We hear
a great deal about the Scandinavian choice of water based
contrast agents over the oil based US technology.
Carl Eden,
who co-produced and narrates the "Arachnoiditis
- Fighting Back" DVD contacted the Swedish
National Board of Welfare and asked them about that decision.
Months went passed without a reply. Then, to our great surprise,
we received the document below which answered our questions
in full. Here is what they had to say:
Author:
Melker Lindqvist,
Associate Professor of Neuroradiology,
Department of Neuroradiology,
Karolinska Hospital,
S-171 76 Stockholm.
From a paper in the American Journal
of Neuroradiology (AJNR) in 1995 (ref.18) about the
Stockholm School of Neuroradiology by the two famous Swedish
Neuroradiologists, Professor Erik Lindgren and Professor
Torgny Greitz, the following paragraph is quoted:
"The
Stockholm School took a stand against the use of these (oil
based) contrast media at an early stage, and they were hardly
ever used in Sweden. Considering the number of post myelographic
arachnoiditis that are now reported, this may seem to have
been a wise
decision."
Instead
of oil based contrast agents gas (air or oxygen) was used
in Sweden for ventriculography and encephalography for investigation
of intracranial lesions. Gas myelography was used for investigation
of the spinal cord, and from the late 1940´s most
centres in Sweden used the ionic water soluble contrast
medium methiodal sodium (Abrodil, Kontrast U) for lumbar
myelography.
The same
techniques were used in most centres in the other Scandinavian
countries and to some extent in Germany and France. The
rest of the world used almost exclusively the oil based
contrast agent iophenylate (Pantopaque, Myodil) for both
intracranial and spinal examinations.
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What
were the reasons for these fundamental differences in neuroradiologic
technique ? Why did the Swedish radiologists avoid oil based
contrast media?
Or,
why were not gas myelography, pneumoencephalography and
lumbar myelography with water soluble contrast agent accepted
as alternatives to examinations with oil based media in
the rest of the world ?
The interesting
question seems to be:
Could
the large number of postmyelographic arachnoiditis, that
have been reported over the years, have been avoided ?
The general
view of the Stockholm School of Neuroradiology on these
issues are presented in a book chapter by Lindgren (ref.
13) and in the above mentioned paper by Lindgren and Greitz
(ref. 18).
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Questions
1 - 2:
1.
Why did Sweden never use oil based contrast agents ?
2.
If Sweden believed that there was a danger with oil based
contrast agents what research did it perform to verify this?
The
risk of arachnoiditis with oil based contrast media.
In the 1930´s and 1940´s the Department of Radiology
at the Serafimer Hospital in Stockholm was headed by the
famous Neuroradiologists, Erik Lysholm and Erik Lindgren,
working together with an equally famous Neurosurgeon, Professor
Herbert Olivecrona.
Patients
from all over the world were referred to Professor Olivecrona,
and many of these patients had been examined elsewhere with
oil based contrast media. During the radiological examinations
of these patients at the Serafimer Hospital the Neuroradiologists
noted remaining contrast medium in the subarachnoid space,
both in the head and in the spinal canal.
The oil
deposits were often fixed (did not move with change of the
patient's position), and they were also associated with
local thickening of the meninges. This was interpreted as
arachnoiditis caused by the contrast medium, and in a
few cases this arachnoiditis caused difficulties in the
removal of a tumor at surgery (ref. 13).
In 1928
Odin, Rundström and Lindblom published a supplement
of Acta Radiologica entitled:
"Iodized
oils as an aid to the diagnosis of lesions of the spinal
cord and a contribution to the knowledge of adhesive arachnoiditis"
(ref. 25).
These authors,
working in Sweden, used their own homemade oily media out
of soya and sesame oils in addition to Lipiodol. Their preparations
made out of sesame oil had less adverse effect than Lipiodol.
They observed clinical signs of acute meningeal reaction
similar to acute meningitis. However, they did not perform
a long term follow up of their patients.
Except
for this supplement (ref. 25) no scientific studies seem
to have been performed in Sweden to test the early or late
adverse effects of the oil based contrast media.
Some
papers on late and persisting sequelae from the use of Myodil
and Pantopaque started to appear in the international literature
in the 1940´s and 1950´s: Tarlov 1945 (ref.
29), Luce 1951 (ref. 19), Hurteau 1954 (ref. 7), Davies
1956 (ref. 4). A case of death following Pantopaque myelography
was reported by Erickson et coll. in 1953 (ref.6)
Top.
Thus the
decision already around 1935 by the leading Swedish Neuroradiologists
not to use oil based contrast media was mainly based on
clinical observations among their own patients rather than
on published or unpublished scientific examinations.
