Category: Multiple Sclerosis

Fewer African Americans than Caucasians develop multiple sclerosis (MS), statistics show, but their disease progresses more rapidly, and they don't respond as well to therapies, a new study by neurology researchers at the University at Buffalo has found.

Magnetic resonance images (MRI) of a cohort of 567 consecutive MS patients showed that blacks with MS had more damage to brain tissue and had less normal white and grey matter compared to whites with the disease.

Results of the study appear in the Feb. 16 issue of the journal Neurology.

Bianca Weinstock-Guttman, MD, UB associate professor of neurology in the UB School of Medicine and Biomedical Sciences, is first author on the study. Weinstock-Guttman directs the Baird Multiple Sclerosis Center in Kaleida Health's Buffalo General Hospital.

"Black patients showed more brain tissue damage and accumulated brain lesions faster than whites, along with rapid clinical deterioration," confirms Weinstock-Guttman. "The results provide further support that black patients experience a more severe disease, calling for individualized therapeutic interventions for this group of MS patients."

"White matter" refers to the parts of the brain that contain nerve fibers sheathed in a white fatty insulating protein called myelin. The white matter is responsible for communication between the various grey matter regions, where nerve cells are concentrated and where cognitive processing occurs.

"Initially, multiple sclerosis was considered primary a white-matter disease," says Weinstock-Guttman, "but today we know that the gray matter may be more affected than white matter."

In general, black MS patients tend to have more severe and more frequent attacks, followed by an incomplete recovery even after the first episode. Studies on signs and symptoms of MS among populations have shown that blacks experience gait problems sooner after their diagnosis, show faster cognitive decline than whites with MS, and become dependent on a wheelchair sooner, she notes.

The study's MRI scans were conducted at the Buffalo Neuroimaging Analysis Center (BNAC), part of the Jacobs Neurological Institute/UB Department of Neurology. Robert Zivadinov, MD, PhD, a UB associate professor of neurology, is director of the center.

Seventy-nine black patients and 488 white patients were entered in the study. Participants were older than 18 and had been scanned within 90 days of their most recent clinical visit. Black participants were significantly younger, and their disease was more severe than white patients, despite having MS for a shorter amount of time.

"Results of the MRI scans showed that the aggressive disease process in blacks appears to be associated with increased macroscopic and microscopic tissue damage, as measured by specific MRI parameters," says Weinstock-Guttman.

"Based on our MRI findings, a plausible hypothesis that would explain the more aggressive disease in blacks compared to whites with MS may be that blacks have a reduced capacity for remyelination, the brain's ability to repair the protective myelin sheath. However, to confirm this hypothesis, we will need to conduct more longitudinal studies."

Murali Ramanathan, PhD, associate professor in the departments of Pharmaceutical Sciences and Neurology in the UB School of Pharmacy and Pharmaceutical Sciences and School of Medicine and Biomedical Sciences, respectively, also contributed significantly to the study.

Additional contributors were David Hojnacki, MD, Michael G. Dwyer, Sara M. Hussein, MD, Niels P. Bergsland and Frederick E. Munschauer, MD, former chair of the UB Neurology department, now vice president of U.S. medical affairs for Biogen Idec in Boston, Mass.

The study was supported by grants from the National Multiple Sclerosis Society and the UB Pediatric MS Center of Excellence.

---

Journal Reference:

1. B. Weinstock-Guttman, M. Ramanathan, K. Hashmi, N. Abdelrahman, D. Hojnacki, M. G. Dwyer, S. Hussein, N. Bergsland, F. E. Munschauer, and R. Zivadinov. Increased tissue damage and lesion volumes in African Americans with multiple sclerosis. Neurology, 2010; DOI: 10.1212/WNL.0b013e3181cff6fb

Low vitamin D blood levels are associated with a significantly higher risk of relapse attacks in patients with multiple sclerosis (MS) who develop the disease during childhood, according to a study conducted by researchers from the University of California, San Francisco.

