Amyotrophic Lateral Sclerosis Presenting with Respiratory Failure

Amyotrophic with

Lateral

Respiratory

Diaphragmatic

and

Ventilation

are

two

patients

tion.

Initially,

each

patient

,4cute

the

cause

was

obscure,

respiratory

large

series

of patients

tion,

there

is

diseases.Ls.4 For

of the sclerosis

quiring of

have respiratory usually occur

A few cases been reported exertional

two

patients

cases

where

mechanical

tom

see page

dyspnea.5 acute

was

lateral

lateral original

our

knowl-

represent

the

failure

the

initial

sclerosis.

CASE

resymp-

The

ventilation

management

was

alert

and

to

wean

him

successful,

Teaching 1973,

was

deemed

oriented.

from and

Hospital to be weaned.

mechanical

the

patient

of the

#{176}Fromthe Veterans partments of Medicine University of Florida, #{176}#{176}Advanced Specialty

on next

unsucfrom

With May

four

with

1973,

weeks,

transferred

of Florida

University

to the on

612

he

attempts were un-

Shands

June

28,

Administration Hospital and the Deand Neurology, College of Medicine, Gainesville. Resident, Pulmonary Section, Veterans

Administration Hospital. tChief Resident, Department of Neurology. Chief, Pulmonary Medicine, Veterans Administration pital and University of Florida College of Medicine.

Manuscript received Reprint requests: Florida 32602

August 30; Dr. Fromm,

FROMM, WISDOM, BLOCK

revision VA

accepted

Hospital,

patient

the

lower

was

in no

dullness

lobe

of

noted.

data

revealed

the

Postmortem

diagnosis.

was

were

sclerosis.

was being ventilated with a vol(Bennett MA-i) with a trache-

and

working

distress.

The

with

the

that

left

only

perti-

decreased

lung.

levels

October

Gainesville,

and

of

breath

No

neurologic

electrolytes,

Hos-

blood

three

bacterial following

infection. treatment

end-expiratory

afebrile, weeks

alert, the

levels

improved;

studies

revealed

pul-

pneumonitis

Twenty-four hours with gentamicin,

pressure

to

in

no distress.

In

the

remained

afebrile,

and

his

and

patient

recurrent

aspiration

12

cm

H00,

but multiple

attempts at decreasing the rate of IMV and weaning the patient from mechanical respiratory support were unsuccessful due to severe respiratory acidosis. On July 16, 1973, we noted weakness of the patient’s distal extremities, with wasting of the interossei muscles. Fluoroscopic examination of his chest revealed paradoxical diaphragmatic movement on the right and no movement on the left. arterial

gas

Electroduagnostic

normal

neural

conductions.

The phremc nerve could be stimulated. Needle study of striated muscles showed a moderate decrease in the number of motor units, fibrillations, and positive waves. The results of a test with edrophonium chloride (Tensilon) were negative. The cell count, glucose level, and protein level of the cerebrospinal fluid were normal. With these findings the diagnosis of asnyotrophic lateral sclerosis was made. The patient died on Aug 4, 1973. Postmortem examination of the lungs revealed congestion of

8.

was

multiple

possiblechronic

superimposed

blood

included

diagnoses

emboli

after admission and heparin, and positive

conserva-

28,

support

ventilatory was

over

subsequent

necessary.

the

finding

the patient

improved;

During

in place

The

REPORTS

the patient

tube physical

monary

A 68-year-old white man was in seemingly excellent health until the spring of 1973, when he became short of breath and a diagnosis of congestive heart failure was made. On May 23, 1973, the patient became restless and tachypneic, a condition believed to be secondary to pulmonary edema. Mechanical

this

in each supported

lower lobes.

