Diagnosis and Management of Idiopathic Normal-Pressure Hydrocephalus

Neurology Clinical Practice
Diagnosis and
management of idiopathic
normal-pressure
hydrocephalus
Michael A. Williams, MD, FAAN
Norman R. Relkin, MD, PhD
Summary
The diagnosis and management of idiopathic normalpressure hydrocephalus (iNPH), a disorder of gait
impairment, incontinence, and dementia that affects
elderly patients, incorporates an organized approach
using familiar principles for neurologists. The starting
point is a comprehensive history and neurologic examination, review of neuroimaging, and evaluation of the
differential diagnosis. Coexisting disorders should be
treated before specific iNPH testing is performed.
Specific iNPH testing includes assessing patient
response to temporary CSF removal and testing CSF
hydrodynamics. In properly selected patients, all iNPH
symptoms, including dementia, can improve after
shunt surgery. The longitudinal care of iNPH patients
with shunts includes evaluation of the differential diagnosis of worsening iNPH symptoms and treatment of
coexisting disorders. Evaluation of shunt obstruction
is often indicated, and if it is found, surgical correction
is likely to result in symptomatic improvement.
diopathic normal-pressure hydrocephalus (iNPH)

is a disorder of the elderly with symptoms of
impaired gait and mobility, urinary urgency
and incontinence, and mild cognitive impairment or dementia in the presence of ventriculomegaly. The clinical presentation alone is usually not sufficient to diagnose iNPH and recommend shunt surgery, as each of the primary iNPH symptoms can have multiple potential
etiologies, and enlarged ventricles can be seen with either hydrocephalus or brain atrophy.
The Sandra and Malcolm Berman Brain & Spine Institute, Adult Hydrocephalus Center (MAW), Sinai Hospital
of Baltimore, MD; and Clinical Neurology and Neuroscience, Department of Neurology and Neuroscience
(NRR), Weill Cornell Medical College, New York, NY.
Funding information and disclosures are provided at the end of the article. Full disclosure form information
provided by the authors is available with the full text of this article at Neurology.org/cp.
Correspondence to: [email protected]
Neurology: Clinical Practice
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www.neurology.org/cp
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Michael A. Williams and Norman R. Relkin
The terms hydrocephalus and ventriculomegaly

are not synonymous. Although all patients with
iNPH should have enlarged ventricles, not all
elderly patients with enlarged ventricles have
iNPH.
Organized approach to diagnosis and treatment
The goal of the evaluation of possible iNPH is to predict whether shunt surgery is likely to benefit
the patient sufficiently to justify the risks of surgery and postoperative morbidities. Following is
an organized approach to evaluation.
1.
2.
3.
4.
5.
Clinical evaluation
Treatment of other disorders before undertaking specific testing for iNPH
Testing that is specific for prognosticating treatment response in iNPH
Shunt surgery
Longitudinal follow-up
Clinical evaluation
Key neurologic features A comparison of key clinical findings for iNPH from the International and Japanese guidelines is presented in table 1.14 By definition, iNPH is idiopathic;
however, the neurologic history should include known risk factors for communicating hydrocephalus, including meningitis, encephalitis, traumatic brain injury (including concussion), subarachnoid hemorrhage, and brain radiation. Enlarged head circumference is also a
risk factor that may indicate a congenital component to the disorder.5 Patients with secondary
communicating hydrocephalus should be evaluated for the need for shunt surgery in the
manner outlined below, except in clinically obvious cases, such as the development of hydrocephalus during hospitalization for subarachnoid hemorrhage.
Symptom onset The onset of iNPH symptoms is insidious and should have been evident for
at least 6 months. Some patients and families are not aware of symptoms until a precipitating
event occurs (e.g., a fall or a change in symptoms after a surgical procedure). Careful questioning can clarify the nature of symptom onset.
Gait In iNPH, a higher-level gait disorder is seen with disturbed postural and locomotor
reflexes in the absence of primary sensorimotor deficits.6 Findings include difficulty with
transitional movements (sitting to standing or standing to sitting); gait initiation failure;
poor foot clearance with shuffling, tripping, falling, or festination; multistep turns with
instability; and retropulsion or anteropulsion of stance.7 The use of a standardized gait
evaluation (e.g., the Tinetti score, Boon Scale, or the timed up-and-go test) can be helpful.
Spasticity, hyperreflexia, and other upper motor neuron findings are not typical. Symptoms of iNPH are symmetric; therefore, lateralizing findings should increase suspicion of
other disorders.
Bladder dysfunction The bladder dysfunction of iNPH is usually urinary urgency with difficulty inhibiting bladder emptying.8 In the early stages, patients may experience urgency
without incontinence or with loss of a few drops of urine before reaching the toilet. Nighttime urinary frequency is common. Patients are usually aware of their need to urinate and are
concerned about their accidents. Incontinence without awareness of urinary urge or that ones
clothes are wet is not characteristic of iNPH.
Dementia The dementia of iNPH includes apathy or amotivation, daytime sleepiness, psychomotor slowing, and other features of frontal-subcortical dysfunction.911 Functional losses
376
2013 American Academy of Neurology
Diagnosis and management of idiopathic normal-pressure hydrocephalus
Table 1
Key clinical features of idiopathic normal-pressure hydrocephalus: Comparison between the International and the
Japanese guidelines
Feature
International guidelines
Japanese guidelines
Essential
symptoms
Findings of gait/balance disturbance must be present,

