Respiration and sleep in Parkinson's disease

Journal

of

Neurology,

Neurosurgery,

and

Psychiatry

1985;48:

1240-1245

Respiration

and

sleep

in

Parkinson's

disease

MCP

APPS,

PC

SHEAFF,

DA

INGRAM,

C

KENNARD,

DW

EMPEY

From

the

Department

of

Respiratory

Medicine

and

the

Section

of

Neurological

Sciences,

The

London

Hospital,

London,

UK

SUMMARY

Sleep

and

respiration

during

sleep

were

studied

in

patients

with

idiopathic

Parkinson's

disease,

patients

with

Parkinsonism

with

autonomic

disturbance,

and

normal

age

and

sex

matched

controls.

Patients

with

idiopathic

Parkinson'

s

disease

showed

significantly

reduced

REM

sleep,

and

more

frequent

and

prolonged

waking

throughout

the

night.

Hypoventilation

and

sleep

apnoea

did

not

occur

in

the

idiopathic

Parkinson'

s

disease

or

normal

groups,

but

respiration

was

disorganised

with

frequent

central

and

obstructive

apnoeas

in

the

autonomic

disturbance

group.

Respiratory

rate

during

non

rapid

eye

movement

sleep

was

similar

in

the

idiopathic

Parkinson's

disease

and

normal

groups,

but

patients

with

idiopathic

Parkinson's

disease

showed

tachypnoea

awake

and

during

REM

sleep.

Abnormal

sleep

has

been

described

in

patients

with

Parkinson's

disease.

They

sleep

poorly,

frequently

waking,

and

have

little

stage

III/IV

or

REM

sleep.'

-3

It

has

been

proposed

that

these

abnor-

malities

are

related

to

a

reduction

in

brain

amines,4

and

treatment

of

Parkinson'

s

disease

with

levodopa

or

bromocryptine

may

lead

to

an

improvement

in

sleep

quality.'

56

None

of

these

studies

has

made

any

comment

on

respiration

during

sleep.

McNicholas

et

a17

studied

three

patients

with

idiopathic

Parkin-

son's

disease,

but

reported

the

data

on

sleep

for

their

normal

subjects

and

Parkinsonian

patients

together,

only

providing

respiratory

data

during

sleep

separately.

Irregular

respiration

was

noted

to

be

a

feature

of

patients

with

Parkinsonism

following

encephalitis

lethargica,

and

was

said

to

be

worse

during

sleep.8

More

recently

there

have

been

several

case

reports

of

hypoventilation

in

patients

with

post-encephalitic

Parkinsonism,9-

"

or

associated

with

familial

Parkinson's

syndrome,'2

3

but

none

of

these

reports

described

sleep

patterns.

We

have

studied

the

patterns

of

sleep

and

respira-

tion

in

patients

with

idiopathic

Parkinson's

disease,

to

document

any

evidence

of

hypoventilation

or

respiratory

arrhythmias

associated

with

this

condi-

tion.

This

group

has

been

compared

with

normal

controls,

and

Parkinsonian

patients

with

autonomic

disturbance,

one

of

whom

had

Shy

Drager

syn-

drome.

Address

for

reprint

requests:

Dr

MCP

Apps,

The

London

Hospital,

Whitechapel,

London

El

1BB,

UK.

Received

28

September

1984

and

in

revised

form

22

March

1985.

Accepted

5

April

1985

Methods

We

studied

12

patients

(3

female,

9

male,

mean

age

57

9

years

SD

+

8

99

years)

with

idiopathic

Parkinson's

dis-

ease,

and

compared

them

with

12

normal

control

subjects,

matched

for

age

and

sex

(mean

age

56-8

years

SD

±

8

2

years).

In

addition

two

patients

with

Parkinsonian

features

and

autonomic

dysfunction

were

studied.

All

of

the

patients

were

in

a

stable

clinical

state,

and

were

on

optimal

therapy

with

anti-Parkinsonian

drugs.

None

of

the

patients

or

controls

had

any

history

of

respiratory

or

cardiac

dis-

ease.

The

subjects

slept

on

a

hospital

bed

in

a

quiet

darkened

room,

with

the

investigator

and

recording

equipment

in

an

adjoining

room.

The

Parkinsonian

patients

were

studied

for

two

nights,

and

the

normal

controls,

who

were

all

members

of

staff

and

accustomed

to

investigation,

for

one

night.

In

the

Parkinsonian

patients

the

record

from

the

second

night

of

study

was

taken

for

analysis.

Sleep

was

assessed

by

standard

methods.'4

The

electro-

encephalogram

(EEG)

was

recorded

from

position

C4

Al,

and

the

electro-oculogram

was

recorded

from

two

elec-

trodes

placed

obliquely,

one

above

the

outer

aspect

of

the

left

eye,

the

other

placed

below

the

outer

aspect

of

the

right

eye.