"We have known for some time that vitamin D insufficiency is a risk factor for developing MS, but this is the first study to assess whether vitamin D levels influence the disease course of those who already have MS," said lead author Ellen Mowry, MD, MCR, a clinical instructor of neurology at the UCSF Multiple Sclerosis Center.

The study, which is now published online in the Annals of Neurology, demonstrates that an increase in vitamin D levels by 10 nanograms per milliliter of blood (ng/mL) corresponds with a 34 percent decrease in the rate of subsequent relapses.

In other words, raising the vitamin D level of a person with MS by 15 ng/mL, which requires about 2,000 international units of vitamin D supplementation a day, could theoretically cut a patient's relapse rate in half, explained Mowry.

"Although we do not yet know if vitamin D supplementation will be beneficial for MS patients, the fact that there is a clear association between vitamin D levels and relapse rate provides strong rationale for conducting a clinical trial to measure the potential impact of supplementation," she said.

"This is an exciting finding because it indicates that it is very possible for vitamin D supplementation to have a profound impact on the course of this disease," said senior author Emmanuelle Waubant, MD, PhD, an associate professor of neurology at UCSF and director of the Regional Pediatric MS Center at UCSF Children's Hospital. Waubant said she expects similar findings in adult patients with MS.

Multiple sclerosis is a chronic and often disabling disease that affects the central nervous system, which comprises the brain, spinal cord and optic nerves. A type of autoimmune disorder, MS causes the body's own defense system to break down a substance called myelin, which surrounds and protects nerve fibers.

Although MS occurs most commonly in adults, a small proportion of cases are diagnosed in children and adolescents. According to the National MS Society, two to five percent of all people with MS experience their first symptoms before the age of 18.

The researchers measured vitamin D levels through blood samples from 110 patients whose MS symptoms began at age 18 or younger. The patients were seen at either UCSF Children's Hospital or the State University of New York Stony Brook's Regional Pediatric MS Center of Excellence — two of six multidisciplinary referral centers in the United States sponsored by the National MS Society.

After providing the initial blood sample, patients were followed for an average of 1.7 years, during which the researchers recorded the total number of relapses each patient experienced. According to Mowry, a relapse or flare-up of MS causes new neurologic symptoms or the worsening of old ones, such as impaired vision, problems with balance, or numbness. Relapses can be very mild or severe enough to interfere with a person's ability to function.

During the follow-up period, the researchers assessed the patients' relapse rates and vitamin D levels after controlling for such factors as age, gender, race, ethnicity, use of MS treatments and the duration of follow-up care.

"If we are able to confirm that vitamin D supplementation is an effective treatment, my hope is that it will help improve the quality of life for all MS patients," Mowry said.

In addition to a randomized clinical trial of vitamin D supplementation in MS patients, Mowry said further studies are also needed to determine the mechanism by which vitamin D affects inflammatory processes and, in turn, eases symptoms of MS.

Additional co-authors from UCSF include Dorothee Chabas, MD, PhD; Jonathan Strober, MD; Jamie McDonald, BS; Jorge Oksenberg, PhD, and Peter Bacchetti, PhD. Co-authors from other institutions are Lauren Krupp, MD; Maria Milazzo, MS, CPNP, and Anita Belman, MD, all of the Pediatric MS Center, State University of New York at Stony Brook.

The study was supported by a National MS Society Sylvia Lawry Fellowship Award and an additional grant from the National MS Society.

---

Journal Reference:

1. Mowry et al. Vitamin D status is associated with relapse rate in pediatric-onset MS. Annals of Neurology, 2010; DOI: 10.1002/ana.21972

A new drug for multiple sclerosis promises to change the lives of the 100,000 people in the UK who have the condition, say researchers at Queen Mary, University of London.

