Key-words: Intracranial aneurysm - nonaneurysmal subarachnoid hemorrhage - non perimesencephalic
- perimesencephalic - subarachnoid hemorrhage
Introduction
Spontaneous nonaneurysmal subarachnoid hemorrhage (NA-SAH) is a heterogeneous disease
with variations in clinical course and outcome as compared to the aneurysmal SAH.[[1 ]] NA-SAH is found in up to 15% of patients with spontaneous SAH,[[1 ]],[[2 ]],[[3 ]],[[4 ]],[[5 ]] whereas 20%–70% of SAH has a perimesencephalic (PM) location.[[6 ]] PM-SAH often shows a favorable prognosis, low risk of complications, and shorter
hospital stay as compared to the aneurysmal SAH,[[1 ]],[[7 ]] or non-PM (NPM) SAH,[[1 ]] respectively. However, both PM-SAH and NPM-SAH have better clinical outcome comparing
to the aneurysmal SAH.[[8 ]]
The clinical course of the NA-SAH is not well defined in the literature. Few series
exist to define the risk factors, clinical presentations, and outcomes in NA-SAH.[[2 ]],[[9 ]],[[10 ]],[[11 ]],[[12 ]],[[13 ]] Therefore, we aimed in our study to identify the risk factors, clinical and neurological
status at the initial presentation, radiographic appearance, complications, and outcome
of the patients with spontaneous NA-SAH at the time of discharge and 3 months' follow-up.
We conducted a retrospective study to investigate the clinical and functional outcomes
of patients with spontaneous NA-SAH in short-term follow-up.
The objective of this study was the analyses of risk factors, clinical observations,
radiologic characteristics, and outcome in patients with NA-SAH.
PM SAH is described as the entity in which the blood is inferior to Liliequist's membrane
(LM) (i.e., PM and/or prepontine cisterns) extension into the suprasellar cistern
is common. Significant amounts of blood penetrating LM to the chiasmatic, Sylvian,
or interhemispheric cisterns should be viewed with suspicion as shown in [[Figure 1 ]]. While an NPM-SAH pattern has a more diffuse blood distribution that exceeds the
previously mentioned regions.[[7 ]] that is, it might extend to areas beyond the cisterns such as the proximal part
of Sylvian fissure either bilaterally or unilaterally as shown in [[Figure 2 ]].
Figure 1: Peri mesencephalic subarachnoid hemorrhage
Figure 2: Non-Peri mesencephalic subarachnoid
Computed tomography (CT) scan images were reviewed by two experienced radiologist,
for diagnosis and formulating a treatment plan, the mean interobserver kappa coefficient
was 0.97
Patients and Methods
Inclusion criteria were as follows: (i) age over 18 years, (ii) spontaneous SAH, (iii)
negative 2 subsequent cerebral angiography, (iv) no previous history of aneurysms,
and (v) regardless of intraventricular hemorrhage (IVH). We collected retrospective
data for the patients with NA-SAH admitted to Hamad General Hospital, Doha, Qatar,
from May 2008 to September 2018. Ninety-two consecutive patients were identified from
the medical database. CT scan confirmed SAH. 6-vessel angiography (digital subtraction
angiography [DSA]) was used twice to rule out any intracranial vascular pathologies
in the early and late stages. Fifteen patients were excluded; 6 had no late follow-up
DSA, 6 cases had no follow-up after discharge, and 3 had incomplete medical records.
Patient demographics and radiological features
The patient characteristics, including medical identification number, age, gender,
comorbidities, neurological status at the initial presentation, clinical course, radiographic
or angiographic features, and clinical outcome were recorded.
Glasgow Coma Scale (GCS) and World Federation Neurosurgical Surgeon (WFNS) Score were
used to evaluate the initial neurological status of the patients with NA-SAH. Patients
were further dichotomized based on the location of blood on the CT scan into PM and
NPM SAH. PM was defined if the SAH was limited mainly to the PM cisterns.[[7 ]],[[14 ]] NPM was defined if the pattern of bleeding was extending to the Sylvian and interhemispheric
cistern, and not limited to the PM cisterns.[[7 ]],[[14 ]]
Prophylactic antiepileptic was given in most patients; calcium channel blocker (Nimodipine)
was added to the patients from the 1st day of admission and stopped after negative
second angiogram (late DSA). All patients underwent a second angiogram with a time
frame of 7–10 days after onset.
Clinical and functional outcome measures
Primary outcome measures included the determination of clinical outcome at discharge
using the modified rankin scale (mRS), as shown in [[Table 1 ]]. Secondary outcome includes any cardiopulmonary complications, vasospasm and/or
electrolyte disturbance. The placement of the intracranial shunt system was also recorded.
Table 1: Modified Rankin scale
The functional outcome of the patients was evaluated with modified Rankin scale (mRS)
at 3 months after the presentation. The patients were followed up by reviewing the
patient clinical data records from the outpatient clinic. Patients clinical status
was further dichotomized into good and poor clinical, functional outcome based on
these scales.
