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The diagnosis and treatment of idiopathic normal pressure hydrocephalusGary L Gallia, Daniele Rigamonti and Michael A Williams*

INTRODUCTIONNormal pressure hydrocephalus (NPH), which was first introduced into the English clinical literature in 1965, describes the syndrome of gait disturbance, cognitive deterioration and urinary incontinence that is associated with ventricular enlargement in the absence of elevated cerebro-spinal fluid (CSF) pressure.1,2 When it occurs secondarily to other disease processes, including subarachnoid hemorrhage, traumatic brain injury, cerebral infarction and meningitis, this syndrome is referred to as secondary NPH.3,4 NPH in patients without known precipitants is termed primary or idiopathic NPH (INPH). In 2002, an international NPH study group was assembled to develop guidelines for INPH. These guidelines, which were published in 2005, covered four major topics: the clinical diagnosis of INPH, the value of supplementary diagnostic tests, surgical management, and outcome of CSF shunting in INPH.5–9 Television and internet media campaigns have increased public aware-ness of INPH,10 and many patients and their families are now asking their physicians about the possibility of a diagnosis of NPH.

CLINICAL PRESENTATION AND RADIOGRAPHIC EVALUATIONINPH is characterized clinically by the triad of gait disturbance, dementia and urinary in continence.1,2 Symptoms typically develop insidiously, and generally occur between the sixth and eighth decades of life.11–14 Gait disturbances are typically the first signs of INPH, and have been variously described as apraxic, bradykinetic, glue-footed, magnetic, parkinsonian and shuf-fling.8,15 Patients often present with a history of falls. The aberrant ambulation observed in INPH is characterized by a slow, wide-based gait, short shuffling steps, and difficulty in turning and tandem walking. Notably, there is no significant motor weakness.

The cognitive deficits are typically of the subcortical type, characterized by inattention, psychomotor retardation and difficulty with

Idiopathic normal pressure hydrocephalus (INPH) is a syndrome that is characterized by gait impairment, cognitive decline and urinary incontinence, and is associated with ventriculomegaly in the absence of elevated cerebrospinal fluid (CSF) pressure. There is significant variation in the clinical presentation and progression of this disorder, and its diagnosis often represents a challenge for neurologists and neurosurgeons. Various supplemental tests, including the CSF tap test, external CSF drainage via spinal catheter, and CSF outflow resistance determination, can improve the accuracy of predicting a response to surgical treatment. CSF shunting provides significant symptom improvement in the majority of appropriately evaluated patients. In 2005, an international study group published evidence-based guidelines for the diagnosis and management of INPH. This review will highlight the clinical presentation, radiographic findings, supplemental prognostic tests, differential diagnosis, surgical treatment and outcomes of INPH.

KEYWORDS cerebrospinal fluid shunt, diagnosis, idiopathic normal pressure hydrocephalus, hydrocephalus, surgery

GL Gallia is a neurosurgery resident, D Rigamonti is Professor of Neurosurgery, Radiation Oncology and Molecular Sciences, Radiology, and Physical Medicine and Rehabilitation, and MA Williams is an associate professor in the Departments of Neurology and Neurosurgery, all at the Johns Hopkins Hospital, Baltimore, MD, USA.

Correspondence*Johns Hopkins Hospital, Adult Hydrocephalus Program, 600 N. Wolfe Street, Phipps 100, Baltimore, MD 21287, [email protected]

Received 31 March 2006 Accepted 12 May 2006

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REVIEW CRITERIAPubMed was used for a literature search from 1966 to the present for articles on “normal pressure hydrocephalus”. The abstracts of retrieved citations were reviewed and prioritized by relative content. Full publications were obtained and also searched for relevant references and related articles.

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executive function.1,16 Apraxia, agnosia and aphasia are rare in INPH.