The

submental

electro-myogram

(EMG)

was

recorded

from

electrodes

positioned

on

the

right

side

of

the

neck.

The

electrocardiogram

(ECG)

was

recorded

from

electrodes

on

the

shoulders

in

lead

I

configuration.

All

of

these

recordings

were

obtained

using

10

mm

silver

cup

electrodes.

Airflow

was

assessed

at

the

nose

and

mouth

by

thermistors

mounted

on

nasal

cannulae,

or

with

a

laryngeal

microphone.

Respiratory

movements

were

recorded

with

inductance

coils

(Respitrace)

placed

around

both

chest

and

upper

abdomen.

Haemoglobin

oxygen

sat-

uration

was

measured

with

a

Hewlett

Packard

ear

lobe

oximeter

attached

to

the

ear

throughout

the

night.

All

information

was

recorded

onto

paper

on

a

16

channel

1240

Table

Patients

details

Age

(yrs)

Sex

Years

with

Severity

Drug

therapy

Parkinson's

disease

(Hoehn

&

Yahr)39

55

M

7

III

Orphenadrine

50

mg

t.d.s.

Sinemet

110

(1/2)

q.d.s

64

M

4

II

Sinemet

275

t.d.s

48

M

2

III

Sinemet

275

t.d.s.

54

M

12

II

Bromocryptine

5

mg

6

times

a

day

Madopar

125

mg

6

times

a

day

68

M

3

II

Sinemet

275

t.d.s.

70

M

12

III

Bromocryptine

10

mg

t.d.s.

L-evodopa

1

gm

t.d.s.

60

M

3

III

Sinemet

110

t.d.s.

57

M

10

II

Bromocrytine

5

mg

t.d.s.

Sinemet

275

t.d.s.

40

M

1

I

Sinemet

Plus

50

mg

t.d.s.

69

F

6

III

Bromocryptine

2-5

mg

t.d.s.

Benzhexol

5

mg

t.d.s.

Sinemet

275

t.d.s.

58

F

1

II

Amantidine

100

mg

b.d.

52

F

12

IV

Bromocryptine

10

mg

q.d.s.

Sinemet

110

5

tmes

a

day

Elema

Schonander

EEG

machine,

with

time

marks

applied

to

the

paper.

Analysis

of

the

record

for

sleep

stage

was

performed

by

two

of

the

investigators,

using

standard

methods.'4

Time

to

go

to

sleep,

time

to

onset

of

rapid

eye

movement

(REM)

sleep,

number

of

wakes

during

the

night,

and

duration

of

stages

W,

I,

II,

III/IV,

and

REM

were

measured,

as

was

total

non

REM

sleep

time,

and

total

sleep

time.

Respira-

tion

during

sleep

was

analysed

to

provide

the

respiratory

rate

when

awake,

taken

from

periods

of

stage

W

before

sleep,

and

during

the

night,

respiratory

rate

during

stage

II

sleep,

and

respiratory

rate

during

REM

sleep,

the

number,

timing,

and

duration

of

apnoeas,

and

the

haemoglobin

oxygen

saturation.

The

haemoglobin

oxygen

saturation

for

each

minute

was

taken

from

the

trace,

and

the

record

ana-

lysed

for

the

whole

night,

to

give

results

for

the

oxygen

saturation

in

each

sleep

stage,

and

the

time

spent

at

each

saturation

percentage

throughout

the

night.

Parameters

for

sleep

and

respiration

for

the

patients

with

idiopathic

Par-

kinson'

s

disease

were

compared

with

those

from

age

and

sex

matched

controls

using

Students

paired

t

test.

400-

300-

E

s

200

100

E]

Normal

Uj

Patient

with

idiopathic

Parkinson's

disease

['hF~~~~~~~~Ti~~~~~~

Stage

Awake

Stage

I

Stagell

Stagelil

/IV

Signif-

p<0.01

NS

NS

NS

icance

NREM

Stage

lbtal

REM

sleep

NS

p

<

005

NS

Fig

1

Steep

stages

in

Parkinsonian

patients

and

normal

controls.

Results

IDIOPATHIC

PARKINSON'S

DISEASE

PATIENTS

AND

NORMAL

CONTROLS

The

12

patients

with

idiopathic

Parkinson's

disease

were

compared

with

an

equal

number

of

age

and

sex

matched

normal

controls.

Details

of

age,

sex,

dura-

tion

of

disease,

severity

of

disease,

and

medication

for

the

patients

is

given

in

the

table.

Sleep

Analysis

of

sleep

revealed

that

the

mean

time

taken

for

Parkinsonian

patients

to

go

to

sleep

was

longer

than

that

for

the

normals,

but

that

this

was

not

statis-

tically

significant

(mean

+

standard

deviation.

