**4. Management**

Even though research in this field has advanced, iNPH still has to be considered a complex pathology whose diagnosis and management continue to present many problems. The main interest is represented by the fact that iNPH can be considered a potentially reversible dementia. Surgical diversion of CSF via a shunt remains the main treatment for this condition. This is based on the presumption that CSF diversion will reduce or normalize the transmantle pressure, thereby stabilizing or improving symptoms [14].

Ventriculo-peritoneal (VP) shunts are the most commonly used [35]; in Japan iNPH is treated mainly with lumboperitoneal (LP) shunts and in the last years also in Western Countries this procedure has began to be adopted. The data are still scarce, but LP shunts seem to have effectiveness rates similar to those of VP shunts. Despite greater rates of device-related complications, LP shunting can be recommended for the treatment of patients with iNPH because of their minimal invasiveness and lack of the lethal complications seen with VP shunts [36].

It must be stressed out that not all patients with iNPH are candidate for shunt surgery. The risk-to-benefit ratio has to be assessed individually. Prior to embarking upon surgical therapy, knowing which patients may benefit from surgery is necessary. All patients with suspected iNPH should undergo diagnostic CSF removal (either large-volume lumbar puncture and/or external lumbar drainage), which has both diagnostic and prognostic value. Detailed testing is performed before and after CSF drainage; improvement in motor symptoms after large-volume drainage supports the diagnosis of iNPH, while improvement does not rule out iNPH. Recently, a novel standardized paradigm with a simultaneous quantification of cognition and gait (dual task gait assessment and mental imagery of locomotion) before and 24 h after CSF tapping has been proposed [37], which can contribute to the identification of patients with iNPH from its mimics. The same authors underline the major limitation of this paradigm (i.e. an expansive and time-consuming evaluation), however it responds to the need of standardized evaluative parameters. Moreover, a levodopa challenge may be helpful to rule out idiopathic Parkinson disease; patients with iNPH have no significant response to levodopa or dopamine agonists.

The best candidates for shunt surgery would show imaging evidence of ventriculomegaly, indicated by a frontal horn ratio exceeding 0.30 on imaging studies, with one or more of the following criteria, as indicated by Schneck [38]:

• Presence of a clearly identified etiology.

Initially is important to identify or exclude other disorders that should be treated before evaluating iNPH. Although iNPH is described as a symptom "triad," patients do not need to have all three symptoms. However, gait impairment is the symptom that affects nearly all patients as described by most published series and guidelines. A patient who has only dementia or incontinence should first be evaluated for other disorders. Patients with gait impairment and urinary symptoms but no cognitive impairment may need evaluation for spinal cord disorders. Although any of the primary iNPH symptoms may be the initial symptom, gait impair-

**Table 1.** Differential diagnosis of idiopathic normal pressure hydrocephalus (iNPH). Taken from [1].

**Gait Dementia Incontinence**

X

X

X

ment is usually either the first or worst symptom.

Degenerative arthritis of the hips,

Prostatic hypertrophy/obstructive

Disorders that can aggravate other

Peripheral vascular disease

50 Hydrocephalus: Water on the Brain

Spinocerebellar degeneration X

Alzheimer dementia X Frontotemporal dementia X Depression X Hypothyroidism X Sleep apnea X

Visual impairment X X Hearing impairment X

Obesity X Cardiovascular disease X Pulmonary disease X Chronic lower-back pain X Vestibular disorders X

Pelvic-floor abnormalities X Interstitial cystitis X

knees, ankles

(claudication)

uropathy

symptoms


Specific criteria and guidelines have been defined for the surgical procedure and the postoperative and long-term care, including the management of complications [7, 9], even if a consensus measurement of CSF shunting outcome is still lacking [14].

especially apathy [48, 49], that is often present in patients with iNPH. However, as it will be detailed in this chapter, a wide range of other cognitive disturbances beside frontal involve-

Clinical and Cognitive Features of Idiopathic Normal Pressure Hydrocephalus

http://dx.doi.org/10.5772/intechopen.73273

53

Boon et al. [26] in a study evaluated global cognitive functioning, memory, and attention in a large sample (101 patients), reported that iNPH patients showed severe impairment of atten-

