Extract
Spinal muscular atrophy was first reported by Guido Werdnig in 1891, when
he described "Two hereditary cases of progressive muscular atrophy
appearing as dystrophy, but on a neurotic
basis."1 A
year later, Professor Johann Hoffmann of the University of Heidelberg used the
term "spinale
muskelatrophie."2
These initial descriptions were the first to correlate the clinical findings
of these patients with the histological analysis that demonstrated a lack of
anterior horn cells with the normal number of motor neurons. Although
classification systems such as the one described by Byers and
Banker3 have been
developed to aid physicians in making a prognosis for these patients, spinal
muscular atrophy is an extremely heterogeneous condition in which clinical
manifestations as well as life span vary widely. The classification system of
Byers and Banker is the one that is most often used; however, neurologists
have used a slightly different nomenclature that is based primarily on the age
of the patient at the time of onset of symptoms.
Spinal muscular atrophy was first reported by Guido Werdnig in 1891, when
he described "Two hereditary cases of progressive muscular atrophy
appearing as dystrophy, but on a neurotic
basis."1 A
year later, Professor Johann Hoffmann of the University of Heidelberg used the
term "spinale
muskelatrophie."2
These initial descriptions were the first to correlate the clinical findings
of these patients with the histological analysis that demonstrated a lack of
anterior horn cells with the normal number of motor neurons. Although
classification systems such as the one described by Byers and
Banker3 have been
developed to aid physicians in making a prognosis for these patients, spinal
muscular atrophy is an extremely heterogeneous condition in which clinical
manifestations as well as life span vary widely. The classification system of
Byers and Banker is the one that is most often used; however, neurologists
have used a slightly different nomenclature that is based primarily on the age
of the patient at the time of onset of symptoms.
Spinal muscular atrophy, a genetic disease affecting the anterior horn
cells, occurs with a prevalence of eight in 100,000 live
births1,2.
It is the most common fatal neuromuscular disease of infancy and the third
most common neuromuscular diagnosis in children who are eighteen years of age
or less.
The classification of spinal muscular atrophy (according to the
classification system of Byers and
Banker3) is based on
the severity of disease and is related to the age at the time of clinical
onset.
Spinal Muscular Atrophy Type 1 (Werdnig-Hoffmann Disease)
Type-1 atrophy is the most severe form of spinal muscular atrophy. It is
usually diagnosed at birth or in the first few months of life, and it often
leads to death as a result of respiratory failure before the child reaches two
years of age. There are often no spontaneous movements in the extremities,
except for a fine tremor in the fingers. The infant often lies in the socalled
frog-leg position and has weak intercostal muscles that cause the child to
rely on diaphragmatic breathing. Tongue fasciculations are common, and deep
tendon reflexes are absent. These infants interact appropriately for their age
but have very little or no motor function.
Infants with spinal muscular atrophy type 1 may have malnutrition secondary
to easy fatigability during feeding. They may lose weight because they are not
able to consume an appropriate number of calories. They also have tenuous
respiratory function and are prone to the development of infections, which can
lead to life-threatening pneumonia.
Spinal Muscular Atrophy Type 2 (Juvenile Spinal Muscular Atrophy,
Intermediate Spinal Muscular Atrophy, or Chronic Spinal Muscular Atrophy)
Although children with spinal muscular atrophy type 2 are often very weak,
these patients manage to achieve normal motor milestones until approximately
six to eight months of age. The lower extremities are more involved than the
upper extremities. Many patients with spinal muscular atrophy type 2 sit
without support, but they rarely stand. The age of death is variable, with
many patients surviving into the third or fourth
decade2.
Spinal Muscular Atrophy Type 3 (Wohlfart-Kugelberg-Welander
Syndrome)
Spinal muscular atrophy type 3 presents in later childhood or early
adolescence and is the mildest form of spinal muscular atrophy. Patients with
this condition often are ambulatory but demonstrate a bilateral Trendelenburg
lurch and lumbar lordosis because of hip extensor and abductor weakness. They
also demonstrate genu recurvatum due to quadriceps weakness. The continued
ability to walk can be correlated with the age of the child at the time of
onset of weakness. Children who are younger than two years of age at the time
of onset of symptoms will stop walking by fifteen years of age, while those
who are two years of age or older at the time of onset are more likely to walk
into the fifth
decade4. In a
prospective clinical study, patients with spinal muscular atrophy type 2 or 3
demonstrated little or no progression over several
years5. The results
of this study suggested that spinal muscular atrophy may not be a degenerative
neurologic disorder.
