**6. Investigations**

#### **6.1. Neuroimaging**

The diagnosis of INPH in the right clinical context relies on the finding of hydrocephalus on brain imaging (**Figure 1A**). Hydrocephalus is not synonymous with ventriculomegaly. Although ventriculomegaly is commonly found in the elderly population, this does not imply the presence of NPH. In NPH, the ventriculomegaly is typically out of proportion to the amount of atrophy present. CT of the brain is a sensitive imaging modality to identify NPH but MRI provides additional information such as aqueductal stenosis, white matter changes or the presence of an underlying aetiology (e.g. AD). A coronal section reveals a narrow subarachnoid space surrounding the outer surface of the brain (hence the term 'tight convex‐ ity') and narrow medial cisterns. The cortical sulci at the vertex are effaced (**Figure 1B**), whereas the temporal horns are widened (**Figure 2A**). The third ventricle is often enlarged, whereas the fourth ventricle can be either dilated or normal. Therefore, a normal‐sized fourth ventricle in the presence of enlarged lateral and third ventricles does not necessarily suggest aqueductal stenosis and is a finding consistent with NPH. Other imaging features of NPH are discussed below.

**Figure 1.** Ventriculomegaly and effacement of sulci at the vertex in a patient with INPH **(A** and **B)**, with some post‐ operative improvement **(C** and **D)**.

Idiopathic Normal Pressure Hydrocephalus: An Overview of Pathophysiology, Clinical Features, Diagnosis and Treatment http://dx.doi.org/10.5772/64198 535

**Figure 2. (A)** Dilated Sylvian fissures and temporal horns. **(B)** Periventricular white matter hyperintensities on MRI. **(C)** Isolated dilated sulci.

#### *6.1.1. Evan's index*

cerebral control of bladder storage. The underlying mechanism for detrusor overactivity in patients with NPH appears to be related to reduced cerebral blood flow in the right frontal cortex, and to a lesser extent impaired basal ganglia function [43]. Reduced mobility could also

The diagnosis of INPH in the right clinical context relies on the finding of hydrocephalus on brain imaging (**Figure 1A**). Hydrocephalus is not synonymous with ventriculomegaly. Although ventriculomegaly is commonly found in the elderly population, this does not imply the presence of NPH. In NPH, the ventriculomegaly is typically out of proportion to the amount of atrophy present. CT of the brain is a sensitive imaging modality to identify NPH but MRI provides additional information such as aqueductal stenosis, white matter changes or the presence of an underlying aetiology (e.g. AD). A coronal section reveals a narrow subarachnoid space surrounding the outer surface of the brain (hence the term 'tight convex‐ ity') and narrow medial cisterns. The cortical sulci at the vertex are effaced (**Figure 1B**), whereas the temporal horns are widened (**Figure 2A**). The third ventricle is often enlarged, whereas the fourth ventricle can be either dilated or normal. Therefore, a normal‐sized fourth ventricle in the presence of enlarged lateral and third ventricles does not necessarily suggest aqueductal stenosis and is a finding consistent with NPH. Other imaging features of NPH are discussed

**Figure 1.** Ventriculomegaly and effacement of sulci at the vertex in a patient with INPH **(A** and **B)**, with some post‐

be contributing to incontinence in these patients [43].

**6. Investigations**

534 Update on Dementia

**6.1. Neuroimaging**

below.

operative improvement **(C** and **D)**.

An objective way of assessing whether the ventricles are enlarged is through the use of Evan's index. It is the ratio of the maximum width of the frontal horns of the lateral ventricles and the transverse inner diameter of the skull, measured at the same level on both axial CT and MRI images [44, 45]. A value above 0.30 is considered significant, although in our own experience, the higher the value, the more specific it is for NPH. Unfortunately, Evan's index is a crude marker of hydrocephalus and varies significantly depending on the location and angle of the slice [46]. It is therefore of limited value on its own.

