February 3, 2011 — "Groundbreaking" new research by Swedish researchers suggests shunt surgery can improve both cognition and gait in elderly patients with dementia caused by white matter changes and idiopathic normal pressure hydrocephalus (NPH).
The randomized, placebo-controlled study showed patients who received a fully functioning shunt experienced significant improvement in motor function and psychometric scores 3 months after surgery.
|Dr. Magnus Tisell|
In contrast, those randomized to receive a nonfunctioning shunt showed no improvement until the shunt was opened 3 months after the initial surgery.
"Surgical placebo studies are highly unusual. However, if you can actually do this kind of study, the level of evidence is the highest possible," lead study author Magnus Tisell, MD, PhD, associated professor at the Sahlgrenska Academy and consultant neurosurgeon and head of the Department of Neurosurgery at the Sahlgrenska University Hospital in Göteborg, Sweden, told Medscape Medical News.
Surgical placebo studies are highly unusual. However, if you can actually do this kind of study, the level of evidence is the highest possible.
"Shunt operations have long been used for hydrocephalus, but this study offers more scientifically conclusive results to support the effect of the treatment and also shows that shunt operations can help far more patients than previously believed with their walking and memory," said Dr. Tisell in a release.
"White matter changes should not exclude patients from being shunt operated," he added.
The study was published online January 14 in the Journal of Neurosurgery.
No Other Effective Treatment
A condition that primarily affects adults older than 60 years, NPH develops slowly over time. It is characterized by the gradual enlargement of the ventricles, resulting in the deterioration of gait and balance and cognitive and bladder dysfunction and is often misdiagnosed as Alzheimer's disease or Parkinson's disease.
The researchers note previous research shows patients with hydrocephalic symptoms and ventricular enlargement improve after shunt surgery even after having negative cerebrospinal fluid (CSF) dynamics tests and extensive white matter lesions.
"Currently, patients and CSF dynamics are best evaluated using CSF drainage, an infusion test, or intracranial pressure wave analyses, all methods of limited predictive value," the study authors write.
However, they add, "without guidelines or appropriate therapeutic studies in a patient population with severe vascular comorbidity and a high risk of complications, it is difficult to advocate shunt surgery."
To evaluate the benefits of this procedure, the investigators conducted a randomized, double-blind, placebo-controlled trial.
A total of 14 consecutive patients (65% male; mean age, 75 years) with NPH, ventricular enlargement, and extensive white matter changes, as seen with Wahlund Scale white matter lesion scores, were enrolled between October 2004 and October 2008.
All participants, who were nonresponders to a CSF tap test, were randomized to receive either open or closed shunts surgically.
Shunts were inserted through a right-sided frontal bur hole and into the right lateral ventricle. Patients randomized to receive closed shunts underwent a second surgery at the 3-month point to remove the clips and open their shunts.
Those who received fully functioning shunts from the beginning underwent a sham operation with a superficial incision at the 3-month point.
"Our main focus for performing this study was the fact that these cases had no other effective treatment and that they might all benefit from a shunt 3 months after its placement," the study authors write.
All participants underwent a series of quantitative psychometric and continuous gait tests before surgery and at 3- and 6-month postoperative time points. A physician-conducted interview was also used during long-term follow-up.
Results showed that at 3-month follow-up patients who received a fully functioning shunt experienced a 30% and 23% improvement in motor function and psychometric scores, respectively, and a 26% overall improvement in outcomes.
With a 28% improvement in motor function, an 18% improvement in cognitive function, and a 23% improvement in overall outcomes, participants who initially received a nonfunctioning shunt that was opened at the 3-month time point experienced similar improvements at 6-month follow-up.
The 6-month improvement rate for all patients was 16% for psychometric, 28% for gait, and 22% for overall outcomes.
A total of 8 procedural complications occurred in 7 of the study participants (50%). Of the 5 who developed subdural hematomas, 1 was discovered at 3-month follow-up and 4 at 6 months. Four of these disappeared after adjusting the Strata valve from 1.0 to 1.5 or 2.0.
In addition, 3 participants had ischemic stroke, with only 1 episode considered major.
During an average long-term follow-up of 42 months, investigators found that 3 patients had died due to stroke, malignancy, and pneumonia.
On the other hand, 7 participants (50%) reported feeling better than before surgery, 6 reported sustained gait improvement, and 5 reported sustained mental improvements.
"Patients with enlarged ventricles, hydrocephalic symptoms, and extensive vascular white matter changes benefit from shunt surgery," the study authors write.
"However, the incidence of complications in this study indicates that the decision of whether to insert a shunt should be made with great caution," they add. Dr. Tisell said he hopes to follow this initial trial with a prospective, multicenter study.
"We want to look at ways of optimizing the clinical effects of shunts and reducing the risk of complications in another randomized, double-blind study," he said.
|Dr. Marvin Bergsneider|
"This is a remarkable study in that it is one of the only randomized controlled studies for [NPH] out there," Marvin Bergsneider, MD, professor of neurosurgery at the University of California, Los Angeles (UCLA), and director of the UCLA Adult Hydrocephalus Program, told Medscape Medical News.
"So in that sense, the investigators are true groundbreakers and are to be highly commended. This is exactly the kind of study that we need in this field," said Dr. Bergsneider, who was not involved with this study.
"Historically, there has been a lot of debate about [NPH]. There are even neurologists who still practice that don't believe it exists. And there's been a move to do studies like this to prove that patients actually do get better. So in that direction, this is a very important study."
The investigators are true groundbreakers and are to be highly commended. This is exactly the kind of study that we need in this field.
However, he said, the finding that shunt surgery relieves pressure and results in people getting better with shunts is well established in the literature.
He also noted that the international NPH guidelines committee, of which he was a member, recommends external lumbar drainage testing, rather than volume lumbar puncture and measurement of CSF outflow resistance used in this study, to help determine whether patients with NPH will get better with a shunt.
These other methods are often criticized because of their high false-negative rates, he said.
The study authors conclude that the presence of what looks like ischemic white matter disease should not be used to determine whether patients will improve or not. However, said Dr. Bergsneider, this interpretation may not be correct.
In other words, he added, almost all of the study patients improved despite the 2 prognostic tests used in the study. The researchers, he said, "should have considered using what is now considered the "gold standard in the guidelines — the external lumbar drainage test."
The study was supported by unrestricted grants from the Edit Jacobson Foundation, the John and Britt Wennerstrom Foundation, the Pfizer Foundation for clinical neurological research, and the Per-Olof Ahl Foundation for research on vascular diseases of the brain. The study authors and Dr. Bergsneider have disclosed no relevant financial relationships.
J Neurosurg. Published online January 14, 2011.
Medscape Medical News © 2011 WebMD, LLC
Send comments and news tips to firstname.lastname@example.org.
Cite this: Surgery May Improve Cognition, Motor Function in Dementia Patients - Medscape - Feb 03, 2011.