**3. Epidemiology**

It is difficult to accurately establish the incidence and prevalence of INPH because several cases are likely to be undiagnosed due to the non‐specific nature of the symptoms. However, it is clear from epidemiological studies that the incidence increases with age. Tisell et al. [3] observed that one to two shunt operations per 100,000 inhabitants were being performed yearly for INPH. Brean and Eide [4] found that the prevalence was up to 181.7 per 100,000 people in the 70–79 years age group in Norway [4]. After randomly subjecting 497 individuals over the age of 65 to magnetic resonance imaging (MRI) of the brain, Tanaka et al. found a prevalence of 1.4% in that age group [5]. It is also estimated that up to 10% of patients with dementia may have INPH [6].

### **4. Pathophysiology**

The CSF space is a dynamic pressure system. It is responsive to changes in CSF formation or reabsorption rates, arterial and venous flow, compliance of the intracranial structures and fluctuations in intracranial pressure (ICP). Around 500 ml of CSF is produced every day and the total volume of CSF at any one point is between 120 and 150 ml. The brain is unique in the sense that it is the only organ enclosed in a non‐expansile box (i.e. the skull). According to the Monro‐Kellie hypothesis, the total volume of the constituents in the cranium is fixed. There‐ fore, an increase in the volume of any of the constituents has to be matched by a decrease in the volume of another to avoid an increase in intracranial pressure. The volume of blood entering the brain varies with the cardiac cycle. There is a net intracranial inflow of blood during systole and a net outflow during diastole. Arterial supply to the brain is pulsatile whereas venous flow is less so, and this mismatch causes transient rises in pressure. The brain and other intracranial constituents can compensate for this in two ways. Firstly, the blood vessels have a degree of compliance which allows for a smoother influx of arterial blood. Secondly, CSF flows back and forth through the cerebral aqueduct in response to pulsatile blood flow, thereby maintaining intracranial pressure stable. However, in INPH, the intracra‐ nial constituents become less compliant [7]. A reduction in vascular compliance especially in the superior sagittal sinus has been found [8]. This can initially be countered by increased pulsatile CSF flow through the aqueduct. If this fails, the amplitude of arterial pulsatility increases during systole inducing large ICP pulsations ('water hammer' effect). These pulsa‐ tions, in addition to causing venous damage in the periventricular region, displace the brain towards the skull [9]. Hydrocephalus occurs as a result of enlarging ventricles at the expense of a reduced subarachnoid space. This is secondary to increasing pressure within the ventricles directed towards the subarachnoid space. The pressure gradient arising between the ventricles and the subarachnoid space is termed 'transmantle pressure'. The transmantle pressure gradient has to be the only force which could cause such changes to the brain [9]. CSF spaces revert to normal following shunting, implying that the transmantle pressure gradient can be reduced or reversed. This pressure gradient also explains why, although there is increased intraventricular pressure, the measured opening pressure during a lumbar puncture is within normal limits. It also implies that 'normal pressure' in NPH is somewhat of a misnomer.

insidious onset and progresses gradually. Shunt surgery results in a positive response in as many as 84% in a European multicentre study [2]. Although the treatment is surgical, neurological input is important for the diagnosis and identification of suitable shunt candi‐ dates. In some countries, hydrocephalus is a purely surgical condition. However, like several authors, we believe that a multidisciplinary approach is essential for the optimal manage‐ ment of these patients. In our neuroscience centre, the management of INPH involves the

This review was prompted by the large number of publications on INPH. We searched the databases of Medline, Embase and the Cochrane Library for articles relating to INPH up to February 2016. We included review articles and research studies according to their relevance.

