Chapter 5

Cerebrospinal fluid circulation and hydrocephalus

VILLE LEINONEN1*, RITVAVANNINEN2, AND TUOMAS RAURAMAA31Department of Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland and Department of Neurosurgery,

NeuroCenter, Kuopio University Hospital, Kuopio, Finland2Department of Radiology, Institute of Clinical Medicine, University of Eastern Finland and Department of Radiology,

Kuopio University Hospital, Kuopio, Finland3Department of Pathology, Institute of Clinical Medicine, University of Eastern Finland and Department of Pathology,

Kuopio University Hospital, Kuopio, Finland

Abstract

Hydrocephalus (HC) is classically defined as dynamic imbalance between the production and absorptionof cerebrospinal fluid (CSF) leading to enlarged ventricles. Potential causative factors include variousbrain disorders like tumors causing obstruction of CSF flow within the ventricular system or the subarach-noid space. Classification of HC is based on the site of CSF flow obstruction guiding optimal treatment,with endoscopic third ventriculostomy in intraventricular obstruction and CSF shunt in communicatingHC. Another clinically relevant classification is acute and chronic; the most frequent chronic form isidiopathic normal-pressure hydrocephalus (iNPH). The reported incidence of HC varies according tothe study population and classification used. The incidence of congenital HC is approximately0.4–0.6/1,000 newborns and the annual incidence of iNPH varies from 0.5/100,000 to 5.5/100,000. Radio-logically, ventricular dilatation may be nonspecific, and differentiation of iNPH from other neurodegen-erative diseases may be ambiguous. There are no known specific microscopic findings of HC but asystematic neuropathologic examination is needed to detect comorbid diseases and possible etiologic fac-tors of HC. Depending on the etiology of HC, there are several nonspecific signs potentially to be seen.

Hydrocephalus (HC) is classically defined as dynamicimbalance between the production and absorption ofcerebrospinal fluid (CSF), leading to enlarged ventricles.However, there are several disorders of CSF circulationnot included in this definition. Furthermore, enlargedventricles are often seen in radiologic imaging withoutclassic symptoms of increased intracranial pressure(ICP). Normal ICP depends on posture, ranging from 5to 15 mmHg in the supine and from –5 to +5 mmHg inthe erect posture.

CSF circulation

In adults, CSF is formed at the rate of approximately20 mL/hour or 500 mL/day (McComb, 1983). CSF is

mostly formed in the choroid plexus (80%), by passivefiltration across the capillary endothelium and regulatedsecretion across the choroid epithelium (Milhorat,1975; McComb, 1983; Brinker et al., 2014). CSF is alsoformed by the ependymal lining of the ventricular systemand the surrounding brain parenchyma (Milhorat, 1975;McComb, 1983; Brinker et al., 2014).

CSF, formed in the lateral ventricles, flows throughthe interventricular foramina of Monro to the thirdventricle and through the cerebral aqueduct to the fourthventricle (Milhorat, 1975). CSF exits the ventricular sys-tem through the median aperture (foramen of Magendie)and lateral apertures (foramina of Luschka) of the fourthventricle into the subarachnoid space or through the obex

*Correspondence to: Ville Leinonen, Department of Neurosurgery, NeuroCenter, Kuopio University Hospital, P.O. Box 100, 70029KYS, Finland. Tel: +358-447172303, E-mail: ville.leinonen@kuh.fi

Handbook of Clinical Neurology, Vol. 145 (3rd series)NeuropathologyG.G. Kovacs and I. Alafuzoff, Editorshttp://dx.doi.org/10.1016/B978-0-12-802395-2.00005-5Copyright © 2018 Elsevier B.V. All rights reserved

http://dx.doi.org/10.1016/B978-0-12-802395-2.00005-5

into the central canal of the spinal cord (Milhorat, 1975).From the subarachnoid space, CSF is absorbed into theblood circulation via the villi of the arachnoid granula-tions that project into the venous sinuses (Milhorat,1975; McComb, 1983; Brinker et al., 2014). The tradi-tional view of CSF circulation has been challenged bythe glymphatic circulation of the brain (Bulat andKlarica, 2011; Brinker et al., 2014, Ueno et al., 2016):CSF seems to drain into the cervical lymphatic vesselsthrough the cribriform lamina (Kida et al., 1993), peri-vascular lymphatic drainage within the walls of cerebralcapillaries and arteries (Weller et al., 2009; Carare et al.,2014), and dural lymphatic system (Aspelund et al.,2015; Louveau et al., 2015).

