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.
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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