Journal of

J Neurol (1987) 234:177-179

Neurology
© Springer-Verlag 1987

Multiple subcortical haemorrhages
following lumbar metrizamide myelography
H. C. Overbeek and A. Keyser
Institute of Neurology, Catholic University, St. Radboud Ziekenhuis, 6500 HB Nijmegen, The Netherlands

Summary. The case is presented of a patient showing multiple
subcortical haemorrhages after lumbar metrizamide myelography. This complication after intrathecally administered
metrizamide contrast medium appears not to have been reported before. Several different possible explanations are proposed for the phenomena observed in this case.
Key words: Brain haemorrhage - Epilepsia partialis continua
- Metrizamide - Drug side-effects - Myelography

Introduction
Neurotoxicity of contrast agents used for intrathecal administration has repeatedly been reported [3, 4, 9, 12, 13, 16].
Imaging of the subarachnoidal space was earlier performed by
means of iophendylate, an intrathecally administered contrast
agent, with arachnoiditis being the only long-term complication.
The introduction of new water-soluble contrast agents,
such as metrizamide (Amipague) or iohexol (Omnipaque),
has led to better visualization of details. In a minority of cases,
however, a variety of side-effects have been reported [6-8].
We recently observed a patient in whom multiple small
subcortical haemorrhages of the telencephalic hemisphere
were diagnosed after an otherwise uncomplicated myelographic procedure, in which metrizamide was used as the
contrast medium. The case is reported to draw attention to
this rare complication of metrizamide myelography.

Case report
A 45-year-old man was admitted to a local hospital because of
progressive low-back pain. General physical examination was
unremarkable; blood pressure was normal. On neurological
examination signs of lumbar nerve root disorder were found.
No other disturbances of neurological functions could be
detected and the patient showed normal mentation.
However, a lumbar myelography, using metrizamide (16
ml, concentration 170mg/ml), demonstrated no nerve root
compression or other abnormalities. The cerebrospinal fluid
had a normal total protein content and white blood cell count.
Two days later the patient complaint of headache. No
fever or signs of meningism were present and the patient's
Offprint requests to: A. Keyser

level of consciousness was normal. The headache improved
after administration of dexamethasone but the patient continued complaining of not being well. This situation persisted
for several days. Eight days after the lumbar myelography the
patient became confused and sporadically showed involuntary
myoclonic movements of the left arm and hand. A C T scan of
the brain with intravenous contrast showed no abnormalities
at that time. The next day (day 9 after myelography) the patient developed a partial epileptic state with myoclonic involuntary movements of the left arm and hand. An E E G on
the same day showed typical spike and wave activity localized
in the right frontotemporal region (Fig. 1A). Examination of
the CSF was repeated and was normal.
The focal seizures did not respond to the intravenous administration of clonazepam or phenytoin. The patient was
transferred to the University Hospital because of this persistent partial epileptic state (epilepsia partialis continua, Kojewnikow).
After higher doses of clonazepam and phenytoin had been
administered as anticonvulsive treatment at the emergency
unit, the patient was admitted to the intensive care department, where prophylactic intubation was deemed necessary;
however, the patient maintained spontaneous respiration.
During the next few hours the focal seizures disappeared;
afterwards, however, complete left-sided hemiplegia was
noticed. A second CT scan of the brain showed multiple small
subcortical haemorrhages in the right parietal region and in
the right occipital lobe (Fig. 2). A second E E G showed diffuse
hypofunction over the right hemisphere, consisting of theta
and delta activity (Fig. 1B). During the next day the left-sided
hemiplegia disappeared, but the patient continued to experience paraesthesia of the left hand for several days more. A
third CT scan showed local atrophy in the area where the
haemorrhages had been observed.
The patient made an uneventful recovery and was discharged 46 days after myelography. On follow-up the patient
had mild subjective complaints compatible with an psychoorganic syndrome; otherwise neurological examination
showed nothing abnormal.

Discussion
The subcortical haemorrhages observed in this patient may be
a side-effect of metrizamide on the neural tissue. In the literature several side-effects of metrizamide have been reported

178

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Fig. 1. A EEG showing spike and wave activity in the right frontotemporal region 9 days after intrathecal administration of metrizamide. B After
cessation of focal seizures diffuse hypofunction is observed over the fight hemisphere

Fig. 2. Plain CT scan of the brain, showing multiple areas of hyperdensity over the right parietal region and the fight occipital lobe (10th day after
intrathecal administration of metrizamide)

[5, 9]. Complications reported after intrathecal administration
of metrizamide are headache, nausea and vomiting, transient
cortical blindness, brain oedema, prolonged confusion due to
absence status, seizures, dysarthria and psycho-organic syndrome. Some of these complaints and symptoms may be related to brain oedema and aseptic meningitis. Koppejan et al.
[10] observed the presence of an abnormally high density of
cortical grey matter on CT scan 14 h after myelography in a
patient who showed a transient organic psychosyndrome. This
observation was subsequently reported several times in the literature [18], which is evidence that the CSF-brain barrier may

be permeated by metrizamide. The appearance of metrizamiderelated side-effects seems dose-dependent [17]. A higher incidence of adverse effects has been reported following cervical
myelography than after lumbar investigations, due to the
higher concentration of the contrast medium used in the former
procedure. After lumbar intrathecal injection metrizamide
slowly diffuses cranially and a small concentration can be
demonstrated in the posterior fossa after 6h; after 24h the
contrast is seen all over the convexity of the hemispheres [7].
Metrizamide is reported to have a half-life in the CSF of
about 4 h after intrathecal administration and is thought to be

