Medical Hypotheses 4: 1,4449, IS THE POLIO VIRUS A. OHRY

M.D.,

Chaim

Sheba

homer.

Israel.

RESPONSIBLE

M.E.

Medical

1978.

BROOKS Center,

FOR LATE CENTRAL

M.D. &R. ROZIN

Affiliated

NERVOUS

SYSTEM TUMORS?

M.D., The Neurological

to the Tel-Aviv

University

Rehabilitation

Sackler

School

Department,

of Medicine,

Tel-Has-

SUMMARY A hypothesis

is advanced

in the central

nervous

known

evidence

is discussed

concerning

system.

the relationship

The literature

of viral and neoplastic

as it applies

behaviour

to this possible

the past year,

poliomyelitis, meningioma tumors

Zilkha could

(7) noted appear

many

years.

later

as these

disease

a progressive

with

AND VIRAL

ACTIVITY

spinal

is whether

clinical

studies

the polio

developing

many

cord tumors,

There

is no definitive

after

developing

30 years after childhood

cell disease.

for

this

and produce developed

in the human

chronic

spinal

tumors

lateral sclerosis-like

A virus can persist

poliomyelitis

phenomenon

other

pathological

of the nervous

the high incidence 3. An immunological

RNA and DNA viruses with human

poliomyelitis

cord tumors

body

picfor

30 years

30 years after

The syndrome of progressive motor neuron Many authors (7-12) have found a is well recognized.

with paralytic

explanation

predisposition

explaining

our patients

having of the

be responsible.

poliomyelitis

of patients

myelitis (14,lS). 4. A hypersensitivity Shield (16) in children with bronchial

system

etiology

findings,

to disease,

of the appearance supported

who developed

although

there

causing

of both

late motor

are several

suggesting

neuron

disease.

possibilities:

1. A

an acute viral ilness (13). 2.

vulnerability

acute

of the anterior

and chronic

by the association

progressive

horn

anterior

of HL-A 3 and 7 with polio-

to drugs with no isolated pathogen as described by Hopkins and asthma whose development of poliomyelitis followed an acute attack “after old poliomyelitis” was described by Anderson et deterioration

of asthma. Another late neurological al (17). This was characterized by frequent falling, recurrent joint additional training. Most of their patients were females in contrast

pain and further instability requiring to the predominantly male patients

described by Campbell (9). Late onset of respiratory and circulatory insufficienty tis characterized by mental and physical fatigue, peripheral edema, and cyanosis, Hamilton

neoplasia based upon

status of world polio incidence

or a late amyotrophic

poliomyelitis.

As both

virus might

of the polio virus without

A hereditary

after

connecting atrophy

a virus can be dormant

suggest.

years

number

muscular

30 years

perhaps

significant

cell thus

patients

aproximately

highly

reactivation

The present

There is other evidence

that

The question

poliomyelitis

horn

female

are advanced.

approaches

were referred to us, one having neurogenic (Schwann cell) sarcoma, and the other (1). This aroused our suspicion concerning the relationship between the appearance

and old viral disease.

(2-6). ture

two

viruses and late developing

and several experimental

relationship.

POLIOMYELITIS During

of poliomyelitis

is surveyed,

after old poliomyelihas been described by

et al (18).

VIRAL

INFECTION

AND PEDIATRIC

TUMORS

There is growing interest in association between events in utero and subsequent health of the child. Stewart et al (19). suggested the possibility of malignant pediatric disease following maternal viral infection. Adelstein and Donovan (20) analyzed mortality occurring in a cohort of children born to mothers who contacted viral infection during pregnancy. Two deaths from leukemia occured among the children whose mothers had chickenpox. maternal

and childhood Heinonen

Other

viral infection. neoplasia

children

in this group

Leek and Steward was from

et al (22) concluded

died from leukemia,

(21) concluded

an immunological

that there

deficiency

is no evidence

44

Ewing’s

tumor,

that an association which

of an excess

and Still’s disease after

between

may predispose of malignancies

maternal

influenza

to both conditions. in children

exposed

in utero

to attenuated

live polio vaccine,

are only a few hints that maternal syndrome

is associated

with progressive

The clinical

value of recognizing

importance

in a patient

This must

be investigated

of prognostic

and

ritation mor

panencephalitis

progressive

more

therapeutic

of the lesion

following

changes.