Nor-

mals

16

±

10

min,

patients

with

idiopathic

Parkin-

sonism

22

5

±

17

min).

During

the

night

there

were

more

frequent

wakes

in

the

patients

with

idiopathic

Parkinson's

disease

(normals

6-1

+

2-0;

patients

8-9

+

3

1:

p

<

0

05),

and

more

time

was

spent

awake

in

this

group

(normals

81

±

50

min.;

patients

169

+

77

min:

p

<

0-01).

This

was

associated

with

a

significantly

shorter

duration

of

REM

sleep

in

the

Parkinsonian

patients

(normals

43

±

19

min;

patients

19-5

±

23

min:

p

<

0-05),

six

of

whom

showed

evidence

of

REM

sleep

for

less

than

1

minute.

There

was

no

difference

in

the

time

spent

in

any

of

the

stages

of

non

REM

sleep

between

the

two

groups.

Total

sleep

time

was

shorter

in

the

patient

group

than

in

the

normal

group,

owing

to

a

reduc-

tion

in

the

duration

of

REM

sleep

in

the

patient

group,

but

this

did

not

reach

statistical

significance

(fig

1).

REM

latency

was

similar

in

the

two

groups

(normals

157

±

93

min;

patients

148

+

50

min).

On

going

to

sleep

the

submental

EMG

decreased

in

both

groups,

and

decreased

further

in

both

groups

equally

on

going

into

REM

sleep.

1241

Respiradon

and

sleep

in

Parkinson's

disease

1242

Haemoglobin

oxygen

saturation

(I/0)

Fig

2

Haemoglobin

oxygen

saturation

during

the

night.

Haemoglobin

oxygen

saturation

Haemoglobin

oxygen

saturation

fell

in

all

subjects

during

sleep,

to

the

same

extent

in

both

groups

(fig

2).

Haemoglobin

oxygen

saturation

was

similar

when

awake

(normals

96-

5

+

1-

3

%;

patients

96-

3

±

1-1%),

in

stage

II

sleep

(normals

95

8

±

1-8%;

patients

95-4

±

0.9%),

and

in

REM

sleep

(normals

95.3

±

1-9%;

patients

95-5

±

0-9%).

Minimum

satu-

ration

was

similar

in

the

two

groups

(normals

91-3

±

4-8%;

patients

95-5

±

2.0%),

and

a

similar

pro-

portion

of

time

was

spent

with

a

haemoglobin

oxygen

saturation

of

<95%,

(normals

16-5%

of

the

night;

patients

17%

of

the

night),

with

very

little

time

spent

with

a

saturation

of

<90%

(normals

3

min;

patients

1

min).

Respiratory

rate

and

rhythm

Respiratory

rate

was

significantly

faster

in

the

patient

group

when

awake,

than

in

the

normal

con-

trols

(normals

13-9

±

1.1

breaths/min;

patients

17-9

±

1-6:

p

<

0.006),

but

on

going

to

sleep

the

respiratory

rate

decreased

in

the

patient

group

so

that

in

stage

II

sleep

the

respiratory

rate

was

no

longer

significantly

faster

than

the

normal

group.

(normals

14*0

±

0-57

breaths/min;

patients

15X0

+

0-69:

NS).

During

REM

sleep

the

mean

respiratory

Respiratory

rate

Patients

with

idiopathic

Parkinsons

disease

iv

l

Awake

Asleep

Asleep

Stage

II

REM

Normal

controls

Avcike

Asleep

Awake

Stagei

REM

Fig

3

Respiratory

rate

awake

and

asleep.

Apps,

Sheaff,

Ingram,

Kennard,

Empey

rate

was

greater

in

the

patient

group,

with

no

significant

change

in

the

normal

group

(normals

14-6

±

1-6/min;

patients

17-0

±

1-4/min:

p

<

0-05)

(see

fig

3).

In

only

one

subject

was

there

any

evidence

of

any

significant

number

of

apnoeic

episodes.

This

was

a

68-year-old

normal

control

subject,

who

gave

no

history

of

snoring

or

disturbance

of

sleep.

During

the

night

he

had

30

central

apnoeas,

and

10

obstruc-

tive

apnoeic

episodes,

all

occurring

in

Stage

I

NREM,

or

in

REM

sleep.

None

of

the

apnoeas

were

longer

than

25

seconds,

mean

apnoea

length

was

20

seconds;

there

were

no

cardiac

dysrhythmias,

and

although

haemoglobin

oxygen

saturation

fell

during

each

apnoea,

only

1

minute

was

spent

during

the

whole

night

with

a

saturation

of

<90%.

