinical and neuroimaging analysis of a family carrying the MAPT K298E mutation associated with frontotemporal dementia (FTD). Initial identification of this mutation in a single clinical case led to a comprehensive investigation involving four affected siblings allowing to elucidate the mutation's phenotypic expression.A 60-year-old male presented with significant behavioral changes and progressed rapidly, exhibiting speech difficulties and cognitive decline. Neuroimaging via FDG-PET revealed asymmetrical frontotemporal hypometabolism. Three siblings subsequently showed varied but consistent clinical manifestations, including abnormal behavior, speech impairments, memory deficits, and motor symptoms correlating with asymmetric frontotemporal atrophy observed in MRI scans.Based on the genotype-phenotype correlation, we propose that the p.K298E mutation results in early-onset behavioral variant FTD, accompanied by a various constellation of speech and motor impairment.This detailed characterization expands the understanding of the p.K298E mutation's clinical and neuroimaging features, underlining its role in the pathogenesis of FTD. Further research is crucial to comprehensively delineate the clinical and epidemiological implications of the MAPT p.K298E mutation.

Olympic Weightlifting Training for Sprint Performance in Athletes: A Systematic Review with Meta-analysis.

This systematic review and meta-analysis aimed to determine whether Olympic weightlifting (OW) exercises would improve sprint performance when compared to a control intervention, (no training, standard sport-specific training, traditional resistance training, or plyometric training). Medline, Web of Science, SportDiscus, CINAHL, and Biological Science from inception to September 2022 was searched. Two authors independently selected the included studies, extracted data, and appraised the risk of bias. Certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. The primary meta-analysis combined the results of the sprint performance over the full length of each sprint test. The secondary meta-analyses combined the results of the sprint performance at 5, 10, and 20 m distance to capture information about the acceleration phase of the sprint tests. Eight studies with 206 athletes (female n=10, age range: 18.9-24.2 years) were identified. Sprint performance did not differ significantly comparing OW to the control intervention, nor at the full length (standardized mean difference=-0.07, 95% CI=-0.47 to 0.34, p=0.75, I2=46%) or during the acceleration phase (p≥0.26) of the sprint test. OW training does not improve sprint performance to a greater extent than comparator interventions.

Reliability of Respiratory System Compliance Calculation During Assisted Mechanical Ventilation: A Retrospective Study.

OBJECTIVES: To compare respiratory system compliance (C rs ) calculation during controlled mechanical ventilation (MV) and, subsequently, during assisted MV. DESIGN: This is a single-center, retrospective, observational study. SETTING: This study was conducted on patients admitted to Neuro-ICU of Niguarda Hospital (tertiary referral hospital). PATIENTS: We analyzed every patient greater than or equal to 18 years old having a C rs measurement in controlled and in assisted MV within 60 minutes. Plateau pressure (P plat ) was considered reliable if it was deemed visually stable for at least 2 seconds. INTERVENTIONS: Inspiratory pause was incorporated to detect P plat in controlled and assisted MV. Calculation of C rs and driving pressure were achieved. MEASUREMENTS AND MAIN RESULTS: A total of 101 patients were studied. An acceptable agreement was found (Bland-Altman plot bias -3.9, level of agreement upper 21.6, lower -29.6). C rs in assisted MV was 64.1 (52.6-79.3) and in controlled MV it was 61.2 (50-71.2) mL/cm H 2o ( p = 0.006). No statistical difference was found in C rs (assisted vs controlled MV) when peak pressure was lower than P plat nor when peak pressure was higher than P plat . CONCLUSIONS: A P plat visually stable for at least 2 seconds leads to reliable C rs calculation during assisted MV.

Neurological soft signs are increased in migraine without aura: relationship with the affective status.

INTRODUCTION: Neurological soft signs (NSS) are subtle non-localizing sensorimotor abnormalities initially reported as increased in primary headache patients. The aims of this study were confirming with full power NSS increased expression in migraine and, collaterally, determining if psychiatric traits or white matter lesions at brain imaging could influence this result. METHODS: Forty drug-free episodic migraine outpatients (MH) were recruited with 40 matched controls. NSS were determined by the 16-item Heidelberg scale; depression, anxiety and QoL by the HAM-D; the STAI-X1/X2; and the SF36, respectively. The Fazekas scale on brain MR studies was applied in n = 32 MH, unravelling deep white matter signal alterations (DWM). MH characteristics, including the headache disability inventory (HDI), were recorded. RESULTS: NSS were 46% increased in MH vs. controls (p = 0.0001). HAM-D and STAI-X1/X2 were increased in MH, while SF36 was unchanged, but they all failed to influence NSS, just as MH characteristics. NSS scores were increased in MH-DWM + (n = 11, + 85%) vs. MH-DWM - (n = 21, + 27%) vs. controls (p < 0.0001). NSS increased expression in MH was influenced by DWM, while psychiatric traits and headache characteristics failed to do so. DISCUSSION/CONCLUSIONS: NSS are increased in MH and probably not influenced by the affective status, possibly marking a dysfunction within the cerebellar-thalamic-prefrontal circuit that may deserve further attention from the prognostic point of view.