plus at least one other area of impairment in cognition,
urinary symptoms, or both
More than one of the clinical triad: gait disturbance,

cognitive impairment, and urinary incontinence
Gait disturbance is the most prevalent feature, followed
by cognitive impairment and urinary incontinence
Symptom
onset
Insidious
Symptoms progress slowly
Symptom
duration
Minimum duration of 36 months
Age at onset
After age 40 years
After age 60 years
Etiology
No evidence of an antecedent event such as head

trauma, intracerebral hemorrhage, meningitis, or other
known causes of secondary hydrocephalus
Preceding diseases possibly causing ventricular dilation

are not obvious, including subarachnoid hemorrhage,
meningitis, head injury, congenital hydrocephalus, and
aqueductal stenosis
Comorbid
disorders
No other neurologic, psychiatric, or general medical

conditions that are sufficient to explain the presenting
symptoms
Clinical symptoms cannot be completely explained by

other neurologic or non-neurologic diseases
Other neurologic diseases, including Parkinson disease,
Alzheimer disease, and cerebrovascular diseases, may
coexist but should be mild
Gait
impairment
At least 2 of the following should be present and not be

entirely attributable to other conditions:
Small stride, shuffle, instability during walking, and

increase of instability on turning
Decreased step height

Decreased step length
Decreased cadence (speed of walking)
Increased trunk sway during walking
Widened standing base
Toes turned outward on walking
Retropulsion (spontaneous or provoked)
En bloc turning (3 or more steps for 180)
Impaired walking balance, as evidenced by 2 or more
corrections out of 8 steps on tandem gait testing
Urinary
urgency/
incontinence
One of the following should be present:
Overactive bladder, mainly manifesting as increased

nocturnal urinary frequency, urgency, and urinary
incontinence
Episodic or persistent urinary incontinence not

attributable to primary urologic disorders
Urinary and fecal incontinence
Or any 2 of the following should be present:
Urinary urgency (frequent perception of a pressing
need to void)
Urinary frequency (more than 6 voiding episodes in an
average 12-hour period)
Nocturia (the need to urinate more than twice a night)
Cognitive
impairment
Documented impairment (adjusted for age and

educational attainment) or decrease in performance on a
cognitive screening instrument, or both
Cognitive impairment is detected on cognitive tests
Continued
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Table 1
Feature
Continued
Japanese guidelines
Or evidence of at least 2 of the following on examination