1

tive

corroborated

then

nitrogen, creatinine, transaminases, creatinine phosphokinase, glucose, vitamin B,0, and folate, as well as the findings from urinalysis, were all within normal limits. Arterial blood gas levels were as follows: arterial oxygen pressure (PaO,), 45 mm Hg; arterial carbon dioxide tension (PaCO0), 39 mm Hg; and arterial pH, 7.45. At this time, intermittent mandatory ventilation (IMV) at a rate of 12/mm with no positive end-expirato,y pressure was being used, and the fractional concentration of oxygen in the inspired gas (F1o2) was 0.4. Chest x-ray films showed bilateral patchy infiltrates of the

correct

diagnosis was pursued only after multiple cessful attempts to “wean” these two patients mechanical ventilatory support.

CASE

lateral

the

Laboratory

respiratory

ventilation

amyotrophic

To

amyotrophic

ventilator

abnormalities

complications, in the course

report

evaluation

admission

sounds

scler-

fluoroscopically

neurologic

urea

of amyotrophic in which the

in this

of

examination

ostomy

566

late

diagnosis

nent

neuromuscular

lateral

Further

On

ventila-

amyotrophic

comment,

was the

with

group

with

known to difficulties

symptom two

small

demonstrated

subsequently

ume-controlled

many

mechanical

was case.

requiring mechanical causes.” In most

has

editorial

disease. have

edge, first

a

was

failure in paralysis

diaphragmatic

needing

Patients

and

ventila-

respiratory

but

support

mechanical

the

failure

ventilatory

osis are but these

of

M.D.;f

symptom

imtial

requiring

on

Patients

I. Wisdom,

whose

failure

respiratory

Dependence

in Two

Gary B. Fromm, M.D.;*O Peggy A. Jay Block, M.D., F.C.C.P.t

acute

Presenting

Failure*

Paralysis

Mechanical

Described

Sclerosis

the

lungs

with

bilateral

pneumonia.

The

brain

and

showed no gross abnormalities. In the spinal cord, was a conspicuous loss of the anterior horn cells, which most marked in the cervical region (Fig 1). No demyelination cord

spinal there was

CHEST, 71: 5, MAY, 1977

his

hours, ing

condition

progressively

and severe

dyspnea

reintubated

and

again

respiratory treated

deteriorated, with increasacidosis. The patient was with a ventilator (Emerson).

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 performed 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. Postmortem examination of the lungs showed severe and extensive bronchopneumonia. Mild centriacinar emphysema was noted in both lungs. The brain and spinal cord revealed no gross abnormalities. In the spinal cord, there was loss of anterior horn cells, which was most marked in the cervical segments (Fig 2). The lateral corticospinal tracts in the spinal cord and the pyramids in the medulla showed mild demyelination. A muscular section taken at autopsy revealed atrophy with fiber angulation. Shortly

FIGURE 1. Anterior horn of cervical depopulation associated with gliosis ating anterior horn cells are seen eosin, original magnffication x 400).

of the

corticospinal

stem

brain

tracts

were

was

cord (case 1). is noted. Two at left (Hematoxylin

and

noted,

the

cortex

Neuronal degener-

and

and the

normal.

2

CASE

patient history

This

medical

was a 69-year-old of alcohol abuse,

white man 50 pack-years

with

a

past

of cigarette

smoking, and reported chronic obstructive pulmonary disease. Results of pulmonary function tests performed at his local hospital six months before admission were thought to show airway obstruction and included the following values: forced vital capacity, 2.25 L; forced expiratory volume in one second, 1.72 L; PaO2, 72 mm Hg; PaCO2, 38 mm Hg; and pH, 7.47. On Nov 11, 1975, generalized weakness, pleuritic chest pain, and shortness of breath began and led

the

patient to seek medical attention on Nov 29, 1975. The patient was believed to be in acute respiratory distress, and an endotracheal tube was placed. Initially, he was treated with a volume-controlled ventilator (Bennett MA-i), antibiotics, and with heparin for suspected pulmonary emboli.

the ensuing two weeks well; however, several

During

sponded with

equipment

for

transferred Hospital

to the on

Dec

IMV,

were

1975,

patient’s

to be

Veterans

weaned

condition

at weaning, The patient

unsuccessful.

