(Stroke. 1995;26:891-895.)
© 1995 American Heart Association, Inc.
Articles |
Acute Lacunar Stroke in Association With Angiogram-Negative Subarachnoid Hemorrhage
Mechanistic Implications of Two Cases
From the Neurosurgical Service, Cerebrovascular Surgery (S.B.T., C.S.O.), and the Department of Neurology (F.S.B.), Massachusetts General Hospital, Boston.
Correspondence to Christopher S. Ogilvy, MD, Director, Cerebrovascular Surgery, Neurosurgical Service, VBK-710, Massachusetts General Hospital, Boston, MA 02114. E-mail ogilvy@helix.mgh.harvard.edu.
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Abstract |
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Background and Purpose Although there is much speculation regarding the source of bleeding in patients with subarachnoid hemorrhage when no angiographic abnormality is found, little direct evidence has been obtained to document a cause. We report two cases of stroke in the distribution of a perforating or lenticulostriate artery occurring at the time of angiogram-negative subarachnoid hemorrhage.
Case Descriptions A 68- and a 60-year-old man each presented with acute onset of headache and meningismus. Computed tomography (CT) revealed subarachnoid hemorrhage in a perimesencephalic pattern and in the left sylvian fissure, respectively. In both instances, immediate CT revealed evidence of an early infarction in the distribution of a perforating artery originating at the site of the subarachnoid blood. Both of these strokes were demonstrated to be acute by evolution on serial imaging studies. No source for the subarachnoid blood could be found in either patient in cerebral angiograms repeated at 2 weeks.
Conclusions These observations suggest that in some cases of angiogram-negative subarachnoid hemorrhage the source of blood may be a small artery that is obliterated at the time of hemorrhage. This observation provides an explanation for the low rate of rehemorrhage among patients with angiogram-negative subarachnoid hemorrhage.
Key Words: angiography • arterial occlusive diseases • cerebral arteries • cerebral infarction • subarachnoid hemorrhage
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Introduction |
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A number of etiologies have been proposed for subarachnoid hemorrhage (SAH) from a source that is occult to angiography and magnetic resonance imaging. These include undetected aneurysms,1 2 3 4 5 6 7 8 ruptured microaneurysms on major intracranial arteries,8 9 hemorrhage from a vein or capillaries,10 11 or rupture of a small artery.12 Angiographically occult aneurysms and microaneurysms have been shown to be the source of hemorrhage by exploration in some cases.4 5 6 7 8 9 Conversely, exploration of other angiogram-negative patients, particularly those with a perimesencephalic pattern of blood on the initial computed tomography (CT), has not revealed the source of hemorrhage.5 8 11 Patients with a perimesencephalic distribution of blood have a particularly low rate of rehemorrhage.10 13 14 15 16 17
For a single instance in which a patient died suddenly in the setting of anticoagulation, the source of SAH was shown to be rupture of a 0.15-mm-diameter branch of the basilar artery.12 This has lead to the proposal that some instances of radiographically occult SAH represent rupture and subsequent thrombosis of a small perforating or lenticulostriate artery. Although an acute lacunar infarct would be expected to occur at the time of SAH in such cases, this has not been previously reported. We describe two patients—one of whom had a perimesencephalic pattern of blood on initial CT—who developed acute lacunar infarction in a distribution consistent with a perforating or lenticulostriate artery. This same artery is postulated to be the source of the SAH.
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Case Reports |
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Patient 1
A 68-year-old right-handed man experienced acute onset of severe headache while watching television. This was followed by mild nausea. He had a history of hypertension and coronary artery disease that had required bypass grafting 3 years previously.
Examination
Physical examination several hours after the onset of symptoms
revealed no abnormalities other than moderate meningismus and an
initial blood pressure of 186/92. CT demonstrated perimesencephalic SAH
with some layering of blood along the tentorium (Fig 1A
). There was an indistinct region of hypodensity less
than 1 cm in diameter apparent in the left putamen (Fig 1B).
Four-vessel cerebral angiography revealed no potential source of
hemorrhage (Fig 2). Occlusion of the right external
carotid artery and intracranial atheromatous disease most prominent in
the siphon of the right internal carotid artery were observed. There
was no vasospasm.
