1036 CMDT 2024 ChAPTEr 26
virus infection) can generally be distinguished by the acute
onset and monophasic course of the illness, as discussed in
Chapter 34. Acute flaccid myelitis following infection with
enterovirus may occur, especially in children, without sen-
sory involvement and resembles poliomyelitis. There is no
specific treatment.
» Clinical Findings
A. Symptoms and Signs
Difficulty in swallowing, chewing, coughing, breathing,
and talking (dysarthria) occurs with bulbar involvement.
In progressive bulbar palsy, there is drooping of the palate;
a depressed gag reflex; pooling of saliva in the pharynx; a
weak cough; and a wasted, fasciculating tongue. In pseudo-
bulbar palsy, the tongue is contracted and spastic and can-
not be moved rapidly from side to side. Limb involvement
is characterized by motor disturbances (weakness, stiff-
ness, wasting, fasciculations) reflecting lower or upper
motor neuron dysfunction; there are no objective changes
on sensory examination, although there may be vague sen-
sory complaints. The sphincters are generally spared. Cog-
nitive changes or pseudobulbar affect may be present. The
disorder is progressive, and ALS is usually fatal within
3–5 years; death usually results from pulmonary infections.
Patients with bulbar involvement generally have the poor-
est prognosis, while patients with primary lateral sclerosis
often have a longer survival despite profound quadriparesis
and spasticity.
B. Laboratory and Other Studies
Electromyography may show signs of acute and chronic
partial denervation with reinnervation. In patients with
suspected ALS, the diagnosis should not be made with
confidence unless such changes are found in at least three
spinal regions (cervical, thoracic, lumbosacral) or two spi-
nal regions and the bulbar musculature. Motor conduction
velocity is usually normal but may be slightly reduced, and
sensory conduction studies are also normal. Biopsy of a
wasted muscle shows the histologic changes of denervation
but is not necessary for diagnosis. The serum creatine
kinase may be slightly elevated but never reaches the
extremely high values seen in some of the muscular dystro-
phies. The cerebrospinal fluid is normal. To diagnose SMA,
molecular genetic testing for pathogenic variants of SMN1
is available. There are abnormal findings on rectal biopsy
and reduced hexosaminidase A in serum and leukocytes in
patients with juvenile SMA due to hexosaminidase
deficiency.
» Treatment
A number of medications are approved by the FDA for
ALS. Riluzole, 50 mg orally twice daily, which reduces the
presynaptic release of glutamate, increased short-term sur-
vival of patients with ALS in randomized trials. Sodium
phenylbutyrate (3 g)/taurursodiol (1 g) dissolved in water
and given orally once daily for 3 weeks then twice daily
thereafter slowed functional decline and prolonged sur-
vival compared to placebo when given within 18 months of
ALS symptom onset. Edaravone, a free radical scavenger,
slows disease progression in patients with mild disease. It is
administered in monthly cycles as a 60 mg intravenous
infusion on days 1–14 in the first month and days 1–10 in
the subsequent months. Ultrahigh dose methylcobalamin
injections (50 g intramuscularly twice weekly) slowed
functional decline in a placebo-controlled randomized
trial of patients within 1 year of symptom onset.
Noninvasive ventilation at least 4 hours per day in
patients with a maximal inspiratory pressure less than
60 cm H2O may prolong survival in ALS. Symptomatic and
supportive measures to treat spasticity (discussed earlier in
the section on spasticity), drooling, and dysphagia, prevent
contractures, and preserve mobility are important. Drool-
ing is treated with over-the-counter decongestants, anti-
cholinergic medications (such as trihexyphenidyl,
amitriptyline, or atropine), botulinum toxin injections into
the salivary glands, or use of a portable suction machine.
Physical and occupational therapy are helpful throughout
the disease course. Combination dextromethorphan/quin-
idine (20 mg/10 mg, one tablet orally once or twice daily)
may relieve symptoms of pseudobulbar affect. A semiliquid
diet or gastrostomy tube feeding may be needed if dyspha-
gia is severe; it is advisable to perform the procedure before
the forced vital capacity falls below 50% of predicted to
minimize the risk of complications. Tracheostomy is some-
times performed if respiratory muscles are severely
affected; however, in the terminal stages of these disorders,
realistic expectations and advance care planning should be
discussed. Information on palliative care is provided in
Chapter 5.
Treatment of spinal muscular atrophy takes advantage
of the fact that the SMN protein is also encoded by a
second gene, SMN2, that usually does not translate func-
tional protein due to aberrant splicing. Nusinersen is an
antisense oligonucleotide that modulates premessenger
RNA splicing of the SMN2 gene and results in increased
production of the full-length protein; it has shown effec-
tiveness in both infants and children with SMA. It is
approved for use in all ages and is administered intrathe-
cally (12 mg every 14 days for three doses, then once after
a 30-day interval, then once every 4 months). Risdiplam
(5 mg orally daily for patients 2 years of age and older
weighing more than 20 kg) is a small molecule SMN2 splic-
ing modifier that also results in production of the full-
length protein and is approved for use in infants and adults.
Gene therapy with intravenous delivery of an intact SMN1
gene using a viral vector (onasemnogene abeparvovec)
improves ventilator-free survival compared to historical
controls and is approved by the FDA for use in children
under 2 years of age with bi-allelic mutations in SMN1.
» When to Refer
All patients (to exclude other treatable causes of symptoms
and signs) should be referred.
» When to Admit
Patients may need to be admitted for initiation or titration
of noninvasive ventilation, or for periods of increased