Keywords
nontraumatic nonaneurysmal subarachnoid hemorrhage - digital subtraction angiography
- perimesencephalic - nonperimesencephalic - Glasgow outcome scale
Introduction
The rupture of intracranial aneurysms is the most common cause of nontraumatic subarachnoid
hemorrhage (NSAH) and is usually accompanied by a high-rate of morbidity and mortality.[1]
[2]
Despite the use of high quality four to six vessel cerebral digital subtraction angiography
(DSA), the obvious source of bleeding is not detected in nearly 15% (5–30%) of patients
with NSAH.[3]
[4]
Some studies suggested a ruptured perforating artery, low-flow vascular malformation,
capillary or venous source, and short segment arterial dissection as a probable source
of the angiogram-negative SAH.[5]
[6] On the other hand, some authors did not agree with this hypothesis and proposed
vasospasm, spontaneous thrombosis, alterations in blood flow, narrowing of the aneurysmal
neck, inadequate angiographic technique, or observer error as the factors responsible
for this event.[5]
[7]
Overall, nontraumatic nonaneurysmal subarachnoid hemorrhage (NNSAH) has a benign clinical
course and has a generally more favorable outcome in comparison with aneurysmal SAH.[3]
[8]
Based on the distribution pattern of the SAH, these cases are usually divided into
two subgroups, perimesencephalic (PM-SAH) and nonperimesencephalic subarachnoid hemorrhage
(nPM-SAH).[4]
[9]
PM-SAH is usually associated with lower complication rates and more favorable outcomes.[3]
[9] However, there is a controversy about the clinical outcomes and complications of
patients with nPM-SAH.[10] Meanwhile, recent studies recommend that the management of the nPM-SAH group should
be more rigorous, keeping in mind its more severe clinical courses and outcomes.[3]
[9]
The present study aimed to investigate the risk factors, complications, and clinical
outcomes of patients with NNSAH who were admitted to our center between April 2009
and April 2019.
Methods
We retrospectively evaluated 498 consecutive patients with NSAH admitted in our center
between April 2009 and April 2019. SAH was diagnosed by CT and/or lumbar puncture.
All patients were investigated by CTA on admission, followed by an emergent DSA examination.
There were 91 (18.27%) SAH patients who had a negative initial CTA finding to demonstrate
a culprit lesion.
Of these, initially, 13 patients had positive DSA results (two with a PM-SAH and 11
with a nPM-SAH). Finally, 78 SAH patients with initial negative DSA findings were
included in the present study.
The patients were divided into the PM-SAH (n = 45 patients) and the nPM-SAH groups (n = 33) based on the bleeding pattern on the initial CT scan.[9]
[11]
All patients underwent cranial and spinal MRI for the recognition of possible underlying
causes. If a vascular lesion was suspected, additional spinal DSA was performed. Repeat
DSA evaluations were performed for 10 to 14 days following the initial DSA. Radiological
vasospasm was defined as the segmental vasoconstriction of cerebral arteries, as shown
by the DSA.[3] The clinical vasospasm was defined as a severe headache with or without focal neurological
deficits or seizures, with no evidence of rebleeding in the presence of radiological
vasospasm.[3] The demographic data and clinic records of all patients, including age, sex, smoking
history, hypertension, diabetes, history of anticoagulant medication, Glasgow coma
score (GCS), Hunt–Hess (H–H) grade, and in-hospital complications were retrospectively
reviewed and compared between the two groups.
The outcomes were evaluated using the Glasgow outcome scale (GOS) at the time of discharge.[5]
[9] We considered GOS = 4 to 5 as a favorable outcome and GOS = 1 to 3 as unfavorable
outcomes.[12]
Statistical Analysis
All statistical analyses were conducted using SPSS for Windows version 22.0 (SPSS
Inc. Chicago, IL, USA). A student’s t-test was used to compare quantitative variants.
Qualitative variants were compared using the Chi-squared test or Fisher’s exact test.
p < 0.05 was considered statistically significant.
Results
There were 41 men (52.56%) and 37 women (47.43%) with the mean age of 53.98 ± 7.7years.
In the present study, 45 (57.69%) patients were in the PM-SAH group and 33 cases (42.30%)
were in the nPM-SAH group. There were no significant differences between the two groups
based on age, sex, smoking history, diabetes, hypertension, anticoagulation medication
history, and H–H grades on admission ([Table 1]). However, a significant difference was found between the two groups with regard
to GCS score on admission (p = 0.012) ([Table 1]).