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Post-SAH Course
CTs obtained 2 and 14 days after the hemorrhage demonstrated
evolution of the lacunar infarct in the inferior left putamen (Fig 1C
and 1D, respectively). A second angiogram obtained at 14 days revealed
no source of hemorrhage but was followed by infarction in the
distribution of the right posterior inferior cerebellar artery. This
resulted in a lateral-medullary syndrome with intractable hiccups,
right vocal cord paralysis, right lower facial palsy, right upper
extremity dysmetria and weakness (manifested as pronator drift),
bilateral ptosis, and miosis greater on the left than the right side.
Heparin anticoagulation was followed by conversion to warfarin
treatment. Magnetic resonance imaging at that time revealed no source
for the patient's SAH.
The patient returned to his neurological baseline over the next several weeks. He remains well 8 months after his SAH.
Patient 2
A 60-year-old right-handed man presented with acute onset of
headache and meningismus. He was amnestic regarding the onset of these
symptoms, which his spouse reported to have occurred while he was
parking a car and which resulted in a low-speed motor-vehicle accident.
A CT obtained at another institution revealed subarachnoid blood that
was most prominent in the left sylvian fissure and extended over the
frontal convexity (Fig 3A). The patient was transferred
to our hospital. Parkinson's disease had been diagnosed 4 years
earlier, and his tremor was initially symptomatic predominantly on the
right side but subsequently had become nearly symmetrical. A CT scan
obtained at that time because of the onset of right-sided tremor and
rigidity showed no abnormalities. The patient's symptoms were well
controlled by L-dopa/carbidopa and deprenyl.
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Examination
The initial blood pressure measurement was 136/71. A mild
abrasion was apparent on the patient's nose, but there was no other
evidence of significant trauma. Neurological examination demonstrated
mild rigidity and cogwheeling, a positive snout reflex, and fine
horizontal nystagmus on right gaze. All of these findings had been
present in examinations before the SAH. There was new mild right
lower facial weakness. No other physical or laboratory abnormalities
were detected. A left carotid angiogram revealed no potential source of
the patient's hemorrhage (Fig 4). There was no
vasospasm.
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Post-SAH Course
Two days after the onset of symptoms, a second CT showed a new
hypodensity in the region of the left putamen and external capsule (Fig 3B). There was enhancement around this lesion after intravenous
contrast administration (Fig 3C). A magnetic resonance scan confirmed
the presence of a T1-hypointense,
T2-hyperintense lesion and showed residual subarachnoid
blood. There were no parenchymal contusions present. Subsequent
cerebral angiography performed 2 weeks after the SAH again revealed no
abnormalities.
During 4 additional years of follow-up, the patient's parkinsonism has progressed gradually and is now partially refractory to L-dopa therapy. He has also experienced the onset of dementia. There have been no further episodes of SAH. This patient is one of 40 patients with angiogram-negative SAH reported previously.8
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Discussion |
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Approximately 10% of patients with SAH have no radiographically apparent etiology for their disorder.8 14 18 19 20 21 22 This "angiogram-negative" SAH is characterized by a lower rate of rehemorrhage than aneurysmal SAH.14 18 20 21 22 23 24 25 Among these patients, those with a perimesencephalic pattern of hemorrhage on the initial CT have a more favorable prognosis and a lower rehemorrhage rate than those with other distributions of subarachnoid blood.10 13 14 Much of the remaining morbidity among patients with angiogram-negative SAH is attributable to patients whose distribution of blood is similar to that seen in patients with intracranial aneurysms.14 Many of these patients with an aneurysmal pattern of blood have a radiographically occult aneurysm or a microaneurysm on a major intracranial vessel that accounts for a rehemorrhage rate similar to that in patients with aneurysms detected by angiography.1 2 3 4 5 6 7 8 9 The pathogenesis of bleeding in the patients who follow a benign clinical course has not, however, been conclusively identified. It is this group, which includes the majority of patients with angiogram-negative SAH, with whom this report is concerned.
