RESEARCH IN PHYSICAL DISABILITIES
|
Steven
J. Stanhope, PhD, Head, Physical
Disabilities Branch Barbara
C. Sonies, PhD, Chief, Oral Motor
Function Section Gloria
Chi-Fishman, PhD, Staff Scientist Jeri
L. Miller, PhD, Staff Scientist Frances
Sheehan, PhD, Staff Scientist Zohara
Cohen, PhD, Postdoctoral Fellow Sungheon
Kim, PhD, Postdoctoral Fellow Thomas
M. Kepple, MA, Senior Research
Assistant Karen
Kelly
Nelson, MS, Engineer Phaedra
Tracy
Rausch, BS, Research Assistant Andrea
Rebmann, MS, Research Assistant Joy
S. Cheng, MS, Technical Training
Fellow Sunanda
Bhatnagar, BS, Postbaccalaureate Fellow Susan
Bender, BS, Kinesiologist |
|
|
The
Physical Disabilities Branch (PDB) was established in part to accelerate the
development of a highly collaborative, multidisciplinary technology
development and rehabilitation research network. It is based on a
collaboration between the Rehabilitation Medicine Department of the Customized
dynamic ankle-foot orthoses for enhanced function Nelson, Kepple,
Siegel, Stanhope; in collaboration with Halstead A
variety of disorders and diseases affecting muscle and nerve function can
cause lower-extremity weakness sufficient to affect gait. Some individuals
may be unable to walk while others have limited ability to walk. Frequently,
such individuals are prescribed orthotic devices to assist their ambulation.
While most orthotic devices provide passive support to a joint, a dynamic
ankle-foot orthosis (AFO) can augment the efforts of weak muscle and provide
ambulatory assistance through its torsion spring-like action. Biomechanical
theory suggests that ideal orthosis shape and “spring” stiffness
characteristics exist for each individual. However, existing dynamic AFO
manufacturing methods are labor-intensive and incapable of adequately
customizing AFO characteristics. The goal of our research is to improve the
lives of people with lower-extremity weakness through the development and
testing of customized (shape-customized, with stiffness and
center-of-pressure “tuning”), low-cost, dynamic ankle-foot
orthoses. We
have developed a method for determining the stiffness of a commercially
available (carbon-fiber) ankle foot-orthosis. Our preliminary studies
indicate that the deformation patterns of the carbon-fiber ankle
foot-orthosis during bench testing and wear during gait are congruent.
Therefore, the stiffness characteristics obtained during bench testing are
valid for determining orthosis-generated moments as the orthosis is worn
during gait. In addition, we have used a method based on induced acceleration
analysis to determine the source of forces that load (bend) the carbon-fiber
ankle foot-orthosis during the dorsiflexion period of the stance phase of
gait. With these analysis methods, we study the contribution of existing
dynamic AFOs to the walking patterns of patients with post-polio syndrome. We
have begun a 12-month study designed to determine the feasibility of using
rapid prototyping technology to produce a suitable prototype brace. We will
demonstrate the prototype’s feasibility by evaluating experimentally
and theoretically determined design concepts based on alterations of a
brace’s geometric shape and material properties and then compare the
performance of the prototype with an existing commercial carbon-fiber Dynamic
Brace. We have recently used DuraformTM GF (glass-filled) in
conjunction with Selective Laser Sintering (SLS) rapid prototyping technology
to match the shape and stiffness characteristics of an existing carbon-fiber
AFO. Using
normal subjects, we have also begun work on the development of a scaled relational
gait database based on instrumented gait analysis. The gait database is a
critical component of the AFO stiffness tuning process. To date, we have
collected motion capture data on 10 normal subjects walking at five scaled
(relative to standing height) walking velocities. We will study the natural
ankle stiffness values obtained from the database to determine optimal
dynamic AFO design characteristics as a function of body weight and targeted
walking velocity. Kepple T, Nelson K, Siegel KL, Stanhope S. Measuring the sources
of deformation of a dynamic ankle foot orthosis during gait. Proceedings:
Gait and Clinical Movement Analysis Society, Nelson KM, Kepple TM, Siegel KL, Halstead LS, Stanhope SJ. Ankle
foot orthosis contribution to net ankle moments in gait. Proceedings:
American Society of Biomechanics, Association
between subject functional status, seat height, and movement strategy in
sit-to-stand performance Stanhope; in collaboration
with Benvenuti, Bimbi, Cappozzo, Mazzà One
of the primary goals of the rehabilitation and geriatric research fields is
the development of an understanding of the process and governing principles
that link impairment to functional movement limitations and, ultimately, to
disability. Impairments may cause inability to perform specific body
functions, resulting in disability when physiological reserve is markedly
reduced and an individual cannot devise successful compensatory strategies.
