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Normal pressure hydrocephalus

Normal pressure hydrocephalus
Author:
Neill R Graff-Radford, MBBCh, FRCP
Section Editor:
Steven T DeKosky, MD, FAAN, FACP, FANA
Deputy Editor:
Janet L Wilterdink, MD
Literature review current through: Dec 2022. | This topic last updated: Feb 11, 2020.

INTRODUCTION — Normal pressure hydrocephalus (NPH) refers to a condition of pathologically enlarged ventricular size with normal opening pressures on lumbar puncture. NPH is a form of communicating hydrocephalus and is distinguished from obstructive or noncommunicating hydrocephalus, in which there is a structural blockage of the cerebrospinal fluid (CSF) circulation within the ventricular system (eg, stenosis of aqueduct of Sylvius).

NPH is associated with a classic triad of dementia, gait disturbance, and urinary incontinence. Because this clinical syndrome is potentially reversible by the placement of a ventriculoperitoneal (VP) shunt, it is important to recognize and diagnose accurately. However, there is little consensus regarding the diagnosis of NPH and the selection of patients for shunt placement, and a sizable minority of patients have evidence of neurodegenerative pathology at the time of shunting or receive a revised diagnosis of Alzheimer disease (AD) or other neurodegenerative dementia within several years of shunting [1]. This is not surprising, as approximately one-third of nondemented adults at the average age of shunt surgery (75 years) have significant AD pathology at the time of autopsy [2].

This topic provides an overview of the epidemiology, clinical features, diagnosis, and management of NPH. Other dementia syndromes are presented elsewhere. (See "Clinical features and diagnosis of dementia with Lewy bodies" and "Etiology, clinical manifestations, and diagnosis of vascular dementia" and "Clinical features and diagnosis of Alzheimer disease" and "Frontotemporal dementia: Clinical features and diagnosis".)

EPIDEMIOLOGY — NPH is a rare condition compared with other causes of dementia in older adults, such as Alzheimer disease (AD). The incidence of NPH has varied in different studies from 2 to 20 per million per year [3-6]. These discrepancies probably reflect inconsistent definitions of NPH as well as differences among populations sampled.

Secondary NPH (those cases associated with an identified etiology) can occur in all age groups. In comparison, idiopathic NPH increases in prevalence with age and is most common in adults over the age of 60 years [7,8]. In one population-based study, the prevalence rose from 0.2 percent in persons 70 to 79 years of age to 6 percent in those over 80 years [9]. It is equally common in both sexes [10].

PATHOPHYSIOLOGY — Cerebrospinal fluid (CSF) is produced by the choroid plexus in the lateral ventricles and flows from the lateral ventricles to the third and fourth ventricles, and then through the basal cisterns, tentorium, and subarachnoid space over the cerebral convexities to the area of the sagittal sinus (figure 1). CSF is absorbed into the systemic circulation primarily across the arachnoid villi into the venous channels of the sagittal sinus.

Idiopathic NPH — When no obvious cause is identified, several possible mechanisms of NPH have been proposed:

Decompensated congenital hydrocephalus – The observation that larger head sizes are more common in patients with NPH than normal controls suggests the possibility that some patients with NPH have congenital hydrocephalus that becomes symptomatic later in life [11-13].

Factors that theoretically could aggravate chronic hydrocephalus and cause it to become symptomatic include systemic hypertension, recent head injury, sleep apnea, heart failure, and lung disease (the last three by raising jugular venous pressure and intracranial pressure [ICP]).

Cerebrovascular disease – Hypertension, coronary artery disease, peripheral arterial disease, and other vascular risk factors occur with increased frequency among patients with idiopathic NPH compared with age-matched controls with and without dementia [14-17]. Patients with NPH also have a higher-than-expected prevalence and severity of periventricular white matter disease on magnetic resonance imaging (MRI).

These associations have led some to propose that chronic periventricular ischemia leads to increased compliance of the ventricular wall and gradual ventricular enlargement due to normal fluctuations of ICP [18]. Intraventricular pulse pressure and systolic hypertension have also been associated with ventricular enlargement [19]. Alternatively, periventricular ischemia may lead to locally increased venous resistance, which may lead to decreased CSF absorption and ventricular enlargement [20].

Decreased CSF absorption – Several studies have shown a good correlation between decreased CSF absorption and outcome with shunt surgery [21]. One of the autopsy findings in some patients with NPH is arachnoid thickening, which is present in up to 50 percent of cases [22,23].

Increased central venous pressure – One ultrasound study in 20 patients with idiopathic NPH found that patients were more likely than controls (95 versus 25 percent) to have evidence of retrograde flow in the internal jugular veins during Valsalva [24]. This finding suggests an underlying incompetence of the jugular valves, which, in theory, could lead to increased central venous pressure and impaired CSF absorption.

