Methodologies to objectively assess gait and postural control features in Rett syndrome – With a comment on specific challenges and how to address them

INTRODUCTION Rett syndrome (RTT, OMIM #312750) is a severe neuro-developmental disorder, characterized by apparently normal initial development for about 6-18 months, followed by a period of regression of skills including loss of functional hand use, language and communication and the emergence of characteristic stereotyped hand movements.1 RTT occurs approximately in 1 in every 10,000 births with the condition almost exclusively affecting females and is associated with mutations of the Methyl-CpG-binding protein 2 (MECP2) [1]. When assessed using the International Classification of Functioning, Disability and Health instrument (version 2.1a), the bodily functions that are most often impaired include Sleep (b134), Attention (b140), Memory (b144), Perceptual functions (b156), Higher level cognitive functions (b164), and Language (b167). These impairments affect communication (d3), mobility (d4), and self-care (d5). RTT symptoms include stereotypical hand wringing, breathing abnormalities, abnormalities in muscle tone, loss of social interactions, lack of language skills and overall impaired cognitive functioning [2]. Gait abnormalities feature prominently; they are part of the main criteria for clinical diagnosis of RTT [1]. About 60% – 70% of girls with RTT acquire ambulation [3-6] and their ambulation parallels disease progression [7]. Ambulation is furthermore an independent modifiable risk factor of survival in RTT [8].This range of complex symptoms presents a unique set of challenges associated with the assessment of gait and posture disorders associated with RTT. The inability to effectively communicate using language makes it difficult for the patient to understand the tasks they are being asked to perform. Additionally, the overall deficiencies in movement control also contribute to the difficulty in collecting data using assessment technologies that are traditionally used in movement control assessment centers. Therefore it has become paramount to develop tools to assess progress made through vigorous efforts to improve educational, medical, and psychosocial issues related to Rett syndrome, such as objective gait and mobility assessment presented in this paper. Other assessment tools, such as eye-gaze based assessments of their communication abilities and educational needs are currently being developed in parallel by other groups. All currently available data on gait in RTT is descriptive in nature, derived on a purely observational basis including, in rare occasions, video assessments by movement disorder specialists [3, 4, 9], and not on quantifiable objective measurements. Gait in RTT has been described in general terms as being dyspraxic, ataxic and influenced by varying degrees of dystonia. It has also been found to be rigid with a tendency for retro-pulsion and contain interspersed freezing episodes [3, 4, 9]. A purely descriptive analysis is intrinsically limited and lacks the potential to clearly discern components that influence overall gait in RTT. As clinical trials designed to test drugs or new therapeutic approaches to RTT are becoming increasingly available, it is important to objectively and accurately measure any potential modification in functioning associated with a given intervention. Without such evaluation, the effectiveness of any potential intervention may be undetected or obscured [10-12]. Both traditional physical therapy interventions, including robot assisted gait training, as well as novel methods such as focused neuromodulation [13] in cortical or cerebellar regions associated with movement control may hold promise for RTT patients but, as mentioned, objective and accurate behavioral measures are necessary to effectively assess the outcomes associated with neuomodulatory interventions. This paper presents a battery of assessments, as performed in a professional gait center, specifically adapted for ambulatory individuals with RTT, which we propose become a standard for gait and postural assessment in RTT. METHODS Participants Eighteen females ranging in age from 4 to 20 served as participants. Sixteen participants had been diagnosed classic RTT, with the remaining two being diagnosed with atypical RTT. All were in the ‘stationary’ stage as defined by Chahrour and Zoghbi [2] as none of the older girls had entered the ‘late motor deterioration’ stage and have remained ambulatory. All were receiving evaluation and treatment at the Blue Bird Circle Rett Center at Baylor College of Medicine in Houston, TX. Besides a diagnosis of RTT, inclusion criteria included the ability to independently ambulate, free of walkers, canes or orthotics, possess a level of cognitive functioning that enabled them to understand the assessment tasks after