Abstract
Article abstract A patient developed signs, symptoms, and radiologic findings compatible with acute subarachnoid hemorrhage after receiving a large dose of heparin and intravascular contrast medium for coronary angiography and stent placement. Subsequent CT indicated the subarachnoid enhancement was due to contrast. Neurotoxicity from contrast agents is well-known, however this is an unusual report of toxicity mimicking subarachnoid hemorrhage clinically and radiologically.
Neurologic complications of cardiac catheterization are well-known, including occasional signs or symptoms of subarachnoid hemorrhage (SAH).1 Neurotoxicity from intravascular contrast, in particular the ionic high-osmolar agents, has been reported.2,3 Retention of contrast in the basal ganglia, diffusely in the cortical and subcortical brain, and in the subarachnoid space resembling an SAH on CT have been reported,2-4 but without clinical findings of SAH. We report a patient who developed signs and symptoms consistent with SAH after administration of heparin and contrast for coronary arteriography. CT findings were also consistent with SAH. These signs and symptoms improved coincident with renal clearance of the contrast media. Rapid clearance of the hyperdensity on follow-up CT suggested contrast primarily in the subarachnoid space rather than blood. Blood pressure and ventilatory support in the interim resulted in complete recovery from neurologic and non-neurologic symptoms.
Case report.
A 73-year-old woman with a history of coronary artery disease, peptic ulcer disease, hypertension, hypercholesterolemia, status-post coronary angioplasty ×2, and right carotid endarterectomy was admitted for cardiac catheterization for evaluation of recurrent substernal chest pain. There was no history of seizures or neurologic disease. Admission physical examination was significant for bilateral carotid bruits. Blood pressure (BP) on admission was 145/70. She was heparinized and received 350 mL iohexol (a nonionic agent) during the catheterization, and subsequently 800 mL diatrizoate meglumine and diatrizoate sodium (an ionic agent) during stent placement the following day. Twitching of the left arm was noted at the end of the stent procedure and was followed 10 minutes later by a generalized tonic–clonic seizure with secondary respiratory arrest. Seizures were controlled with 20 mg/kg phenytoin and the patient was placed on ventilatory support. Postarrest she was unresponsive except to deep pain, with disconjugate gaze, no spontaneous movements, symmetrically increased reflexes, and extensor plantar responses. BP was labile, with systolic BPs varying from 160 mm Hg to a low of 80 mm Hg. Laboratory studies showed white blood cell count, 14.8; hematocrit, 29; Na, 138 meq/L; K, 4.4 meq/L; Cl, 106 meq/L; HCO3, 19 meq/L; blood urea nitrogen, 18 mg/dL; creatinine, 1.3 mg/dL; and glucose, 229 mg/dL. Noncontrast CT showed CSF and cortical hyperdensity greater on the right, interpreted as SAH, greater on the right (figure 1). MRI was not performed due to the recent stent placement. EKG showed signs of an inferior infarction with Q waves in leads II, III and AVF, and T-wave inversion. Nimodipine therapy was considered in view of possible SAH-induced vasospasm, but not instituted due to her labile BPs.
Figure. (A) Axial CT image through the frontoparietal region obtained immediately after cardiac catheterization shows high attenuation signal within the subarachnoid space outlining the sulci and falx cerebri. (B) Image obtained 1 day after presentation and at the same level as (A) shows marked decrease (>50%) of the high attenuation signal in the subarachnoid space. (C) One week after presentation the subarachnoid contrast has cleared completely.
On the following day she became responsive and was extubated. She was noted to have slurred speech, difficulty in word finding, gait and balance instability, and a bilateral postural tremor. Repeat CT showed increased density interpreted as SAH, although decreased from the previous day (figure 2). Speech and language slowly improved over the following 3 days, as did balance and coordination. By the third day her BP had stabilized as well. An EEG demonstrated diffuse slowing with no epileptiform abnormalities. EKG and cardiac enzymes did not confirm the suspected infarction, and a repeat EKG demonstrated resolution of the previous abnormalities.
Because the second (figure 2) and third (figure 3) CT scans showed rapid resolution of the CSF signal, the markedly high attenuation within the subarachnoid space was reevaluated and appeared consistent with contrast. This was confirmed by measuring 80 to 160 Hounsfield units in the first CT. (Blood typically has a maximal range of 40 to 60 Hounsfield units and only about 50% clearance from the subarachnoid space in 1 day.5) The patient had no additional seizures and continued to improve, although she did not remember the first 24 hours of this event.
Discussion.
Our patient demonstrated many of the multisystem signs and symptoms associated with SAH. The seizures, lethargy, mental status changes, pulse and BP instability, increased white blood cell count, and EKG findings, although not classic, were compatible with that diagnosis. Sudden loss of consciousness may occur in as many as 45% of patients, often without preceding headache, nausea, vomiting, or dizziness. Seizures (focal or generalized tonic–clonic) are reported in up to 26% of patients, the majority occurring shortly after bleeding.6 Cardiac findings simulating ischemic heart disease with EKG findings of ectopic beats, bundle branch block, arrhythmias, prolonged QT, and ST segment and T-wave changes have frequently been reported.7
Radiographic findings in our patient demonstrated enhancement in the subarachnoid space consistent with SAH, but dissimilar to the pattern of contrast uptake in the basal ganglia, thalamus, and subarachnoid space as reported by May et al.3 Brain uptake was originally reported associated with intrathecal injection of contrast and subsequently with vascular injection.1-4 Abnormal uptake has been reported as causing cardiovascular and CNS complications (including seizures in patients receiving large amounts of contrast, with underlying seizure disorders, or in renal failure),1-4 but not findings typical for SAH.
Postulates for the mechanism of contrast neurotoxicity include 1) a dramatic shift in fluid due to the hyperosmolality of the contrast agent with efflux of water, shrinkage of cells, and opening of tight junctions; and 2) increased permeability of the blood–brain barrier with facilitation of contrast into the brain and subarachnoid space secondary to the high osmolar load and chemical structure of the contrast agent. Direct stimulation and excitation of neuronal cells from contrast has been reported in animal studies, with the spontaneous appearance of slow waves and electrographic seizures in EEG recordings. The epileptogenic activity of contrast agents may be mediated by depression of inhibitory synaptic events, similar to several classic epileptogenic agents such as picrotoxin.8-10 Our patient demonstrated no radiologic evidence of marked edema or fluid shift denoting a significant osmotic effect. This suggests a direct irritant effect as the primary mechanism, although as has been suggested in other reports,3,4 a combination of mechanisms is the most likely.
- Received October 21, 1998.
- Accepted in final form January 16, 1999.
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