Normally, the rate of CSF formation and absorption isthought to be balanced. The total volume of CSF in adultsis 90–200 mL (McComb, 1983; Kohn et al., 1991;Brinker et al., 2014)with up to 100 mL in the spinal canal

(Edsbagge et al., 2011). In the pathologic states of CSFturnover, formation and absorption are in disequilibrium,leading to disproportionately enlarged volume of CSF,or HC. Potential causative factors include a papillomaof the choroid plexus (increased formation) and anobstruction of CSF flow within the ventricular system(Fig. 5.1) or in the subarachnoid space (decreasedabsorption) (Milhorat, 1975).

CLASSIFICATION

Clinically the most relevant classification is based on thesite of CSF flow obstruction guiding the primary treat-ment modality (Rekate, 2011). Most frequent sites ofintraventricular obstruction starting from the lateral ven-tricle are the foramen ofMonroe (typically caused by col-loid cyst), third ventricle (Fig. 5.2), aqueduct of Sylvius(aqueduct stenosis, Fig. 5.3), and fourth ventricle (typi-cally tumor, Fig. 5.4). Although extraventricular obstruc-tion is traditionally classified as communicating HC,extraventricular (but subconvexity) obstruction is alsothought to occur (Fritsch et al., 2014). Accurate neuroim-aging techniques are needed to demonstrate CSF path-ways precisely.

Based on the symptoms HC can be classified as acuteor chronic. Both forms can be either communicating orobstructive.

Nonobstructive HC can be classified also based onthe etiology. Up to 95% of HC is thought to becaused by impaired absorption of CSF. Choroid plexustumors (Fig. 5.2) are the rare cause of potentiallyincreased formation of CSF. Increased CSF pressurecan occur without enlargement of brain ventricles andwithout obvious etiology such as idiopathic intracranialhypertension (IIH).

Fig. 5.1. Acute obstructive hydrocephalus (*) caused by bilat-

eral cerebellar infarction (arrows) in an elderly man.

Fig. 5.2. Nine-month-old boy with rapidly growing head and tense fontanel but no obvious clinical symptoms. Choroid plexus

papilloma (homogeneous contrast enhancement and no infiltration into brain parenchyma) fulfilling third ventricle and causing

obstructive hydrocephalus.

40 V. LEINONEN ET AL.

Chronic hydrocephalus

Adult chronic HC is often called normal-pressure HC(NPH). NPH is classically characterized with a clinicaltriad of symptoms, including cognitive impairment, gaitdifficulty, and urinary incontinence. Enlarged brain ven-tricles usually occur with obliterated parasagittal corticalsulci (Relkin et al., 2005).

When predisposing factors such as subarachnoidhemorrhage or brain trauma are obvious, the NPH isregarded as secondary (sNPH) (Relkin et al., 2005).NPH is regarded as idiopathic (iNPH) in the absenceof known predisposing factors. NPH can also beclassified according to disproportionately enlargedsubarachnoid space HC (DESH) as DESH and non-DESH (Kitagaki et al., 1998; Mori et al., 2012).Long-standing overt ventriculomegaly in adults(LOVA) is separated from iNPH, occurs with evenlarger ventricles, and may have an obstructive etiology(Oi et al., 2000).

EPIDEMIOLOGY

Since HC is not an easily determined simple disease butrather a divergent continuum of various conditions, theepidemiologic literature is rather scarce and the reportednumbers vary according to the study population andclassification used.

