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532
ARTH
ROGRYPOSIS
A Clinical
and
Pathological
Study
of Three
Cases
By Abram Kanof, M.D., Stanley M. Aronson, M.D., and Bruno W. Volk, M.D.
Departments of Pediatrics, Jewish Chronic Disease Hospital and the State University of New York
College of Medicine, and Department of Laboratories, Jewish Chronic Disease Hospital,
Brooklyn, New York
T
HF: TERM arthrogryposis multiplexcon-genita is used to describe a syndrome
Cf congenital malformations, the chief of
which is flexion deformity of the joints.1
This name, and multiple congenital articu-tar rigidities, used in the first description
of this entity by Rocher’ did not seem
ap-propriate to Sheldon’ because they seemed
to indicate primary involvement of the
joints. He was impressed by the clinical
and histologic changes in the muscles about
the affected joints, and coined the name
amyoplasia congenita. However Gilmour,’
while in agreement with Sheldon’s concept. re1)Orted that the anterior horn cells in his
case were reduced in number and size.
Adams et a!.’ reported an instance in
which all 4 extremities were involved, and
in which lesions were demonstrated in the
spinal cord. Brandt has also reported a case
interpreted by him as indicating the
dis-ease to be one of primary involvement of
the central nervous system.0
The present cases are reported because
they represent typical examples of this
un-usual disease, and because histologic study
of tile muscles in all :3 cases, as well as
post-mortem study of 1 case, seem to direct
at-tention to the central nervous system.
Case 1
CASE REPORTS
HIsToisv. M. A., a 23-year-o1d girl of Italian
extraction, was admitted in August, 1952,
be-cause of multiple malformations. The family
history was not remarkable. Two siblings are
well. She was delivered with some difficulty,
sustaining a fracture of the right humerus. The
fliOtiOIl of several joints was restricted and
et1uiiiovarus deformities of both feet were
noted. Swallowing was complicated by a cleft
palate.
PHYSICAL FiNDINGs. The patient was
de-scribed as an undernourished, poorly developed
child able to sit up only with support. The
significant findings were facial asymmetry with
narrowing of the right palpebral fissure, mild
flexion deformities of the shoulder joints,
web-bing of 1)0th axillae, mild flexion deformities
of both wrist joints, and flexion deformities of
the distal interphalangeal joints. The thumbs
of both hands were kept in a flexed, apposed
position. The knees were held in extension with
markedly limited motion. The feet were fixed
ill partial eqtimovarus.
Neurologic examination demonstrated a right
facial weakness and some spasticit of the
muscles of the right upper extremity. The
dee-troencephalogram was interpreted as normal.
LABORATORY FINDINGs. Biochemical study of
the blood for cholesterol, chlorides, potassium,
sodium, urea nitrogen, fibrinogen,
CO,-combin-ing power, alkaline phosphatase, phosphorous,
total protein, A/C ratio, total lipids, and
17-ketosteroids showed normal values. The
electro-phoretic pattern of serum demonstrated a very
high alpha-2, a somewhat high beta globulin,
and a low gamma globulin fraction. The
cere-brospinat fluid was not unusual. The glucose
tolerance curve was normal. The urine was
normal. There was a definite abnormality of
the creatine metabolism. Sixty per cent of
the total creatine plus creatinine was excreted
as creatine. Eighty per cent of an orally
ad-ministered dose of 1.32 gm of creatine was
excreted unchanged.
Roentgen studies confirmed the presence of
the flexion deformities noted in the physical
examination. Epiphyseal development was
nor-mat. Poor muscular development with
consid-erable replacement of portions of the
muscula-ture by adipose tissue was noted in alt films of
CLINICAL NOTES 533
tower limbs. A roentgenogram of the chest
demonstrated a shadow in the lower chest.
Pneumoperitoneum studies showed this to be
within the right cardiophrenic angle and due
probably to an eventration of the mesial half
of the right diaphragm.
At 19 months of age an operation to repair
the eventration of the diaphragm was
per-formed. An interesting finding at operation was
the complete absence of the serratus and
latissmus dorsi muscles, while the rhomboids
and trapezius muscles were found to be only
partially developed.7 Biopsy of the diaphragm
taken at operation showed no notable changes.