Cantu

If we assume

leakage.

and Wright

has considerable of poliomyelitis.

following

of a tumor

POSSIBLE

MECHANISM

may be infection

viral infection equina

characteristic

to keratin

OF VIRAL

appear

that a chronic

a case of cauda release,

caused

epidermoid

of aseptic

tu-

meningitis

but a viral etiology

may

ACTION

can cause late malignancy, in general

early diagnosis

and viral or bacterial

development of congenital teratoma Both cases suffered from chronic ir-

episodes

meningitis

a history

whose

tumors

(27) reported

two preoperative the aseptic

The viruses

rubella

symptoms

cases associating

They related

that slow viral infection

in neurones.

Thus, there

The congenital

years after acute viral infection

(26) have reported delayed malignant associated with myelomeningocele.

in an 8 year old boy who experienced

virus cause

many

for the possibility

Reported

viral infection.

in children.

(23-24).

neurological

specifically value.

or to spontaneous

at the site of the spina bifida and it is conceivable

malignant

likely due to tumor explain this.

vaccine

may cause malignancies

such a connection

showing

are scarce. Love (25) and Thorp with spina bifida and carcinoma the

influenza

viral infection

we must discuss

to be obligatorily

the changes

that polio-

parasites

(28). They

intracellular

damage the nervous system by directly attacking the ganglion cells. In this acute form there are necrosis of the neurones, diffuse and focal microglial proliferation and finally inclusion bodies in the neurones. Sometimes matory tropic

mesodermal

reaction viruses

are some

changes,

to some

is for the grey

hints

that

such

viruses

as perivascular

involve

matter

the primary

both

cuffing

and meningeal

glial and mesodermal

of nervous

demyelinating

infiltration

elements.

resembling

‘The affinity

system:

they

diseases

may be due to a neurotropic

have thus been called

infla-

of the neuro-

“poliocalstic”.

There

virus. Pietsch

and

Morris (14) found a relationship HL-A and an immune response

between HL-A3 and 7 poliomyelitis representing an association between gene determining an immune response to the virus or a product of viral

infection of the central haps similar etiology.

nervous

system.

The polio virus attacks

the anterior

hemorrhages

into the grey matter.

lysis to complete smaller

number

Recovery

from

rely damaged. the affected

destruction

horn Changes

the acute

regions

cell causing in ganglion

with neurophagia

of polymorphnuclar

Severely

Such an association

by restoration

cells disappear

with secondary

degeneration

response

(3 1). It was suggested

with a potent response an immune

replicating

in serum. reaction.

There

viral antigen is therefore

3. late motor

to experimental

gives a specific evidence

neuron

is mainly

has been noted

poliovirus

reaction

with per-

with small

by lymphocytes

have not been too seve-

of cells in the anterior

ventral

with a

(29-30).

cells, which

and a paucity

in the corresponding

sclerosis

horns range from slight chromo-

cuffing

of ganglion

completely

of Rhesus

was studied

attack

in multiple

and an inflamatory

cells of the anterior

(28). Perivascular

is seen (28). The local antibody monkeys

degeneration

cells and white matter

stage is attended

damaged

has been found

roots,

and peripheral

horns of nerves

infection

in the central

nervous

system

that local stimulation

of the central

nervous

system

local antibody

of polio

response

virus causing

which is independent

: 1. destruction

of nerve

of the cells. 2.

disease.

RESEARCH

METHODOLOGY

The problem of Koch’s postulates and slow viral infection by Johnson and Gibbs (32). They stressed that reports

45

of the nervous system was interestingly discussed of viral infection associated with chronic neuro-

logical

diseases

raised

This necessitated by Koch. sease.

the

question

modification

The development

Therefore

be isolated

of tumor

in relating

virus can not be isolated

Koch’s

in pure culture

be attacked

niques

and spinal cord tumors 1949-1955

paralytic

registration

tumor

tumor

patients.

the agent.

epidemic

and a fortuitous

affected female

exsists

in Israel,

principle

problems

stage.

can be either

about

6000 patients. is localization

have since changed

making

feasible

resources

by the scienfitic

Neoplasia

has been published

finally,

for epidemiological

with

apparent

cal syndromes ther even those Wyatt against ves that

However,

were

never

between curiously

in

success three

satisfactorily

of

solved:

to a technical

solution

without

have a high incidence

suggested

among

U.S.A.

that

virulent

He suggested

and was partly

countries. He observed demics of poliomyelitis

of poliovirus

responsible

potential

before

became

pressure

for the pronounced

changes

with several cliniis whe-

tumors.

