Delirious After Undergoing Workup for Stroke Veeraraghavan Iyer, MBBS, MD, and Douglas Opler, MD

Cases That Test Your Skills

Delirious after undergoing workup for stroke Veeraraghavan Iyer, MBBS, MD, and Douglas Opler, MD

Ms. L, age 91, experiences acute altered mental status after How would you undergoing routine evaluation of an episode of left-sided handle this case? Answer the challenge weakness. What could be causing her symptoms? questions at MDedge.com/ psychiatry and see how your colleagues responded

CASE Altered mental status after Which laboratory and/or imaging tests should stroke workup Ms. L undergo next? Ms. L, age 91, is admitted to the hospi- a) repeat BUN and creatinine levels tal for a neurologic evaluation of a recent b) urinalysis and comprehensive metabolic episode of left-sided weakness that profile occurred 1 week ago. This left-sided weak- c) repeat CT scan of the head ness resolved without intervention within d) diffusion-weighted MRI 2 hours while at home. This presentation e) blood culture for signs of infection is typical of a transient ischemic attack (TIA). She has a history of hypertension, bradycardia, and pacemaker implanta- The authors’ observations tion. On initial evaluation, her memory Due to her acute altered mental status is intact, and she is able to walk normally. (AMS), Ms. L underwent an emergent Her score on the St. Louis University Mental CT scan of the head to rule out any acute Status (SLUMS) exam is 25, which suggests intracranial hemorrhages or thromboem- normal cognitive functioning for her aca- bolic events. The results of this test were demic background. A CT scan of the head negative. Urinalysis, BUN, creatinine, basic reveals a subacute stroke of the right poste- chemistry, and complete blood count pan- rior limb of the internal capsule consistent els were unrevealing. On a repeat SLUMS with recent TIA. exam, Ms. L scored 9, indicating cognitive Ms. L is admitted for a routine stroke impairment. workup and prepares to undergo a CT Ms. L also underwent a comprehensive angiogram (CTA) with the use of the metabolic profile, which excluded any iodinated agent iopamidol (100 mL, 76%) electrolyte abnormalities, or any hepatic to evaluate patency of cerebral vessels. or renal causes of AMS. There was no sign Her baseline blood urea nitrogen (BUN) of dehydration, acidosis, hypoglycemia, and creatinine levels are within normal hypoxemia, hypotension, or bradycardia/ limits. Dr. Iyer is a PGY-4 resident, and Dr. Opler is Assistant Professor of A day after undergoing CTA, Ms. L starts Psychiatry, Rutgers New Jersey Medical School, Newark, New Jersey. mumbling to herself, has unpredictable Disclosures mood outbursts, and is not oriented to time, The authors report no financial relationships with any company whose products are mentioned in this article, or with manufacturers Current Psychiatry place, or person. of competing products. Vol. 18, No. 1 43 Cases That Test Your Skills

Figure 1 were unable to conduct Radiologic findings of subarachnoid contrast this test because Ms. L had 2 enhancement a pacemaker. Barber et al suggested that in the set- ting of acute stroke, the use of MRI may not have an added advantage over the CT scan of the head.

Which of the following is the most likely diagnosis for Ms. L? Clinical Point a) post-ictal phenomenon A B b) new-onset ischemic Delayed reactions changes to contrast agents c) contrast-induced involve a T-cell encephalopathy mediated response d) new-onset that most commonly hemorrhagic changes e) hyperperfusion results in pruritus and syndrome urticaria

C D TREATMENT Rapid improvement with supportive therapy Intravenous fluids are tachycardia. A urinalysis, chest X-ray, administered as supportive therapy to Ms. L complete blood count, and 2 blood cul- for suspected contrast-induced encephalopa- tures conducted 24 hours apart did not thy (CIE). The next day, Ms. L experiences a reveal any signs of infection. There were notable improvement in cognition, beyond no recent changes in her medications that attributed to IV hydration. By 3 days post- and she was not taking any sleep medi- contrast injection, her SLUMS score increases cations or other psychiatric medications to 15. By 72 hours after contrast administra- that might precipitate a withdrawal tion, Ms. L’s cognition returns to baseline. She syndrome. is monitored for 24 hours after returning to There have been multiple reports baseline cognitive functioning. After observ- of contrast-induced nephropathy (CIN), ing her to be in no physical or medical distress which may be evidenced by high and at baseline functioning, she is discharged BUN-to-creatinine ratios and could cause home under the care of her son with outpa- Discuss this article at AMS in geriatric patients. However, CIN tient follow-up and rehab services. www.facebook.com/ was ruled out as a potential cause in our MDedgePsychiatry patient because her BUN-to-creatinine was unremarkable. The authors’ observations Routine EEG was clinically inconclusive. For Ms. L, the differential diagnosis Diffusion-weighted MRI may have been included post-ictal phenomenon, new- helpful to identify ischemic strokes that a onset ischemic or hemorrhagic changes, Current Psychiatry 44 January 2019 CT scan of the head might miss,1 but we hyperperfusion syndrome, and CIE. Cases That Test Your Skills