Hydrocephalic presentation of neurodegenerative disorders – Some patients with NPH are later diagnosed as having a neurodegenerative dementia, or have evidence of "dual pathology" at the time of shunting. Such cases have suggested that neurodegeneration such as Alzheimer disease (AD) may play a role in the ventricular enlargement [1].

Secondary NPH — Impaired absorption of CSF is the suspected mechanism in most cases of secondary NPH.

The most common identified underlying causes are intraventricular or subarachnoid hemorrhage (either from aneurysm or trauma) and prior acute or ongoing chronic meningitis (from infection, cancer, or inflammatory disease). Paget disease at the skull base, mucopolysaccharidosis of the meninges, and achondroplasia are other rarely reported causes of secondary NPH [25].

These conditions are understood to cause inflammation and subsequent fibrosis at the base of the brain and/or the arachnoid granulations, and thereby impair CSF resorption. Decreased CSF resorption leads to gradual accumulation of CSF within the ventricular system. While increased pressure is not necessarily measured on lumbar puncture, a pressure effect is nonetheless believed to occur locally on periventricular white matter tracts, producing the observed pathology and clinical symptoms.

CLINICAL FEATURES — NPH is classically described as having three cardinal features: gait difficulty, cognitive disturbance, and urinary incontinence [26]. These manifestations are believed to arise from dysfunction of supplementary motor areas of the frontal lobe and periventricular white matter tracts, particularly those subserving frontal lobe connections [27]. Patients need not have all three cardinal features, but gait must be the predominant problem. In other words, a patient can have gait difficulty as the only clinical symptom but cannot have only one of the other two (incontinence or cognitive impairment). Of note, often the earliest urinary problem is urgency rather than incontinence.

Gait dysfunction — Gait difficulty is the most prominent clinical feature in NPH [28]. It is also believed to be the clinical feature most responsive to shunting.

The gait abnormality of NPH is somewhat hard for both patients and clinicians to characterize; it is variably described as a magnetic or "glue-footed" gait, gait apraxia, or a frontal ataxia. Clinicians should not be fixated on these terms when making the diagnosis. Patients with NPH move slowly and take small steps, often with a wide base. They have difficulty turning (eg, they take several steps to turn 180 or 360 degrees) and are most vulnerable to falls when turning. Postural instability demonstrated by the pull test is often present [29,30].

The parkinsonian gait may bear a resemblance to that of NPH but is distinguished by a narrow base and responsiveness to visual and acoustic cues [30]. Other features of Parkinson disease may also be present, including asymmetry, rest tremor, decreased facial expression, and bradykinesia of the hand and arm movements; these features are usually absent in patients with NPH. (See "Clinical manifestations of Parkinson disease", section on 'Cardinal features'.)

Long tract signs may be observed, with lower-extremity spasticity, hyperreflexia, and extensor plantar responses. In late stages, frontal release signs, akinetic mutism, and quadriparesis may occur.

Cognitive impairment — The cognitive disturbance of NPH evolves over months to years and usually develops after the onset of gait dysfunction. Patients typically have both subcortical and frontal features, including:

Psychomotor slowing

Decreased attention and concentration

Impaired executive function

Apathy

Patients may appear depressed but lack depressed thought content. Executive function, the ability to conceptualize all facets of an activity and translate that into appropriate and effective behavior, is impaired early in the course and may be more resistant to treatment [31]. Cortical features (eg, aphasia) are less prominent [32,33].

The Mini-Mental State Examination and other brief cognitive tests may be an insensitive measure of cognitive impairment in NPH. Other cognitive measures and neuropsychological tests may aid in its characterization. (See 'Cognitive evaluation' below.)

Urinary incontinence — Urinary urgency rather than incontinence may be present at early stages. Also, the gait disorder of NPH delays the patient reaching the bathroom in time. In later stages, urinary incontinence is accompanied by a lack of concern, reflecting its probable origin in frontal lobe impairment.

Notable negatives — By definition, patients with NPH have a normal opening pressure at the lumbar cistern. The clinical presentation is therefore notable for an absence of signs and symptoms related to diffusely increased intracranial pressure (ICP), such as:

Headaches

Nausea and vomiting

Visual loss

Papilledema

If performed, findings during lumbar puncture and cerebrospinal fluid (CSF) analysis should be normal; the following are inconsistent with a diagnosis of idiopathic NPH:

Significantly elevated opening pressure (>25 cm water) [34].

Abnormal CSF profile, including pleocytosis and marked elevation of protein. A mild elevation of protein in isolation is a common nonspecific finding. Pleocytosis requires a rigorous evaluation to determine the underlying etiology. (See "Approach to the patient with chronic meningitis", section on 'CSF examination and other laboratory testing'.)