Urinary incontinence is the third primary symptom of INPH. In early stages of INPH, urinary frequency and urgency are present. With disease progression, urinary and even fecal incontinence can be observed. Urodynamic testing demonstrates bladder hyperactivity.17

There is significant variation in the clinical presentation, severity and progression of these symptoms, and the entire triad need not be present in order to consider a diagnosis of INPH. Typically, however, gait and balance impair-ment appear either before or concurrently with urinary incontinence or the onset of dementia. The full diagnosis of INPH requires evidence from the patient’s clinical history, physical examination and neuroimaging.

An essential part of the evaluation of patients with suspected INPH is neuroimaging with either CT or MRI to assess ventricular size (Figure 1). Although no findings on imaging studies of the brain are sufficient on their own to diagnose INPH, ventricular enlargement is necessary to establish the diagnosis of INPH for patients with appropriate symptoms. A frontal horn ratio (Evans’ index), defined as the maximal frontal horn ventricular width divided by the transverse inner diameter of the skull, signi-fies ventriculo megaly if it is 0.3 or greater.8,18 Other radiographic findings associated with INPH include the following: periventricular

hyperintensities, which are often associated with subcortical microvascular ischemia (so-called small-vessel disease), but do not exclude the possibility of INPH; increased CSF flow velocity in the aqueduct; thinning and eleva-tion of the corpus callosum on sagittal images; and no visible evidence of obstruction to CSF flow.8,14,19–22

Several other brain imaging techniques have been investigated in patients with INPH, including single-photon emission CT, PET, nuclear cisternography, and CSF flow velocity. The diagnostic value of these tests has not been established, and, at present, these examinations are not part of the routine work-up of patients with suspected INPH.7,8

DIFFERENTIAL DIAGNOSISBecause INPH is a disease of the elderly popula-tion, an age-group in which gait difficul-ties, dementia, and urinary incontinence are common, a diverse differential diagnosis of the individual symptoms should be considered, including neurodegenerative diseases, vascular etiologies and urological disorders. INPH is one of many disorders affecting gait; other common conditions include peripheral neuropathy, cervical or lumbar stenosis, arthritis, vestibular diseases and Parkinson’s disease. The differentia-tion between INPH and Parkinson’s disease can be challenging. Both diseases share a hypo-kinetic gait owing to a decreased stride length, but specific features associated with INPH include a broad-based gait pattern with outward rotated feet and a diminished step height, rela-tively preserved arm swing, and erect trunk.23 Additionally, external cues only mildly improve gait in INPH, whereas they are effective at raising the stride length and cadence in patients with Parkinson’s disease.23

Dementia is a common clinical syndrome in the elderly and has numerous underlying causes.24 The cognitive impairment observed in INPH has some similarity to other subcortical dementias, including Parkinson’s disease, diffuse Lewy body disease and vascular dementia. The absence of apraxia, agnosia and aphasia can help differentiate INPH from cortical dementias, including the most common dementing illness, Alzheimer’s disease.

As with gait disturbances and cognitive decline, there are numerous etiologies of urinary incontinence in the elderly, all of which should be evaluated in the work-up of INPH. Urinary

A B

Figure 1 Neuroimaging of two patients with idiopathic normal pressure hydrocephalus. (A) Head CT scan demonstrating ventriculomegaly without significant cortical atrophy. (B) Brain MRI demonstrating ventriculomegaly and evidence of subcortical ischemic changes. Both patients’ idiopathic normal pressure hydrocephalus symptoms improved following shunt placement.



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incontinence might reflect prostate disease in men, or stress incontinence or chronic urinary tract infections in women.