Seizures were ruled out because EEG Figure 2 was inconclusive, and Ms. L did not have CT scan of the head showing the clinical features one would expect in prior chronic hypodensity an ictal episode. Transient ischemic attack is, by definition, an ischemic event with clinical return to baseline within 24 hours. Although a CT scan of the head may not be the most sensitive way to detect early isch- emic changes and small ischemic zones, the self-limiting course and complete resolution of Ms. L’s symptoms with return to baseline is indicative of a more benign pathology, such as CIE. New hemorrhagic conversions Clinical Point have a dramatic presentation on radiologic studies. Historically, CIE presentations on Patients may be at imaging have been closely associated with increased risk for the hyperattentuation seen in subarachnoid contrast reactions if hemorrhage (SAH). The absence of typical they have asthma, radiologic and clinical findings in our case arrhythmias, or ruled out SAH. hyperthyroidism Typical CT scan findings in CIE include abnormal cortical contrast enhancement such dyes. As a general rule, contrast agent and edema, subarachnoid contrast enhance- reactions can be categorized as immediate ment, and striatal contrast enhancement (<1 day) or delayed (1 to 7 days after contrast (Figure 1 [page 44], Figure 2, and Figure 3 administration). Immediate reactions are [page 46]). Since the first clinical description, immunoglobulin E (IgE)-mediated anaphy- reports of 39 CT-/MRI-confirmed cases of lactic reactions. Delayed reactions involve a CIE have been published in English lan- T-cell mediated response that ranges from guage medical literature, with documented pruritus and urticaria (approximately 70%) clinical follow-up3 and a median recovery to cardiac complications such as cardiovas- time of 2.5 days. In a case report by Ito et cular shock, arrhythmia, arrest, and Kounis al,4 there were no supportive radiographic syndrome. Other less prevalent complica- findings. Ours is the second documented tions include hypotension, bronchospasm, case that showed no radiologic signs of and CIN. Patients with the following factors CIE. With a paucity of other etiologic evi- may be at higher risk for contrast-induced dence, negative lab tests for other causes of reactions: delirium, and the rapid resolution of Ms. L’s • asthma AMS after providing IV fluids as support- • cardiac arrhythmias ive treatment, a temporal correlation can • central myasthenia gravis be deduced, which implicates iodine-based • >70 years of age contrast as the inciting factor. • pheochromocytoma • sickle cell anemia Iodine-based contrast agents have been • hyperthyroidism used since the 1920s. Today, >75 million pro- • dehydration cedures requiring iodine dyes are performed • hypotension. annually worldwide.5 This level of routine Although some older literature reported iodine contrast usage compels a mention of correlations between seafood and shellfish Current Psychiatry risk factors and complications from using allergies and iodine contrast reactions, Vol. 18, No. 1 45 Cases That Test Your Skills