A major trial of the oral drug Cladribine — results of which are published in the New England Journal of Medicine on 20 January 2010 — has shown that it significantly reduces relapse and deterioration of the disease, and goes a long way to eliminating the unpleasant side effects associated with existing therapies. Cladribine promises to be the first ever treatment in tablet form for MS, and only needs be taken for between 8 to 10 days a year, eliminating the need for regular injections and intravenous infusions otherwise endured by sufferers. The ease with which Cladribine tablets can be administered, combined with its relatively few side effects, make it a hugely exciting development in the world of MS.

Multiple sclerosis is a disabling neurological condition which usually starts in young adulthood. It results from the body's own immune system damaging the central nervous system. This interferes with the transmission of messages between the brain and other parts of the body and leads to problems with vision, muscle control, hearing and memory. Cladribine tablets work by suppressing the immune system thus compromising its ability to further attack the central nervous system.

Led by Professor Gavin Giovannoni at Barts and The London School of Medicine and Dentistry, the new study involved over 1,300 MS patients who were followed up for nearly two years and monitored using MRI scans. Patients were given either two or four short treatment courses of Cladribine tablets per year, or a placebo. Each course consists of one or two tablets per day for four or five days, adding up to just eight to 20 days of treatment each year.

Compared to patients who were taking a placebo, those taking Cladribine tablets were over 55 per cent less likely to suffer relapse, and 30 per cent less likely to suffer worsening in their disability due to MS.

Professor Giovannoni said: "The introduction of an oral therapy, particularly one that has no short term side effects and is as easy to use as oral Cladribine, will have a major impact on the treatment of MS.

"However, the use of this drug as a first line therapy will have to be weighed up against the potential long term risks which have yet to be defined."

---

Journal Reference:

1. Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Sorensen PS, Vermersch P, Chang P, Hamlett A, Musch B, Greenberg SJ. A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis. New England Journal of Medicine, 2010; DOI: 10.1056/NEJMoa0902533

In the February 1st issue of Genes & Development, Dr. Brian Popko (The University of Chicago) and colleagues describe how mutation of a gene called ZFP191 leads to disordered central nervous system (CNS) myelination in mice — reminiscent of what is seen in human multiple sclerosis (MS) patients.

MS is a chronic autoimmune disorder, in which the body attacks and destroys the myelin sheath that insulates and protects nerve fibers of the central nervous system (the brain, spinal cord and optic nerves). Demyelination disrupts the conduction of electrical impulses along nerve fibers, and results in regional neural deficits. MS symptoms range from tingling and numbness in limbs, to loss of vision and paralysis.

It is estimated that MS affects 400,000 people in the US and approximately 2.5 million worldwide.

Dr. Popko and colleagues identified a gene called ZFP191 as being necessary for the development of oligodendrocyte cells, which — in their fully mature form — produce myelin. The researchers found that mice harboring a single mutation in ZFP191 display tremors and seizures, caused by a severe deficiency in CNS myelination.

ZFP191 appears to be the first factor identified to be critical for the myelinating function of oligodendrocytes.

The failure of Zfp191-mutant mouse oligodendrocytes to successfully myelinate their targets is reminiscent of human MS lesions, where re-myelination of damaged tracts fails to occur efficiently even when apparently mature oligodendrocytes are present in the area.

While further research to delineate the precise targets of ZFP191 is needed, this work holds promising clinical value as a potential therapeutic pathway to promote re-myelination, reduce the accumulation of MS lesions and slow disease progression.

The paper will be released online ahead of print at www.genesdev.org.

Glial cells, which help neurons communicate with each other, can leave the central nervous system and cross into the peripheral nervous system to compensate for missing cells, according to new research in the Dec. 2 issue of The Journal of Neuroscience. The animal study contributes to researchers' basic understanding of how the two nervous systems develop and are maintained, which is essential for the effective treatment of diseases such as multiple sclerosis.