Striations and myofibrils were well maintained. Motor end plates, as delineated by the Ranvier
gold chloride procedure, showed no
abnormal-ity or deficit. Two biopsies of the skeletal
musculature were performed. Muscle taken
from the left thigh at the age of 21 months
showed a mild muscle fiber atrophy
character-ized by patchy myofibrillar degeneration and
transverse narrowing but no detectable
in-crease in interstitial fat or fibrous content.
COURSE. The patient was subjected to inten-sive physiotherapy, including stretching of the
extremities and muscle re-education.
Adminis-tration of ACTH during one period, and
prostig-mine during another, resulted in no beneficial
effects from either of these drugs.
Beginning in August, 1953, her progress
ac-celerated. She first began to walk between
parallel bars, and finally learned to stand and
walk and to feed herself. Mobility, by
measure-‘
ments taken approximately 1 year apart,showed improvement. In addition, she also
made progress in her speech, accumulating a
considerable vocabulary. Psychologic evaluation
indicated development slightly below par.
How-ever, during her hospital stay, significant
prog-ress was made in her emotionat as well as in
her social development.
Case 2
HIsTORY. M. K., a 53-year-old girl, was
ad-mitted on March 8, 1954, with a diagnosis of
pronounced generalized arthrogryposis. The
family history was not pertinent. She had been
delivered by breech extraction. Birth weight
was 2040 gm. Gross deformity of all
extremi-ties and stiffness of all joints were noted and
also a right femoral fracture, which had been
sustained at birth. Four days later, during
routine handling, a fracture of the left femoral shaft occurred.
PHYSICAL FINDINGS. At the time of admission the patient was a diminutive, severely crippled
child weighing 9776 gm. She was responsive,
cooperative and intelligent, but could not sit
alone. There was marked spinal deformity with
a left thoracic scoliosis and a lumbar lordosis.
The joint motion in all extremities was
re-stricted, but less so in the upper extremities.
In general, movement was less restricted in
flexion and extension than in the other planes
of motion. Manual muscle tests confirmed the
above findings. Motion was possible at the
ankles though severe contractures were
pres-ent. Neurologic examination was deemed
nor-mal. The external genital labiae were absent.
Psychologic examination indicated at least
average capacitY though the patient was
Un-able fully to utilize her intellectual endowment.
Her course in the hospital was marked by OIie
upper respiratory infection and an episode of
unexplained vomiting. A rehabilitation program
has been undertaken for her, involving
psycho-logic readjustment, consideration of vocational
possibilities, efforts toward weight gain, and
the maintenance of strength in the available
musculature through active exercise.
LABORATORY FINDINGS. Biochemical
determi-nation of the blood values for calcium,
phos-phorous, glucose, cholesterol, total proteins,
sodium, urea nitrogen, total lipids, lipid
phos-phorus, 1 7-ketosteroids and protein-hound
iodine showed them to be normal. A glucose
tolerance test, a Thorn test and insulin
toier-ance tests were also within normal limits. The
electrophoretic pattern was normal except for
a slightly lowered gamma globulin and &evated
alpha-2 and slightly elevated alpha-i fractions.
There was increased excretion of creatine with
a reversal of the ratio. After administration of
1.32 gm. of creatine, the ratio of creatine to
creatinine was 3 : 1 in the urine.
A biopsy of the left gastrocnemius muscle
taken soon after admission disclosed a severe
degree of atrophy. The muscle cells were
re-duced to slender slips of sarcoplasm, the
mvo-fibrils of which were maintained. There was
an increase in the number of muscle nuclei
as-sociated with hyperplasia of sarcolemmal cells.
A fatty replacement around the fibers was
clearly evident, but no fibrosis could be demon-strated.
Case 3
HISTORY. D.Y., a 1-year-old female of
534 KANOF - ARTHROGRYPOSIS
Fic. 1. 1).Y., showing left facial parcsis, flexion deforiiiities of hips, feet, arms and fingers, extension
of knees, and a dimple n left buttock indicating displacement of femur.