As an example
of this type of clinical observation the following case
was reported by Lindgren in a lecture in 1984. The manuscript
of this lecture was published in Swedish by Nycomed, Stockholm
in 1994 (ref. 17):
"It
may seem strange that oily based contrast media, especially
Pantopaque, were used to such a large extent (especially
in America), since these contrast media doubtless caused
arachnoiditis, although the clinical importance of these
changes were and are debated. We had a nurse with some vague
symptoms and performed a pneumoencephalography on her with
negative result.
She
was convinced that she had an intracranial lesion, so she
went to America, where she was examined with positive contrast
medium, also with negative result. She came back to Sweden,
and after two years she developed serious symptoms.
We
performed a new pneumoencephalogram. No air entered the
intracranial space in a normal way. An air ventriculography
was performed and showed a dilated ventricular system, including
the fourth ventricle. At surgery extensive adhesions were
found in the posterior fossa.
In
my opinion it is thus clear that positive contrast media,
at least in some cases, can cause clinically significant
arachnoiditis."
What
other reasons, except for the risk of arachnoiditis, contributed
to the Swedish decision ?
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The physical
properties of the oil based media were not ideal. They did
not mix with the cerebrospinal fluid (CSF), had high viscosity
and had a tendency to be split up in droplets. For these
reasons they did not fill out narrow spaces, for instance
the subarachnoid pockets surrounding the spinal roots and
the narrow parts of the intracranial subarachnoid cisterns,
and
thus did not allow visualisation of fine anatomical details.
The Swedish
Neuroradiologists were masters of air studies and claimed
that air encephalography and ventriculography in the hands
of skilled Neuroradiologists had proved capable of giving
equally good results as examinations performed with oil
based media (ref. 17).
Several
publications on Neuroradiologic investigations with gas
(air or oxygen) emanated from
"The Swedish School of Neuroradiology" at the
Serafimer Hospital.
Examples
of important papers are:
Lysholm
et coll. published "Das Ventrikulogramm" part
I -III 1931 - 1937 (ref. 20-22).
Lindgren
published "On the diagnosis of tumors of the spinal
canal by aid of gas myelography" in 1939 (ref. 15),
"A
pneumographic study of the temporal horn with special reference
to tumors in the temporal region" in1948 ( ref. 16)
and
"Some
aspects on the technique of encephalography" in 1949
(ref. 14).
The Neuroradiologists
at the Serafimer Hospital became famous for their clinical
and scientific achievements and attracted many colleges
from abroad who came to the Serafimer Hospital for training.
One of
them was James Bull from London, and he made the
following statement at the Symposium Neuroradiologicum in
Rotterdam in 1949:
"There
is no doubt that air or oxygen is the contrast material
of choice. The degree of success one obtains with air is
an index of ones ability as a neuro-radiologist. In my view
the more often one falls back on positive contrast material,
the less capable one proves oneself as a neuroradiologist."
(ref. 13).
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The organisation of Swedish radiology.
The first and main prerequisite for the international success
of Swedish radiology was the fact that independent departments
of radiology were created already when diagnostic radiology
was introduced in Sweden. The man who had the main responsibility
for this was Gösta Forssell, the first director of
the Roentgen* Institute at the Serafimer Hospital in 1908.
He managed
to convince the authorities that each hospital should have
only one x-ray department, and the heads of Roentgen departments
in Sweden should have the same position as other clinical
heads. (In most European countries, as well as in the US,
each clinical speciality
had its own small roentgen department, usually run by a
clinician.)
The Swedish
organisation meant that specially trained radiologists took
the full responsibility not only for the "interpretation"
of the images, but also for the choice of technique, including
the risk of complications involved. (ref. 18). For this
reasons Swedish radiologists were in charge of all parts
of the diagnostic procedures, for instance lumbar puncture
and the injection of air for the air studies and all parts
of the angiographic procedures.
(* MF Note:
Roentgen is the German Scientist who invented x-rays on
his own, despite scepticism from his own colleagues. Therefore
most early x-ray departments and the early medical imaging
periodicals were named after him. A full biography of this
man and details of his work will be appearing in our "History"
section in due course.)
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Technical
development.
The independent status of the Radiology Department at the
Serafimer Hospital gave the
Radiologists the opportunity not only to develop examination
technique, but also to work together with the local industry
in developing new technical equipment for radiology.
To give
just one example: Lysholm, in co-operation with the Elema
Schoenander company, in
1931 constructed the "Lysholm Skull Table" that
for many years was used for encephalography and angiography.