The nervous system is divided into the central nervous system (the brain and spinal cord) and the peripheral nervous system (sensory organs, muscles, and glands). A major difference between the systems is that each has its own type of glial cells. In a healthy body, glial cells are tightly segregated and aren't known to travel between the two systems. The peripheral nervous system also regenerates more than the central nervous system, due in part to its glial cells — a characteristic that, if better understood, might be used to improve the regenerative capabilities of the central nervous system.

Glial cells serve nerve cells by insulating them with layers of fats and proteins called myelin. Myelin coatings are necessary for nerve signals to be transmitted normally; when the sheaths are lost, disorders involving impairment in sensation, movement and cognition such as multiple sclerosis or amyotrophic lateral sclerosis develop. Glial cells named oligodendrocytes produce myelin around nerves of the central nervous system, while those named Schwann cells make myelin that insulates peripheral nerves.

This study shows that in the absence of Schwann cells, oligodendrocytes migrate from the central nervous system along motor nerves and form myelin on peripheral nerves, indicating that glial cell movement across the border is controlled by a self-policing mechanism.

"Past studies have hinted that Schwann cells can cross into the central nervous system after peripheral nerves near the border are damaged, or after central nerves lose their myelin sheath," said Bruce Appel, PhD, of the University of Colorado Denver Anschutz Medical Campus, one of the study's authors. "However, migration across the border has never been observed directly, nor was there any evidence that oligodendrocytes can move in the opposite direction."

The authors used time-lapse video of mutant zebrafish to study the glial cell movement. Movies of translucent live zebrafish that lacked Schwann cells showed that oligodendrocytes left the central nervous system to wrap peripheral nerves with myelin — effectively attempting to compensate for the missing Schwann cells.

"This new observation is not only relevant to normal nerve function, but also to potential causes of disease in the peripheral nervous system. We're still unsure as to exactly how foreign glial cells interact with the other system. Do they help heal or do they act as a toxin?" said Bruce Trapp, PhD, at the Cleveland Clinic, who is unaffiliated with the study. "Knowing the mechanisms that anatomically restrict peripheral and central nervous system glia could help develop therapies that treat or prevent certain nervous system diseases."

Appel and his colleagues said that future investigations are needed to determine how different glial cells communicate to restrict their movements between nervous systems, and whether oligodendrocyte myelin can fully substitute for Schwann cell myelin on motor nerves.

The research was supported by the National Institute of Neurological Disorders and Stroke and a zebrafish initiative funded by the Vanderbilt University Academic Venture Capital Fund.

New findings from an international team of researchers probing the nerve-insulating myelin sheath were bolstered by the work of Boston College biologists, who used x-rays to uncover how mutations affect the structure of myelin, a focal point of research in multiple sclerosis and other neurological disorders.

The findings were central to the group's broader conclusion that a set of protein processes required in the early-stage conversion of glucose into fatty acids are critical to the proper formation and layering of myelin membrane, the researchers report in the Proceedings of the National Academy of Sciences.

Boston College Professor of Biology Daniel Kirschner, Senior Research Associate Hideyo Inouye, graduate student Adrienne Luoma, and undergraduate Michelle Crowther partnered with Dutch, Italian, Swiss and Japanese scientists. The research group looked at the composition of myelin lipids for clues about their role in myelin structure and stability, Kirschner said. Myelin sheaths surround the axons of neurons and are considered critical to the proper functioning of the nervous system.

"Myelin is a stack of membranes providing insulation to the axon and with that insulation comes rapid nerve conduction," said Kirschner. "If myelin becomes defective, the membranous insulator becomes leaky and the nerve doesn't conduct as well. If myelin is totally missing along part of an axon, the nerve conduction is blocked."

Using x-ray diffraction, Kirschner's group captured a view of the dynamic membrane assembly in whole nerve samples taken from mice engineered to mimic myelinic diseases. Compared to other microscopy techniques used in the study of myelinated tissue, x-ray diffraction delivers clearer, cleaner and quicker results about the structural integrity of internodal myelin, Kirschner said.