DIFFERENTIAL DIAGNOSIS — In the absence of a known secondary cause of hydrocephalus, idiopathic NPH is a diagnosis of exclusion that requires careful consideration of neurodegenerative causes of dementia, especially when cognitive impairment is a prominent symptom. In particular, neurodegenerative dementias that include prominent, early gait dysfunction (eg, dementia with Lewy bodies [DLB], progressive supranuclear palsy [PSP]) are important to consider. Since the size of the ventricles increases with age, it is not uncommon for older adults with these dementias to be suspected of having NPH. In such cases, a degree of cortical atrophy accompanying the ventricular enlargement (hydrocephalus ex vacuo) may be helpful in differentiating NPH from neurodegenerative disorders.

Dementia with Lewy bodies – DLB and other parkinsonian disorders are associated with gait abnormalities that bear resemblance to those of NPH (see 'Gait dysfunction' above). Additional clinical features that suggest an alternative diagnosis of DLB include prominent psychotic features, especially visual hallucinations, cognitive fluctuations, and rapid eye movement (REM) behavior disorder (RBD) (table 1). (See "Clinical features and diagnosis of dementia with Lewy bodies".)

Parkinson disease dementia – Cognitive impairment and dementia related to Parkinson disease typically present as a later-stage finding, at a time when typical motor features (eg, tremor, bradykinesia, rigidity) are prominent. Patients with a triad of dementia, gait dysfunction, and urinary incontinence due to Parkinson disease dementia rather than NPH are therefore usually distinguishable by these additional parkinsonian signs. (See "Cognitive impairment and dementia in Parkinson disease", section on 'Clinical features'.)

Progressive supranuclear palsy – PSP is one of the more common revised clinical diagnoses made in patients referred to tertiary clinics for possible NPH [1]. Patients with PSP have voluntary gaze impairment (supranuclear ophthalmoplegia), axial rigidity, and early falls. Although gaze impairment is a hallmark, it may take years to develop, thereby creating diagnostic confusion in the early stages in patients with enlarged ventricles. In addition to eye movement abnormalities, speech and swallowing difficulties are features of PSP that are not present in patients with NPH. (See "Progressive supranuclear palsy (PSP): Clinical features and diagnosis", section on 'Clinical characteristics'.)

Multiple system atrophy – Multiple system atrophy (MSA) is characterized by autonomic dysfunction leading to postural intolerance, bladder or bowel dysfunction, impotence in men, and abnormal sweating. In addition, patients can have either cerebellar ataxia or a parkinsonian form of gait dysfunction. The autonomic features as well as inspiratory stridor, dysarthria, and RBD can help distinguish MSA from NPH. (See "Multiple system atrophy: Clinical features and diagnosis", section on 'Clinical characteristics'.)

Corticobasal syndrome – Clinical features that suggest corticobasal syndrome include an asymmetric presentation of limb rigidity or akinesia, limb dystonia, limb myoclonus, alien limb phenomena, and cortical sensory loss. Although most patients have gait dysfunction and ventricles may appear enlarged due to striatal atrophy, the asymmetric nature of the cortical signs and symptoms usually distinguishes corticobasal syndrome from NPH. (See "Corticobasal degeneration", section on 'Clinical features'.)

In addition to these syndromes, it is important to consider Alzheimer disease (AD) and cerebrovascular disease, as these conditions are increasingly common with advancing age and therefore commonly coexist with enlarged ventricles. While AD and cerebrovascular disease can coexist with idiopathic NPH, they can also mimic NPH, particularly when other age-related comorbidities exist that may better explain urinary incontinence or gait dysfunction [35].

Alzheimer disease – The average age of patients who undergo shunt surgery for NPH is 70 to 75 years. By this age, autopsy series find evidence of significant Alzheimer pathology in approximately one-third of individuals without clinical dementia [2]. Thus, it is common to have comorbid AD in NPH. While AD itself does not impair gait early in the disease course, gait impairment from a variety of causes is common in older adults and may coexist with AD [36]. Similarly, urinary incontinence from other causes (eg, prostate hypertrophy, pelvic organ prolapse) is common in older adults and may coexist with AD [37]. When dementia starts before the gait abnormality or has features of aphasia, clinicians should suspect AD as the predominant factor in the dementia, rather than NPH [32,33,38].

Cerebrovascular disease – Cerebrovascular disease and vascular risk factors are often comorbid with NPH. In fact, the only double-blind study of shunting for NPH was carried out in 14 patients who were shown to have normal cerebrospinal fluid (CSF) flow dynamics but had evidence of brain vascular disease (eg, severe white matter changes) [39]. All were shunted and randomly assigned to have the shunt open immediately or closed for the first three months. Gait and cognitive scores in the open group improved by approximately 25 to 30 percent compared with the closed group at three months and remained stable at six months. Thus, vascular comorbidity should not dissuade shunt surgery if alternative explanations for the classic NPH triad are not found. (See "Etiology, clinical manifestations, and diagnosis of vascular dementia".)

DIAGNOSTIC EVALUATION — Diagnostic tests are required in the evaluation of patients with clinical evidence of NPH to exclude other conditions, to provide confirmation of the diagnosis, and to identify patients likely to respond to surgical intervention (algorithm 1).