It is difficult to accurately establish the incidence and prevalence of INPH because several cases are likely to be undiagnosed due to the non‐specific nature of the symptoms. However, it is clear from epidemiological studies that the incidence increases with age. Tisell et al. [3] observed that one to two shunt operations per 100,000 inhabitants were being performed yearly for INPH. Brean and Eide [4] found that the prevalence was up to 181.7 per 100,000 people in the 70–79 years age group in Norway [4]. After randomly subjecting 497 individuals over the age of 65 to magnetic resonance imaging (MRI) of the brain, Tanaka et al. found a prevalence of 1.4% in that age group [5]. It is also estimated that up to 10% of patients with

The CSF space is a dynamic pressure system. It is responsive to changes in CSF formation or reabsorption rates, arterial and venous flow, compliance of the intracranial structures and fluctuations in intracranial pressure (ICP). Around 500 ml of CSF is produced every day and the total volume of CSF at any one point is between 120 and 150 ml. The brain is unique in the sense that it is the only organ enclosed in a non‐expansile box (i.e. the skull). According to the Monro‐Kellie hypothesis, the total volume of the constituents in the cranium is fixed. There‐ fore, an increase in the volume of any of the constituents has to be matched by a decrease in the volume of another to avoid an increase in intracranial pressure. The volume of blood entering the brain varies with the cardiac cycle. There is a net intracranial inflow of blood during systole and a net outflow during diastole. Arterial supply to the brain is pulsatile whereas venous flow is less so, and this mismatch causes transient rises in pressure. The brain

neurologists, neurosurgeons and physiotherapists.

**2. Methods**

530 Update on Dementia

**3. Epidemiology**

dementia may have INPH [6].

**4. Pathophysiology**

What triggers the initial reduction in compliance that results in INPH? Most theories on INPH attempt to explain the pathophysiology around the finding of reduced cerebral blood flow (CBF). There is a strong association between impaired CBF and INPH. Patients with INPH are more likely to have concomitant cerebrovascular disease [10]. MRI shows increased white matter changes (WMCs) [11] and this is further supported by neuropathological studies showing microvascular infarctions but also interstitial oedema, ependymal disruption, gliosis and neuronal degeneration [12, 13]. In addition, there is an association between high ICP and impaired cerebrovascular autoregulation [14]. Age‐related atherosclerosis has been proposed as being responsible for the reduction in vascular compliance [15]. This would explain the association between NPH and vascular disease (VD). Bateman [8], on the other hand, proposes that increased transvenular resistance in the territory of the superior sagittal sinus is the initiating event in NPH. While some consider that CSF resorption occurs at the level of the arachnoid villi or arachnoid granulations, others believe that the majority of CSF resorption occurs through brain parenchyma at the levels of capillaries and veins [9, 16–18]. If the latter hypothesis is true, CSF resorption would be affected with increased transvenular resistance. Indeed, CSF resorption is unequivocally abnormal in INPH [19]. CSF outflow resistance or conductance (which is inversely proportional to resistance) has been investigated in a few studies [20–22] and found to be impaired. Early studies in animals and humans suggest that, in the initial stages, mounting CSF intraventricular pressure secondary to abnormal CSF flow causes ventricular dilatation [8]. It is therefore possible that CSF outflow disturbance, occurring secondary to reduced venous compliance, is directly related to the ventriculomegaly seen in INPH.

But why would venous resistance increase in an elderly patient? Bradley believes that deep white matter ischaemia is the triggering event [23]. Due to ischaemia, surrounding arterioles are already maximally dilated, and this would explain the loss of autoregulation [23]. When the arterioles are obstructed, venous collapse ensues, followed by impaired CSF drainage and ventricular enlargement [23]. The problem we have with this hypothesis is that if one wants a unifying theory with ischaemia as the initiating trigger, one would struggle to explain the appearance of NPH in disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease (AD). Periventricular white matter ischaemia is an uncommon finding especially in PSP and CBD. Yet, there has to be a final common pathway which results in hydrocephalus in all these conditions. We hypothesise that neurodegeneration has a role to play in INPH, at least in some cases. The following findings would support this:


Finally, we take the opportunity to emphasise the possibility that INPH has different causes which form a pathophysiological continuum. This would not only explain the differences with shunt response and rates of progression but would also explain why a universal theory remains elusive. It would perhaps be more appropriate to refer to these conditions, where known, as VD‐associated NPH, AD‐associated NPH, etc.