To assess the association between a subject’s functional status and the
role and effectiveness of compensatory movement strategies, we investigated
131 elderly subjects, divided into five functional groups, who performed an
experimental sit-to-stand (STS) paradigm. Results of our investigation show
the existence of a hierarchy of compensatory movement strategies in which the
effectiveness of each strategy to maintain standing ability is strongly
influenced by both the individual’s general functional status and the difficulty
of the sit-to-stand task. As the functional status of the subject declines,
the effectiveness of compensatory movement strategies likewise declines. In a
related study involving a sample of hemiparetic stroke patients, we used a
novel approach to identify the motor strategies adopted for the execution of
a STS motor task followed by the maintenance of upright posture. Beginning by
recording external forces only and using a musculoskeletal system model based
on a telescopic inverted-pendulum (TIP) moved by a linear and two rotational
muscle-equivalent actuators, we extracted parameters describing the
kinematics and dynamics of the actuators during an STS task. The motor act
involves both dynamic and static balance control, and we used the TIP model
to interpret the ground reactions data. The result indicated that the TIP
model and simplified data capture scheme have the capacity to discriminate
movement alterations, consequent functional limitations, and the level of
disability in stroke patients. Benvenuti F, Mazzà C, Bimbi C, Cappozzo A, Stanhope SJ.
Interaction between determinants in the sit-to-stand movement. Gait
Posture 2003;18:14-15. Mazzà C, Benvenuti F, Bimbi C, Stanhope
SJ. Association between subject functional status, seat height and movement
strategy in sit-to-stand performance. J Am Geriatr Soc
2004;52:1750-1754. Mazzà C, Stanhope S, Benvenuti F,
Cappozzo A. Sit-to-stand modeling for functional evaluation of
stroke subjects. Proceedings: Gait and Clinical Movement Analysis Society,
Induced
acceleration analysis for rehabilitation Kepple, Siegel,
Stanhope; in collaboration with Neptune, Selbie By
studying the contribution of net joint moments and individual muscle forces
to the control of human movement and the performance of activities of daily
living, we intend to link the capabilities of a physically challenged person
to his or her ability to perform activities of daily living. Measuring the
contribution of net joint movements is critical for defining adaptive
movement control strategies, understanding the process whereby the strategy
of movement control is selected and implemented, and determining the
contribution of assistive technologies in enhancing function. Earlier
efforts to determine the contribution of net muscular joint moments and
individual muscle forces to human movement control have been limited by the
assumption that the relative contribution of muscular effort to the control
of movement is proportional to the magnitude of the effort and independent of
the position of body segments. A generalized coordinate formulation of the
equations of motion shows that the assumption is incorrect and can lead to
errors in interpreting human movement analysis data. We have extended
existing movement analysis methodology by developing a mechanical linkage
model that provides direct estimates of the influence of a given joint moment
or muscle force on the movement of all joints and body segments and the joint
moment’s/muscle force’s contribution to overall task performance.
Our
earlier research revealed that the generation of forward velocity during
normal gait arises primarily from ankle joint plantar flexor push-off rather
than through a controlled fall. We found that the ankle joint plantar flexor
muscle group produces forward acceleration of the upper body during periods
in which the same muscle group acts eccentrically. We examined the relative
contribution of the lower-extremity joint moments to the maintenance of
upright posture (support) and found that, during the single-limb support
phase, ankle moments generate the greatest contribution to support. We also
examined the relative sensitivity of joint accelerations to the joint moments
during the flat-foot phase and found that ankle, knee, and hip joint accelerations
are almost twice as sensitive to moments generated at the knee than to
moments at any other lower-extremity joint. During the heel-off phase of
gait, the acceleration sensitivities at both the ankle and hip joints
increase in response to moments at their own joint. It is clear from the data
that there is significant redundancy in controlling the motion of the stance
limb. Our findings explain, in part, the ability of persons with muscle
weakness to compensate via the use of alternative movement control
strategies. We have further extended the model to estimate the source of
mechanical energy exchange between segments and used it to determine the
muscle groups responsible for the intersegment transfer of mechanical energy
during gait. We found that energy transfer depends on the sign of joint
moment rather than on the sign of joint power and that pairs of net joint
moments function in combination to balance energy flow through the leg and
trunk segments during normal gait. Recently,
we further enhanced the induced acceleration analysis models to track the
deformations in an AFO. By measuring the visco-elastic properties of the AFO
and then applying our latest models, we are now able to track which muscle
groups are working to bend the AFO and thus store energy in the device.