Essential tremor and cognitive impairment: who, how, and why.

BACKGROUND AND AIMS: Recent years have witnessed the switch from considering essential tremor (ET) a monosymptomatic disorder to consider it as part of a spectrum, including other neurological signs, such as mild cognitive impairment and dementia, thus defining it as "ET plus." There are few data on cognitive impairment in ET patients. The aim of this review is to analyze the clinical characteristics of ET patients developing cognitive impairment, their neuropsychological profile, the underpinning mechanisms, and the possible biomarkers. METHODS: The authors performed a narrative review on cognitive decline in essential tremor, including articles written in English since the year 2000. DISCUSSION: The most recent pathogenetic theories of cognitive impairment in ET rely on the cerebellar dysfunction, being part of the Cerebellar Cognitive Affective Syndrome spectrum. Cognitive impairment in ET patients could be assessed through many tests that demonstrate the involvement of different domains, such as attention, executive functions, and language. There are some clinical characteristics of ET that may indicate a greater risk of developing cognitive impairment, namely, cerebellar symptoms, falls, age at onset, and family history. However, there are no established clinical, neurophysiological, neuropathological, and fluid biomarkers of cognitive impairment in ET. CONCLUSIONS: Increasing data are showing in ET the presence of cerebellar symptoms and cognitive impairment. Further studies are needed to better understand cognition in ET patients, and to define the boundary between ET and ET plus, since deeper phenotyping might have important clinical and therapeutic implications.

Development of shoulder pain with job-related repetitive load: mechanisms of tendon pathology and anxiety.

BACKGROUND: The paucity of longitudinal clinical studies limits our understanding of the development of shoulder pain with repetitive shoulder tasks, and its association with underlying mind and body mechanisms. Tendon thickening characterizes painful shoulder supraspinatus tendinopathy, and the perception of pain can be affected by the presence of psychological factors such as anxiety and depression. This study determined the incidence of shoulder pain in novice individuals exposed to repetitive shoulder tasks, and the associated change in outcomes of supraspinatus tendon morphology and measures of anxiety and depression. METHODS: We recruited dental hygiene (DH) students (n = 45, novice and exposed to shoulder repetitive tasks) and occupational therapy (OT) students (n = 52, novice, but not exposed to shoulder repetitive tasks), following them over their first year of training. We measured shoulder pain, supraspinatus morphology via ultrasonography, and psychosocial distress via the Hospital Anxiety and Depression Scale. We compared the incidence of shoulder pain (defined as a change of visual analog scale for pain score greater than the minimal clinically important difference) between DH and OT students using Fisher exact test. We used mixed effects models to longitudinally compare the change in outcomes between 3 groups: DH students who develop and did not develop shoulder pain, and OT students. RESULTS: The incidence of shoulder pain is higher in DH students (relative risk = 4.0, 95% confidence interval [CI] 1.4, 11.4). After 1 year, DH students with pain had the greatest thickening of the supraspinatus (0.7 mm, 95% CI 0.4, 0.9). The change in supraspinatus thickness of DH students with pain was greater than both DH students with no pain (0.4 mm, 95% CI 0.1, 0.8) and OT students (0.9 mm, 95% CI 0.5, 1.2). Anxiety score increased 3.8 points (95% CI 1.6, 5.1) in DH students with pain, and 43% of DH students with pain had abnormal anxiety score at 1 year (relative risk = 2.9, 95% CI 1.0, 8.6). CONCLUSION: Our results provide support for the theoretical model of repetitive load as a mechanism of tendinopathy. The supraspinatus tendon thickens in the presence of repetitive tasks, and it thickens the most in those who develop shoulder pain. Concurrently, anxiety develops with shoulder pain, indicating a potential maladaptive central mechanism that may impact the perception of pain.

