ARTICLE IN BRIEF
While patients with immunodeficiency or a malignancy can clearly benefit from a brain biopsy, the procedure was found to have more limited value for patients whose neurologic status was rapidly deteriorating.
Doing a brain biopsy in patients who have acute progressive neurologic decline but no mass lesion or immunodeficiency is frequently not helpful at all, according to study by investigators at Emory University in Atlanta.
Researchers reviewed the records for 51 patients to determine what impact biopsy had on diagnosis and treatment and found that often nothing was gained from the procedure.
“The overall sensitivity, or likelihood of a pathological abnormality, of a diagnostic brain biopsy was 35 percent (18 of 51 patients),” the researchers reported in the Aug. 3 edition of Neurology. “Eight percent (four out of 51 patients) of open biopsies performed resulted in a change in treatment or start of a new treatment.”
“By concentrating on not only the diagnosis, but also the treatment options prior to surgery, we can avoid in many cases a potentially unwarranted surgical risk, added expense, and emotional hardship that accompanies an open brain biopsy,” the study concluded.
The paper's senior author Jeffrey J. Olson, MD, professor of neurosurgery, hematology and medical oncology at Emory University School of Medicine, told Neurology Today that the study “considers an important topic that faces practicing neurologists and neurosurgeons on a regular basis.” He said the study raises concern that often biopsies don't result in an “advantage for the patient or the managing physician.”
Joseph Berger, MD, chair of the department of neurology at the University of Kentucky and an expert in the neurologic complications of HIV/AIDS, said clinicians need to be careful, however, not to misinterpret the study results, which were based on a small, carefully-selected group of patients seen at one medical center.
“I wouldn't want anyone to be left with the impression that biopsies are of little value,” Dr. Berger, who was not involved with the study, told Neurology Today. He noted that the study was “a very skewed population” — it did not include patients with a suspected malignancy or immunodeficiency. Still, Dr. Berger said the findings do offer an important reminder for clinicians no matter what the circumstances.
“The first question you have to ask yourself in doing a biopsy is, ‘Am I going to find a treatable condition?’” he said. “That question is of paramount importance when you're going to subject a patient to that a procedure that carries risk of both morbidity and mortality.”
The Emory team reviewed the medical and surgical records of 51 patients, all 20 years or older, who underwent a craniotomy for open brain biopsy at Emory University Hospital from January 1999 to September 2008. They looked at pre-surgical lab results, imaging, operative reports, pathology findings, and discharge summaries, as well as follow-up medical records, which, on average, covered 15 months after biopsy for each patient.
The investigators found the most common presenting symptom was rapid cognitive decline, as defined as less than six months since onset. Less common symptoms were memory loss, headache, focal weakness, and ataxia. Almost all of the 51 patients were given a CSF analysis, and about half underwent cerebral diagnostic subtraction angiography, especially if vasculitis was suspected. All of the patients had an MRI.
The most common presumed, pre-surgical diagnosis was vasculitis, followed by encephalitis, Creutzfeldt-Jakob disease (CJD), and demyelinating diseases. In most cases, the biopsy was removed from the right middle frontal lobe gyrus, unless the pre-surgical workup suggested another location would make sense.
The pathology results yielded an abnormality in 18 of 51 patients (35 percent). Eight of the 51 (15. 7 percent) were found to have CJD and three patients (six percent) were diagnosed with amyloidosis. Other biopsy findings included demyelinating disease, primary central nervous system lymphoma (PCNSL), viral encephalitis, infarction, and sarcoidosis. Most of the biopsies found normal brain tissue or showed signs of mild, nonspecific inflammatory changes.
In just four of the 51 patients did the biopsy results lead directly to a change in treatment or the state of a new treatment, and only two of those ended up with a “meaningful therapeutic benefit” as a result of the biopsy, the researchers reported. “This was only seen in those two patients who were newly diagnosed with lymphoma and subsequently initiated chemotherapy,” they reported. Thirteen of the 51 patients (25 percent) were started on a treatment even when their biopsy results were negative or inconclusive — a finding that suggests that perhaps such treatment should have been tried in the first place.
BETTER EVALUATION NEEDED
The research suggests the need for clinicians need to look more critically at the information gathered in pre-surgical tests before proceeding to biopsy. In the case of most of the CJD patients in the study, for instance, there were telltale signs evident on MRI, and some also had suspicious electroencephalogram and CSF results — findings that suggested that a biopsy perhaps was unnecessary to make a diagnosis. The Emory researchers noted that “our institution currently has a rigorous protocol for biopsies without a radiographic mass, viewing all cases as possible CJD transmissible. This often unnecessary safety protocol adds an additional expense to the already high cost of a brain biopsy.”
They also noted that while 24 of 51 patients were suspected of having primary CNS vasculitis, none turned out to have positive biopsy finding for that condition.
“Clearly, cerebral vasculitis continues to be a diagnostic dilemma,” they noted, adding: “The lack of a well documented therapy for central nervous system vasculitis further clouds the real value of biopsy in the diagnostic algorithm.”
None of the patients died as a direct result of biopsy; two (4 percent) developed hemorrhaging. “It is important to weigh the four percent potential therapeutic benefit against the four percent risk of a post-biopsy hemorrhagic event,” the researchers said.
David B. Clifford, MD, Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology at Washington University School of Medicine, told Neurology Today that the study “helps put the risk-benefit ratio in a thoughtful perspective.”
“There is no doubt that ‘blind’ brain biopsies are costly in dollars and risk —mostly to the patient but in theory to those in the operating rooms as well — with a very modest return of treatable conditions where the biopsy critically informed the treating physician on the proper course,” Dr. Clifford, who was not involved with the study, noted. “It is likely that even the small numbers of biopsies done in most academic centers represent a degree of overuse of this technique.”
The fact that in a number of cases “therapy was selected and tried after a non-diagnostic biopsy might reasonably suggest that the treatment could have been tried prior to biopsy, with the potential to obviate the biopsy, or at a minimum buy time to establish a more probable target tissue for sampling,” he said.
But Dr. Clifford said brain biopsy is still overall a valuable tool. “Establishing a diagnosis in puzzling cases remains important to improvement in medicine and has a place in academic medical centers,” he said. “The trend toward failing to obtain autopsies, and thus failing to complete a clinical pathological correlation by examination of the brain when patients die without a confirmed diagnosis, has real hazard to the quality of care and diagnosis for the future.”
“Too often these patients if not fully assessed during life, are transported to hospice care, and die without full consideration of the problems,” Dr. Clifford said. “I would hope that the appropriate concerns about the risks and benefits of open, blind brain biopsy would enhance, and not deter thoughtful management and final assessment of these patients.”