Hydrocephalus after Subarachnoid Hemorrhage ... Hydrocephalus after Subarachnoid Hemorrhage: Pathophysiology,

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  • Review ArticleHydrocephalus after Subarachnoid Hemorrhage:Pathophysiology, Diagnosis, and Treatment

    Sheng Chen,1,2 Jinqi Luo,1,2 Cesar Reis,3,4 Anatol Manaenko,5 and Jianmin Zhang1,2,6

    1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China2Brain Research Institute, Zhejiang University, Hangzhou, China3Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA4Department of Preventive Medicine, Loma Linda University, Loma Linda, CA, USA5Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany6Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, China

    Correspondence should be addressed to Jianmin Zhang; zjm135@vip.sina.com

    Received 18 November 2016; Accepted 1 February 2017; Published 8 March 2017

    Academic Editor: Robert M. Starke

    Copyright 2017 Sheng Chen et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Hydrocephalus (HCP) is a common complication in patients with subarachnoid hemorrhage. In this review, we summarize theadvanced research on HCP and discuss the understanding of the molecular originators of HCP and the development of diagnosesand remedies ofHCP after SAH. It has been reported that inflammation, apoptosis, autophagy, and oxidative stress are the importantcauses of HCP, and well-known molecules including transforming growth factor, matrix metalloproteinases, and iron terminallylead to fibrosis and blockage ofHCP. Potential medicines forHCP are still in preclinical status, and surgery is themost prevalent andefficient therapy, despite respective risks of different surgicalmethods, including lamina terminalis fenestration, ventricle-peritonealshunting, and lumbar-peritoneal shunting. HCP remains an ailment that cannot be ignored and even with various solutions themedical community is still trying to understand and settle why and how it develops and accordingly improve the prognosis of thesepatients with HCP.

    1. Introduction

    Hydrocephalus (HCP) is a serious and common complicationin the clinical course of subarachnoid hemorrhage (SAH),which continues to be vague until now. According to var-ious background and clinical circumstances, wide range ofincidence of HCP in SAH patients from 6 to 67% has beenreported; in most recent studies this percentage is about20% 30%.

    HCP occurs in about one fifth of patients in the earlycourse (acute in the first 3 days or subacute in the 414 days)of SAH,while chronic hydrocephalus happens in 10%20%ofpatients later in the course of SAH (after 2 weeks). Regardlessof the occurring period, HCP impairs patients neurologicfunction and leads to deterioration of functional outcomes,especially with intraventricular hemorrhage (IVH), even ifthe primary SAH has been treated [1]. On the contrary, betteroutcomes occur if SAH is recognized early and treated.

    Despite not having satisfactory preventive treatments,there have been several therapeutic methods developed todeal with hydrocephalus or to minimize the necessity ofpermanent shunts. Intraoperatively, lamina terminalis fen-estration (LTF) with thorough lavage of blood clots out ofventricles and cisterns is carried out in order to reconstructthe normal flow course of cerebrospinal fluid (CSF) andalso to eliminate the impairments by blood clots and itsby-products. Postoperatively, temporary intraventricular orlumbar drainage is a technique used to transfer CSF reab-sorption. For patients without intraventricular catheters orlumbar drains but with persistent symptoms, serial lumbarpunctures are necessary. Despite these efforts to prevent theoccurrence, a considerable number of patients are in need ofa perennial shunt for CSF.

    In this review we summarize the research of SAH-induced HCP and discuss the etiology, diagnosis, andtreatment. With this field advancing thanks to the efforts

    HindawiBioMed Research InternationalVolume 2017, Article ID 8584753, 8 pageshttps://doi.org/10.1155/2017/8584753

  • 2 BioMed Research International


    Normal brain Sah with thickened leptomeninx

    Dura mater

    Superior sagittal sinus

    Subarachnoid space

    Cerebral parenchyma

    Arachnoid granulation

    Figure 1: After SAH, the subarachnoid space is filled with blood cells and products. Leptomeninx is detected thickened with hemosiderindeposits, which has also been confirmed histologically.

    Blocked by blood clots

    Normal arachnoidgranulation

    granulationNormal arachnoid

    Arachnoid fibrosis

    Obstructed arachnoidgranulation

    Figure 2:This picture shows the major pathological mechanisms in arachnoid granulations; the upper ones demonstrate the blood clots andcorresponding products blocking the outflow tract of CSF and the inferior ones show the fibrosis of arachnoid membrane meanwhile.

    of many researchers, questions and problems on treatmentand prevention remain to be solved and applied to clinicalpractice.