CLINICAL NOTES 535
defects (Figs. 1 and 2). The family, including
1 sibling, were normal. The pregnancy was
unremarkable. She was born by breech
de-livery and weighed 2273 gm. at birth. The
pres-ence of multiple anomalies was noted immedi-ately.
PHYSICAL FINDINGS. On admission to this
hospital, on January 16, 1952, she was a pale,
poorly nourished and developed, irritable,
child with a dull and immobile face. She could
not sit up, nor hold her head erect. Her weight
was 7727 gm. Both hips were dislocated. There
was a marked adduction contracture of both
hips, and abduction was limited to 15#{176}on the
right and 25#{176}on the left. Flexion of the hips
was limited to 90#{176}on the left and 110#{176}on
the right. Rotation was unaffected. In both
knees, extension was limited to about 175#{176}to
180#{176},flexion to 160#{176}to 165#{176}.The right foot
showed a forefoot varus with a mild equinus.
The left foot had a moderate valgus with slight
calcaneous deformity. There was shortening of
the great toe of both feet, and a flexion
con-tracture of the metatarso-phalangeal joints of both feet.
There was fixed adduction and flexion of both
shoulders. The tightness of the pectoral muscles
formed a kind of web between the thorax and
shoulder. Flexion of the right elbow was limited
to between 90#{176}to 170#{176}.The left elbow flexed
normally but was restricted to 170#{176}in
exten-sion. There was a pronation contracture of both
forearms, inhibiting supination on both sides
to no more than neutral position. The wrists
were normal. Both hands showed microdactyly.
The thumbs were in abduction, the index
fingers showing a mild flexion contracture of
the terminal interphalangeal joints, and an
equally slight hyperextension of the proximal
interphalangeal joints. The middle fingers
showed a flexion contracture of the
metatarso-phalangeal and the interphalangeal joints,
which were fixed at 90#{176}.The little fingers were
fixed rigidly in adduction with a very mild flexion attitude of the terminal interphalangeal
joint.
The neck was very short and the
sternocle-idomastoid muscles were tight. The cervical
spine seemed to be in slight extension.
Neurologic examination revealed a ptosis
of the left upper eyelid, an alternating divergent
squint, and a high degree of myopia. The
ten-don reflexes in the upper extremities were brisk, but were absent in the lower extremities. There
was some dorsiflexion of the great toe on
plantar stimulation of the left sole. Abdominal
reflexes were present. Sensation was normal
throughout, and muscular activity was normal
where not limited by the joint stiffness. Mental
development was severely retarded and at the
age of 2 years was estimated to be less than
that of a 3 months infant.
LABORATORY FINDINGS. An
electrocardio-gram was normal. Musculature of the bladder,
studied by cvstogram and cystography, was
found to be normal. Gastrointestinal fluoroscopy
revealed normal muscular activity.
Roentgenologic examination of the
extremi-ties disclosed bilateral dislocation of the hips.
The left acetabular cavity was well formed,
though the right appeared to be somewhat
shallow. Epiphyseal development appeared
normal. Both thighs had marked reduction in
muscle volume with replacement by bands
with the density of fat. There was a relative
increase in subcutaneous fat throughout both
thighs, and this layer constituted most of the
volume of this region. The feet showed almost
complete absence of musculature. Some
web-bing of the toes was noted. There was a varus
deformity of the feet. The upper extremities
showed fatty infiltration of the muscles of the
forearms in conjunction with reduction in
mus-dc volume. Epiphyseal and bone development
was normal. The hands showed webbing and
flexion deformities of the proximal
interphalan-geal joints of the middle finger. In the hands
and forearms also, the amount of subcutaneous
fat was excessive in contrast to the poorly
de-veloped musculature. Involvement of lower
extremities was more marked than that of the
upper extremities. Some osteoporosis of the
hands and feet was recorded.
