How to zero in on an accurate NPH diagnosis

BY:
Padraig O'Suilleabhain, M.D.
Neurology
Jon White, M.D.
Neurological Surgery
Jeffrey Schaffert, Ph.D.
Psychiatry

Whenever an older person starts having cognitive difficulties, or trouble walking or holding their urine, families immediately fear the diagnosis will be Alzheimer’s or Parkinson’s disease – progressive neurologic conditions that currently have no cure.

But in an estimated 800,000 patients in the U.S., the cause is a lesser known – and potentially reversible – condition called normal-pressure hydrocephalus (NPH).

NPH is caused by buildup of cerebrospinal fluid in the brains of older adults. The fluid is supposed to surround and protect the brain in caverns called ventricles, but in some cases excess fluid accumulates, causing the ventricles to enlarge and leaving less space for the brain. This interferes with cognition, gait, and urinary continence.

Some NPH symptoms and features observed on brain scans overlap with other common neurodegenerative conditions, which is one reason why that up to 80% of NPH cases may go unrecognized, untreated, or misdiagnosed (e.g., some patients diagnosed with Alzheimer’s disease may actually have NPH).

Getting an accurate diagnosis is crucial, but few health care centers have the depth of expertise to diagnose and treat NPH effectively.

At UT Southwestern’s Peter O’Donnell Jr. Brain Institute we have created a one-of-a-kind, patient-centered clinic that focuses on NPH, integrating care and research. The NPH clinic is staffed by a multidisciplinary team of experts from the departments of Neurosurgery, Neurology, Psychiatry, and Physical Medicine & Rehabilitation.

Together, we are refining the diagnostic criteria for NPH and raising the standard for effective surgical and nonsurgical treatment options. We are also creating a database of knowledge to enhance clinicians’ understanding of NPH, so more patients will have access to care for one of the few forms of dementia that can be controlled or even reversed.  

What causes NPH?

In many cases we believe the problem is a partial blockage of the outflow of cerebrospinal fluid. A specific cause for this cannot usually be determined. This is called idiopathic NPH. In secondary NPH a cause can be identified, such as

• Infections such as meningitis
• Inflammation of cerebrospinal fluid spaces
• Bleeding on the brain
• Head injury
• Complications from previous brain surgery
• Brain tumor

Researchers have identified some characteristics that may make a person more likely to develop the condition. These include:

• Advanced age: NPH is most often seen in patients older than 70.
• Obstructive sleep apnea
• Diabetes
• Mutated cilia: The brain’s ventricles contain tiny “hairs” that help keep cerebrospinal fluid flowing freely. In some patients with NPH, a genetic mutation impairs cilia function.
• Increased skull size: Some patients with NPH have larger-than-average skulls, which may indicate a brain infection before birth or in infancy.

Having one of these associated conditions or risk factors does not mean neurological symptoms are automatically diagnosed as NPH. Specialized exams, imaging, and testing can provide a clear diagnosis.

How do we diagnose NPH?

There is no one specific test to identify NPH. Instead we view the totality of the picture, from the history and exam through a series of diagnostic tests. Getting an accurate diagnosis requires expertise in recognizing evidence for and against NPH versus lookalike neurologic degenerations such as Alzheimer’s, Parkinson’s, or progressive supranuclear palsy. This is especially challenging in those patients who have both NPH and other potential neurodegenerative conditions.

Diagnosis typically starts with analyzing a patient’s symptoms in the context of their health history. Patients may have some or all these symptoms, which may be mild to severe:

• Gait disturbances, such as difficulty walking, are often among the first signs of NPH. Patients may walk slowly with a shuffling gait and heavy feet or have trouble turning, along with frequent falls.
• Cognitive decline, which can include short-term memory loss, difficulty making decisions, mood changes, and loss of interest in activities.
• Urinary incontinence, which causes patients to need to urinate often or urgently. In severe cases, NPH can cause total loss of urinary control due to malfunction of the nerves that control the detrusor muscle in the bladder wall.

Advanced brain imaging is done to measure enlargement of cerebrospinal fluid spaces and to help differentiate between the normal aging brain, fluid buildup, and structural brain damage.

The neuropsychological assessment can reveal patterns that help specialists distinguish between NPH and other causes of dementia. Neuropsychological assessment can help the neuropsychologist determine which areas of the brain are functioning better than others, which is determined by formalized measures of memory, attention, processing speed, language, visuospatial skills, and higher-level skills like problem solving, divided attention, and abstract thinking.

By means of a small drainage tube temporarily placed in the spine, we can remove cerebrospinal fluid over the course of three days. In some patients, this results in noticeable improvement in symptoms. We can also monitor variation in pressure and perform a stress test of the cerebrospinal fluid system using the same tube. This series of tests can be very helpful in diagnosing NPH.

When we can identify a patient with NPH, we start discussing treatment options immediately. Unlike many causes of dementia, it is possible for NPH to be significantly improved or even reversed with surgical procedure.  

Related reading: What genetic testing can reveal about your Alzheimer's disease risk

What are the treatment options for NPH?

The gold-standard treatment for NPH is a neurosurgical procedure to place a shunt in the brain that helps regulate its cerebrospinal fluid levels. The shunt consists of a valve and a flexible tube that drains excess cerebrospinal fluid into the abdomen.

There are some risks associated with the surgery, which can include complications from anesthesia, bleeding in the brain, infection, malfunction of the shunts, or seizures. Some people’s symptoms improve only partially, while others may improve only temporarily.

Among all surgical candidates, shunting has been shown to improve symptoms in 5% to 84% of cases – an extremely wide range that can be challenging for families to fathom. The expanse is due to factors such as concurrent health conditions and disease severity at the time of surgery. UT Southwestern is a high-volume center for NPH surgery, and for many of our patients the potential benefits of surgery outweigh the risks.

Research has not shown nonsurgical treatments to be effective long term. However, patients often benefit from physical therapy to increase strength, which can help improve gait and balance after or in lieu of surgery.

Our dedicated NPH clinic unites multidisciplinary specialists to provide well-rounded, thorough diagnoses, treatment options, and surgical assessments – all with a single clinic visit.

Related reading: Parkinson’s disease patients living better, longer with advances in care