(Fla)

Gainesville

16,

the attempts

re-

even was

Administration

from

mechanical

ventilatory support. On admission the patient was alert, cooperative, in no distress, and on a ventilator (Emerson). Rales were heard at both bases of the lungs, but findings from the rest of the

physical

examination

were

normal.

The

neurologic

DISCUSSION

ties

Segmental are the

lateral

atrophy initial

sclerosis

in

and weakness manifestations most

in the extremiof amyotrophic

patients,

although

cent of the patients will have bulbar patients with bulbar paralysis would to respiratory complications earlier their

illness

and

repeated

because

initial

symptom

tory

complications

bulbar Only tial

of

aspiration.

respiratory

In

is spinal

symptom

tract

those

in

atrophy.5 We are unaware logic documentation

patients

whose

atrophy,

occur

or intercostal dyspnea been

with

with

respira-

the

muscular reported

of previous of findings

per-

infections

patients

muscular

usually

paralysis rarely has

25

paralysis.8 The be predisposed in the course of

onset

of

paralysis. as the ini-

spinal reports in

with patients

muscular pathowith

exasnina-

tion revealed mild generalized weakness and muscular wasting, 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,

vitamin

B12,

lobes

compatible

calcium,

phosphorus,

transarninases,

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 The

patient

with

pneumonia.

was

at first believed to have chronic obstructive pulmonary disease with acute hactenal pneumonia and possible pulmonary emboli. Within six hours of admission, his arterial blood gas levels were stable, despite a reduction of the respirator’s rate of IMV to 2/mm. At this point the patient himself removed the endotracheal tube. Over the next ten

CHEST, 71: 5, MAY, 1977

2. Anterior

FIGURE

ating

anterior

appearing magnification

horn anterior

x

horn cell horn 400).

of cervical

cord

is seen in upper cell (Hematoxylin

2). DegenerLipofuscin-filled and eosin, original

(case

field.

AMYOTROPHIC LATERAL

SCLEROSIS

613

acute

respiratory

failure

amyotrophic ported

lateral here

were

dependent

unsuccessful

made,

addition

to

of

at autopsy

which

was

Respiratory motor

the

loss in

was

neurons

horn

attributed

con-

peared

cells,

vascular

region.

symptoms nosis. We

were

and

final that

agree

as a result compromise;

strikingly clinical bacterial

and

and

each patient patients were

of returned being

arterial

of the

to nearly normal ventilated with low

severity

testing

of pulmonary

performed.

Goldstein

on

could

with

the Dur-

not

endotracheal

be in

the

resix

place. In sults

patient 2, we of pulmonary

months

before

vealed The

tory

admission.

evidence pattern

etiologies Goldstein

of

of the but and

as

patients

by

with

plaint

in

trophic lateral associates8 in ing in patients

phragmatic reported

oroscopic

614

paralysis. that develop

patterns

first

values

studies

ventilatory

and dyspnea

muscular

et al7 had probably

also

comparable

as the atrophy

receiving

FROMM, WISDOM, BLOCK

and testThe reports dia-

associates9 mechanical

palsy.

The

flu-

and

not

may

in

the

in-

due

to

be

and blood gas exoutput, to a hypermetabolic weakness.1#{176} Recently, IMV of in

patients, but even our two patients.1’

this A

such as amyotrophic latto respiratory muscular

diaphragmatic

paralysis

should,

respiratory reasons.

support

thank Ann

Mrs. Alice Cullu, Cobb, who edited

Ballinger of the

and Dr. pathologic

EL, Bryan

Mrs. and Robert speci-

H: Application of ventilators in acute Med Clin North Am 57:1551, 1973

failure.

