Month: March 2021

It’s a Stroke – of the Eye?

As we are well aware, a brain globally deprived of oxygen, for even the briefest moments, suffers irreversible damage. Cerebrovascular events, those depriving a smaller distribution of the brain of oxygen, do so likewise – excepting the potential for recovery provided by the so-called “ischemic penumbra”. There is great heterogeneity between stroke syndromes and potential for recovery, but perfusion- and tissue-based treatments quite clearly demonstrate some protective effect of collateral circulation.

Does the eye work like that? That is the working theory – or, at least, working wishes and hopes of the neurology and neuro-ophthalmology community.

There is typically only one blood vessel supplying the inner retina – the central retinal artery. If this vessel becomes occluded, widespread ischemia is inevitable. The outer retina is supplied by the choriocapilaris, derived from separate branches of the ophthalmic artery. A further, non-trivial percentage of individuals have a cilioretinal artery, supplying a part of the macula. These other vessels may provide some additional perfusion to parts of the eye, with intact survival approaching 90 minutes in animal studies. Widespread, irreversible damage seems complete by four hours.

So, is there a window of opportunity for early thrombolysis? The American Heart Association thinks so: “The current literature suggests that treatment with intravenous tissue plasminogen activator may be effective.”

This “current literature” of which they speak is primarily a citation from last year’s Stroke, a single-center cohort study and updated patient-level meta-analysis. In the “cohort” portion, this site treated 16 patients with CRAO with alteplase within 4.5 hours, and compared them with 87 others who received “Standard of Care”. Patients in this treatment cohort did better than those who were not – hardly surprising, considering those treated had fewer signs of damage to the retina on initial fundoscopic examination.

The “patient-level meta-analysis” includes 238 patients from studies dating back to the 1980s. The 9 patients for whom treatment was provided within 90 minutes displayed better outcomes than those treated in later time windows, as well as those patients whose outcomes describe the “natural history” of the disease. The guideline authors’ interpretation of these data: “An updated meta-analysis including these modern cohorts again demonstrated a strong effect with treatment within 4.5 hours.”

Little heed is paid to the 5 patients within their meta-analysis reported as having intracranial hemorrhage, 1 with angioedema, and 1 with extracranial hemorrhage.

CRAO is devastating, and there is no known effective treatment. Thrombolysis may be beneficial, but treatment is associated with well-established harms. Along with all the stroke mimics and low-NIHSS patients currently being treated, it’s not surprising these authors contort themselves into recommendations overstating the strength of the evidence. Clinical trials are underway – wait and see.

“Management of Central Retinal Artery Occlusion”
https://www.ahajournals.org/doi/pdf/10.1161/STR.0000000000000366

“Intravenous Fibrinolysis for Central Retinal Artery Occlusion”
https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.028743

Minor Stroke is Our Favorite Stroke

While most facilities are using non-contrast CT, CT angiograms, and/or CT perfusion as part of their initial triage of possible stroke, there are a few using rapid MRI-based protocols. MRI is vastly superior to CT for its specificity for stroke, quite useful in reducing early diagnostic closure and unnecessary treatment with thrombolytics.

One of these MRI-based stroke systems has published a brief, retrospective look at their tPA cohort – focusing, in this report, on the particularly controversial “minor stroke”. Specifically, they teased out patients with presenting NIHSS 0-6, tried to classify them as “clearly disabling”, “potential disabling”, and “non-disabling”. Then, they looked at 90-day outcomes from these groups, trying to discern any useful conclusions regarding the efficacy and safety of tPA in these patients.

Over the 2015-17 study period, there were 1,440 patients evaluated for potential stroke treatment. Of these, 792 fell into their “minor stroke” definition – only 255 of which received a provisional diagnosis of acute ischemic stroke. The remainder were diagnosed as stroke mimics, transient ischemic attacks, or intracranial hemorrhage. Of these 255, about 80% were able to be evaluated with MRI as their primary mode of evaluation, and about 3/5ths were treated with tPA. Ultimately, they end up with 119 patients in their primary comparison, looking at features and outcomes of 30 patients with “clearly disabling” deficits and 89 without.

How effective is tPA in this cohort? Who knows! This study doesn’t answer that question in the slightest. There is no untreated population with 90-day outcomes gathered for comparison. The authors mostly use this study to tout MRI-based screening technology, along with descriptive statistics of frequent perfusion abnormalities present in their untreated cohort. The general gist of their discussion is akin to the oculostenotic reflex in cardiac catheterization – if a stenosis is seen, it will be treated, regardless of known benefit. For using MRI to screen for stroke, they tend to wax optimistically the identification of these perfusion abnormalities in non-disabling strokes might better encourage acute treatment.

This ought to be considered nonsense, as tPA treatment of non-disabling strokes remains bereft of evidence of value. And, just to describe the scope of the problem – of the 305 patients treated with IV tPA, 75 did not have “clearly disabling” deficits. A full quarter of the tPA treatment population based on wishes and hopes! There was one upside to screening with MRI, at least: 454 of those 792 with “minor stroke” received a diagnosis of stroke mimic. I shudder to think of the unnecessary carnage at hospitals without the capacity to exclude stroke mimics with such ease.

Non-disabling stroke should never be treated with thrombolysis in clinical practice, not after PRISMS, nor after looking at the NIHSS 0-5 group in IST-3. The new European Stroke Organization guidelines recommend against thrombolysis. Just stop!

“Prevalence of Imaging Targets in Patients with Minor Stroke Select for IV tPA Treatment Using MRI”
https://n.neurology.org/content/96/9/e1301