All the biochemical tests performed in the
first 2 patients were done in this patient and
gave normal results. A Sulkovitch test showed
a trace of calcium in the urine. Hematologic
studies revealed a persistent, mild, hypochromic
anemia. Creatinine excretion in the urine for
24 hours was 0.105 gm. The value for creatine
was 0.114 gm. After ingestion of 1.32 gm. of
creatine, the 24-hour urine showed only
0.122 gm. of creatinine and 0.424 gm. of
creatine.
A biopsy of an adductor muscle of the left
thigh obtained at the age of 17 months failed
to exhibit any structural changes. A subsequent
biopsy, from the same region, at the age of
26 months showed a diffuse diminution in the
5:36 KANOF - ARTHROGRYPOSIS
\%,as associated with an irregularly incremented
nnotiiit of adipose ail(l collagenous tissue.
Some of the muscle fibers in addition showed
fragmentation and hyperplasia of the
sar-colemma cells. Ranvier stains, however, failed
to show any abnormalities of the motor end
plates.
COURSE. Aside from her neurologic and
orthopedic handicaps, the child suffered from
severe constitutional symptoms. Fever was an
almost constant feature except for the periods
when she was receiving ACTH or cortisone.
The fever was irregularly intermittent and did not correspond to any evident visceral infection.
She sweated profusely and was generally
irrita-ble. She underwent several episodes of
gen-eralized furunculosis, and twice developed
hronchopneumonia. Nutrition was extremely
poor and during the 23 years of hospitalization
she gained less than 4500 gm.
Extensive laboratory investigation was
di-rected towards discovery of the cause of the
persistent fever. A tuberculin skin test was
negative. The cerebrospinal fluid showed no
cells, and normal protein, chloride and glucose
content. Nose and throat cultures showed no
al)nOrmal organisms. Blood culture and
ag-glutinations for organisms of the
typhoid-para-typhoid, proteus and dysentery groups were
negative. Numerous examinations of the urine
revealed nothing beyond a trace of albumin
and a few white cells. The erthrocyte
sedi-mentation rate was within normal limits.
The extent and severity of the involvement tended to discourage attempts at
rehabilita-tion. However, experience with Case 1 had
in-dicated that ACTH and cortisone tended to
mobilize )artially ankylosed joints, and Snow
aIld Coss8 have reported encouraging results
from combined treatment with these steroids and physical therapy. After a precise program
of physical therapy had been outlined, the
child was given 50 mg. of ACTH daily for 1
month. The combination of steroid and
physi-cal therapy was discontinued for 8 months and
then recommended for a 6-week interval, the
child this time receiving 25 mg. of ACTH
daily. There was no objective improvement in
the large joints, although there appeared to
be greater flexibility in the handling of these
joints. The small (peripheral) joints did seem
improved.
Death occurred suddenly. Her temperature, which had been moderately elevated, suddenly
rose to 108#{176}F.The child exhibited convulsions
,ti1(I expired.
NECROPSY FINDINGs. External examination
failed to disclose any visible features not noted
clinically. Primary incision showed an
ab-normally thickened paniculus adiposus.
In-creased amounts of subcutaneous tissue were
present about all limbs, particularly in the
vicinity of the knee joints. In this location, the
fatty layer measured approximately 1.1 cm.
No visible admixture of fibrous tissue was
noted within the confines of the lipid tissue.
The abdominal musculature was attenuated
and often separated by extensions of fat, but
was of normal consistency and color. The
peritoneal contents were deemed normal.
Within the thoracic cavity an enlarged thymus,
weighing 50 gm., overshadowed the superior
mediastinum. No cardiac abnormalities were
seen grossly. A severe degree of pulmonary
consolidation was apparent in all 5 lobes.
Microscopic sections confirmed the presence of an overwhelming pneumonia.
The diaphragmatic, pelvic and paravertebral
musculature were of normal bulk, color and
consistency. Dissection in the ankle region
showed a disparate degree of muscle atrophy. The peroneal muscles (longus and brevis) were reduced to inconsequential structures smaller in
cross-sectional diameter than the terminal
ten-dons. The post-mortem examination having
been delayed for over an hour, Ranvier stains
for motor end plates were not performed. Large amounts of fatty tissue surrounded and sepa-rated the muscles in this region. In contrast, the distal aspects of the gastrocnemius and soleus
muscles were only mildly diminished in
vol-ume. The articular surfaces comprising the
ankle joint were smooth and glistening. No
changes were observed in the surrounding
synovial membranes.
