Oddbj!2lrn Hauge1

Hans Falkenberg 1, 2

This article appears in the May/June 1982 issue of AJNR and the AU9ust 1982 issue of AJR,

Received March 23, 1981 ; accepted after re­vision November 27 , 1981.

'Department of Neuroradiology, Ulleval Hospi­tal, Oslo 1, Norway. Address reprint requests to O. Hauge.

2Present address: Department of Radiology, Telemark Sentralsykehus, 3700 Skien, Norway.

AJNR 3:229-232, May/ June 1982 0195- 6108/ 82 / 0303-0229 $00.00 © American Roentgen Ray Society

229

Neuropsychologic Reactions and Other Side Effects After Metrizamide Myelography

One hundred patients were questioned after metrizamide myelography about the side effects of the examination . The number and type of side effects were tabulated and correlated with investigated region (e.g., cervical , lumbar) and with use of medi­cation (e.g., analgesics, diuretics). The number of side effects, particularly neuropsy­chologic, were higher than previously reported. The most common side effects were minor meningeal irritations (headache, nausea, dizziness, and vomiting) and were regarded by the patients as inconsequential. All side effects became apparent during the first 24 hr after myelography and all were transitory. The side effects, being minor, should not limit the use of metrizamide for myelography. However, those caring for patients who have undergone the study should be aware of the possible side effects.

Metrizamide has considerably less toxicity than previously used myelographic water-soluble contrast media CDimer-X , Conray meglumine) [1 -6]. Serious side effects are few considering the large number of examinations performed , but the frequency of minor adverse reactions seems to be simi lar to those with other water-soluble contrast media (Oimer-X, Conray meg lumine) [7].

We have often noted neuropsychologic reactions after the use of metrizamide; however, there are relatively few reports of such reactions [8, 9]. This study was designed to record the reactions and other sid e effects after lumbar, thoraci c, and cervical myelography with metrizamide.

Subjects and Methods

The subjects were 100 patients admitted from August 10 Oc tober 1979 to the neurora­diological department , Ulievii.1 Hospital, Oslo, for metri zamide myelog raphy. All the myelo­grams on patients admitted to eith er the neurological department or neurosurg ica l depart­ment in this period were inc luded in the study. There were 59 men and 41 wo men aged 19-78 years ; most were aged 30-59 years.

Lumbar myelography was performed in 72 pati ents, tho rac ic mye lography in seven patients , and cervical myelography in 20 patients. In one patient with a tumor in th e th oracic spin e with a complete subarachnoid block , contrast med ium was injected into both th e lumbar and cervical subarachnoid space.

A 22 gauge needle was used for th e spinal puncture. For lumbar and thoracic investi­gations, the punctures were made at the L2-L3 or L3-L4 levels. Lateral C1-C2 punc tures were used for all cervical studies.

In 65 patients, 10 ml of metrizamide at a concentration of 170 mg Il ml was used for lumbar myelography. In six patients with a wide dura l sac, 15 ml of 170 mg Il ml was used, and in one patient 10 ml of 250 mg Il ml was accidenta lly used. Investigation of the conus medullaris was inc luded in all lumbar investigations. Lumbar myelog raphy also routinely inc luded lateral radiograph s in the sitting position with ex tension and fl ex ion of the lumbar spin e.

For thorac ic mye log raphy, 12-1 5 ml of metri zamide at a conce ntrat ion of 210 mg Il ml was used . The contrast medium was allowed to flow from th e lumbar to the thoracocervical junction. For ce rvica l myelog raph y, 6- 10 ml of metri zamide at a concentration of 300 mg

Il ml was routinely used .

230 HAUGE AND FALKENBERG AJNR:3, May / June 1982

After myelography th e patients were kept recumbent unti l the next morning with the head of the bed elevated 15° above the hor izontal. All patients were interv iewed by the authors before the stud ies were performed . As well as informing the patients about the investigation, we also informed them about possible general side effects. All patients were subsequently interviewed 24 and 48 hr after myelography.

Results

Of the 100 patients, 77 (35 women and 42 men) had side effects after metrizamide myelography . All the side effects began during the day of the examination. Patients without complaints on the first day had no furthe r reactions after 48 hr. Side effects are summarized in table 1.

Headache, Dizziness, Nausea, and Vomiting

Forty-three patients had headache on the day of exami­nation and 22 the next day. Twelve noted dizziness. Sev­enteen were nauseated and 11 vomited on the day of examination.

Muscular Pain

Thirty-one of the patients complai ned of muscu lar pain in various parts of the body. The pain was different from that of the presenting complaints. The lower back and legs were the usual locations, but neck pain was also frequently re­ported . We interpreted this pain as caused by spinoradicular irritation.

