Spontaneous intracranial hypotension (SIH) is believed responsible for reversible frontotemporal dementia in a 66-year-old man who had chronic headaches, memory loss, and progressive changes in behavior and personality over an 18-month period.
In addition to inappropriate and offensive behavior, the patient experienced chronic bifrontal daily headaches that disappeared when he was lying down, reported Norman L. Foster, MD, Professor of Neurology at the University of Michigan School of Medicine in Ann Arbor, in Neurology (2002;Jun 5;58: 1285–7).
“Taken together, his clinical features all pointed to spontaneous intracranial hypotension and his behavioral changes were characteristic of frontotemporal dementia,” Dr. Foster told Neurology Today in a phone interview. Dr. Foster, a senior research scientist at the university's Institute of Gerontology, added: “As far as I know, this has never been previously described with frontotemporal dementia.”
The patient's wife told doctors her husband's personality had changed dramatically over a period of months. He repeatedly made offensive and sexually explicit remarks in public, stopped paying attention to personal hygiene, and had become increasingly lethargic at home, often spending 12 hours each day in bed.
“The wife was at her wit's end,” Dr. Foster said. “Other physicians were at a loss and she was ready to have him institutionalized. He had stopped bathing and his episodes of memory loss were getting worse. At times he would forget where he was going while driving or lose track of what he was talking about moments before. He also started making irresponsible decisions, including purchasing a home without consulting her.”
Upon examination, the husband's physical and neurological status were normal, as was his gait, speech, and reflexes, said Dr. Foster. Blood tests also were within the normal range. Mild declines in intellectual ability and memory were observed, especially those tasks involving concept formation and “frontal” thinking in standardized neuropsychological and intelligence performance tests.
An MRI revealed meningeal thickening and pachymeningitis, with crowding of posterior fossa structures and descent of the cerebellar tonsils. A lumbar puncture showed a low opening pressure of six cm, but normal glucose and cell count levels. Cerebrospinal fluid (CSF) protein was slightly elevated but no leakage was discovered, and a SPECT perfusion scan was normal.
The results of a meningeal biopsy ruled out other possible causes of pachymeningeal enhancement, leaving no other explanation for the patient's CSF hypovolemia than SIH, Dr. Foster said. “There was no CSF leakage that we could find using radioisotopes. His meninges were swollen but when we biopsied the tissue we found no signs of a tumor or bacterial infection to explain the swelling.”
A two-week tapered course of prednisone starting at 80 mg per day initially resulted in significant improvement in symptoms, but they returned once therapy was discontinued. A second course of 60 mg prednisone again reversed symptoms and improvement was sustained as the regimen was slowly tapered over four months.
“His cognitive and behavioral symptoms continued to improve eight months after treatment ended,” said Dr. Foster, and a follow-up MRI showed marked improvement in pachymeningitis and brain sagging.
“We were pleasantly surprised that prednisone was so effective in reversing symptoms. These cognition measurements have not been reported previously. Of course, this is just one case,” he added.
“Without postmortem examination of the brain it is impossible to fully exclude the possibility that some underlying neurodegenerative disease caused the patient's symptoms,” Dr. Foster noted. “However, the normal SPECT results and the fact that symptoms reversed with treatment makes this unlikely.”
Although the exact mechanism by which intracranial CSF hypovolemia caused the man's cognitive impairments remain unknown, Dr. Foster said patients with signs of frontotemporal dementia and headaches should be given an MRI, and special attention should be paid to changes indicating pachymeningitis and hypovolemia.
COMMENTARY ON STUDY
Bahram Mokri, MD, Professor of Neurology at Mayo Medical School in Rochester, MN, is not surprised by Dr. Foster's findings. “For many years, the medical community believed SIH manifested itself simply with pounding headaches, similar to those after a spinal tap, that stopped when the patient would lie down,” he said. “But in the last decade it has become apparent in clinical practice that it sometimes occurs with very different symptoms. These may or may not include headache, but also MRI abnormalities that can vary quite a lot.”
Today, four distinct syndromes are recognized, explained Dr. Mokri, the author of a number of studies on CSF hypovolemia and SIH. The first is classical SIH, with severe bifrontal headache and pachymeningeal enhancement and sinking of the brain visible by MRI.
In the second syndrome there is a proven CSF leak, MRI abnormalities, but no headaches. Patients with the third syndrome have confirmed leakage, headache, MRI abnormalities, but normal spinal pressure, and in the fourth there is low pressure, confirmed leakage, headaches, but no abnormalities visible by MRI.
“There are also a number of additional one- or two-case reports of other unusual manifestations, such as parkinsonism, ataxia, coma, and others, and now frontotemporal dementia. I have no doubt of this, given the other single reports of odd manifestations of this condition,” Dr Mokri said. “The truth is we're still in the learning phase.”
ABOUT FRONTOTEMPORAL DEMENTIA AND SPONTANEOUS INTRACRANIAL HYPOTENSION
Frontotemporal dementia attacks the frontal and temporal lobes of the brain, interfering with judgment, language, and planning. It typically affects peoplebetween ages 40 and 65, but can arise in patients in their 30s or younger. FTD accounts for between 10 and 15 percent of all dementias in persons under 65, according to the National Institute for Mental Health.
SIH is a syndrome characterized primarily by headache because of a rupture of the membranes that encase the cerebrospinal fluid. As a result fluid leaks out – hypovolemia occurs – the CSF pressure drops and the brain sags.