Table 1
Patient characteristics
|
NSAH
|
PM-SAH (%)
|
nPM-SAH (%)
|
p-Value
|
|
Abbreviations: GCS, Glasgow coma scale; GOS, Glasgow outcome scale; H–H grade, Hunt–Hess
grade; NSAH, nonaneurysmal subarachnoid hemorrhage; PM, perimesencephalic; nPM, nonperimesencephalic;
SAH, subarachnoid hemorrhage.
|
|
No. of patients
|
78 (100%)
|
45 (57.69%)
|
33 (42.30%)
|
N/A
|
|
Age
|
53.98 ± 7.7
|
53.11 ± 8.4
|
54.71 ± 7.4
|
0.433
|
|
Smoker (%)
|
23 (29.4%)
|
15 (33.3%)
|
8 (24.24%)
|
0.721
|
|
Diabetes (%)
|
17 (21.79%)
|
9 (20.0%)
|
8 (24.24%)
|
0.691
|
|
Hypertension (%)
|
38 (50.66%)
|
21 (46.66%)
|
17 (51.51%)
|
0.554
|
|
Anticoagulant consumption (%)
|
6 (7.69%)
|
4 (8.88%)
|
2 (6.06%)
|
0.912
|
|
GCS
|
Severe[3]
[4]
[5]
[6]
[7]
[8]
|
3 (3.84%)
|
0 (0.00%)
|
3 (9.09%)
|
0.012
|
|
Moderate[9]
[10]
[11]
[12]
|
10 (12.8%)
|
3 (6.66%)
|
7 (21.21%)
|
|
Mild[13]
[14]
[15]
|
65 (83.33%)
|
42 (93.33%)
|
23 (69.69%)
|
|
H-H grade
|
Good (I-II)
|
71 (91.02%)
|
43 (95.5%)
|
28 (84.84%)
|
0.083
|
|
Poor (III-IV)
|
7 (8.97%)
|
2 (4.44%)
|
5 (15.15%)
|
|
Clinical outcome
|
Favorable
(GOS=4–5)
|
74 (94.8%)
|
45 (100.00%)
|
29 (87.87%)
|
0.037
|
|
Unfavorable
(GOS=1–3)
|
4 (5.12%)
|
0 (0.00%)
|
4 (12.12%)
|
Following the negative initial DSA, cranial MRI was performed on all patients within
the first 10 days after SAH. These evaluations revealed a cavernoma as the underlying
cause of bleeding in three cases (3.84%), all of which belonged to the nPM group ([Table 2]).
Table 2
Imaging modalities for further investigation and complications
|
NSAH
|
PM-SAH (%)
|
nPM-SAH (%)
|
p-Value
|
|
Abbreviation: DSA, digital subtraction angiography; EVD, external ventricular drain;
NSAH, nonaneurysmal subarachnoid hemorrhage; PM, perimesencephalic; nPM, nonperimesencephalic; SAH, subarachnoid hemorrhage.
|
|
Repeat DSA (positive)
|
5 (6.41%)
|
0 (0.00%)
|
5 (15.15%)
|
0.237
|
|
Cranial MRI (positive)
|
3 (3.84%)
|
0 (0.00%)
|
3 (9.09%)
|
0.67
|
|
Spinal MRI (positive)
|
2 (2.56%)
|
0 (0.00%)
|
2 (6.06%)
|
0.316
|
|
Radiologic vasospasm
|
17 (21.79%)
|
4 (8.88%)
|
13 (39.39%)
|
0.023
|
|
Clinical vasospasm
|
11 (14.10%)
|
2 (4.44%)
|
9 (27.27%)
|
0.041
|
|
Early rebleeding
|
4 (5.12%)
|
0 (0.00%)
|
4 (12.12%)
|
0.511
|
|
EVD placement
|
7 (8.97%)
|
0 (0.00%)
|
7 (21.21%)
|
0.032
|
|
Ventriculoperitoneal shunt
|
3 (3.84%)
|
0 (0.00%)
|
3 (9.09%)
|
0.67
|
|
Mean hospital stays
|
9.8 ± 6.4
|
8.3 ± 6.4
|
13.11 ± 7.3
|
0.038
|
Five (6.41%) patients were found to have an intracranial aneurysm on the second angiogram,
all of which belonged to the nPM-SAH group. All five aneurysms detected in the repeat
DSA investigation were anterior communicating artery aneurysms and treated with clipping
or coiling.
Spinal pathologies were found in two patients (2.56%). The cervical MRI showed two
spinal arteriovenous malformations (AVMs) in the nPM-SAH group. The patients with
spinal AVMs underwent endovascular treatment.
The nPM-SAH group was significantly associated with a higher incidence of radiologic
and clinical vasospasm (p < 0.05) ([Table 2]).
Four patients (5.12%) experienced rebleeding but no definite cause of bleeding was
found even though a repeat DSA was conducted.
Hydrocephalus, which needed external ventricular drainage (EVD) placement, developed
in seven patients (8.97%), and permanent cerebrospinal fluid (CSF) diversion with
ventriculoperitoneal shunts was done in three patients (3.84%), all of which belonged
to the nPM-SAH group ([Table 2]).