In

five

other

normal

subjects

there

were

central

apnoeas

(1,

1,

2,

2,

1,

apnoeas

each),

and

in

five

of

the

patient

group

(1,

1,

2,

3,

4,

apnoeas

each),

but

none

of

these

apnoeas

lasted

longer

than

20

s,

and

all

apnoeas

occurred

during

stage

I

NREM,

or

in

REM

sleep.

PATIENTS

WITH

AUTONOMIC

DYSFUNCTION

Two

patients

with

autonomic

disturbance

and

Par-

kinsonian

features

were

studied.

Patient

1

This

57-year-old

lady

had

a

5

year

his-

tory

of

Parkinsonism,

severe

postural

hypotension,

snoring

and

constipation.

She

showed

severe

lability

of

blood

pressure,

and

had

evidence

of

autonomic

failure,

with

no

change

in

pulse

rate

during

a

Val-

salva

manoeuvre.

It

was

felt

that

this

patient

had

orthostatic

hypotension

and

idiopathic

Parkinson's

disease.

There

was

no

stridor

when

awake,

and

vocal

cord

movement

was

normal.

The

sleep

study

revealed

a

low

(85%)

haemoglobin

oxygen

satura-

tion

when

awake,

which

fell

further

on

going

to

sleep

(mean

asleep,

82%,

minimum

80%).

The

respiratory

rhythm

whilst

asleep

was

irregular

both

in

rate

and

volume,

and

respiration

was

noisy.

There

were

occasional

episodes

of

obstructive

apnoea,

in

which

there

was

no

airflow

despite

continuing

respiratory

movement,

and

paradoxical

movement

of

the

chest

inwards

during

attempted

inspiration.

There

was

little

sleep,

but

frequent

wakings

after

episodes

of

apnoea.

Patient

2

This

43-year-old

man

had

first

presented

with

urinary

retention

three

years

previously

and

been

found

to

have

a

neuropathic

bladder.

Subse-

quently

he

developed

a

right

extensor

plantar

response,

pyramidal

weakness

of

the

right

arm,

min-

imal

cerebellar

signs,

and

mild

extrapyramidal

signs.

Initially

there

was

no

postural

hypotension,

but

this

developed

later,

with

an

absent

heart

rate

response

to

the

Valsalva

manoeuvre.

This

patient

had

many

features

of

the

Shy-Drager

syndrome.

Sleep

study

revealed

grossly

disturbed

sleep,

with

frequent

obs-

LJ~

c

1

20.

(A~

10'

i

Respiration

and

sleep

in

Parkinson's

disease

tructive

apnoeas

leading

to

waking.

The

haemoglo-

bin

oxygen

saturation

was

normal

when

awake,

but

fell

on

going

to

sleep,

falling

further

during

apnoeic

episodes.

During

sleep

the

respiratory

rate

and

rhythm

were

irregular.

When

awake

there

was

evi-

dence

of

upper

airway

obstruction

and

stridor,

and

indirect

laryngoscopy

revealed

paralysis

of

abduc-

tion

of

the

vocal

cords.

Discussion

Sleep

studies

in

patients

with

Parkinson's

disease

have

shown

a

wide

variety

of

abnormalities.

An

increase

in

sleep

latency,

frequency

of

waking

dur-

ing

the

night,

and

increased

time

spent

awake,

have

all

been

described.'

2

5

15

The

authors

have

reported

reduced

stage

III/IV

sleep,

and

a

reduction

in

the

duration

of

REM

sleep.

Other

workers

have

reported

normal

stage

III/IV

sleep,"6

or

even

com-

pletely

normal

sleep.'7

These

discrepancies

have

been

explained

in

terms

of

there

being

two

groups

of

patients

with

Parkinson'

s

syndrome,

one

group

with

reduced

REM

sleep,

and

increased

submental

mus-

cle

activity

during

REM

sleep,

and

the

other

with

normal

REM

sleep,

and

repetitive

blinking

at

the

beginning

of

the

night.'8

Few

of

these

studies

have

attempted,

however,

to

differentiate

patients

according

to

aetiology,

age,

or

severity

of

disease.3

Friedman's

has

shown

for

patients

with

Parkinson'

s

disease

that

impairment

of

sleep

may

be

directly

related

to

the

severity

of

dis-

ease.

In

addition,

some

of

the

abnormalities

described

in

association

with

Parkinson'

s

disease

are

present

in

a

normal

ageing

population'9

which

makes

the

assessment

of

more

elderly

patients

difficult.

We

have

studied

a

relatively

young

group

of

patients

with

idiopathic

Parkinson's

disease,

and

compared

them

with

age

and

sex

matched

controls.

Our

results

show

frequent

and

prolonged

waking

in

the

Parkinsonian

patients.

There

was

a

reduction

in

the

duration

of

REM

sleep,

but

no

abnormalities

of

NREM

sleep.