"We were able to tell that the packing of the membranes was abnormal, which could affect the electrophysical properties of myelin," said Kirschner. "We also saw that the packing of the lipids in the myelin lipid bilayers was more disordered in samples from the transgenic mice used here."

Other types of microscopy introduce chemical modifications to the tissue under study. These agents and the time involved in preparing and analyzing such samples can alter the molecular structure and mask the dynamic interactions of myelin. X-ray diffraction requires no chemical treatments and can be completed in about an hour, Kirschner said.

"The advantages of x-ray diffraction are that we can examine and analyze whole pieces of tissue and give information about the effect of the mutation on the native structure of the myelin as well as on its stability," said Kirschner.

The researchers have been focusing on genetically modified mice for approximately four years as part of research into the role of myelin degeneration in a range of diseases of the central and peripheral nervous systems. Kirschner says his team is also exploring use of the technique in animal models of spinal cord injury and repair.

Current research suggests that a common oral bacterium may exacerbate autoimmune disease. Multiple sclerosis (MS), a disease where the immune system attacks the brain and spinal cord, affects nearly 1 in 700 people in the United States. Patients with multiple sclerosis have a variety of neurological symptoms, including muscle weakness, difficulty in moving, and difficulty in speech.

Porphyromas gingivalis, a common oral bacterium in humans, produces a unique type of lipid, phosphorylated dihydroceramides (DHCs), which enhance inflammatory responses. These lipids are also likely produced by bacteria found in other parts of the body including the gastrointestinal tract. To determine if these lipids accentuate immune-mediated damage in autoimmune disease, researchers led by Robert B. Clark and Frank C. Nichols of the University of Connecticut Health Center administered phosphorylated DHCs in a mouse model of MS. The severity of disease was significantly enhanced by the addition of these lipids in a manner that was dependent on activation of the immune system. These data suggest that phosphorylated DHCs from bacteria commonly found in humans may trigger or increase the severity of autoimmune diseases such as multiple sclerosis.

The authors state that "while it is clear that the immune system in most individuals has the potential to attack self-tissues, the "tipping" factors that initiate and propagate autoimmune diseases such as multiple sclerosis in only a subset of individuals remain unknown. Overall, [their] results represent the first description that phosphorylated DHCs derived from common human bacteria are capable of enhancing autoimmune disease." Thus, these lipids may function as "tipping" factors, playing a previously unrecognized role in initiating or exacerbating human autoimmune diseases. In future studies, Dr. Clark and colleagues plan to characterize the effects of phosphorylated DHCs on specific cells of the immune system and to identify how and where these lipids are deposited in tissues throughout the body. In addition to the role of these lipids in triggering and worsening MS, the authors believe that phosphorylated DHCs may have the potential to serve both as new markers of MS disease activity and as new targets for therapeutic intervention.

This work was supported by grants from the National MS Society (RG4070-A-6) (RBC) and the Patterson Trust Foundation (FN).

There is a provisional patent application pending for the use of bacterial phosphorylated dihydroceramides. This application pertains to Dr. Frank Nichols and Dr. Robert B. Clark.

---

Journal Reference:

1. Nichols FC, Housley W, O'Conor C, Manning T, Wu S, Clark RB. Unique Lipids from a Common Human Bacterium Represent a New Class of TLR2 Ligands Capable of Enhancing Autoimmunity. Am J Pathol, 175: 2430-2438

There is good news for women with multiple sclerosis (MS) who are pregnant or thinking about becoming pregnant. A new study shows that pregnant women with multiple sclerosis are only slightly more likely to have cesarean deliveries and babies with a poor prenatal growth rate than women who do not have MS.

Plus, the women with MS were no more likely to have other pregnancy problems, such as preeclampsia and other high blood pressure problems and premature rupture of membranes, than women in the general population. The study is published in the November 18, 2009, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The large study used a national database from all non-federal short-stay hospitals in 38 states. The data included an estimated 18.8 million deliveries, with about 10,000 of those occurring in women with MS.