Accordingly, during the later part of stance phase, we are able to determine
how much energy is released by the device and where the released energy goes.
Our method has found application in clinical research to study the efficacy of
various compensatory strategies used by individuals with lower-extremity
muscle weakness to produce knee extension during the stance phase of walking.
The results of that research revealed that a variety of adaptive strategies,
both within and across limbs, can control knee position during gait. Present
efforts directed to developing a three-dimensional biomechanical model to
determine the actual contribution of individual muscles in controlling
pathologic motion during functional tasks show promise. Kepple T, Nelson K, Siegel KL, Stanhope S. Measuring the sources
of deformation of a dynamic ankle foot orthosis during gait. Proceedings:
Gait and Clinical Movement Analysis Society. Siegel KL, Kepple TK, Stanhope SJ. Alternative strategies to
produce knee extension during gait used by persons with quadriceps femoris
weakness. Proceedings: Annual Conference and Exposition of the American
Physical Therapy Association (APTA), Siegel KL, Kepple T, Stanhope SJ. Joint moment control of
mechanical energy flow during normal gait. Gait Posture 2004;19:69-75. Virtual
functional anatomy Sheehan, Cohen,
Rebmann, Rausch, Stanhope; in collaboration with Boden, Gokhin, Graham, Li,
Lu, Luo, Mohammed, Weston, Wirick, The
Virtual Functional Anatomy (VFA) project is designed to fill the important
knowledge gap that exists in the relationship of normal or impaired joint
structure/function and the functional movement limitations associated with
performing activities of daily living. We are focusing on the development and
ultimate validation of a combined set of tools that will allow accurate and
precise measurement, analysis, and visualization of three-dimensional (3D)
static and dynamic musculoskeletal anatomy (i.e., bone shape, skeletal
kinematics, tendon and ligament strain, muscle force, and joint space). We
plan to combine MRI imaging and analysis capabilities with a highly accurate,
imaging-based measurement and analysis technique for the noninvasive
quantification of complete joint anatomy and tissue dynamics during
functional movements. Our effort will require the development of a method for
creating 3D digital images of loaded and moving joint tissues (bone,
cartilage, and connective tissues) to reveal joint contact patterns and
tissue loads. We will also evaluate the variability of bone shape and
sensitivity of defined joint posture (translation and rotation of one bone
relative to another) to osteo-based coordinate system definition. We intend
to use the various tools to document and evaluate the function of normal and
impaired joint structures (e.g., ACL rupture and patellar tracking syndrome)
under simulated conditions experienced during activities of daily living. Over
the past year, we maintained a research focus on developing the backbone of
VFA and, to that end, began exploring the issues surrounding the dynamic MR
scanning of muscle and tendon. The key focal points for algorithm development
were the image registration process along with continued progress in
improving the integration algorithms. We reached a significant milestone with
the completion of a preliminary registration algorithm. Fast-PC MRI can
provide 3D kinematics information for the bones of a joint (e.g., knee and
ankle) as the subject brings the joint through a specified range of motion.
Yet, the information cannot be readily applied to 3D models of the bones,
which are created from static high-resolution scans of the joint. To apply
the kinematics from the fast-PC MRI to the static models, the two image data
sets must be aligned (e.g., registered). Programs written in-house with
Matlab’s scripting language have made visualization possible while
registration has demonstrated an accuracy that ranges from 1.3 mm for the
translations of the femur to 4.3 mm for the translations of the tibia and
from 1.5° for the rotations of the femur to 7.2° for the rotations of the
patella. On
the experimental side, we have focused on developing the imaging protocols
needed to quantify forces in the quadriceps muscles, patellar tendon,
anterior cruciate ligament, and cartilage during the knee joint’s
extension/flexion cycle. Given that we are calculating the forces in the
muscles by measuring the strain in the tendons, error minimization during
measurement is imperative. Thus, we have decided to maximize the strain
within the tendons by using nonmagnetic ankle weights to maximize the load
raised in extension. We are currently conducting a study to test the maximum
weight that can be used without compromising the repeatability of the motion.