These

results

are

similar

to

those

of

Friedman,'5

who

found

reduced

stage

III/IV

sleep

only

in

patients

with

severe

disease

(Hoehn

and

Yahr

grade

IV/V,

and

only

one

of

our

patients

was

in

this

group).

We

did

not

find

either

increased

sub-

mental

activity,

or

repetitive

blinking

in

any

of

our

patients,

so

it

was

not

possible

to

analyse

our

data

as

did

Mouret.'8

In

our

patients

there

was

no

correla-

tion

between

the

severity

of

disease

and

limitation

of

REM

sleep.

Several

reports

of

an

improvement

with

dopaminergic

therapy,

with

prolongation

of

REM

sleep

duration,

have

suggested

that

dopamine

defi-

ciency

is

important

in

causing

the

sleep

abnor-

1243

malities

seen

in

these

patients.256202'

All

of

our

patients

were

receiving

either

Sinemet,

Madopar,

levodopa,

amantidine,

or

bromocryptine,

which

increase

dopamine

activity

centrally.

It

is

possible

that

the

abnormalities

of

sleep

seen

in

our

patients

would

have

been

more

marked

had

they

not

been

receiving

such

therapy,

and

this

may

explain

why

our

results

show

less

abnormality

of

sleep

than

some

of

the

earlier

studies.

It is

unlikely

that

the

drug

therapy

itself

caused

the

abnormalities

seen,

as

pre-

vious

studies

have

demonstrated

similar

abnor-

malities

prior

to

therapy,

with

improvement

on

therapy.

In

contrast

to

the

patients

with

idiopathic

Parkin-

son's

disease,

who

showed

only

mild

abnormalities

of

sleep,

the

two

patients

with

Parkinsonism

and

autonomic

dysfunction

showed

grossly

disturbed

sleep.

In

neither

patient

was

there

much

organised

sleep;

apnoeas

and

obstructive

episodes

caused

fre-

quent

arousals.

McNicholas

et

a17

and

Guil-

leminault22

have

reported

similar

findings

in

patients

with

the

Shy-Drager

syndrome,

although

Parkinson-

ism

was

not

a

major

feature

in

all

their

patients.

Most

of

the

abnormalities

of

sleep

appear

to

be

related

to

waking

in

response

to

arousal

after

central

or

obstructive

apnoeas,

which

are

rare

in

other

Par-

kinsonian

patients.

It

is

probable

that

these

abnor-

malities

are

more

related

to

the

autonomic

failure

in

these

patients,

and

are

not

related

to

the

Parkinson-

ism.

McNicholas

et

al7

have

reported

on

respiration

during

sleep

in

three

patients

with

idiopathic

Parkin-

son's

disease.

They

showed

no

evidence

of

sleep

apnoea

or

desaturation

during

sleep,

and

noted

a

regular

respiratory

rhythm

awake

and

asleep;

they

suggested

that

automatic

control

of

respiration

was

normal

in

their

patients

with

this

condition.

Our

patients

showed

similar

results,

with

no

evidence

of

hypoventilation

or

significant

sleep

apnoeas.

All

case

reports

of

hypoventilation

in

Parkinsonian

patients

have

appeared

in

patients

with

post-

encephalitic

Parkinsonism,

or

familial

Parkinson-

ism.9"-

I

l13

23

In

Parkinsonism

following

encephalitis

lethargica

there

is

evidence

of

more

widespread

brainstem

damage

than

in

idiopathic

Parkinson's

disease.24

Even

after

encephalitis

lethargica

only

a

small

proportion

of

patients

showed

respiratory

complications.25

Perhaps

only

with

the

widespread

brainstem

damage

present

in

a

few

cases

of

encephalitis

lethargica

is

there

failure

of

automatic

control

of

respiration,

which

may

then

lead

to

the

hypoventilation

and

respiratory

dysrhythmias

which

are

characteristic

of

such

failure

of

respiratory

control.22

26

We

observed

a

tachypnoea

in

our

patients

with

idiopathic

Parkinson's

disease,

which

decreased

on

1244

going

to

sleep.

This

tachypnoea

might

be

related

to

central

factors,

either

to

the

disease

itself,

or

the

effect

of

drugs,

to

the

presence

of

respiratory

dis-

ease,

or

to

chest

wall

rigidity

and

stiffness

as

a

result

of

the

disease.

Tachypnoea

was

a

frequent

finding

during

the

encephalitic

epidemic

of

the

1920s,8

and

has

been

reported

since

in

patients

with

Parkinson's

syndrome

prior

to

the

introduction

of

levodopa

therapy.27

-29

Tachypnoea,

breathlessness,

and

respiratory

dysrhythmias

have

been

reported

follow-

ing

levodopa

therapy.30-34

Similar

irregularity

of

respiration

in

patients

with

tardive

dyskinesia,

in

whom

excess

dopamine

activity

has

been

implicated,

have

been

reported.35

All

these

observations

suggest

that

both

dopamine

deficiency

and

dopamine

excess

may

lead

to

tachypnoea

and

affect

the

respiratory

rate

and

rhythm.

