Typically affecting the elderly, normal pressure hydrocephalus (NPH) is one of the more difficult conditions to diagnose. In addition to gait difficulty and incontinence, the signs and symptoms include cognitive impairment, which is often characterized as memory loss. 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 pulse pressure or systolic blood pressure, or both, and brain atrophy.
Neill R. Graff-Radford, M.D., a neurologist at Mayo Clinic in Florida, and his neurosurgical colleague Robert E. Wharen Jr., M.D., have broad experience in treating NPH and assessing factors that may predict outcomes.
After other causes of gait disturbance have been ruled out, patients at Mayo 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 shunting.
Treatment consists of a neurosurgically placed shunt that drains cerebrospinal fluid into the peritoneal cavity. Dr. Wharen explains that one of the known complications in the past has been overdrainage, which can cause the brain to shrink and may result in subdural hemorrhage or subdural hygroma. 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.
Dr. Wharen notes 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 more patients.
Not all symptoms improve with treatment. Often, gait and incontinence improve, but memory and cognition may not. Dr. Graff-Radford has long suspected that 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 (AD).
As Dr. Graff-Radford points out, 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.
Dr. Graff-Radford and colleagues presented findings at the American Academy of Neurology meeting in New Orleans in April, from data collected by the Atherosclerosis Risk in Communities (ARIC) Study, a prospective epidemiologic study sponsored by the National Heart, Lung, and Blood Institute (NHLBI).
Looking at the MRI scans of study participants taken 10 years apart, Dr. Graff-Radford and his co-authors found that both increased systolic blood pressure and increased pulse pressure correlated with increased ventricle size. In earlier research, Dr. Graff-Radford and colleagues showed 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 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.