Complications
Delayed cerebral ischemia (DCI) was defined if the patient has deteriorated in the
neurological status that cannot be defined by any other factor.[[15 ]] It was identified either by clinical presentation or CT scan perfusion.
Hydrocephalus was defined if the CT scan showed the temporal horns to be over 3 mm.
Early hydrocephalus was defined from the initial presentation to 3 days, whereas late
hydrocephalus was considered from 4 to 14 days. While Hyponatremia defined as serum
sodium level less than 135 mmol/l.
Statistical analysis
Continuous variables are summarized by mean and standard deviations and were compared
by performing the unpaired Student's t-test. Categorical data were expressed by absolute
frequencies (n) and percentages (%) and were analyzed by Chi-square test or Fisher's
exact test. We focused on clinical, functional outcome by dichotomizing it into favorable
and poor clinical outcome. We performed all statistical analysis using IBM® SPSS®
Statistics V22.0 (IBM, Chicago, Illinois, USA). A P = 0.05 or less showed a statistically
significant difference.
Results
Statistic of the independent variable is shown in [[Table 2 ]] and [[Table 3 ]].
Table 2: Demography of all patients after
Table 3: Statistical analysis of different features with the corresponding P value
Gender
Twenty-two females and 55 males with a mean age of 48.5 ± 8.4 and a range of 30–71
years were identified.
Comorbidities
About 55.8% of the patients were previously healthy with no comorbidities, 15.6% had
hypertension, while diabetes mellitus (DM) was found in 15.6% of the patients, 6.8%
were smokers, 13% were asthmatic or had deep venous thrombosis or a history of chronic
obstructive pulmonary disease (COPD).
Clinical presentation
Clinical presentation includes headache in 73 patients (94.8%), along with vomiting
in 24 patients (31.6%) and low level of consciousness in 8 patients 10.4%, all (100%)
of them were of NPM SAH subtype [[Graph 1 ]]. In our series WFNS score at presentation was 75.3%, 14.3% and 10.4% for Grade
I, II and IV respectively as shown in [[Graph 2 ]].
Graph 1: Clinical presentation, please notice that headache is the most common presenting
symptoms in our series
Graph 2: Initial World Federation Neurosurgical Surgeon grades at presentation. Grade I World
Federation Neurosurgical Surgeon was the most common grade at presentation followed
by Grade II and then Grade IV
Radiographic features
Forty-seven (61.03%) on CT scan had NPM SAH distribution, while 30 (38.96%) had PM
SAH distribution. Eighteen patients (23.4%) of the patient had an IVH; however, 77%
(14 patients) of these 18 were NPM SAH subtype. In addition to that 76.6% of the patients
has Grade III on Modified fischer scale as shown in [[Graph 3 ]].
Graph 3: Modified Fischer grading System, Grade III was the most common grade at presentation,
please notice the at Grade I and II were not seen in our series
Clinical outcome
All patients had GCS 15 at discharge with good clinical outcome functional outcome
(mRS 1) at 3 months after discharge, as stated in [[Graph 4 ]].
Graph 4: Functional outcome at 3 months, functional outcome was associated with good outcome
in both groups of nonaneurysmal subarachnoid hemorrhage
Complications
During the stay in our hospital, only 2 patients had seizures and 2 patients had low
Na+ (below 135 mmol). Eighteen patients had an IVH, Around 77% (14 patients of IVH
patients) were NPM SAH subtype, and none of the patients had clinical or radiological
evidence of vasospasm, and around 8 patients from patients who had IVH needed external
ventricular drain (EVD) insertion, but none of them needed a permanent shunt as shown
in [[Graph 5 ]].
Graph 5: Complication, external ventricular drain need and hydrocephalus was common at presentation,
but no patients need any permanent shunt
Thirteen patients developed hydrocephalus, and 13 patients needed EVD placement with
no permanent shunt placement in our series of patients, 77% (10 patients out of 13
patients) who needed EVD have NPM SAH subtype.
Discussion
About 15% of patients with spontaneous SAH approximately have negative findings regarding
the bleeding source.[[1 ]] Spontaneous SAH is not a homogenous disease. There are differences in the clinical
course and outcome in patients with and without aneurysmal SAH.[[1 ]] PM-SAH makes up 21%–68% of negative DSA.[[16 ]] Even if the angiographic results are negative, repeated angiography reserves its
essential to identify a potential source of bleeding after an acute phase.[[17 ]] In our cohort, all patients underwent a second angiogram within 7–10 days from
presentation, around 17% of cases with spontaneous SAH, has negative angiogram, we
take this percentage from a review done within our center.