Auditory Symptoms

Two patients noticed a high-frequency tone, and one patient heard bell-ringing for several hours.

Visual Disturbances

The symptoms varied considerably. Hemianopia occurred in one woman and lasted for several hours . Previously in this patient , th is symptom had occurred only in assoc iation with headache. Three patients noticed cloudiness of vision , four saw spots and stripes, and one experienced changes in color vision . One patient had clifficulties in focusing . One hypermetropic patient was able to read his newspaper with­out glasses for some hours. (Usually without glasses he could only read the largest headlines.) Two patients expe­ri enced dimensional distorsion .

All symptoms were transient and lasted for some minutes up to 4-5 hr. None of the patients was examined by an ophthalmologist during or after the visual disturbances.

Dysphasia and Dysarthria

One patient (referred to later) had, in add ition to confu­sion, amnesia, and hallucinations, moderate dysphasia and dysarthria . Three other patients had mild dysarthria during the first 24 hr after myelography.

TABLE 1: Side Effects of Metrizamide Myelography

First Second Side Effect Day Day

Headache: Mild 17 16 Moderate . .... . . .. . 13 5 Severe 13 1

Dizziness . . . . . . . . . . . . . 12 4 Nausea:

Mild 14 3 Moderate ...... .. .. 2 0 Severe 0

Nausea and vomiting: Mild 7 2 Moderate . . . . . . . . . . . 3 0 Severe 0

Muscular pain: Cervical . . . . . . . . . . . . 11 3 Thoracic 1 0 Abdomen . .. . . . . .... 3 0 Lumbar 5 0 Legs . . . . . . . . 11 2

Auditory disturbances 3 0 Vision disturbances 11 2 Dysphasia . . . .. . . .. 1 0 Dysarthria 4 0 Confusion :

Mild 4 1 Severe .... . . ... 2 0

Memory disturbances: Mild . . . . . . . . . . . . 2 0 Severe .......... . . . 1 0

Hallucinations . . . . . . . . . . . . . . .. 6 0 Depression 6 0 Unease and anxiety:

Mild .. . ... . .. . 4 3 Moderate . ... . . . ... .. . 3 0 Severe .... . . . . .. 1 0

Sleep d isturbances 19 Nightmare . . ...... .. .. .. . . 7 Vegetative symptoms 0 Exanthema . . .. .. . .. . . ... . 1

Confusional States and Amnesia

There were two patients with pronounced neuropsycho­log ic symptoms. After thoracic myelography, a 60-year-old man experienced cons iderable confusion in addition to al­most complete memory loss for recent and more distant events . He experienced visual and aud itory hallucinations as we ll as dysarthria and dysphasia lasting 24 hr. He re­covered completely over the next 24 hr.

A 58-year-old woman became considerably confused after lumbar myelography. She refused all further examina­tion and treatment and insisted on being discharged . She also developed a generalized allerg ic rash . In a telephone conversation 2 days later she said she felt better and had difficulty in explaining her reactions . The rash persisted for 2 weeks . Four other patients had less severe and brief confusional episodes.

Halluc inations

Four patients had visual hall ucinations, another had au­ditory hallucinations only, and another had both visual and

AJNR:3, May / Ju ne 1982 SIDE EFFECTS AFTER METRIZAMIDE MYELOGRAPH Y 23 1

auditory hallucinations . The halluc inations lasted between a few minutes and 4 - 5 hr.

Depression, Unease, and Anxiety

Twelve patients experienced changes in mood the day of the examination . Seven patients had a vague feeling of unease and anxiety, and two of them also fe lt depressed and cried more easily than usual. One patient had an anxiety reaction . Six felt depressed and were unusually worred about their illness and what it would mean for them in the future.

Sleep Disturbances and Nightmares

Twenty-si x patients complained of a rest less night after metrizamide myelography. This varied from frequent awak­en ings to unpleasant nightmares. Several of the patients described being half-asleep with intermittent dreaming .

Side Effects Related to Region of Investigation

Table 2 shows the frequency and type of side effects according to the type of examination. Of the 20 patients undergoing cervical myelography, 13 had side effects : nine meningeal, four spinorad icular, and five cerebral. All seven patients who had thoracic studies had side effects: si x meningeal and four cerebral. Of the 72 patients having lumbar myelography, 57 had side effects: 42 meningeal, 22 spinoradicular, and 33 cerebral.

Side Effects Related to Drug Usage

Routinely we permit the patients to take their usual drugs during myelography. The relationship of the side effec ts to drug usage is shown in table 3 . Of all 100 patients, 63 used various medications, including analgesics and neuroleptic drugs, during myelography and 37 did not. Of the 77 pa­tients with side effects , 46 were on medication; of the 23 patients without side effects, 17 used drugs.