SUPPLEMENTAL PROGNOSTIC TESTSAccording to the INPH consensus guidelines, patients can be categorized as having probable, possible or unlikely INPH on the basis of history, neurological examination and neuroimaging (see Supplementary Box 1 online).8 Without addi-tional testing, between 46% and 61% of probable and possible INPH patients will improve with surgical treatment.7 There are several supple-mental tests that improve diagnostic accuracy and should be considered in patients with probable and possible INPH. These tests include a CSF tap test, external CSF drainage via spinal drainage, and CSF outflow resistance determination.7

The CSF tap test, also called a large-volume lumbar puncture, involves the withdrawal of 40–50 ml of CSF by means of lumbar punc-ture. Symptomatic improvement after CSF removal increases the likelihood of a favorable response to shunt placement (positive predic-tive value 73–100%).7 The CSF tap test has a low sensitivity (26–61%), however, and a nega-tive test cannot be used to exclude a diagnosis of INPH.7 The opening pressure should also be measured. The range of INPH opening pres-sure is 60–240 mm H2O, or 4.4–17.6 mmHg.7,8 Detailed documenta tion of the clinical examina-tion findings by a physician or other qualified health-care professional before and after CSF removal is strongly recommended, as patients and families might be biased by their hope of recovery, and can over-interpret changes in function after the lumbar puncture.

Assessing clinical response to prolonged CSF drainage via a spinal catheter has a combina-tion of high sensitivity (50–100%), specificity (60–100%) and positive predictive value (80–100%).7 This approach requires hospitaliza-tion and nursing staff trained and competent in managing external CSF drainage, and can be associated with a higher complication rate (infection, nerve root irritation). Consequently, it is currently only performed at a limited number of centers in the US. Identification of abnormally elevated CSF outflow resistance also increases the likelihood of a favorable response to shunt placement compared with the clinical and radiographic evaluations,7 and this tech-nique is in more common use in Europe than in the US.

TREATMENTThe treatment for INPH is surgical diversion of CSF. This is accomplished by implanting a shunt to drain CSF from either the intracranial ventricular system or the lumbar subarachnoid space to a distal site, such as the peritoneal or pleural cavity or the venous system, where the CSF can be re absorbed. The most common shunts utilized today are ventriculo peritoneal (VP) and ventriculo atrial (VA) shunts. Several factors are considered when evaluating patients for placement of a shunt, including the risk:benefit ratio of the procedure, sites of the prox-imal and distal catheter, valve specifics, and shunt-related complications.6

Placement of a shunt is a neurosurgical procedure performed under general anesthesia, taking less than an hour to complete. There are few intraoperative and perioperative complica-tions. As with other invasive surgical procedures, a risk:benefit ratio evaluation should take into account comorbidities, functional status and life expectancy of the patient.

The selection of the proximal and distal cath-eter sites and valve type is individualized. The proximal catheter is typically placed within the ventricles, although the lumbar subarachnoid space can be used in patients for whom there is concern of injury to the brain from inserting a ventricular catheter—for example, a patient with previous injury to the right hemisphere, in whom a complication of shunt insertion into the left hemisphere could result in bilateral cere-bral injury. The distal catheter site depends on assessment of the patient’s anatomy and surgical history. For example, previous abdo minal surgery or a history of peritonitis might render the peritoneal cavity less suitable for CSF absorp-tion. In these situations, VA shunts are useful; a third option is to place the distal catheter into the pleural cavity.

Various types of valve design are available, including differential pressure valves (DPVs), and flow-limiting valves. In the case of DPVs, the shunt opens and CSF flows when the pres-sure difference across the valve exceeds a set value. These valves can generally be classified as low, medium or high pressure. With a DPV, change in body position from supine to upright can cause overdrainage of CSF by a siphoning effect if the hydrostatic pressure gradient (i.e. the vertical distance between the ventricles and the distal catheter) is greater than the opening pressure of the DPV. To reduce this



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gravity-dependent drainage, anti-siphon devices were developed.25,26 Flow-limiting valves were designed to operate more ‘physiologically’ by maintaining a constant flow rate over a range of pressure differentials. The flow through these valves is typically regulated by increasing the resistance as intracranial pressure increases. Under conditions of high intracranial pres-sure, however, these valves operate in a high flow-rate mode. As yet, there is no evidence that one particular shunt design or configuration produces better outcomes in treating INPH than any other, and the selection usually depends as much on the surgeon’s preference as it does on other factors.