Theories are controversial, but it can be assumed that the NA-SAH may be due to rupture
of the perforating arteries or capillaries, arterial dissection, especially basilar,
cavernous malformations, arteriovenous malformations, and superficial or deep vein
thrombosis.[[16 ]],[[17 ]],[[18 ]],[[19 ]],[[20 ]],[[21 ]] In our study, we have found 15.6% of the patients who had arterial hypertension,
15.6% had DM, 6.4% were smoker and 13% of the patients have other comorbidities (asthmatics,
COPD, and deep venous thrombosis), these comorbidities share in the potential high
venous pressure, Although none of these comorbidities has statistical significance
(P > 0.05) [[Table 3 ]] which could be due to small study sample. This might be a risk factor for developing
NA-SAH, but case–control study remains needed with large sample size.
It is different among various studies in identifying the incidence of NA-SAH among
gender; it varies from female predominance,[[6 ]],[[22 ]] to no predominance,[[23 ]] to male predominance.[[8 ]],[[2 ]],[[23 ]] In our study, 71.4% of males had NA-SAH. However, younger age and female sex have
been considered as a risk factor for NA-SAH.[[17 ]],[[23 ]] In our cohort, female sex reaches a statistical significance with P = 0.037. Male
predominance in our cohort could be due to male predominance in Qatar. In 2015, male
to female ratio for Qatar was 316.85 males per 100 females.[[24 ]]
Clinical presentation
As Konczalla et al.[[25 ]] 2014 reported, 85% of the patients with NA-SAH had WFNS Grade I–III at their initial
presentation (P < 0.07). Our study also suggested that almost 58 (75.3%) of the patients
had GCS 15 (WFNS Grade 1) at their initial presentation. PM-SAH has relatively favorable
initial neurological status.[[18 ]],[[19 ]],[[25 ]] In our data, patients with NPM-SAH had initial severe symptoms with low GCS (GCS
≤12) as all patients with WFNS Grade IV had NPM SAH, and 3 of them had GCS <10 as
compared to the PM-SAH.
Radiographic features
The percentage of patients with PM SAH (38.96%) in our cohort is lower than what reported
by Van Calenbergh et al.[[26 ]] and Cánovas et al. (56%).[[27 ]] This is because SAH is relatively different percentages from regions to others.
In our series, NPM-SAH had higher modified Fisher grade in comparison to PM SAH, as
77% of patients (14 Patients) with Grade IV Modified Fisher grade were NPM SAH subtype,
while only 4 patients were with PM SAH.
Clinical outcome and complications
Compared to aneurysmal SAH, NA-SAH excellent clinical outcome and prognosis, with
low risk of complications that include rebleeding, vasospasm, hydrocephalus, and DCI.[[18 ]],[[19 ]] The rebleeding rate in PM SAH is lower than NPM-SAH,[[25 ]] and thus, it has a great impact on the clinical outcome of the patients with SAH.[[20 ]] In our retrospective study, no patient had rebleeding. Clinical vasospasm unrelated
to angiography is rare,[[27 ]] and there is only 1 case reported by Sheehan et al.[[26 ]] with good clinical outcomes. In our series, none of the patients developed clinical
or radiological vasospasm clear by the second angiogram.
Rinkel et al.[[14 ]] described hyponatremia in 29% of cases with NA-SAH (Na+ low than 135 mM). In our
study, only two patients developed asymptomatic hyponatremia (Na dropped to <135)
and were treated with salt supplementation and improved over the next days. This correlates
with the findings in case series by Cánovas et al.[[27 ]] in which none of the patients developed hyponatremia.
Early hydrocephalus had a higher rate of incidence in patients with the PM-SAH as
found in 1 series,[[25 ]] but the placement of permanent of the ventricular shunt system is 3%–13.5%.[[6 ]],[[8 ]],[[16 ]],[[21 ]] As per Cánovas et al.,[[27 ]] only one patient with PM bleeding pattern had hydrocephalus that required the shunt
placement. This correlates with our findings as stated in our study, 13 patients had
initial EVD placement as shown in Graph 4, but none of the patients had a permanent
shunt in place. However, it worth to mention here that 77% (10 patients out of 13
patients) who needed EVD where exclusively have NPM SAH subtype.
The prognosis of the patients with NA-SAH is much more favorable than aneurysmal SAH
as clear by studies.[[4 ]],[[6 ]],[[27 ]] Our study also suggested that NA-SAH has a favorable outcome apart from whether
it occurred, at PM or NPM location. Although NPM-SAH might have a worse initial presentation,
higher Fisher grade, and more patients need EVD insertion, but the functional outcome
at 3 months is the same.
Conclusions
NA-SAH does not affect the short- and long-term prognosis. In our results, the pattern
of bleeding affects the initial presentation, clinical course, and complications.
The clinical and functional outcomes in the majority of our patients were comparable
in both groups with good prognosis. Hypertension, smoking, and elevated venous pressure
like a history of deep venous thrombosis and asthma might be considered as a risk
factor.
Limitations
A limitation of our monocentric study is the retrospective design and relatively small
number of patients after NA-SAH. In addition, we based our data on the retrospective
chart review of a detailed clinical outcome; therefore, there are potential errors
in charting and individual history.