    2. Etiology

    About one third of patients admitted with SAH have perma-nent CSF diversion. A large-scale meta-analysis reported thatshunt-dependent HCP accounts for a proportion of 17.4% [2].Patients with acute course, in-hospital complications, IVH,poor admission status, rehemorrhage, location of rupturedaneurysm, and age 60 reported a higher risk of shuntdependency [35].

    Achievements and progress in studying hydrocephalyinevitably fall short of elucidating the entire mechanism ofHCP after SAH. The theories mentioned hereinbefore meetthe questions of researchers approximately through damageto arachnoid granulations (AGs) as well as to brain tissue.Mechanisms seem to be interweaving among the pathogen-esis of acute and chronic HCP. It is generally accepted thatthe inflammatory reaction (either chronic or acute) and the

    ensuing fibrosis process impede fluent CSF flow outwardto sinus, terminally from AGs. Beside the proliferation ofleptomeningeal cells (Figure 1), studies at present primar-ily target the pathological obstruction of AGs, includingthe mechanical blockage and fibrosis of AGs (Figure 2).Researchers have been long working on attenuating thispathogenesis to deal with HCP [6, 7].

    Researchersmostly focus on the pathophysiology of braininjury after SAH, and prevalent theories include inflamma-tion, apoptosis, autophagy, and oxidative stress (Figure 3).Vasospasm of choroidal artery probably originates HCPthrough stenosing the aqueduct and impairing ependymalcells after SAH [8]. Devascularization of brain parenchymalikely results from sequential vasospasm of SAH and isconfirmed to induce the proliferation of neural stem cellsdirected by glia cells [9]. Gliocytes, different from otherorgans of the body, play the destructive and curative rolesand release plenty of cytokines when the brain suffers variouslesions [10]. Matrix metalloproteinases are believed to becrucial and versatile participants in breaking down blood-brain barrier (BBB) [11], and the tissue inhibitors of matrix

  • BioMed Research International 3

    Necrosis Apoptosis



    Fibrosis ofCsf tract

    Hydrocephalus &neuropathy



    MMPs Hemosiderin

    Chemical stimulus



    Injury versus repair

    Oxidative injury




    Figure 3: This picture shows some broadly verified molecules or pathways that are involved in the pathophysiogenesis of hydrocephaluscaused by SAH.

    metalloproteinases have been verified to share the homol-ogous protective effects in vasospasm after SAH for BBBintegrity in apoplectic patients [12]. In addition, researchersfound that the vegetative nervous system plays an auxiliaryrole in the inflammatory response and may contribute to thebreakdown of BBB, which consists of glia cell both struc-turally and functionally [13]. Vascular endothelial growthfactor protein levels rise and restrict the growth of abnormalblood vessels [14]. Subsequently, the hypersecretion of CSFtriggers or exacerbates its circulatory disorder and eventuallyleads to HCP.

    Acute HCP contributes to the causes of early braininjuries [15], usually thought as the noncommunicating (orobstructive) type, and is largely attributed to the mass effector blood clots within the ventricles and aqueduct, preventingCSF flow out of the cranial vault. In addition, inflammationis believed to be the crucial biomolecular mechanism thatinduces acute HCP through disruption of BBB [16]. Nev-ertheless, recent research illustrated radiologically similarperformances between acute and chronic HCP, indicatingpartially similar pathogenesis. Phase-contrast MRI demon-strated that chronic HCP turns out to be of communicatingform; however, some of these individuals still develop acuteHCPafter SAHdespite the absence of IVHor blood clot in theventricles [17, 18]. Parallel parameters of CSF flow found intheir studies also indicated that obstructionmight not be soleinitiator of acute HCP. Additionally, Kanat et al. postulatedthat blood clots play the initial role in triggering hypersecre-tion of CSF and fibrosis of arachnoid granulations, leading tolong-term communicatingHCP rather thanmerely aqueductobstruction or stenosis [19]. Whether it is communicating,obstructive, or a pathophysiological hybrid, it may directlyaffect the treatment decision and corresponding prognosis ofthese patients. Despite many discoveries and advances, more

    evidence is needed to uncover and explain the etiology ofacute HCP following hemorrhage.

    Conversely, a considerable number of patients withchronic HCP have no increased in