The women with MS were more likely than women without chronic medical conditions (2.7 percent for women with MS compared to 1.9 percent for women without chronic medical conditions) to have a fetus with intrauterine growth restriction, defined as a weight less than the tenth percentile for the gestational age, as measured by ultrasound. Women with MS were more likely to have a cesarean delivery than those in the general population (42 percent versus 33 percent).

"These results are reassuring for women with MS," said study author Eliza Chakravarty, MD, MS, of Stanford University School of Medicine in Stanford, CA. "Women and their doctors have been uncertain about the effect of MS on pregnancy, and some women have chosen to delay or even avoid pregnancy due to the uncertainty. We found that women with MS did not have an increased risk of most pregnancy complications."

Chakravarty said that previous studies on MS and pregnancy have focused on the impact of pregnancy on disease activity.

The study also looked at women who had diabetes prior to becoming pregnant (not gestational diabetes), and found that they had higher rates of complications than women with MS and high rates of complications in areas where the women with MS did not have increased rates.

Magnetic resonance images (MRI) of patients diagnosed with multiple sclerosis in childhood show that pediatric onset multiple sclerosis is more aggressive, and causes more brain lesions, than MS diagnosed in adulthood, researchers at the University at Buffalo have reported.

Interestingly, however, patients with pediatric-onset MS — which comprise up to 5 percent of total MS cases — develop disabilities at a slower pace than patients with adult-onset MS, the data showed.

"Patients with pediatric-onset MS have three times as many relapses annually than patients with adult-onset disease, which suggests there is greater disease activity in this population," said Bianca Weinstock-Guttman, MD, associate professor of neurology in the UB School of Medicine and Biomedical Sciences and corresponding author.

"But surprisingly, the average time to reach the secondary progressive phase of the disease is longer in patients who develop MS in childhood than in adult onset MS," she continued. "Reaching the next stage of disability is almost 10 years longer in pediatric-onset patients."

Weinstock-Guttman directs the Pediatric Multiple Sclerosis Center of Excellence located at Women and Children's Hospital, and the William C. Baird MS Center in Buffalo General Hospital (BGH), both Kaleida Health affiliates and UB teaching hospitals.

Eluen A. Yeh, MD, UB assistant professor of neurology and co-director in the Pediatric Multiple Sclerosis Center, is first author on the study, which was published online Nov. 5 in Brain.

The National Multiple Sclerosis Society estimates that 8,000 to 10,000 children (defined as up to 18 years old) in the U.S. have multiple sclerosis, and another 10,000 to 15,000 have experienced at least one symptom suggestive of MS. The disease causes demyelination — destruction of the sheath that protects and insulates nerve fibers. Breaks in the myelin sheath disrupt the flow of electrical impulses, causing loss of sensation and coordination.

The UB study involved four sets of patients:

• 17 children with an average age of 13.7 who were diagnosed with MS 2.7 years earlier
• 33 adults with an average age of 36.5 years who were diagnosed with pediatric MS 20 years earlier
• 81 adults with an average age of 40 who have had MS for an average of 2.6 years
• 300 adults with an average age of 50.5 who've had MS for 20 years

All participants underwent a brain MRI scan at facilities at BGH and at Women and Children's Hospital, while the specific MRI metric analysis was performed at the Buffalo Neuroimaging Analysis Center (BNAC), part of the UB Department of Neurology/Jacobs Neurological Institute, located in BGH. Robert Zivadinov, MD, PhD, UB associate professor of neurology, is director of the BNAC.

The MRI measured two types of brain tissue damage: T1-lesion volume, which shows "black holes," or hypointense lesions, which are areas of permanent axonal damage; and T2-lesion volume, which shows the total number of lesions (lesion load) and overall disease burden.

Both of these measures indicated that MS is more aggressive in children in the early stages, said Yeh.

"This corresponds with recent data that suggest a higher lesion burden in pediatric MS than adult-onset MS. These findings are somewhat surprising, considering we have assumed that children generally have a greater capacity for central nervous tissue repair."