that is not fully attributable to other conditions:
Psychomotor slowing (increased response latency)
Decreased fine motor speed
Decreased fine motor accuracy
Difficulty dividing or maintaining attention
Impaired recall, especially for recent events
Executive dysfunction
Behavioral or personality changes
Data for table assembled from references 1 and 4.
with dementia in iNPH overlap with those of other dementias, including difficulty managing
finances, taking medications properly, driving, and keeping track of appointments. Impaired
expressive or receptive language, impaired naming, agnosia, poor immediate recall that does
not benefit from cueing, hallucinations, and failure to recognize close family or friends should
raise concern for other causes of dementia. Delirium implies the presence of a concomitant
disorder or medication side effect.
Neuroimaging The terms hydrocephalus and ventriculomegaly are not synonymous. Although all patients with iNPH should have enlarged ventricles, not all elderly patients with enlarged ventricles have iNPH. In neurodegenerative disorders, cerebral atrophy results in
ventriculomegaly (so-called hydrocephalus ex vacuo). Neuroimaging can be used to raise or
lower suspicion of iNPH; however, it can rarely exclude it entirely. A comparison of key neuroimaging findings from the International and Japanese guidelines is presented in table 2.14
The distinction between normal and enlarged ventricular size for age is difficult to ascertain;
however, for screening purposes, the Evans ratio (the ratio of the widest diameter of the frontal
horns to the widest diameter of the brain on the same axial slice) suffices (figure). The International and Japanese guidelines use a threshold of $0.3, but research on normal elderly
subjects suggests a threshold of $0.33.14,12
MRI is considered superior to CT in terms of providing more information on diagnostic
relevance and avoiding exposure to ionizing radiation. High-speed and high-resolution MRI
techniques can better identify aqueductal stenosis, and MRI phase-contrast techniques show
the hyperdynamic aqueductal CSF flow that has been associated with shunt-responsive iNPH.
Features that distinguish hydrocephalus from atrophy

The Japanese guidelines for iNPH4 identify several features that distinguish iNPH from
atrophy, including disproportionately enlarged subarachnoid spaces (particularly in the Sylvian fissure and basal cisterns) and the tight high convexity, which is effacement of the
subarachnoid space over the convexity.13,14 These findings may suggest a block of CSF flow
between the basal cisterns and the arachnoid granulations, a condition that has been termed
disproportionately enlarged subarachnoid space hydrocephalus (DESH). By implication, the
absence of DESH on brain imaging is suggestive of brain atrophy, but it does not exclude the
possibility of iNPH.4,14
Enlargement of the ventricles from iNPH will change the shape of the corpus callosum, with
bowing and effacement seen on sagittal views (figure),15 and impingement against the falx
cerebri, resulting in an acute callosal angle (#90) seen on coronal views.
Cisternography Radionuclide cisternography has a high false-positive rate, and the International and Japanese guidelines recommend against it.14
378
Table 2
Key imaging and CSF pressure features of idiopathic normal-pressure hydrocephalus: Comparison between the
International and the Japanese guidelines
Feature
Japanese guidelines
Ventricular
size
Ventricular enlargement not entirely attributable to cerebral

atrophy or congenital enlargement (Evans index .0.3 or
comparable measure)
Ventricular dilation (Evans index .0.3)
Other
neuroimaging
features
No macroscopic obstruction to CSF flow
Sylvian fissures and basal cistern are usually

enlarged
Periventricular changes are not essential
At least one of the following supportive features:
CSF pressure
Enlargement of the temporal horns of the lateral ventricles not

entirely attributable to hippocampus atrophy
Callosal angle of 40 or more
Evidence of altered brain water content, including

periventricular signal changes on CT and MRI not attributable
to microvascular ischemic changes or demyelination
An aqueductal or fourth ventricular flow void on MRI
CSF opening pressure in the range of 518 mm Hg

(or 70245 mm H2O), as determined by LP or a comparable
procedure; appropriately measured pressures that are
significantly higher or lower than this range are not consistent
with a probable NPH diagnosis
Narrowing of the sulci and subarachnoid

spaces over the high convexity/midline
surface (DESH)
CSF pressure of #200 mm H2O and normal

CSF content
Abbreviations: DESH 5 disproportionately enlarged subarachnoid space hydrocephalus; LP 5 lumbar puncture.