and adults

the attack

rate of

in 1972 was 24% . The gap in immunity

susceptibles

against became

susceptibility

because

occured

(34) stated out in all pa-

What must be proven

system

adolescents

their genetic

dominant

An editorial be carried

can persist

paralysis.

nervous

and U.K. was examined

most

that this selection

without

in the U.S.A.

in the U.S.A.

should

as poliomyelitis

nonimmune

schools

countries,

to late neoplasia.

viral studies

of central

that among

virus or by infection

strains

system

or encephalitis

Science

children

and other

reasons,

of the nervous

meningitis

in Christian

ASSOCIATION

in relation

aseptic

poliomyelitis

(36).

poliomyelitis

carriers

evidence

tion

a very compre-

of poliomyelitis

of virus along nerves. 3. Relation of constituof poliomyelitis was solved in a way which

AND LATE TUMOR

paralytic

by an avirulent

tires

However

(3 3) shows a relationship

may also prove susceptible

including

poliomyelitis in the

about

virus infections

infection Metselaar

all those diagnosed

of a history

committee

who suffer In Israel, the

There was no centralized

their surname.

for the research.

research

as well as diagnostic

(35) in his hypothesis

paralytic

includes

tech-

poliomyelitis

development.

patients.

an investigation

on poliomyelitis

between

of those patients

This number of these

the problem

resolution.

No literature tients

a

cannot

or immunologic

a correlation

of late tumor

patients

POLIOMYELITIS

that

to di-

disease,

parasites

tumors

serologic,

Investigation

in research

problems.

of neurogenic

for evidence

and financial

listed

those fundamental

a scientific

as required agents

neurological

and non-pathogenic

histologic,

1. Pathology of the poliomyelitis in human 2. Transmission tion to susceptivility. The technical problem of prevention bypassed

for the disease.

in relating

and chronic

patients

The problem

of the poliomyelitis

fundamental

a virus etiology problems

to slow viral infection

The first stage of investigating

and many

- contractor

of investigation

even greater

the polio virus) is the etiology

is an epidemiological

registry

The customer

has caused

for the electromicroscopic

poliomyelitis.

of names

hensive

the

(including

or of all poliomyelitic

poliomyelitic

as having

virology

postulates

epidemiologically

poliomyelitis

exist for establishing

since no virus can be grown in pure culture

(32).

may fail to identify

from

criteria

postulates

in every case of the disease,

Thus if a slow viral infection must

of what

of Koch’s

of selection

earlier

this mode.

either

became

manifest.

pressure

in economically

in the epidemiology

Wyatt belie-

immune

through Other

was shown developed

of polio

by

coun-

seen in such

in Kenya a remarkable periodicity in the circulation of type 1 poliovirus: a epiwas caused by this type. Types 2 and 3 showed less priodicity and this observa-

led to his hypothesis.

Paul (cited

by Metselaar)

suggested

that

improved

hygiene

was largely

sible for the increased number of poliomyelitis epidemics, although there are reports from loped countries (37-39), somewhat similar to those from more developed countries (40-41). We have tried to compare the above epidemiological data of poliomyelitis nervous system tumors. In Israel, there is a high frequency of these tumors

46

respon-

the less deve-

to the parallel data of central (42). The frequency of nervous

system

tumors

has been

reported

to differ

in ethnic

and racial groups.

Blacks have been reported

to have

a lower frequency of brain tumors than whites, especially with respect to meningiomas. In South Africa, the frequency was highest among whites, intermediate in colored people and lowest in Asians. in Israel the European population includes a higher proportion Israel-born groups. Thus the difference in the incidence

of older individuals than the Afro-Asian and the among ethnic groups may have an age dependent

factor.

But it is fascinating

population

central among

nervous tumors and multiple sclerosis (43). The next question these diseases. Barker et al (44), found geographical clustering

mas and meningiomas. is comparable

The annual

with the findings

(47). The medical sease

a tame

of a virus and cellular Our hope

is that

and that research

incidence

found

has a high incidence

in the polio virus is prominent: organism,

it converts

problem

this hypothesis

from

an excellent

and our interest will arouse

out either

Israel (45), North

to substantiate

within

nervous

for studying

(48). Weinstein

and the investigation

some interest

is a relationship acoustic neurosystem

tumors

America (46) and Newfoundland “the agent of a once dreaded di-

instrument

to that purpose”

of poliomyelitis,

is whether there of ependymomas,

by them for’ali forms of central

interest

laboratory

will be carried

the white

surveys

machinery

is still a persistent

that

of other

and scientific

has become

myelitis

to consider

the multiplication

(49) reminded

us that polio-

of the disease should

the medical

or to contradict

and scientific

not ccasc.

communities

this theory.