Cognitive evaluation — The evaluation of a patient with dementia first establishes the presence of cognitive impairment and provides a measure of its severity. Treatable conditions are excluded. In general, this evaluation includes a brief cognitive assessment and laboratory evaluations (vitamin B12 level and thyroid function tests). This is discussed in detail elsewhere. (See "Evaluation of cognitive impairment and dementia".)

In addition, a formal neuropsychological assessment may provide useful information in the evaluation of patients with NPH. While no single finding or combination of findings is particularly sensitive or specific for NPH or predicts a response to shunting [10], neuropsychological testing can be useful for several reasons:

It provides a baseline measurement for future comparison, especially after a diagnostic or surgical procedure. The Mini-Mental State Examination may be an insensitive measure of cognitive impairment in NPH, as it does not measure executive function sufficiently.

The characteristic pattern in NPH is that of "frontal-subcortical" dysfunction, in which the patient is slower in timed tasks, performs poorly on tests of divided attention and executive function, has difficulty with fluency tests, and has poor learning and better preserved recognition memory [31,40].

It may aid in the diagnosis of comorbid disease (eg, Alzheimer disease [AD] and other causes of dementia). Cortical features (eg, aphasia, apraxia) are atypical for NPH, particularly early in the disease course.

It may also aid in prognosis. The presence of anomia, in particular, has been associated with a lesser benefit from surgery [32,33].

Alternative causes of gait and urinary dysfunction — In all patients, alternative causes of gait dysfunction, both neurologic and non-neurologic, should be considered and evaluated, such as:

Cervical or lumbosacral spondylosis

Vestibular dysfunction

Osteoarthritis

Visual impairment

Peripheral neuropathy

Medication side effects (eg, sedatives, antipsychotics)

Similarly, neurologic and non-neurologic causes of urinary incontinence should be considered and evaluated. Common causes vary by the type of incontinence:

Urge incontinence (urinary tract infection, prostatic hypertrophy, myelopathy, neurodegenerative dementias)

Stress incontinence (pelvic organ prolapse, history of prostate surgery)

Overflow incontinence (bladder outlet obstruction, prostatic hypertrophy)

Functional incontinence (decreased mobility combined with other factors such as diabetes, diuretics, other medication side effects)

The evaluation of men and women with urinary incontinence is reviewed in detail separately. (See "Urinary incontinence in men" and "Female urinary incontinence: Evaluation".)

Magnetic resonance imaging — While both magnetic resonance imaging (MRI) and computed tomography (CT) can evaluate ventricular and sulcal size, MRI is superior to CT in the evaluation of patients with possible NPH because it allows visualization of other markers of NPH and provides additional information that can exclude other potential etiologies in the differential diagnosis. However, a CT scan can exclude NPH and is appropriate for screening purposes and in patients who cannot undergo MRI.

Ventriculomegaly — The hallmark finding of NPH on CT or MRI is ventriculomegaly in the absence of, or out of proportion to, sulcal enlargement, with no evidence of obstruction at the level of the third or fourth ventricles.

Ventriculomegaly is considered to be present if the modified Evans ratio is greater than 0.31 (image 1) [41]. This is calculated by measuring the maximal diameter of the frontal horns of the lateral ventricles (at the slice where the frontal horns are largest) to the maximum width of the cranial cavity measured at the inner tables of the skull at the same level.

Ventriculomegaly is not specific to NPH, however, and the next step is to examine the degree of cortical atrophy to help distinguish NPH from age- or neurodegeneration-related ventricular enlargement (sometimes referred to as hydrocephalus ex vacuo). Ventricular enlargement occurs normally with age as a result of progressive cortical atrophy; the rate of enlargement increases after the age of 60 years [42]. In general, atrophy associated with age or neurodegenerative dementia produces a proportionate enlargement of both ventricular and sulcal size (image 2).

Prominent cortical atrophy, as manifested by diffuse sulcal enlargement, argues against the diagnosis of NPH and predicts a lesser likelihood of improvement with shunting (image 2) [43,44]. In one series, for example, a measurement of the largest sulcus in the frontal or parietal region of less than 1.9 mm was associated with universal improvement with shunting (in all 17 patients), while sulci ≥5 mm were associated with improvement in fewer patients (15 of 27) [45]. Others have also found that sulcal enlargement does not exclude the possibility of improvement with shunting [25].

Limited data suggest that other qualitative structural MRI findings may aid in identifying ventriculomegaly that is more likely to respond to shunting (ie, NPH). As an example, a group in Japan has coined the term "disproportionately enlarged subarachnoid space hydrocephalus" (DESH) as a characteristic feature of NPH [46]. DESH is characterized by:

Ventriculomegaly

Tight high-convexity and medial subarachnoid spaces (easiest to visualize on coronal MRI) (image 3)

Disproportionate enlargement of the Sylvian fissures

Focally dilated or entrapped sulci without adjacent cortical atrophy (image 4)

Several observational studies have found that DESH is associated with increased likelihood of response to shunting [47,48], and DESH is incorporated into the Japanese guidelines for NPH [49].