The most recent advance in shunt valve design is the development of adjustable or programmable valves.27–31 These valves, which are designed to enable a range of pressure settings from 20–200 mm H2O, depending on the make and model, can be adjusted transcutaneously by the use of a magnetic device. These valves are partic-ularly beneficial in the management of INPH, because both overdrainage and under drainage can be managed noninvasively (Figure 2). An important limitation of adjustable shunts is that they are susceptible to external magnetic fields. Although this magnetic susceptibility is not usually problematic for adults in daily life, magnetic fields from MRI scanners and even small magnets (such as kitchen magnets) that are

placed too close to the shunt might alter the pres-sure setting of the valve.32,33 As a general rule, patients with adjustable shunts can have MRI scans, but they should be advised to have the shunt re-programmed as soon as possible afterwards to limit the risk of inadvertent over drainage or underdrainage.

RISKS AND COMPLICATIONSAlthough CSF shunting is a relatively straight-forward neurosurgical procedure, it is asso-ciated with numerous potential complications. These complications can be categorized into three main groups: first, those related to the operative procedure (e.g. intracerebral hema-toma, catheter malposition, shunt infection); second, those related to the shunt system (e.g. valve malfunction, proximal or distal catheter obstruction); and third, those attributable to the flow character istics of the shunt system (e.g. overdrainage-associated headaches, or subdural hygroma or hematoma).

The most common complication after shunt placement is obstruction. In INPH, this is clini-cally manifested by recurrence of the original INPH symptoms after a period of recovery, but it should also be suspected for patients who have no improvement after shunt surgery.34 Injection of a radionuclide tracer into the shunt reservoir can determine whether flow through the shunt is partially or totally obstructed.35,36

A B C

Figure 2 Development and noninvasive treatment of bilateral subdural hygromas following placement of a programmable shunt for idiopathic normal pressure hydrocephalus. (A) Postoperative head CT shows no evidence of subdural fluid collections. (B) Head CT demonstrating bilateral subdural hygromas (arrows). The patient noted worsening gait and balance similar to her preoperative symptoms. To treat the hygromas, the pressure setting of the shunt was increased. (C) Head CT scan 4 weeks later demonstrating resolution of the subdural fluid collections. The patient’s symptoms concomitantly improved.



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The INPH guidelines list complications that include shunt malfunction (20%), subdural hematoma (2–17%), seizure (3–11%), shunt infection (3–6%) and intracerebral hematoma (3%).6 In our recent series of 132 INPH patients, 33% had their shunts revised, 7% developed an infection, 2% developed a subdural hematoma, and 1% developed an intracerebral hema-toma.14 Because our clinical approach includes monitoring and investigation of the possibility of shunt obstruction, our rate of shunt revision might be higher than the rates reported in other published series.

OUTCOMESVariable improvement rates after CSF shunting have been reported in the literature. This varia-tion can be explained mainly by differing methods of patient selection criteria and post-operative assessment, and variations in follow-up periods. The INPH guidelines reported improvement rates of 30–96%.5 A 2001 meta-analysis reported that 59% of patients improved after shunting, and 29% experienced prolonged improvement. Although all symptoms can resolve following shunt surgery, gait is the most likely to improve.3 We found that 75% of patients had improvement in at least one INPH symptom, and 46% had improvement in all INPH symptoms at 18 months. Altogether, 93% had gait improvement, but dementia and urinary incontinence were only half as likely to improve. The time to intervention is important: numerous studies have demonstrated that a longer dura-tion of INPH symptoms is associated with lower likelihood of response to shunting.14,37,38

Of the three classic symptoms, cognitive impairment is the least likely to improve following treatment.3 Although variable rates of improve-ment have been reported,5,39 we and others have observed significant cognitive improvement in more that 50% of patients following shunting.40–43 This is in contrast to the outcomes observed with Alzheimer’s disease, in which fewer than half of the patients exhibit a clinically significant response to anti cholinesterase therapy.44