In

our

patients

there

were

no

respiratory

dysrhythmias

or

very

fast

tachypnoea

characteristic

of

dopamine

overactivity,

but

a

slightly

faster

rate

than

normals,

similar

to

that

reported

by

Kim.29

It

is

possible

that

this

abnormal-

ity

could

be

caused

by

dopamine

underactivity

from

the

disease,

as

despite

therapy,

the

patients

still

had

signs

of

Parkinsonism.

Since

we

did

not

study

the

effect

of

alteration

of

drug

dosage,

it

is

not

possible

to

say

that

the

abnormality

was

not

related

to

drug

therapy.

An

alternative

explanation

for

our

results

would

be

that

the

patients

had

evidence

of

respiratory

dis-

ease,

but

his

was

denied

by

our

patients,

and

all

patients

had

a

normal

awake

haemoglobin

oxygen

saturation,

which

suggests

that

there

was

no

respiratory

disease

sufficient

to

cause

hypoxia.

A

further

possible

explanation

for

our

results

might

be

that

the

tachypnoea

was

caused

by

increased

stiff-

ness

of

the

chest

wall.

Awake

patients

with

Parkin-

son'

s

syndrome

show

increased

intercostal

muscle

activity

throughout

the

respiratory

cycle,36

and

this

leads

to

increased

stiffness

of

the

chest

wall.

This

might

be

expected

to

lead

to

increases

in

respiratory

rate

in

compensation

for

the

increased

work

of

brea-

thing.37

On

going

to

sleep

patients

with

Parkinson's

dis-

ease

lose

their

rigidity

and

tremor,

and

in

our

patients

this

was

observed.

Similarly

on

going

to

sleep

the

respiratory

rate

fell

in

the

Parkinsonian

patients

but

not

in

the

normal

controls.

This

may

be

explained

in

terms

of

alterations

in

the

central

con-

trol

of

breathing,

or

may

be

due

to

relaxation

of

the

chest

wall

muscles,

resulting

in

reduced

work

for

breathing,

hence

leading

to

a

reduction

in

respirat-

ory

rate.37

Either

of

these

explanations

fits

our

results.

During

REM

sleep

there

is

characteristically

even

more

hypotonia

than

in

non

REM

sleep,

but

respiration

is

less

automatic,

and

depends

more

upon

voluntary

control.

In

our

normal

subjects

there

Apps,

Sheaff,

Ingram,

Kennard,

Empey

was

a

small

increase

in

the

respiratory

rate;

in

the

Parkinsonian

patients

there

was

no

evidence

of

a

further

fall

in

respiratory

rate,

as

might

be

expected

if

peripheral

chest

wall

muscle

tone

was

the

sole

determinant

of

rate.

The

respiratory

rate

increased

slightly

in

those

patients

who

had

enough

REM

sleep

for

analysis,

suggesting

that

central

factors

were

more

important

in

determination

of

the

respiratory

rate

than

the

chest

wall

tone.

These

minor

abnormalities

of

respiratory

rate

seen

in

the

patients

with

idiopathic

Parkinson's

dis-

ease

are

in

complete

contrast

to

the

changes

seen

in

patients

with

evidence

of

autonomic

dysfunction.

Both

of

these

patients

showed

frequent

apnoeic

episodes

when

asleep,

with

falls

in

haemoglobin

oxygen

saturation,

and

a

disorganised

respiratory

rhythm

both

awake

and

sleeping.

It

has

been

sug-

gested

that

the

disordered

respiratory

pattern

seen

in

these

patients

is

associated

with

a

defect

in

the

automatic

respiratory

rhythm

generator

in

the

brain

stem.7

In

addition,

the

obstructive

episodes

seen

in

our

patients,

and

in

those

cases

previously

reported,7'21

are

due

to

a

failure

of

abduction

of

the

vocal

cords,

causing

obstruction

of

the

larynx

during

inspiration.38

This

vocal

cord

palsy

was

also

present

in

one

of

our

two

patients

when

awake.

As

none

of

these

abnormalities

was

seen

in

any

of

our

patients

with

idiopathic

Parkinson's

disease,

it

is

probable

that

their

occurrence

is

due

to

the

disease

which

results

in

the

central

autonomic

dysfunction

in

these

patients

and

not

the

Parkinson's

disease

itself.

Patients

with

idiopathic

Parkinson's

disease

show

abnormal

sleep

with

frequent

waking

and

reduced

REM

sleep.

