Amyotrophic lateral sclerosis presenting with

respiratory failure. Diaphragmatic paralysis and

dependence on mechanical ventilation in two
patients.
G B Fromm, P J Wisdom and A J Block

Chest 1977;71;612-614
DOI 10.1378/chest.71.5.612
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© 1977 American College of Chest Physicians
Amyotrophic Lateral Sclerosis Presenting
with Respiratory Failure*
Diaphragmatic Paralysis and Dependence on
Mechanical Ventilation in Two Patients

Gary B. Fromm, M.D.;*O Peggy I. Wisdom, M.D.;f and

A. Jay Block, M.D., F.C.C.P.t

Described are two patients whose imtial symptom was was subsequently demonstrated fluoroscopically in each
acute respiratory failure requiring mechanical ventila- case. Further neurologic evaluation then supported the
tion. Initially, the cause of the respiratory failure in diagnosis of amyotrophic lateral sclerosis. Postmortem
each patient was obscure, but diaphragmatic paralysis examination corroborated this diagnosis.

,4cute respiratory failure requiring mechanical On admission the patient was being ventilated with a vol-
ventilatory support has many causes.” In most ume-controlled ventilator (Bennett MA-i) with a trache-
ostomy tube in place and was in no distress. The only perti-
large series of patients needing mechanical ventila-
nent physical finding was dullness with decreased breath
tion, there is a small group with neuromuscular sounds over the lower lobe of the left lung. No neurologic
diseases.Ls.4 Patients with amyotrophic lateral scler- abnormalities were noted.
Laboratory data revealed that levels of electrolytes, blood
For editorial comment, see page 566
urea nitrogen, creatinine, transaminases, creatinine phospho-
kinase, glucose, vitamin B,0, and folate, as well as the findings
osis are known to have respiratory complications,
from urinalysis, were all within normal limits. Arterial blood
but these difficulties usually occur late in the course
gas levels were as follows: arterial oxygen pressure (PaO,),
of the disease. A few cases of amyotrophic lateral 45 mm Hg; arterial carbon dioxide tension (PaCO0), 39 mm
sclerosis have been reported in which the original Hg; and arterial pH, 7.45. At this time, intermittent manda-

symptom was exertional dyspnea.5 To our knowl- tory ventilation (IMV) at a rate of 12/mm with no positive
end-expirato,y pressure was being used, and the fractional
edge, the two patients in this report represent the
concentration of oxygen in the inspired gas (F1o2) was 0.4.
first two cases where acute respiratory failure re- Chest x-ray films showed bilateral patchy infiltrates of the
quiring mechanical ventilation was the initial symp- lower lobes.
tom of amyotrophic lateral sclerosis. The correct The working diagnoses included multiple recurrent pul-

diagnosis was pursued only after multiple unsuc- monary emboli and possible chronic aspiration pneumonitis
with superimposed bacterial infection. Twenty-four hours
cessful attempts to “wean” these two patients from
after admission and following treatment with gentamicin,
mechanical ventilatory support. heparin, and positive end-expiratory pressure to 12 cm H00,

CASE REPORTS the patient was afebrile, alert, and in no distress. In the
subsequent three weeks the patient remained afebrile, and his
CASE 1
arterial blood gas levels improved; but multiple
attempts at
A 68-year-old white man was in seemingly excellent health
decreasing the rate of IMV and weaning the patient from
until the spring of 1973, when he became short of breath and
mechanical respiratory support were unsuccessful due to
a diagnosis of congestive heart failure was made. On May
severe respiratory acidosis.
23, 1973, the patient became restless and tachypneic, a
On July 16, 1973, we noted weakness of the patient’s distal
condition believed to be secondary to pulmonary edema.
extremities, with wasting of the interossei muscles. Fluoro-
Mechanical ventilation was deemed necessary. With conserva-
scopic examination of his chest revealed paradoxical diaph-
tive management the patient improved; on May 28, 1973, he
ragmatic movement on the right and no movement on the left.
was alert and oriented. During the next four weeks, attempts
Electroduagnostic studies revealed normal neural conductions.
to wean him from mechanical ventilatory support were un-
The phremc nerve could be stimulated. Needle study of
successful, and the patient was transferred to the Shands
striated muscles showed a moderate decrease in the number
Teaching Hospital of the University of Florida on June 28,
of motor units, fibrillations, and positive waves. The results
1973, to be weaned.
of a test with edrophonium chloride (Tensilon) were nega-
#{176}Fromthe Veterans Administration Hospital and the De- tive. The cell count, glucose level, and protein level of the
partments of Medicine and Neurology, College of Medicine, cerebrospinal fluid were normal. With these findings the
University of Florida, Gainesville. diagnosis of asnyotrophic lateral sclerosis was made. The
#{176}#{176}Advanced
Specialty Resident, Pulmonary Section, Veterans
Administration Hospital. patient died on Aug 4, 1973.
tChief Resident, Department of Neurology. Postmortem examination of the lungs revealed congestion
Chief, Pulmonary Medicine, Veterans Administration Hos- of the lungs with bilateral pneumonia. The brain and spinal
pital and University of Florida College of Medicine. cord showed no gross abnormalities. In the spinal cord, there
Manuscript received August 30; revision accepted October 8.
was a conspicuous loss of the anterior horn cells, which was
Reprint requests: Dr. Fromm, VA Hospital, Gainesville,
Florida 32602 most marked in the cervical region (Fig 1). No demyelination