The need for an EVD placement because of the development of hydrocephalus was significantly
higher in the nPM group (p < 0.05). However, no significant difference was detected between the two groups based
on the need for a permanent CSF diversion. Meanwhile, there was a significant difference
between patients who developed hydrocephalus and those without hydrocephalus, based
on the presence of intraventricular hemorrhage (5/7 [71.4%] compared with 11/71 [15.49%],
[p < 0.05]).
The mean hospital stays of the patients with nPM-SAH (13.11 ± 7.3days) were significantly
longer than that in the patients with PM-SAH (8.3 ± 6.4 days, p = 0.038).
Our results showed that patients with PMN-SAH experienced a better clinical outcome
than those with nPM-SAH (p = 0.037) ([Table 2]). We had only one mortality (1.28%) which belonged to the nPM group.
Discussion
Our results showed a better clinical outcome for patients with PM-SAH compared with
those with nPM-SAH. Moreover, patients in the PM group had a lower rate of complications.
It has been shown that patients with NSAH have a more favorable clinical outcome and
a lower incidence of complications in comparison with those with aneurysmal SAH.[13]
[14] Most studies reported a lower chance of complications for patients with PM-SAH.[3]
[15] However, there is a controversy exists in relation to the clinical outcomes and
complications of patients with nPM-SAH.[10] Andaluz and Zuccarello reported that patients with nPM-SAH have clinical outcomes
and complication rates similar to those with aneurysmal SAH. Furthermore, they found
longer hospital and intensive care stays, worse outcomes, and higher complication
rates for the nPM group compared with PM group.[16] Besoglu et al reported poorer long-term clinical outcomes and less favorable quality
of life scores for patients with nPM-SAH than those with PM-SAH.[17] Our findings are compatible with these studies. In a retrospective study in 2017,
Liang Xu et al evaluated 137 patients with NSAH. Their results showed that patients
with PM-SAH had a better clinical outcome than those with nPM-SAH at 1-year follow-up.
Furthermore, cases with PM-SAH had a lower rate of complications.[9] In another study, Konczalla et al investigated 125 subjects with NSAH. They reported
a favorable outcome for 83% of their cases. In their study, good clinical outcome
was related to good admission status, absence of hydrocephalus, and younger age.[4]
In our study, the PMN-SAH group was significantly associated with a lower incidence
of radiological and clinical vasospasm.
Akcakaya et al evaluated 81 patients with angiographic-negative SAH. They dichotomized
patients into three groups as follows: PM-SAH group (40.7%), nPM-SAH group (50.6%),
and CT-negative group (8.6%).
Repeated DSA was positive in only two cases (2.5%), both in the nPM group. Moreover,
spinal MRI revealed the responsible lesion in all the three patients (7.3%) belonged
to the nPM group. However, cranial MRI results were negative in all of the patients.
Patients with perimesencephalic bleeding had shorter hospital stays and lower Fisher
grades at the admission CT-scans.[3]
Because of the benign course and lower mortality and morbidity rates of NSAH, some
experts do not agree with further DSA investigations for cases with initial negative
angiograms.[18]
[19] On the other hand, some studies showed that repeated DSA could reveal the culprit
lesion in 2 to 21% of NSAH patients.[20]
[21] In the present study, repeat DSA investigations were positive in five patients (6.41%).
Some studies suggested a variety of conditions, including vasospasm, thrombosis, the
mass effect caused by hematoma, or technical issues such as the probable causes of
initial negative angiogram.[3]
[22]
Some studies recommended cranial MRI within the first week following the SAH[3]
A cranial MRI can detect angiographic negative vascular malformation-like cavernoma.[3]
[22] Andaluz and Zuccarello performed cranial MRI on 92 patients of their study group
with no positive results[16] Topcuoglu et al performed cranial MRI on 49 patients with NNSAH. Their results were
also 100% negative.
Some studies have reported spinal lesions as a source of bleeding in approximately
1 to 3% of cases with NSAH.[16]
[23] However, the significance value of spinal MRI as a diagnostic modality for NSAH
has not been evaluated in clinical studies. Spinal pathologies were found in two cases
(2.56%) of our patient series.
Maslehaty et al performed craniocervical MRI in all 179 patients with NSAH and reported
negative results in all of the patients.[24]
Germans et al detected a 9% incidence of spinal pathologies in their patients with
nPM-SAH.[25] However, they performed whole spine MRI in 51 patients with PM-SAH and reported
100% negative results.[26]
Limitations
The present study has several limitations. This is a retrospective study and some
confounding variables may have not been measured and collected due to the retrospective
nature of this study. Furthermore, the single-center study could have limited the
generalizability of our findings despite the good outcome. Further investigations
with long-term functional, psychological, and social outcomes would be of great interest.
Conclusions
Our results showed that patients with NSAH had favorable clinical outcomes. The PM
group had better clinical outcomes and lower complication rates in comparison with
the nPM group. Repeated DSA examinations are strongly recommended for patients with
nPM-SAH.