Dissection of the knees was accomplished with difficulty because of the abnormally in-creased amount of fat covering and intervening
between the residual muscle masses. These
latter structures constituted only a small frac-tion of the cross-sectional area at this level. The anterior thigh musculature was irregularly
atrophic. The sartorius and rectus femoris were
mildly decreased in volume. The remaining
elements of the quadriceps femoris, however,
were markedly atrophic, and in the case of the
vastus intermedius, totally inapparent. Such
CLINICAL NOTES 5:37
usual reddish brown hue. Longitudinal section
revealed a greyish tan coloration with numerous
linear areas of yellow. An extensive degree of
atrophy was also apparent in adductor and
hamstring muscles. The proximal segments of
the gastrocnemius muscles were only
mod-erately involved. The knee joint, following
removal of the encompassing fatty tissue, was
freely movable. The synovial membranes were
not thickened, abbreviated or otherwise
ab-normal. Similarly, the articular cartilages
ap-peared normal.
creased ill numl)er, but not to the extent shown
by
the sarcolemmal cells. These latter elemeiitsoften OvershadOVe(l the involved muscle
struc-ture. No excessive fibrosis was evident, 1)ut a
ubiquitous fatty replacement and separation
was seen in conjunction with localized muscle
atrophy (Fig. 4). No globoid or fusiform hyaline
swellings, characteristic of primary dystrophy,
were seen. Sections of diaphragmatic and
in-tercostal musculature failed to demonstrate
any abnormalities.
Sections of svnovia and articular cartilage
Fic. 3 (Left). Histologic section of quadriceps muscle. Note extensive atrophy by preservation of
cross-striation. Focal zones of sarcolemmal cell hyperplasia also evident. H & E stain.
Fic. 4 (Right). Histologic section of gastrocneniius muscle showing n#{236}arkedatrophy and exte:isivc adipose
tissue replacement. No dystrophic changes are evident. H & E stain.
Microscopic examination of the skeletal
muscles showed a variable degree of atrophy
which roughly paralleled the extent of atrophy
described macroscopically. The majority of
fibers were diminished in transverse diameter
(Fig. 3). More striking, however, was the
ir-regularity of involvement. Within the same
microscopic field, it was not unusual to find a
few relatively normal fibers adjoining a group
which had undergone severe atrophy. The
most involved fibers presented a typically
em-bryonal appearance. The sarcoplasm was often
deeply eosinophilic and the cross striations
indistinct but present. Muscle nuclei were
in-from the knee region were considered normal.
The brain weighed 1,025 gm. The cerebral
hemispheres were of normal volume, contour
and symmetry. No unusual features were
visi-ble upon external examination or following
dis-section. The ventricles were normal throughout.
Myelination was considered complete within
the cerebrum, cerebellum and brain stem. The
spinal cord appeared questionably diminished
in volume. Numerous microscopic sections
de-rived from the brain failed to reveal any
ccitt,-lar or interstitial abnormality. Specifically, the
motor cortex Betz cells and the occulomotor
538 KANOF - ARTHROGRYPOS1S
particularly in the lower cervical regions (Fig.
5). A full complement of anterior horn cells
was seen in the lower lumbar segments. No
changes were evident in the lateral or
pos-tenor ganglionic masses. No gliosis was seen in
the anterior horn areas following Mallory’s
phosphotungstic acid-hematoxylin stains.
Mye-lin stains disclosed a loss or absence of myelin
in the bilateral corticospinal tract areas at all
levels (Fig. 6). The anterior motor roots were
often severely demyelinated. Posterior roots
appeared normal with this staining procedure.
Longitudinal sections through the femoral
nerves showed active degeneration of contained
axons, exemplified by swelling, club-formation
and zones of basophilic discoloration.