612 FROMM, WISDOM, BLOCK CHEST, 71: 5, MAY, 1977

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© 1977 American College of Chest Physicians
 hours, his condition progressively deteriorated, with increas-
ing dyspnea and severe respiratory acidosis. The patient was
reintubated and again treated with a ventilator (Emerson).
Shortly thereafter, moderate distal muscular weakness,
with prominent fasciculations, was noted. On Jan 8, 1976,
fluoroscopic examination of the chest revealed paradoxical
movement of the right diaphragm and no movement of
the left. The result of a test with edrophonium chloride
(Tensilon) was negative. Electrodiagnostic studies were per-
formed and showed normal neural conductions and a normal
evoked-potential electromyogram. Needle study of striated
muscles showed fasciculations, fibrillations, and positive
waves. The cell count, glucose level, and protein of the
cerebrospinal fluid were normal. With the preceding findings
the diagnosis of amyotrophic lateral sclerosis was made.
Shortly thereafter, the patient died.
FIGURE 1. Anterior horn of cervical cord (case 1). Neuronal
depopulation associated with gliosis is noted. Two degener-
Postmortem examination of the lungs showed severe and
ating anterior horn cells are seen at left (Hematoxylin and extensive bronchopneumonia. Mild centriacinar emphysema
eosin, original magnffication x 400). was noted in both lungs.
The brain and spinal cord revealed no gross abnormalities.
of the corticospinal tracts was noted, and the cortex and the
In the spinal cord, there was loss of anterior horn cells, which
brain stem were normal. was most marked in the cervical segments (Fig 2). The
CASE 2 lateral corticospinal tracts in the spinal cord and the pyramids
This patient was a 69-year-old white man with a past
in the medulla showed mild demyelination. A muscular sec-
medical history of alcohol abuse, 50 pack-years of cigarette tion taken at autopsy revealed atrophy with fiber angulation.
smoking, and reported chronic obstructive pulmonary dis-
DISCUSSION
ease. Results of pulmonary function tests performed at his
local hospital six months before admission were thought to Segmental atrophy and weakness in the extremi-
show airway obstruction and included the following values:
ties are the initial manifestations of amyotrophic
forced vital capacity, 2.25 L; forced expiratory volume in
lateral sclerosis in most patients, although 25 per-
one second, 1.72 L; PaO2, 72 mm Hg; PaCO2, 38 mm Hg;
and pH, 7.47. On Nov 11, 1975, generalized weakness, cent of the patients will have bulbar paralysis.8 The
pleuritic chest pain, and shortness of breath began and led patients with bulbar paralysis would be predisposed
the patient to seek medical attention on Nov 29, 1975. to respiratory complications earlier in the course of
The patient was believed to be in acute respiratory dis-
their illness because of respiratory tract infections
tress, and an endotracheal tube was placed. Initially, he was
and repeated aspiration. In those patients whose
treated with a volume-controlled ventilator (Bennett MA-i),
antibiotics, and with heparin for suspected pulmonary emboli. initial symptom is spinal muscular atrophy, respira-
During the ensuing two weeks the patient’s condition re- tory complications usually occur with the onset of
sponded well; however, several attempts at weaning, even bulbar paralysis or intercostal muscular paralysis.
with equipment for IMV, were unsuccessful. The patient was
Only rarely has dyspnea been reported as the ini-
transferred to the Gainesville (Fla) Veterans Administration
Hospital on Dec 16, 1975, to be weaned from mechanical
tial symptom in patients with spinal muscular
ventilatory support. atrophy.5
On admission the patient was alert, cooperative, in no We are unaware of previous reports with patho-
distress, and on a ventilator (Emerson). Rales were heard at logic documentation of findings in patients with
both bases of the lungs, but findings from the rest of the
physical examination were normal. The neurologic exasnina-
tion revealed mild generalized weakness and muscular wast-
ing, with normal sensation. Deep tendon reflexes were brisk,
except for absent ankle reflexes, and the findings from the
remainder of the examination were normal.
Laboratory data revealed levels of electrolytes, blood urea
nitrogen, creatinine, calcium, phosphorus, transarninases,
vitamin B12,
magnesium, and folate, as well as the results
of urinalysis, to be normal. Arterial blood gas levels were as
follows: PaO2, 78 mm Hg; PaCO,, 36 mm Hg; and pH,
7.45. The rate of IMV was 6/mm and the Flo, was 0.4. A
chest x-ray film disclosed bilateral infiltrates of the lower
lobes compatible with pneumonia.
The patient was
at first believed to have chronic obstructive
pulmonary disease with acute hactenal pneumonia and pos-
sible pulmonary emboli. Within six hours of admission, his
FIGURE 2. Anterior horn of cervical cord (case 2). Degener-
arterial blood gas levels were stable, despite a reduction of
ating anterior horn cell is seen in upper field. Lipofuscin-filled
the respirator’s rate of IMV to 2/mm. At this point the patient appearing anterior horn cell (Hematoxylin and eosin, original
himself removed the endotracheal tube. Over the next ten magnification x 400).