Iddon et al. [50], on the basis of Mini-Mental State Examination (MMSE) score cutoff, divided their sample of 11 patients into two groups: demented and non-demented. By the means of neuropsychological instruments which evaluated different cognitive functions, two cognitive profiles in iNPH have been identified, one observed in patients at a less advanced disease stage, who presented isolated frontal lobe dysfunction, and the other observed in those who have reached a more advanced stage and presented severe global cognitive dysfunction. The non-demented iNPH patients obtained a worse performance on attentional tasks, thus suggesting a deficit in cognitive flexibility, similar to patients with frontal lobe excision and patients with fronto-subcortical dementia such as Parkinson's disease [51, 52], and unlike

Ogino et al. [46], in a well-controlled study, analyzed 21 patients with iNPH and 42 patients with AD, using a neuropsychological assessment investigating different cognitive domains. iNPH patients had more severe impairment of attention, psychomotor speed and calculation than those with AD, while memory function and orientation were more preserved. Impairment in frontal functions in iNPH, but not in AD, was reported also by Miyoshi et al. [54], who compared the scores recorded on the Frontal Assessment Battery (FAB), on verbal fluency subtests and on subtests of the MMSE in patients with iNPH and AD, matched for

Tarnaris et al. [47], analyzing cognitive performances of 10 patients with iNPH through a complete neuropsychological assessment (language, memory, executive functions, visuospatial abilities, and attention), confirmed that all the patients had subcortical cognitive impairment, characterized in particular by dysexecutive dysfunction and slowed mental

Therefore, some studies have tried to relate the cognitive impairment in iNPH to damage the frontal lobe The results of single photon emission computed tomography and positron emission tomography (PET) studies showed that iNPH patients mainly presented hypoperfusion

On the basis of the finding that periventricular white matter cerebral blood flow was reduced in iNPH [56] it has been suggested that the frontal lobe dysfunction might be secondary to a disturbance of the subcortical area connecting with the frontal lobe cortex [50, 57, 58]. The relatively preserved memory and orientation functions may be explained by a lower involvement of memory systems, including the medial temporal lobe, in iNPH than in AD [46]. However, a neuroimaging study [59] demonstrated a reduction in the medial temporal volume in iNPH. Parietal regional cerebral blood flow reduction in iNPH has also been shown in

patients with AD in which frontal functions usually are spared [53].

ment can be detected.

tion and psychomotor speed.

age, sex, and MMSE score.

of the frontal lobe [55–57].

other neuroimaging studies [60, 61].

processing.

Many studies have investigated the benefit of shunt surgery. Only one assessed the benefit of shunting surgery in a randomized manner and showed that, among the 14 patients included, only those with CSF shunts improved at 3 months follow-up. In particular, the patients with effective (open) shunts showed an improvement in motor and psychometric scores (30 and 23% increase, respectively) at 3 months, whereas those with placebo (ligated) shunts were unchanged. Of note, this latter group also improved after opening the shunts, although with less benefit (28 and 18%, respectively) [39].This rate of benefit is in line with the results of a systematic review, which reported a long-term response of 29% [40]. A double-blind randomized trial on the clinical effect of different shunt valve settings was also performed [41]; improvement after shunt surgery was evident within 3 months, irrespective of valve setting.

Recent studies showed higher rates of success (around 80–90%) [42, 43]; all these outcomes must be interpreted with caution, given the lack of standardized method of comparison. Besides the possible benefit, information about the risks of complications should also be provided, since they appear to be very common [44].

The complication ratio of CSF shunt was found on average of 38%. Potential complications include infection, seizures, abdominal problems (peritonitis, perforation, volvulus, and ascites), shunt failure or blockage, shunt over-drainage and intracranial hemorrhage. The most common complication was the shunt over-drainage occurring in up to one-third of the patients within the first year [40]. Of course, the complication rates differ across centers. The Eu-iNPH study revealed a complication rate of 28% [42], while a recent study over more 230 subjects found a complication rate of less than 12% [43].

In any case, the clinical follow-up of the patients is essential. The follow-up helps the management of the complication, identifying the patients who need adjustments or revision of the shunt. Repeated brain imaging is usually performed after shunting and can support the identification and early treatment of subdural hemorrhage [14].

As previously reported, the response to levodopa/carbidopa is absent or scarce. In patients who are poor candidates for shunt surgery, repeated lumbar punctures in combination with acetazolamide may be considered [45]. Recent studies on aquaporin-4 channels suggest interesting perspectives for future pharmacological treatment of iNPH [31].