Periventricular white matter changes — In patients with NPH, MRI may show a characteristic high signal abnormality around the ventricles, which is thought to represent transependymal egress of fluid or small blood vessel damage. It is difficult, however, to distinguish this finding from the ubiquitous white matter changes in older adults or from that representing subcortical vascular dementia. The extent of white matter disease may correlate with the degree of cognitive impairment [31].

The association between white matter lesions and the response to shunting have been variable. Most studies have found that the more extensive the white matter lesions, the less likely and significant the improvement after shunting [50-52]. However, there are studies showing a good response to shunting in such patients [44,45,53] or no correlation with outcome [7,18,54].

It is unclear whether the usually poor response to shunting means that extensive white matter disease represents a late stage of NPH no longer amenable to treatment or an alternative pathophysiology (subcortical vascular dementia). In at least two series, there was evidence of reduction of periventricular white matter lesions around the frontal lobes after surgery in patients who improved compared with those who did not, suggesting that the observed white matter changes may, at least in part, represent a reversible, secondary phenomenon of NPH [53,54]. It is also possible that white matter lesions do not cause NPH, but that they commonly coexist [55].

Aqueduct flow void — MRI in patients with NPH frequently demonstrates loss of signal in the aqueduct of Sylvius, a finding that has been called aqueduct flow void and is thought to represent higher-than-normal flow velocity of cerebrospinal fluid (CSF) in the aqueduct (image 5). However, this finding is not useful in diagnosis or prediction to response to shunting.

Multiple studies have found no difference between the extent of flow void in patients with idiopathic NPH compared with age-matched controls, and a poor correlation with postoperative outcome [55-57]. Postoperative clinical improvement is not associated with resolution of this finding [54,58].

Other findings — Other findings on MRI may provide evidence of a diagnosis other than NPH that explains or contributes to the patient's clinical syndrome:

MRI permits better visualization of the posterior fossa than CT, possibly detecting aqueductal stenosis or a Chiari malformation that may cause obstructive hydrocephalus.

MRI allows volumetric assessment of medial temporal lobe structures, which may be important because medial temporal atrophy suggests the diagnosis of AD [59]. In two series, medial temporal atrophy, as manifested by either more dilated perihippocampal fissures or as a lower hippocampal volume, was significantly greater in patients with AD compared with NPH [60,61]. Among patients with NPH, one series found a nonsignificant trend between higher hippocampal volumes (ie, less temporal atrophy) and a greater likelihood to benefit from shunting [61].

MRI is sensitive for the diagnosis of cerebrovascular disease; however, the distinction between transependymal fluid flow and subcortical white matter ischemia is difficult. (See 'Periventricular white matter changes' above and "Etiology, clinical manifestations, and diagnosis of vascular dementia".)

Confirmatory tests — Given the invasive nature of the treatment for NPH, and a substantial failure rate, it is generally recommended that an additional test be performed to provide some measure of the patient's likelihood of responding to surgery (algorithm 1). These tests vary considerably in their invasiveness and requirements for hospitalization and technical expertise, and none have clearly defined sensitivity or specificity [62].

We use the lumbar tap test, a simple, outpatient procedure, to select patients for surgery. Some institutions prefer inpatient lumbar drain trials. These two tests have gained the most acceptance in the diagnosis of NPH and selection of patients for surgery [3,63].

High-volume lumbar puncture — The simplest test can be done as an office procedure. Using lumbar puncture, 30 to 50 mL of CSF is removed with documentation of the patient's gait function before and within 30 to 60 minutes after the procedure. Common parameters measured before and after CSF removal include measures of gait speed, stride length, and number of steps it takes to turn 180 or 360 degrees. We find it useful to make a videotape of the gait before and after the tap. In addition to recording these measures in the office, it is useful to get feedback from the patient and family regarding any subjective improvement over the next few days.

Documented improvement in one or more of these measures following the procedure suggests that the patient will have a better outcome after placement of a ventriculoperitoneal (VP) shunt [64]. Most studies suggest that this test has excellent positive predictive value (90 to 100 percent), but limited negative predictive value (30 to 50 percent), with a number of patients who show no response to removal of CSF but later improve with surgery [25,65,66]. Others report that this test does not add predictive value over clinical and radiographic criteria [67].

Lumbar drain trial — An alternative method involves continuous CSF drainage at a rate of 5 to 10 mL/hour via a temporary catheter in the lumbar CSF space. Clinicians, patients, and family members evaluate the clinical response over an observation period in hospital of two to seven days. Clinical improvement after CSF drainage is not associated with change in ventricular size; hence, neuroimaging is not a routine part of this assessment [68]. In small series (<20 patients), this technique has reportedly had 100 percent sensitivity and specificity in predicting subsequent response to shunting [69,70].