#### *6.1.2. Callosal angle*

The concept of callosal angle with respect to NPH was first described on pneumoencephalo‐ gram by Benson et al. [47] and thereafter by Sjaastand and Nordvik [48]. The International guidelines mention an angle of greater than 40° as supportive of NPH [49]. However, using MRI, Ishii et al. [50] found that a callosal angle of less than 90°, measured on a coronal plane, which is perpendicular to the AC–PC plane on the posterior commissure plane, helped in differentiating INPH patients from AD and normally aged subjects. The narrow angle is caused by the elevation of dilated ventricles and compression due to dilated Sylvian fissures (**Figure 2A**). When combined with Evan's index of >0.3, INPH could be discriminated from AD with a sensitivity and specificity of 97 and 94%, respectively [50].

#### *6.1.3. White matter changes (WMC)*

INPH is known to be associated with deep white matter changes (DWMC) and smooth periventricular hyperintensity (PVH) [51] on MRI (**Figure 2B**). As discussed earlier, there is an element of cerebral hypoperfusion in INPH which is thought to contribute to the development of INPH. It is, however, unclear whether the WMC are cause or effect. Regardless of the underlying pathophysiological mechanisms implicated in NPH, there is consistent neuropa‐ thological evidence demonstrating the involvement of white matter. A diversity of patholog‐ ical observations, such as direct mechanical compression of the periventricular white matter, ischaemic demyelination and infarction, have been noted in INPH [12, 13, 52]. Indeed, DWMC and subcortical infarctions are commonly seen in patients with Binswanger's disease, and these patients often have similar symptoms to those with INPH. Tullberg et al. [51] evaluated the diagnostic features of DWMC and PVH using MRI, and found that no MRI variable could reliably differentiate NPH from BD. One explanation for this result, put forward by the authors, is that NPH and BD are two disorders with similar pathophysiological mechanisms or that they form a pathophysiological continuum of increasing microangiopathy [51].

#### *6.1.4. CSF flow void*

As mentioned earlier, CSF flows back and forth the aqueduct during the cardiac cycle in response to arterial blood flow to the brain. This was initially observed as a flow void, consisting of a decreased MRI signal, mainly in the aqueduct on T2‐weighted images of early MR scans in patients with communicating hydrocephalus [53–55]. CSF flow void can be observed in normal individuals, but it is more prominent in INPH [56]. Increased aqueductal CSF flow initially appeared to be predictive of a good response with shunting [55, 57, 58], but further studies have found poor correlation between the extent of CSF flow void and surgical outcome [56, 59].

#### **6.2. CSF tap test**

Patients with suspected INPH, based on clinical features and neuroimaging, should undergo a high‐volume CSF tap to predict response with shunting. The rationale for a CSF tap is that it simulates the physiological effect of a shunt [45]. The patient is assessed pre‐ and post‐CSF tap for gait and cognitive improvements. About 40–50 ml of CSF is usually removed. Gait is most likely to ameliorate following CSF tap; therefore, it is the best indicator of response. In our centre, we use the 10‐m timed‐walk test and Tinetti test to assess gait and balance before and after CSF removal. Our patients are also consented for video recordings as these can be useful to retrospectively assess patients especially when the improvement following CSF tap is not clear. It is common that some patients or their carers only notice an improvement a couple of days down the line. We therefore carry out follow‐up telephone assessments in all our patients 3 days after they have undergone a CSF tap. This is quite a subjective measure for improvement. Nevertheless, it reduces the chances of missing potentially suitable candidates for shunt surgery. Unfortunately, although the CSF tap test has a high positive‐predictive value for shunt success, it has a low sensitivity [60] and should not be used to exclude patients from shunt surgery. There are patients who do respond to shunt surgery after a negative tap test. The first edition of the Japanese guidelines advocated repeating the tap test if initially negative [61], but the more recent edition suggests that further investigation may be required [62]. Recently, Yamada et al. have shown that the timing of the CSF tap affects the accuracy of the test [63]. It should be carried out as soon as symptoms appear [63]. An external lumbar drain, which provides continuous drainage, has a similar predictive value to the CSF tap test, a higher sensitivity [64, 65], but a low negative-predictive value. It is important to note that this test is more invasive, and can give rise to complications such as radicular pain and meningitis.