REFERENCES 1.

Ohry A, Rozin R. Late neoplasia

2.

Sabin

3.

Proc Nat Acad Sci USA. 70: 3225, 1973. Zhdanov VM, Mazurenko NP, Yakovleva LS, Trushinskaya

AB, Tarro

G. Herpes

after poliomyelitis.

simplex

and Herpes

Lancet Genitalis

2: 823, 1975. viruses in etiology

of some

GN, Gogichadze

human

GK. Isolation

cancers. of C-type

4.

RNA-viruses from stable cell cultures of human tumors. Neoplasma 20: 5 39, 1973. Nonoyoma M, Kawai Y, Huang CH, Hirshav Y, Levine PH, Pagan0 JS. Epstein Barr virus-DNA Hodgkin’s disease, American Lymphoma and other human tumors. Cancer Res. 34: 1228, 1974.

5.

Dmochowski

6. 7.

1973. Rafferty KA jr. Herpes viruses and cancer. Sci Amer. 229: 26, 1973. Zilkha KS. Discussion on motor neuron disease. Proc Roy Sot Med. 5.5 : 1128, 1962.

L, Bowen JM. The search for a virus in known

8.

Solmon LA, Riley HA. The relation between muscular atrophy and an antecedent attack

9.

Campbell

cancer.

chronic anterior of acute anterior

in

Proc Nat Cancer Conf. 7: 607,

poliomyelitis poliomyelitis.

or progressive spinal Bull Neurol lnst NY.

4: 35,1953. AMG,

Williams

logy (Minneap).

ER,

Pearce

J. Late

neuron

degeneration

following

poliomyelitis.

Neuro-

19: 1101, 1969.

10. Poskanzer DC, Cantor HM, Kaplan N. The frequency of preceding poliomyelitis in amyotrophic lateral sclerosis in Motor neuron diseases. p. 286 in Research on Amyotrophic Lateral Sclerosis and Related Disorders. Edited

by FH Morris Jr. & LT Kurland.

New York, Grune & Stratton,

11. Mulder DW, Rosenbaum RA, Layton DA Jr. Late progression ral sclerosis? Mayo Clin Proc. 47: 756, 1972. 12. Polosin YP. Results of some paraclinical adults. Sov Med. 34: 129, 1971. 13. Steegman AT. Poliomyelitis Arch NeuroI Psychiatry. 14. Pietsch MC, Morris 4: 50,1974. 15. Morris PI, Pietsch 2: 847,1973. 16. Hopkins IJ, Shield 760, 1974.

(poliomyelopathia) 38: 537, 1937.

PJ. An association MC. A possible LK.

investigation

in progressive

chronica,

report

between

illness

47

poliomyelitis

associated

with

or amyotrophic

bulbospinal

of a case

of HL-A3 and 7 with paralytic

association

Poliomyelitis-like

of poliomyelitis

with

poliomyelitis, and multiple

asthma

1969. late-

amyotrophias histologic

of

study.

Tissue Antigens. sclerosis.

in childhood.

Lancet.

Lancet.

1:

17. Anderson

AD, Levine SA, Gellert

litis. Lancet 18. Hamilton

H. Loss of ambulatory

ability

in patients

with old anterior

poliomye-

. 2: 1061, 1972.

EA, Nichols

PJR, Tait BW. Late onset

of respiratory

insufficiency

after

poliomyelitis.

Ann

Phys Med. 10: 223, 1969. 19. Stewart

A, Webb J, Hewitt

D. A survey of childhood

malignancies.

20. Adelstein AM, Donovan JW. Malignant diseases in children or rubella in pregnancy. Brit Med J. 4: 629, 1972. I, Steward JK. Incidence 4: 631, 1972.

of neoplasms

in children

Brit Med J. 1: 1495, 1958.

whose

mothers

born after

had chickenpox,

21.

Leek

22.

Heinonen OP, Shapiro S, Monson RR, Hartz SC, Rosenber L, Slone D. Immunization during pregnancy against poliomyelitis and influenza in relation to childhood malignancy. Int J Epidem.

2: 229, 1973. 23. Townsend JJ, Bariger JR, Wolinsky JS, Malamud N, Mednick Oshiro IS, Cremer NF. Progressive rubella panencephalitis

influence

epidemics.

mumps

Brit Med J.

N, Mednick JP, Panitch HS, Scott RA, - late onset after congenital rubella,

New Eng. J Med. 292: 990,1975. 24. Weil ML, Itabashi cephalitis 25.