However, others report that, while correctly identifying shunt responders, the negative predictive value is low [71]. In one series, for example, 38 patients with a negative response to lumbar tap underwent lumbar drainage, with an 87 percent positive predictive value for surgical response [65]. However, 63 percent of patients with a negative response improved after shunting.

Meningitis and subdural hematoma are potential serious complications of these tests, particularly prolonged lumbar drainage [10,65]. These are, in general, rare, but occurred in 2 of 38 patients in one series [65].

CSF evaluation — When either a lumbar puncture or a lumbar drain trial is performed, it is reasonable to send routine diagnostic tests (cell count, protein, glucose) on the CSF when a lumbar puncture is performed in this setting. In most cases of idiopathic NPH, it is expected that these test results will be normal, although a mild elevation of protein in isolation is a common nonspecific finding. Pleocytosis requires a rigorous evaluation to determine the underlying etiology. (See "Approach to the patient with chronic meningitis", section on 'CSF examination and other laboratory testing'.)

Cisternography — Isotope cisternography consists of injection of a radiolabeled isotope into the lumbar cistern and visualizing its distribution through the cisterns, ventricles, and brain convexities at set time periods following its introduction (4, 24, 48, and 72 hours). NPH is suggested by nonappearance of the isotope over the brain convexities at 72 hours.

While still often performed in the evaluation of patients with NPH, the utility of this test is limited with poor predictive values for surgical response [3,25,43,50,63,72].

Other tests (not recommended)

CSF biomarkers – There are excellent CSF biomarkers for AD that include low CSF Aβ42 and high phospho-tau levels. Unfortunately, these biomarkers cannot be used to discriminate those with NPH and comorbid AD from those with NPH without AD [73]. The reason is that NPH itself, as well as shunting, may alter biomarker levels [73]. The typical CSF findings in a preshunt NPH patient are low Aβ42 and low phospho-tau. After shunting, levels of both proteins typically increase.

VENTRICULAR SHUNTING — The treatment for NPH is an implanted ventricular shunt.

Patient selection — Because of the lack of a gold standard for diagnosing NPH, the limited predictive ability of confirmatory tests, and the invasive nature of implanted shunts, patient selection for shunting is complicated and should be individualized. The absence of any one favorable predictor or the presence of a negative predictor does not rule out the possibility of a shunt response. The predictive values of diagnostic test findings are discussed above. (See 'Diagnostic evaluation' above.)

In practice, we suggest ventricular shunting in patients who have typical clinical and imaging findings for NPH, a positive clinical response to a lumbar tap test or lumbar drain trial, and limited or absent negative prognostic indicators (table 2 and algorithm 1).

The following factors are the most important to consider in assessing the probable response to surgery.

Dementia – Patients with moderate to severe dementia are unlikely to improve after shunting [25]. This may reflect progression of NPH to an advanced stage in which neurologic injury is fixed or an underlying degenerative dementia such as Alzheimer disease (AD) is the cause of or contributor to the patient's syndrome. (See 'Differential diagnosis' above.)

In two case series that included a cortical biopsy, AD pathology was associated with limited or absent postoperative improvement [74,75]. In comparison, others have suggested that AD pathology is not associated with a poor surgical response, but these studies had a follow-up period of only a few months [22,76].

Cause of NPH – Patients with idiopathic NPH have lower rates of improvement after shunt placement compared with patients with a known etiology [25,44,50,72].

Duration of symptoms – Data regarding the preoperative duration of symptoms reveal the strongest association with outcome at the extremes of symptom duration; patients with less than six-month duration have the highest chance of improvement, while those with symptoms, particularly dementia, present for more than two or three years have lower rates of improvement [7,10,32,77]. In one series, dementia present for more than two years was associated with shunt failure in 5 of 7 patients, while 21 of 23 patients with a shorter duration of symptoms improved after surgery [32]. However, others have not found an association between duration of symptoms and surgical response [21,25].

Age – Most studies do not find that age influences surgical outcome [50]. However, selection bias may influence these results. In one series, advanced age predicted a worse response to temporary lumbar drainage [10]. However, among the 84 patients with a positive response to lumbar drainage who went on to surgery, age did not influence surgical response.

Clinical manifestations – The relative prominence of the gait disorder versus cognitive impairment, especially early in the course of the syndrome, is felt by many to be associated with surgical outcome [25,32,77]. Late-presenting or no gait disorder predicts a poor surgical outcome in more than 80 percent of patients, while early gait disorder was less strongly predictive of surgical success in 40 to 50 percent [25,43,78].

Urinary incontinence – Despite the fact that urinary incontinence is a late sign of NPH, its presence does not clearly impact on a patient's chance of improvement after surgery [7,25].

Efficacy — When patients are appropriately selected, shunting for NPH has a sustained effect in one-half to two-thirds of patients with an acceptable complication rate. Supporting evidence is low quality and consists largely of observational studies with relatively short-term follow-up, however.

