The World Health Organization Disability Assessment Schedule II (WHO-DAS II) is a non-disease-specific International Classification of Functioning, Disability, and Health-based disability assessment instrument developed to measure activity limitations and restrictions to participation. The aim of this pilot study is to evaluate WHO-DAS II responsiveness in detecting short-time changes following the provision of an Assistive Technology, which is important to define its utility in performing daily activities. Adult inpatients with a diagnosis of Disease of the Nervous System (included in Chapter VI of the ICD-10), who were prescribed an Assistive Technology to be used in the household settings, were enrolled. The WHO-DAS II was administered in individual interview at baseline and at a 2 months follow-up: in this period patients were transitioning from the hospital to home. Changes in disability profiles were detected by calculating the effect size (ES) for each WHO-DAS II domain. Ten patients with different neurological diseases were enrolled. Few longitudinal changes in disability level are reported: mild improvement is observed in the household activities (ES 0.28), whereas mild worsening is reported in self-care and participation in society domains (ES -0.27 and -0.26, respectively). Our study shows that the WHO-DAS II is responsive in detecting domain-specific changes over a short-term period and provides preliminary encouraging evidence for the utility of its utilization in clinical settings. However, changes in setting between baseline and follow-up could have an impact on the findings and interpretation of this study.