Individuals with NGLY1 Deficiency, an inherited autosomal recessive disorder, exhibit hyperkinetic movements including athetoid, myoclonic, dysmetric, and dystonic movements impacting both upper and lower limb motion....Individuals with NGLY1 Deficiency, an inherited autosomal recessive disorder, exhibit hyperkinetic movements including athetoid, myoclonic, dysmetric, and dystonic movements impacting both upper and lower limb motion. This report provides the first set of laboratory-based measures characterizing the gait patterns of two individuals with NGLY1 Deficiency, using both linear and non-linear measures, during treadmill walking, and compares them to neurotypical controls. Lower limb kinematics were obtained with a camera-based motion analysis system and bilateral time normalized lower limb joint time series waveforms were developed. Linear measures of joint range of motion, stride times and peak angular velocity were obtained, and confidence intervals were used to determine if there were differences between the patients and control. Correlations between participant and control mean joint waveforms were calculated and used to evaluate the similarities between patients and controls. Non-linear measures included: joint angle-angle diagrams, phase-portrait areas, and continuous relative phase (CRP) measures. These measures were used to assess joint coordination and control features of the lower limb motion. Participants displayed high correlations with their control counterparts for the hip and knee joint waveforms, but joint motion was restricted. Peak angular velocities were also significantly less than those of the controls. Both angle-angle and phase-portrait areas were less than the controls although the general shapes of those diagrams were similar to those of the controls. The NGLY1 Deficient participants’ CRP measures displayed disrupted coordination patterns with the knee-ankle patterns displaying more disruption than the hip-knee measures. Overall, the participants displayed a functional walking pattern that differed in many quantitative ways from those of the neurotypical controls. Using both linear and non-linear measures to characterize gait provides a more comprehensive and nuanced characterization of NGLY1 gait and can be used to develop interventions targeted toward specific aspects of disordered gait.展开更多
NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems ...NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 Deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 Deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 Deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3D initiation area as a percentage of the complete movement. The statistical tests of these measures revealed no significant differences between the two participants, possibly suggesting a common underlying motor control strategy. The 3D techniques used in this report effectively characterized arm movements of an individual with NGLY1 deficiency and can be used to provide information to evaluate the effectiveness of genetic, pharmacological, or physical rehabilitation therapies.展开更多
文摘Individuals with NGLY1 Deficiency, an inherited autosomal recessive disorder, exhibit hyperkinetic movements including athetoid, myoclonic, dysmetric, and dystonic movements impacting both upper and lower limb motion. This report provides the first set of laboratory-based measures characterizing the gait patterns of two individuals with NGLY1 Deficiency, using both linear and non-linear measures, during treadmill walking, and compares them to neurotypical controls. Lower limb kinematics were obtained with a camera-based motion analysis system and bilateral time normalized lower limb joint time series waveforms were developed. Linear measures of joint range of motion, stride times and peak angular velocity were obtained, and confidence intervals were used to determine if there were differences between the patients and control. Correlations between participant and control mean joint waveforms were calculated and used to evaluate the similarities between patients and controls. Non-linear measures included: joint angle-angle diagrams, phase-portrait areas, and continuous relative phase (CRP) measures. These measures were used to assess joint coordination and control features of the lower limb motion. Participants displayed high correlations with their control counterparts for the hip and knee joint waveforms, but joint motion was restricted. Peak angular velocities were also significantly less than those of the controls. Both angle-angle and phase-portrait areas were less than the controls although the general shapes of those diagrams were similar to those of the controls. The NGLY1 Deficient participants’ CRP measures displayed disrupted coordination patterns with the knee-ankle patterns displaying more disruption than the hip-knee measures. Overall, the participants displayed a functional walking pattern that differed in many quantitative ways from those of the neurotypical controls. Using both linear and non-linear measures to characterize gait provides a more comprehensive and nuanced characterization of NGLY1 gait and can be used to develop interventions targeted toward specific aspects of disordered gait.
文摘NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 Deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 Deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 Deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3D initiation area as a percentage of the complete movement. The statistical tests of these measures revealed no significant differences between the two participants, possibly suggesting a common underlying motor control strategy. The 3D techniques used in this report effectively characterized arm movements of an individual with NGLY1 deficiency and can be used to provide information to evaluate the effectiveness of genetic, pharmacological, or physical rehabilitation therapies.