Because none of the currently available prog-nostic tests have 100% sensitivity, there are patients who will not improve after shunting. If a head CT scan demonstrates no problems requiring surgical intervention, evaluation of shunt patency is indicated.34 If the shunt is obstructed, it should be revised. If the shunt is functioning adequately and the patient has

not improved clinically, either the patient does not have NPH, or, alternatively, they have comorbid conditions severe enough that treatment of INPH is unable to improve the patient’s sympto matology.

MODEL OF CNS DISEASEINPH may represent a unique reversible form of neuronal injury. The precise impact of this disease on the CNS, and how the associated neurological symptoms that might be present for months or years can reverse in weeks or months, is not fully understood. Future basic science and clinical studies exploring hydrocephalus will not only help us to understand the mechanisms of neuronal injury and recovery in INPH, but might also elucidate mechanisms that could be applicable to other CNS disorders. The National Institutes of Neurological Disorders and Stroke, in collaboration with other NIH Institutes, spon-sored a 2-day workshop on hydrocephalus in September 2005 to promote awareness of and interest in hydrocephalus research.

EPIDEMIOLOGYOnly a few epidemiological studies on INPH are available, so the incidence and prevalence of this disorder are difficult to determine. The inci-dence of INPH has been reported to be between 1.8 cases per 100,000 individuals and 2.2 cases per 1,000,000 individuals.45,46 A door-to-door survey of individuals older than 65 years of age in two German villages reported that the preva-lence of NPH was 0.41% in this age-group.47 It has been reported that between 1.6% and 5.4% of patients with dementia have NPH,48,49 and a recent analysis of ‘nondegenerative non vascular dementia’ from a registry in Rochester, MN, found no cases of NPH from 1990 to 1994. The authors concluded, however, that with a popula tion of 70,745, failure to find NPH was ‘not unexpected’.50

CONCLUSIONSINPH is a potentially treatable condition consisting of gait disturbance, dementia and urinary incontinence, and it should therefore be included in the differential diagnosis of elderly patients presenting with such symptoms. Patients are categorized into those with probable, possible and unlikely INPH on the basis of their clinical history, physical examination, radio-graphic evalua tion and supplemental testing. The mainstay of treatment remains the surgical



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placement of a shunt, and in properly selected patients shunting is associated with significant symptom improvement. The recently published inter national INPH guidelines providing the framework for standardization of patient evalua-tion, diagnostic work-up and outcome assessment are useful in guiding the clinical management of INPH patients.

Supplementary information is available on the Nature Clinical Practice Neurology website.

KEY POINTS■ Idiopathic normal pressure hydrocephalus

(INPH) is characterized by gait disturbance, cognitive deterioration and urinary incontinence, and is associated with ventricular enlargement in the absence of elevated cerebrospinal fluid (CSF) pressure

■ INPH may represent a unique reversible form of neuronal injury, the mechanism of which is not well understood

■ Only a few epidemiological studies on INPH are available, so the incidence and prevalence of this disorder are difficult to determine

■ An essential part of the evaluation of patients with suspected INPH is neuroimaging with either CT or MRI to assess ventricular size

■ Because INPH is a disease of the elderly population, a diverse differential diagnosis of the individual symptoms should be considered, including neurodegenerative diseases, vascular etiologies and urological disorders

■ Treatment for INPH is surgical diversion of CSF, which is accomplished by implanting a shunt to drain CSF from either the intracranial ventricular system or the lumbar subarachnoid space to a distal site, where the CSF can be reabsorbed

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Competing interestsD Rigamonti and MA Williams have declared associations with the following companies/organizations: Medtronic, the Hydrocephalus Association. See the article online for full details of the relationship. GL Gallia declared he has no competing interests.



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