Preseason shoulder range of motion screening and in-season risk of shoulder and elbow injuries in overhead athletes: systematic review and meta-analysis.

OBJECTIVE: To characterise whether preseason screening of shoulder range of motion (ROM) is associated with the risk of shoulder and elbow injuries in overhead athletes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Six electronic databases up to 22 September 2018. ELIGIBILITY CRITERIA: Inclusion criteria were (1) overhead athletes from Olympic or college sports, (2) preseason measures of shoulder ROM, (3) tracked in-season injuries at the shoulder and elbow, and (4) prospective cohort design. Exclusion criteria were (1) included contact injuries, (2) lower extremity, spine and hand injuries, and (3) full report not published in English. RESULTS: Fifteen studies were identified, and they included 3314 overhead athletes (baseball (74.6%), softball (3.1%), handball (16.1%), tennis (2.0%), volleyball (2.0%) and swimming (2.2%)). Female athletes are unrepresented (12% of the overall sample). Study quality ranged from 11 to 18 points on a modified Downs and Black checklist (maximum score 21, better quality). In one study, swimmers with low (<93°) or high (>100°) shoulder external rotation were at higher risk of injuries. Using data pooled from three studies of professional baseball pitchers, we showed in the meta-analysis that shoulder external rotation insufficiency (throwing arm <5° greater than the non-throwing arm) was associated with injury (odds ratio=1.90, 95% confidence interval 1.24 to 2.92, p<0.01). CONCLUSION: Preseason screening of shoulder external rotation ROM may identify professional baseball pitchers and swimmers at risk of injury. Shoulder ROM screening may not be effective to identify handball, softball, volleyball and tennis players at risk of injuries. The results of this systematic review and meta-analysis should be interpreted with caution due to the limited number of studies and their high degree of heterogeneity. PROSPERO REGISTRATION NUMBER: CRD42017072895.

The American Society of Shoulder and Elbow Therapists' consensus statement on rehabilitation for anatomic total shoulder arthroplasty.

Anatomic total shoulder arthroplasty is the gold standard shoulder replacement procedure for patients with an intact rotator cuff and sufficient glenoid bone to accommodate prosthetic glenoid implant and offers reliable patient satisfaction, excellent implant longevity, and a low incidence of complications. Disparity exists in the literature regarding rehabilitation strategies following anatomic total shoulder arthroplasty. This article presents a consensus statement from experts in the field on rehabilitation following anatomic total shoulder arthroplasty. The goal of this consensus statement is to provide a current evidence-based foundation to inform the rehabilitation process after anatomic total shoulder arthroplasty. These guidelines apply to anatomic total shoulder arthroplasty (replacement of the humeral head and glenoid), hemiarthroplasty (replacing only the humeral head), and hemiarthroplasty with glenoid reaming or resurfacing. The consensus statement integrates an extensive literature review, as well as survey results of the practice patterns of members of the American Society of Shoulder and Elbow Therapists and the American Shoulder and Elbow Surgeons. Three stages of recovery are proposed, which initially protect and then gradually load soft tissue affected by the surgical procedure, such as the subscapularis, for optimal patient outcomes. The proposed guidelines should be used in collaboration with surgeon preferences and patient-specific factors.

Supraspinatus tendon micromorphology in individuals with subacromial pain syndrome.

STUDY DESIGN: Cross-sectional cohort. INTRODUCTION: Tendon collagen organization can be estimated by peak spatial frequency radius (PSFR) on ultrasound images. Characterizing PSFR can define the contribution of collagen disruption to shoulder symptoms. PURPOSE OF THE STUDY: The purpose of this was to characterize the (1) supraspinatus tendon PSFR in participants with subacromial pain syndrome (SPS) and healthy controls; (2) PSFR between participants grouped on a tendon visual quality score; and (3) relationship between PSFR with patient-reported pain, function, and shoulder strength. METHODS: Participants with SPS (n = 20) and age, sex, and arm-dominance-matched healthy controls (n = 20) completed strength testing in scaption and external rotation, and patient-reported pain, and functional outcomes. Supraspinatus tendon ultrasound images were acquired, and PSFR was calculated for a region of interest 15 mm medial to the supraspinatus footprint. PSFR was compared between groups using an independent t-test and an analysis of variance to compare between 3 groups for visually qualitatively rated tendon abnormalities. Relationships between PSFR with pain, function, and strength were assessed using Pearson correlation coefficient. RESULTS: Supraspinatus tendon PSFR was not different between groups (P = .190) or tendon qualitative ratings (P = .556). No relationship was found between PSFR and pain, functional loss, and strength (P > .05). CONCLUSIONS: Collagen disruption (PSFR) measured via ultrasound images of the supraspinatus tendon was not different between participants with SPS or in those with visually rated tendon defects. PSFR is not related to shoulder pain, function, and strength, suggesting that supraspinatus tendon collagen disorganization may not be a contributing factor to shoulder SPS. However, collagen disruption may not be isolated to a single region of interest. LEVEL OF EVIDENCE: 3b: case-control study.