In
looking ahead, we have identified three major focus areas for our work. The
first is to quantify healthy knee joint dynamics during loaded tasks that
mimic functional activities of daily living. We will then compare the data
with the knee joint dynamics of impaired subjects (e.g., patellar maltracking
problems and anterior cruciate ligament loss). In a second similar project,
we are quantifying the 3D kinematics of the bones of the ankle joint during
loaded tasks mimicking functional activities of daily living. Third, we
continue to progress toward improvements in imaging time and data accuracy
through algorithm and image sequence development. Rebmann A, Sheehan FT. Precise 3D skeletal kinematics using
fast-PC MRI. J Magn Reson Imaging 2003;17:206-213. Shibanuma N, Sheehan FT, Lipsky PJ, Stanhope S. Sensitivity of
femoral orientation estimates to condylar surface and MR image plane
location. J Magn Reson Imaging 2004;20:300-305. Movement
visualization and analysis for rehabilitation Kepple, Siegel,
Nelson, Stanhope, Bender; in collaboration with Manal, Selbie An
ongoing challenge for the Biomechanics and Biomedical Engineering (BBE)
section is the continued development, enhancement, and maintenance of our
powerful set of human movement analysis tools. Since 1988, the section
(formerly part of the Biomechanics Laboratory) has been developing
generalized computational tools for the analysis of human movement disorders,
with a particular focus on rehabilitation. Historically, command-line
versions of the NIH software package have resided in the public domain and
have been licensed to numerous facilities throughout the world under the
material transfer agreement mechanism. The
objective of our ongoing project is to create a powerful yet cost-effective
software environment that provides clinicians, scientists, and engineers with
access to the PDB’s existing biomechanical modeling and human movement
analysis methodologies and permits the development of a software
infrastructure in support of our new and emerging biomechanical modeling and
analysis techniques. Plotting
a patient’s kinematic and kinetic data on movement relative to
normative values (i.e., mean and ± 1 SD) is a method commonly used by
clinicians for visually assessing deviations and interpreting gait analysis
data. This method of data interpretation is often time-consuming and complex,
especially when it requires the inspection of a host of line graphs for
several variables displayed across several report pages. By color-coding the
magnitude and direction of the deviation, we have developed an alternative
method for displaying movement pattern deviations relative to normative data.
The method effectively transforms the ordinate scale to a unidimensional
color map by producing a single-page summary of all deviation magnitudes
displayed simultaneously in a concise and visually effective manner while
reducing complexity. Manal K, Stanhope SJ. A Novel method for displaying gait and
clinical movement analysis data. Gait Posture 2004;20:222-226. Accuracy
and reliability of movement analysis techniques Stanhope; in
collaboration with Holden, Manal, Selbie The
general purpose of our ongoing projects is to evaluate and improve the
accuracy and reliability of biomechanical modeling and human movement
analysis techniques. We follow a generalized approach with the intent that
the methods and findings will universally support the rehabilitation
field’s emerging quality assurance needs. The
percutaneous skeletal tracker (PST) is a device designed by Steven Stanhope
to achieve minimally invasive skeletal fixation of kinematic targets to human
limbs. The PST permits measurement of actual bone movement for direct
comparison with motion measured simultaneously with the use of
surface-mounted targets. Using PST to determine the optimal method for
attaching surface-mounted markers, we learned that optimal surface-mounted
target attachment techniques are incapable of locating proximal tibial
position with sufficient accuracy to measure strain on joint structures such
as the anterior cruciate ligament. The results of our work formed the basis
for initiating imaging-based methods for obtaining in vivo
measurements of skeletal motion. We
also developed and tested a powerful technique for simultaneously evaluating
the performance of all components of a clinical movement analysis laboratory.
The Commission for Motion Laboratory, Inc., recently endorsed use of the
technique by clinical movement analysis laboratories seeking accreditation.
C-motion, Inc., has implemented the method in the program CALtester, with the
testing device currently distributed by Motion Lab Systems, Inc. The
ability to test and achieve the necessary accuracy and reliability of the
numerous measurements obtained from PDB research and clinical investigations
is a basic requirement for the demonstration of both competence and
excellence. We are seeking generalized solutions that meet the research and
patient care needs of the highly diversified and broadly focused area of
human movement analysis, establish and support international standards, and
support the information exchange needs of the diverse, multidisciplinary rehabilitation
research community. Substantial effort will be required to evaluate the
accuracy and reliability of new measurement techniques proposed by the PDB
(i.e., the Virtual Functional Anatomy Initiative and the Instrumented Walker
Grant). The development of methods and procedures to accommodate future
initiatives will continue as needed. Holden J, Selbie S, Stanhope SJ. A proposed test for the
Clinical Movement Analysis Laboratory Accreditation Process. Gait Posture
2003;17:205-213. Manal K, Davis IM, Galinat B, Stanhope S. Efficacy of proximal
tibial translation estimates during natural cadence walking: bone vs. skin
mounted targets. Clin Biomech 2003;18:126-131. “Sounding”
the Depths of Human Development: Biomedical Advances in Prenatal Sonography to
Quantify Fetal Behavior Organization and the Interplay of Maternal-Fetal
Environments in Emerging Developmental Processes The
human aerodigestive system undergoes extensive morphogenetic change during
prenatal development, thereby making early detection of dysmorphism an
important aspect of confirming genetic syndromes and identifying the
etiopathogenesis of further neonatal ingestive and respiratory functions.