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reabsorbed from the CSF into the blood largely through the
arachnoid granulations. Diffusion of the drug in the cranial
direction may be delayed by keeping the patient in an upright
position [14].
Several possible explanations may be offered for the observed complication. Beck et al. [1] studied the effect of
metrizamide on regional brain glucose metabolism in the rat
after intracisternal administration. They found a general reduction of glucose metabolic rate in all regions measured and
postulated that metrizamide may have an indirect effect by inhibiting excitatory brain-stem neurons projecting to the cerebral cortex. Using a direct topical application of metrizamide
on the cerebral cortex, however, the same authors observed a
significant increase of glucose metabolic rate in the cerebral
cortex [2]. This increase of cerebral metabolism may be accompanied by a compensatory dilatation of the cerebral blood
vessels. The occurrence of local cortical dysfunction (cortical
blindness, aphasia), as reported in the literature, is suggestive
of a direct transpial influence of the contrast medium on cortical neurons.
The epileptogenic influence of metrizamide may be attributed to its acetylcholinesterase inhibitory activity, as demonstrated by Marder et al. [11]. Topical application of acetylcholinesterase inhibitor and of acetylcholine itself may cause
epileptiform activity and this may be an explanation for the
epileptic state observed in our patient [11].
The two factors, i.e. a direct vasodilatatory influence of
the cerebral blood vessels and the induction of epileptiform
activity in cortical neurons, may give rise to a considerable
strain on the local cortical metabolic state. It is difficult to decide whether these facts are sufficient to explain the haemorrhages observed on the CT scan or whether the additional osmotic injury of intravenous contrast administration before CT
scanning was contributory to this damage too.
In order to avoid toxic intracranial levels of metrizamide
after myelographic procedures, some measures might be
advisable. The patient should remain in a half sitting position
for at least 6 h after the intrathecal spinal administration of the
drug. The total amount of contrast medium introduced into
the intrathecal space should not exceed 12 ml (concentration
200 mg iodine/ml) [15].
Additional intravenously administered contrast medium
for CT scanning purposes after metrizamide myelography may
be potentially harmful and should be used judiciously.

2. Beck L, Diemer NH, Giedde A (1985) Metabolic effect of topical
application of metrizamide to rat brain cortex. Acta Neurol Scand
72 : 427--431
3. Bertoni JM, Schwartzman RJ, Horn G van, Partin J (1981) Asterixis and encephalopathy following metrizamide myelography;
investigations into possible mechanisms and review of the literature. Ann Neurol 9:366-370
4. Butler M, Cornell SH, Damasix AR (1985) Aphasia following
pluridirectional tomography with metrizamide. Arch Neurol 42:
39-45
5. Ekholm S, Fischer H (1985) Neurotoxicity of metrizamide. Arch
Neurol 42: 24-25
6. Gonsette RE (1973) Biological tolerance of the central nervous
system to metrizamide. Acta Radiol [Suppl] (Stockh) 335 : 25--44
7. Hindmarsch T (1975) Myelography with the nonionic water
soluble contrast medium metrizamide. Acta Radiol [Diagn]
(Stockh) 16: 209-222
8. Irstam L (1978) Lumbar myelography with Amipaque. Spine
3 : 70-82
9. Junk L, Marshall WH (1983) Neurotoxicity of radiological contrast agents. Ann Neurol 13 : 469-484
10. Koppejan EH, Begeer N, Bosch DA, Vencken LM (1981) Organic psychosyndrome correlated with high density of grey matter on
CT following metrizamide cervical myelography. Clin Neurol
Neurosurg 83 : 63-66
11. Marder E, Neil MO, Davis RI, Taveras JM (1983) Cholinergic
actions of metrizamide. AMJR 4: 61-65
12. Pritchard PB III, O'Neil DB (1984) Nonconvulsive status epilepticus following metrizamide myelography. Ann Neurol 16:252254
13. Ropper AH, Chiappa KH, Young RR (1979) The effect of
metrizamide on the electro-encephalogram; a prospective study in
61 patients. Ann Neurol 6: 222-226
14. Speck U, Schmidt R, Volhardt H (1978) The effect of position of
patient and the passage of metrizamide (Amipaque), meglumine
iocarmate (Dimer-X) and isoerimate (Myelografin) into the blood
after lumbar myelography. Neuroradiology 14: 251-256
15. Stoddart PGP, Watt I (1984) The symptomatic complications of
iopamidol (Niopam) and metrizamide (Amipaque) following lumbar radiography. Br J Radiol 57 : 349-350
16. Volmer M, Weiss H, Beamland L, Krumholz A (1985) Prolonged
confusion due to absence status following metrizamide myelograplay. Arch Neurol 42 : 1005-1008
17. Wilmink JT, Lindeboom SF, Vencken LM, Burg W van den
(1984) Relationship between contrast medium dose and adverse
effects in lumbar myelography. Diagn Imag Clin Med 53 : 208-214
18. Winkler SS, Sacket JF (1980) Explanation of metrizamide brain
penetration. A review. J Comput Assist Tomogr 4:191

References
1. Beck L, Diemer NH, Giedde A (1984) The effect of metrizamide
on regional brain glucose metabolism in the rat. Acta Neurol
Scand 69: 249-253

Received July 7, 1986 / Received in revised form August 18, 1986 /
Accepted August 21, 1986