Accepted: 27 March 2018 DOI: 10.1111/jar.12462
BRIEF REPORT
Published for the British Institute of Learning Disabilities
Identification of spatiotemporal gait parameters and pressure- related characteristics in children with Angelman syndrome: A pilot study Joseph C. Grieco1
| Arnaud Gouelle2,3
1 Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida 2
Gait & Balance Academy, ProtoKinetics, Gometz-le-Châtel, France
| Edwin J. Weeber1
Background: Angelman syndrome (AS) leads to clinical manifestations that include intellectual impairments, developmental delay and poor motor function. Initiatives to develop therapeutics implie an urgent need to identify methods that accurately measure the motor abilities.
UFR STAPS de Reims, Laboratoire Performance, Santé, Métrologie, Société (PSMS, EA 7507), Reims, France
Methods: Six children with AS (6 to 9 years old) walked on an instrumented walkway
Correspondence Arnaud Gouelle, Gait & Balance Academy, ProtoKinetics, Gometz-le-Châtel, France. Email:
[email protected]
and 20 TD 4 to 5 years old.
Funding information Foundation for Angelman Syndrome Therapeutics
viduals, except step length, STPs were different. Analysis of the CoP pathway
3
to get spatiotemporal parameters (STPs) and center of pressure (CoP). These outcomes were compared to typically developing children (TD): 44 TD 6 to 9 years old Results: Analysis revealed differences in all STPs and gait variability index when compared to TD individuals. When AS participants were compared to younger TD indirevealed a less consistent and efficient pathway in AS. Conclusions: We could delineate the functional difference between children with AS and TD children. The variability of STP and the CoP were the most valuable components in gait to be considered in AS. KEYWORDS
Angelman, center of pressure, gait, motor impairment, outcome measure, variability
1 | I NTRO D U C TI O N
which in turn may ameliorate the motor and cognitive deficiencies experienced by individuals with AS. For instance, recent research
Angelman syndrome (AS) is a rare genetic disorder affecting about
in UBE3A-d eficient mouse demonstrated the administration of 4,
1/12,000 births. This disorder arises through the genetic disruption
5,6,7-tetrahydroisothiazolo[5,4-c]pyridine-3-ol (THIP, Gaboxadol)
of the maternal UBE3A allele which, when coupled with epigenetic si-
improved the aberrant firing of the cerebellar Purkinje cells and
lencing of the paternal UBE3A allele, gives rise to an absence of UBE3A
reduced the cerebellar ataxia that is normally associated with the
protein ligase in the central nervous system. This enzyme is involved in
AS mouse (Egawa et al., 2012). Studies such as this suggest that
the degradation of proteins, localizes to pre-synaptic and post-synaptic
a pharmacologic treatment with the potential ability to improve
compartments of neurons and is required for normal synaptic function
the functioning in AS exists. Unfortunately, previous research has
(Gustin et al., 2010). Its absence during brain development leads to
shown the behavioural characteristics of AS interfere with the
clinical manifestations that vary in severity, including severe intellec-
functional assessment of ability in these individuals when stan-
tual impairments, deficits in language ability and poor motor function.
dard cognitive and behavioural assessments such as the Bayley
There is an ongoing initiative to develop or identify therapeu-
Scales of Infant and Toddler Development- 3 rd Ed. (BSID- III,
tics with the potential to improve the aberrant synaptic function,
Bayley, 2005) and/or the Vineland Adaptive Behaviour Scales-2nd Ed. (VABS, Sparrow, Cicchetti, & Balla, 2005) are employed. An
All authors were fully involved in the study and preparation of the manuscript, and the material within has not been and will not be submitted for publication elsewhere.
J Appl Res Intellect Disabil. 2018;1–6.
inability to perform on this scale type results in raw scores at the
wileyonlinelibrary.com/journal/jar © 2018 John Wiley & Sons Ltd | 1
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GRIECO et al.
2 Published for the British Institute of Learning Disabilities
bottom of the range, and a lack of variance between individuals (a
children between 4 and 5 years old (to determine whether the gait
floor effect) leads to inability to detect change (Grieco et al., 2012;
of the children with Angelman is similar to younger TD children). The
Hessl et al., 2009). Therefore, there is an urgent need to identify
exclusion criteria for TD included the presence of torsion disorder
a method that accurately measures the abilities of these patients
in the lower limb, any neurological conditions, any gait disorders or
and can demonstrate treatment benefit for pharmacologic or be-
history of lower limb surgery.
havioural interventions. For individuals with AS, development of walking ability is delayed and has been described as unsteady, with a wide base of sup-
2.2 | Procedures
port, in conjunction with rigid, ataxic movements of the legs and
Gait features were assessed on a Zeno walkway (ProtoKinetics LLC,
often pronated or valgus-positioned ankles (Williams et al., 2006).