Pediatric neurologists now use the following system to classify spinal
muscular atrophy: type 1—the clinical onset of symptoms occurs before
six months of age; type 2—the onset of symptoms takes place between six
and eighteen months of age; and type 3—the onset of symptoms occurs at
eighteen months of age or older. Patients can also be subdivided on the basis
of the greatest motor milestone achieved and the rate of mortality. For
example, type-1 patients whose symptoms occur at three months of age or
younger have been found to have an extremely high rate of mortality, whereas
patients whose symptoms occur after three months of age may survive to
adulthood.
Spinal muscular atrophy has an autosomal recessive mode of inheritance with
nearly equal gender distribution, although there is a slight male
predominance. Autosomal dominant transmission is a rare occurrence. In 1990,
Gilliam et al.6
reported that the autosomal recessive linkage was on chromosome 5q11.2-13.3.
At this 5q locus, two genes were identified: the gene for the neuronal
apoptosis inhibitory protein, which was present in 67% of patients, and the
gene for the survival motor neuron (SMN), which was found to contain deletions
in >98% of the patients with spinal muscular
atrophy7.
There are two copies of the SMN gene (telomeric SMNt and
centromeric SMNc). Two alleles of the SMNt and
SMNc genes are seen in normal individuals, and the disease seems to
be caused by mutations in both alleles of the SMNt with none or
only a small portion of the SMNc present. Although the function of
the protein encoded by the SMN gene is not exactly understood, it seems to
interact with ribonucleic acid-binding proteins. This protein appears to be
present in both the nucleus and the cytoplasm of motor
neurons8.
The initial evaluation includes the elicitation of a thorough history to
identify a delay in reaching motor milestones. The physical examination should
be focused on the assessment of motor strength and the ability to sit, the
assessment of deep tendon reflexes, and the identification of tongue
fasciculations. Patients with spinal muscular atrophy type 1 or 2 may
demonstrate a fine tremor in the fingers (polyminimyoclonus).
When a patient is suspected of having spinal muscular atrophy on the basis
of the physical examination, the diagnostic work-up is expanded to include a
hematologic test to identify the SMN gene. As some deletions in this gene are
found in >98% of patients with spinal muscular atrophy, this test is the
first diagnostic test performed. If the results of this test are negative,
further work-up is necessary. Laboratory evaluation includes measurement of
serum creatine phosphokinase and aldolase levels, the result of which is
usually normal although the level may be mildly elevated in patients with
spinal muscular atrophy type 3. For the diagnosis of spinal muscular atrophy
to be made, motor and sensory nerve conduction velocities must be normal.
Electromyography must demonstrate denervation with fibrillation potentials and
reinnervation in the form of large polyphasic motor units and increased
recruitment. Muscle biopsy, when performed, usually demonstrates neurogenic
atrophy and/or evidence of reinnervation, and the infantile pattern of
neurogenic atrophy, including preservation of large, round fibers and
denervated fasciculi, is seen.
There are currently no specific medical treatments for spinal muscular
atrophy. However, the life span of individuals has been extended through the
use of intermittent positive-pressure
ventilation9.
Proposed future therapies for patients with spinal muscular atrophy include
increasing the transcription level of SMN ribonucleic acid, stabilization of
the SMN protein, repair of degenerated motor neurons, and stem-cell therapy to
replace degenerated motor
neurons10.
The prevalence of scoliosis is directly related to the ambulatory status of
the patient and the severity of the disease. Also, depending on the form of
spinal muscular atrophy studied, the prevalence varies. Evans et al. analyzed
forty-nine patients with spinal muscular atrophy, of which forty-five (92%)
had development of
scoliosis11.
Scoliosis developed in all patients who had spinal muscular atrophy type 1 or
2 but only developed in approximately half of the patients who had spinal
muscular atrophy type 3. The age at the time of onset of scoliosis increased
in accordance with the severity of the spinal muscular atrophy: scoliosis
developed at two years of age or less in type-1 patients; between one and
seven years of age in type-2 patients; and between four and fourteen years of
age in type-3 patients. Similarly, Russman et al. studied forty-eight
patients, all of whom developed a scoliosis that was
>15°12. In
the study by Schwentker and Gibson, 70% of patients had spinal curves that
measured
>20°13. This
number is likely to be high, however, because the base population was 130
patients, of which seventy-three had died by the time of their review. When
they divided the curves relative to the size of the deformity, they
demonstrated that sixteen of the thirty-five living patients who had spine
deformity had curves that were <60°, while nineteen had curves that
were >60°. They similarly noted that the ability to walk correlated
directly with the severity of the scoliosis.
