Many of the findings described in the landmark
Acheson 1959 paper are very much relevant to our
understanding of ME today. The disease was
initially thought to resemble poliomyelitis
until distinguishing features occurred; no
patient developed the paralysis and muscle
wasting seen in poliomyelitis which is a disease
of the spinal cord.
Naldrett White, a Canadian neurologist, and
Robert Burtch, an American family physician,
described an epidemic in 1950 in Upper New York
State in the USA in an area close to the
Canadian border. They thought that muscles were
directly involved during the initial infection.
Accompanying a mildly elevated temperature to
99–100 ºF (37.2–37.8 ºC) in nearly every
patient, there was pain and tenderness in
various muscles sometimes with increased skin
sensitivity over the affected areas making
contact with clothes or bedding very unpleasant.
In contrast to hypersensitivity, difficulty in
moving limbs and numbness with diminished skin
sensation on clinical testing suggested
peripheral nerve involvement. Where there was
weakness on using a hand and sensory symptoms,
examination revealed an ulnar nerve disorder.
Nerve roots were sometimes involved in the legs
and were tender to pressure. This was associated
with dragging of the legs on walking or foot
drop. Another feature was
lymphadenopathy in
some patients. Enlarged tender anterior neck or
axillary lymph glands are mentioned.
Examination of the blood and cerebrospinal fluid
showed only minor abnormalities in two patients.
White and Burtch thought that they might be
dealing with an infection affecting muscle. The
standard test for muscle damage at that time was
24 hour urinary
creatine excretion, and this was
found to be raised in the 13 patients who were
tested with a tendency for the urinary creatine
to fall to normal levels as the patients
recovered. The creatine phosphokinase enzyme
test for muscle damage was not available at that
time. Subsequently, it was found to be normal or
only slightly elevated in ME suggesting that the
disturbance is different from that found in
other muscle diseases.
The illness had a striking resemblance to the
disease described by Sigurdsson and others in
Iceland during the winter of 1948–1949, and
hence the name Iceland Disease was suggested for
the illness.
In a leading article published anonymously in
the Lancet in May 1956, Acheson reviewed eight
similar outbreaks and suggested a title Benign
Myalgic Encephalomyelitis for the new clinical
entity based on the presumed underlying
pathology. He considered the disease to be
"benign" compared with other epidemic infections
of the nervous system seen in various types of
encephalitis and in poliomyelitis due to the
absence of patients dying. However, "benign" was
later deleted from the title, leading to the
abbreviation to ME, because in some cases the
severity and duration of the disability
resulting from the disease was far from being
benign. He mentioned that hepatitis and
enlargement of the spleen might occur in
addition to lymph gland involvement indicating
the reticuloendothelial system participated in
the clinical picture in some of the epidemics.
Alexis Shelokov and colleagues investigated an
outbreak involving 50 student nurses and their
tutors participating in residential courses at a
psychiatric hospital near Washington DC, USA in
1953. Half the patients had muscle weakness and
poliomyelitis was suspected then eliminated. No
other cause for the muscle weakness was found.
All patients had features of a generalised
illness similar to that described in patients
with Iceland Disease. After the initial illness
there was a subacute phase lasting several
months consisting of episodes of feeling unwell
and further muscle weakness.