Data for table assembled from references 1 and 4.
Differential diagnosis Each of the primary symptoms of iNPH has multiple potential etiologies (table 3). Most patients with iNPH have other conditions contributing to their
symptoms, and it is uncommon to see pure iNPH. Further, patients without iNPH may
appear to have the iNPH syndrome because of multiple comorbidities. The first step is to
identify or exclude other disorders that should be treated before evaluating iNPH.
Although iNPH is described as a symptom triad, patients need not have all 3 symptoms.
However, most published series and guidelines indicate that nearly all patients have gait
impairment. 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 impairment is usually either the first or
worst symptom.
The tests ordered to evaluate the differential diagnosis include the so-called dementia bloodwork (complete blood count, biochemical profile, B12, folate, thyroid-stimulating hormone,
and when indicated, rapid plasma reagin, Lyme, vitamin D); neuropsychological testing;
MRI of the cervical, thoracic, or lumbar spine; EMG/nerve conduction velocity; and urology
consultation.
Treatment of other disorders

Several rationales support excluding or treating other disorders before pursuing iNPH testing.
First, no evidence suggests that the time required to identify and treat other disorders diminishes
the likelihood of response to shunt surgery. Patients who have had iNPH symptoms for several
years can still respond to shunt surgery. Patients can be reassured that it is more beneficial to undertake a thorough evaluation than it is to rush. Second, should the patients symptoms resolve
with treatment of other disorders, then testing for iNPH may no longer be necessary. Finally,
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Figure
MRI of a 73-year-old woman with impairment of gait and balance, bladder control,
and cognition for 3 years
The patient had not improved with treatment for parkinsonism. A trial of CSF removal via external lumbar drainage
produced substantial gait improvement, and she was treated with a ventriculoperitoneal shunt. At baseline, the
Tinetti score was 1216/28, which is significantly impaired; 9 months after shunt surgery, the score was 26/28,
and the patient walked effortlessly. (A) Axial T2 imaging consistent with the Japanese high and tight criteria for
the convexity. The interhemispheric fissure is effaced. (B) Axial T1 imaging shows a widened IIIrd ventricle with a
span of 10 mm. (C) Sagittal T1 imaging shows bowing of the corpus callosum and a pulsation artifact (flow void) in
the Sylvian aqueduct. (D) Axial fluid-attenuated inversion recovery imaging shows measurement of the Evans ratio.
The diameter of the frontal horns is 4.4 cm, the widest brain diameter is 13.7 cm, and the Evans ratio is 0.32.
initiating treatment of an underlying disorder while testing for iNPH makes it difficult to
determine whether the patients response to CSF removal is a result of 1) the removal of CSF or
2) the treatment of the underlying disorder. Any trials of initiating treatment (e.g., carbidopa/
levodopa) or withdrawing treatment (e.g., benzodiazepines or neuroleptics) should be completed or at a stable dosage before tests for iNPH are initiated. If delirium is present, testing for
iNPH should be deferred because resolving delirium can create a false-positive response to CSF
removal, and a persistent delirium can cause a false-negative response.
Testing specific for iNPH

The International and Japanese guidelines recommend tests of CSF drainage (lumbar puncture
[LP] or CSF drainage via spinal catheter); however, the International guidelines also recommend infusion testing.14
The rationale for testing a patients response to CSF drainage is that doing so emulates the
physiologic effect of a shunt. If iNPH is present, a response to CSF removal should be seen
and shunt surgery should help. However, if iNPH is absent or contributes only minimally, no
response to CSF removal is seen and shunt surgery is unlikely to help.
380
Table 3
Differential diagnosis of idiopathic normal-pressure hydrocephalus (iNPH)

Gait
Dementia
Incontinence
iNPH, with or without comorbidities
Parkinsonism
Lewy body dementia
Corticobasal degeneration
Progressive supranuclear palsy
Multiple system atrophy
Vascular dementia
Neurosyphilis
Disorders that may have all 3 symptoms
Medication side effects
Multifactorialany combination of diagnoses, with or without iNPH
Multifactorialany combination of diagnoses, with or without iNPH
iNPH, with or without comorbidities
Vitamin B12 deficiency
Cervical stenosis and myelopathy
Lumbosacral stenosis
Peripheral neuropathy
Disorders that may have 2 symptoms
Disorders that may have only one symptom

iNPH
Degenerative arthritis of the hips, knees, ankles
Spinocerebellar degeneration
Peripheral vascular disease (claudication)
Alzheimer dementia
Frontotemporal dementia
Depression
Hypothyroidism
Sleep apnea
Prostatic hypertrophy/obstructive uropathy
Pelvic-floor abnormalities
Interstitial cystitis
Disorders that can aggravate other symptoms

