Prostigmine therapy in hemiplegia

Case Report Prostigmine

Therapy

JOSEPH C. DOANE,

I. LAPINSOHN,

PHILADELPHIA.

T

report

because

it seems

the

an added

treatment

of paralysis In

that

the

if not nents

affords

relative

impulse

originated

ylcholine

it

other

to the

theory

is associated

with, of acet-

physiological

of the nervous

acci-

interesting

by the interaction

with

to

aid in the

due to vascular

material nerve

weight prostigmine

therapeutic

addition,

speculative

to add

M.D.

PENNSYL.VANI.4

of interest

that

suggestion

represents dents.

appears

H. KRAVITZ? M.D.

M.D., CHARLES

and LEONARD

HIS case

in Hemiplegia*

compo-

mechanism.

ished female, face,

with stertorous

confused

and

On February female,

age

was elicited

cussion.

There

present.

The

Jewish

Hospital vascular

was admitted

accident.

marked

hypertension

covering

Flaccid

paralysis

About

prior

the patient

to admission

apparently

sound

Spinal

of five

two and a half years

central

to light

facial

palsy

of the right

was present,

of numb-

thrills

but the left

was

upper

with

present.

and lower

hyperactive

deep

reflexes in the upper, and absent

rigidity

There

and a suggestive

tap revealed

was slight

Kernig

sign.

a bloody spinal fluid with a

pressure of 350 mm. of HzO. The blood pressure on admission and

was 25Ojl50,

the pulse and

and 25 per minute, Phlebotomy

awoke from an

sleep complaining

or

of the head and eyes to the left was A

to the

a period

and per-

murmurs

eyes reacted

noted.

nuchal

of a recent

left ventricular

pupil was larger than the right and a conjugate deviation

a white

A history of a rather

years was obtained.

no

heart

sinus tachy-

on paipation

reflexes in the lower extremity.

with the diagnosis

cerebral

were

flushed

The

in intensity,

cardia was present, and moderate enlargement

extremity

15, 1946, the patient,

thirty-nine,

semi-stuporous.

sounds were increased

and superficial

CASE REPORT

respiration,

98.2”~., were

120

performed

on

admission,

of 400 cc. of blood. The blood

ness in the left side of her face and weakness in

pressure

her left arm. Following

moval of 10 cc. of spinal fluid over a period of

tion she eventually limb.

She

treatment

regained

for this condi-

full control

was apparently

of her

well following

this

fifteen

after

rates

respectively.

was

with the removal

temperature

respiratory

minutes

pressure

from

episode until her present illness, except for some

Following

varying degree of headache,

patient appeared

and

constipation,

attributed On

which

nervousness, her family

fatigue, physician

the night

of admission

the patient,

be-

per

employed

cent

of feeling

sisted of sodium

tingling

ill and

of numbness

and

on the right side of her body. She be-

and

pressure.

in spinal spinal

by

gr. iii, and phenobarbital,

fluid

of H&. tap,

enemas

intravenously,

Further

nitrite,

Re-

the

more alert although

Dehydrating

glucose,

180,‘140.

to 90 mm.

to become

as indicated

intracranial

was

a drop

mm.

phlebotomy

coming excited during a card game, complained generally

caused 350

still semi-stuporous. 50

to hypertension.

phlebotomy

and were

signs of increased medication

con-

gr. iss, aminophylline, gr. ss four times a day.

came semi-stuporous and finally lapsed into complete unconsciousness, developing a flaccid

An electrocardiogram myocardial damage

paralysis of the right side of her body. Physical examination revealed a well nour-

tion revealed moderately advanced arteriosclerotic changes. The patient’s course was a

* From .Jewiah Hospital,

Phila.,

Pa.

revealed no evidence of and eye ground examina-

Prostigmine in Hemiplegia-Doaw

224 stormy days

one from

the time of admission

following

remained

and

extremely

her

to recognize

appeared

became

visitors

somewhat.

improved

to

more alert,

and

Her

appeared

general

be

patient’s

prognosis

improved,

improvement

there

the

physical

signs

admission

improvement

there

of

of her paralyzed

mately the same as on admission. following

survival

remaining

approxi-

Nineteen

days

was still little

in the movement

or no

of her paralyzed

limbs. Barnes

and

cholinergic healing and

Beutner112

of central

Kennard

.Jepson

have

nervous

treatment

to

with

Thirty

$isn

ministered 5th,

the

mg.

in the patient’s of motion,

paralysis.

supervened,

immediately

days after

of range

within twentycramps, atropine

these symptoms.

Prostig-

for a day following

barbital

strength

act

was added supposition

as a depressant

reactions.

* This

to each

speed

finger to her nose, her grip became coordination

improved

greatly.

leg of

her right

stronger and

On March

12th

she was able to place her hand on the top of her head,

and

slowly

adduct, pronate speech

and

flex,

extend,

abduct

and

and supinate her right arm. Her

vision

were

also

improved.