Question
3:
Has Sweden found any problems with water based contrast
agents ?
Gas myelography
was not a good technique for the diagnosis of lumbar disc
disease because the air did not give enough contrast. Oil
based media had the physical disadvantages mentioned above
and were thus not ideal. The Swedish radiologist Arnell
had been experimenting with the water soluble contrast medium
methiodal sodium (Abrodil, Kontrast U) and finally reached
the conclusion that Abrodil could be used for lumbar myelography
(ref.2).
However
it was so irritating that it had to be combined with spinal
anaesthesia, and even so the medium was so toxic that it
was not allowed to reach the spinal cord. Thus the examination
had to be restricted to the lumbar region, but in that region
it proved to give excellent visualisation of the lumbosacral
nerve roots and their sleeves.
Improved
technique for lumbar myelography with Abrodil was published
by Lindblom in 1946 (ref.11). For Swedish radiologists the
need for spinal anaesthesia, before the injection of the
contrast medium, was not regarded as a big problem since
they were in charge of the whole procedure. The contrast
medium was excreted via the kidneys, and no residual contrast
medium could be seen in the spinal canal after one day.
Top
In 1937
Lindblom published an investigation of complications of
myelography by Abrodil (ref. 12). The investigation was
based on 721 cases collected from several Swedish hospitals.
Several cases with complications were noted, for instance
drop in blood pressure with shock, lumbar pain, spasm in
the legs and even 3 cases with "secondary shock, and
paralysis of the legs and sphincters for weeks". However,
no complications with persistent neurological symptoms were
found among these 721 patients.
In spite
of the limitations Abrodil had such great advantages for
the diagnosis of lumbar disc disease that it soon became
the medium of choice for lumbar myelography. For many years
permanent complications to myelography with methiodal sodium
were unknown. In 1956 Munroe (ref. 24) and in 1959 Söderberg
et coll. (ref. 28) published a few cases with cauda equina
syndrome after myelography with methiodal sodium.
However,
their papers were not published in the radiological literature,
and for a long time their
observations remained unknown to the Radiologists.
In 1972
came the first publication (ref. 3) on adhesive arachnoiditis
after myelography with ionic water soluble contrast media,
and since then several papers have been published with reports
on adhesive arachnoiditis after water soluble contrast media
(ref. 1,5, 8, 9, 10, 26, 27 ).
Top
By that
time the new nonionic contrast medium Metrizamide was already
on its way, and methiodal sodium was withdrawn from the
market in 1974.
Since the
introduction of the water soluble nonionic contrast media
Metrizamide (Amipaque) and later Iohexol (Omnipaque) complications
of clinical importance are practically unknown.
Swedish Neuroradiologists were strongly opposed to oil based
contrast media because of their tendency to give arachnoiditis,
and still they were so late to discover the same type of
complications caused by Methiodal Sodium (Abrodil, Kontrast
U) which was used extensively in Sweden for many years.
The explanation
for this seems to be that the water soluble media, as opposed
to the oil based, disappear completely from the subarachnoid
space. If a patient was examined a second time there was
thus nothing in the pictures that indicated that the arachnoiditis
like changes that had
developed since the previous examination were caused by
the contrast medium.
The incidence
of postmyelographic arachnoiditis was also low with methiodal
sodium as compared both to oil based media and to later
introduced water soluble ionic contrast media like Conray
and Dimer-X.
Top
Question
4:
What is Sweden´s position on epidural steroid injections?
Are they considered safe?
Conclusions
from Professor Melker Lindqvist.
"The
question about the safety of epidural steriod injections
is difficult for me, as a Neuroradiologist, to answer. I
have consulted Björn Meyerson who is Professor of Neurosurgery
with treatment of chronic pain as his special interest.
He in turn has discussed the problem with Associate Professor
Staffan Arnér, head of the Pain Treatment Clinic
at the Karolinska Hospital.
They
agree that the beneficial effect of epidural steroid injections
in patients with arachnoiditis and similar chronic pain
syndromes can be questioned, and this type of treatment
is not much used in Sweden.
However,
except in the case of inadvertent injection into the subarachnoid
space, they do not think this treatment is harmful. In an
extensive report in 2000 on "Back and neck pain"
by the Swedish Council on Technology Assessment in Health
care (SBU Report 145) the conclusions seem to be the same."
