Normal Pressure Hydrocephalus (NPH)

A 75-year-old man with a history of hypertension and type 2 diabetes mellitus presents to the neurology clinic with progressive difficulty walking, cognitive impairment, and urinary incontinence over the past year. His wife reports that he has become increasingly forgetful, frequently misplacing items and repeating conversations, although he continues to recognize family members and remains able to perform activities of daily living. She also reports urinary urgency that has progressed to incontinence. On examination, the patient has a slow, broad-based gait with difficulty initiating steps and a tendency for the feet to appear “stuck to the floor,” consistent with a magnetic gait. There are no focal neurological deficits, and deep tendon reflexes are normal. There are no clinical features of sustained increased intracranial pressure, such as headache, vomiting, or papilledema. CT imaging of the head demonstrates ventriculomegaly disproportionate to the degree of cerebral atrophy. Lumbar puncture demonstrates an opening pressure within the normal range. Diagnosis?

Diagnosis is Idiopathic normal pressure hydrocephalus.

1. Definition

Normal pressure hydrocephalus (NPH) is a syndrome characterized by ventriculomegaly associated with gait disturbance, cognitive impairment, and urinary dysfunction, typically without sustained elevation of cerebrospinal fluid pressure on routine lumbar puncture.

When no identifiable preceding cause is present, the condition is termed idiopathic normal pressure hydrocephalus (iNPH).

NPH is clinically important because it is a potentially reversible cause of gait impairment and cognitive dysfunction in older adults.

The term “normal pressure” does not imply that intracranial pressure is continuously normal. CSF pressure may fluctuate, but a single lumbar puncture typically demonstrates an opening pressure within the conventional normal range.

2. Etiology and Classification

2.1 Idiopathic NPH

Idiopathic normal pressure hydrocephalus occurs predominantly in older adults without an identifiable precipitating event.

The precise pathogenesis is incompletely understood and is probably multifactorial.

2.2 Secondary NPH

A similar clinical syndrome may develop after conditions that interfere with normal CSF circulation or absorption, including:

1.      Subarachnoid hemorrhage

2.      Meningitis

3.      Traumatic brain injury

4.      Intracranial surgery

5.      Other disorders affecting CSF pathways

In this patient, the absence of an identifiable precipitating event favors idiopathic NPH.

3. Pathophysiology

The pathophysiology of iNPH is complex and incompletely understood and should not be attributed solely to failure of CSF absorption at the arachnoid granulations.

Proposed mechanisms include:

1.      Altered cerebrospinal fluid dynamics

2.      Reduced intracranial and cerebral vascular compliance

3.      Impaired CSF outflow or clearance

4.      Abnormal pulsatile transmission of CSF pressure

5.      Periventricular white matter dysfunction

6.      Cerebral small-vessel and vascular factors

7.      Possible abnormalities of glymphatic clearance

Progressive ventricular enlargement may stretch or distort periventricular neural pathways involved in gait, executive function, and bladder control.

The patient's hypertension and diabetes are relevant because cerebrovascular comorbidity is common in older patients and may coexist with iNPH.

4. Clinical Features

4.1 Classic Clinical Triad

The traditional clinical triad consists of:

1.      Gait disturbance

2.      Cognitive impairment

3.      Urinary dysfunction

All three features do not need to be equally severe or appear simultaneously.

Gait impairment is usually the earliest and most prominent clinical manifestation.

4.2 Gait Features

Characteristic gait abnormalities include:

1.      Difficulty initiating gait

2.      Short, slow steps

3.      Broad-based gait

4.      Reduced step height

5.      Impaired turning

6.      Postural instability

7.      Reduced foot clearance

8.      A magnetic gait, in which the feet appear stuck to the floor

Upper limb function is often relatively preserved compared with lower limb gait dysfunction.

The gait may resemble parkinsonism, but prominent resting tremor and classic limb rigidity are usually absent.

4.3 Cognitive Features

The cognitive impairment of iNPH typically has a frontal-subcortical pattern rather than the predominantly amnestic pattern characteristic of typical Alzheimer disease.

Common manifestations include:

1.      Psychomotor slowing

2.      Reduced processing speed

3.      Executive dysfunction

4.      Impaired attention

5.      Reduced mental flexibility

6.      Apathy

7.      Working-memory impairment

Recognition memory and other cortical functions may remain relatively preserved early in the disease.

Marked early aphasia, agnosia, or severe episodic memory impairment should raise consideration of an alternative or coexisting neurodegenerative disorder.

