Reversal of ischemic cortical blindness with tenecteplase

Abstract

Purpose

Tenecteplase (TNK) is a bioengineered variant of alteplase that has a longer half-life, a higher fibrin binding specificity, and a lower effect on systemic fibrinolytic activity. We reported a case of reversible bilateral vision loss to homonymous hemianopsia after TNK administration.

Case description

A 56-year-old African American male presented with acute onset of visual loss to no light perception (NLP) in both eyes (OU), left hemiparesis, decreased sensation, and dysarthria. Brain MRI revealed acute infarct involving the right posterior cerebral artery distribution without evidence of hemorrhagic transformation. CTA showed 4mm long segmental occlusion on the right P2 PCA. After the patient was given intravenous 23mg TNK after two and half hours since symptom onset, he recovered vision from NLP OU to 20/25 OU, but he had a residual left homonymous hemianopsia (HH), in addition to hemiparesis and decreased sensation on the left. The patient was eventually discharged to rehabilitation and outpatient follow up.

At the two-month follow up, patient only had residual left HH.

Conclusions and importance

Clinicians should be aware of the various treatment options in acute ischemia related cortical visual loss such as TNK. Future providers should also add comprehensive ophthalmological exam before and after patient receiving TNK to determine if our case is generalizable.

1. Introduction

There are 795,000 people in the United States who experience a stroke annually, and 87 % of them are ischemic stroke.¹ Posterior cerebral artery stroke presents with various symptoms such as visual, cognitive and behavioral dysfunction, posing a diagnostic challenge. Alteplase, a tissue plasminogen activator (tPA), is a thrombolytic drug approved for ischemic stroke by FDA in 1996. It is a glycoprotein with 526 amino acids which activates the fibrinolytic system in vivo.² Alteplase, which requires refrigeration, is administered intravenously over an hour and is cleared by the liver.³ It has been shown that compared to placebo, patients with ischemic stroke who received alteplase were at least 30 % more likely to have minimal or no disability at three months after the stroke, without any increase in mortality.⁴ However, alteplase has some disadvantages including a relatively short half-life and long infusion times, as well as post treatment incomplete recanalization rates or secondary intracranial hemorrhage risk.² In contrast, Tenecteplase (TNK), which does not require refrigeration, can be administered in a single IV injection over seconds, is a bioengineered variant of alteplase with protein structure changes at three amino acids sites resulting in a longer half-life, a higher fibrin binding specificity, and a lower effect on systemic fibrinolytic activity.^2,5

Previous studies comparing alteplase with TNK in acute ischemic stroke showed that TNK was more effective in early neurological improvement, blood vessel recanalization, and neurological recovery at 90 days.^2,6 One prior study demonstrated that patients presenting with isolated homonymous hemianopia experienced visual field improvement after thrombolysis with alteplase.⁷ However, no randomized control trial has been done for TNK and visual loss. One case report of TNK in recanalization of basilar artery occlusion reported significant improvement in neurological outcomes.⁸ Another case of acute basilar artery occlusion that failed to recanalize after conventional alteplase, improved after TNK.⁹ Here, we describe a case of reversible cortical blindness after TNK administration.

2. Case presentation

A 55-year-old African American male with past medical history of recurrent transient ischemic attacks and ischemic strokes (the most recent one was 6 months ago), variably controlled hypertension, congestive heart failure (left ventricle ejection fraction 74 % last year), type 2 diabetes mellitus, and hyperlipidemia presented with left-sided weakness, painless complete vision loss in both eyes (OU), and last known well was 2 h ago. Patient did not have baseline neurological deficits from previous strokes per the family, and he takes aspirin 81mg daily.

Code stroke was activated. International normalized ratio, complete blood count, comprehensive metabolic panel were mostly within normal range. B-type natriuretic peptide was elevated (863). Initial computed tomography (CT) of brain (Fig. 1) without contrast showed hypodensity at the right precuneus and cuneus gyri, which was consistent with an acute infarct at the right precuneus and cuneus gyri. The patient's family was consented and patient was given intravenous 23 mg TNK, 22 minutes after the patient's arrival at the ED.

Fig. 1.

CT Brain without contrast showing hypodensity at the right precuneus and cuneus gyri (arrow) consistent with acute infarct at the right precuneus and cuneus gyri.

CT Angiogram of head and neck revealed approximately 4mm long segmental occlusion of right P2 segment of posterior cerebral artery (PCA). No significant stenosis or occlusion along bilateral vertebral arteries, basilar artery, cerebellar arteries and left PCA. There was arteriosclerosis of the carotid bifurcations without stenosis (0 % by NASCET criteria). Neurology was consulted. On the exam, patient had a left hemiparesis and decreased sensation, slurred speech, and left homonymous hemianopsia (HH) OU. A diagnosis of cortical blindness was made. National Institute of Health (NIH) Stroke Scale score was 6 (2 points for complete left hemianopsia, 1 point for left leg drift, 1 point for partial sensory loss on the left, 2 points for dysarthria). Post-thrombolytic therapy brain magnetic resonance imaging (MRI) revealed diffusion restriction involving the right posterior cerebral artery distribution without evidence of hemorrhagic transformation, which was consistent with acute infarct (Fig. 2). Furthermore, although there was some loss of gray-white matter differentiation on the contralateral left occipital cortex on the CT head indicating ischemia, there was no diffusion restriction indicating acute infarct on the MRI DWI. Interestingly, the patient recovered vision from NLP OU to 20/25 OU, but he had a residual left homonymous hemianopsia with macular sparing. A full stroke work up was completed. Transthoracic echocardiogram showed normal left ventricle with ejection fraction 50–55 %. Left atrium and right ventricle were normal in size. No atrial septal defect or patent foramen ovale were noted. Cardiac rhythm monitoring showed normal sinus rhythm. His A1c was elevated with 9.3 %, LDL was mildly elevated at 116. He was discharged to rehabilitation and follow up with his primary care physician.