Hydrocephalus in children

The incidence of congenital HC is approximately0.4–0.6/1,000 newborns (Fernell et al., 1994; Garneet al., 2010; Jeng et al., 2011), with a slight downwardtrend (Massimi et al., 2009; Sun et al., 2011). Prematurebabies are at increased risk of intraventricular hemor-rhage, which is the most frequent cause of HC in infants.Later, tumors (most often in the posterior fossa, espe-cially in the fourth ventricle causing obstructive HC)become the most frequent cause of HC. Some of thepotential etiologic factors of HC in children are listed

Fig. 5.3. Aqueduct stenosis in an 11-year-old girl causing chronic hydrocephalus with headache and dizziness. Midsagittal con-

structive interference in steady state (CISS) magnetic resonance imaging indicating open fenestration from third ventricle intobasal cisterns (flow).

Fig. 5.4. A tumor in the fourth ventricle (neurocytoma) causing hydrocephalus in a 7-year-old boy. (Reproduced from B€ohm J,ImmonenA, Riikonen P, et al. (2006) Case report: central neurocytomawith concomitant cerebral involvement by acute lymphatic

leukemia. Hum Pathol 37: 488–492.)

CEREBROSPINAL FLUID CIRCULATION AND HYDROCEPHALUS 41

in Table 5.1. Still in the time ofmagnetic resonance imag-ing (MRI), idiopathic HC counts for approximately 10%.In MRI, obstructive membranes in CSF pathways, espe-cially in the fourth ventricular exit foramina, may berevealed by three-dimensional constructive interferencein steady state (3D-CISS) sequences at 3.0 T, while con-ventional images remain insensitive (Dinçer et al., 2009).HC itself is a treatable condition and thus seldom fatal,leading to its gradually increasing prevalence with age.The mortality is mostly caused by malignant etiologiesor severe congenital malformations.

Chronic hydrocephalus

The most common form of adult HC is iNPH. iNPH isseldom seen under the age of 60 (when it is usuallydue to a known etiology, i.e., sNPH); after that the inci-dence increases gradually with aging, the median age ofdiagnosis being over 70. The reported annual incidenceof iNPH varies from 0.5/100,000 to 5.5/100,000(Vanneste et al., 1992; Brean and Eide, 2008). The esti-mated prevalence is 22/100,000, increasing with age andvarying in elderly populations from 0.5% up to 5.9%(Brean and Eide, 2008; Iseki et al., 2009; Tanaka et al.,2009; Jaraj et al., 2014). The female-to-male ratio is closeto equal. iNPH is probably underdiagnosed since higherincidence is reported in population-based studies. The

incidence of sNPH is less studied but is estimated toinclude approximately half of cases.

Idiopathic intracranial hypertension

In Israel, the annual incidence of IIH was observed to be3.17 per 100,000 for women and 0.85 per 100,000 formen. The incidence rate in females of child-bearingage (18–45 years) was 5.49 per 100,000. The female-to-male ratio for individuals >17 years old was 6.1:1(252 females and 41 males) and 2.1:1 (60 females and28males) for ages 11–17 years. Obesitywas documentedin 83.4% of patients and the incidence of IIH seems to beincreasing, probably due to increasing obesity (Kesleret al., 2014).

CLINICAL PHENOTYPES AND IMAGING

Symptoms of acutely increased ICP include typicallyheadache, nausea, vomiting, and eventually coma. Fre-quent symptoms are also visual disturbance (gaze pare-sis, reduced vision) and dizziness. Acutely computedtomography (CT) indicates or excludesHC. For etiologicevaluation MRI (also MR angiography is considered) isusually needed (Fig. 5.5). Acute HC can be either com-municating or obstructive.MRI should also be advocatedin children and adolescents as well as in follow-up exam-inations after, for example, CSF shunting for radiationprotection reasons.