Appropri-ate stains also showed severe loss of myelin.
Sections from nerves comprising the brachial
1lexus showed essentially similar findings. In
addition, a mild degree of Schwann cell
hper-plasia was seen.
DISCUSSION
Fic. 5. (Upper). Anterior horn region, cervical
5P1uul cord. There is diniinution in the number of
ganglia of this region with a (1uestioaahle increase
in interstitial ghial cells. No evidence of any
in-flammatory response.
FIG. 6. (Lower). Spinal cord, lumbar region, (leillo’:strating demyelination of lateral
cortico-S1)iIial tract and, to a lesser degree other lo:g
tracts in lateral white matter. Mahon stain.
III the spinal cord, sections were taken at
every segmental level. There was an evident
decrease in the number of anterior horn cells,
The 3 patients herein described exhibited
most of the features typical of this disease;
i.e., marked adduction and flexion
deformi-ties of the joints, secondary dislocations
due to prolonged and unopposed action of
certain muscle groups, anomalies of the
extremities such as microdactyly and
web-hing, and reduction in the size of some
peripheral muscles with complete absence
of others.
In addition to the recognized clinical
manifestations of this disease, all 3 of our
patients presented spasticity and
hyper-activity of the tendon reflexes of the lower
extremities. Two showed palpebral ptosis
and other evidence of seventh nerve
weak-ness. One showed alternating divergent
squint, retarded mental development and
prolonged severe bouts of unexplained
fever. Such evidence of brain involvement
in conjunction with general rigidity and
limb muscle atrophy first suggested that
disease of the central nervous system rather
than a primary anomaly of either the joint
or muscle was operative in these patients.
This hypothesis seemed to be confirmed by
the histologic findings, particularly in the
case which was autopsied.
The 3 cases share a number of
micro-CLINICAL NOTES 539
scopic evidence of muscle atrophy,
exemp-lified by a decreased number of striated
muscle fibers and diminution in the
trans-verse diameter of individual fibers. The
atrophy was not accompanied by any
significant loss of cross striations until very
late in the process. No fiber swelling,
hy-aline degeneration or other dystrophic
changes were demonstrable. Sarcolemmal
hypertrophy was variably present and often
paralleled the intensity of muscle fiber
atrophy. Interstitial changes were limited
to a moderate degree of fatty replacement.
No fibrosis or myositis was evident. Normal
bundles of muscle were not infrequent
even in severely involved areas.
Occa-sionally there was an intimate
intermingi-ing of atrophied and unaffected fibers.
There appeared to exist a notable
dis-parity in the degree of atrophy
encoun-tered in various parts of the body. In Case
1 a diaphragmatic biopsy was normal,
while a specimen derived from the lower
limb 2 months later revealed early changes
of muscular atrophy. In Case 3, multiple
sections of diapragm and intercostal muscle
showed no demonstrable abnormalities,
while sections of limb muscle displayed
marked involvement. It is of interest to
note, in this case, that the more peripheral
musculature (i.e., ankle muscles) revealed
the severest degree of alteration.
The skeletal muscle changes did not
ap-pear to be static. In Case 8, early biopsy
from the left lower limb disclosed no
nota-ble structural changes. Nine months later
biopsy from the same region revealed
ob-vious microscopic atrophy. At autopsy, the
extent of the histologic changes in this
area was still more marked. These findings
seem to suggest that there is a progressive
element to the disease but it must be
re-called that the characterisic irregularity
of involvement may lead to an erroneous
interpretation. If progression is indeed a
fundamental aspect of the disease, then
histologic examination of muscle derived
from older individuals afflicted with the
disease should show the more profound
changes. Case 2 was the oldest of the
chit-dren in this series, and a gastrocnemius
biopsy showed a more marked degree of
atrophy than did specimens derived from
the other 2 children.
Examination of the central nervous
sys-tem in Case 3 revealed changes confined to
the spinal cord and emergent motor roots.
There was a moderate diminution in the
number of anterior horn cells in the rostral
half of the cord, especially in the lower
cervical segments. This was difficult to
evaluate since no reaction (viz., satellitosis,
neuronophagia or interstitial inflammatory
infiltration) was evident. Some degree of
chromatolysis and cell shrinkage was also
observed at the higher spinal levels.