Sit-To-Stand Biomechanics Before and After Total Hip Arthroplasty.

The purpose of this study was to evaluate changes in movement patterns during a sit-to-stand (STS) task before and after total hip arthroplasty (THA), and to compare biomechanical outcomes after THA to a control group. Forty-five subjects who underwent THA and twenty-three healthy control subjects participated in three-dimensional motion analysis. Pre-operatively, subjects exhibited inter-limb movement asymmetries with lower vertical ground reaction force (VGRF) and smaller moments on the operated limb. Although there were significant improvements in movement symmetry 3 months after THA, patients continued to demonstrate lower VGRF and smaller moments on the operated limb compared to non-operated and to control limbs. Future studies should identify the contributions of physical impairments and the influence of surgical approach on STS biomechanics.

Neuromuscular control during stepping down in continuous gait in individuals with and without ankle instability.

Ankle sprains are a common injury and those affected are at a risk of developing chronic ankle instability (CAI). Complications of an acute sprain include increased risk of re-injury and persistent disability; however, the exact link between ankle sprains and chronic instability has yet to be elucidated. The purpose of this study was to investigate neuromuscular control (including kinematics, kinetics and EMG) during stepping down from a curb, a common yet challenging daily activity, in persons with ankle instability (n = 11), those with a history of ankle sprain without persistent instability, called ankle sprain "copers" (CPRs) (n = 9) and uninjured controls (CTLs) (n = 13). A significant group difference was noted as the CPR group demonstrated increased tibialis anterior activity in both the preparatory (pre-touchdown) and reactive (post-touchdown) phases when compared to healthy and unstable groups (P < 0.05). It follows that the CPR group also demonstrated a significantly less plantar-flexed position at touchdown than the other two groups (P < 0.05). This is a more stable position to load the ankle and this strategy differed from that used by participants with CAI and uninjured CTLs. These findings provide insight into the neuromuscular control strategies of CPRs, which may allow them to more appropriately control ankle stability following sprains.

Preseason lower extremity range of motion, flexibility, and strength in relation to in-season injuries in NCAA division I gymnasts.

OBJECTIVES: To determine if preseason lower extremity ROM, flexibility, and strength differ in collegiate gymnasts (NCAA Division 1) who do or do not sustain an injury during the competitive season. METHODS: Over four seasons, a total of 15 female gymnasts (age = 20.5 ± 1.0 years) underwent preseason screening (30 gymnast-season). We tested joint ROM (hip: flexion, internal and external rotation; ankle: weightbearing dorsiflexion), muscle flexibility (passive straight leg raise, Thomas,' Ober's, Ely's tests) and strength (hip extensors, abductors, and flexors isometric strength via a handheld dynamometer; knee: quadriceps and hamstring isokinetic strength at 60°/sec). The team athletic trainer tracked overuse lower extremity injuries (restricted gymnasts from full participation, occurred as from participation in organized practice or competition, and required medical attention) during each season. For athletes that tested multiple seasons, each encounter was considered independent, and each preseason assessment was linked to overuse injuries sustained during the same competitive season. Gymnasts were dichotomized into injured and non-injured groups. An independent t-test was used to measure differences in preseason outcomes between injured and non-injured groups. RESULTS: During four years, we recorded 23 overuse lower extremity injuries. Gymnasts that sustained an in-season overuse injury demonstrated significantly lower hip flexion ROM (mean difference: -10.6°; 95% confidence interval: -16.5, -4.6; p < 0.01) and lower hip abduction strength (mean difference: -4.7% of body weight; 95% confidence interval: -9.2, -0.3; p = 0.04). CONCLUSION: Gymnasts who sustain an in-season overuse lower extremity injury have significant preseason deficit of hip flexion ROM and weakness in the hip abductors. These findings indicate potential impairments in the kinematic & kinetic chains responsible for skill performance and energy absorption during landing.

Brain Health and Cognition in Older Adults: Roadmap and Milestones towards the Implementation of Preventive Strategies.

