Typically affecting the elderly,
normal pressure hydrocephalus (NPH) is one of the more difficult conditions to
diagnose. In addition to a wide based gait, ataxia, and incontinence, the signs and
symptoms include cognitive impairment, which is often characterized as progressive memory
The cause of enlarged ventricles, found on CT scans or MRI, is uncertain.
However, NPH has been shown experimentally to be associated with decreased
absorption of spinal fluid, increased systolic blood pressure, and brain
After other causes of gait
disturbance have been ruled out, patients have a test that mimics a temporary
shunt to determine whether decreasing cerebrospinal fluid volume improves gait.
Typically, 30 cubic centimeters of fluid is removed during a spinal tap, and
pre- and post-procedure videos of the patient walking are compared.
Separately, tests for cognitive
function are conducted to help determine if memory problems are isolated or are
accompanied by other impairments. The presence of aphasia, for example,
suggests an additional degenerative pathology that likely will not improve with
Treatment consists of a
neurosurgically placed shunt that drains cerebrospinal fluid into the
peritoneal cavity. One of the known complications in the past has been over-drainage,
which can cause the brain to shrink and may result in subdural hemorrhage or
The recent introduction of programmable shunt valves,
however, has improved outcomes and reduced the need for additional surgical
procedures to adjust the rate of drainage.
It should be noted that NPH may have
a degenerative component. Even in patients with initial success, it may be
necessary to adjust the rate of drainage six months to several years later. The
programmable valve readily enables such adjustments and has made surgery more
viable for patients.
Not all symptoms improve with
treatment. Often, gait and incontinence improve, but memory and cognition may
not. Overlapping conditions may be important to the cognitive decline
associated with NPH. The presence of aphasia or even mild naming deficits may
signal coexisting pathology, such as vascular disease or Alzheimer's disease
Studies have shown that among people
older than 74 years, the brains of more than 30 percent of patients show
evidence of AD pathology on autopsy. Cerebrovascular disease is also frequent
in this age group because hypertension is common.
Several studies show that
hypertension is associated with hydrocephalus in animal models and with
hydrocephalus in humans.
The Atherosclerosis Risk in
Communities (ARIC) Study, a prospective epidemiologic study sponsored by the
National Heart, Lung, and Blood Institute (NHLBI), looked at the MRI scans of
study participants taken 10 years apart. The investigators found that both
increased systolic blood pressure and increased pulse pressure correlated with
increased ventricle size.
In earlier research, it was found that head size also
correlates with increased risk of NPH. Approximately 10 to 20 percent of people
with NPH have a head size at or above the 98th percentile. Thus, it may be that
people born with a large head have congenital hydrocephalus that becomes
symptomatic as they age.
The question of the contribution of
head size, vascular disease and underlying AD pathological factors is important
to predicting outcomes for surgical shunting.
To address these issues, Drs.
Graff-Radford and Wharen at the Mayo Clinic, are initiating a prospective study
in which 25 NPH patients who have agreed to shunt surgery will be given a
battery of neuropsychological tests and PET imaging to screen for amyloid
plaque buildup before surgery. They will also have gait evaluation and
neuropsychological testing at one-year follow-up.
The goal of the study is to
determine whether the presence of amyloid in the brain influences cognitive
outcomes from shunt surgery in NPH. The investigators hope their findings will
help physicians in counseling patients about which symptoms may improve with a
shunt and whether shunting is a good option.