To our knowledge, this is the first study investigating both self-perceived mental and physical health status over COVID-19 emergency in patients with ALS.
More than 30% of respondents from our survey reported either anxiety, depressive, or motor worsening symptoms over the quarantine period, suggesting a discrete impact of the emergency on this vulnerable population.
Concerning the mental health status, our findings are in line with recent studies describing an increase of anxiety and depression symptoms over the emergency compared to the pre-COVID phase .
Notably, we further found that the presence and degree of a self-perceived health worsening was modulated by several factors, including demographic and disease-specific features, as well as clinical care changes imposed by the quarantine.
Significant predictors of more severe self-perceived anxiety symptoms over the quarantine period were female gender, more severe motor impairment, and a more aggressive disease course.
Significant associations between female gender and higher anxiety-depressive symptoms in ALS have already been reported in the literature , and more recently, a work by Ozdin and colleagues has identified female gender and accompanying chronic disease as significant risk factors for health anxiety during COVID-19 pandemic .
We observed that a faster disease progression was predictive of more severe anxiety symptoms. By definition, patients with fast disease progression rates are those with shorter disease duration and more severe motor impairment. Our results are therefore in agreement with recent studies reporting a significant decrease of anxiety over time  as well as higher levels of emotional well-being associated with slower disease progression in ALS .
Similarly, a more aggressive disease course further predicted more severe depressive symptoms, in line with previous studies reporting a decrease of depressive symptoms over time since diagnosis , and the well-known association between greater motor impairment and more severe depressive symptoms in ALS.
More than 30% of ALS patients in our cohort perceived a motor worsening over the quarantine period, with most common symptoms being selective motility decline, a combination of motility and respiratory symptoms, followed by pain and mixed symptoms.
To date, no study has investigated self-perceived motor worsening over the quarantine period in patients with ALS. However, the relative frequencies of symptoms reported in our sample are in agreement with the general manifestations of the disease, mainly mobility and respiratory deterioration, accompanied by variable degrees of pain symptoms .
Shorter disease duration was predictive of the presence of a self-perceived motor worsening, suggesting that patients in the earliest disease phases might be those more sensitive to subtle variations in their functional status.
We found that the vast majority of patients were subjected to clinical care changes over the quarantine period, mainly rehabilitation therapy suspension, and exams and/or visits cancelation. This finding is in line with recent studies in other affected countries, such as the USA, reporting COVID-19-related challenges to ALS clinical care and research .
Notably, in line with recent reports describing a significant association between healthcare system changes during COVID-19 emergency and anxiety in patients with ALS , we found that clinical care changes imposed by the quarantine exerted a significant impact on self-perceived anxiety in our sample.
Furthermore, we observed that these changes were significant predictors of a self-perceived motor worsening, highlighting the importance of continuous and integrated care management for self-perceived health status in neurological patients.
In this context, it is noteworthy that significant efforts have been made in order to handle ALS patients care management over COVID-19 emergency. The application of telemedicine, in particular, holds promise to enable maintaining a multidisciplinary approach to the care of patients  and monitoring disease progression  over the pandemic. A previous Italian study has shown that, even if the majority of patients and caregivers would have preferred a face-to-face visit, there was a global satisfaction with the telemedicine service . A subsequent study has further confirmed these findings, showing that the majority of subjects were willing to continue the remote evaluation programs . Taken together, these preliminary evidences suggest that telemedicine might be a valid tool to improve clinical management of ALS patients over the emergency.
The study is not without limitations. The first shortcoming deals with the relatively small ALS sample size, which was mainly determined by (a) stringent inclusion criteria (patients were included only if they had a clinical evaluation within 6 months and absence of cognitive impairment), and (b) the web-based administration of the questionnaire imposed by the quarantine, which limited the applicability in older patients. Furthermore, even if the absence of significant differences between the respondents and non-respondents samples in our study points towards a moderate generalizability of the results, the long mean disease duration and mild mean progression rate we observed in our cohort suggest the possibility that some of the newly diagnosed cases with short disease duration and rapid disease course might have been missed. Future studies in larger samples are therefore warranted to further explore the effects of COVID-19 emergency on this particularly vulnerable category of patients.
The second shortcoming is the absence of standardized anxiety and depression scales in order to avoid an overlap with the mood disorders scales recently administered as part of the routine behavioral examinations preceding the emergency.
Despite these limitations, our work provides a preliminary panoramic of the effects of COVID-19-related quarantine on self-perceived health status in patients with ALS.
Our results indicate that clinical care changes imposed by the emergency exerted significant negative impacts on patients with ALS, particularly in those in the earliest disease phases, and with a more aggressive disease course.
Knowledge of the factors contributing to self-perceived health worsening over the quarantine period in vulnerable populations, such as patients with ALS, is pivotal to better inform healthcare policies on adequate future strategies. These findings have potential to facilitate personalized medicine strategies in the next phase.