Donald Henderson and Alexis Shelokov reviewed 23
similar epidemics in 1959. They found that the
affected muscles were tender either diffusely or
in focal discrete areas, which felt "oedematous,
doughy or rubbery in consistence". They
introduced the term Epidemic Neuromyasthenia,
linking neurasthenia with myasthenia to describe
the clinical picture. The term neurasthenia is
unfortunate as it implies a disturbance of
behaviour, which can follow an infection or be
the result of stress, in the form of
irritability and an inability to take exercise
without excessive fatigue. Similar disturbances
including crying spells without provocation are
also seen during the convalescence of patients
who have had strokes or head injuries. The
association of similar behavioural disturbances
with brain cell disorders such as cranial nerve
palsies and hemiparesis with extensor plantar
response is mentioned by Henderson and Shelokov
(1959) as an occasional finding in some
epidemics. The association is clearly
illustrated by Melvin Ramsay in a serious of
sporadic cases admitted to an infectious
diseases department of a local hospital from the
population of North West London in 1955 and
1956. Rather than labelling the illness
neuromyasthenia a slight change to
neuronomyasthenia
indicating a disease of nerve cells (or
neurones) and muscle cells with muscle weakness
might be more appropriate. Neurologists prefer
to limit the term myasthenia to myasthenia
gravis, a disorder of the neuromuscular junction
which may present as a severe type of muscle
weakness. In patients with Myalgic
Encephalomyelitis/Neuronomyasthenia (ME/NM),
"myasthenia mitis" has been used to describe a
milder form of myasthenia in which muscle
weakness develops during normal daily
activities. Clinical tests were subsequently
developed, which measure the declining muscle
performance with activity and the slow recovery
of muscle afterwards. In 1998 this delayed
recovery of muscle function after a fatiguing
isometric exercise test was confirmed in 1999 by
Lorna Paul and colleagues.
ME Research UK has funded research which has
revealed abnormalities in the function of blood
vessels and blood cells. Abnormalities of blood
vessels have been described in these epidemics
of ME/NM. Infectious material was transferred
from patients to monkeys during an epidemic in
Adelaide, Australia in 1949–1950. The monkeys
became ill and post-mortem examinations were
carried out a month later. The only
abnormalities discovered by Pellew and Miles
(1955) were minute red spots along the course of
the sciatic nerves. Under the microscope the red
spots contained localised collections of
inflammatory cells, which had also infiltrated
the area where the nerve roots come out of the
spinal cord. The red colour of the spots was due
to leakage of red blood cells. ME/NM is very
rarely fatal so that a post-mortem study showing
similar haemorrhages in humans is unique.
However, during the North of England epidemic in
1955 Andrew Wallis described the findings in a
patient in her fifties, who developed the
characteristic febrile illness leaving her
debilitated and emotional. During the next
fifteen months she continued to run a low grade
fever with continued mental deterioration before
she died. The post-mortem revealed numerous
small haemorrhages around blood vessels in the
cerebral cortex extending into the mid-brain,
which were considered to be the cause of her
death. These abnormalities may be found when
patients die as the result of severe chronic
alcoholism. This was not a factor in her case;
she had had a febrile illness. Vasculitis
involving the skin was recorded during outbreaks
in Cumberland, Durham and North West London in
1955. A
maculopapular rash may appear during the
return of features of the initial illness such
as flu-like symptoms and enlargement of lymph
glands and liver. This skin overlying areas of
localised muscle weakness may be affected at the
time of these attacks.
In conclusion, Iceland Disease and ME/NM is a
muscle/brain disorder, which occurs as clusters
of cases in families, in institutions such as
hospitals or schools, in districts as far apart
as the northern townships in Iceland and
Adelaide in Australia or sporadically. It is an
infectious disease with an incubation period of
5 to 8 days. Acheson in 1959 used the expression
"in a greater or lesser degree" to describe "the
symptoms and signs of damage to the brain and
spinal cord" in this disease. This expression
can also be applied to the febrile illness and
muscle involvement. Many patients recover and
return to normal activities in weeks or months,
while others have relapses with reactivation of
features of the initial illness and further
damage to new areas of the brain or muscles. In
extreme cases deterioration may lead to death.
Muscle weakness has been measured in a few
patients. After activity the recovery of muscle
power is prolonged to an extent not recorded in
any other disease. The association between these
findings in muscle and vascular abnormalities in
blood vessels and blood components needs
exploring. For research purposes ME/NM patients
with these physical signs should not be coupled
with patients whose main illness is chronic
fatigue on exertion and who do not have these
signs.
