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Thomas Campbell: Reversing Dementia

Houston resident Thomas Campbell* was working on contract with a civil engineering group when he noticed he was tripping frequently when he walked.

 The Symptoms

“My walking speed had slowed over time,” the 66-yearold recalls. “I had minor spells when I felt a little dizzy or off balance, and they got progressively worse. I also noticed I had less agility. It seemed like there was less connection between what I wanted to do with my feet and legs and what was actually happening. I wrote it off to old age.” His wife Julia Campbell believed his symptoms were caused by something else. 

“We’d been traveling back and forth between Houston and California, and when we came home permanently, it really hit me that Thomas had changed,” says Campbell, who describes herself as a relentless researcher. “When you’ve been married for a long time, you get to know your husband really well. I noticed physical and behavioral changes that were part of the progression of symptoms, and told him that this was just not normal for people our age. I started researching his symptoms online and one by one, I eliminated the neurological disorders.” She was left with normal pressure hydrocephalus (NPH), a rise in cerebrospinal fluid (CSF) in the brain that causes the ventricles to swell, putting pressure on brain tissue that can result in temporary or permanent damage. She believed her husband’s symptoms were consistent with what she had read.

Meeting the Doctor 

In July 2012, the couple discussed a possible diagnosis of NPH with Raymond Martin, M.D., a professor of neurology at UTHealth Medical School and medical director of outpatient neurology at Mischer Neuroscience Institute (MNI). After evaluating Campbell, Dr. Martin referred him to neurocognitive disorders expert Paul E. Schulz, M.D., whose clinical interests include dementias, such as Alzheimer’s disease and frontotemporal dementia, and disorders of memory, mood and behavior. 

“The question of normal pressure hydrocephalus is not straightforward and requires thorough neuropsychological testing and evaluation of imaging studies to help us differentiate it from Alzheimer’s disease,” says Dr. Schulz, a professor of neurology at UTHealth Medical School. “Here was a man who had been charming, warm and outgoing, whose personality had progressively changed. As physicians dealing with the range of possible neurocognitive disorders, it’s our job to look for clues that help us piece together the total picture for each of our patients.”

Series of Tests 

On a series of basic cognitive tests, Campbell lost only 4 points out of a possible 30, but the pattern did not clearly point to a single disorder. “His initial MRI showed some small-vessel ischemic changes – small strokes,” Dr. Schulz says. “But were those ischemic changes enough to produce the results we saw on the cognition tests, or was something else going on? 

His MRI revealed enlarged ventricles, and his pattern of changes in attention and speed of thinking was consistent with increased pressure in the ventricles. All these clues made his condition look more like NPH than Alzheimer’s disease.”

 To gain more evidence, Dr. Schulz ordered a lumbar puncture and timed how long it took Campbell to walk 50 feet before and after the procedure. His speed in covering the distance dropped from 19 seconds to 15 seconds after the spinal tap. Dr. Schulz also tested his cognitive function. “When we withdrew some cerebrospinal fluid and noticed that the lowering of pressure led to improvement, we had another clue,” he says. “Both his gait and personality improved after the lumbar puncture.”

 Dr. Schulz ordered another test to help support the diagnosis of NPH – a radionuclide cisternogram, a nuclear scan used to diagnose spinal fluid circulation problems and CSF leaks. After a lumbar puncture, small amounts of a radioisotope are injected into the fluid in the lower spine.

 “On the cisternogram, we can observe how long it takes the contrast material to travel to the brain and exit into the blood, from which it is excreted,” he says. “Normally, CSF goes through this cycle about every 300 minutes. At 24 hours, the dye was still visible in Thomas’s brain and spine, and at 48 hours, we could still see it. Clearly, the spinal fluid was not being turned over at the normal rate.” 

The cisternogram results showing delayed CSF outflow, MRI findings of enlarged ventricles, the pattern of change on cognitive testing, and the slowed walking and improvement following lumbar puncture provided strong evidence of normal pressure hydrocephalus, as Julia Campbell suspected. The treatment for NPH is ventriculoperitoneal shunting, in which a burr hole is drilled in the skull and a small, thin catheter is passed into a ventricle of the brain. Another catheter is placed under the skin behind the ear and moved down the neck to the chest or abdomen. A valve connected to the two catheters is placed under the skin behind the ear. When pressure builds up in the ventricles, the valve opens and excess fluid drains into the chest or abdomen, decreasing intracranial pressure. 

To add to the complexity of diagnosis, NPH is accompanied by Alzheimer’s disease (AD) in about 50 percent of cases. “In these cases, a shunt for NPH may improve walking and incontinence, but not cognition,” Dr. Schulz says. “However, new diagnostic tools give us the capability to determine in advance which patients are likely to have AD and therefore are less likely to improve cognitively after placement of a shunt. In the past, before we could rule out Alzheimer’s contributing to dementia, we had to tell our patients there was a 50-50 chance they’d improve with the shunt. You can imagine how you would feel as a physician if you recommended the surgery and your patient didn’t improve. We can feel more confident about sending a patient to surgery and expecting a positive outcome by performing a florbetapir PET scan to rule out a contribution to altered cognition by Alzheimer’s disease.”

 Florbetapir (Amyvid™) is a radioactive agent that binds to amyloid proteins in the brain, a hallmark of Alzheimer’s disease, and allows them to be visualized on a PET scan. A negative scan reduces the likelihood that cognitive impairment is due to Alzheimer’s disease. MNI was the first in Houston to offer this new diagnostic tool. In December 2012, when Campbell’s diagnosis was more certain, Dong Kim, M.D., director of MNI and chair of the Vivian L. Smith Department of Neurosurgery at UTHealth Medical School, placed the shunt. Campbell describes his response as “immediate and very positive.” 

When Dr. Schulz saw his patient in January after the surgery, he immediately recognized a dramatic change. “I could tell the moment he walked in that he was a different guy, but after normal pressure hydrocephalus, which causes a reversible dementia, it takes some time for the entire personality to return to normal. When I first saw him in January, he wasn’t like the funny, charming man he is now.” 

Campbell describes Dr. Schulz as “excellent and very helpful in trying to figure out what was wrong with me. He determined with testing that I was suffering from some dementia. As I remember it, when I took the cognitive tests, I was not feeling as peppy as I normally am. I also wasn’t very interested in taking the tests, I was there to get my brain shunt,” he says, with characteristic wit. “My wife and I were both convinced I had NPH. The doctors said they had to do some tests first to be sure. After a while, they agreed with us.” 

Normal pressure hydrocephalus usually occurs in adults over the age of 60, and in most cases the cause remains unknown. If caught early and correctly diagnosed and treated, the resulting dementia can be reversed, as in Campbell’s case. 

The End of NPH

He says he noticed more physical and intellectual energy after placement of the shunt. “I’ve received a tremendous benefit from it – no problems at all.”

 Julia Campbell adds, “It’s important for families not to assume a loved one has Alzheimer’s disease when the problem may lie elsewhere and be correctable. A little research of symptoms and the order in which they appeared really does help you get to the right medical specialist more quickly, speeding up the process leading to effective treatment. 

“It’s hard to find doctors who have good bedside manner,” she says. “All the doctors who treated Thomas were great. Dr. Schulz is a good listener and was very attentive to my particular needs. It’s really stressful when a family member undergoes physical and behavioral changes and you’re trying to get him back to normal. Everything worked out really well.”

 

*The patient’s name has been changed at the family’s request.