Assess-ment of such changes is clouded by the
frequent observation of such degeneration
in many agonal states. A bilateral
demye-lination of the pyramidal tracts caudal to
the foramen magnum was apparent.
Demye-lination was also visible in the Inotor roots
associated with active axonal degeneration.
Theories regarding pathogenesis of
arthrogryposis have been contradictory. It
has been considered a primary deficiency
of muscle fibers and has even been
in-eluded within the broad category of
pri-mary muscular dystrophy.9 Attention has
also been drawn to the central nervous
system. Some authors have recorded a
diminution in the number of anterior horn
cells6 and in ganglionic changes in
con-junction with demyelination of the lateral
spinal cord tracts, similar to the findings in
our Case 3, were reported.
All 3 cases in the present report
con-tam peripheral muscle lesions characteristic
of muscular atrophy. There is some
cvi-dence to suggest that the disease is
pro-gressive, which if true would preclude
intrauterine injury or immobility as the
.
cause. The distributional pattern of atrophyin Case 3 is of considerable interest. The
severity of lesions in distal muscles in
con-junction with relative lack of involvement
of proximal muscles is suggestive of
pro-gressive spinal atrophy. The spinal and
motor root changes in Case 3 are in accord with this contention. Brandt also called
at-tention to the pathologic similarity between
atro-540 KANOF - ARTHROGRYPOSIS
phy.0 There are, however, important
clini-cat distinctions between cases of
arthrogry-posis and instances of infantile progressive
spinal atrophy (amyotonia congenita). The
multiple joint contractures which are
fun-damental to arthrogryposis are not seen
in arnvotena congenita. Dissection of the
knee and ankle joints of Case 3 failed to
display any cause for the clinically evident
joint rigidity. One might conjecture that
patchy muscle spasticity affecting some of
the encompassing muscles might
immo-bilize an otherwise normal joint. If the
hi-lateral pyramidal tract dlemyelinatir n is
considered in the light of this conjecture,
integration emerges. The combination of
anterior horn cell loss andi pyramidlal tract
degeneration iii an adult would be
sugges-tive of amyotrophic lateral sclerosis, a
dis-ease allied to progressive spinal atrophy.
(
In such adult cases, peripheral jointrigidity is a common finding.) The joint
abnormalities of arthrogryposis, however,
are mor#{128}than mere rigidity; deformity is
also displayed. It is possible that the
articu-lar distortion follows muscle rigidity
occur-ring during a critical phase of joint
de-velopment. Aside from the common form
of amyotrophic lateral sclerosis occurring
ill nhi(I(lle age, there is an heredofamilial
disease characterized by degeneration of
the pyramidal tracts and of the motor cells
of the gray matter with an onset in early
childhood. However, this form seems to
be familial, while arthrogryposis usually
occurs singly in a family. Aside from this
minor objection our Case 3 might be
con-sidered a case of intrauterine amyotrophic
lateral sclerosis. If more such cases
show-ing pyramidal tract destruction appear in
the literature, “infantile amyotrophic lateral
sclerosis, with arthrogryposis” might be a
suitable designation. This term while
ver-hose, is perhaps most accurate and allies
the disease to a broader and more clearly
understood pathologic entity.
SUMMARY
Three ty)ical cases of arthrogryposis are
presented.
Neurological examination points to
in-volvement of the central nervous system in
this illness.
Repeated muscle biopsies in all 3 patients
and a complete post-mortem examination in
1, suggest that this may be an infantile form
of neuromuscular atrophy rather than a
pri-mary disease of either the joints or the
mus-des.
Neither the use of steroid therapy nor
prostigmine produced lasting benefits .
at-though ACTH did seem to produce a
defi-nite, though slight, effect in freeing motion in the smaller, peripheral joints.
One patient may have benefited from
ap-plication of rehabilitation techniques.
REFERENCES
1. Stern, W. G. : Arthrogryposis multiplex
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