Idiopathic intracranial hypertension

The classic sign of IIH is papillary edema and the mostsevere consequence is loss of vision. Another typicalsymptom is headache. Thus, these patients should becarefully evaluated by ophthalmologist and neurologist.The primary treatment is most often acetazolamide but ifthe effect ofmedication is inadequate or themedication isintolerable, the treatment of choice is either ventricular orlumbar CSF shunt. The etiology of IIH is still open butobesity and female gender seem to be obvious risk fac-tors (Johnston et al., 2007). The preferred imagingmethod isMRI, which excludes any secondary etiologiesand classic HC. In IIH, the ventricles are small and ingeneral the imaging findings are otherwise normal butoptic nerve sheet can be dilated and an empty sella canbe observed (Fig. 5.6). Obstruction in venous sinuseshas been proposed as a potential etiology in a subgroupof patients (Higgins et al., 2002). Thus venous angiogra-phy is indicated and, in cases of obstruction, venous dila-tation with or without stenting could be attempted;however, this treatment is still considered experimentaland has the potential for severe complications.

Table 5.1

Etiology of hydrocephalus for initial shunt in children –

single-center experience in Eastern Finland 2003–2013

Etiology n (total 80) %

Intraventricular hemorrhage 15 18.8Intracerebral hemorrhage 1 1.3Aqueductal stenosis 10 12.5Arachnoid cyst 2 2.5Meningitis 2 2.5Trauma 2 2.5Tumor 22 27.5Congenital – total 18 22.5Aicardi syndrome 1Clover-leaf skull 1Dandy–Walker syndrome 1Encephalocele 1Holoprosencephaly 1Hydranencephaly 2Interhemispheric cyst 1Porencephalic cyst 1Schizencephaly 2Spina bifida 6Other anatomic abnormality 1Other 1 1.3Idiopathic hydrocephalus 7 8.8

42 V. LEINONEN ET AL.

Chronic hydrocephalus – normal-pressurehydrocephalus

The classic Hakim triad of NPH includes gait difficulty(magnetic gait with broad base and short step length),cognitive decline (typically decline in frontal executivefunctions, including amnesia, apraxia, and psychomotorslowing), and urinary incontinence. The triad is full onlyin around 50% of cases and in contrast dizziness, head-ache, and various psychiatric symptoms are rather fre-quently observed (Relkin et al., 2005; Williams andRelkin, 2013). The only effective treatment so far allevi-ating symptoms, including cognitive decline, is CSFshunt (Kazui et al., 2015). It is noteworthy that a carefulselection of patients for surgery is crucial since comorbiddiseases like Alzheimer disease (AD) often hamper thetreatment effect (Koivisto et al., 2013; Malm et al.,2013; Fritsch et al., 2014; Pomeraniec et al., 2016).

MRI is the primary imagingmodality for patients withmemory problems. MRI defines changes seen in amnes-tic disorders with higher accuracy than CT (Figs 5.7 and5.8). Accordingly, patients with presumed NPH shouldalways undergo an MRI scan. DESH is indicative ofsuprasylvian block in CSF absorption (Kitagaki et al.,1998; Mori et al., 2012).

Long-standing overt ventriculomegalyin adults

A subgroup of LOVA is usually noncommunicating (Oiet al., 2000; Fritsch et al., 2014). The ventricles are largerthan in typical communicating NPH and patients haveincreased risk of over-drainage-related complicationwith shunt and thus the primarily recommended treat-ment is endoscopic third ventriculostomy followed by

Fig. 5.5. Acute obstructive hydrocephalus in a 9-year-old boy, detected after mild trauma and headaches. Magnetic resonance

imaging with constructive interference in steady state (CISS) sequence reveals a tumor inside the aqueduct (grade II oligodendro-glioma in biopsy).

Fig. 5.6. Signs indicative of idiopathic intracranial hypertension in a 10-year-old boy with headaches. Distended perioptic sub-

arachnoid space and flattening of posterior sclera, together with elongation and kinking of the left optic nerve (left), a partially

empty sella (middle), and hypoplastic left transversal sinus together with a stenotic right sigmoid sinus in venous magnetic res-

onance angiography (right).

CEREBROSPINAL FLUID CIRCULATION AND HYDROCEPHALUS 43

CSF shunt if there is no response to endoscopic thirdventriculostomy.