The scoliosis that is most often seen with spinal muscular atrophy is a
typical neuromuscular spinal deformity with a long, c-shaped curve. Single
curves are seen in approximately 90% of patients. Of these, thoracolumbar
curves are the most common, occurring in 80% of patients, whereas thoracic
curves are seen in approximately 20% of patients. Single curves are typically
right sided, whereas double-curve patterns have right-sided thoracic and
left-sided lumbar components. The flexibility tends to be higher than in a
typical idiopathic curve; however, progression is often more rapid. Kyphosis
can often be seen in association with this type of scoliosis, but it is
usually not severe.
The natural history of untreated scoliosis includes loss of independent
function of the upper extremities secondary to the necessity to support the
trunk, ischial bursitis with necrosis, and fairly appreciable back
pain11. In
addition, pain from impingement of the ribs on the iliac crest and
cardiopulmonary compromise have been noted; however, these conditions are
difficult to diagnose with certainty in this patient population.
For patients with spinal muscular atrophy, orthotic management can be used
to slow progression of the scoliotic curve and to delay surgical treatment.
Orthotic management is not a definitive treatment, however, because curve
progression invariably occurs. It is most often utilized in younger patients
with large curves, as it allows further growth of the spine prior to
definitive
fusion14. Aprin et
al. reported that fifteen of the twenty-two patients that they studied
underwent bracing and had a mean curve of
88°14. Only
three of these patients had curves that were <60°, and a variety of
orthoses were utilized. The use of an orthosis was discontinued in five of the
patients as a result of respiratory difficulty. The remaining ten patients
continued to wear an orthotic device but had progression of the
curve14. Merlini et
al. demonstrated variable orthotic success, depending on the severity of
spinal muscular atrophy, with a mean curve increase of 8° per year in
patients who had severe spinal muscular atrophy and 3° per year or less in
the patients who had milder forms of
atrophy15. It has
been my experience that orthotic management is less effective in patients with
spinal muscular atrophy type 1, while it may be extremely useful in patients
with spinal muscular atrophy type 3.
In general, to delay surgical treatment, an orthosis is recommended for
young patients with large curves (40° or greater). For the older patient
(ten years of age or older), an orthosis may not be useful because rapid curve
progression can occur.
The decision to proceed with operative intervention to treat spinal
deformity in these patients is, in part, dependent on the type of spinal
muscular atrophy that the patient has and the progression of the deformity.
Patients with spinal muscular atrophy type 1 have a short life expectancy;
thus, surgical treatment may be considered risky and may not provide an
improved outcome in these patients. Despite these concerns, surgical treatment
is often safe; severe acute respiratory complications following surgery are
relatively uncommon and continue to lessen with improved medical management. A
discussion that includes the family, the neurologist, the pulmonologist, and
the anesthesiologist is necessary prior to surgical treatment of patients with
spinal muscular atrophy type 1. Indications for surgery include progressive
deformity despite orthotic management and curve measurements that are
generally >50° to 60°. Despite this recommendation, most of the
patients in the literature regarding the surgical treatment of scoliosis in
spinal muscular atrophy have mean preoperative coronal curves that are larger
(usually
>80°)14,16-18.
This may be a reflection of the small number of patients in each series and
the concern about performing early surgical treatment without a clear
understanding of the curve progression and the natural history of the disease
at the time of treatment. Shapiro and Bresnan suggested that earlier surgery,
when curve magnitude was not so great, would allow for improved outcomes and
less
complications19.
The goal of surgical treatment is to obtain spinal arthrodesis in a
position that will improve the balance and sitting ability of the patient. In
preparation for the operation, each patient should undergo a careful
evaluation by the pulmonologist, the neurologist, and the anesthesiologist to
ensure that pulmonary function is maximized by the time of surgery.
Preoperative physical therapy can be useful in improving the walking ability
or sitting tolerance of
patients16.
Preoperative traction offers an excellent method to improve the flexibility of
the spine while also improving pulmonary function. Piasecki et al. reported on
the use of preoperative traction in sixteen of nineteen
patients18, and
Aprin et al. reported on its use in six of twenty-two patients and recommended
it for patients with a low vital
capacity14.
Surgical treatment usually involves posterior spinal fusion and segmental
spinal instrumentation but, because of the general flexibility of these
hypotonic patients, does not usually require an anterior release or fusion.
Anterior surgery to achieve a release and fusion prior to the posterior
procedure would be indicated for patients with larger curves (>100°),
for very young patients to prevent development of the crankshaft phenomenon,
and for patients who have no substantial pulmonary difficulties.
Anterior surgery alone with fusion and instrumentation is not recommended
because long-term correction and balance of the patient have not been found to
occur after this
procedure14,16.
Aprin et al. reported on six patients who underwent anterior spinal fusion
with Dwyer instrumentation and who ranged in age from 5.6 to twenty-seven
years of age14.
Postoperatively, a thoracolumbosacral orthosis was utilized for a mean of six
months. Secondary changes and progression of the curves either above or below
the fusion occurred in nearly all of these
patients14.
