Summary: Some patients diagnosed with behavioral-variant frontotemporal dementia (bv-FTD) may instead be suffering from a cerebrospinal fluid leak that leads to brain sagging.
Source: Cedars Sinai Medical Center
A new Cedars-Sinai study suggests that some patients diagnosed with behavioral-variant frontotemporal dementia (bvFTD)—an incurable condition that robs patients of the ability to control their behavior and cope with daily living—may instead have a cerebrospinal fluid leak, which is often treatable.
Researchers say these findings, published in the peer-reviewed journal Alzheimer’s & Dementia: Translational Research and Clinical Interventions, may point the way to a cure.
“Many of these patients experience cognitive, behavioral and personality changes so severe that they are arrested or placed in nursing homes,” said Wouter Schievink, MD, director of the Cerebrospinal Fluid Leak and Microvascular Neurosurgery Program and professor of Neurosurgery at Cedars-Sinai.
“If they have behavioral-variant frontotemporal dementia with an unknown cause, then no treatment is available. But our study shows that patients with cerebrospinal fluid leaks can be cured if we can find the source of the leak.”
Cerebrospinal fluid (CSF) circulates in and around the brain and spinal cord to help cushion them from injury. When this fluid leaks into the body, the brain can sag, causing dementia symptoms. Schievink said many patients with brain sagging—which can be detected through MRI—go undiagnosed, and he advises clinicians to take a second look at patients with telltale symptoms.
“A knowledgeable radiologist, neurosurgeon or neurologist should check the patient’s MRI again to make sure there is no evidence for brain sagging,” Schievink said.
Clinicians can also ask about a history of severe headaches that improve when the patient lies down, significant sleepiness even after adequate nighttime sleep, and whether the patient has ever been diagnosed with a Chiari brain malformation, a condition in which brain tissue extends into the spinal canal. Brain sagging, Schievink said, is often mistaken for a Chiari malformation.
Even when brain sagging is detected, the source of a CSF leak can be difficult to locate. When the fluid leaks through a tear or cyst in the surrounding membrane, it is visible on CT myelogram imaging with the aid of contrast medium.
Schievink and his team recently discovered an additional cause of CSF leak: the CSF-venous fistula. In these cases, the fluid leaks into a vein, making it difficult to see on a routine CT myelogram. To detect these leaks, technicians must use a specialized CT scan and observe the contrast medium in motion as it flows through the cerebrospinal fluid.
In this study, investigators used this imaging technique on 21 patients with brain sagging and symptoms of bvFTD, and they discovered CSF-venous fistulas in nine of those patients. All nine patients had their fistulas surgically closed, and their brain sagging and accompanying symptoms were completely reversed.
“This is a rapidly evolving field of study, and advances in imaging technology have greatly improved our ability to detect sources of CSF leak, especially CSF-venous fistula,” said Keith L. Black, MD, chair of the department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai.
“This specialized imaging is not widely available, and this study suggests the need for further research to improve detection and cure rates for patients.”
The remaining 12 study participants, whose leaks could not be identified, were treated with nontargeted therapies designed to relieve brain sagging, such as implantable systems for infusing the patient with CSF. However, only three of these patients experienced relief from their symptoms.
“Great efforts need to be made to improve the detection rate of CSF leak in these patients,” Schievink said.
“We have developed nontargeted treatments for patients where no leak can be detected, but as our study shows, these treatments are much less effective than targeted, surgical correction of the leak.”
About this dementia research news
Original Research: Open access.
“The reversible impairment of behavioral variant frontotemporal brain sagging syndrome: Challenges and opportunities” by Wouter I. Schievink et al. Alzheimer’s & Dementia: Translational Research & Clinical Interventions
The reversible impairment of behavioral variant frontotemporal brain sagging syndrome: Challenges and opportunities
Due to loss of brain buoyancy, spontaneous spinal cerebrospinal fluid (CSF) leaks cause orthostatic headaches but also can cause symptoms indistinguishable from behavioral variant frontotemporal dementia (bvFTD) due to severe brain sagging (including the frontal and temporal lobes), as visualized on brain magnetic resonance imaging. However, the detection of these CSF leaks may require specialized spinal imaging techniques, such as digital subtraction myelography (DSM).
We performed DSM in the lateral decubitus position under general anesthesia in 21 consecutive patients with frontotemporal dementia brain sagging syndrome (4 women and 17 men; mean age 56.2 years [range: 31–70 years]).
Nine patients (42.8%) were found to have a CSF-venous fistula, a recently discovered type of CSF leak that cannot be detected on conventional spinal imaging. All nine patients underwent uneventful surgical ligation of the fistula. Complete or near-complete and sustained resolution of bvFTD symptoms was obtained by all nine patients, accompanied by reversal of brain sagging, but in only three (25.0%) of the twelve patients in whom no CSF-venous fistula could be detected (P = 0.0011), and who were treated with non-targeted therapies.
Concerns about a spinal CSF leak should not be dismissed in patients with frontotemporal brain sagging syndrome, even when conventional spinal imaging is normal. However, even with this specialized imaging the source of the loss of spinal CSF remains elusive in more than half of patients.