On

March

13th she was able completely

extend

her leg to an angle of 60 degrees against

gravity in a sitting position,

to flex and

able to throw a ball,

and her right

was approximately

thumb

On March patient

attempted

this

after this improved after her discharge 20th,

gradually

19th

she appeared

to be clinically

lack of coordination

in her gait. Prostigmine

continued

during her convalescence

employed

during

hospitalization, examination

patient

has made a rather

dose, on the theowould

untoward no

* It has been shown experimentally by Barnes and BeutneP in vitro experiments that both phenobarbital and dilantin sodium give rise to positive currents in their oil cell experiments. This generation of a positive

on March well except

for slight weakness of her right arm, and a slight

Follow-up

lower

until eight weeks

from the hospital

period.

to cause

18th the

to stand, and on March

of

appeared

less 16th

17th she was allowed to sit in a chair

by her bed for a half hour. On March

and coordination

drug

On March

she was able to turn from side to side in her bed.

on her

the latter

the same.

and fingers appeared

spastic, and better coordinated.

was kept

and

except

less nasal in quality,

watch

of any further

dosage

her

and

able to touch

in

of the upper

that

she became

On March

extend

strength

to be a.regression

limbs. The dose of prbstigmine was then reduced to 15 mg. four times a day and x gr. of phenoretical

execution;

in

and

she was able to take a few steps. Her condition

which

and there seemed movement

admis-

administered

mine was discontinued

voluntary

ad-

on March

whereupon

was

relieved

of motion,

limb

bromide

nausea, abdominal

>iaa ,

gr.

increased

It was

were

with increase

and diarrhea

to flex

14th her condition

of

sulfate

which was manifested

sulfate,

partially

ability

Her speech was somewhat

in this case in an

of prostigniine

condition

the

in the

to be marked improvement

four hours. However,

range

primates.s

restoration

nineteen

sion. There appeared

episode,

in

three times a day starting

approximately

11 th

the

for a slight nasal quality to her voice. On March

of atropine

gr.

nerve palsies were greatly improved.

from

dory1

cerebral

hasten

two inches

and her vision and speech were normal

decided to employ prostigmine endeavor

that

stimulate

the use of prostigmine

of infantile

her lower extremity

and to raise her arm to an angle of 15 degrees,

system lesions. Ward

employed

suggested

function.

suggested

drugs should theoretically

slowly to flex and extend

condition

10th she was able

and lift it approximately

was no evidence

in the movement

and the patient’s On March

flat surface of her bed. Her seventh and twelfth

to be

to

reaction

rapidly improved.

her

condition

as

untoward

was

greatly during the following week, but

the

limbs,

She

did not react well to

prognosis

the patient

improving

steadily

to five

accident.

grave. On the sixth day following

admission,

while

cerebral

semi-stuporous,

stimuli,

able

her

et al.

and

progress

a close

during

this

reveals that this

unusual

view of the severity of her cerebral her poor prognosis on admission. Of interest,

was

in the doses

recovery, accident

in and

also, in this case, is the sustained

drop

in blood

with

the

pressure

administration

noted of

in conjunction prostigmine

and

charge directly antagonizes the negative charge set up by acetylcholine, hence the rationale for the use of phenobarbital and dilantin in the treatment of epilepsy. The view that excess acetylcholine with resultant increased negativity and stimulation plays a part in the etiology of epilepsy has long been held by these investigators. AMERICAN

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Prostigmine

in Hemiplegia-bane

sodium nitrite. This lowering of arterial pressure has persisted during her convalescence rising but slightly on resumption of activity.

Kabat6 muscular are

cerebral

Of particular

This

palsy.

in spasticity,

observer

and

reports

a

range

of

increased

deformity,

relief

in voluntary

in his cases of hemiplegia.

Improve-

in his cases of monoplegia

improvement

in the

of spasticity

in strength

cases

and

and coordi-

of cerebral

palsy

which prostigmine was employed. Kabat recommends the subcutaneous jection

in-

once or twice daily of 2 cc. of neo-

stigmine i{00

in

methyl sulfate l-2000

solution plus

gr. to T.iso gr. of atropine

sulfate.

One of us (J. C. D.) has recently fully employed

prostigmine

nervous

use

the

is brought

and Kennardg aid in healing of prostigmine.

drug, was used in their

to treat

accelerated

lesions

in

of the central

monkeys,

recovery

and

of function

here

was

re-

ported. Prostigmine 0.01 per cent has been used by Welsh lo to aid in the regeneration of a cut planarian. tylcholine, is

a

integrity

excess

agent,

maintaining

and hence

Whether choline

neutralizing

that ace-

cholinergic

substance

of neurones

in healing. allows

He maintains

a physiologic

trophic

the

should aid

prostigmine acts by esterase and thus

acetylcholine

to accumulate

and achieve a therapeutic effect, or whether it has an independent cholinergic action of its own hand

is as yet

unknown.

seems to suggest

position

that

Evidence the latter

at sup-

is correct.

Nikers

in oral

produces

doses of 15 to 30 mg. three times a day for the relief of spasticity in multiple sclerosis,

the

system

success-

bromide

Ward

that actual

a cholinergic

experiments

of

monoplegia,

decreased

some improvement nation

interest

of hemiplegia

from muscle pain and increase

and definite

is not known.