"Our findings, which are limited to a cross-sectional study design, suggest that children have a somewhat better reserve and functional adaptability than adults, but less support for a better remyelination process," added Weinstock-Guttman. "However, the remyelination process may require a more in-depth prospective analysis"

Weinstock-Guttman said the data support the need for early diagnosis and therapeutic intervention in pediatric MS patients.

Murali Ramanathan, PhD, associate professor in the departments of Pharmaceutical Sciences and Neurology in the UB School of Pharmacy and Pharmaceutical Sciences and School of Medicine and Biomedical Sciences, respectively, also contributed significantly to the research. Additional contributors were Jennifer L. Cox, PhD, research assistant professor and BNAC's director of neuroimaging, and neurology research assistants Deepa Preeti Ramasamy and Laura M. Willis.

The research was supported in part by grants from the National Multiple Sclerosis Society and Children's Guild Foundation of Buffalo.

A woman is six times more likely to be separated or divorced soon after a diagnosis of cancer or multiple sclerosis than if a man in the relationship is the patient, according to a study that examined the role gender played in so-called "partner abandonment." The study also found that the longer the marriage the more likely it would remain intact.

The study confirmed earlier research that put the overall divorce or separation rate among cancer patients at 11.6 percent, similar to the population as a whole. However, researchers were surprised by the difference in separation and divorce rates by gender. The rate when the woman was the patient was 20.8 percent compared to 2.9 percent when the man was the patient.

"Female gender was the strongest predictor of separation or divorce in each of the patient groups we studied," said Marc Chamberlain, M.D., a co-corresponding author and director of the neuro-oncology program at the Seattle Cancer Care Alliance (SCCA). Chamberlain is also a professor of neurology and neurosurgery at the University of Washington School of Medicine.

The study, "Gender Disparity in the Rate of Partner Abandonment in Patients with Serious Medical Illness," was published in the Nov. 15 issue of the journal Cancer. The other corresponding author is Michael Glanz, M.D., of the Huntsman Cancer Institute at the University of Utah School of Medicine.

Why men leave a sick spouse can be partly explained by their lack of ability, compared to women, to make more rapid commitments to being caregivers to a sick partner and women's better ability to assume the burdens of maintaining a home and family, the study authors said.

Researchers at three medical centers — the SCCA, Huntsman and Stanford University School of Medicine — enrolled a total of 515 patients in 2001 and 2002 and followed them until February 2006. The men and women were in three diagnostic groups: those with a malignant primary brain tumor (214 patients), those with a solid tumor with no central nervous system involvement (193 patients) and those with multiple sclerosis (108 patients). Almost half of the patients were women.

Chamberlain said the study was initiated because doctors noticed that in their neuro-oncology practices, divorce occurred almost exclusively when the wife was the patient. The researchers enrolled groups of patients with other cancers and with multiple sclerosis to separate the impact of oncologic versus neurological disease. The results showed a stronger gender disparity for divorce when the wife was the patient in the general oncology and multiple sclerosis groups (93 percent and 96 percent respectively, compared to 78 percent for the primary brain tumor group).

The study also found correlations between age and length of marriage and the likelihood of divorce or separation. The older the woman was the more likely her partnership would end. However, longer marriages remained more stable.

Researchers also measured some health and quality of life outcomes among the patients who separated or divorced. They found that patients used more antidepressants, participated less in clinical trials, had more frequent hospitalizations, were less likely to complete radiation therapy and more likely not to die at home, according to the study.

"We believe that our findings apply generally to patients with life-altering medical illness," the authors wrote. "We recommend that medical providers be especially sensitive to early suggestions of marital discord in couples affected by the occurrence of a serious medical illness, especially when the woman is the affected spouse and it occurs early in the marriage. Early identification and psychosocial intervention might reduce the frequency of divorce and separation, and in turn improve quality of life and quality of care."