4.4 Urinary Features

Urinary manifestations usually begin with:

1.      Urinary urgency

2.      Increased urinary frequency

3.      Nocturia

4.      Urge incontinence

With progression, urinary control may deteriorate further.

5. Diagnostic Evaluation

5.1 Clinical Diagnosis

The diagnosis of iNPH is based primarily on compatible clinical features and characteristic neuroimaging, with CSF drainage testing providing additional supportive and prognostic information when performed.

Important diagnostic elements include:

1.      Compatible gait disturbance

2.      Cognitive and/or urinary dysfunction

3.      Ventriculomegaly on neuroimaging

4.      Exclusion of alternative disorders that adequately explain the clinical presentation

5.      Supportive response to CSF drainage testing when present

Gait impairment is particularly important diagnostically and is commonly the dominant symptom.

A negative CSF drainage test does not by itself exclude iNPH.

5.2 Neuroimaging

MRI of the brain is generally preferred when available because it provides better characterization of ventricular morphology, white matter abnormalities, and alternative neurological disorders. CT can also demonstrate the characteristic ventriculomegaly.

Important imaging findings include:

1.      Ventriculomegaly disproportionate to the degree of cerebral volume loss

2.      Evans index of 0.30 or greater, which supports ventriculomegaly but is not specific for iNPH

3.      Enlargement of the temporal horns

4.      A relatively reduced callosal angle

5.      Disproportionately enlarged subarachnoid space hydrocephalus (DESH)

5.3 DESH Pattern

The DESH pattern includes a characteristic combination of:

1.      Ventriculomegaly

2.      Enlarged Sylvian fissures

3.      Narrowed or compressed sulci over the high convexities and medial cerebral surface

DESH strongly supports the diagnosis of iNPH in the appropriate clinical setting, but its absence does not completely exclude the disorder.

DESH and other characteristic imaging findings support the diagnosis and may strengthen the case for shunting, but imaging findings alone should not determine shunt candidacy.

5.4 Evans Index

The Evans index is calculated as the maximal width of the frontal horns of the lateral ventricles divided by the maximal internal diameter of the skull on the same axial image.

An Evans index of 0.30 or greater is commonly used as evidence of ventriculomegaly.

However, it is not specific for iNPH and should be interpreted together with the clinical presentation and other imaging features.

5.5 Lumbar Puncture and Opening Pressure

Lumbar puncture commonly demonstrates a CSF opening pressure within the normal or mildly elevated range.

A normal opening pressure is compatible with NPH but is not sufficient to establish the diagnosis.

The diagnosis depends on the overall clinical and radiological pattern rather than a single CSF pressure measurement.

5.6 CSF Tap Test

The large-volume lumbar puncture, or CSF tap test, is commonly used to assess the likelihood of improvement after CSF diversion.

Typical evaluation includes:

1.      Removal of approximately 30 to 50 mL of CSF

2.      Objective assessment of gait before and after CSF removal

3.      Evaluation of cognition and urinary symptoms when appropriate

Gait can be assessed using measures such as:

1.      Timed Up and Go test

2.      Timed walking tests

3.      Gait speed

4.      Step length and number of steps

Improvement in gait after CSF removal provides supportive evidence that the patient may respond to shunt surgery.

A positive tap test has useful predictive value, but a negative tap test does not exclude iNPH or eliminate the possibility of shunt responsiveness.

5.7 Extended Lumbar Drainage and Additional Testing

Extended lumbar drainage may be considered in selected patients with high clinical suspicion and a negative or equivocal tap test.

It may provide additional prognostic information, although testing protocols and comparative evidence remain heterogeneous.

Other specialized investigations may include:

1.      CSF infusion testing to assess resistance to CSF outflow

2.      Intracranial pressure monitoring in selected cases

These tests are generally performed in specialized centers and should be interpreted in the context of the overall clinical and imaging findings.

6. Differential Diagnosis

Conditions that may mimic or coexist with iNPH include:

6.1 Alzheimer Disease

Alzheimer disease typically produces more prominent episodic memory impairment and cortical cognitive dysfunction.

Alzheimer pathology may coexist with iNPH and can reduce the degree of cognitive improvement after shunting.

6.2 Vascular Cognitive Impairment

Cerebral small-vessel disease can produce:

1.      Cognitive slowing

2.      Executive dysfunction

3.      Gait impairment

4.      Urinary symptoms

Hypertension and diabetes increase the likelihood of cerebrovascular comorbidity.