In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that might benefit the most from risk-based approaches-namely, people with subjective cognitive decline. Additionally, we consider universal prevention in cognitively unimpaired middle-aged and older adults. Delving into multidomain personalized preventive strategies, we report on empirical evidence surrounding modifiable risk factors and interventions crucial in mitigating cognitive decline. Next, we highlight the emergence of brain health services (BHS). We explain their proposed role in risk assessment, risk communication, and tailored interventions to reduce the risk of dementia. Commenting on ongoing BHS pilot experiences, we present the inception and framework of our own BHS in Monza, Italy, outlining its operational structure and care pathways. We emphasize the need for global collaboration and intensified research efforts to address the intricate determinants of brain health and their potential impact on healthcare systems worldwide.

The COVID-19 lockdown as a model of detraining in division 1 college softball players.

BACKGROUND: The COVID-19 pandemic interrupted the organized training of softball players, similar to the abrupt cessation of sports participation that can happen after an injury. Thus, the COVID-19 pandemic offers a unique model to study how sudden detraining influences softball players. METHODS: We recruited a sample of convenience of National Collegiate Athletic Association Division 1 softball players. They participated in three data collections: pre-lockdown (Jan 2020, T1), post-lockdown (Sept 2020, T2), and before the 2021 season (Jan 2021, T3). Between T1 and T2, players received an at-home conditioning and throwing program, but compliance was not strictly monitored. Between T2-T3, players resumed formal fall training (team-organized workouts, on-field practice, and within-team scrimmage games). At each time point, we collected bilaterally: 1) shoulder internal rotation (IR) and external rotation (ER) range of motion (ROM); 2) shoulder IR and ER strength; 3) hip IR and ER ROM; and 4) hip abduction and extension strength. We used four independent (2 Sides × 3 Timepoints) MANOVA with repeated measures; we followed up significant MANOVA main effect of time with Sidak posthoc tests for pairwise comparisons between time points. RESULTS: Fifteen players participated in this study. We found a significant MANOVA main effect of time for shoulder and hip ROM (p < 0.01). Between T1-T2, dominant shoulder ER ROM decreased 6.5°, dominant shoulder IR ROM increased 4.3°, and lead hip IR ROM increased 4.4°. Between T2-T3, dominant shoulder ER ROM increased 6.3° and trail hip ER ROM increased 5.9°. We found a significant MANOVA main effect of time for shoulder strength (p = 0.03) but not for hip strength (p = 0.18). Between T2-T3, non-dominant shoulder IR and ER increased 1.8 kg and 1.5 kg, respectively. CONCLUSION: A sudden and prolonged cessation of organized training generated changes in shoulder and hip ROM but affected strength to a lesser extent. The loss of shoulder ER and increased lead hip IR ROM are maladaptive as they are associated with injury in overhead athletes. Resuming team-organized training and scrimmage reversed some (shoulder ER), but not all of these changes. Practitioners should monitor clinical variables regularly and be aware of potential changes due to unexpected and prolonged interruptions in training, such as when players suffer sports-related injuries.

A ROI-based quantitative pipeline for 18F-FDG PET metabolism and pCASL perfusion joint analysis: Validation of the 18F-FDG PET line.

In Mild Cognitive Impairment (MCI), the study of brain metabolism, provided by 18F-FluoroDeoxyGlucose Positron Emission Tomography (18F-FDG PET) can be integrated with brain perfusion through pseudo-Continuous Arterial Spin Labeling Magnetic Resonance sequences (MR pCASL). Cortical hypometabolism identification generally relies on wide control group datasets; pCASL control groups are instead not publicly available yet, due to lack of standardization in the acquisition parameters. This study presents a quantitative pipeline to be applied to PET and pCASL data to coherently analyze metabolism and perfusion inside 16 matching cortical regions of interest (ROIs) derived from the AAL3 atlas. The PET line is tuned on 36 MCI patients and 107 healthy control subjects, to agree in identifying hypometabolic regions with clinical reference methods (visual analysis supported by a vendor tool and Statistical Parametric Mapping, SPM, with two parametrizations here identified as SPM-A and SPM-B). The analysis was conducted for each ROI separately. The proposed PET analysis pipeline obtained accuracy 78 % and Cohen's к 60 % vs visual analysis, accuracy 79 % and Cohen's к 58 % vs SPM-A, accuracy 77 % and Cohen's к 54 % vs SPM-B. Cohen's к resulted not significantly different from SPM-A and SPM-B Cohen's к when assuming visual analysis as reference method (p-value 0.61 and 0.31 respectively). Considering SPM-A as reference method, Cohen's к is not significantly different from SPM-B Cohen's к as well (p-value = 1.00). The complete PET-pCASL pipeline was then preliminarily applied on 5 MCI patients and metabolism-perfusion regional correlations were assessed. The proposed approach can be considered as a promising tool for PET-pCASL joint analyses in MCI, even in the absence of a pCASL control group, to perform metabolism-perfusion regional correlation studies, and to assess and compare perfusion in hypometabolic or normo-metabolic areas.