They

also

show

a

tachypnoea

when

awake,

that

disappears

when

they

go

to

sleep,

and

have

a

normal

haemoglobin

oxygen

saturation

both

awake

and

asleep,

with

no

evidence

of

sleep

apnoea.

Patients

with

autonomic

dysfunction

and

Parkinson-

ism,

in

contrast,

show

grossly

disturbed

respiration,

with

hypoventilation

and

disorganised

respiratory

rhythm,

and

wake

frequently,

showing

very

little

normal

sleep.

Both

Parkinson's

disease,

and

the

drugs

used

in

its

treatment

appear

to

affect

both

respiration

and

sleep.

These

respiratory

effects

may

be

due

to

either

direct

central

effects

on

the

respiratory

rhythm

generation,

to

effects

on

the

respiratory

rate

due

to

changing

chest

wall

tone,

or

to

a

combination

of

the

two.

References

Kales

A,

Anael

RD,

Markham

CH,

Dcharf

MB,

Tijauw

Ling

Tan.

Sleep

in

patients

with

Parkinson's

disease

and

normal

subjects

prior

to

and

following

levodopa

administration.

Clin

Pharmacol

Therap

1971;4:

397-

406.

2

Kendel

K,

Beck

U,

Wita

C,

Hohneck

E,

Zimmerman

H.

Respiration

and

sleep

in

Parkinson's

disease

Der

Einfluss

von

L

dopa

auf

den

Nachtschlaf

bei

patienten

mit

Parkinson-Syndrom.

Arch

Psychiatr

Nervenkr

1972;216:82-100.

3

Traczynska

Kubin

D,

Atzef

E,

Petre

Quadens

0.

Le

Sommeil

dans

la

maladie

de

Parkinson.

Acta

Neurol

Belg

1969;69:

727-33.

Jouvet

M.

The

role

of

monoamines

and

acetylcholine

containing

neurones

in

the

regulation

of

the

sleep

waking

cycle.

Rev

Physiol

Biochem

Pharmacol

1972;64:

166-307.

Bergonzi

P,

Chiurulla

C,

Tempesta

E.

Clinical

phar-

macology

as

an

approach

to

the

study

of

biochemical

sleep

mechanisms.

The

action

of

L

dopa.

Confin

Neurol

1974;

36:

5-22.

6

Rabey

J,

Vardi

J,

Glaubman

H,

Streifler

M.

EEG

sleep

study

in

Parkinsonian

patients

under

bromocryptine

treatment.

Eur

Neurol

1978;

17:345-50.

I

McNicholas

WT,

Rutherford

R,

Grossman

R,

Mol-

dofsky

H,

Zamel

N,

Phillipson

EA.

Abnormal

respiratory

pattern

generation

during

sleep

in

patients

with

autonomic

dysfunction.

Am

Rev

Respir

Dis

1983;

128:429-33.

8

Turner

WA,

Critchley

M.

Respiratory

disorders

in

Epidemic

Encephalitis.

Brain

1925;48:72-104.

9

Da

Costa

JL.

Chronic

hypoventilation

due

to

diminished

sensitivity

of

the

respiratory

centre

associated

with

Parkinsonism.

Med

J

Aust

1972;

1:

373-6.

'°

Garlind

T,

Linderholm

H.

Hypoventilation

syndrome

in

a

case

of

chronic

Epidemic

Encephalitis.

Acta

Med

Scand

1958;162:333-49.

"

Streider

DJ,

Baker

WG,

Baringer

JR,

Kazemi

H.

Chronic

Hypoventilation

of

central

origin.

A

case

with

encephalitis

lethargica

and

Parkinson'

s

syndrome.

Am

Rev

Respir

Dis

1966;

96:

501-97.

12

Perry

TL,

Bratty

PJA,

Harsen

S.

Hereditary

mental

depression

and

Parkinsonism

with

taurine

deficiency.

Arch

Neurol

1975;32:108-13.

'3

Purdy

A,

Hahn

A,

Barnett

JM,

et

al.

Familial

fatal

Par-

kinsonism

with

alveolar

hypoventilation

and

mental

depression.

Ann

Neurol

1979;6:

523-31.

14

Rechtschauffen

A,

Kales

A.

A

Manual

of

standardised

Terminology,

Technique,

and

scoring

for

sleep

stages

in

human

subjects.

Brain

Information

Service/Brain

Research

Institution,

University

of

California,

1968.

,s

Friedman

A.

Sleep

pattern

in

Parkinson's

disease.

Acta

Med

Pol

1980;21:

193-9.

16

Wein

A,

Golubev

V,

Yakhno

N.

Polygraphic

analysis

of

sleep

and

wakefulness

in

patients

with

Parkinson's

syndrome.

Waking

and

Sleeping

1979;3:33-40.

Greenberg

R,

Pearlman

CA.