While two-dimensional sonographic imaging remains the standard for biometric
and behavioral evaluation of the living human fetus, full appreciation of the
three-dimensional complexity of aerodigestive development within comparative
matched control groups is lacking. Three- and four-dimensional ultrasound
techniques have recently shown enormous potential for enhancing our
understanding of prenatal development and the foundations of infant feeding,
swallowing, and respiratory processes. Our work focuses on biomedical
applications of these state-of-the-art imaging technologies to quantify
craniofacial and upper-airway morphogenesis and emergent oral, ingestive, and
respiratory behaviors in the human fetus. We derive our data from an ongoing
collaborative intramural research protocol between the National Institutes of
Health and the Using
on-line, real-time, four-dimensional surface-rendered imaging of the fetus,
we are able to observe the interactions between the fetal and maternal
environments. Our NIH biomedical team develops reconstructions viewed from
multiple rotations that are used as a catalogued database of craniofacial and
upper-airway development for virtual dissection according to anatomical
rules. Embedded features of system software and in-house–developed
software routines extract two- and three-dimensional biometric indices of
muscular, osseous, and cartilaginous structures within the aerodigestive
complex. Our analyses then focus on the documentation of morphologic growth
across gestation and on the emergent patterns of fetal behaviors (suckling,
lingual-labial-jaw movement, swallowing, oronasal respiratory patterns, and
laryngeal and pharyngeal contractions). The project provides a sonographic
reference for human prenatal craniofacial growth and developmental
malformations. In fact, we are developing a three-dimensional database of
development from 16 to 38 weeks gestation with descriptions of observed
behavioral patterns in healthy controls and selected cases with identified
anomalies, polyhydramnios-oligohydramnios, or susceptibility within the
maternal-fetal “environment.” We will incorporate the data into
complex computerized models of morphological and functional relationships to
permit a better understanding of neonatal aerodigestive functions. Classification
of fetal breathing patterns in the maturing upper airway: spectral waveform
analysis of amniotic fluid flow dynamics in normal development,
polyhydramnios/ oligohydramnios Miller, Cheng,
Bhatnagar; in collaboration with Bloom, Borenstein, Driggers, Fries, Gebreab,
Macedonia, Mun, Sarcone The
aerodigestive tract is a complex system of integrated anatomical structures
supporting ingestive and respiratory functions. The developmental origins of
the system are in utero, where the prenatal growth of morphologic
structures and their associated emerging behaviors form the physiologic
foundations necessary to sustain life at birth. The quality of aerodigestive
development is thus inextricably related to both the structural integrity of
the tract’s growing anatomy and the emergence of processes that promote
aerodigestive functioning. Our earlier research focused specifically on
emerging oropharyngeal and laryngeal movements of neonatal swallowing and
phonation. Through innovative sonographic techniques, the work documented
ingestive development in the living fetus; however, the work did not explore
respiratory aspects. Intuition suggests that disruptions to the
fetal-maternal environment also influence respiratory development. Therefore,
an arrest, disorder, or delay in maturation of upper- airway mechanisms may directly
affect subsequent postnatal respiratory function. Thus, the purposes of our
protocol are (1) to continue exploring human fetal development by elucidating
the association between upper-airway growth and emerging prenatal respiratory
function and (2) to determine identifiable patterns of normal respiratory
maturation that may provide indicators of postnatal airway performance. The
project is based on the premise that amniotic fluid volumes are influenced by
the integrity of upper-airway mechanisms and are thus important for
aerodigestive-related development and fetal well-being. In a continued
collaborative effort with the Macedonia C, Miller JL, Sonies BC. Power Doppler imaging of the
fetal upper aerodigestive tract: a four-point standardized evaluation. J
Ultrasound Med 2002;21:869-878. Miller JL, Macedonia C, Sonies BC. Fetal aerodigestive fluid
dynamics. Am J Obstet Gynecol 2002;187:S163. Miller J, Sonies BC, Macedonia C. Emergence of oropharyngeal,
laryngeal, and swallowing activity in the developing fetal upper
aerodigestive tract: an ultrasound evaluation. Early Hum Dev
2003;71:61-87. Comparative
analysis of growth and development in the fetal aerodigestive system:
evidence of early gender disparity Miller; in
collaboration with Driggers, Gegreab, Macedonia, Mun, Sarcone, Smith An
