Haemorrhagic transformation of a recent silent cerebral infarct during thrombolytic stroke treatment

BACKGROUND

This case report describes a patient who, during thrombolytic treatment for a cerebral infarction, had an intracranial haemorrhage at a location distant from the infarction. Re-examination of the initial computed tomography (CT) scan revealed subtle changes compatible with a 1- to 2-week-old clinically silent infarction on the site of the haemorrhage. Interestingly, the patient had had a transient ischaemic attack 3 weeks before admission to our hospital and magnetic resonance imaging (MRI) of the brain undertaken shortly after this transient ischaemic attack was normal (also after careful re-examination).

Intracerebral haemorrhages during thrombolytic treatment can occur remotely from the anatomical site of the ischaemia and have been reported previously in thrombolysis trials. One explanation for this might be the haemorrhagic transformation of (recent) silent infarcts, which are not uncommon in patients presenting with a symptomatic ischaemic stroke.

To the best of our knowledge, this case is the first to illustrate that a recent silent infarct was indeed the cause of a haemorrhage at an unexpected site during intravenous thrombolytic treatment with recombinant tissue plasminogen activator. The case also shows that a close examination of CT and MRI scans, with special attention given to lesions indicating silent ischaemia, might help to prevent such a complication.

CASE PRESENTATION

A patient in her 60s presented to the emergency department with a sudden loss of power in her right arm and leg, right sided facial weakness and difficulties with speaking. Symptoms started 90 min before arrival in the hospital. On admission her blood pressure was 154/96 mm Hg and the pulse rate was 64 beats/min and regular. On neurological examination there was a slight droop of the right corner of her mouth and slightly decreased strength in her right arm and leg. She was fully awake but had aphasia. It was difficult to examine her any further neurologically, as she did not fully cooperate because of the aphasia. Her NIHSS score was 12.

The patient had no significant past medical history, except for a transient ischaemic attack 3 weeks before admission, in which she experienced a sudden loss of power in her right arm and leg. These symptoms resolved completely within 30 min. Shortly after this episode an MRI scan was performed, which showed no abnormalities. For reasons which are not clear, antiplatelet drugs were not started after this transient ischaemic attack.

The patient lived with her husband and had retired a few years ago.

INVESTIGATIONS

A CT scan showed a hyperattenuated left middle cerebral artery (fig 1).

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Figure 1 Pre-treatment CT scan showing a hyperattenuated left middle cerebral artery.

DIFFERENTIAL DIAGNOSIS

The patient was diagnosed with having an acute ischaemic stroke in the left hemisphere.

TREATMENT

Intravenous thrombolytic treatment with recombinant tissue plasminogen activator (total dose 63 mg) was started approximately 2 h 30 min after stroke onset.

OUTCOME AND FOLLOW-UP

After receiving 38 mg of the planned total dose of recombinant tissue plasminogen activator the patient’s blood pressure suddenly rose and she became restless. The infusion was stopped and an emergency CT scan performed. This scan showed a focal area of high density, indicating an intracranial haemorrhage, in the right frontal gyrus and a slightly hypoattenuated and swollen adjacent cortex (fig 2A). Closer examination of the pretreatment CT scan (fig 2B,C) revealed subtle hypoattenuation in the right caudate nucleus consistent with an established infarct and subtle hyperattenuation consistent with a petechial haemorrhage, in the right frontal cortex. The adjacent cortex was slightly hypoattenuated and swollen. These findings suggested a relatively recent silent infarct. On examination the patient had no neurological deficits on the left side of her body, attributable to the right sided lesion, but higher cerebral dysfunction was difficult to test. She was awake and still had the initial stroke symptoms.

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Figure 2 (A) Post-treatment CT scan showing a focal area of high density, indicating an intracranial haemorrhage, in the right frontal gyrus and a slightly hypoattenuated and swollen adjacent cortex.

(B, C) Pre-treatment CT scans showing subtle hypoattenuation in the right caudate nucleus consistent with an established infarct and subtle hyperattenuation in the right frontal cortex consistent with petechial haemorrhage.

An MRI brain scan was performed 5 days after admission and showed, besides the recent infarct in the left middle cerebral artery region, relatively recent (previous 1–2 weeks) ischaemic changes associated with sulcal haemorrhage in the right posterior frontal cortex and frontal pole (fig 3). A re-examination of the MRI brain scans that were made 3 weeks before the patient had the ischaemic stroke revealed no abnormalities.

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Figure 3 (A–C) Series of MRI scans performed 5 days after admission and showing a recent infarct in the left hemisphere and relatively recent ischaemic changes associated with sulcal haemorrhage in the right posterior frontal cortex and frontal pole.

A month later the patient was discharged to a rehabilitation centre. She still suffered from a partial paralysis in her right arm and leg, but could now walk without help. We concluded that the patient had had a silent ischaemic stroke in the right hemisphere 1–2 weeks before the presenting stroke. As the ischaemic event in the right hemisphere was located in a clinically relatively silent area, it was not apparent to the patient. Thrombolytic treatment led to a small haemorrhage into the adjacent gyri from petechial haemorrhage in this silent infarct, without any lasting symptoms.

DISCUSSION

Silent infarctions are not uncommon in patients presenting with symptomatic ischaemic strokes.12 To the best of our knowledge, this case is the first to illustrate that haemorrhagic transformation of recent silent infarct was the cause of a haemorrhage at an unexpected site during thrombolytic treatment. Haemorrhagic transformation occurs in 15–43% of patients with cerebral ischaemia.3 Symptomatic intracranial haemorrhages among patients that received intravenous thrombolytic treatment occurring outside of the vascular distribution of the presenting stroke were reported in 20% of all patients with symptomatic intracranial haemorrhages in the NINDS trial.4 Asymptomatic intracranial haemorrhages occurred in 4.1% of all patients during the first 36 h post-treatment.4

Recent findings from the SITS-MOST study, which assessed the safety of intravenous thrombolytic treatment with recombinant tissue plasminogen activator, showed that primary intracranial haemorrhages (type 1 and 2) were located remote from the actual infarct in 2.8% of 6268 patients on CT or MRI scans taken 22–36 h after treatment.5 This accounted for 16% of all intracranial haemorrhages that were seen on CT or MRI scans taken shortly after treatment.5

Based on appearances on both the CT and MRI scans the silent infarct in our patient was 1–2 weeks old at the time of the symptomatic ischaemic stroke in the left hemisphere and definitively not older than 3 weeks, as the MRI brain taken at that time was completely normal. The high densities in the right frontal cortex, which were missed on the pre-thrombolysis CT scan, were petechial haemorrhages in a silent infarct. These haemorrhages clearly increased during treatment. In hindsight, our patient should therefore not have received thrombolytic treatment. The early treatment cessation may have limited the size of the haemorrhage in our patient and prevented negative effects on the clinical outcome. A close examination of pretreatment CT or MRI scans, with special attention given to lesions indicating recent silent infarcts and haemorrhagic transformation, might help to prevent such a complication and increase the safety of thrombolytic treatment.