CHEST, 71: 5, MAY, 1977 AMYOTROPHIC LATERAL SCLEROSIS 613

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© 1977 American College of Chest Physicians
acute respiratory failure as the first manifestation of the consistent paradoxical movement we report.
amyotrophic lateral sclerosis. The two patients re- Diaphragmatic paralysis can certainly lead to a re-
ported here were in acute respiratory failure and strictive pattern on pulmonary function tests and
dependent on mechanical ventilatory support. After to respiratory compromise, and it was the major
many unsuccessful attempts at weaning had been contributing factor in both of our patients’ de-
made, diaphragmatic paralysis was demonstrated, pendence on mechanical ventilation.
in addition to clinical and electrodiagnostic evi- Our inability to wean these two patients from
dence of spinal muscular atrophy. The clinical mechanical ventilation, in the face of what ap-
diagnosis of amyotrophic lateral sclerosis was con- peared to be limited intrinsic pulmonary or cardio-
firmed at autopsy by the loss of anterior horn cells, vascular disease, prompted our thought that they
which was most severe in the cervical region. might have a neuromuscular problem. Difficulty in
Respiratory paralysis was attributed to involvement weaning patients has been a problem since the in-
of motor neurons innervating the diaphragm and ception of artificial ventilation and may be due to
intercostal muscles. abnormal pulmonary mechanics and blood gas ex-
These patients were strikingly similar in initial change, to low cardiac output, to a hypermetabolic
symptoms and final clinical and pathologic diag- state, or to muscular weakness.1#{176} Recently, IMV
nosis. We agree that bacterial infection, probably has facilitated weaning of patients, but even this
as a result of aspiration, accelerated respiratory method was unsuccessful in our two patients.1’ A
compromise; however, subsequent chest x-ray films disease of motor neurons, such as amyotrophic lat-
and determinations of arterial blood gas levels in eral sclerosis, that leads to respiratory muscular
each patient returned to nearly normal while the weakness and diaphragmatic paralysis should,
patients were being ventilated with low F1o2. Dur- therefore, be considered when respiratory support
ing postmortem examination, minimal evidence of must be continued for unclear reasons.
chronic obstructive pulmonary disease was found.
ACKNOWLEDGMENT: We thank Mrs. Alice Cullu, Mrs.
Because of the severity of both patients’ illnesses, Marjorie Rider, and Mrs. Mary Ann Cobb, who edited and
typed our report. Dr. William Ballinger and Dr. Robert
routine testing of pulmonary function could not be
Schimpif assisted in the interpretation of the pathologic speci-
performed. Goldstein and associates7 have sug- mens.
gested that maximum midinspiratory flow and max-
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614 FROMM, WISDOM, BLOCK CHEST, 71: 5, MAY, 1977

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© 1977 American College of Chest Physicians
 Amyotrophic lateral sclerosis presenting with respiratory failure.
Diaphragmatic paralysis and dependence on mechanical ventilation in two
patients.
G B Fromm, P J Wisdom and A J Block
Chest 1977;71; 612-614
DOI 10.1378/chest.71.5.612
This information is current as of September 1, 2010
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