Havertown, PA, USA), which is based on electronic sensing array
To our knowledge, the gait of AS is mainly documented through case
technology (3.66 m per 1.22 m) and allows for the collection of STP
of studies while specificities of the pattern have not been studied. To
and relative-pressure data during walking. The technology has al-
some extent, features of AS are close to ataxia and previous research
ready demonstrated its high interest for the assessment of both mat-
has shown patients exhibiting an ataxic gait (without AS) present
uration processes in TD (Gouelle et al., 2016) and gait impairment
some similar characteristics (Pavone et al., 2017). Further analysis
in rare diseases (Gouelle et al., 2013; Pickett et al., 2012). Lynall,
of spatiotemporal parameters (STPs) in these patients with ataxia re-
Zukowski, Plummer, and Mihalik (2017) also demonstrated that cen-
vealed lower cadence and step length while step width, stance phase
tre of pressure (CoP) outcomes were highly correlated with force
and double support are increased in comparison with age-matched
plate outcomes and were reliable between testing sessions.
healthy individuals (Milne et al., 2014; Stephenson et al., 2015). A
Participants walked back and forth at spontaneous speed, with
marker of the disease severity in ataxia is also the increased gait
each walk starting from a standing position approximately 1.5 m
variability that translated to dynamic instability (Gouelle, Mégrot,
outside the active area. Due to characteristics inherent to the syn-
Husson, Yelnik, & Penneçot, 2013). These mean parameters and the
drome, such as a short attention span, the inability to understand
gait variability might be a solid base for AS assessment. In addition,
and/or to follow directions, not all data collected could be used.
subtle pressure-related changes that are not detectable with more
Hence, several passes were recorded until a minimum of 40 usable
common spatiotemporal outcomes might be also investigated.
steps (5–10 passes on the walkway) were acquired. Data were re-
The objectives of this pilot study were to (i) compare STP of individuals with AS to typically developing (TD) children and (ii) de-
corded and processed using ProtoKinetics Movement Analysis Software (PKMAS v.508c4).
termine the most valuable parameters related to gait impairment in individuals with AS. We hypothesized that individuals with AS would have spatiotemporal alterations reflective of strategies to main-
2.3 | Dependent variables
tain balance and/or have the inability to maintain dynamic stability
Seven STPs were analysed: gait speed, cadence, step length, walk
during gait.
ratio, stride width, single and double support percentages. The walk ratio represents the relationship between the amplitude
2 | M ATE R I A L S A N D M E TH O DS 2.1 | Participants
and the frequency of movement of the legs. It is calculated as the mean step length divided by the cadence. Its main advantage is that it is relatively invariant through a speed range from slow to very fast that is independent of the speed (Sekiya, Nagasaki, Ito,
Six individuals were diagnosed with AS (two females/four males,
& Furuna, 1996). A composite measure of variability across sev-
mean age 7.7 ± 1.0 years, range 6–9 years). Children were recruited
eral gait parameters, the Gait Variability Index (GVI; Gouelle et al.,
through an Angelman syndrome advocacy group. Inclusion and ex-
2013), was also calculated. The GVI has been proposed to be use-
clusion criteria included (i) a molecular diagnosis of AS; (ii) the abil-
ful for the evaluation of gait in children, both for the follow-up of
ity to walk without assistance; and (iii) a confirmation participants
the effect of pathologies on gait and to evaluate child develop-
have not received any therapeutic to treat the symptoms of AS
ment (Gouelle et al., 2016). Moreover, PKMAS provides numerous
within the preceding 12 months. The University of South Florida
other parameters from the walkway’s pressure data, information
Institutional Review Board approved all study procedures. Parents
relative to the CoP was so considered. The symmetry of propul-
of the participants provided informed consent for their child, and
sion feature, also known as cyclogram or “gaitogram” (Kalron &
verbal assent was obtained from each child older than 7 years old.
Frid, 2015; Roerdink et al., 2014), illustrates the mediolateral and
For normative references, we used data set from the article by
anteroposterior weight shifts associated with alternating steps. A
Gouelle, Leroux, Bredin, and Mégrot (2016) that described the matu-
graphical display of typical cyclogram performance looks like an
ration of the gait variability in 140 typically developed (TD) children
hourglass (Figure 1), while pathological gaits present alteration in
from 1 to 17 years. The data were reprocessed with PKMAS, and
the pattern (e.g. asymmetry, irregularity). The mean mediolateral
two normative groups were created: one with 44 children between
position of the cyclogram intersection point (ML CISP) was ob-
6 and 9 years old (age-matched control group) and another with 20
tained, as well as its standard deviation (SD). Finally, the stance
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GRIECO et al. Published for the British Institute of Learning Disabilities
decreased cadence and consequently lower speed, higher stride width, less time spent in single support and more time spent in double support than TD children. The GVI was significantly lower in the AS group (p