Visual impairment
Hearing impairment
Obesity
Cardiovascular disease
Pulmonary disease
Chronic lower-back pain
Vestibular disorders
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If delirium is present, testing for iNPH should be

deferred because resolving delirium can create
a false-positive response to CSF removal, and a
persistent delirium can cause a false-negative
response.
If properly performed, the large-volume LP (also known as the tap test) has a high positive
predictive value. If improperly done, it can be inaccurate. Proper tap test performance hinges
on 2 principles. First, because the test is used to assess the patients response to CSF removal,
the patient must be examined before and after the LP. Gait is most likely to respond, and use
of a standardized evaluation of gait, with or without video recording or computer-assisted
assessment, is helpful. The evaluation should be done by qualified health care professionals.16
Without pre- and post-LP examinations, the physician must rely on patient and family
reporting, which is less accurate and may be influenced by a desire to see improvement.
Second, the volume of CSF removed must be adequate to influence NPH symptoms long
enough to assess the change. Typical tap test protocols remove 3050 mL of CSF and observe
change in gait and cognition 30 minutes to 4 hours afterward. Although it is standard practice
that patients lie flat for 1030 minutes after the LP, some experts believe the sensitivity of the
test is increased by having the patient remain upright and engage in modest activity as
tolerated. Although the safety of this approach has not been rigorously evaluated, headache
and nausea after LP are uncommon in the elderly iNPH population.
Although the interval between the LP and the follow-up examination can be as little as
30 minutes, observation over several hours is often needed, as the response is variable in
latency and only rarely persists for more than a few days. If the response is considerable, shunt
surgery can be recommended. Absence of response to the tap test does not exclude shunt
responsiveness, and external lumbar drainage (ELD) can be considered if iNPH is still clinically suspected.
ELD has been used for more than 20 years to diagnose iNPH, but it is not widely available.17,18 The procedure requires a brief hospitalization to insert a 16-gauge spinal catheter
for controlled CSF drainage of approximately 10 mL/h. The patients gait should be examined before the procedure, daily during CSF drainage, and after removal of the catheter. Gait
testing is standard and neuropsychological testing before and after ELD may also be helpful.
Most publications have cited 72 hours of CSF drainage, although some centers drain CSF for
shorter periods. ELD is said to be accurate, with both a high positive predictive value and a
high negative predictive value. The most frequent serious complication of ELD is bacterial
meningitis, seen in 2%3% of patients.17,18
Infusion testing for assessment of hydrodynamics and Rout is more commonly used in
Europe. This test involves infusing artificial CSF (usually Ringer lactate) via one spinal needle
while simultaneously recording CSF pressure via a second spinal needle.19 Several variables
that characterize intracranial compliance can be calculated, including Rout and CSF conductance. Several methods for infusion testing exist, and the value of Rout is method-dependent.19
Reference values for healthy elderly exist.20 Infusion testing requires specialized equipment
and considerable expertise on the part of the physicians who perform it.
Shunt surgery
Shunt surgery is indicated for patients who respond to CSF drainage or who have CSF hydrodynamic variables consistent with iNPH. The International and Japanese guidelines support
shunt surgery.14 Evidence does not yet support the use of one type of shunt over another.
382
Endoscopic third ventriculostomy has not proven effective in treatment of iNPH. As of 2013,
no medical treatments are effective in iNPH.4
The goal of treating with a shunt is to improve the patients symptoms while avoiding
complications of overdrainage, such as subdural effusion or hematoma. The International and
Japanese guidelines find that adjustable shunt valves offer the advantage of being able to
gradually lower the pressure setting until symptom improvement and to raise the pressure
setting if low-pressure symptoms or complications emerge.14 Severe complications, such as
subdural hematoma with significant mass effect, shunt infection, and shunt obstruction,
typically require neurosurgical intervention. Adjustable shunts can be used to safely manage
iNPH patients who need chronic anticoagulation.21
The choice of shunt valve and configuration (e.g., ventriculoperitoneal, ventriculoatrial,
lumboperitoneal) depends on the neurosurgeons recommendation and the patients preference.
When compared to other intracranial procedures, the risk of shunt surgery is relatively low.
When these risks are placed in the context of the benefits expected on the basis of specific