Of the patients with side effects, 34% used neuroleptic drugs; whereas 38% of the patients without side effects were on neuroleptic medication . With few exceptions, the neuroleptic used was levomepromazine in doses of 20 mg / day.

Discussion

Most of the complications after myelography using water­soluble contrast media can be divided into three groups [1 0 , 11]: (1) meningeal irritation , such as headache, nausea, dizziness, and vomiting ; (2) spinoradicular symptoms , such as radicu lar pain , hyperesthesia, hyper-reflexia, and urinary retention ; and (3) cerebral and spinocerebral symptoms, such as convulsions, hyperrefl ex ia, visual and auditory dis­turbances, and confusion.

The meningeal reactions (headache, nausea, vomiting, and dizziness) are mainly caused by the lumbar puncture. The frequency of these reactions are related to the size of

TABLE 2: Incidence and Type of Side Effects According to Investigated Region

Type of Side Effects No.

Investigated Region

Cervical ( n = 20) Thoracic ( n = 7) .. Cervical plus thoracic (n = 1) Lumbar (n = 72)

Menin-geat

9 6 0

42

Spino-radicular

4 0 0

22

TABLE 3: Side Effects and Medication Use

M edication

No medication Analgesics Neuro leptic drugs Diuretics

With Side

Effects (n ~ 77)

3 1 (40 ) 28 (36) 25 (32 )

(1)

With Cere- Side bra I Effec ts

5 13 4 7 0 0

33 57

W ithout Side

Effects (n ~ 23)

6 (26) 9 (39)

10 (43) 4 (17)

Nole. - Some patients were on more than one medication . Numbers in parentheses are percentages.

the needle, the number of punctures, and the length of ti me the needle is left in the subarachnoid space [1 2, 13]. Leak­age of cerebrospinal flu id is the most probable cause of these symptoms which are due to traction or pressure on the meninges. The number of patients in our investigati on who had symptoms of meningeal irritation corresponds to those of other stud ies [14 - 16]. The frequency of these symptoms after myelography is similar to those experienced after diagnostic lumbar puncture [12, 13]. The subarachnoid puncture, and to a lesser degree the neurotoxic effect of the contrast medium , might therefore be mainly responsible for these symptoms. The spinoradicular and cerebral symp­toms are not seen after an ordinary spinal puncture. These symptoms are therefore caused by the neurotoxic ity of the contrast materi al.

In our patients , side effects became apparent usuall y 4-6

hr after the examination, peaking during the first 24 hr and disappearing during the following 24 hr. Computed tomog­raphy after the intraspinal injecti on of metri zamide shows the contrast agent in the intracranial subarachnoid space with enhancement of the cortex [ 17]. Th is distribution of contrast material depends on several fac tors, such as the injection site, contrast concentrati on and amount, the pa­tient's positioning , hydrati on, and changes in the intraab­dominal pressure [17]. After the metrizamide is introduced into the intracranial subarachnoid space, the concentration of corti cal contrast material inc reases for the first 12 hr, then declines [8]. We attribute the adverse symptoms to the penetrati on of contrast material from the subarachnoid space into the cortical tissue. The varying time intervals before the symptoms appear corresponds to the time nec­essary for the contrast material to circulate through the intracranial subarachnoid space and to penetrate into the cortical substance. The wide variety of symptoms may be caused by different patient positioning as we ll as di ffering intracranial c irculations and local absorbt ion conditions.

232 HAUGE AND FALKENBERG AJNR:3, May / June 1982

The number of cerebral side effects in our patient group is high in comparison with previous publications from our department [14 , 18, 19]. The types of patients and exami­nation techniques have not changed since our previous studies describing the side effects of metrizamide. The reason for the high incidence of side effects might be our detailed questioning of the patients and that we filled out the questionnaire ourse lves, not delegating it to other hos­pital personel. During the interviews, the patients were first allowed to spontaneously discuss any possible reactions; when we went through a li st of side effects, we avoided direct leading questions. Many patients were reluctant to tell of their often marked bizarre perceptions that they knew were unreal. Occasionally they were prompted by neigh­bouring patients. It was often time-consuming to analyze observations that the patients thought were irrelevant. A certain amount of denial of these symptoms is therefore possible. Similar to most other investigators, we found a higher rate of side effects in women [14].