A 2013 systematic review identified 64 studies in over 3000 patients with idiopathic NPH, including 27 retrospective studies, 36 prospective observational studies, and 1 randomized trial [79]. The average rate of sustained improvement for three years after shunting was 40 percent in studies in the 1990s, 70 percent in the 2000s, and 73 percent since 2006. The average mortality rate was 9.5 percent in the 1970s and 0.2 percent since 2006. Infection rates decreased from 8.2 percent in the 1970s to 3.5 percent since 2006. The shunt revision rate also decreased from 17.8 percent in the 1970s to 13 percent since 2006.

Two small, randomized, unblinded crossover trials have examined the value of shunting for idiopathic NPH in selected patients [39,79]. In the larger of the two trials, 93 patients were randomly assigned to immediate lumboperitoneal shunting versus waiting for three months, followed by shunting [80]. The primary endpoint was improvement on the modified Rankin scale (mRS). At three months, 65 percent of those shunted immediately improved by one point or more on the mRS, compared with 5 percent of those not shunted. At one year postshunt, the early and delayed groups had similar rates of improvement (67 and 58 percent). The serious adverse event rate was 15 percent at three months and 28 percent at one year.

Types of shunts — Most shunts divert cerebrospinal fluid (CSF) from a catheter in the lateral ventricle into the abdomen (ventriculoperitoneal [VP]) or, less commonly, into the heart (ventriculoatrial). Limited data from Japan indicate that lumboperitoneal shunting may be an effective alternative that does not require cranial surgery [80-82], although larger studies are needed to better determine the safety and efficacy of such shunts compared with the more commonly used VP shunts.

CSF flow is controlled via a one-way valve in the shunt; many different models of VP shunts are in clinical use [83,84]. Shunts are often classified into low-, medium-, and high-pressure systems. A programmable valve has been developed that allows pressure adjustments without reoperation. In the setting of subdural hematoma, an increase in the pressure setting can aid in hematoma resorption [63]. In patients without a clinical response to shunt placement, the pressure setting can be lowered to increase drainage.

Studies comparing efficacy and complications of different VP shunts are limited. Most are unblinded comparisons, and mostly retrospective [85]. In general, lower-pressure systems may be slightly more likely to result in clinical benefit than higher-pressure systems, but at the expense of an increased risk for symptomatic overdrainage and subdural hematoma formation. Programmable shunts do not seem to lower the risk of complications compared with fixed-valve shunts, but the ability to titrate to a lower-pressure setting with a programmable valve may result in clinical improvement in some patients. Examples of individual studies include the following:

A retrospective comparison of programmable versus standard shunt valves among 407 patients with NPH found a higher incidence of nontraumatic subdural hematoma and hygromas for the programmable valve versus the standard valve (8.5 versus 3 percent) [84]. However, there was no significant difference in the number of surgical decompressions or the number of subsequent surgical shunt revisions (25 versus 23 percent). The cost of implanting a programmable valve was estimated to be three times as much as the standard valve.

A Dutch NPH trial randomly assigned 96 patients with NPH to receive either a low (40 mm H2O) or medium-high (100 mm H2O) pressure shunt [86]. There was a strong trend toward a higher rate of improvement on a combined measure of gait and cognition in patients receiving a low-pressure shunt (74 versus 53 percent with a medium-pressure shunt, p = 0.06). Subdural effusions were more common in the low-pressure shunt group (71 versus 34 percent), but these did not affect clinical outcome. Unblinded outcome assessments limit the ability to draw firm conclusions from this study.

A randomized trial that compared a fixed medium-pressure valve setting (120 mm H20) with an initial valve setting of 200 mm H20 that was gradually reduced to 40 mm H20 over a six-month period found a similar rate of shunt complications and overdrainage symptoms in the two groups [87,88]. Efficacy data were available for 55 out of 68 randomized patients (81 percent); in this subset, maximum clinical improvement was seen by three months postoperatively in both groups, and efficacy outcomes were similar between groups. In the adjustable-pressure group, overdrainage was significantly more common with valve settings ≤120 mm H20 than >120 mm H20 (seven versus zero patients). This indicates that a different trial design, in which shunt pressure was only lowered to symptomatic improvement rather than a fixed target pressure, may have resulted in fewer complications in the adjustable-shunt group.

A retrospective comparison of a flow-regulated shunt system with the more traditional pressure-regulated system found no differences in complication rate, shunt malfunctions, or operative success [89].

Shunt complications — A systematic review of studies of shunting in NPH reported a pooled mean shunt complication rate of 38 percent [25]. Six percent of patients had complications resulting in permanent neurologic sequelae or death and 22 percent required a second surgery. A subsequently published case series that was relatively large (55 patients) reported that 53 percent of their patients required a shunt revision over six years of follow-up [90].