With kind
regards:
Marianne Thorén
Principal Administrative Officer
The Division of Medical Quality Development
The Department of Health and Medical Services
The National Board of Health and Welfare
S-106 30 Stockholm
Top
SWEDEN
References
1. Ahlgren P: Long term side effects after myelography with
water soluble contrast media:
Conturex, Conray meglumin 282 and Dimer-x. Neuroradiology
(1973), 206
2. Arnell T et coll.: Myelography with skiodan (Abrodil).
Acta Radiologica 12 (1931), 287
3. Autio E et coll: Adhesive arachnoiditis after lumbar
myelography with meglumine iothalamate (Conray). Acta Radiological
Diagnosis 12 (1972), 17
4. Davies FL: Effect of unabsorbed radiographic contrast
media on the central nervous system.
Lancet 2 (1956), 747
5. Dullerud R et coll.: Adhesive arachnoiditis after lumbar
radiculography with Dimer-X and Depo-Medrol. Radiology 119
(1976), 153
6. Erickson TC et coll.: Late meningeal reaction to
ethyl idophenylundecylate (MF: chemical name of Pantopaque/Myodil)
used in myelography. Report of a case that terminated fatally.
JAMA 153 (1953), 636
7. Hurteau EF et coll.: Arachnoiditis following the use
of iodized oil. The Journal of Bone and Joint Surgery 36-A
(1954), 393
8. Irstam L et coll.: Water-soluble contrast media and adhesive
arachnoiditis. I. Reinvestigation of nonoperated cases.
Acta Radiologica Diagnosis 14 (1973), 497
9. Irstam L et coll.: Water-soluble contrast media and adhesive
arachnoiditis. II. Reinvestigation of operated cases. Acta
Radiologica Diagnosis 15 (1974), 1
10. Irstam L et coll.: Water-soluble contrast media and
adhesive arachnoiditis Acta Radiologica Diagnosis 15 (1974),
356
11. Lindblom K: Lumbar myelography with Abrodil. Acta Radiologica
27 (1946), 1
12. Lindblom K: Complications of myelography by Abrodil.
Acta Radiologica 28 (1947), 69
13. Lindgren E: A history of neuroradiology. In: Newton,
Potts, eds. Radiology of the skull and brain. Skull. Vol
1, Book 1. St Louis: C.V.Mosby, 1971:1-25
14. Lindgren E: Some aspects on the technique of encephalography.
Acta Radiologica 31 (1949), 161
15. Lindgren E: On the diagnosis of tumors of the spinal
cord by the aid of gas myelography.
Acta Chirurgica Scandinavica 82 (1939), 303
16. Lindgren E: A pneumographic study of the temporal horn
with special reference to tumors in the temporal region.
Acta Radiologica, suppl. 69 (1948)
17. Lindgren E: En tillbakablick på neuroradiologiens
tidigaste utveckling. (In Swedish)
Nycomed, Stockholm 1994
18. Lindgren E and Greitz T: The Stockholm school of neuroradiology.
AJNR 16 (1995), 351
19. Luce JC et coll.: Pantopaque meningitis due to hypersensitivity.
Radiology 57 (1951), 878
20. Lysholm E et coll.: Das Ventrikulogramm, part 1. Acta
Radiologica, suppl. 24 (1931) 1
21. Lysholm E et coll.: Das Ventrikulogramm, part 3. Acta
Radiologica, suppl. 25 (1935) 1
22. Lysholm E et coll.: Das Ventrikulogramm, part 2. Acta
Radiologica, suppl. 26 (1937) 1
23. Mason MS et coll.: Complications of Pantopaque myelography.
Case report and review.
Journal of Neurosurgery 19 (1962), 302
24. Munro D: Lumbar and sacral compression radiculitis (herniated
lumbar disc syndrome).
The New England Journal of Medicine 254 (1956), 243
25. Odin M et coll.: Iodized oils as an aid to the diagnosis
of lesions in the spinal cord and a contribution to the
knowledge of adhesive arachnoiditis. Acta Radiologica, suppl.
VII, 1928
26. Rådberg C et coll.: Late sequelae following lumbar
myelography with water-soluble contrast media. Acta Radiologica
Diagnosis 14 (1973), 507
27. Skalpe IO: Adhesive arachnoiditis following lumbar radiculography
with water-soluble contrast agents. A clinical report with
special reference to metrizamide. Radiology 121 (1976),
647
28. Söderberg L et coll.: Neurological complications
following myelography with water soluble contrast medium.
Acta Ortopaedica Scandinavica 28 (1959), 220
29. Tarlov IM: Pantopaque meningitis disclosed at operation.
JAMA 129 (1945), 1014
30. The Swedish Council on Technology Assessment in Health
Care. SBU Report 145, May 2000. Nachemson A ed: Back and
neck pain.
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