Posterior spinal fusion and segmental spinal instrumentation should be
performed from T2 to the pelvis in all patients who are nonambulatory. Fusion
short of the pelvis in these patients results in progressive pelvic obliquity,
seating imbalance, and the need for further surgical
treatment13. Most
series have reported good overall results following either Harrington rod
instrumentation or Luque rod
instrumentation14,15-18,20-23.
Post-operatively, most patients are managed with immobilization with any of a
variety of casts and/or orthoses. Coronal plane correction was reported to be
between 33% and
50%11,14,16,17,23
(Figs. 1-A through 1-D). Modern
implant systems with more segmental fixation allow for improved correction
without the need for postoperative immobilization
(Figs. 2-A through 2-D).
The postoperative course can be difficult secondary to the pulmonary
issues. Pulmonary problems occur most commonly in the early postoperative
period and often require ventilatory support. Aprin et al. reported that
atelectasis and pneumonitis developed in ten of twenty-two patients and that
those complications were more common in patients who underwent anterior
surgery than in patients who underwent posterior spinal fusion (five of six
patients compared with five of sixteen,
respectively)14.
Four of the twenty-two patients required endotracheal
intubation14. The
risk of complications following surgery is greater in older patients and in
those with larger
curves20,24.
Riddick et al. reported that patients with a mean curve of 105° and a mean
age of sixteen years had a 40% prevalence of complications compared with
patients with a mean curve of 82° and a mean age of thirteen years, who
had no
complications24.
Although uncommon, long-term complications have included pseudarthrosis with
loss of correction, prominent implants, pulmonary embolism, and diaphragmatic
rupture with major pulmonary
compromise24, Aprin
et al. reported the major complication to be narrowing of the chest secondary
to postoperative cast pressure and progressive muscle
weakness14.
Long-term outcome following surgical treatment in patients with spinal
muscular atrophy is varied. In most studies, the patients and family have
expressed satisfaction with the results and a willingness to have the surgery
again if faced with that
decision14,22.
Bridwell et al. reported that the parents of thirteen of their nineteen
patients believed that there was a major or moderate improvement in their
child's life following surgery, and those authors further reported that no
family believed that the condition of their child had
worsened22. Aprin
et al. reported that 86% of patients and relatives were happy with the
surgical results despite the fact that only three of the nineteen patients had
some improvement in the performance of daily
activities14.
Granata et al. reported similar functional challenges following
surgery17. In their
series, two ambulatory patients lost the ability to walk following surgery,
while six patients who previously had been able to sit independently could not
maintain a sitting position without support postoperatively. Furumasu et al.
have suggested that the patients who are most at risk for loss of function are
those who were weakest
preoperatively25.
Granata et al. reported an improved outcome in sitting balance, cosmesis with
respect to trunk position, and overall quality of life as well as
intermediate-to-good outcomes with regard to pulmonary status, pain, and
self-image17. It is
worth noting that positive outcome parameters were seen with regard to the
ability of the patient to maintain walking status and use of the upper
extremities. Preserving the ability to use the upper extremities is
challenging because surgical treatment results in a lengthening of the trunk
and because the patients have proximal upper-extremity weakness that limits
their ability to use the upper extremities.
Long-term pulmonary function appears to be at least stabilized and possibly
improved following surgical treatment. This positive result may be attributed
to the increased length of the chest as well as to the improved posture of the
patient while sitting in the upright
position22,26.
Robinson et al., in their report on forty-three patients with spinal muscular
atrophy, demonstrated an inverse relationship between curve severity and
percentage of predicted vital
capacity26. Nine of
the sixteen patients who were managed surgically underwent both preoperative
and postoperative pulmonary function testing, the results of which revealed a
postoperative increase in vital capacity in eight patients and a postoperative
increase in peak air flow in seven patients. For ten of twelve patients,
family members reported a major or moderate improvement in pulmonary function
following surgical treatment of the
scoliosis22.
Although improvements have been seen, it is unclear how surgery will impact
the life expectancy of these patients.
In patients with spinal muscular atrophy, spinal deformity is very common,
progressive, and most often leads to surgical treatment. Orthotic management
of the deformity can delay surgical treatment in the younger patient;
therefore, careful monitoring for rapid progression of the curve is essential.
Surgical treatment, usually consisting of posterior spinal fusion and
segmental spinal instrumentation to include the pelvis, has been associated
with overall good success and should be performed in the patient with
progressive scoliosis. Careful preoperative evaluation by a multidisciplinary
team and aggressive postoperative pulmonary care are necessary for a
successful outcome. Most patients and parents report satisfaction with
surgical treatment, and pulmonary function is often improved postoperatively.
?
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