Shunt overdrainage is the most common complication in the first year, occurring in up to one-third of patients [25,86,91]. Overdrainage may be asymptomatic or present with sustained or postural headaches; radiologic signs of overdrainage range from subdural effusions to subdural hematoma. Serious overdrainage, defined as a symptomatic subdural hematoma requiring surgery, occurs in less than 10 percent of patients and may be more likely in those with a high lumbar puncture opening pressure (eg, >160 mm H2O), a large difference between the lumbar and valve opening pressures (eg, >40 mm H2O), a high body mass index [91], and use of aspirin or other antiplatelet agents [92]. In most cases, subdural hematomas are thought to result from tearing of bridging veins in the setting of shunt overdrainage.

Other reported complications include:

Intracranial infection.

Seizures.

Intracerebral hemorrhage from catheter placement.

Mechanical shunt failures or blocked shunts.

Abdominal injury (ascites, peritonitis, abdominal perforations, volvulus) in VP shunts.

Arrhythmias from incorrect distal catheter placement, systemic emboli in ventriculoatrial shunts.

Intracerebral hemorrhage is an immediate surgical complication, occurring in 3 to 6 percent of cases.

Shunt infections usually present within the first month after operation (or reoperation), but can appear later [90]. The manifestations may be quite vague with varying degrees of headache, malaise, nausea, vomiting, and fever. The most common pathogens arise from skin flora.

Direct aspiration of CSF from the shunt is often required for diagnosis. Removal of the shunt as well as antibiotic treatment is usually recommended. This topic is discussed separately. (See "Infections of cerebrospinal fluid shunts and other devices".)

Shunt malfunction or suboptimal function may be to blame if a patient fails to improve after surgery [50]. If a programmable valve was placed, lowering the pressure setting to improve drainage may be indicated. Otherwise, lumbar tap tests and CSF infusion tests may be used to determine if shunt revision should be considered [93].

While most shunt complications have the highest incidence within the first year, shunt malfunction is an enduring risk [90,94].

The routine performance of a brain computed tomography (CT) in follow-up has undetermined clinical utility. While ventricular size may decrease postoperatively, studies have mixed results in associating this with postoperative improvement [74]. Thus, CT scan cannot be considered a reliable indicator of shunt functioning. CT scan may also detect a subclinical subdural effusion or hematoma, but as these are unlikely to require treatment, the utility of diagnosing them is uncertain.

Regular follow-up and attention to symptoms are required. When patients experience neurologic deterioration, a brain CT scan should be performed to exclude the possibility of subdural hematoma and check the catheter position. A shunt series of plain radiographs that visualize the entire shunt system should be performed, looking for visible obstruction. An abdominal ultrasound may also detect obstruction of the shunt tip.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Normal pressure hydrocephalus".)

SUMMARY AND RECOMMENDATIONS — Normal pressure hydrocephalus (NPH) refers to a condition of pathologically enlarged ventricular size with normal opening pressures on lumbar puncture.

Secondary NPH is most commonly associated with subarachnoid hemorrhage or meningitis, occurs in any age group, and is associated with impaired cerebrospinal fluid (CSF) resorption. Idiopathic NPH is more common in older adults. Its pathogenesis is uncertain. (See 'Pathophysiology' above.)

NPH is associated with a classic triad of cognitive impairment, gait disturbance, and urinary incontinence. Shunt-responsive NPH is more likely when the gait disturbance appears early on and is more prominent than the cognitive impairment. (See 'Clinical features' above.)

The evaluation of a patient with possible NPH includes cognitive assessment and exclusion of alternative causes of gait dysfunction, both neurologic and non-neurologic. (See 'Cognitive evaluation' above and 'Alternative causes of gait and urinary dysfunction' above.)

The brain magnetic resonance imaging (MRI) is an essential test in a patient with NPH and demonstrates ventriculomegaly out of proportion to sulcal enlargement and no evidence of CSF flow obstruction. Features of disproportionately enlarged subarachnoid space hydrocephalus (DESH) suggest a good surgical prognosis. Extensive white matter disease and cortical atrophy, particularly involving the medial temporal lobe, are unfavorable indicators. (See 'Magnetic resonance imaging' above.)

In patients with clinical and MRI features suggestive of NPH, we use a lumbar tap test to help identify patients likely to respond to shunt placement (algorithm 1). A lumbar drain trial is preferred by some clinicians. The sensitivity and specificity of these tests are uncertain. (See 'Confirmatory tests' above.)

We suggest ventricular shunting in patients who have clinical and MRI evidence of NPH, a positive test result associated with response to shunting (eg, lumbar tap test), and limited or absent negative prognostic indicators (table 2) (Grade 2C). (See 'Patient selection' above.)

In selected populations, up to two-thirds of patients can expect some degree of sustained benefit after shunting. Some prognostic indicators may identify those more or less likely to achieve benefit (table 2). (See 'Patient selection' above and 'Efficacy' above.)

Shunt complications are common and potentially severe, even fatal, and require vigilance in follow-up on the part of patients and families. (See 'Shunt complications' above.)

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