NEUROPATHOLOGY

Macroscopy

Macroscopic evaluation in HC, including NPH, showsenlarged ventricles and usually relatively well-preservedcerebral cortex (Fig. 5.9). The angles of the lateral ven-tricles can be blunted (Lowe et al., 2008). In sNPHlesions related to subarachnoid hemorrhage, braintrauma, or other predisposing factors can be seen. Cere-brovascular lesions are frequently seen also in patientswith presumed iNPH (Leinonen et al., 2012).

Microscopy/immunohistochemistry

There are no known specific microscopic findings of HCbut a systematic neuropathologic examination is neededto detect comorbid diseases and possible etiologic factorsof HC. Depending on the etiology of HC, there are sev-eral nonspecific signs potentially to be seen. In chronicHC, frequent pathologic findings include lesions andchanges related to neurodegeneration such as amyloid-b (Ab) aggregates and hyperphosphorylated tau(Figs 5.10–5.12) to a variable extent but usually notsevere enough to fulfill the accepted diagnostic criteriafor AD or other known neurodegenerative diseases.The minimal immunohistochemical staining shouldinclude antibodies for Ab and hyperphoshorylated tau.The use of p62 is also recommended as a screening

immunohistochemistry stain. In addition, vascular alter-ations and nonspecific findings, such as gliosis, poorlystaining periventricular myelin on periventricular whitematter, chronic meningitis, meningeal and arachnoidfibrosis, and meningeal thickening, can be observed(Bech et al., 1999; Lowe et al., 2008).

Overview of the diagnostic approach

Esiri and Rosenberg (2004) described neuropathologicfindings in hydrocephalic dementia. Based on their rec-ommendations the principal goal is exclusion of definedneuropathologic entities. The alterations observedinclude ventricular dilatation with preserved cerebralcortex, fragmented ependymal lining of the lateral ventri-cles, variable gliosis of subependymal tissue, and lepto-meningeal thickening without inflammation. AD-relatedneurodegenerative lesions such as neuritic plaquesand/or neurofibrillary tangles may appear, althoughinsufficiently for the diagnosis of AD. In Esiri andRosenberg’s series, only 1 patient was shunted, i.e., thediagnosis of HC was set postmortem. Furthermore, inthe early reports most of the patients died shortly afterdiagnosis, hampering the determination of the responseto shunt treatment (Leinonen et al., 2012).

Obviously, patients with shunt-responsive iNPH mayhave several concomitant brain pathologies, especiallyvascular and AD-related lesions. All studies publishedso far have failed to detect any novel neuropathologicfeatures specific for hydrocephalic dementia (Cabralet al., 2011; Leinonen et al., 2012; Del Bigio, 2014).

Fig. 5.7. Normal-pressure hydrocephalus is often initially suspected on computed tomography based on disproportionately

enlarged ventricles compared to narrow parasagittal sulci. Radiologically, ventricular dilatation may be nonspecific, and differ-

entiation of idiopathic normal-pressure hydrocephalus from other neurodegenerative diseases may be ambiguous.

44 V. LEINONEN ET AL.

Fig. 5.8. (A–C) Clinical symptoms indicative of normal-pressure hydrocephalus correspondwith neuroradiologic findings of ven-

tricular enlargement disproportionate to the size of the sulci of cerebral convexity. Vascular degenerative changes (C) are frequent

but periventricular lucency caused by leakage of cerebrospinal fluid into the parenchyma (G) could mimic these changes and

should be noted. Enlargement of temporal horns (D) may lead to overestimation of hippocampal atrophy (E). Evan’s index

(F) is calculated as a/b. Flow void is measured from aqueduct (H). Callosal angle is measured from the level of posterior com-missura (I and J). (Reprinted with permission from Kojoukhova M, Koivisto AM, Korhonen R, et al. (2015) Feasibility of radio-

logical markers in idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien) 157: 1709–1719.)

CEREBROSPINAL FLUID CIRCULATION AND HYDROCEPHALUS 45

General limitations in all reported series of chronic HCare small number of cases, selection of the material,and various protocols in brain sampling. It is noteworthythat none of the patients autopsied so far have had iNPHas the only final clinical diagnosis. Based on the clinicalfollow-up of the basic study cohort (Koivisto et al., 2013,2016), we argue that there are selected iNPH cases withdementia but without clinical signs, neuroradiologic andbrain biopsy findings of any other known dementing dis-ease. Thus, iNPH can be a distinct pathologic entity.