L

dopa,

Parkinsonism,

and

sleep.

Psychophysiology

1970;7:

314.

18

Mouret

J.

Differences

in

sleep

in

patients

with

Parkin-

son's

disease.

Electroencephalogr

Clin

Neurophysiol

1975;38:653-7.

9

Dement

WC,

Miles

LE,

Carskadon

MA.

"White

Paper"

on

sleep

and

ageing.

J

Am

Geriatr

Soc

1982;30:25-

50.

20

Bricolo

A,

Turella

G,

Mazza

CA,

Buffati

P,

Gross-

lercher

JC.

Modificazioni

del

sonno

notturno

in

Par-

kinsoniani

con

L

dopa-Sist

Nerv

1-970;22:

181-90.

1245

21

Schneider

E,

Maxion

H,

Ziegler

B,

Jacobi

P.

Das

Schlar-

ferhalten

von

Parkinsonkranken

und

seine

Beinflussung

durch

1

dopa.

J

Neurol

1974;207:95-

108.

22

Guilleminault

C,

Tilkian

A,

Lehrman

K,

Forno

L,

Dement

WC.

Sleep

apnoea

syndrome,

states

of

sleep,

and

autonomic

dysfunction.

J

Neurol

Neurosurg

Psychiatry

1977;40:.718-25.

23

Phillipson

EA.

Regulation

of

breathing

during

sleep.

Am

Rev

Respir

Dis

1977;

115(Suppl):

217-24.

24

Greenfield

JG,

Bosanquet

FS.

The

brainstem

lesions

in

Parkinsonism.

J

Neurol

Neurosurg

Psychiatry

1953;

16:213-26.

25

Ziegler

LH.

Follow

up

studies

in

persons

who

have

had

epidemic

encephalitis.

JAMA

1928;91:

138-41.

26

Remmers

JE.

Effects

of

sleep

on

control

of

breathing.

In:

Widdicombe

JJ,

ed.

International

Review

of

Physiology.

Respiratory

Physiology

111,

vol

23.

Balti-

more:

University

Park

Press,

1981:113-34.

27

Grewel

F.

Dysarthria

in

post

encephalitic

Parkinsonism.

Acta

Psychiatrica

Neurol

Scand

1957;32:440-9.

28

Neu

HC,

Connolly

JJ,

Schwertley

FW,

Ladwig

HA,

Brody

AW.

Obstructive

respiratory

dysfunction

in

Parkinsonian

patients.

Am

Rev

Respir

Dis

1967;95:33-47.

29

Kim

R.

The

chronic

residual

respiratory

disorder

in

post

encephalitic

Parkinsonism.

J

Neurol

Neurosurg

Psychiatry

1968;31:393-8.

30

Granerus

AK,

Jagenburg

R,

Nilsson

NJ,

Svanborg

A.

Respiratory

disturbance

during

levodopa

treatment

of

Parkinson'

s

syndrome.

Acta

Med

Scand

1974;

195:39-43.

3'

Sacks

OW,

Kohl

M,

Schwartz

W,

Meseloff

C.

Side

effects

of

1

dopa

in

postencephalitic

Parkinsonism.

Lancet

1970:1006.

32

Barbeau

A.

L

dopa

in

Parkinson's

disease,

a

critical

review

of

nine

years

experience.

Can

Med

Assoc

J

1969;

101:

59-68.

33

Calne

DB,

Stern

GM,

Lawrence

DR,

Sharkey

J,

Armit-

age

P.

L

dopa

in

postencephalitic

Parkinsonism.

Lan-

cet

1969:744-7.

34

Newsom

Davis

J.

Pattem

of

breathing

in

disease,

general

considerations.

Bull

Eur

Physiopathol

Respir

1975;11:

113-liSP.

3S

Wiener

WJ,

Goetz

CG,

Nausieda

PA,

Klawans

HL.

Respiratory

dyskinesias,

extrapyramidal

dysfunction,

and

dyspnoea.

Am

J

Int

Med

1978;88:327-31.

36

Delhex

L,

Petit

JM.

Quelques

modalites

de

l'activite

des

muscles

respiratoire

chez

le

Parkinsonien

(Controle

Electromyographique).

Rev

Franc

Etudes

Clin

et

Biol

1961;6:580-4.

37

Mead

J.

Control

of

respiratory

frequency.

J

Appl

Physiol

1960;

15:325-36.

38

Williams

A,

Hanson

D,

Calne

DB.

Vocal

cord

paralysis

in

the

Shy

Drager

Syndrome.

J

Neurol

Neurosurg

Psychiatry

1979;42:151-3.

39

Hoehn

MM,

Yahr

MD.

Parkinsonism:

onset,

progres-

sion,

and

mortality.

Neurology

(Minneap)

1967;:17:527-42.