Nivedita Agarwal1,2, Ardalan Zolnourian3, Ian Galea4, Roxana O Carare5, and Diederik Bulters6
1Radiology, Santa Maria del Carmine Hospital, Rovereto, Italy, 2Center for Mind/Sciences, CIMeC, Rovereto, Italy, 3Neurosurgery, University of Southampton, Southampton, United Kingdom, 4Clinical neurosciences, University of Southampton, Southampton, United Kingdom, 5Neuropathology, Faculty of medicine, Southampton, United Kingdom, 6Neurosurgery, University Hospital Southampton, Southampton, United Kingdom
Synopsis
One of the
major complications of subarachnoid hemorrhage (SAH) is vasospasm which could
last days. This could affect the clearance of interstitial fluid (ISF) from the
brain parenchyma by restricting its movement along the intramural periarterial
drainage (IPAD) pathway. This would result in dilated perivascular spaces (PVS)
which have been shown to be an MR biomarker of failure of IPAD. We explore the
hypothesis that patients with hemorrhage will present with an increased
prevalence of PVS at six months.
BACKGROUND
Annual incidence
of aneurysmal subarachnoid hemorrhage (aSAH) is 9.1/100,000 population. Microvascular
spasm can lead to one of the major complication of aSAH known as delayed
ischemic neurological deficit, affecting 20-30% of patients. This could affect
the clearance of interstitial fluid (ISF) from the parenchyma. ISF and solutes
are eliminated from the parenchyma along the walls of the capillaries and
arteries via the intramural periarterial drainage pathway (IPAD) 1. The motive force for IPAD appears
to be derived from the strength of arterial smooth muscle cell contraction.
Dilated PVS are a sign of failure of fluid drainage through IPAD2. There is also evidence that there
is an increased risk of dementia amongst survivors of SAH3,4. In this study we explore the
hypothesis that after SAH there is increased prevalence of dilated PVS by
reviewing magnetic resonance scans of patients with SAH and without SAH. MATERIALS AND METHODS
We
retrospectively collected MRI data from 38 patients with aSAH (Fisher 3 and 4)
performed at six months (Group A) and from 17 patients with asymptomatic
aneurysms and no prior history of brain hemorrhage (Group B). MR was performed
on a Siemens 3T scanner and data was evaluated using the following sequences:
T2-weighed SPACE (TR/TE 3200/210ms; 1mm slice thickness; no gap) and T1-MPRAGE
(TR/TE 2200/2.45ms; 1mm slice thickness; no gap). All data was anonymized and
examined by an external experienced neuroradiologist. All scans were rated for
the prevalence of prominent PVS and their location. The presence of lacunes,
gliotic foci were also noted to identify small vessel disease and was ranked
according to Fazekas classification. RESULTS
The two
groups were matched for age and sex. There was a significant difference
(p=0.0002) in the prevalence of prominent PVS in patients in Group A and B
(76.3% vs 23.5% respectively). The distribution of PVS was mostly seen in
either the basal ganglia only or both basal ganglia and centrum semiovale (CSO)
(52.6% and 26.3%). The presence of PVS in basal ganglia alone was also
significantly increased (p=0.004) in patients who suffered SAH with respect to
patients in Group B. The presence of
white matter hyperintensities (WMH) or lacunes was not significantly different
among the two groups. MR representative images for a patient in Group A and
Group B are illustrated in Figures 1, 2 and 3. DISCUSSION
In this
study the prevalence of dilated PVS was significantly higher in patients with
SAH as compared to controls. This suggests that there is impaired drainage of
ISF. A possible mechanism is that fibrin or blood breakdown products from CSF
can enter the glymphatic pathway consisting of pial basement membrane thereby interfering
with arterial constriction and IPAD (Figure 4). Future studies should aim to test this in
experimental models. Therapeutic strategies should consider prevention of
dementia due to failed drainage. Acknowledgements
We are grateful to Prof. Roy Weller for his precious suggestions. References
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Page AM, Nicoll JAR, Perry VH, et al. Solutes, but not cells, drain from the
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DJ, Carare RO. White Matter Changes in Dementia: Role of Impaired Drainage of
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D, Charidimou A, et al. MRI-visible perivascular space location is associated
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