However, most of the cases have mixed pathologiesand furthermore the clinical syndrome of iNPHmay haveseveral initiating pathologies.

Sampling of meninges, including dural sinuses andfresh frozen samples, is heavily encouraged.

In case there is any suspicion of CSF shuntobstruction/malfunction, the whole shunt systemshould be evaluated to find unexpected mechanical dis-ruptions potentially not noticed in the clinical evaluation(Fig. 5.13).

Fig. 5.9. Enlarged ventricles and relatively well-preserved cerebral cortex (male, 74 years).

Fig. 5.10. Cortical biopsy.Fig. 5.11. Hyperphosporylated τ positivity in a cortical biopsy(AT8 antibody).

46 V. LEINONEN ET AL.

Diagnostic criteria

As discussed above, in chronic HC AD-related changes,vascular alterations, and nonspecific findings such asgliosis and meningeal thickening have been observed.In a neuropathologic series of 10 patients with presumedNPH vascular pathology was frequent in patients withcognitive impairment (Leinonen et al., 2012; DelBigio, 2014). It is noteworthy that specific NPH lesionshave not been identified by current methodologies.

Autopsy studies of chronic HC with and withoutdementia are still urgently needed. Furthermore, the pro-tocol with extensive sampling (including meninges)beyond standard neuropathology for dementia ispreferred.

PATHOGENESIS, EXPERIMENTALMODELS, AND BIOCHEMISTRY

The clinical syndrome of hydrocephalic brain dysfunc-tion is thought to occur due to subcortical disconnection.

Enlargement of the cerebral ventricles causes gradualdestruction of periventricular white-matter axons. Sec-ondary changes occur in neuronal cell bodies and synap-ses, but with minimal death of neurons. Destroyed axonscannot be restored, but some of the brain dysfunction isreversible byCSF shunting, probably through restorationof cerebral blood flow and normalization of the extracel-lular environment (Del Bigio, 2010a, b).

White-matter rarefaction in iNPH can be caused bothby gradual CSF leakage into brain tissue and continuinghypoperfusion (Edwards et al., 2004; Krauss and vonStuckrad-Barre, 2008). Gliosis, which is usually empha-sized in periventricular white matter, is probably a con-tinuum of this process. White-matter changes seen inNPH are also associated with vascular pathologies,which is in line with the assumption that decreased cere-bral blood flow due to increased ICP is a potential path-ophysiologic mechanism causing the symptoms of NPH(Brusa et al., 1991; Silverberg et al., 2010). Fragmentedependymal lining and subependymal gliosis are probablyreactive changes to the long-standing increased pressurerather than predisposing factors leading to iNPH. Ciliastructure and function are rarely studied in the clinicalsetting (Fig. 5.14). Nevertheless, all these nonspecificlesions are likely to be only secondary to the so farunknown pathophysiologic process causing the diseaseto be not yet determined (Fig. 5.15). On the other hand,metabolite transporter expression alterations at theblood–brain barrier, deterioration of blood–brain barrierintegrity leading to protein leakage, CSF production andturnover decline, and vascular changes may all convergeon the pathology of aging and the age-related dementias.Thus, all these changes seen in iNPH patients may be ini-tiated by aging and therefore age-matched clinicallyasymptomatic autopsy controls would be of great impor-tance when assessing the significance of those lesions.

Fig. 5.12. Amyloid-b aggregates in a cortical biopsy.

Fig. 5.13. Chronically dilated ventricles in a 29-year-old male with mental retardation and repeated shunt malfunctions (fluctu-

ating headache) and consequent shunt revisions. Broken (probably intermittently drained) catheter (circled) noted from the old

X-ray only after sudden death and then confirmed in a forensic autopsy.

