Normal pressure hydrocephalus has a large prevalence. For example, in a US population-based study of a 2 in 1000 for those younger than 79 years, and up to almost 6 in 100 for those age 80 and above1. It’s also a controversial diagnosis among neurologists, since agreed-upon universal diagnostic criteria are difficult to come by, with diagnostic methods themselves varying from clinic to clinic. However, it’s worth addressing, since it represents a potentially reversible cause of dementia in some patients.

Normal pressure hydrocephalus is a condition typically affecting those of advanced age, and even the condition’ name, itself, is confusing. ‘Hydrocephalus’ refers to increased amounts of cerebrospinal fluid (CSF) in and around the brain, which - in a closed system like the skull and spinal canal - should correspond with increased fluid pressure. This can be from overproduction of the CSF or underabsorption of the CSF as it circulates, among other causes2:

The ‘normal’ part of the condition’s name, however, seems like an oxymoron; how can there be more fluid in a closed system, without increased pressure?

Well, the thought is that this is possible because the brain tissue, itself, compresses to ‘make room’ for the extra fluid. In NPH, this occurs around the tracts that make up the ‘white matter’ surrounding the fluid-filled spaces of the brain. These tracts serve as the important conduits between areas of ‘gray matter’ (cerebral cortex), which themselves have important local computational functions. The concept for NPH is that the resultant compression of these white matter tracts leads to impairment of signaling between parts of the brain, resulting in the classical characteristics of the condition3. Theoretically, then, reducing the amount of cerebrospinal fluid should reduce this compression, and relieve the symptoms of the condition.

A diagnostic conundrum

The classical triad characteristics of the NPH often quoted among neurologists can be summed as “the three W’s - wet, wacky, and wobbly.” Meaning: urinary incontinence, cognitive changes, and gait difficulties define the condition. However, these findings are notoriously nonspecific in the age group of patients typically presenting to neurologists with cognitive concerns, so progress for a universal set of criteria has been slow. As of right now, there are at least two sets of criteria; one is international, and one is Japanese4,5.

For example, in the US: gait abnormalities occur in ~20% of individuals older than 75 fulfill criteria for dementia6. Urinary incontinence is found in ~38% of women and 18% of men older than 757. Finally, up to 14% of people over the age of 75 can qualify for a diagnosis of dementia from one cause or another8.

So, what about more ‘objective’ tests? There are imaging characteristics for brain scans done via MRI that have been used for attempting to narrow down patients who could have NPH. These include a measure called the ‘Evans index’ and a collection of findings summarized as DESH - ‘disproportionately enlarged subarachnoid space’9:

Unfortunately, these findings on MRI alone are still not perfect, as they rely on human recognition and imperfect imaging measurement tools to conduct. The Evans index findings, for instance, can be found in about 20% of people over the age of 70, without the symptoms of NPH10.

That’s why neurologists and neurosurgeons have determined a series of tests that, taken together with some of the imaging findings and symptomatology, seems to capture at least some proportion of cases, and possibly give patients a path toward treatment. Unfortunately - those numbers are difficult to come by in the scientific literature, since many variations of these testing methods exist9; this, in itself, makes research on the subject difficult, and frustrates neurologists in the clinic, like me.

The general idea behind the final diagnosis of normal pressure hydrocephalus (NPH) is that a patient should have some form of cognitive testing at baseline, after some imaging and symptoms suspicious for the condition. The patient should have some numerical measurements made of their walking speed and turning ability. Next, the patient should undergo a lumbar puncture (‘spinal tap’) to remove a significant amount of cerebrospinal fluid (CSF), and within a short period of time, have all the above repeated. Comparing the ‘before’ and ‘after’ results in different ways typically determines who likely has ‘true idiopathic’ normal pressure hydrocephalus that might respond to treatment, and who does not. Those patients who qualify then get sent for neurosurgical procedures that install permanent, internalized ‘release valves’ called ‘shunts’ to prevent the cerebrospinal fluid from building up naturally to previous levels.

The problem is that - even among patients who qualify for a shunt - immediate and long-term results of the procedure vary, with truly randomized controlled trials on these outcomes being few and far between11. Still, a recent meta-analysis of studies seemed to indicate some form of long-term improvement in up to 75% of patients with NPH who underwent a shunting procedure12. Surgical complications and other underlying conditions that may have predisposed patients to the effects of normal pressure hydrocephalus in the first place are part of the problem. It is therefore difficult to predict ahead of time who will - and who will not - benefit from surgery. Specialized imaging testing methods (such as functional MRI, diffusion tensor imaging, and others) may be useful for diagnosis, but are relatively resource-intensive, largely not covered by health insurance in the US, and do not predict response to shunting very well13.

How new tools like BrainKey can help

The process of diagnosing normal pressure hydrocephalus (NPH) takes many steps, and there are probably many patients getting missed. While no single imaging measurement can diagnose the condition, there have been strides made in so-called ‘machine learning’ models of image manipulation that can be leveraged to more precisely determine patterns of changes in brain scans over time, and across large numbers of patients.

The BrainKey software is in the process of receiving constant updates to its capabilities, with incorporation of measures like the Evans index and DESH. It is built to function automatically with the data given it from a patient’s MRI imaging files, and represents a potential streamlined approach for aiding in the diagnosis of NPH. The rigorous and frustrating manual testing needed for the final diagnosis is still invaluable, and I don’t expect that this will disappear from the clinic soon. However, data collected through all the steps of flagging potential NPH cases, testing for it with a lumbar puncture, and treating it with surgical intervention would all be useful for building a predictive model for care. This would, in turn, make the process of diagnosing the condition less cumbersome and resource-intensive, which ultimately would benefit the significant (and possibly unknown) cohort of patients with dementia that don’t even know they have a potentially treatable cause.

Jakob Mrozewski, MD is a practicing cognitive neurologist in the mountain West of the United States. He completed his subspecialty fellowship training in Behavioral Neurology and Neuropsychiatry, as well as Epilepsy, at the University of Colorado.

As one of a handful of clinically-focused cognitive neurologists in his region, one of his goals is gradual process improvement for optimizing patient education, healthcare delivery, and integration of multiple disciplines in the care of patients with cognitive manifestations of neurodegenerative diseases.

References

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3. Lenfeldt N, Larsson A, Nyberg L, et al. Idiopathic normal pressure hydrocephalus: increased supplementary motor activity accounts for improvement after CSF drainage. Brain 2008; 131(pt 11):2904–2912. doi:10.1093/brain/awn232.
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11. oma AK, Papadopoulos MC, Stapleton S, et al. Systematic review of the outcome of shunt surgery in idiopathic normal-pressure hydrocephalus. Acta Neurochir (Wien) 2013;155(10):1977–1980. doi:10.1007/s00701-013-1835-5.
12. Giordan E, Giorgio P, Giuseppe L, et al. Outcomes and complications of different surgical treatments for idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis. 2018. doi:10.3171/2018.5.JNS1875.
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