6.3 Parkinson Disease and Atypical Parkinsonian Syndromes

Parkinsonian disorders may cause:

1.      Bradykinesia

2.      Gait initiation difficulty

3.      Postural instability

Features such as prominent resting tremor, asymmetric rigidity, or characteristic abnormalities of eye movements may suggest alternative diagnoses.

6.4 Structural and Spinal Disorders

Other important considerations include:

1.      Cervical myelopathy

2.      Lumbar spinal stenosis

3.      Peripheral neuropathy

4.      Intracranial mass lesions

5.      Obstructive hydrocephalus

These disorders should be considered when the clinical examination or imaging is atypical for iNPH.

7. Management

7.1 CSF Diversion

Definitive treatment consists of surgical CSF diversion in appropriately selected patients.

The most commonly used procedure is:

Ventriculoperitoneal shunt placement

The shunt diverts CSF from the cerebral ventricles into the peritoneal cavity.

7.2 Shunt Selection

Modern treatment commonly uses programmable shunt valves, allowing postoperative adjustment of the opening pressure without additional surgery.

Alternative procedures may include:

1.      Lumboperitoneal shunting

2.      Ventriculoatrial shunting

The optimal procedure depends on individual anatomy, comorbidities, surgical expertise, and institutional practice.

7.3 Patient Selection

Factors supporting consideration of shunt treatment include:

1.      A characteristic gait disorder

2.      Compatible ventriculomegaly

3.      Supportive imaging findings such as DESH

4.      Objective improvement after CSF drainage

5.      A clinical picture not better explained by another neurological disorder

DESH and other imaging findings should be interpreted as part of the overall clinical assessment and should not be used alone to determine shunt candidacy.

The presence of comorbid neurodegenerative or cerebrovascular disease does not automatically exclude shunt treatment, but it may influence the magnitude and pattern of improvement.

8. Complications of Shunt Treatment

Potential complications include:

1.      Subdural hygroma

2.      Subdural hematoma

3.      Shunt infection

4.      Shunt obstruction or malfunction

5.      Overdrainage

6.      Underdrainage

7.      Need for shunt revision

Programmable valves may help manage some complications related to overdrainage or inadequate drainage.

9. Prognosis

1.      Properly selected patients frequently experience meaningful improvement after shunt surgery.

2.      Gait disturbance is generally the symptom most likely to improve and often shows the earliest improvement.

3.      Urinary symptoms may also improve substantially.

4.      Cognitive improvement is possible but may be less predictable, particularly when coexisting neurodegenerative disease is present.

5.      Approximately 70% to 90% of appropriately selected patients may experience symptomatic improvement after shunt treatment, although outcomes vary according to patient selection, comorbidities, and outcome definitions.

6.      Earlier recognition and treatment, before severe and prolonged neurological impairment develops, are generally associated with better functional outcomes.

7.      Long-term follow-up is important because recurrent symptoms may reflect shunt malfunction, inadequate drainage, disease progression, or a coexisting neurological disorder.

10. Key Clinical Insight

Progressive gait disturbance with a magnetic gait, urinary urgency or incontinence, cognitive impairment, and ventriculomegaly disproportionate to cerebral atrophy is highly characteristic of normal pressure hydrocephalus.

In this patient, the absence of an identifiable secondary cause makes idiopathic normal pressure hydrocephalus the most likely diagnosis.

A normal lumbar puncture opening pressure is compatible with the diagnosis, but clinical findings, characteristic neuroimaging, and response to CSF drainage testing are more important than a single pressure measurement.

Because iNPH is a potentially treatable cause of gait and cognitive impairment, appropriate patients should undergo assessment for CSF shunt surgery.

References

1.      Nakajima M, Yamada S, Miyajima M, et al. Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus, Third Edition: Endorsed by the Japanese Society of Normal Pressure Hydrocephalus. Neurol Med Chir (Tokyo). 2021;61(2):63-97. doi:10.2176/nmc.st.2020-0292.

2.      Maroufi SF, Yasar S, Moghekar A, Luciano MG. Idiopathic Normal Pressure Hydrocephalus: A Review. JAMA. Published online September 14, 2026. doi:10.1001/jama.2026.15519.

3.      Thavarajasingam SG, El-Khatib M, Rea M, et al. Clinical predictors of shunt response in the diagnosis and treatment of idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis. Acta Neurochir (Wien). 2021;163(10):2641-2672. doi:10.1007/s00701-021-04922-z.