HH, Cremer

994,197s. GJ. Delayed

Love

NE, Oshiro

LS. Laennette

due to rubella virus simulating malignant

subacute

development

EH, Cavanay

sclerosing

of a congenital

L. Chronic

panencephalitis.

teratoma

with

progressive

panen-

New Engl J Med 292:

spina

bifida

J Neurosurg.

29: 532, 1968. 26. Thorp

RH. Carcinoma

27.

RC, Wright RL. Aseptic

Cantu

associated

with myelomeningocele. meningitis

syndrome

27 : 446, 1967.

J Neurosurg. with cauda

equina

epidermoid

tumor.

J Pediatr.

73: 114, 1968. 28. Brain R. Virus infections University 29.

Foley

of the nervous

system.

In Diseases of the Nervous

System,

London,

Oxford

Arch

Neurol.

Press, 1969.

KM, Beresford

HR.

Acute

poliomyelitis

beginning

as transverse

myelopathy.

30: 182, 1974. 30. Segev J, Ohry A, Rozin R, Rubinstein 31. Ogra PL, Ogra SS, Alnakeeb fection 32. Johnson

in the central

RT, Gibbs

E. Sensory

S, Coppola

nervous

CJ. Koch’s

system

losses in polimyelitis.

Arch Neural

PR. Local antibody

response

of Rhesus

Infect

postulates

monkeys.

and slow infection

33: 664, 1976.

to experimental Immun.

poliovirus

in-

8: 931, 1973.

of the nervous

system.

Arch

Neurol.

30: 36,1974. 33. Wyatt HV. Is polio a model for consumer 34. Editorial 35. Wyatt

HV.

Hypothesis:

1974. 36. Metselaar D. Hypothesis:

The

immunity

possible

gical survey in Kenya.

39.

EN. Acute

5 1: 246, 1974. Lewis TH, Branon

paralytic

gap and

selection

Lancet, 1: 174, 1976. 37. Nottay BK, Metselaar D. Poliomyelitis 38. Ayim

research?Nature

241: 247, 1973.

Brit Med J. 1: 415, 1975. vaccination

of virulent

epidemiology

against

poliovirus

poliomyelitis. strains

and prophylaxis.

Lancet,

in third

world

1. A longitudinal

1: 784, countries.

epidemiolo-

Bull Wld Hlth Org. 48: 421, 1973. poliomyelitis

WL. Poliomyelitis

at Kenyatta in isolated

National American

Hospital. Indian

1969-1971.

population.

East Afr Med J.

JAMA,

230:

1295,

41.

1974. Renandet J, Seigneurin JM. Virus poliomyelitiques: enquete grenobloise au sujet de 64 isolements recents en milieu hospitalier. Ann Pdiat. 19: 815, 1972. in Japan during the period 1962-1968, after the Takatsu T, Tagaya I, Hirayama M. Poliomyelitis

42.

introduction of mass vaccination with Sabin vaccine. Bull Wld Hlth Org. 49 : 129, 1973. Leibowitz U, Yablonski M, Alter M. Epidemiology of tumors of the nervous system in Israel.

43.

Med Sci. 7: 1491,197l. Poskanzer DC, Schapira K, Miller

40.

H. Hypothesis:

48

Multiple

sclerosis

and

poliomyelitis.

Lancet,

Isr J 2:

917, 1963. 44.

Barker

JP, Weller

a regional

RO, Garfield

JS. Epidemiology

survey in Southern

England.

of primary

45.

Cohen A, Modan B. Some epidemiological aspects tion III Brain tumors, Cancer. 22: 1323, 1968.

46.

Schoenberg

BS, Christine

epidemiological 47.

Maroun

FB, Jacob

trends

BW. Neoplasms

of intracranial

diseases

and cranial

(Mineap)

of the brain and spinal

Psychiatr

of neoplastic

of the brain

and survival. Neurology

JC. The frequency

tumors

J Neurol Neurosurg

in Israeli-immigrant

meninges:

a study

48.

Spector Weinstein

DH, Baltimore L. Editorial:

D. The molecular Poliomyelitis,

biology

neoplasms

in Newfoundland.

of polio virus. Sci Amer.

a persistent

problem.

49

popula-

of incidence

20: 399, 1970. Canad J Pub1 Hlth.

64: 53, 1973. 49.

cord in

39: 290, 1976.

232: 25, 1975.

New Eng J Med. 288: 370, 1973.