important factor in assessing the development of young children is the delineation
of gender differences in patterns of physical growth and function. These
differences occur very early in human development, most likely before birth,
when prenatal patterns of morphologic development form the antecedents of
subsequent postnatal behaviors. Prenatal detection of motor activity is a
fundamental aspect of determining fetal integrity. Progressive, simple to
complex, differentiated patterns of movement represent a developmental
trajectory of neurobehavioral maturation and serve as markers of fetal
well-being. Awareness of gender variations in motor activity is essential in
evaluating behaviors that must reach functional maturation before birth, such
as the oral, pharyngeal, and laryngeal movements required for newborn
feeding, respiration, and ingestion. While male fetuses are biometrically
more advanced in general body weight, length, and head circumference, they
display fewer mouthing movements in utero than their female
counterparts. Males born prematurely generate fewer active suckling episodes
with lower amplitudes and frequencies than pre-term females. The same pattern
holds following full-term birth, with males reported to produce fewer
rhythmical mouthing patterns and fewer lingual movements during bottle
feedings. We
are investigating whether early differences in oral motor skills may precede
gender-specific patterns of speech production and create a predisposition for
oral motor impairment in male children. We examined a cross-sectional
biometric database containing a cohort of 85 healthy fetuses across genders,
15 to 38 weeks gestational age (GA), with regard to the growth and function
of oropharyngeal, lingual, and laryngeal structures. The morphology of these
regions provides the anatomic support for basic prenatal behaviors such as
mouthing, suckling, or swallowing and serves as the structural foundation for
later phonatory, ingestive, and respiratory functions at birth. Our interest
in how the system develops is based on a growing number of epidemiological
studies suggesting that gender-specific differences in basic oral motor and
precommunication skill development may have early prenatal origins. Our goal
was to identify whether such prenatal data might elucidate early gender
differences in developmental patterns of both growth and motor function. Our
results suggest that gender differences occur in prenatal lingual and
pharyngeal morphology. Males demonstrate greater development in the second
trimester while females demonstrate “catch-up” growth by the
third trimester. Despite greater physical growth, males demonstrate fewer
advanced patterns of lingual movement and laryngeal-pharyngeal contractions.
However, both genders achieve mature patterns of motor behavior by the third
trimester. Our data suggest a gender-specific trajectory of motor skill
development. Prediction models incorporating prenatal gender data on motor
development may identify variables of populations at risk for postnatal motor
speech and oral skill impairments. Characterization
of swallowing dysfunction in nephropathic cystinosis Almajid, Sonies; in
collaboration with Bernardini, Gahl, Kleta Nephropathic
cystinosis is a rare, multisystem, autosomal recessive disease characterized
by the accumulation and crystallization of cystine within the lysosomes of
different cell types. Accumulation of cystine affects various organs and
causes renal tubular and glomerular disease, growth retardation,
deterioration of vision, myopathy, central nervous system involvement,
hypogonadism, pulmonary insufficiency, and swallowing and oral motor
dysfunction. We found that swallowing abnormalities represent a clinical
manifestation of cystinosis, caused by gradual deterioration of oropharyngeal
and esophageal muscle function that occurs at a late stage of the disease.
The gradual deterioration reduces muscle mass and impairs the contractile
function of muscles. Cysteamine treatment is the only known treatment for the
condition. When patients originally underwent evaluation in the late 1980s
and early 1990s, the use of cysteamine was in its infancy and its effects
were not well understood. The
goal of our project is to determine if cysteamine is effective in preventing
swallowing and oral motor muscular dysfunction. We were interested in
determining whether compliance with cysteamine therapy could be separated
from the general effects of aging on the oral motor system and whether
swallowing, muscle deterioration, and disease severity evidenced any
relationship. We assessed the swallowing function of 101 patients with
nephropathic cystinosis seen at the NIH Clinical Center between 1987 and
2004; their ages ranged from six to 45. Diagnosis was based on elevated
leukocyte levels or the presence of cystine crystals in the cornea. One
hundred patients were oral feeders, and one fed through a gastrostomy tube.