Fig. 2.

Post thrombolytic brain MRI without contrast axial view (A-T2 FLAIR, B-GRE, C-DWI, D-ADC), showing diffusion restriction involving the right PCA distribution without evidence of hemorrhagic transformation (arrows in A, C, and D).

One month later, his vision remained 20/25 OU and automated perimetry (Humphrey visual field 24-2) showed a persistent left complete HH with macular sparing (Fig. 3) due to the right PCA distribution infarct. The remainder of the structural eye exam was normal OU.

Fig. 3.

Humphrey Visual Field Test revealed a complete left homonymous hemianopsia.

At the two-month neurology follow up, patient still had left HH, which he has been following up with occupational therapy. The rest of neurological exam was unremarkable. Patient continued with dual antiplatelet therapy for a total of 90 days, and would continue with aspirin monotherapy indefinitely afterwards. Patient was also on atorvastatin with a goal of LDL of 70. Patient also continued to follow up with endocrinology for better blood glucose control. His last reported HbA1c 1 year later was 6.5 %.

3. Discussion

We believe this case is unique in several aspects. Although imaging only revealed a right PCA infarct, patient presented with left hemiparesis, dysarthria and bilateral complete vision loss. Some of these symptoms were consistent with an anterior circulation stroke. However, it has been reported that proximal P2 segment occlusion can result in a ventral lateral and ventral posterior thalamic stroke characterized by contralateral hemiparesis, hemisensory loss and dysarthria, which mimics a MCA stroke.¹⁰ Our patient's MRI (Fig. 1) also revealed an infarct involving thalamic territory in addition to the occipital lobe. Together with CTA showing a right 4 mm long segmental occlusion on mid right P2 PCA, it was likely the thalamic stroke that contributed to the hemiparesis and sensory loss. PCA is divided into four segments, with deep segments P1 and P2 supplying midbrain and thalamus, and superficial segments P3 and P4 supplying temporal and occipital lobe.¹¹ After the patient received TNK that catalyzed the activation of plasmin, the fibrin was subsequently degraded and therefore the blood clot in P2 was dissolved and the blood flow was recanalized.⁵ On the other hand, the presentation of bilateral NLP was most likely because of transient reversible bilateral ischemia from more proximal arteries such vertebral arteries or basilar artery, especially given that our patient did have arteriosclerosis at carotid bifurcations. Therefore, our patient most likely had global hypoperfusion or more proximal vertebrobasilar ischemia, together with right PCA infarct, which explained his initial NLP OU, dysarthria, and hemiparesis, as well as left HH with macular sparing after receiving TNK, which recanalized the blood vessel.

Our patient received TNK 2.5-h since the last known well time, within the 4.5-h window. The thrombolysis within 3–4.5 hour window was implemented rapidly since 2008, and not only did it not result in delayed treatment, it still provided equal benefits that outweigh the minor increased risk of intracerebral hemorrhage and mortality.¹²

Furthermore, based upon our review of the English language ophthalmic literature, we believe that this case of reversible cortical blindness following TNK is novel. TNK has a longer half-life, higher fibrin specificity, and more rapid vascular recanalization potential than alteplase.² A recent meta-analysis showed that there was no statistical differences in safety profile between TNK and alteplase.^2,6 Previous randomized trial comparing alteplase and TNK in acute ischemic stroke revealed that patients with large artery occlusions had better recanalization rates, and better functional outcomes with TNK, compared to alteplase.¹³ However, in patients without large vessel occlusion, TNK was reported to be associated complications such as symptomatic intracranial hemorrhage, compared to alteplase.¹⁴ Fortunately, this did not occur in our patient. It is recommended that future neurologists who are consulted for code stroke also involve ophthalmologist who can perform a more thorough ophthalmological exam. The neuro-ophthalmological exam changes between pre and post TNK treatment should be documented. This will be helpful to document the treatment benefits associated with TNK.

Our case highlighted that clinicians should be aware of the various treatment options in acute stroke related cortical visual loss such as TNK. Future providers should also add comprehensive ophthalmological exam before and after patient receiving TNK to determine if our case is generalizable.

CRediT authorship contribution statement

Rui Tang: Conceptualization, Writing – original draft. Maryam Naser: Conceptualization, Writing – review & editing. Saif Aldeen Alryalat: Data curation, Writing – review & editing. Osama Al deyabat: Data curation, Writing – review & editing. Andrew G. Lee: Supervision, Writing – review & editing.

Patient consent

Written consent to publish this case has not been obtained. This report does not contain any personal identifying information.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work, and have given their approval for this version to be published.

Disclosures

Rui Tang, Maryam Naser, Saif Alryalat, Osama Al deyabat and Andrew G. Lee, declare that they have no conflict of interest.

Publication originality statement

We confirm this publication is original.

Claims of priority

Based upon our review of the English language ophthalmic literature, we believe that this case of reversible cortical blindness following TNK is novel.

Statement of authorship

Category 1:

a. Conception and design: Rui Tang, Maryam Naser, Saif Alryalat, Osama Al deyabat

b. Acquisition of data: Rui Tang

c. Analysis and interpretation of data: Rui Tang.

Category 2:

a. Drafting the manuscript: Rui Tang

b. Revising it for intellectual content: Saif Alryalat, Osama Al deyabat.

Category 3:

a. Final approval of the completed manuscript: Andrew G. Lee.

Funding

There was no funding or grant support.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.