Figure 3 CT scan of the head showing lack of contrast enhancement

A B

Clinical Point Encephalopathy has been documented after administration of iopromide, iohexol, ioxilan, and metrizamide more recent reports suggest there may not the endothelial cells to shrink and to sepa- be a direct correlation, or any correlation rate at tight junctions directly affecting at all.5,6 the blood-brain barrier. Alternatively, the Iodinated CIE is a rare complication of increase in intraluminal pressure caused contrast angiography. It was first reported by injection of the contrast agent, in con- in 1970 as transient cortical blindness after cert with contrast agent-induced cere- coronary angiography.7 Clinical mani- bral vasodilatation, might contribute to festations include encephalopathy evi- increasing vascular wall tension, further denced by AMS, affected orientation, and separating tight junctions. A third theory acute psychotic changes, including para- suggests that vesicular transport may be noia and hallucinations, seizures, cortical a mechanism of osmotic barrier open- blindness, and focal neurologic deficits. ing. Further studies would be required to Neuroimaging has been pivotal in con- investigate these mechanisms. firming the diagnosis and in excluding Regardless of the mechanism, all the thromboembolic and hemorrhagic compli- above-mentioned studies note a rever- cations of angiography.8 sal of radiologic and neurologic findings Encephalopathy has been documented without any deficits within 48 to 72 hours after administration of iopromide,9,10 (median recovery time of 2.5 days).3 All iohexol,11 ioxilan,4 and metrizamide. The reported cases of CIE, including ours, were mechanism of neurotoxicity is unclear, found to be completely reversible without but several theories have been formu- any neurologic or radiologic deficits after lated. The contrast agent may disturb the resolution (48 to 72 hours post-contrast blood-brain barrier and enter the brain. administration). This may be a primary mechanism lead- Clinicians should have a high index of ing to encephalopathy when the hyper- suspicion for CIE in patients with recent tonic contrast agent draws water out of iodine-based contrast exposure. From a the endothelial cells of brain capillaries, practical standpoint, such a mechanism Current Psychiatry 46 January 2019 arterioles, and venules. This may cause could be easily missed because while use of Cases That Test Your Skills

a single-administration contrast agent may appear in procedure notes or medication Related Resources administration records, it might not neces- • Donepudi B, Trottier S. A seizure and hemiplegia following contrast exposure: Understanding contrast-induced sarily appear in documentation of currently encephalopathy. Case Rep Med. 2018;2018:9278526. doi: administered medications. Also, such cases 10.1155/2018/9278526. might not always present with unique radio- • Hamra M, Bakhit Y, Khan M, et al. Case report and literature review on contrast-induced encephalopathy. Future Cardiol. logic findings, as illustrated by Ms. L’s case. 2017;13(4):331-335. Drug Brand Names References Iohexol • Omnipaque Iopromide • Ultravist 1. Moreau F, Asdaghi N, Modi J, et al. Magnetic resonance imaging versus computed tomography in transient ischemic Iopamidol • Isovue-370 Ioxilan • Oxilan attack and minor stroke: the more you see the more you know. Cerebrovasc Dis Extra. 2013;3(1):130-136. 2. Barber PA, Hill MD, Eliasziw M, et al. Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted Clinical Point imaging. J Neurol Neurosurg Psychiatry. 2005;76(11): 1528-1533. 7. Fischer-Williams M, Gottschalk PG, Browell JN. Transient cortical blindness: an unusual complication of coronary Clinicians should 3. Leong S, Fanning NF. Persistent neurological deficit from angiography. Neurology. 1970;20(4):353-355. iodinated contrast encephalopathy following intracranial have a high index aneurysm coiling: a case report and review of the literature. 8. Lantos G. Cortical blindness due to osmotic disruption of Interv Neuroradiol. 2012;18(1):33-41. the blood-brain barrier by angiographic contrast material: of suspicion for CIE CT and MRI studies. Neurology. 1989;39(4):567-571. 4. Ito N, Nishio R, Ozuki T, et al. A state of delirium (confusion) following cerebral angiography with ioxilan: 9. Kocabay G, Karabay CY. Iopromide-induced in patients with a case report. Nihon Igaku Hoshasen Gakkai Zasshi. encephalopathy following coronary angioplasty. Perfusion. 2002; 62(7):370-371. 2011;26:67-70. recent iodine-based 5. Bottinor W, Polkampally P, Jovin I. Adverse reactions to 10. Dangas G, Monsein LH, Laureno R, et al. Transient contrast iodinated contrast media. Int J Angiol. 2013;22:149-154. encephalopathy after carotid artery stenting. Journal of contrast exposure Endovascular Therapy. 2001;8:111-113. 6. Cohan R. AHRQ Patient Safety Network Reaction to Dye. US Department of Health and Human Services Agency for 11. Sawaya RA, Hammoud R, Arnaout SJ, et al. Contrast Healthcare Research and Quality. https://psnet.ahrq.gov/ induced encephalopathy following coronary angioplasty webmm/case/75/reaction-to-dye. Published September with iohexol. Southern Medical Journal. 2007;100(10): 2004. Accessed March 5, 2017. 1054-1055.

Bottom Line Have a high index of suspicion for contrast-induced encephalopathy, especially in geriatric patients, even in the absence of radiologic findings. A full delirium/ dementia workup is warranted to rule out other life-threatening causes of altered mental status. Timely recognition could enable implementation of medication- Current Psychiatry sparing approaches to the disorder, such as IV fluids and frequent reorientation. Vol. 18, No. 1 47