Doryl,

origin,

ment was noted

lesions

in various cases of neuro-

cerebral

motion

system

nervous

following

decrease

passive motion,

central

results

in cases

vascular

aid in healing

results

encouraging

and poliomye-

actual

evidence

dysfunction.

his results

of arthritis

present

has reported

using neostigmine

as in treatment litis, or whether about,

COMMENT

225

et al.

et

After blocking a suitable

al.

believe

cholinergic choline

that

effects esterase

physiological

agent)

prostigmine of

its

own.

effects

with

they noted

and of postoperative hemiplegia in a patient with a pituitary gland tumor. Jepson5 treated twenty-five cases of in-

with prostigmine.

fantile cerebral paralysis using oral prostigmine bromide in doses of 5 mg. three times

posedly produces its effect solely by neutralization of choline esterase with subse-

a day. The medication

was continued

for at

least six months or as long as improvement was noted. The chief results achieved in this series seemed to be a decrease spasm

and

an increase

muscles involved. The results noted above are similar

in the references

quent

a cholinergic

increase

could be elicited drug

which

sup-

in acetylcholine,

has been

shown to have less physiological

effect than

of the cited

smaller amounts than eserine increased petit ma1 brain waves in epileptics. Barnes2

to the results noted in the

case presented. The rapid rate of recovery seen in this patient coincided with the period during which prostigmine was administered. Whether the drug brings about its therapeutic

Eserine,

contractions

prostigmine both in vitro and in vivo experiments. Williams’l reports that intravenous administration of prostigmine in much

in muscle

in function

that muscular

effect through relief of spasticity,

found that the electrical potential set up by prostigmine in oil cell experiments is much more lasting than that caused by eserine. He states that the electrical effects ot prostigmine are the factors important in nerve cell regeneration and that the action

Prostigmine in Hemiplegia-Deane currents

thus set up aid in bridging

neural

improved

Of note also in this case is the reduction in blood

pressure

-ministration

coincident

with

of the drug. Although

fested

far surpassed

to have some periaction

vasoconstricting

and Ravin,’ peripheral

by Mendez

still as a cholinergic action

of vasodilation. prostigmine

should

drug the

be primarily

If the cholinergic

as a vasodilator

one

action

of

is of use; as

suggested by this case, in bringing about the lowering of blood pressure in selected of essential

hypertension,

avenues of investigation of the theories hypertension

then

are opened

generally

rich

in view

held that essential

is of neurogenic

origin.4

Its

main action, however, may be only the prevention of the overstimulation of sympafibers,

the

antagonistic

cholinergic

and adrenergic

effects

peripheral

being

on

an accepted

of

drugs and their

vascular

physiological

possible relationship

action

structures fact.

of prostigmine

This

therapy

to the drop in blood pressure must as yet of necessity be limited to the sphere of theoretical speculation. SUMMARY

A report probably presented. peutic

of a patient

due

It seemed

results

prostigmine

with hemiplegia

to cerebral were

bromide

that

hemorrhage excellent

obtained orally.

by

Rapid

is

therausing return

in range of motion,

spasticity,

general

the ad-

mine has been reported

thetic

an increase

prostig-

pheral

cases

of strength,

and decreased

connections.

et al.

promptly.

as well as a greatly

condition, The

were

mani-

therapeutic

the prognostic

results

hopes held for

the patient. Reports and

of other

a brief

plications

patients

discussion

involved

thus

treated

of theoretical

im-

are presented.

REFERENCES 1. BARNES, T. C. and BBUTNER, R. The chemical and electrical origin of nervous energy. Hahnemann. Monthly, 81: 56, 1946. 2. BARNES, T. C. A personal communication from the departments of physiology and pharmacology. Hahnemann Medical College and Hospital of Philadelphia. 3. FELDBERG, W. Present views on the mode of action of acetylcholine in the central nervous system. Physiol. Rev., 25: 596, 1945. 4. GUBNER, R., SILVERSTONE:F., and UNGERLEIDER, H. E., Range of blood pressure in hypertension. .7. A. M. A., 130: 325, 1946. 5. JEPSON, P. M. The use of prostigmine in the management of infantile cerebra! paralysis. J. Pediat., 28: 65, 1946. 6. KABAT, H. M. Studies on neuromuscular dysfunction. Pub. Health Rep., 59: 1635, 1944. 7. MENDEZ, R. and RAVIN, A. On the action of prostigmine on the circulatory system. 3. Pharmacol. B Exjer. The@., 72: 80, 1941. 8. RIKER, W. F., WESCOE, W. C., CATTEL, MC., and SHORR, E. Fed. Proc., 5: 198, 1946. 9. WARD, A. A. and KENNARD, M. A. Effect of cholinergic drugs on recovery of function following lesions of central nervous system in monkeys. Yale 3. Biol. B Med., 15: 189, 1942. 10. WELSH, J. H. Evidence of trophic action of acetylcholine in a planarian. Anat. Rec. 94, No. 3 Supplement: 421, 1946. 11. WILLIAMS, D. Effect of choline-like substances on cerebral electrical discharges in epilepsy. 3. Neural. & Psychiat., 4: 32, 1941.

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