AG, Walker CC: Respiratory Med Clin North Am 55:1217-1231, 1971 3 Zwillich CW, Pierson DJ, Creagh CE, etal: of

assisted

ventilation:

secutive 4

6

7

amyo-

McCredie function paralysis.

they

since

intensive

2 Shapiro

com-

and

and

discoordination

1 Chusid

three

initial

radiographic representing

diaphragmatic

to

in

that Difficulty

REFERENCES

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O’Donohue failure in Miller

8 9 10

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A

J

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con-

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WJ Jr, Baker neuromuscular intensive care

RD,

sive

a

ap-

or cardio-

thought

and

We

dyspnea:

the

from

what

mechanics

ACKNOWLEDGMENT:

reported by with respira-

co-workers5

ventilation

when unclear

5

of

of

a problem

therefore, be considered must be continued for

respiratory

many

of

been

disease of motor neurons, eral sclerosis, that leads

defect.

manifestation

Pontoppidan patients

re-

with

involvement are

Miller

reveal

performed

limited

sclerosis and also by a report of pulmonary with diaphragmatic

patient of Goldstein of “high diaphragms,”

have

to studies in a patient

the

exertional

progressive

to

is compatible

with

The

nerve.

reported

ventilation

a restrictive studies

neuropathy

phrenic

have

These

was similar associates7

insufficiency

peripheral those

were fortunate function tests

de-

patients

problem.

weaning unsuccessful

respiratory

tubes

major

patients’

two face

our

Rider, and Mrs. Mary our report. Dr. William Schimpif assisted in the interpretation mens.

sug-

of respiratory and could

has

and

and

the

pulmonary

prompted

of artificial

tests

was

our

these the

in

a neuromuscular

Marjorie typed

be

have

ception

it

of

intrinsic

patients

to a re-

ventilation.

limited

disease, have

weakness

flow and maxused as tests to

of weakness may be of value

patients

in

illnesses,

associates7

midinspiratory flow may be

the diagnosis These tests

performed

patients’

to be

has facilitated method was

evidence of was found.

function

and

that maximum midexpiratory

aid in muscles.

both

levels while F1o2.

minimal disease

of

initial

respiratory x-ray films gas

both

report.

lead

function and

in

abnormal pulmonary change, to low cardiac state, or to muscular

pathologic diaginfection, probably

blood

ing postmortem examination, chronic obstructive pulmonary routine

in

of aspiration, accelerated however, subsequent chest

determinations

Because

similar

factor

weaning

diaphragm

pulmonary

mechanical

we

certainly

compromise, on

might

to involvement the

on

respiratory

can

Our inability to wean mechanical ventilation,

clinical

cervical

movement

paralysis

pendence

was

paradoxical

pattern

contributing

evi-

of anterior the

strictive

been

had

The

consistent

Diaphragmatic to

demonstrated,

sclerosis

innervating

patients

gested imum

and

the

After

muscles.

These

and

was

atrophy.

severe

paralysis

intercostal

weaning

lateral

by

most

failure

electrodiagnostic

muscular

of amyotrophic

re-

support.

at

and

of

patients

respiratory

paralysis

clinical

firmed

manifestation

two

ventilatory

attempts

spinal

diagnosis

first

The

acute

diaphragmatic

dence

of

in

on mechanical

many in

as the

sclerosis.

JP, Bell CM, et al: Respiratory disease: Management in a unit. JAMA 235:733-735, 1976 DW, Fowler WS, et al: Exertional complaint in unusual cases of progres-

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muscular

atrophy

and

amyotrophic

lateral

sclerosis.

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convalescing

in

H,

Bushnell surgical

LS:

Respiratory

patients

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lung

for dis-

eases, Holaday D (ed): Clinical Anesthesia and Lung Disease. Philadelphia, FA Davis Co, 1967 11 Downs JB, Klein EF Jr, Desautels D, et al: Intermittent mandatory ventilation: A new approach to weaning patients

from

mechanical

ventilators.

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1973

CHEST, 71: 5, MAY, 1977