The duration of cysteamine treatment (five to 23 years) varied by chronologic
age group. We administered a standard battery of assessments to all subjects,
including a swallowing self-assessment questionnaire, a cranial
nerve–based oral sensory-motor examination, oropharyngeal ultrasound,
and a modified barium swallow study. We calculated a swallowing severity
score (SSS) based on the ultrasound and modified barium swallow studies and
an oral motor composite score (OMCS) and general muscle score (GMS) based on
all the tests. We
found a significant positive correlation between SSS and years without
cysteamine therapy; swallowing worsened in patients who were medicated for
shorter times while deterioration in swallowing either stabilized or improved
in patients medicated for longer periods. The OMCS worsened as a function of
years without cysteamine therapy and improved with years on cysteamine. SSS
varied directly with GMS, indicating that changes in muscle dysfunction
accompanied changes in swallowing. More than half of the subjects had
swallowing complaints, with abnormalities found in the oral (25 percent),
pharyngeal (51 percent), and esophageal (73 percent) phases. For each phase,
frequency of findings increased with age, with all the oldest subjects
demonstrating esophageal findings. One subject was nonoral. In the 20
subjects who did not survive, nine deaths resulted from aspiration or severe
dysphagia. Our study showed that oral motor and swallowing dysfunction in
cystinosis increases progressively with age and correlates with generalized
muscle dysfunction but not with general disease severity. Long-term oral
cysteamine therapy decreases the severity of oral motor and swallowing
dysfunction. Sonies BC. Swallowing studies: non renal complications. First
NIH-ORD Conference on Cystinosis: Past, Present, and Future. May 2004. Sonies BC et al. A long-term study of the effects of age and
medication on swallowing in patients with nephropathic cystinosis. Thirteenth
Annual Dysphagia Research Society Meeting, Montréal, Canada, October,
2004. Task-induced
physiological and biomechanical changes of the in vivo human tongue Chi-Fishman, Kim; in
collaboration with Barnett, Butman, Ozturk, Pierpaoli We have
designed a protocol to address several important issues regarding lingual
anatomy and biomechanics, including (1) the compressibility of the human
tongue and its common, yet untested reference as a muscular hydrostat; (2)
task-induced interactions between lingual musculature and vasculature and
region-specific vascular demands; (3) changes in lingual fiber orientation
and strain distribution as a function of contraction tasks; and (4) effects
of aging, disease, and exercise on lingual myoarchitecture and
structure-function integration. Using Doppler ultrasonography and MR imaging
techniques, we hope to address these issues and contribute to a better
understanding of the functional myoarchitectural and biomechanical
intricacies of the in vivo human tongue. In
lingual volumetry, our MRI studies have identified significant task-induced
tongue volume changes in vivo. We have successfully validated our
segmentation and volume estimation method by using ex vivo models. The
consistent finding of volume increase during maximum voluntary
linguopharyngeal contractions raises serious question about the concept of
the tongue as a muscular hydrostat. In
lingual morphology, we have proven that, through our novel regularization
method (based on normalized convolution) used with a new skewness similarity
measure for segmentation, we can optimally analyze our Diffusion Tensor MRI
(DT-MRI) data to visualize the complex compartmentalized lingual musculature
in three dimensions. Specifically, our method has enabled us to maintain the
boundaries between linear and planar tensor regions, estimate the orientation
of muscle fibers based on diffusivity characteristics, and delineate in
detail the intrinsic and extrinsic tongue muscle compartments in fresh
excised calf tongues. To our knowledge, we are the first group to demonstrate
the feasibility of such a method. Our next task is to apply SENSE-DTI to in
vivo studies of the tongue in dramatically shortened scan time. While
studying lingual morphology using DT-MRI, we conducted additional constant
b-value/constant gradient experiments with varying diffusion intervals and
found cylindrically restricted and nonrestricted diffusion, which permitted
the estimation of restricting compartment size and volume fraction. To our knowledge,
we are the first group to demonstrate apparent restricted water diffusion in
muscle tissues. Continued work in this direction may open an avenue for
measuring cellular morphological changes in muscle tissues. In
lingual hemodynamics, we have compared the hyperemia patterns in three
lingual arterial sites, as induced by maximum voluntary isometric contraction
(MVIC) tasks, with the reperfusion characteristics of dry swallows. Through
vessel diameter, flow volume, velocity, and vessel resistance measurements,
we have found that dry swallows have a significantly faster post-swallow
onset of reperfusion and return to baseline pattern. Although the increase in
vessel diameter post-swallow is similar to that measured post–MVIC,
flow volumes and velocities are lower. The findings suggest much more
efficient patterns of lingual flow recovery for swallowing and a vasculature
highly tuned for endurance and fatigue resistance. In
lingual deformation, our in vivo tagged MRI studies of the tongue
during gated effortful swallows have demonstrated (1) moderate to moderately
high positive strain (tissue expansion) in anterior and mid-tongue across
subjects, (2) mild tissue expansion in genioglossus, (3) striking difference
across subjects in strain type and magnitude in tongue base, and (4) regional
specificity in the determinants of deformation gradient tensors. The findings
suggest mechanistically different task accommodation strategies and
task-induced regional volume changes. Our multislice tagged MRI with assumption-free
analysis holds considerable promise for a better understanding of 3D lingual
functional mechanics. Chi-Fishman G, Kim S, Ozturk C. 3D lingual strain distribution
at the height of effortful swallow. Dysphagia 2004;20, in press. Chi-Fishman G, Miller JL, Butman J. Volumetric changes of the in
vivo human tongue: current findings. Dysphagia 2003;18:151. Chi-Fishman G, O’Quinn RP, Geisler NS, Wade RS, Hisley CK.