There was a higher incidence of side effects in the patients with lumbar myelograms as compared to those with cervical myelograms. In comparing the patients who had side effects after cervical myelography with those who had side effects after lumbar myelography, we found that the incidence of meningeal irritation (e.g., headache, dizziness) was lower after cervica l (9 / 20 , 45%) than lumbar myelograms (42 / 72 , 58%). Also the incidence of both spinoradicu lar and cerebral symptoms was lower after cervical (4 / 20,20% and 5 / 20, 25%) than after lumbar myelograms (22/72 , 30% and 33 / 72, 46%). All seven patients who had thoracic studies had side effects, but no definite conc lusions can be drawn from thi s small series. The examination technique with thorac ic myelography may cause more intracranial metrizamide dispersion than with other techniques.

Our present patient group is different from many others in that neuroleptics were not discontinued before the exam i­nation. Many of the patients rece ived phenothi azines in addition to analgesics to relieve radicular pain . This is in accordance with the conclusion reached by an investigation performed in our department in 1978 which showed no correlation between side effects and analgesic and neuro­lepti c drug usage [18]. Since then, no preex isting medica­tion is discontinued in our department. Our results confirm that there is no increase of side effects after metrizamide myelography in pati ents using moderate doses of phenothi­azines.

REFERENCES

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2. Buchele W, Kunitsch G, Brandt TH . Die lumbale Myelog raphie mit Meth ylg lucam iniocarmat (Dimer-X). Roentgenblaetter

1979;32: 39-45 3. Oftedal S, Kayed K. Epileptic effects of water soluble contrast

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[Suppl] (Stock h) 1973;335: 5-1 3 5. Salvesen S. Experimental invest igations with metrizamide with

relevance to the myelographic use. Acta Radiol [Suppl] (Stockh) 1977;355: 9 -1 6

6. Skalpe 10. Myelog raphy with metrizamide meg lumine iothala­mate and meglumine iocarmate. An experimental investig ation in cats. Acta Radiol [Suppl] (Stockh) 1973;335: 57 - 66

7. Skalpe 10. Adverse effects of water-soluble contrast med ia in myelography, c isternography and ventricu lography. A review with special reference to metrizamide. Acta Radial [Suppl] (Stockh) 1973;335 : 359-370

8. Drayer BP, Rosenbaum AE. Metrizamide brain penetrance. Acta Radiol [Suppl] (Stockh) 1977;355: 280- 293

9. Sortland 0 , Lundervold A, Nesbakken R. Mental confusion and epileptic following cervical myelography with metrizam ide. A report of a case. Acta Radial [Suppl] (Stockh) 1977;355: 403-406

10. Irstam L, Selden U. Adverse effects of lumbar myelography with Amipaque and Dimer-X. Acta Radial [Oiagn] (Stockh) 1976; 1 7: 1 45-1 59

11 . Oberson R, Azam F. La radiculo-myelog raphie a I·Amipaque. Med Hyg (Geneva) 1977;35 : 2485- 2490

12. Knuck le EC, Bronson SR, Wolff HG. Experim ental studies of headache. Arch Neura l Psychiatr 1943;32: 323-358

13. Tourtelotte WW, Henderson WG , Tucker RP , Gilland 0 , Walker JE, Kokman E. A randomized double-blind tria l comparing th e 22 versus 26 gauge need le in the production of the postiumbar puncture syndrome in normal individual s. Headache 1972;12:73-78

14. Skalpe 10, Amundsen P. Lumbar radiculography with metriza­mide. Radiology 1975;115: 91-95

15. Grainger RG , Kendall BE , Wyle IG . Lumbar myelography with metrizamide- a new non-ionic contrast medium. Br J Radiol 1976;49: 996-1003

16. Hindmarsh T. Lumbar myelography with meglumine iocarmate and metrizamide. Acta Radiol [Oiagn] (Stockh) 1976; 1 7 : 1 45-1 59

17. Sackett JF, Strother CM. Computer tomography and subarach­noid metrizamide for evaluation of cerebrospinal fluid flow . Acta Radiol [Suppl] 1977;3 55 : 338- 344

18. Lilleas F, Larsen T. Hvilken betydning har interaksjon mellom metrizamid og neuroleptica ved lumbal rad iculografi. Pre­sen ted at the meeting of the Nordic Neurorad iological Society , Lund , May 1979

19 . Dugstad G, Eldevik P. Lumbar myelog raphy. Acta Radiol [Suppl ] (Stockh) 1977;355: 280- 293

Editor's Note

Other articles on a similar theme are: 1. Gelmers HJ . Adverse side effects of metrizamide in myeolog­

raphy . Neuraradiology 1979; 18: 11 9-123 2. Chehrazi B, Virapongse C. Transient encephalopathy and as­

teri xis following metrizamide myelography. J Neurosurg 1981 ;55: 826-829