Two possible sources of hemorrhage in these cases have been proposed: bleeding from a vein10 11 or rupture of a small artery.12 In a single instance, rupture of a 0.15-mm arterial branch of a short circumferential pontine artery at a region of muscularis deficiency in the media has been histologically documented as the source of hemorrhage in a case of angiogram-negative SAH.12 That case occurred in the pre–CT scan era, and the patient died in the acute phase because of concurrent anticoagulation. Serial sections of the region of hemorrhage identified the site of arterial rupture, leading to the proposal that the benign prognosis of the majority of angiogram-negative SAHs is accounted for by the thrombosis of the small artery that hemorrhaged. The acute lacunar infarctions in the distribution of a perforating or lenticulostriate artery distal to the site of hemorrhage in the cases presented here suggest that a similar mechanism was operative.
This proposed etiology is similar to that demonstrated in hypertensive cerebral hemorrhage,26 27 28 29 30 31 32 33 which also has an extremely low rate of rebleeding.34 Lacunes have been detected radiographically and at autopsy in patients with hypertensive parenchymal hemorrhages.28 29 35 Conversely, the most careful autopsy study found that 41 of 114 (35%) consecutive patients with a lacune also had an associated cerebral hemorrhage.35
Failure to detect an acute lacunar infarct in most patients with benign angiogram-negative SAH and in most patients with parenchymal hypertensive hemorrhages may have several explanations. In most cases, the infarcts may be too small to be visualized radiographically or detected clinically. Alternatively, collaterals that prevent infarction may develop, particularly in lesions associated with chronic degeneration of small cerebral arteries. Finally, serial CT may be required to distinguish an old incidental lesion from an acute lesion related to the cause of hemorrhage.
It is unlikely that the acute lacunar infarcts presented here occurred coincidentally at the time of SAH because neither patient had radiographic evidence of prior lacunar infarctions. It is possible that lacunar infarctions could be caused in the acute phase by subarachnoid blood rather than by thrombosis of a ruptured artery, but several factors argue against this in the present cases. First, there was no vasospasm present on angiography in these patients. Second, there was CT evidence of infarction within hours after the onset of these patients' symptoms, which is too soon for vasospasm to be the cause. Finally, acute lacunar infarction is not observed in aneurysmal SAH.
The lesions of small arteries that might lead to benign angiogram-negative SAH may be one of the four types delineated by Fisher27 : lipohyalinosis (also known as segmental arterial disorganization), saccular microaneurysm (classic Charcot-Bouchard microaneurysm), fusiform microaneurysm, or a nonaneurysmal "bleeding globe." Lipohyalinosis occurs almost exclusively in small intraparenchymal arteries and spares arterial segments in the subarachnoid space.27 Hemorrhage from such a lesion might still cause an SAH if it occurred at the parenchymal/subarachnoid junction. Fisher26 27 found no evidence that either saccular or fusiform microaneurysms were the source of hypertensive parenchymal hemorrhages and suggested that these lesions are unlikely to be responsible for such hemorrhages because of the small size of the parent vessels, the consistent presence of a sealing layer of fibrin, and the failure to find traces of such structures in serial sections of regions of hypertensive hemorrhage. Similar considerations likely exclude microaneurysms of small arterial branches as the cause of most cases of angiogram-negative SAH. Finally, a nonaneurysmal defect such as a muscular media deficiency may be the most likely cause of rupture of a small artery in the subarachnoid space.12 Such lesions are more likely to occur with age, particularly in hypertensive patients, and also occur selectively in perforating and lenticulostriate arteries.36
Hypertension occurs with greater frequency in patients with angiogram-negative SAH than in age-matched control subjects, suggesting that it may play a role in the pathogenesis of this entity.18 Both of the patients reported here had evidence of vascular disease before their SAH, consistent with a role of vascular degeneration in the etiology of benign angiogram-negative SAH.
In summary, the two patients presented here provide evidence that certain cases of benign angiogram-negative SAH—including the perimesencephalic variant—may be caused by rupture and subsequent thrombosis of a small branch of an intracerebral artery. We believe that it is important to distinguish such cases, which represent the majority of instances of angiogram-negative SAH, from lesions that occur in the circle of Willis and its major tributaries and branches and that are associated with a higher rate of morbidity and mortality.
Received January 12, 1995; revision received February 9, 1995; accepted February 9, 1995.
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