ARIEL SHARON'S STROKE
THE TREATMENT HE RECEIVED – AND WHY
“Sharon's Stroke Puts Spotlight on Care for Intracerebral Hemorrhage” (Jan. 17, page 1) covered Prime-Minister Sharon's illness, and highlighted some issues in stroke management with interviews of American stroke experts. Although the article specifically stated that all interviewees could make only general statements because they had no knowledge of the specific details of the Prime Minister's condition, the general attitude could be interpreted as criticism of the medical decisions made in his care.
Unfortunately, the article was written just a few days after Sharon was hospitalized, when he was fighting for his life, and treating physicians were not at liberty at that time to explain their medical judgment. As members of the team of physicians who treated him, we want to clarify some of issues raised in the Neurology Today article.
Seventy-eight-year-old Sharon was admitted to the hospital on Dec. 18, 2005 with aphasia of sudden onset. Except for obesity and his age, he had none of the common vascular risk factors. Specifically, he did not have hypertension, diabetes mellitus, or hypercholesterolemia, and he did not smoke.
His neurological condition improved gradually over the next 36 hours, as assessed by normal findings on neurologic and cognitive examination. His brain was normal on MRI, except for small subcortical “unidentified bright objects” and scattered old deep and subcortical microbleeds. There was also a small cortical ischemic lesion in the left temporal lobe. His cerebral and cervical vessels appeared normal on MR angiography, and his heart, ascending aorta, and arch were all normal on transesophageal echocardiography (TEE). TEE, however, showed a significant patent foramen ovale (PFO), with a significant atrial septal aneurysm (ASA), and a spontaneous right-to-left shunt.
CARE PROVIDED TO SHARON
The Prime Minister was under the care of a large team of specialists, including neurologists, cardiologists, internists, anesthesiologists, and experts in coagulopathies. They discussed many issues regarding the nature and source of the stroke and how to prevent future events, including the following issues:
- The sudden onset of a neurological deficit of cortical distribution was followed by gradual improvement over the next 36 hours and was considered clinically typical of a major embolic event.
- The lack of major risk factors for stroke, lack of evidence of advanced atherosclerotic disease, including the normal cervical arteries, aortic root and arch, and the normal heart, except for the PFO, raised the possibility that there had been a cardioembolic event due to the PFO.
- The likelihood that the PFO was relevant was discussed extensively, including the high prevalence of PFO in the population, as well as literature reports suggesting that small PFOs may be irrelevant. However, there is considerable literature indicating that a combination of PFO and a large atrial septal aneurysm plus a spontaneous shunt may be a significant risk factor for embolism (NEJM 2001:345:1740–1746; Stroke 2000;31:2407–2413).
- The significance of a PFO in advanced age was discussed as well. In fact, the investigators who published the original PICCS (PFO in Cryptogenic Stroke Study) study, suggesting that the mere presence of PFO may not increase the risk of recurrent stroke in patients treated with aspirin or warfarin (Circulation 2002;105:2625–2631), subsequently published data from the same cohort, suggesting that PFO in advanced age increases the risk of stroke three-fold, as compared to young adults (Stroke 2004;35:2145–2149).
- Given the probability that Mr. Sharon had suffered from a cardioembolic stroke in association with a PFO, several therapeutic options were considered. Most important, the high risk of recurrent ischemic events was weighed against the increased risk of brain hemorrhage in a patient with old cerebral microhemorrhages.
RISK FOR RECURRENT ISCHEMIC EVENTS
There is an extensive literature on the risk of recurrent ischemic events. Although the exact risk is unknown, it is clearly highest in the early period after the index event, up to 30 percent in the first week in untreated patients, in one MRI-based study (Neurology 2005;65:513–517). In most stroke centers, standard treatment after a cardioembolic stroke includes full anticoagulation.
It is known by now that a significant proportion of brain hemorrhages in the elderly, and specifically those associated with anticoagulant therapy, are related to old microbleeds (Neurology 2000;55:947–951). However, the exact risk in using anticoagulants to treat these patients is still unknown. The risk of bleeding is cumulative over time. While chronic anticoagulation in patients with microbleeds may be dangerous, short-term therapy may be safer. For example, one study found that thrombolytic therapy, which has the highest risk of brain hemorrhage, was not associated with increased likelihood of brain hemorrhage in stroke patients with microbleeds (Neurology 2005;65:1175–1178).
We concluded that although the exact risk-to-benefit ratio in this specific situation is unknown, most data suggest that not treating the Prime Minister would carry a substantially higher risk of recurrent ischemic events than the risk of hemorrhage in a short course of anticoagulation. It was decided to cover him with low molecular weight heparin (Enoxaparin) and to close the PFO as soon as possible in order to switch thereafter to antiplatelet therapy. We monitored the effect of heparin according to standard practice by testing for anti-factor Xa activity, and the level was perfectly within the therapeutic range. Mr. Sharon was scheduled for cardiac catheterization within two weeks of the initial acute ischemic event.
RESPONSE TO SECOND STROKE
Unfortunately, the Prime Minister had a second hemorrhagic stroke on Jan. 4, the night before the cardiac procedure, after the last injection of heparin. On his way to the hospital, his condition deteriorated into stupor shortly before he arrived at the emergency room. After a brief resuscitation to stabilize his condition, CT showed extensive right hemispheric hemorrhage. He immediately received a bolus of recombinant-activated factor VII to limit the size of the hematoma, and he was taken to the operating room for emergency decompressive craniectomy and partial removal of the superficial part of the hematoma. This rapid intervention undoubtedly saved his life.
It should be noted, however, that the treating physicians do not advocate surgical management in every patient with intracerebral hemorrhage, only in selected cases.
Prime Minister Sharon suffered an embolic stroke, related to a PFO with ASA and spontaneous right-to-left shunt. This event on the one hand and the relatively increased risk of hemorrhagic complications on the other hand prompted the compromise to provide short-term anticoagulation followed by PFO closure and antiplatelet therapy thereafter. Since we were aware that VIP patients often are at risk for a different standard of care, the treating physicians made sure that the prime minister was neither overtreated nor undertreated. After learning of the specific facts, several stroke experts have expressed support of these individually tailored therapeutic decisions.