CEREBROSPINAL FLUID CIRCULATION AND HYDROCEPHALUS 47

Only few animal models of HC are available. Themost often used is kaolin-induced HC. Genetic defectscausing ciliopathies or ciliary dyskinesia cause severeor even fatal HC (Zang, 2014). The first gene (SFMBT1)potentially related to iNPH is expressed in choroidplexus (Kato et al., 2011). Aquaporins (AQPs) areplasma membrane proteins, which have a significant rolein the water homeostasis of the CNS. AQP-1, expressedin the choroid plexus, is involved in CSF secretionand AQP-4 in CSF absorption (Papadopoulos andVerkman, 2013). Chronic HC potentially interferes withprotein clearance. Ab pathology seems to be related todisturbed CSF dynamics since accumulation of Ab andhyperphoshorylated tau has been observed in experimen-tal HC in elderly rats (Deren et al., 2009), but interest-ingly, not in young rats (Mawuenyega et al., 2010).

Brain biopsies during HC surgery may help in the dif-ferential diagnostics and detection of concomitant neuro-degenerative diseases (Leinonen et al., 2012; Elobeidet al., 2015; Pomeraniec et al., 2016). Furthermore, theyopen a novel window for the pathobiologic research(Laiter€a et al., 2015).

Secondary hydrocephalus

HC after subarachnoid hemorrhage has been reportedto occur in 6–67% of cases (van Gijn et al., 1985;Tapaninaho et al., 1993; Vale et al., 1997). The acutephase can be self-limiting in some patients, whileothers will require CSF diversion by external ventric-ular drainage to alleviate HC symptoms (Tapaninahoet al., 1993). The mechanisms of HC developmenthave not been fully elucidated, but studies have sug-gested deterioration of CSF dynamics as a cause.Other proposed mechanisms are obstruction due toblood products, a disrupted absorption process at thearachnoid granulations level, or possibly a result ofinflammation and fibrosis (van Gijn et al., 1985;Auer and Mokry, 1990; Massicotte and Del Bigio,1999), but resolving the exact mechanisms causingthe disturbance of CSF circulation still requires furtherstudy (McAllister et al., 2015). After aneurysmal sub-arachnoid hemorrhage, ventricular and sulcal enlarge-ment, together with reduced gray-matter volume, mayalso indicate general atrophy rather than HC. EnlargedCSF spaces have been shown to correlate with cogni-tive deficits after aneurysmal subarachnoid hemor-rhage (Bendel et al., 2010).

Like acute subarachnoid hemorrhage, severe trau-matic brain injury can lead to disturbance of CSF circu-lation both acutely and later on. Acute HC aftersubarachnoid hemorrhage or traumatic brain injurymay require permanent shunt but also significantlyincrease the risk of later developing chronic HC. Alsomeningitis, both per se and related to invasive neurosur-gical procedures like prolonged external ventriculardrainage, may lead to HC. Interestingly, in some rarecases with long-standing need of external ventriculardrainage, especially with concomitant meningitis, ventri-cles may enlarge and the patient may deteriorate and thusrequire CSF drainage despite normal or unexpectedlylow ICP.

Fig. 5.15. Suggested disease course of normal-pressure hydrocephalus (NPH). AD, Alzheimer disease; iNPH, idiopathic NPH;SAH, subarachnoid hemorrhage; sNPH, secondary NPH; TBI, traumatic brain injury.

Fig. 5.14. Cilia of ventricular wall visualized by scanning

electron microscopy.

48 V. LEINONEN ET AL.

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Cerebrospinal fluid circulation and hydrocephalusCSF circulationClassificationChronic hydrocephalus

EpidemiologyHydrocephalus in childrenChronic hydrocephalusIdiopathic intracranial hypertension

Clinical phenotypes and imagingIdiopathic intracranial hypertensionChronic hydrocephalus - normal-pressure hydrocephalusLong-standing overt ventriculomegaly in adults

NeuropathologyMacroscopyMicroscopy/immunohistochemistryOverview of the diagnostic approachDiagnostic criteria

Pathogenesis, experimental models, and biochemistrySecondary hydrocephalus

References