Validation of in vivo MRI lingual volume measurement using ex vivo models. Proceedings
of the International Society for Magnetic Resonance in Medicine
2004;11:1527. Kim S, Ozturk C, Chi-Fishman G. Application of tagged MRI in the
study of synergistic actions of lingual muscles during contraction tasks. Proceedings
of the International Society for Magnetic Resonance in Medicine
2004;11:1514. Miller JL, Chi-Fishman G. Lingual hemodynamics following
isometric contractions and swallows: preliminary inferences for therapeutic
exercise in dysphagia. Dysphagia 2003;18:151. COLLABORATORS Alan S. Barnett, PhD, Clinical Brain
Disorders Branch, NIMH, Francesco Benvenuti, MD, Istituto
Nazionale Riposo e Cura Anziani (INRCA), Isa Bernardini, MEd, Medical Genetics
Branch, NHGRI, Carlo Bimbi, MS, Istituto Nazionale Riposo
e Cura Anziani (INRCA), Dianne Bloom, RN, National Naval Medical
Center, Barry Boden, MD, The Orthopaedic Center, Lea Borenstein, BA, George Washington
University, Washington, DC John A. Butman, MD, PhD, Diagnostic
Radiology Department, Warren Grant Magnusson Clinical Center, Bethesda, MD Aurelio Cappozzo, PhD, Istituto
Universitario di Scienze Motorie, Rita Driggers, MD, National Naval Medical
Center, Melissa Fries, MD, National Naval Medical
Center, William Gahl, MD, PhD, Medical Genetics
Branch, NHGRI, Tadesse Gebreab, RTR, RDMS, Georgetown
University Medical Center, Washington, DC Neil Geisler, BS, Oregon State University, David Gohkin, BS, University of
Pennsylvania, Jeanine Graham, Catholic University of
America, Washington, DC Lauro Halstead, MD, MPH, National
Rehabilitation Hospital, Washington, DC Calvin K. Hisley, PhD, Maryland State
Anatomy Board, John P. Holden, PhD, U.S. Food and Drug
Administration, Robert Kleta, MD, PhD, Medical Genetics
Branch, NHGRI, Jeffrey Li, Stanford University, Xiaohong Lu, MS, Catholic University of
America, Washington, DC Weidong Luo, MS, Catholic University of
America, Washington, DC Christian Macedonia, MC, National Naval
Medical Center, Kurt Manal, PhD, University of Delaware, Claudia Mazzà, PhD, Universitario di
Scienze Motorie, Nizamuddin Mohammed, BS, Catholic
University of America, Washington, DC Seong K. Mun, PhD, Georgetown University
Medical Center, Washington, DC Richard R. Neptune, PhD, University of
Texas at Austin, Ryan O’Quinn, BS, North Carolina
State University, Cengizhan Ozturk, PhD, Laboratory of
Cardiac Energetics, NHLBI, Carlo Pierpaoli, PhD, Laboratory of
Integrative and Medical Biophysics, NICHD, Anita Sarcone, RTR, RDMS, Georgetown
University Medical Center, Washington, DC W. Scott Selbie, PhD, C-Motion, Inc., Gladys Smith, PhD, Howard University, Ronald S. Wade, BS, University of Maryland
Medical Systems, Neil Weston, MS, National Oceanic &
Atmospheric Administration, Beth Wirick, BS, Catholic University of
America, Washington, DC Larry Yao, MD, Diagnostic Radiology
Department, Warren Grant Magnusson Clinical Center, Bethesda, MD
|
|