iNPH testing results, most patients will elect to proceed with shunt surgery.
Longitudinal follow-up
Neurologists have not traditionally been involved in the longitudinal management of patients
with iNPH after shunt surgery. Many patients find that neurosurgeons will see them only if
they have a shunt complication that requires surgery, and most neurologists are not trained
to manage patients after shunt surgery.
All symptoms in iNPH can improve after shunt surgery. The robust improvement in dementia
is not widely appreciated, although it has been shown in multiple studies.911 Cognitive improvement has been shown not to be the result of the practice effect in properly structured batteries.22
The principle of differential diagnosis is key to the management of patients after shunt surgery.
If a patient worsens after initial improvement, the question that most frequently arises is whether
the cause is shunt malfunction or concomitant disorders. Typical scenarios are lagging symptom
recovery, transient worsening, and insidious worsening.
Some patients recover from only 1 or 2 symptoms after shunt surgery, while 1 symptom lags
behind. In most circumstances, another disorder is responsible for the lagging symptom and
should be investigated further.
After initial improvement, some patients will have transient worsening of their iNPH symptoms in association with another illness (e.g., urinary tract infection) or with hospitalization or
surgery. This phenomenon is similar to the transient worsening of latent symptoms seen in
many neurologic disorders when patients experience other illnesses. Often, iNPH symptoms
will improve after the underlying illness is identified and treated.
Insidious worsening of symptoms over weeks or months may result from shunt malfunction
or the emergence or worsening of a comorbidity. In this circumstance, evaluation of shunt malfunction is indicated. The evaluation of shunt malfunction is straightforward. Disconnection of
the shunt components is easily detected by plain x-rays. Depression of the shunt reservoir to
assess the rate of refilling is not helpful in distal shunt obstruction.
Radionuclide shunt patency study and CSF infusion testing can be used to assess shunt
function.4,23,24 Both of these techniques involve procedural skills for which most neurologists
are not trained, and they will need to collaborate with neurosurgeons. If shunt obstruction is
detected and treated, approximately 75% of patients will improve.23
The diagnosis and management of iNPH can be accomplished through an organized
approach that incorporates familiar principles, including differential diagnosis; treatment of
other disorders before specific testing for iNPH; use of specific iNPH tests; and, for patients
treated with shunt surgery who have subsequent return of iNPH symptoms, the application
of the differential diagnosis process to the worsening symptoms.
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STUDY FUNDING
No targeted funding reported.
DISCLOSURES
M. Williams has received speaker honoraria from the American Academy of Neurology; is the Associate
Editor for Ethics for Continuum; is the President of the International Society for Hydrocephalus and
CSF Disorders; is an author on patents re: Shunts and Self-sealing catheter for deformable tissue;
performs lumbar punctures and external lumbar drainage as part of his practice at the Adult Hydrocephalus Program at Sinai Hospital of Baltimore (60% clinical effort); receives research support from
the National Institute of Neurological Disorders and Stroke, NeuroDx Development, and the national
Space Biomedical Research Institute; owns a 5% interest in Mensana Therapeutics, a start-up with
intellectual property that is related to CSF shunting for the treatment of Alzheimer dementia; and his
spouse owns stock in Ecolab, General Electric, Life Technologies, Medtronic, and Pfizer. N. Relkin is
Associate Editor of Neurology Alert; performs NPH-related research, brain imaging, and clinical practice
at Weill Cornell Memory Disorders Program (25% of effort); has received research support from the
Leon Levy Foundation, ONeill Foundation, NY Community Trust, the National Institute on Aging,
the US Department of Defense, Eisai, Merck, and Baxter Healthcare; serves as a consultant to Eisai and
Kyowa Kakko Kirin; is head of the Taskforce on Neuroimaging of Hydrocephalus for the International
Society for Hydrocephalus and CSF Disorders; and is inventor on a patent application for use of
diffusion-tensor-histogram analysis in the differential diagnosis of NPH. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
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Diagnosis and Management of Idiopathic Normal-Pressure Hydrocephalus

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Diagnosis and Management of Idiopathic Normal-Pressure Hydrocephalus

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Neurology Clinical Practice

diopathic normal-pressure hydrocephalus (iNPH)

Michael A. Williams and Norman R. Relkin

The terms hydrocephalus and ventriculomegaly

2013 American Academy of Neurology