Can Traditional Board Games Prevent or Slow Down Cognitive Impairment? A Systematic Review and Meta-Analysis.

BACKGROUND: Traditional board games can entail significant skills encompassing several cognitive functions across different domains. Therefore, they may potentially represent effective cognitive interventions in the aging population with or without Alzheimer's disease or other types of dementia. OBJECTIVE: We aimed at verifying the hypothesis that traditional board games can prevent or slow down cognitive decline, through a systematic review on traditional board games and dementia. METHODS: We searched five databases with tailored search strings. We included studies assessing the impact of board games on elderly subjects at risk of or suffering from cognitive impairment, or subjects with cognitive impairment irrespective of age. Studies where the effect of board games was not separated by cards or other games were excluded. A meta-analysis was performed for specific cognitive and non-cognitive outcomes. RESULTS: Board games improved mental function, as measured by Montreal Cognitive Assessment (p = 0.003) and Mini-Mental State Examination (p = 0.02). Ska and Go improved Trail Making Test -A, while Mahjong improved executive functions. There was no consistent effect across different games on Digit Span or Categorical Fluency. Chess improved quality of life measured with the WHO-QoL-OLD scale (p < 0.00001). Mahjong temporarily improved depressive symptoms. Go increased BDNF levels and left middle temporal gyrus and bilateral putamen metabolism. CONCLUSIONS: Traditional board games may slow global cognitive decline and improve the quality of life in elderly subjects. Different games have varying impacts on specific cognitive domains, possibly mediated by functional and biological factors.

Assessing behavioral and psychological symptoms of dementia: a comprehensive review of current options and future perspectives.

The behavioral and psychological symptoms of dementia (BPSD) are a heterogeneous set of challenging disturbances of behavior, mood, perception, and thought that occur in almost all patients with dementia. A huge number of instruments have been developed to assess BPSD in different populations and settings. Although some of these tools are more widely used than others, no single instrument can be considered completely satisfactory, and each of these tools has its advantages and disadvantages. In this narrative review, we have provided a comprehensive overview of the characteristics of a large number of such instruments, addressing their applicability, strengths, and limitations. These depend on the setting, the expertise required, and the people involved, and all these factors need to be taken into account when choosing the most suitable scale or tool. We have also briefly discussed the use of objective biomarkers of BPSD. Finally, we have attempted to provide indications for future research in the field and suggest the ideal characteristics of a possible new tool, which should be short, easy to understand and use, and treatment oriented, providing clinicians with data such as frequency, severity, and triggers of behaviors and enabling them to find appropriate strategies to effectively tackle BPSD.

Sensory neuropathy in amyotrophic lateral sclerosis: a systematic review.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and non-motor symptoms. Recent evidence suggests that ALS is indeed a multisystem disorder, associated with cognitive impairment, dysautonomia, pain and fatigue, excess of secretions, and sensory symptoms. To evaluate whether sensory neuropathy could broaden its spectrum, we systematically reviewed its presence and characteristics in ALS, extracting data on epidemiological, clinical, neurophysiological, neuropathological, and genetic features. Sensory neuropathy can be found in up to 20% of ALS patients, affecting both large and small fibers, although there is a great heterogeneity related to different techniques used for its detection (electromyography vs skin biopsy vs nerve biopsy). Moreover, the association between CIDP-like neuropathy and ALS needs to be better explored, although it could be interpreted as part of the neuroinflammatory process in the latter disease. Sensory neuropathy in ALS may be associated with a spinal onset and might be more frequent in SOD1 patients. Moreover, it seems mutually exclusive with cognitive impairment. No associations with sex and other genetic mutation were observed. All these data in the literature reveal the importance of actively looking for sensory neuropathy in ALS patients, and suggest including sensory neuropathy among ALS non-motor features, as it may explain sensory symptoms frequently reported throughout the course of the disease. Its early identification could help avoid diagnostic delays and improve patients' treatment and quality of life.